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A systematic review of the evidence for Canada's Physical Activity Guidelines for Adults Warburton, Darren E; Charlesworth, Sarah; Ivey, Adam; Nettlefold, Lindsay; Bredin, Shannon S May 11, 2010

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REVIEW Open AccessA systematic review of the evidence for Canada’sPhysical Activity Guidelines for AdultsDarren ER Warburton1,2*, Sarah Charlesworth1,2, Adam Ivey1,2, Lindsay Nettlefold1,2, Shannon SD Bredin3AbstractThis systematic review examines critically the scientific basis for Canada’s Physical Activity Guide for Healthy ActiveLiving for adults. Particular reference is given to the dose-response relationship between physical activity and pre-mature all-cause mortality and seven chronic diseases (cardiovascular disease, stroke, hypertension, colon cancer,breast cancer, type 2 diabetes (diabetes mellitus) and osteoporosis). The strength of the relationship between phy-sical activity and specific health outcomes is evaluated critically. Literature was obtained through searching electro-nic databases (e.g., MEDLINE, EMBASE), cross-referencing, and through the authors’ knowledge of the area. Forinclusion in our systematic review articles must have at least 3 levels of physical activity and the concomitant riskfor each chronic disease. The quality of included studies was appraised using a modified Downs and Black tool.Through this search we identified a total of 254 articles that met the eligibility criteria related to premature all-cause mortality (N = 70), cardiovascular disease (N = 49), stroke (N = 25), hypertension (N = 12), colon cancer (N =33), breast cancer (N = 43), type 2 diabetes (N = 20), and osteoporosis (N = 2). Overall, the current literature sup-ports clearly the dose-response relationship between physical activity and the seven chronic conditions identified.Moreover, higher levels of physical activity reduce the risk for premature all-cause mortality. The current Canadianguidelines appear to be appropriate to reduce the risk for the seven chronic conditions identified above andall-cause mortality.IntroductionThere is considerable literature supporting the impor-tance of habitual physical activity in the primary andsecondary prevention of varied chronic conditions[1-16]. Routine physical activity is thought to be of ben-efit for over 25 chronic conditions [17]. Seven chronicdiseases in particular have been associated with a physi-cally inactive lifestyle including coronary artery disease,stroke, hypertension, colon cancer, breast cancer, type 2diabetes (diabetes mellitus) and osteoporosis [18-20].Canada has played a leading role in the developmentof physical activity guidelines for individuals across thelifespan. This includes the development (in 1998) of“Canada’s Physical Activity Guide to Healthy Active Liv-ing” for adults between the ages of 20 and 55 yr [21],which was followed by “Canada’s Physical ActivityGuide to Healthy Active Living for Older Adults” [22],and “Canada’s Physical Activity Guide to Healthy ActiveLiving for Children and Youth” [23]. The adultguidelines (which are now approximately 10 years old)state generally that 20-55 yr adults should accumulate60 min of daily physical activity or 30 min of moderateto vigorous exercise on at least 4 days a week [18,19].We reported recently that Canada’s adult guidelineswere consistent with other international guidelines andwere supported by a compelling body of literature[18,19]. We revealed strong evidence that routine physi-cal activity was effective in the primary prevention of car-diovascular disease, stroke, hypertension, breast cancer,colon cancer, type 2 diabetes and osteoporosis. More-over, physical activity appears to play an important rolein the prevention of obesity and obesity-related co-mor-bidities. However, implicit in the adult guidelines is thebelief that there is a dose-response relationship betweenphysical activity and the associated health benefits. More-over, a central belief in these guidelines and most inter-national physical activity guidelines is that the dose-response relationship is curvilinear with the greatesthealth benefits seen in physically inactive individuals whobecome “more physically active.” In fact, a consistent pat-tern (shown in Figure 1) has been hypothesized, wherein* Correspondence: darrenwb@interchange.ubc.ca1Cardiovascular Physiology and Rehabilitation Laboratory, University of BritishColumbia, Vancouver, CanadaWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39© 2010 Warburton et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.there are marked changes in health status with relativelyminor increments in physical activity/fitness in indivi-duals that are the least active/fit. Generally, the healthbenefits have been thought to level off at the upper endof the physical activity/fitness continuum (Figure 1).However, recent work (such as that provided by Gledhilland Jamnik in the Canadian Physical Activity and Life-style Approach) has speculated that there are likely mul-tiple dose-response curves for various endpoints [24].The primary purpose of this systematic review was toexamine critically the current literature to determinewhether or not a dose-response relationship existsbetween habitual physical activity and chronic disease.In particular, we sought to determine whether the keymessaging “Every little bit counts, but more is even bet-ter - everyone can do it!” of the adult physical activityguidelines is supported by a strong body of evidence.Due to the breadth of literature, we have chosen tofocus on the relationship between physical activity andall-cause mortality, and the seven chronic conditionsthat are thought to be reduced greatly with habitualphysical activity (i.e., cardiovascular disease (excludingstroke), stroke, hypertension, colon cancer, breast can-cer, type 2 diabetes and osteoporosis) (see Table 1).Owing to the nature of the physical activity guidelines,the emphasis of this paper was on primary prevention,despite the clear evidence that routine physical activityis also an effective secondary preventative strategyagainst many chronic conditions [16,18,19]. Accordingly,our primary objectives were to examine the evidence fora dose-response relationship between: 1) physical activ-ity and all-cause mortality, and 2) physical activity andincidence of the following chronic conditions (cardiovas-cular disease (except stroke), stroke, hypertension, type2 diabetes, colon cancer, breast cancer, and osteoporosis.MethodsCriteria for considering studies for this reviewOur research team utilized a rigorous, systematic, andevidence-based approach to examine critically the levelsof evidence on physical activity and the risk for prema-ture mortality and chronic disease. Any studies thatevaluated the relationship between at least three differ-ent levels of physical activity and mortality or incidenceof chronic disease were eligible for inclusion. Therefore,excluded studies included those that examined only themost active versus least active populations (e.g., seden-tary/inactive vs. physically active). Any form of physicalactivity/exercise measurement (e.g., self-report, ped-ometer, accelerometer, maximal aerobic power (VO2max)) was eligible for inclusion. The key outcomes weremortality and incidence of chronic disease. Only pub-lished, English language studies examining adults (e.g.,19-65 yr) were included. Participants must have pre-viously been healthy (asymptomatic) adults withoutestablished chronic disease. There was no restrictionaccording to study design.To examine the relative risk reductions associatedwith physical activity, we calculated the mean and med-ian risk reductions across studies focusing on the high-est level versus the lowest level of physical activity/fitness. For each study we also determined whether ornot a dose-response relationship was present (i.e.,reflecting a progressive decrease in the risk with increas-ing physical activity/fitness levels).Search strategyLiterature searches were conducted in the followingelectronic bibliographical databases:• MEDLINE (1950-March 2008, OVID Interface);• EMBASE (1980- March 2008, OVID Interface),• CINAHL (1982- March 2008, OVID Interface);Inactive/Unfit Active/FitLowRelative Risk of Chronic DiseaseHighFigure 1 Theoretical relationship between the risk for chronicdisease and physical activity/fitness.Table 1 Relative risks (RR) and population attributablerisks (PAR%) for physical inactivity in Canada, Australia,and the USA.Canada Australia USADisease RR PAR% RR PAR% RR PAR%CHD 1.45 19.4 1.5 18 2.0 22Stroke 1.60 24.3 2.0 16 na NaHypertension 1.30 13.8 na na 1.5 12Colon Cancer 1.41 18.0 1.5 19 2.0 22Breast Cancer 1.31 14.2 1.1 9 1.2 5Type 2 Diabetes 1.50 21.1 1.3 13 1.5 12Osteoporosis 1.59 24.0 1.4* 18* 2.0 18*Source: Canadian Data [20]; Australian Data [161]; US Data: [162]. *Evaluatedthe incidence of falls/fractures.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 2 of 220• PsycINFO (1840- March 2008, Scholars PortalInterface);• Cochrane Library (-March 2008),• SPORTDiscus (-March 2008).The Medical Subject Headings (MeSH) were keptbroad. See tables 2, 3, 4, 5, 6, 7, 8 and 9 for the com-plete search strategy and keywords used. The electronicsearch strategies were created and carried out byresearchers experienced with systematic reviews of theliterature (DW and LN). The citations and applicableelectronic versions of the article (where available) weredownloaded to an online research management system(RefWorks, Bethesda, Maryland, USA).ScreeningTwo reviewers (LN and SC) screened independently thetitle and abstract of the citations to identify potentialarticles for inclusion. Duplicate citations were removed.The reviewers were not blinded to the authors or jour-nals. Biographies of key studies and reviews in the fieldwere also cross-referenced for further articles. For thosearticles that appeared relevant, the full text wasobtained and data was extracted using a common tem-plate. In cases of disagreement, discussion with a thirdreviewer (DW) was used to achieve consensus. Full(100%) consensus was achieved. All studies that wereexcluded during the citation and full-article screeningprocesses were recorded along with the reasons forexclusion.Table 2 Results of the MEDLINE literature searchregarding all-cause mortality.# Searches (28 Feb 2008) Results1 exp Physical Fitness/ 152362 Motor Activity/ 497213 exp Physical Endurance/ 153834 exp Exercise/ 577425 exp Exertion/ 889036 exp Sports/ 718877 exp exercise therapy/ 172318 exp exercise tolerance/ 41929 exp health behaviour/ 5940910 leisure time physical activity.mp 99611 occupational physical activity.mp 19012 exp Pliability/ 227913 exp Muscle Strength/ 571714 musc$ power.mp 96515 exp Back/ 1282116 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or12 or 13 or 14 or 1529163517 dose-response.mp 32106618 intensity.mp 14288119 volume.mp 29847120 exp Energy Metabolism/ 20680821 exp oxygen consumption/ 8335222 exp time factors/ 76371223 17 or 18 or 19 or 20 or 21 or 22 165163324 16 and 23 6769825 exp Mortality/ 19005826 all cause mortality.mp 461827 25 or 26 19272028 24 and 27 42129 limit 28 to (english and humans and “all adult (19 plusyears)”)279Table 3 Results of the MEDLINE literature searchregarding cardiovascular disease.Search#Searches (3 Mar 2008) Results1 exp Physical Fitness/ 152442 Motor Activity/ 497513 exp Physical Endurance/ 154084 exp Exercise/ 578065 exp Exertion/ 889676 exp Sports/ 719317 exp exercise therapy/ 172438 exp exercise tolerance/ 42059 exp health behaviour/ 5946710 leisure time physical activity.mp 99811 occupational physical activity.mp 19112 exp Pliability/ 228913 exp Muscle Strength/ 573114 musc$ power.mp 96515 exp Back/ 1282216 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or11 or 12 or 13 or 14 or 1529181717 dose-response.mp 32119818 intensity.mp 14295519 volume.mp 29862020 exp Energy Metabolism/ 20688621 exp oxygen consumption/ 8338722 exp time factors/ 76409123 17 or 18 or 19 or 20 or 21 or 22 165237224 16 and 23 6776025 exp Cardiovascular Diseases/ 141173026 exp Heart diseases/ 67508327 exp Myocardial infarction/ 11607028 exp Death, Sudden Cardiac/ 677229 exp Coronary Artery Disease/ 1813730 exp Coronary Disease/ 14423631 exp Vascular Diseases 101827532 25 or 26 or 27 or 28 or 29 or 30 or 31 141173033 24 and 32 960334 limit 33 to (english language and humans and “alladult (19 plus years)”)5544Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 3 of 220Data ExtractionTwo reviewers (LN and SC) completed standardizeddata extraction forms, which were verified by two otherreviewers (DW and SB). We extracted informationregarding the study design, the country where the studywas conducted, the participant characteristics, the sam-ple size, the objectives of the study, the methodologiesemployed, the major outcomes (i.e., mortality, incidenceof chronic disease, physical activity levels/classifications),and the comments and conclusions made based on thefindings of the study. The reviewers were not blinded tothe journal or the author names when extracting infor-mation from the articles.Level of EvidenceThe approach used to establish the level and grade ofevidence was consistent with that used during creationof the “Canadian clinical practice guidelines on themanagement and prevention of obesity in adults andchildren” [25]. The level of evidence provides informa-tion regarding the strength of the evidence in favour ofphysical activity/exercise in the primary prevention ofpremature mortality and the seven chronic diseases ofprimary interest. This evaluation process is based on apre-defined and objective criteria (see Table 10).The grade for each article provides informationregarding whether physical activity is effective in the pri-mary prevention of the varied conditions evaluated(Table 10). Where applicable this grade informs thereader about the potential risk of the physical activity. Astudy that receives the highest grading would indicateTable 4 Results of the MEDLINE literature searchregarding stroke.Search#Searches (29 Feb 2008) Results1 exp Physical Fitness/ 152412 Motor Activity/ 497443 exp Physical Endurance/ 153874 exp Exercise/ 577645 exp Exertion/ 889216 exp Sports/ 719077 exp exercise therapy/ 172378 exp exercise tolerance/ 41969 exp health behaviour/ 5943010 leisure time physical activity.mp 99611 occupational physical activity.mp 19012 exp Pliability/ 228813 exp Muscle Strength/ 572014 musc$ power.mp 96515 exp Back/ 1282116 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or11 or 12 or 13 or 14 or 1529171817 dose-response.mp 32113318 intensity.mp 14291919 volume.mp 29852620 exp Energy Metabolism/ 20683721 exp oxygen consumption/ 8335922 exp time factors/ 76387123 17 or 18 or 19 or 20 or 21 or 22 165195824 16 and 23 6772025 exp Stroke/ 4524326 exp Cerebrovascular Disorders/ 19624327 exp Brain Ischemia/ 5894328 exp Brain Infarction/ or exp Cerebral Infarction 2135729 exp Infarction, Middle Cerebral Artery/ or expIntracranial Aneurysm/ or exp Subarachnoid4672530 Hemorrhage/ or exp Cerebral Hemorrhage/expIschemic Attack, Transient/1475331 25 or 26 or 27 or 28 or 29 or 30 19624332 24 and 31 69233 limit 32 to (english language and humans and “alladult (19 plus years)”)291Table 5 Results of the MEDLINE literature searchregarding hypertension.Search#Searches (3 Mar 2008) Results1 exp Physical Fitness/ 152442 Motor Activity/ 497513 exp Physical Endurance/ 154084 exp Exercise/ 578065 exp Exertion/ 889676 exp Sports/ 719317 exp exercise therapy/ 172438 exp exercise tolerance/ 42059 exp health behaviour/ 5946710 leisure time physical activity.mp 99811 occupational physical activity.mp 19112 exp Pliability/ 228913 exp Muscle Strength/ 573114 musc$ power.mp 96515 exp Back/ 1282216 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or11 or 12 or 13 or 14 or 1529181717 dose-response.mp 321198718 intensity.mp 14295519 volume.mp 29862020 exp Energy Metabolism/ 20688621 exp oxygen consumption/ 8338722 exp time factors/ 76409123 17 or 18 or 19 or 20 or 21 or 22 165237224 exp Hypertension/ 16846625 exp Blood Pressure/ 20557126 exp Blood Pressure Determination/ or exp BloodPressure Monitoring, Ambulatory/ or exp Blood1824427 Pressure Monitors/24 or 25 or 26 33602528 16 and 23 and 27 564729 limit 28 to (english language and humans and “alladult (19 plus years)”)3642Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 4 of 220that the benefits clearly outweigh the risks and receive astrong recommendation.Quality AssessmentThe quality of each study was also established using theprocedures of Gorber et al. [26]. Owing to the fact thatonly observational study designs were included in oursystematic review, we used the Downs and Black [27]scale to assess the quality of non-randomized investiga-tions. Similar to the work of Prince et al. [28] we choseto include the most relevant components of the scoringtool. Therefore, a modified version of the Downs andBlack checklist was used with the final checklist consist-ing of 15 items with a maximum score of 15 points.Higher points reflected a superior quality ofinvestigation.ResultsPhysical Inactivity and All-Cause MortalityA total of 2040 citations were identified during the elec-tronic database search (Figure 2). Of these citations, 288were identified in MEDLINE, 222 in EMBASE, 496 inCochrane, and 1034 in the CINAHL/SportDiscus/Psy-chInfo search. A total of 167 duplicates were found,leaving a total of 1873 unique citations. A total of 1696articles were excluded after scanning, leaving a total of177 articles for full review. From these articles 130 wereexcluded after full review leaving 47 articles for inclu-sion in the systematic review. An additional 23 articleswere added to the review based on the authors’ knowl-edge of the area. The reasons for exclusion includedreview articles (n = 26), commentary (n = 10), did notreport 3 levels of physical activity (n = 24), no objectivemeasure of physical activity (n = 2), report (n = 15), nota formal study (n = 11), not related to all-cause mortal-ity (n = 27), the participants were too young (n = 1),not able to retrieve articles (n = 7), and other (n = 7).Therefore, a total of 70 articles were included in theTable 6 Results of the MEDLINE literature searchregarding colon cancer.Search#Searches (3 Mar 2008) Results1 exp Physical Fitness/ 152442 Motor Activity/ 497513 exp Physical Endurance/ 154084 exp Exercise/ 578065 exp Exertion/ 889676 exp Sports/ 719317 exp exercise therapy/ 172438 exp exercise tolerance/ 42059 exp health behaviour/ 5946710 leisure time physical activity.mp 99811 occupational physical activity.mp 19112 exp Pliability/ 228913 exp Muscle Strength/ 573114 musc$ power.mp 96515 exp Back/ 1282216 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or11 or 12 or 13 or 14 or 1529181717 dose-response.mp 32119818 intensity.mp 14295519 volume.mp 29862020 exp Energy Metabolism/ 20688621 exp oxygen consumption/ 8338722 exp time factors/ 76409123 17 or 18 or 19 or 20 or 21 or 22 165237224 exp Colonic Neoplams/ 5178025 exp Rectal Neoplasms/ 2801126 exp Colorectal Neoplasms/ 9998227 exp Colorectal Neoplasms/, HereditaryNonpolyposis/ or exp Intestinal Neoplasms.11756328 24 or 25 or 26 or 27 11756329 16 and 23 and 28 10830 limit 29 to (53nglish language and humans and “alladult (19 plus years)”)77Table 7 Results of the MEDLINE literature searchregarding breast cancer.Search#Searches (28 Feb 2008) Results1 exp Physical Fitness/ 152362 Motor Activity/ 497213 exp Physical Endurance/ 153834 exp Exercise/ 577425 exp Exertion/ 889036 exp Sports/ 718877 exp exercise therapy/ 172318 exp exercise tolerance/ 41929 exp health behaviour/ 5940910 leisure time physical activity.mp 99611 occupational physical activity.mp 19012 exp Pliability/ 227913 exp Muscle Strength/ 571714 musc$ power.mp 96515 exp Back/ 1282116 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or11 or 12 or 13 or 14 or 1529163517 dose-response.mp 32106618 intensity.mp 14288119 volume.mp 29847120 exp Energy Metabolism/ 20680821 exp oxygen consumption/ 8335222 exp time factors/ 76371223 17 or 18 or 19 or 20 or 21 or 22 165163324 exp Breast Neoplasms/ 14981725 16 and 23 and 24 29626 limit 25 to (54 nglish language and humans and “alladult (19 plus years)”216Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 5 of 220systematic review of the literature regarding the rela-tionship between physical activity and prematuremortality.The majority of the studies included in our systematicreview were prospective cohort investigations (Table11). These studies involved a total of 1,525,377 partici-pants; averaging 21,791 participants per study (range302-252,925). There were a total of 111,125 reportedcases of premature all-cause mortality (ranging perstudy from 43-10,952). The total length of study follow-up for the prospective cohort studies averaged 11.1 yr(ranging from 0.5-28 yr). The articles were publishedover a 22 yr period ranging from 1985 to 2007. Thesestudies involved large samples of men and women fromregions throughout the world.We observed a mean 31% lower risk for all-cause mortal-ity in the most active individuals. The median risk reduc-tion was 32%. It is important to highlight that many ofthese studies included women, with sub-analyses thatrevealed similar risk reductions between sexes. Our find-ings are consistent with previous reports [15,16,29-31]. Themajority (90%) of the studies supported the health benefitsof physical activity demonstrating a significant risk reduc-tion in physically active individuals. The level of evidencewould be considered to be a Level 2A based on the presenceof overwhelming evidence from observational trials. Thestudies examined were generally of a good quality with amean (and median) score of 12 out of 15 (range 10-14).Table 8 Results of the MEDLINE literature searchregarding type 2 diabetes.Search#Searches (29 Feb 2008) Results1 exp Physical Fitness/ 152412 Motor Activity/ 497443 exp Physical Endurance/ 153874 exp Exercise/ 577645 exp Exertion/ 889216 exp Sports/ 719077 exp exercise therapy/ 172378 exp exercise tolerance/ 41969 exp health behaviour/ 5943010 leisure time physical activity.mp 99611 occupational physical activity.mp 19012 exp Pliability/ 228813 exp Muscle Strength/ 572014 musc$ power.mp 96515 exp Back/ 1282116 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or10 or 11 or 12 or 13 or 14 or 1529171817 dose-response.mp 32113318 intensity.mp 14291919 volume.mp 29852620 exp Energy Metabolism/ 20683721 exp oxygen consumption/ 8335922 exp time factors/ 76387123 17 or 18 or 19 or 20 or 21 or 22 165195824 16 and 23 6772025 exp Blood Glucose/or exp Diabetes Mellitus, Type 2/ 13258326 exp Hyperglycemia/ 1621427 exp Glucose Intolerance/ or exp Glucose ToleranceTest/2498628 exp Hyperinsulinism/ 3049029 25 or 26 or 27 or 28 16515730 29 and 24 300631 Limit 30 to (english language and humans and “alladult (19 plus years)”)1985Table 9 Results of the MEDLINE literature searchregarding osteoporosis.Search#Searches (29 feb 2008) Results1 exp Physical Fitness/ 152412 Motor Activity/ 497443 exp Physical Endurance/ 153874 exp Exercise/ 577645 exp Exertion/ 889216 exp Sports/ 719077 exp exercise therapy/ 172378 exp exercise tolerance/ 41969 exp health behaviour/ 5943010 leisure time physical activity.mp 99611 occupational physical activity.mp 19012 exp Pliability/ 228813 exp Muscle Strength/ 572014 musc$ power.mp 96515 exp Back/ 1282116 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or10 or 11 or 12 or 13 or 14 or 1529171817 dose-response.mp 32113318 intensity.mp 14291919 volume.mp 29852620 exp Energy Metabolism/ 20683721 exp oxygen consumption/ 8335922 exp time factors/ 76387123 17 or 18 or 19 or 20 or 21 or 22 165195824 exp Osteoporosis, Postmenopausal/ or expOsteoporosis/3153225 exp Fractures, Bone/ or exp Bone Density/ 12526926 exp Bone Diseases/ or exp Bone Diseases,Metabolic/30808427 exp “Bone and bones"/ 36963428 exp Tensile Strength/ 1205029 exp Compressive Strength 283830 24 or 25 or 26 or 27 or 28 or 29 64215831 16 and 23 and 30 213832 limit 31 to (english language and humans and “alladult (19 plus years)”)1193Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 6 of 220A clear dose-response relationship was also observedwith marked reductions in the risk for all-cause mortal-ity occurring with relatively small increments in physicalactivity (Figure 3). To examine more closely the tem-poral relationship between physical activity and all-causemortality we calculated the (unadjusted) relative risksassociated with incremental levels of physical activity/fit-ness using the reported cases of all-cause mortality andthe number of participants (per group) in each investi-gation. In some instances, we were required to calculatethe number of participants based on the reported inci-dence rates and person years, or based on data obtaineddirectly from the authors (2 investigations). We werenot able to obtain this information in 18 investigations,and as such this analysis was restricted to the remaining52 investigations. There was considerable variability inthe methods of classifying the physical activity/fitnesslevels of the participants. Accordingly, Figure 3 illus-trates the mean relative risk reduction according tothree separate study types including those that subdi-vided participants into tertiles, quartiles and quintiles,respectively. This figure demonstrates clearly the dose-response relationship between physical activity and all-cause mortality. Collectively, the literature is consistentindicating that the current Canadian guidelines(approximately 4.2 MJ/wk, 1000 kcal/wk) are associatedwith a 20-30% lower risk for premature all-cause mor-tality, with greater health benefits with high volumesand/or intensities of activity. In our analyses it wasapparent that the greatest differences in risk occurredbetween the lowest adjacent activity/fitness categories,suggesting that sedentary individuals can markedlyreduce their risk for all-cause mortality with relativelyminor increments in physical activity. This is consistentwith the current messaging of Canada’s physical activityguidelines.The strength of the relationship between physical fit-ness and premature mortality has been well-established[6,32,33]. In our analyses there were greater risk reduc-tions in studies that took objective measures of physicalfitness. We observed an average risk reduction ofapproximately 45%, which was consistent between menand women. A risk reduction of greater than 50% wasnot uncommon in these studies. For instance, Myerset al. (2004) reported that being fit or physically activewas associated with greater than 50% lower mortalityrisk in men. They also noted that a 4.2 MJ/wk (1000kcal/wk) increase in physical activity, or a 1 metabolicequivalent (MET) higher physical fitness level was asso-ciated with a mortality benefit of around 20%. It is alsoimportant to highlight that longitudinal studies evaluat-ing changes in physical activity or fitness have revealed alower premature mortality risk [16,34-41]. As we pre-viously reported, routine physical activity or elevatedphysical fitness also appears to reduce the risk for pre-mature mortality in individuals with risk factors forchronic disease [42,43].ImplicationsSince the seminal work of Morris and colleagues (in the1950s [44,45]) and the early work of Paffenbarger (inthe 1970s [46,47]) there has been considerable research(especially epidemiological evidence) documenting thehealth benefits of engaging in routine physical activityand/or being physically fit [17,48]. Both physical activityTable 10 The levels and grade of evidence scaling criteria applied to the articles.Level of Evidence CriteriaLevel 1 Randomized control trials without important limitationsLevel 2 • Randomized control trials with important limitations• Observational studies (non-randomized clinical trials or cohort studies) with overwhelming evidenceLevel 3 Other observational studies (prospective cohort studies, case-control studies, case series)Level 4 Inadequate or no data in population of interestAnecdotal evidence or clinical experienceGrade of Evidence CriteriaGrade A Strong recommendation (action can apply to most individuals in most circumstances)• Benefits clearly outweigh risks (or vice-versa)• Evidence is at Level 1, 2, or 3Grade B Weak recommendation (action may differ depending on individual’s characteristics or other circumstances)• Unclear if benefits outweigh risks• Evidence is at Level 1, 2, or 3Grade C Consensus recommendation (alternative actions may be equally reasonable)• Unclear if benefits outweigh risks• Evidence is at Level 3 or 4Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 7 of 220(a behaviour) and physical fitness (an attained state)appear to be related to health status in a dose-depen-dent fashion, with physical fitness demonstrating thestrongest relationship [18,19]. Numerous reports indi-cate that physical inactivity and/or low physical fitnessare associated with an increased risk for chronic diseaseand premature all-cause and disease-specific mortality[2,43,49-51]. Some of the most compelling researchincludes the relationship between physical activity/fitness and all-cause mortality. As demonstrated belowand in Table 11 and Figure 1, this literature is extensive.The assessment of the relationship between all-causemortality is complicated by the inclusion of deathsrelated to suicides, homicide, and accidents [18,19,52].Nonetheless, the available evidence is incontrovertible;individuals who are habitually physically active and/orphysically fit are at a markedly reduced risk for prema-ture all-cause mortality [15,16,18,19]. In Canada, physi-cal inactivity is a major cause of premature mortalityfrom diseases of the cardiovascular system (33.3%), can-cers (29.1%), and type 2 diabetes (3.5%) [53]. Globally,physical inactivity has been linked with 2 million prema-ture deaths per year, including 22% of cases of coronaryheart disease, and 10-16% of cases of breast cancer,colon cancer, rectal cancer and type 2 diabetes [54]. Assuch, the promotion of the health benefits of physicalactivity is of paramount importance for the effectiveprevention of chronic disease and premature mortalityon a national and international scale.In summary, there is a clear dose-response relation-ship between physical activity and premature all-causemortality. Physically active individuals have an approxi-mate risk reduction of 31% in comparison to physicallyinactive individuals. When objective measures of aerobicfitness are taken the risk reductions are even greaterapproximating 45%.Recommendation #1For a reduced risk for premature mortality, it isrecommended that individuals should participate in30 min or more of moderate to vigorous exercise onmost days of the week. Greater health benefits appearto occur with higher volumes and/or intensities ofactivity. [Level 2, Grade A]Primary Prevention of Cardiovascular DiseaseIn our systematic search of the literature, a total of 9408citations were identified during the electronic databasesearch (Figure 4). Of these citations, 5973 were identi-fied in MEDLINE, 2561 in EMBASE, 193 in Cochrane,and 681 in the CINAHL/SportDiscus/PsychInfo search.A total of 923 duplicates were found, leaving a total of8485 unique citations. A total of 8138 articles wereexcluded after scanning, leaving a total of 347 articlesfor full review. An additional 20 articles were addedthrough cross-referencing. From these articles 319 wereexcluded after full review leaving 33 articles for inclu-sion in the systematic review. The reasons for exclusionincluded non-experimental studies (n = 45), only effecton cardiovascular disease risk factors (n = 115), did notreport 3 levels of physical activity (n = 12), subjects lessthan 18 yr of age (n = 4), reviews, summaries, disserta-tions, thesis, and abstracts (n = 30), clinical population(n = 14), not on cardiovascular disease or did not fitFigure 2 Results of the Literature Search for All-CauseMortality.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 8 of 220Table11Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsBlairetal1989[7]Tostudyphysicalfitness(PF)andriskofall-causemortalityinmenandwomen.•n=13,344(10,224men;3,120women)Baselineand8yearfollow-up•283deathsLowlevelsofPFincreasetheriskforprematuremortality.•Sex:MenandwomenAdjustedriskratio(RR),95%confidenceinterval(CI)USA•Age:20->60years(yr)PFassessment:Maximaltreadmillexercisetest.Prospectivecohort•Characteristics:ParticipantsweregivenapreventativeMedicineexaminationincludingmaximaltreadmillexercisetestFitnesscategorizedintoquintiles:MenD&Bscore=12Q1=leastfit•Q1=3.44(2.05-5.77)Q2•Q2=1.37(0.76-2.50)Q3•Q3=1.46(0.81-2.63)Q4•Q4=1.17(0.63-2.17)Q5=mostfit•Q5=1.00(referent)Women •Q1=4.65(2.22-9.75)•Q2=2.42(1.09-5.37)•Q3=1.43(0.60-3.44)•Q4=0.76(0.27-2.11)•Q5=1.00(referent)Myersetal2004[32]TodeterminetheeffectsofPFandphysicalactivity(PA)onall-causemortality.•n=6,213Baselineandmean5.5±2.0yearfollow-Up•1,256deathsBeingfitoractiveisassociatedwith>50%reductionsinmortalityrisk.•Sex:MenUSA•Age:Mean59.0±11.2yrPFLevelhazardratio(HR)(95%CI)•Characteristics:MenreferredforexercisetestingPFassessment:TreadmilltesttomeasureVO2peak•G1=1.00(referent)PFpredictedmortalitymorestronglythanPA.Prospectivecohort•G2=0.59(0.52-0.68)•G3=0.46(0.39-0.55)•G4=0.28(0.23-0.34)IncreasingPA(by1000kcal/wkor1MET)confersamortalitybenefitof20%.D&Bscore=12PAassessment:SelfreportedPAdividedinto4groupsPALevelHR(95%CI)G1=Lowestlevel•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 9 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)G2•G2=0.63(0.36-1.10)G3•G3=0.42(0.23-0.78)G4=Highestlevel•G4=0.38(0.19-0.73)Blairetal1995[36]ToevaluatetherelationshipbetweenchangesinPFandriskofmortalityinmen.•n=9,7774.9yearmeanfollow-up•223deathsMenwhomaintainedorincreasedadequatePFhadareducedriskforall-causemortalitythanindividualswhowereconsistentlyunfit.•Sex:Men•Age:20-82yrRR(95%CI)USA•Characteristics:ParticipantsweregivenapreventativemedicineexaminationincludingmaximaltreadmillexercisetestPFassessment:Maximalexercisetestatbaselineandfollow-up•G1=1.00(referent)Prospectivecohort•G2=0.56(0.41-0.75)•G3=0.52(0.38-0.70)•G4=0.33(0.23-0.47)D&Bscore=13GroupsbasedonchangesinPFG1=unfittounfitG2=unfittofitG3=fittounfitG4=fittofitBijnenetal1999[37]ToexaminetheassociationofPAatbaselineand5years•n=4721985and1990•118deathsRecentlevelsofPAweremoreimportantformortalityriskthanPA5yearspreviously.•Sex:Men•Age:>65yrPAassessment:Questionnaire,dividedintotertiles:LowestMiddleHighestMultivariateadjustedRR(95%CI)Netherlandspreviouslywithall-causemortalityriskinacohortofelderlyDutchmen.•Characteristics:Mostlyindependentlylivingelders(~95%)PAin1985:Lowesttertile=1.00(referent)MiddletertileRetrospectivecohort•ZutphenElderlyStudy•Totalactivity=1.25(0.79-1.99)Becomingorremainingsedentaryincreasedthemortalityrisk.D&Bscore=12•Walking=0.97(0.60-1.57)•Bike=0.97(0.59-1.57)•Gardening=0.66(0.39-1.10)•Other=1.08(0.66-1.78)•Heavyactivity=0.73(0.45-1.17)•Nonheavyactivity=0.89(0.57-1.40)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 10 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) Highesttertile•Totalactivity=1.25(0.73-2.12)•Walking=0.94(0.58-1.55)•Bike=1.07(0.61-1.88)•Gardening=0.77(0.42-1.39)•Other=1.24(0.74-2.07)•Heavyactivity=0.76(0.44-1.32)•Nonheavyactivity=0.94(0.58-1.53)PAin1990:Lowesttertile=1.00(referent)Middletertile•Totalactivity=0.56(0.35-0.89)•Walking=0.82(0.51-1.32)•Bike=0.49(0.29-0.82)•Gardening=1.67(1.00-2.79)•Other=0.93(0.53-1.65)•Heavyactivity=1.19(0.73-1.92)•Nonheavyactivity=0.61(0.38-0.99)Highesttertile•Totalactivity=0.44(0.25-0.80)•Walking=1.17(0.70-1.96)•Bike=0.43(0.23-0.80)•Gardening=1.03(0.55-1.94)•Other=0.74(0.44-1.23)•Heavyactivity=0.72(0.40-1.31)•Nonheavyactivity=0.65(0.40-1.05)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 11 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Greggetal2003[39]ToexaminetherelationshipofchangesinPAandmortalityamongolderwomen.•n=9,518Baseline(1986-1988)andmedian10.6yearfollow-up(1992-1994)•2,218deathsIncreasingandmaintainingPAlevelscouldlengthenlifeforolderwomenbutappearstoprovidelessbenefitforwomenagedatleast75yearsandthosewithpoorhealthstatus.•Sex:WomenPAAssessment:Questionnaire,dividedintoquintilesofPA(kcal/wk)•Age:≥65yrMultivariateadjustedHRRUSA•Characteristics:Whitecommunitydwellingparticipantsfrom4USresearchcentres(95%CI):QuintilesoftotalQ1=<163PAProspectivecohortQ2=163-503•Q1=1.00(referent)Q3=504-1045•Q2=0.73(0.64-0.82)Q4=1046-1906•Q3=0.77(0.68-0.87)D&Bscore=13Q5=≥1907•Q4=0.62(0.54-0.71)•Q5=0.68(0.59-0.78)WalkingHRR(95%CI)•Q1=1.00(referent)Quintilesofwalking(kcal/wk)•Q2=0.91(0.81-1.02)Q1=<70•Q3=0.78(0.68-0.88)Q2=70-186•Q4=0.71(0.63-0.82)Q3=187-419•Q5=0.71(0.62-0.82)Q4=420-897Q5=898MultivariateadjustedHRR(95%CI)Changeinactivitylevel:Sedentaryatbaseline•Stayingsedentary=1.00(referent)•Becameactive=0.52(0.40-0.69)Mod/highactiveatbaseline•Becamesedentary=0.92(0.77-1.09)•Stayedactive=0.68(0.56-0.82)Wannametheeetal1998[40]Tostudytherelationshipbetweenheartrate,PAandall-causemortality.•n=5,934Baseline(1978-1980)and12-14yearfollow-up•219deathsMaintainingortakinguplightormoderatePAreducesmortalityinoldermen.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 12 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•Sex:Men•Age:Mean63yrMultivariateadjustedRR(95%CI),UK•Characteristics:Healthy,sedentary(4,311wereconsidered“healthy”in1992)PAassessment:Questionnaire,splitintogroupsPAProspectivecohort•TheBritishRegionalHeartStudy•G1=1.00(referent)•G2=0.61(0.43-0.86)•G3=0.50(0.31-0.79)D&Bscore=12PAscore•G4=0.65(0.45-0.94)G1=Inactive/occasionalRegularwalkingG2=Light•G1=1.00(referent)G3=Moderate•G2=1.15(0.73-1.79)G4=Moderately•G3=1.06(0.75-1.50)vigorous/Vigorous•G4=0.97(0.65-1.46)Regularwalking(min/d)•G5=0.62(0.37-1.05)G1=0RecreationalactivityG2=<20•G1=1.00(referent)G3=21-40•G2=0.95(0.43-1.07)G4=41-60•G3=0.68(0.43-1.07)G5=≥60•G4=0.34(0.35-1.00)Recreationalactivity,4groupsSportingactivityG1=Inactive/fairlyInactive•G1=1.00(referent)G2=Average4hr/weekend•G2=0.50(0.25-1.03)G3=Fairlyactive>4h/weekend•G3=0.88(0.64-1.23)G4=VeryactiveSportingactivity,3GroupsG1=NoneG2=OccasionalG3=>1time/monthPaffenbargeretal1986[63]ToexaminethePAandlife-stylecharacteristicsofHarvardalumnifortherelationshipwithall-causemortality.•n=16,93612-16yearfollow-up(1962to1978)•1,413deathsThefindingssuggestaprotectiveeffectofexerciseagainstall-causemortality.•Sex:MenAgeadjustedRR(95%CI):•Age:35-74USA•Characteristics:HarvardalumniRecordsoffreshmanyearphysicalexaminationsandrecordsofintercollegiatesportThosewhowalkedProspectivecohort•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 13 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•G2=0.85•G3=0.79D&Bscore=14Trendp=0.0009PAassessment:MailedquestionnairessurveyingpostcollegePhysicalActivityIndex(95%CI):PA•G1=1.00(referent)•G2=0.78•G3=0.73•G4=0.63Exercisereported:Walking(miles/wk)3•G5=0.62groups•G6=0.52G1=<3•G7=0.46G2=3-8•G8=0.62G3=≥9Trendp=<0.0001PAindex(kcal/wk)3groups:G1=<500G2=500-999G3=1000-1499G4=1500-1999G5=2000-2499G6=2500-2999G7=3000-3499G8=>3500CoxproportionalhazardmodelsSchnohretal2007[64]Todeterminetheimpactofwalkingdurationandintensityonall-causemortality.•n=7,308(3,204male;4,104female)Baselineandanaverageof12year•1,391deathsThefindingsindicatethattherelativeintensityandnotdurationofwalkingisthemostimportantinrelationtoall-causemortality.Denmark•Sex:Maleandfemalefollow-upMultivariateadjustedHR(95%CI):•Age:20-93yrPAassessment:Questionnaire,4durationsand3intensitiesProspectivecohort•Characteristics:ParticipantswithnohistoryofCHD,strokeorcancerandwhohadnodifficultyinwalkingMenD&Bscore=12•TheCopenhagenCityHeartStudy•G1=1.00(referent)•G2=0.38(0.25-0.58)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 14 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•G3=0.38(0.18-0.79)Duration(hours/day)•G4=0.69(0.44-1.07)1=<0.5•G5=0.37(0.26-0.54)2=0.5-1•G6=0.33(0.18-0.61)3=1-2•G7=0.78(0.50-1.23)4=>2•G8=0.41(0.29-0.59)•G9=0.33(0.20-0.54)Intensity•G10=0.43(0.22-0.82)Slowintensity(SI)•G11=0.42(0.29-0.60)Averageintensity(AI)•G12=0.28(0.16-0.48)Fastintensity(FI)Women12groups•G1=1.00(referent)G1=1andSI•G2=0.82(0.52-1.29)G2=1andAI•G3=0.78(0.27-2.21)G3=1andFI•G4=1.22(0.82-1.81)G4=2andSI•G5=0.74(0.52-1.05)G5=2andAI•G6=0.56(0.33-0.96)G6=2andFI•G7=0.94(0.60-1.47)G7=3andSI•G8=0.87(0.61-1.23)G8=3andAI•G9=0.48(0.28-0.83)G9=3andFI•G10=0.88(0.40-1.88)G10=4andSI•G11=0.64(0.44-0.95)G11=4andAI•G12=0.38(0.21-0.69)G12=4andFIKushietal1997[65]ToevaluatetheassociationbetweenPAandall-causemortalityinpostmenopausalwomen.•n=40,4177yearfollow-up•2,260deathsTheresultsdemonstrateagradedinverseassociationbetweenPAandall-causemortalityinpostmenopausalwomen.•Sex:Women•Age:55-69yrPAassessment:QuestionnaireforfrequencyofmoderateandvigorousLTPAMultivariateadjustedFrequencyofmoderatePAperweekRR(95%CI):USA•Characteristics:PostmenopausalIowawomenProspectivecohort•G1=1.00(referent)•G2=0.71(0.63-0.79)D&Bscore=13Dividedbyfrequency/week•G3=0.63(0.56-0.71)•G4=0.59(0.51-0.67)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 15 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)G1=Rarely/neverTrendp=<0.001G2=1time/weektoafewtimes/monthFrequencyofvigorousPAperweekG3=2-4times/weekG4=>4times/week•G1=1.00(referent)•G2=0.83(0.69-0.99)•G3=0.74(0.59-0.93)Activityindex•G4=0.62(0.42-0.90)G1=LowTrendp=0.009G2=MediumG3=High•G1=1.00(referent)•G2=0.77(0.69-0.86)•G3=0.68(0.60-0.77)Trendp=<0.001Paffenbargeretal1993[67]ToanalyzechangesinthelifestylesofHarvardCollegealumniandtheassociationofthesechangeswithmortality.•n=10,269Baseline(1977)and8yearfollow-up(1985)•476deathsBeginningmoderatelyvigoroussportsactivitywasassociatedwithlowerratesofdeathfromallcausesamongmiddleagedandoldermen.•Sex:Men•Age:45-84yr(in1977)Beginningmoderatesportsactivitywasassociatedwith23%lowerriskofdeath(95%CI4%-42%,p=0.015)thanthosenottakingupmoderateactivityUSA•Characteristics:Participantswithnoreportedlife-threateningdiseasePAAssessment:Questionnaire–blockswalkeddaily,stairsclimbeddailyandtype,frequencyanddurationofweeklysportsandrecreationalactivitiesProspectivecohortD&Bscore=13Physicalactivityindex(kcal/wk)SportsandrecreationalactivitiesLight<4.5METsModerate>4.5METsWeeklylistsofdeathswereobtainedfromtheHarvardcollegealumniofficeWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 16 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)ProportionalhazardmodelswithPoissonregressionmethodsKatzmarzykandCraig2002[154]Toquantifytherelationshipbetweenmusculoskeletalfitnessandall-causemortality.•n=8,116(3,933male;4,183female)Baseline(1981)and•238deathsSomecomponentsofmusculoskeletalfitnessarepredictiveofmortality.13yearfollow-up•Sex:MenandwomenRR(95%CI)adjustedforage,smokingstatus,bodymassandVO2maxCanadaMusculoskeletalfitness(situps,pushups,gripstrength,sitandreach)measuresdividedintoquartiles•Age:20-69yrQ1=lowestSitupsProspectivecohort•Characteristics:ParticipantswhohadmusculoskeletalfitnessmeasurementstakenQ2MenQ3•Q1=2.72(1.56-4.64)Q4=highest•Q2=1.32(0.73-2.41)D&Bscore=11•Q3=1.61(0.90-2.87)•Q4=1.00(referent)•CanadianFitnessSurveyCoxproportionalhazardratiomodelWomen•Q1=2.26(1.15-4.43)•Q2=2.24(1.07-4.67)•Q3=1.27(0.59-2.72)•Q4=1.00(referent)Push-upsMen•Q1=1.25(0.77-2.05)•Q2=1.17(0.71-1.90)•Q3=0.94(0.55-1.62)•Q4=1.00(referent)Women•Q1=0.61(0.32-1.17)•Q2=0.81(0.45-1.47)•Q3=0.87(0.48-1.58)•Q4=1.00(referent)Gripstrength(kg)Men•Q1=1.49(0.86-2.59)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 17 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •Q2=1.42(0.82-2.45)•Q3=1.59(0.95-2.68)•Q4=1.00(referent)Women•Q1=1.08(0.58-1.99)•Q2=0.62(0.44-1.56)•Q3=1.25(0.70-2.23)•Q4=1.00(referent)Sitandreach(cm)Men•Q1=1.06(0.64-1.74)•Q2=1.01(0.61-1.66)•Q3=1.20(0.74-1.95)•Q4=1.00(referent)Women•Q1=1.18(0.66-2.10)•Q2=1.07(0.60-1.91)•Q3=0.77(0.44-1.46)•Q4=1.00(referent)Andersenetal2000[163]ToevaluatetherelationshipbetweenlevelsofOPA,LTPA,cyclingtoworkandsportsparticipationandall-causemortality.•n=30,640(17,265men;13,375women)14.5yearfollow-up•8,549deathsLTPAwasinverselyassociatedwithall-causemortalityinbothmenandwomeninallagegroups.PAassessment:QuestionnaireforLTPA,dividedinto:Incidenceofall-causemortalityandPADenmark•Sex:MenandwomenProspectivecohort•Age:20-93years(yr)MultivariateadjustedRR(95%CI)G1=Low•Characteristics:ParticipantsoftheCopenhagenCityHeartStudy,GlostrupPopulationStudyandCopenhagenMaleStudyG2=ModerateD&Bscore=13G3=HighAge20-44yrMen•G1=1.00(referent)•G2=0.73(0.56-0.96)•G3=0.74(0.55-1.01)Women•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 18 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •G2=0.75(0.54-1.04)•G3=0.66(0.42-1.05)Age45-64yrMen•G1=1.00(referent)•G2=0.75(0.67-0.84)•G3=0.75(0.67-0.85)Women•G1=1.00(referent)•G2=0.73(0.65-0.83)•G3=0.66(0.56-0.77)Age>65yrMen•G1=1.00(referent)•G2=0.62(0.53-0.73)•G3=0.60(0.50-0.72)Women•G1=1.00(referent)•G2=0.52(0.45-0.61)•G3=0.49(0.39-0.61)AllagegroupsMen•G1=1.00(referent)•G2=0.72(0.66-0.78)•G3=0.71(0.65-0.78)Women•G1=1.00(referent)•G2=0.65(0.60-0.71)•G3=0.59(0.52-0.67)Barengoetal2004[164]ToinvestigatewhethermoderateorhighLTPAareassociatedwithreducedCVDandall-causemortality,independentofCVDriskfactorsandotherformsofPAinmenandwomen.•n=31,677(15,853men;16,824women)20yearfollow-upHRR(95%CI)ModerateandhighlevelsofLTPAandOPAareassociatedwithreducedprematureall-causemortality.•Sex:MenandwomenPAassessment:QuestionnaireselfadministeredtomeasureOPA,LTPAandcommutingactivityLTPAFinland•Age:30-59yr•1.00(referent)=low•Characteristics:Participantsfromeasternandsouth-westernFinland•0.91(0.84-0.98)=mod,MenWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 19 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Prospectivecohort•0.79(0.70-0.90)=high,MenD&Bscore=14•0.89(0.81-0.98)=mod,women•0.98(0.83-1.16)=high,womenOPA•1.00(referent)=low•0.75(0.68-0.83)=mod,men•0.77(0.71-0.84)=active,men•0.79(0.70-0.89)=mod,women•0.78(0.70-0.87)=active,womenBath2003[165]Toexaminedifferencesbetweenoldermenandwomenontheself-ratedhealthmortalityrelationship.•n=1,042(406men;636womenatbaseline)Baseline,4and12yearspostNumberofdeaths:At4years242(106men;136women)Theself-ratedhealth-mortalityrelationshipcanbeexplainedbyhealthandrelatedfactorsamongoldermenandwomen.UK•Sex:Menandwomen•At12years665(287men;378women)Prospectivecohort•Age:>65yr•Characteristics:Community-dwellingElderlyGeneralphysicalhealth14-itemhealthindex(Ebrahinetal1987)scoringfrom0-14(nohealthproblems–multiplehealthproblems)MultivariateadjustedHR(95%CI)D&Bscore=11•TheNottinghamLongitudinalStudyofActivityandAgeingMenafter4years•High=1.00(referent)•Med=1.19(0.61-2.33)PAassessment:Self-ratedhealthsurveys,dividedinto3levelsofPA:•Low=1.51(0.75-3.03)HighWomenafter4yearsMedium•High=1.00(referent)Low•Med=1.03(0.58-1.82)•Low=1.51(0.86-2.67)Menafter12yearsWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 20 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)CoxproportionalhazardsregressionModels•High=1.00(referent)•Med=1.28(0.94-1.74)•Low=1.13(0.82-1.55)Womenafter12years•High=1.00(referent)•Med=1.20(0.90-1.61)•Low=1.23(0.93-1.62)Bijnenetal1998[166]TodescribetheassociationbetweenPAandmortality(CVD,stroke,all-cause)inelderlymen.•n=80210yearfollow-up•373deathsPAmayprotectagainstall-causemortalityinelderlymen•Sex:Men•Age:64-84yrPAassessment:Questionnaire,dividedintogroups:MultivariateadjustedRR(95%CI)Netherlands•Characteristics:RetiredDutchmen•G1=1.00(referent)ProspectivecohortG1=Lowest•G2=0.80(0.63-1.02)G2=Middle•G3=0.77(0.59-1.00)G3=Highestp=0.04D&Bscore=12Blairetal1993[167]Toevaluatetherelationshipofsedentarylivinghabitstoall-causemortalityinwomen.•n=3,120Baselineand8yearfollow-up•43deathsThereisagradedinverserelationshipbetweenPFandall-causemortalityinwomen.•Sex:Women•Age:NotavailableAgeadjusteddeathrates(per10,000personyears)byfitnessUSA•Characteristics:ParticipantsweregivenapreventativemedicineexaminationPFassessment:PFmeasuredviamaximaltreadmillexercisetest;Prospective•LowFitness=40ThelackofrelationshipbetweenPAanddeathratewasbelievedtobeduetoaninadequateassessmentofPA.•ModFitness=16D&Bscore=14•HighFitness=7PAassessment:QuestionnaireNodifferencebetweenlevelsofPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 21 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Blairetal1996[168]ToreviewtheassociationofPFtoall-causeandCVDmortality.•n=32,421(25,341men;7,080women)Baselineandaverage8yearfollow-up(range0.1-19.1years)•601deathsinmenThestudyobservedasteepinversegradientofdeathratesacrosslow,moderateandhighPFlevels.Theassociationwasstrongandremainedafteradjustmentforpotentialconfoundingfactors.•89deathsinwomen•Sex:MenandwomenUSA•Age:20-80yr(mean43yr)RR(95%CI)inlowPFvs.PFassessment:Treadmilltest;durationwasusedtoassignparticipantstosexspecificgroups:highPFProspectivecohort•Characteristics:Participantswereexcludediftheydidnotreach85%oftheiragepredictedmaximalheartrateonthemaximalexercisetreadmilltestMen•1.52(1.28-1.82)WomenD&Bscore=14•2.10(1.36-3.26)Low(leastfit20%)Adjusteddeathsper10,000personyearsaccordingtoPFModerate(next40%)High(mostfit40%)Men•AerobicsCenterLongitudinalStudyProportionalhazardmodeling•Low=49•Med=27•High=23Women•Low=29•Med=13•High=14Boyleetal2007[169]ToexaminetheassociationbetweenPAandtheriskofincidentdisability,includingimpairmentinactivitiesofdailylivingandinstrumentalactivitiesofdailylivingincommunitybasedolderpersonsfreefromdementia.•n=1,0202.6yearfollow-up•156deathsTheriskofdeathdecreased11%witheachhourofPA/wk.•Sex:Menandwomen•Age:54-100yrPAassessment:Questionnaire,hr/wkofPAIncidenceofall-causemortalityHRforall-causemortalityWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 22 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)USA•Characteristics:Participantsfrom40retirementcommunitiesacrossChicagoTheriskofdeathwas11%lowerforeachhr/wkofPAProspectivecohortD&Bscore=13•RushMemoryandAgingProjectBuckschetal2005[170]ToexaminetheeffectofmoderatelyintensePAonall-causemortality.•n=7,187(3,742men;3,445women)Baseline(1984-1986)and12-14yrfollow-up(1998)•943deathsParticipantswhoachievedrecommendedamountsofMPAorVPAwereatasignificantlylowerriskofdeaththantheirsedentarycounterparts.•Sex:MenandwomenRR(95%CI)forachievingrecommendedPAvs.notachievingrecommendationGermany•Age:30-69yrProspectivecohort•Characteristics:ParticipantswerehealthyandphysicallyactiveduringleisuretimePAassessment:Questionnaire(MinnesotaLeisureTimePhysicalActivityquestionnaire)dividedintogroupsbasedon:AchievingrecommendedamountofMPA(30min,5d/wk(≥2.5h/wk))Women•MPA=0.65(0.51-0.82)D&Bscore=13•VPA=0.78(0.57-1.08)•MPAorVPA=0.60(0.47-0.75)Men•MPA=0.90(0.77-1.01)•VPA=0.74(0.61-0.90)•MPAorVPA=0.80(0.68-0.94)AchievingrecommendedamountofVPA(20min,3d/wk(≥1h/wk))RR(95%CI)forvolumeoflifestyleactivities(kcal/kg/wk)Volumeoflifestyleactivities(kcal/kg/wk)WomenG1=0•G1=1.00(referent)G2=<14•G2=0.79(0.57-1.08)G3=14-33.5•G3=0.68(0.50-0.94)G4=≥33.5•G4=0.57(0.41-0.79)p<0.001Men•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 23 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •G2=0.98(0.76-1.17)•G3=0.80(0.63-1.00)•G4=0.91(0.74-1.13)p=0.20Adjustedforage,otherrecommendation,socialclass,smoking,BMI,cardioriskfactorindex,alcoholintake,chronicdiseaseindexanddietaryfactorsBuckschandHelmert2004[171]ToexamineLTPAandprematuredeathinthegeneralpopulationofformerWestGermany.•n=7,187(3,742men;3,445women)Baseline(1984-1986)and12-14yearfollow-up(1998)•943deathsLTPAisinverselyassociatedwithall-causemortalityinmenandwomen.•Sex:MenandwomenRR(95%CI)•Age:30-69yrMen,LTPAGermany•Characteristics:ParticipantswereselectedonthebasisoftheGermanCardiovascularPreventionStudyPAassessment:Questionnaire(MinnesotaLeisureTimePhysicalActivityquestionnaire)dividedintogroupsbasedon:LTSA(h/wk)•G1=1.00(referent)•G2=0.85(0.78-0.93)Prospectivecohort•G3=0.64(0.50-0.82)•G4=0.70(0.54-0.91)p<0.001D&Bscore=14•TheNationalHealthSurveyoftheGermanFederalInstituteofPopulationResearch(1984-1998)Men,LTPAindexG1=0•G1=1.00(referent)G2=<1•G2=0.92(0.70-1.23)G3=1-2•G3=0.89(0.69-1.17)G4=>2•G4=0.61(0.44-0.84)p<0.01TheLTSA-index(kcal/kg/wk)G1=0Women,LTPAG2=1-10•G1=1.00(referent)G3=10-25•G2=0.93(0.82-1.04)G4=>25•G3=0.69(0.48-0.98)•G4=0.57(0.35-0.94)Mortality–Recordsfromthemandatorypopulationregistriesp<0.01Women,LTPAindex•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 24 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Coxproportionalhazardregressionmodel•G2=0.68(0.45-1.01)•G3=0.79(0.51-1.21)•G4=0.46(0.25-0.85)p<0.01Adjustedforage,socialclass,smoking,BMI,cardioriskfactorindex,alcoholintake,chronicdiseaseindexanddietaryfactorsCarlssonetal2006[172]ToinvestigatetheassociationbetweenPAandmortalityinpost-menopausalwomen.•n=27,734Baseline(1997)and2-7yearfollow-up(1999-2004)•1,232deathsThestudyindicatesthatevenfairlysmallamountsofactivitywillreducemortalityinolderwomen.•Sex:Women•Age:51-83yrRR(95%CI)adjustedforlifestyleandmedicalproblemsSweden•Characteristics:WomenwhoparticipatedinapopulationbasedScreeningprogrammein1987ProspectivecohortPAassessment:Questionnairesfor:METs/day,differentPA(walking/biking),LTPA,OPA,householdPA,TVwatchingandreadingPA(METs/day)•>50=1.00(referent)D&Bscore=12•45-50=1.05(0.77-1.42)•TheSwedishMammographyCohort•40-45s=1.09(0.81-1.46)•45-40=1.26(0.94-1.70)•<35=2.56(1.85-3.53)Mortality–RecordsfromtheNationalPopulationRegisterDifferentPAWalking/biking(min/d)•>90=1.00(referent)•60-90=1.01(0.76-1.34)•40-60=0.92(0.70-1.20)•20-40=0.96(0.75-1.23)•<20=1.16(0.90-1.50)•Almostnever=1.94(1.51-2.50)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 25 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) LTPA(hr/wk)•>5=1.00(referent)•4-5=0.95(0.74-1.22)•2-3=1.02(0.83-1.26)•1=1.09(0.88-1.36)•<1=1.91(1.56-2.35)OPA•Heavymanuallabour=1.00(referent)•Walking/lifting/alotcarrying=0.96(0.55-1.70)•Walking/lifting/notalotcarrying=1.00(0.60-1.68)•Mostlystanding=0.91(0.52-1.61)•Seated50%oftime=0.97(0.58-1.62)•Mostlysedentary=1.93(1.15-3.25)Householdwork(hr/d)•>8h/d=1.00(referent)•7-8=0.68(0.49-0.93)•5-6=0.66(0.51-0.87)•3-4=0.83(0.64-1.06)•1-2=0.89(0.69-1.15)•<1=1.73(1.30-2.32)AdjustedforageCrespoetal2002[173]TostudytherelationshipbetweenPAandobesitywithall-causemortalityinPuertoRicanmen.•n=9,136(1962-1965)Baselineand12yearfollow-up•1,445deathsSomePAisbetterthannoneinprotectingagainstall-causemortality.Thebenefitsareindependentofbodyweight.PuertoRico•Sex:MenPAassessment:Questionnaire,dividedinto4groupsbasedonMETsMultivariateOR(95%CI)adjustedforageG1=lowG2G3G4=highProspectivecohort•Age:35-79yrMultivariatelogisticfunctionmodel•C1=1.00(referent)D&Bscore=12•Characteristics:Participantswithnoknowncoronaryheartdisease•C2=0.67(0.57-0.78)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 26 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•ThePuertoRicoHeartHealthProgram•C3=0.63(0.54-0.74)•C4=0.54(0.46-0.64)p<0.0001MultivariateadjustedOR(95%CI)•C1=1.00(referent)•C2=0.68(0.58-0.79)•C3=0.63(0.54-0.75)•C4=0.55(0.46-0.65)p<0.0001DaveySmithetal2000[174]ToexaminetherelationshipofPAandvariouscausesofdeath.•n=6,702(atbaseline)Baseline(1969-1970)and25yearfollow-up•926deathsInthestudy,aninverseassociationofbothLTPAandwalkingpacewithmortalityfromall-causeswasseen.UK•Sex:MenPAassessment:Questionnairewith3groupsforwalkingpace(Slower,same,faster)and3groupsforLTPA(inactive,moderatelyactive,active)AgeadjustedRR(95%CI)forwalkingpaceProspectivecohort•Age:40-64yr•Slower=2.47(2.2-2.8)D&Bscore=13•Characteristics:ParticipantsfromruralnorthernJapan•Same=1.35(1.2-1.5)•Whitehallstudy•Faster=1.00(referent)p<0.001FullyadjustedRR(95%CI)forwalkingpace•Slower=1.87(1.6-2.1)•Same=1.21(1.1-1.3)•Faster=1.00(referent)p<0.001AgeadjustedRR(95%CI)forLTPA•Inactive=1.44(1.3-1.6)•Mod=1.13(1.0-1.2)•Active=1.00(referent)p<0.001FullyadjustedRR(95%CI)forLTPA•Inactive=1.20(1.1-1.3)•Mod=1.07(1.0-1.2)•Active=1.00(referent)p<0.001Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 27 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Eatonetal1995[175]Todeterminewhetherself-reportedPApredictsadecreasedrateofCHDandall-causemortalityinmiddleagedmen.•n=8,46321yearfollow-up•2,593deathsBaselinelevelsofself-reportedLTPApredictedadecreasedrateofCHDandall-causemortality.Europe,Israel,mideasternAsia,NorthernAfrica•Sex:MenPAassessment:QuestionnaireforLTPAAgeadjustedRR(95%CI)LTPAProspectivecohort•Age:≥40yrG1=Sedentary•G1=1.00(referent)D&Bscore=12•Characteristics:GovernmentemployeeswithoutknownCVDG2=Light•G2=0.84(0.74-0.94)G3=Lightdaily•G3=0.81(0.73-0.90)G4=Heavy•G4=0.84(0.72-0.98)OPAQuestionnaireforOPA•G1=1.00(referent)G1=Sitting•G2=0.99(0.88-1.12)G2=Standing•G3=1.09(0.99-1.20)G3=Walking•G4=1.16(1.03-1.30)G4=PhysicallabourFangetal2005[176]ToassesstheassociationofexerciseandCVDoutcomeamongpersonswithdifferentbloodpressurestatus.•n=9,791(3,819men;5,972women)17yearfollow-upIncidenceofall-causemortalityandPAAsignificanteffectofexerciseonmortalityinnormotensivesubjectswasnotfound.USA•Sex:MenandwomenPAassessment:Questionnairewith3groupsMultivariateadjustedHR(95%CI)Prospectivecohort•Age:25-74yrG1=Leastexercise•G1=1.00(referent)D&Bscore=12•Characteristics:Non-institutionalizedparticipantsG2=Moderateexercise•G2=0.75(0.53-1.05)G3=Mostexercise•G3=0.71(0.45-1.12)Friedetal1998[177]Todeterminethedisease,functionalandpersonalcharacteristicsthatjointlypredictmortality.•n=5,8865yearfollow-up•646deathsPAwasapredictorof5-yearmortality.USA•Sex:MenandwomenPAassessment:Selfreportedexercise(5groups)Incidenceofall-causemortalityandPAProspectivecohort•Age:≥65yrMPAorVPA(kJ/wk)MultivariateadjustedRR(95%CI)D&Bscore=11•Characteristics:CommunitydwellingeldersG1=≤282•G1=1.00(referent)G2=283-1789•G2=0.78(0.60-1.00)G3=1790-4100•G3=0.81(0.63-1.05)G4=4101-7908•G4=0.72(0.55-0.93)G5=>7908•G5=0.56(0.43-0.74)p<0.005Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 28 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Fujitaetal2004[178]Toexaminetherelationshipbetweenwalkingdurationandall-causemortalityinaJapanesecohort.•n=41,163(20,004men;21,159women)Baseline(1990)and11yearfollow-up(2001)•1,879deathsTimespentwalkingwasassociatedwithareducedriskforall-causemortality.Japan•Sex:MenandwomenPAassessment:QuestionnaireWalking,3levels:AgeandsexadjustedRR(95%CI)fortimespentwalking(hr/d)G1=≤30minG2=30minto1hrG3=≥1hrProspectivecohort•Age:40-64yrCoxproportionalhazardmodelWholegroupD&Bscore=13•Characteristics:Healthy,sedentary•G1=1.22(1.09-1.35)•G2=1.09(0.95-1.22)•G3=1.00(referent)p<0.001Menonly•G1=1.14(1.00-1.30)•G2=1.03(0.90-1.19)•G3=1.00(referentp=0.061Womenonly•G1=1.40(1.16-1.68)•G2=1.23(1.01-1.49)•G3=1.00(referent)p<0.001RR(95%CI)fortimespentwalking(hr/d)(adjustedforage,education,maritalstatus,pasthistoryofdiseases,smoking,drinking,BMIanddietaryvariables)Wholegroup•G1=1.17(1.04-1.31)•G2=1.06(0.93-1.20)•G3=1.00(referent)p=0.011Men•G1=1.08(0.94-1.25)•G2=0.98(0.84-1.14)•G3=1.00(referent)p=0.318Women•G1=1.38(1.12-1.70)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 29 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •G2=1.24(1.00-1.54)•G3=1.00(referent)p<0.001Glassetal1999[179]Toexamineanyassociationbetweensocialactivity,productiveactivityandPAandmortalityinolderpeople.•n=2,761(1,169men;1,143women)13yearfollow-upIncidenceofall-causemortalitybyfitnessactivityquartileMoreactiveelderlypeoplewerelesslikelytodiethanthosewhowerelessactive.USA•Sex:MenandwomenPAassessment:Interview,Amountofactivity13yrmortalitybyamountofactivityProspectivecohort•Age:≥65yrG1=Low•G1=74.0D&Bscore=12•Characteristics:HealthyeldersG2=Low-medium•G2=69.8G3=Medium-high•G3=62.4G4=High•G4=55.2Gulatietal2003[180]Todeterminewhetherexercisecapacityisapredictorforall-causemortalityinasymptomaticwomen.•n=5,721Baseline(1992)and8yearfollow-up(2000)•180deathsThisstudyconfirmedthatexercisecapacityisanindependentpredictorofdeathinasymptomaticwomen,greaterthanwhathasbeenpreviouslyestablishedamongmen.USA•Sex:WomenPFAssessment:TreadmillstresstestExercisecapacity(METs)G1=<5G2=5-8G3=>8Forevery1METincreasetherewasareduceddeathriskof17%(p<0.001)Prospectivecohort•Age:Mean52±11yrAge-adjustedRRD&Bscore=11•Characteristics:Asymptomaticwomen•G1=2.0(1.3-3.2)•StJamesWomenTakeHeartProject•G2=1.6(1.1-2.4)•G3=1.00(referent)AdjustedforFraminghamRiskScore•G1=3.1(2.1-4.8)•G2=1.9(1.3-2.9)•G3=1.00(referent)Haapanenetal1996[181]ToexaminetheassociationbetweenLTPAandall-causemortality.•n=1,072Baselineanda10yr10monthfollow-up•168deathsLowPAisariskfactorforall-causemortality.Finland•Sex:MenPAassessment:Self-reportedLTPA,dividedinto4groupsbyEE(kJ/wk)G1=0-3349G2=3350-6279G3=6280-8791G4=>8791RR(95%CI)accordingtoEEgroupWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 30 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Prospectivecohort•Age:35-63yrMortality–NationalDeathIndexsearch•G1=2.74(1.46-5.14)D&Bscore=14•Characteristics:Healthy,sedentaryCoxproportionalHR•G2=1.10(0.55-2.21)•G3=1.74(0.87-3.50)•G4=1.00(referent)Hakimetal1998[182]Toexaminetheassociationbetweenwalkingandmortalityinretiredmen.•n=707Baselineand12yrfollow-up•208deathsThefindingsinolderphysicallycapablemenindicatethatregularwalkingisassociatedwithaloweroverallmortalityrate.USA•Sex:MenRR(95%CI)accordingtodistancewalkedProspectivecohort•Age:61-81yrAdjustedforageD&Bscore=12•Characteristics:Retirednon-smokingmenwhowerephysicallycapableofparticipatinginlowintensityactivitiesonadailybasisPAassessment:QuestionnaireDistancewalked(miles/day)•G1vs.G3=1.9(1.3-2.9)G1=0.0-0.9•G1vs.G3=1.6(1.2-2.2)G2=1.0-2.0•G2vs.G3=1.2(0.8-1.7)G3=2.1-8.0Trendp=0.002•HonoluluHeartProgramAdjustedforriskfactors•G1vs.G3=1.8(1.2-2.7)•G1vs.G2=1.5(1.1-2.1)•G2vs.G3=1.1(0.8-1.7)Trendp=0.01Hillsdonetal2004[183]ToexaminewhetherVPAisassociatedwithall-causemortality.•n=10,522(4,929men;5,593women)>10yearfollow-up•825deathsQuestionnairerespondentswhoreportedengaginginVPAlessthantwiceaweekexperienceda37%reducedriskofall-causemortalitycomparedwithrespondentswhoreportedalowerfrequencyofVPA.•Sex:MenandwomenPAassessment:QuestionnaireforfrequencyofVPAAgeandsexadjustedRR(95%CI)UK•Age:35-64yrG1=Never,<1time/month•Characteristics:Healthy,sedentaryG2=<2times/wk•G1=1.00(referent)ProspectiveCohort•OXCHECKstudyG3=>2times/wk•G2=0.57(0.42-0.79)•G3=0.72(0.54-0.95)D&Bscore=11FullyadjustedRR(95%CI)•G1=1.00(referent)Mortality–RecordedfromtheOfficeofNationalStatistics•G2=0.63(0.45-0.89)•G3=0.81(0.60-1.09)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 31 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)CoxproportionalHRHuetal2005[184]ToexaminetheassociationofPAandBMIandtheircombinedeffectwiththeriskoftotal,CVDandcancermortality.•n=47,212(22,528men;24,684women)17.7yearfollow-up•7,394deathsRegularPAisanimportantindicatorfordecreasedriskofall-causemortality.PAhasastrongindependenteffectonmortality.•Sex:MenandwomenFinland•Age:25-64yrPAassessment:QuestionnaireforPAlevel,dividedinto3groupsAdjustedHR(95%CI)•Characteristics:ParticipantsfromeasternFinlandMenProspectivecohort•G1=1.00(referent)•G2=0.74(0.68-0.81)G1=Low•G3=0.63(0.58-0.70)D&Bscore=12G2=ModerateTrendp=<0.001G3=HighWomen•G1=1.00(referent)•G2=0.64(0.58-0.70)•G3=0.58(0.52-0.64)Trendp=<0.001Huetal2004[185]ToexaminetheassociationofBMIandPAwithdeath.•n=116,564Baseline(1976)and•10,282deathsReducedPAisastrongandindependentpredictorofdeath.•Sex:Women24yearfollow-up•Age:30-55yrMultivariateRR(95%CI)byPA(hr/wk)USA•Characteristics:FemalesfreeofknownCVDandcancerPAassessment:QuestionnaireforPAlevel,dividedinto3groups(hr/week)•G1=1.00(referent)G1=≥3.5•G2=1.18(1.10-1.26)ProspectivecohortG2=1.0-3.4•G3=1.52(1.41-1.63)D&Bscore=11G3=<1.0MultivariateRR(95%CI)byPAadjustedforBMI•G1=1.00(referent)BMI(kg/m2 )•G2=1.14(1.06-1.22)G1=<25•G3=1.44(1.34-1.55)G2=25-29G3=30CoxproportionalHRKampertetal1996[186]ToexaminePFandPAinrelationtoall-causeandcancermortality.•n=32,421(25,341men;7,080women)Baseline(1970)and~8yearfollow-up(1989)•690deathsThedatasupportthehypothesisthatanactiveandfitwayoflifedelaysdeath.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 32 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•Sex:MenandwomenAdjustedRR(95%CI)byquintilesofactivityUSA•Age:20-88yr(mean~43)Prospectivecohort•Characteristics:PredominantlywhiteandfromthemiddleanduppersocioeconomicstrataPAassessment:Questionnaire,dividedintoquintilesofactivity(min/wk)Men•Sedentary=1.00(referent)•C1-2=0.71(0.58-0.97)D&Bscore=13•C3=0.83(0.59-1.16)Maleactivitycategories•C4=0.57(0.30-1.08)•C5=0.92(0.29-2.88)Sedentary=855Trendp=0.011C1-2=1,072C3=1,292WomenC4=1,453•Sedentary=1.00(referent)C5=1,601•C1-2=0.68(0.39-1.17)•C3=0.39(0.09-1.65)Femalesactivitycategories•C4-5=1.14(0.27-4.80)Sedentary=605Trendp=0.217C1-2=792C3=979C4-5=1,158CoxproportionalHRKaplanetal1996[187]ToassessLTPAanditsassociationwithallcausemortality.•n=6,131(3298men;2833women)28yearfollow-up•1,226deathsThedataprovidefurthersupportfortheimportanceofPAandindicatethattheprotectiveeffectofPAisarobustone.•Sex:MenandwomenPAassessment:ThreequestionsaboutPA,withscores0(never),2(sometimes)or4(often).Incidenceofall-causemortalityandPAUSA•Age:16-94yr•Characteristics:NorthernCalifornianadultsProspectivecohortDeathrates/1000personyearsMenD&Bscore=13•T1=24.68TertilesofPAscore•T2=11.37T1=0-2•T3=7.59T2=4-6WomenT3=8-12•T1=18.03Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 33 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •T2=7.66•T3=3.88Khawetal2006[188]ToexaminetherelationshipbetweenPApatternsover1yearandtotalmortality.•n=22,191(9,984men;12,207women)8yearfollow-up•1,553deathsEvenverymoderatelevelsofusualPAareassociatedwithreductionsinmortality.•Sex:MenandwomenPAassessment:Questionnaire,dividedinto4groupsofPAIncidenceofall-causemortalityandPAUK•Age:45-79yrAdjustedRR(95%CI)•Characteristics:CommunitylivingparticipantsAllProspectivecohortG1=Inactive•G1=1.00(referent)G2=Moderatelyinactive•G2=0.83(0.73-0.95)D&Bscore=13•G3=0.68(0.58-0.80)G3=Moderatelyactive•G4=0.68(0.57-0.81)G4=ActiveAge<65•G1=1.00(referent)•G2=1.01(0.78-1.31)•G3=0.81(0.62-1.07)•G4=0.82(0.62-1.09)Age>65•G1=1.00(referent)•G2=0.77(0.66-0.91)•G3=0.65(0.53-0.79)•G4=0.64(0.50-0.80)Kohletal1996[189]Todeterminetheassociationofmaximalexercisehemodynamicresponseswithriskofall-causemortality.•n=26,621(20,387men;6,234women)Average8.1yearfollow-up•348deathsinmenand66inwomenTheresultssuggestanexaggeratedSBPoranattenuatedheartrateresponsetomaximalexercisemayindicateanelevatedriskformortality.•Sex:MenandwomenUSA•Age:Malemean42.2yr;femalemean41.9YrAdjustedRH(95%CI)bymaximalexercisetestHRProspectivecohortMen•Characteristics:ApparentlyhealthypatientsofapreventivemedicinecentrePFassessment:MaximalexercisetestHR(bpm),dividedinto4Groups:•Q1=1.00(referent)G1=<171•Q2=0.61(0.44-0.85)D&Bscore=12G2=171-178•Q3=0.69(0.51-0.93)G3=179-188•Q4=0.60(0.41-0.87)G4=>188Trendp<0.05Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 34 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) Women•Q1=1.00(referent)•Q2=1.23(0.65-2.32)•Q3=0.69(0.30-1.63)•Q4=0.71(0.22-2.24)Trendp>0.05Kujalaetal1998[190]ToinvestigateLTPAandmortalityinacohortoftwins.•n=15,902(7,925men;7,977women)Baseline1975anddeathoutcomefrom1977-1994•1,253deathsLTPAisassociatedwithreducedmortality,evenaftergeneticandotherfamilialfactorsaretakenintoaccount.•Sex:MenandwomenHR(95%CI)Finland•Age:25-64yr•Characteristics:Healthy,FinnishsamesextwinsPAassessment:Questionnaire,quintilesoffitnessinMEThours/dayAdjustedforageandsexProspectivecohort•Sedentary=1.00(referent)•OE=0.71(0.62-0.81)•TheFinnishTwinCohort•CE=0.57(0.45-0.74)D&Bscore=13Q1=<58Trendp=0.001Q2=59-1.29Q3=1.30-2.49Adjustedforage,sex,smokingQ4=2.50-4.49Q5=>4.50•Sedentary=1.00(referent)•OE=0.76(0.67-0.87)Categorizedinto:•CE=0.68(0.53-0.88)-Sedentary-Occasionalexerciser(OE)Trendp=0.001-Conditioningexerciser(CE)Adjustedforage,sex,smoking,occupationalgroup,alcohol•Sedentary=1.00(referent)•OE=0.80(0.69-0.91)•CE=0.76(0.59-0.98)Trendp=0.002HR(95%CI)among434samesextwinpairscomparedwithsedentarycategoryin1975•Sedentary=1.00(referent)•OE=0.66(0.46-0.94)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 35 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •CE=0.44(0.23-0.83)Trendp=0.005Adjustedforsmoking•Sedentary=1.00(referent)•OE=0.70(0.48-1.01)•CE=0.56(0.29-1.09)Trendp=0.04Adjustedforsmoking,occupationalgroup,alcohol•Sedentary=1.00(referent)•OE=0.73(0.50-1.07)•CE=0.56(0.29-1.11)Trendp=0.06OR(95%CI)inquintilesamong434samesextwinpairscomparedwithsedentarycategoryin1975•Q1=1.00(referent)•Q2=0.85•Q3=0.72•Q4=0.68•Q5=0.60LaCroixetal1996[191]TodeterminewhetherwalkingisassociatedwithareducedriskofCVDhospitalizationanddeathinolderadults.•n=1,645(615men;1030women)4.2yearfollow-upRR(95%CI)bycategoryofwalkingWalkingmorethan4hr/wkwasassociatedwithareducedriskofmortalityfromall-causes.•Sex:MenandwomenPAassessment:Questionnaireforwalkingh/wk,dividedinto3groupsUSA•Age:≥65yrG1=<1hr/weekMenCharacteristics:Participantsfromagrouphealthco-operativeG2=1-4hr/week•G1=1.00(referent)ProspectivecohortG3=>4hr/week•G2=0.78(0.43-1.45)•G3=0.89(0.49-1.62)D&Bscore=12Women•G1=1.00(referent)•G2=0.50(0.28-0.90)•G3=0.48(0.25-0.83)Age65-74yr•G1=1.00(referent)•G2=0.81(0.40-1.61)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 36 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •G3=1.13(0.60-2.15)Age≥75yr•G1=1.00(referent)•G2=0.63(0.37-1.08)•G3=0.46(0.25-0.84)Highfunctioning•G1=1.00(referent)•G2=0.73(0.38-1.41)•G3=0.89(0.48-1.65)Limitedfunctioning•G1=1.00(referent)•G2=0.60(0.34-1.05)•G3=0.51(0.28-0.92)Lametal2004[192]ToinvestigatetherelationshipLTPAandmortalityinHongKong.•n=24,079cases(13,778men;10,301women);10yearspriorMultivariateadjustedOR(95%CI)byLTPAThedataconfirmandextendpreviousfindingsinCaucasianpopulationsontheassociationbetweenLTPAandlongevity.PAassessment:MenHongKong•n=13,054controls(3,918men;9,136women)QuestionnaireforLTPA,dividedinto3groups•G1=1.00(referent)•G2=0.60(0.54-0.67)Case-Control•G3=0.66(0.60-0.73)•Sex:MenandwomenG1=<1timespermonthD&Bscore=12•Age:≥35yrWomen•Characteristics:AllethnicChineseG2=1-3timespermonth•G1=1.00(referent)•G2=0.81(0.74-0.88)G3=≥4timespermonth•G3=0.71(0.66-.077)Lanetal2006[193]Toinvestigatetherelationshipbetweenexerciseandall-causemortality.•n=2,113(1,081men;1,032women)Baselineand2yearfollow-up•197deathsOlderpersonsarerecommendedtoexpendatleast1000kcal/wkthroughregularexerciseformortalityreduction.•Sex:MenandwomenHR(95%CI)byLTPAfrequencyTaiwan•Age:≥65yrPAassessment:QuestionnaireforLTPA(frequency/wk)Prospectivecohort•Characteristics:Non-institutionalizedeldersAdjustedforageandsexProtectionofexerciseagainstdeathalsoincreaseswiththenumberofactivities.G1=Sedentary•G1=1.00(referent)•TaiwanNationalHealthInterviewSurveyG2=1time/wk•G2=0.49(0.36-0.67)D&Bscore=13G3=≥2times/wk•G3=0.20(0.09-0.46)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 37 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) Trendp=<0.001QuestionnaireforEE(kcal/wk),dividedinto5groups:Multivariateadjusted•G1=1.00(referent)G1=Sedentary•G2=0.70(0.50-0.98)G2=<500•G3=0.35(0.15-0.82)G3=500-999Trendp=0.014G4=1000-1999G5=≥2000HR(95%CI)byEEAdjustedforageandsex•G1=1.00(referent)•G2=0.64(0.41-1.01)•G3=0.55(0.35-0.85)•G4=0.30(0.17-0.53)•G5=0.24(0.12-0.48)Trendp<0.001Multivariateadjusted•G1=1.00(referent)•G2=0.80(0.49-1.30)•G3=0.74(0.46-1.17)•G4=0.50(0.27-0.90)•G5=0.43(0.21-0.87)Trendp=0.043Laukkanenetal2001[194]Toexaminetherelationshipbetweenmaximaloxygenuptakeandoverallmortality.•n=1,294Baselineand10.7yearfollow-up•124deathsPFhasastrong,graded,inverseassociationwithoverallmortality.•Sex:MenAdjustedRR(95%CI)byquartileFinland•Age:42.0-61.3yr(mean52.1)•Characteristics:MenfreefromCVD,COPD,andcanceratbaselinePFassessment:Exercisetolerancetest,4groupsbymaximaloxygenuptake(ml/kg/min)ProspectivecohortMaximaloxygenuptake•G1=1.00(referent)•G2=1.47(0.71-3.01)D&Bscore=14•G3=2.79(1.44-5.39)G1=>37.1•G4=3.85(2.02-7.32)G2=32.3-37.1Lineartrendp=<0.001G3=27.6-32.2Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 38 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)G4=<27.6Testduration•G1=1.00(referent)Testduration(min)•G2=2.22(1.08-4.55)G1=>11.2•G3=2.23(1.11-4.49)G2=9.6-11.2•G4=3.94(2.01-7.74)G3=8.2-9.5Lineartrendp<0.001G4=<8.2LeeandPaffenbarger2000[195]TocomparevariouslevelsofPAwithmortality.•n=13,485Baselineand15yearfollow-up•2,539deathsThestudyprovidessomesupportforrecommendationsthatemphasizeMPA.AbenefitofVPAisalsoevident.•Sex:Men•Age:Mean57.5yrRR(95%CI)•Characteristics:Menwhomatriculatedasundergraduatesin1916-1950PAassessment:•G1=1.00(referent)USAQuestionnairesforLTPAindex(includingwalking,stairclimbing,sportsandrecreationalactivity),•G2=0.80(0.72-0.88)•G3=0.74(0.65-0.83)Prospectivecohort•G4=0.80(0.69-0.93)•TheHarvardAlumniHealthStudy•G5=0.73(0.64-0.84)Trendp=<0.001D&Bscore=125groups(kJ/wk)G1=<4200G2=4200-8399G3=8400-12599G4=12600-16799G5=≥16800Leeetal1995[196]Toexaminetheindependentassociationofvigorousandnon-vigorousPAwithlongevity.•n=17,321Follow-up22-26years•3,728deathsThereisagradedinverserelationshipbetweenPAandmortality.Vigorous,butnotnon-vigorousactivitiesareassociatedwithlongevity.•Sex:Men•Age:Mean46yrPAassessment:QuestionnairesforEE(kJ/wk),quintilesRR(95%CI)byEE(kJ/wk)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 39 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)USA•Characteristics:HarvardUniversityalumni,withoutself-reportedphysiciandiagnosedcardiovasculardisease,cancerorchronicobstructivepulmonarydiseaseQ1=1.00(referent)•Q2=0.94(0.86–1.04)ProspectivecohortQ1=≤630•Q3=0.95(0.86–1.05)Q2=630-1680•Q4=0.91(0.83-1.01)Q3=1680-3150•Q5=0.91(0.82-1.00)D&Bscore=12Q4=3150-6300Q5=>6300RR(95%CI)byEE(Vigorousactivity,kJ/wk)•Q1=1.00(referent)•TheHarvardAlumniHealthStudy•Q2=0.88(0.82-0.96)•Q3=0.92(0.82-1.02)•Q4=0.87(0.77-0.99)•Q5=0.87(0.78-0.97)Leeetal2004[197]ToinvestigatetheeffectofvariousPApatternsonall-causemortality.•n=8,421Baseline1988andfollow-up1993•1,234deathsTheresultssuggestthatregularPAgenerating1000kcal/wkormoreshouldberecommendedforloweringmortalityrates.Amongthosewithnomajorriskfactors,even1-2episodesperweekgenerating1000kcalormorecanpostponemortality.•Sex:Men•Age:Mean66yrAgeadjustedRR(95%CI)byPApatternUSA•Characteristics:ParticipantsfreeofmajorchronicdiseasePAassessment:QuestionnaireforPA(kcal/wk),4groups•G1=1.00(referent)Prospectivecohort•G2=0.75(0.63-0.90)G1=<500•G3=0.82(0.63-1.07)•TheHarvardAlumniHealthStudy(Sedentary)•G4=0.61(0.53-0.69)D&Bscore=11G2=500-999(Insufficientlyactive)MultivariateadjustedG3=≥1000(Weekendwarrior)•G1=1.00(referent)G4=Regularlyactive•G2=0.75(0.62-0.91)•G3=0.85(0.65-1.11)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 40 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •G4=0.64(0.55-0.73)Leitzmannetal2007[198]ToexaminePAguidelinesinrelationtomortality.•n=252,925(142,828male;110,097women)Baselineand6monthfollow-up•7,900deathsFollowingPAguidelinesisassociatedwithlowerriskofdeath.Mortalitybenefitmayalsobeachievedbyengaginginlessthanrecommendedactivitylevels.USA•Sex:MenandwomenPAassessment:QuestionnaireforMPAandVPA,5groupseachMPA(h/wk)MultivariateadjustedRR(95%CI)accordingtoactivity•Age:50-71yrMPAProspectivecohort•Characteristics:ParticipantsfreeofCVD,canceroremphysema•G1=1.00(referent)•TheNationalInstituteofHealth-AmericanAssociationofRetiredPersons•G2=0.85(0.79-0.93)•G3=0.79(0.74-0.85)D&Bscore=13G1=sedentary•G4=0.76(0.71-0.82)G2=<1•G5=0.68(0.63-0.74)G3=1-3Trendp=<0.001G4=4-7VPAG5=>7VPA(frequency/wk)•G1=1.00(referent)G1=inactive•G2=0.77(0.71-0.83)G2=<1•G3=0.77(0.72-0.82)G3=1-2•G4=0.68(0.63-0.73)G4=3-4•G5=0.71(0.66-0.77)G5=≥5Trendp=<0.001CoxproportionalHRLeonetal1997[199]Toexaminethelong-termassociationofLTPAandriskofdeathfromcoronaryheartdiseaseandall-causes.•n=12,13816yearfollow-up•1,904deathsThedatasuggestthatarelativelysmallamountofdailymoderateintensityLTPAcanreduceprematuremortalityinmiddle-agedandoldermenathighriskforCHD.•Sex:Men•Age:35-57yrPAassessment:MinnesotaLTPAquestionnaire,categorizedbyfrequency/monthandaverageduration,deciles(min/d)MultivariateadjustedRR(95%CI)bydecilesofLTPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 41 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)USA•Characteristics:MenwhoatentrytothestudywerefreeofclinicalevidenceofCHDorotherseriousmedicalproblemsbutwereattheupper10%-15%ofaCHDprobabilityscoredistributionderivedfromtheFHSdataProspectivecohort•D1=1.00(referent)•D2-4=0.85(0.73-0.99)•D5-7=0.87(0.75-1.02)D&Bscore=12•D8-10=0.83(0.71-0.97)D1=4.9D2-4=22.7D5-7=53.9D8-10=140.4•MultipleRiskFactorInterventionTrialCoxproportionalHRLissneretal1996[200]ToexaminetherelationshipofOPAandLTPAonall-causemortalityinwomen.•n=1,405Baselineand20yearfollow-up•277deathsDecreasesinPAaswellaslowinitiallevelsarestrongriskfactorsformortality.•Sex:Women•Age:38-60yrRR(95%CI)byLTPASweden•Characteristics:FreefrommajordiseaseatbaselinePAassessment:QuestionnaireforOPAandLTPA,3groups20yearfollow-upProspectivecohortLTPAduringage20-38years•TheGothenburgProspectiveStudyofWomen•Low=1.00(referent)G1=Low•Med=0.66(0.34-1.26)D&Bscore=10G2=Medium•High=0.46(0.21-1.01)G3=HighLTPAduringage39-60yearsProportionalhazardregression•Low=1.00(referent)•Med=0.56(0.35-0.90)•High=0.44(0.22-0.91)LTPAduringthepast12months•Low=1.00(referent)•Med=0.56(0.39-0.82)•High=0.45(0.24-0.86)20yearfollow-upOPAduringage20-38yearsWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 42 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •Low=1.00(referent)•Med=0.59(0.18-1.87)•High=0.50(0.16-1.58)OPAduringage39-60years•Low=1.00(referent)•Med=0.66(0.21-2.08)•High=0.47(0.14-1.52)OPAduringthepast12months•Low=1.00(referent)•Med=0.28(0.17-0.46)•High=0.24(0.14-0.43)Maninietal2006[201]Todeterminewhetherenergyexpenditureisassociatedwithall-causemortalityinolderadults.•n=302(150men;152women)Meanfollow-upof6.15years•55deathsFree-livingactivityEEwasstronglyassociatedwithlowerriskofmortality.•Sex:MenandwomenHR(95%CI)bytertilesofPAEEUSA•Age:70-82yrPAassessment:Questionnaire,dividedintotertilesofPAEE(kcal/d)Prospectivecohort•Characteristics:High-functioningcommunitydwellingeldersAdjustedforage,sex,raceandstudysiteT1=<521•T1=1.00(referent)D&Bscore=13T2=521-770•T2=0.63(0.29-1.18)T3=>770•T3=0.37(0.15-0.76)Trendp=0.009Adjustedforage,sex,race,studysite,weight,height,percentbodyfatandsleepduration•T1=1.00(referent)•T2=0.57(0.30-1.09)•T3=0.31(0.14-0.69)Trendp=0.004Adjustedforage,sex,race,studysite,selfratedhealth,education,smoking,CVD,lungdisease,diabetes,hiporkneeosteoarthritis,osteoporosis,canceranddepression•T1=1.00(referent)•T2=0.65(0.33-1.28)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 43 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •T3=0.33(0.15-0.74)Trendp=0.007Matthewsetal2007[202]Todeterminetheeffectsofexerciseandnon-exercisePAonmortality.•n=67,143Baselineandanaverageof5.7yearfollow-up•1,091deathsOverallPAlevelsareanimportantdeterminantoflongevity.•Sex:Women•Age:40-70yrRR(95%CI)China•Characteristics:Womenwithoutheartdisease,strokeorcancerPAassessment:Interviewtoreport(METh/d),4groupsOverallactivityMultivariateadjustmentProspectivecohortOverallactivity(METhr/d)•G1=1.00(referent)•TheShanghaiWomen’sHealthStudy•G2=0.81(0.69-0.96)D&Bscore=12G1=≤9.9•G3=0.67(0.57-0.80)G2=10.0-13.6•G4=0.61(0.51-0.73)G3=13.7-18.0Trendp=0.000G4=≥18.1Adultexercise(METhr/d)Adultexercise•G1=1.00(referent)G1=0•G2=0.84(0.74-0.96)G2=0.1-3.4•G3=0.77(0.59-0.99)G3=3.5-7.0•G4=0.64(0.36-1.14)G4=≥7.1Trendp=0.008CoxproportionalhazardmodelsMenottiandSeccareccia1985[203]ToinvestigatetherelationshipbetweenOPAandall-causemortality.•n=99,029Baselineand5yearfollow-up•2,661deathsTheresultssuggestthatPAmayplayaroleinthepredictionoffatalevents.•Sex:Men•Age:40-59yr•Characteristics:MenemployedontheItalianrailwaysystemPAassessment:QuestionnaireMenatriskclassifiedby3levelsofPAand3levelsofjobresponsibility,combinedtocreate8groupsofPA-jobresponsibilityAgeadjusteddeathratesper1000over5yearsclassifiedbyPAonlyItaly•Sedentary=26.20Prospectivecohort•Moderate=27.05•Heavy=27.35Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 44 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)D&Bscore=12Ageadjusteddeathratesper1,000over5yearsclassifiedbyPAandjobresponsibilityG1=sedentary–low•G1=30.00G2=sedentary–med•G2=25.20G3=sedentary–high•G3=25.80G4=moderate–low•G4=26.30G5=moderate–med•G5=28.50G6=moderate–high•G6=25.80G7=heavy–low•G7=26.90G8=heavy–med•G8=30.80Mensinketal1996[204]TocomparevariousindicesforPAandtheirassociationwithcardiovascularriskfactorsaswellastotalandCVDmortality.•n=15,436(7,689men;7797women)5-8yearfollow-upIncidenceofall-causemortalityandPAAninverserelationofPAandtotalmortality.Germany•Sex:MenandwomenPAassessment:QuestionnaireTotalactivity,3groupsAdjustedRR(95%CI)•Age:25-69yrProspectivecohort•Characteristics:ParticipantsfromcommunitiesinWesternGermanyTotalactivity,menG1=Low•G1=1.00(referent)G2=Moderate•G2=0.56(0.30-1.04)D&Bscore=12G3=High•G3=0.78(0.42-1.44)Totalactivity,womenLTPA,3groups•G1=1.00(referent)G1=Low•G2=1.24(0.60-2.58)G2=Moderate•G3=1.29(0.58-2.85)G3=HighConditioningactivity,3groupsLTPA,men•G1=1.00(referent)G1=Noactivity•G2=0.61(0.35-1.05)G2=Moderate•G3=0.79(0.48-1.31)G3=HighLTPA,women•G1=1.00(referent)Sportsactivity,4groups•G2=0.94(0.51-1.75)•G3=0.81(0.44-1.49)G1=nosportsG2=<1hourConditioningactivity,menG3=1-2hours•G1=1.00(referent)G4=>2hours•G2=0.76(0.44-1.34)•G3=0.67(0.36-1.25)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 45 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) Conditioningactivity,women•G1=1.00(referent)•G2=0.38(0.13-1.06)•G3=0.80(0.42-1.54)SportsActivity,men•G1=1.00(referent)•G2=0.49(0.26-0.95)•G3=0.57(0.30-1.09)•G4=0.36(0.16-0.79)Sportsactivity,women•G1=1.00(referent)•G2=0.38(0.12-1.23)•G3=0.52(0.23-1.17)•G4=0.28(0.07-1.17)MorganandClarke1997[205]ToassessthevalueofbroadlybasedcustomaryPAscoresinpredicting10-yearmortalityinelderlypeople.•n=1,042(407men;635women)10yearfollow-upIncidenceofall-causemortalityandPAAwiderangeofcustomaryorhabitualPA,canprovideindicesshowingbothcrosssectionalandpredictivevalidityfor10yearmortality.•Sex:MenandwomenPAassessment:QuestionnaireforPA,3groupsUK•Age:≥65yrHR(95%CI)•Characteristics:BritisheldersMenProspectivecohortG1=Low•G1=1.59(1.12-2.25)•NottinghamLongitudinalStudyofActivityandAgingG2=Intermediate•G2=1.35(0.96-1.89)G3=High•G3=1.00(referent)D&Bscore=12Women•G1=2.07(1.53-2.79)•G2=1.53(1.12-2.09)•G3=1.00(referent)Myersetal2002[206]TocomparePFandPAlevelswithall-causemortality.•n=6,213Baselineandmean6.2±3.7yearfollow-up•1,256deathsExercisecapacityisamorepowerfulpredictorofmortalityamongmenthanotherestablishedriskfactorsforCVD.•Sex:Men•Age:Mean59±11yrAgeadjustedRR(95%CI)byquintileWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 46 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)USA•Characteristics:Participantswithanormalexercisetestresult(n=2,534)andparticipantswithanabnormalexercisetestorCVDorboth(n=3,679)PFassessment:TreadmilltestforVO2peak,dividedintoquintiles(METs)•Q1=4.5(3.0-6.8)Prospectivecohort•Q2=2.4(1.5-3.8)•Q3=1.7(1.1-2.8)•Q4=1.3(0.7-2.2)D&Bscore=12Q1=Lowestlevel•Q5=1.00(referent)1.0-5.9Q2Q3Q4Q5=Highestlevel≥13.0Ostbyeetal2002[207]Toanalyzetheeffectofsmokingandothermodifiableriskfactorsonillhealth,definedinamultidimensionalfashion.•n=12,9566yearfollow-up•782deathsQuittingsmokingandincreasingexerciselevelsarethelifestyleinterventionsmostlikelytoimproveoverallhealth.•Sex:Menandwomen•Age:50-60yrPAassessment:QuestionnaireforPA,4groupsIncidenceofall-causemortalityandPAUSA•Characteristics:ParticipantsfromtheHealthandRetirementStudy(HRS)onlyProspectivecohortG1=SedentaryDeathrates(95%CI)per1000population/yrG2=LightG3=Moderate•G1=20.6(17.8-24.0)D&Bscore=13G4=Heavy•G2=9.1(8.1-9.5)•G3=8.3(7.5-9.2)•G4=4.4(3.5-5.6)Paffenbargeretal1994[208]TostudytheadoptionormaintenanceofPAandotheroptionallifestylepatternsfortheirinfluenceonmortalityratesofHarvardCollegealumni.•n=14,786Follow-upbetween•2,343deathsAdoptingaphysicallyactivelifewaydelaysmortalityandextendslongevity.•Sex:Men1977and1988•Age:45-84yr(in1977)RR(95%CI)ofmortalityaccordingtoPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 47 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)USAPAassessment:Questionnaireforblockswalkeddaily,stairsclimbeddailyandtype,frequencyanddurationofweeklysportsandrecreationalactivitiesCharacteristics:HarvardCollegealumniProspectivecohortPhysicalactivityindex(kcal/wk)•G1=1.00(referent)D&Bscore=14•G2=1.13(1.01-1.26)•G3=0.72(0.64-0.82)•G4=0.77(0.69-0.85)Physicalactivityindex(kcal/wk)SportsandrecreationalactivitieswerescoredaccordingtointensityanddurationWalking(km/wk)•G1=1.00(referent)•G2=1.21(1.08-1.35)•G3=0.94(0.83-1.07)•G4=0.89(0.78-1.01)Moderatelyvigoroussportsplay(METs)Light<4.5METsModerate≥4.5METs•G1=1.00(referent)•G2=1.11(0.93-1.33)•G3=0.73(0.65-0.81)•G4=0.72(0.64-0.80)AdjustedforpotentialconfoundinginfluencesRichardsonetal2004[209]Toinvestigatetheimpactofasedentarylifestyleonall-causemortality.•n=9,611(4,642men;4,969women)Baseline(1992)and8yearfollow-up•810deathsAsedentarylifestyleisassociatedwithahigherriskofdeathinpre-retirementagedadults.•Sex:MenandwomenOR(95%CI)USA•Age:51-61yrPAassessment:QuestionnaireforPA,3groups:•G1=1.00(referent)Prospectivecohort•Characteristics:Participantsbornbetween1931-1941andwhonotinstitutionalizedin1992•G2=0.64(0.52-0.81)G1=Sedentary•G3=0.62(0.44-0.85)G2=occasionalorlightp=0.01D&Bscore=13G3=RegularMVPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 48 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•HealthandRetirementStudyRockhilletal2001[210]TodeterminetheassociationbetweenrecreationalPAandmortalityinwomen.•n=80,348Baseline(1980)andfollow-upbetween1982-1996•4,871deathsPeoplewhoaremorephysicallyactiveareatreducedmortalityriskrelativetothosewhoarelessactive.•Sex:Women•Age:30-55yrMultivariateadjustedRR(95%CI)by(hr/wk)USA•Characteristics:FreefromCVDorcanceratbaseline•NursesHealthStudyPAassessment:Questionnairein1980andup-datedevery2-4years,5groupsofPA(hr/wk)•G1=1.00(referent)Prospectivecohort•G2=0.82(0.76-0.89)•G3=0.75(0.69-0.81)•G4=0.74(0.68-0.81)D&Bscore=11•G5=0.71(0.61-0.82)p<0.001G1=<1G2=1-1.9G3=2-3.9G4=4-6.9G5=≥7RosengrenandWilhelmsen1997[211]ToinvestigatetheeffectofOPAandLTPAonriskofdeath.•n=7,142Baseline(1970-1973)and20yearfollow-up•2,182deathsThestudydemonstratestheprotectiveeffectofLTPAonmortality.•Sex:Men•Age:47-55yrUnadjustedRR(95%CI)•Characteristics:WithoutsymptomaticCHDPAassessment:Postalquestionnaires,3groups:•G1=1.00(referent)Sweden•G2=0.74(0.68-0.82)•G3=0.73(0.68-0.79)ProspectivecohortG1=SedentaryG2=ModeratelyactiveMultivariateadjustmentG3=Regularexercise•G1=1.00(referent)D&Bscore=13•G2=0.84(0.77-0.93)•G3=0.83(0.77-0.90)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 49 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Schnohretal2003[212]ToassesstheassociationsofregularLTPAandchangesinLTPAwithriskofdeath.•n=7,023(4,471men;5,676women)18yearfollow-up•2,725deathsMaintainingoradoptingamoderateorhighdegreeofPAwasassociatedwithlowerriskofdeath.•Sex:MenandwomenPAassessment:Questionnaire,9groupsIncidenceofall-causemortalityandPAandchangesinPADenmark•Age:20-79yr•Characteristics:ParticipantsfromtheCopenhagenCityHeartRegisteredPopulationProspectivecohortG1=Low–lowG2=Low–moderateAdjustedRR(95%CI)G3=Low–highMenD&Bscore=12G4=Moderate-low•G1=1.00(referent)G5=Moderate-Moderate•G2=0.64(0.49-0.83)•G3=0.64(0.47-0.87)G6=Moderate-high•G4=0.73(0.56-0.96)G7=High-low•G5=0.71(0.57-0.88)G8=High-moderate•G6=0.64(0.51-0.81)G9=High-high•G7=1.11(0.76-1.62)•G8=0.66(0.51-0.85)•G9=0.61(0.48-0.76)Women•G1=1.00(referent)•G2=0.75(0.57-0.97)•G3=0.72(0.50-1.05)•G4=0.70(0.54-0.91)•G5=0.64(0.52-0.79)•G6=0.58(0.45-0.73)•G7=0.72(0.48-1.07)•G8=0.61(0.47-0.80)•G9=0.66(0.51-0.85)Schnohretal2004[213]Toexaminewhethertherelationshipbetweenestablishedriskfactorsandmortalitydifferswithsocioeconomicstatusasmeasuredbylevelofeducation.•n=30,635(16,236men;14,399women)16yearfollow-up•10,952deathsThestudyshowsthestrongpredictiveeffectofPAonmortalityisindependentofeducationlevel.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 50 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•Sex:MenandwomenSocioeconomicstatusassessment:levelofeducationIncidenceofall-causemortalityandPAstratifiedbyyearsofeducationDenmark•Age:20-93yr•Characteristics:ParticipantsfromtheCopenhagenCityHeartRegisteredPopulationProspectivecohortPAassessment:QuestionnaireDeaths<8yearsofeducationD&Bscore=12Men4groupsofPAG1=916G1=noneorverylittleG2=1693G2=2-4h/wkofLPAG3=1012G3=>4h/wkofLPAor2-4h/wkofhighlevelactivityG4=67G4=Competitionlevelor>4h/wkofhardlevelactivityWomen•G1=872•G2=1298•G3=346•G4=108-11yearsofeducationMen•G1=432•G2=1040•G3=616•G4=33Women•G1=363•G2=852•G3=268•G4=10>11yearsofeducationMen•G1=104•G2=302•G3=182•G4=11WomenWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 51 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued) •G1=48•G2=129•G3=61•G4=3Schnohretal2006[214]ToinvestigatetheassociationbetweenLTPAandmortality.•n=4,894(2,136men;2,758women)Baseline(1976)andstartoffollow-upin1981-1983(to2000)•1,787deathsLong-termmoderateorhighPAwasassociatedwithsignificantlylowermortalityinmenandwomen.•Sex:MenandwomenRR(95%CI)Denmark•Age:20-79yr•Characteristics:HealthymalesandwomenUnadjustedProspectivecohortPAassessment:SurveyforLTPA,3groups:•G1=1.00(referent)•G2=0.64(0.56-0.73)•TheCopenhagenCityHeartStudy•G3=0.56(0.48-0.65)D&Bscore=13G1=LowTrendp<0.001G2=ModG3=HighMultivariateadjustment•G1=1.00(referent)•G2=0.78(0.68-0.89)•G3=0.75(0.64-0.87)Trendp=0.001Schoolingetal2006[215]ToexaminehowaComprehensiveassessmentofbaselinehealthstatusaffectstherelationshipbetweenobesityorPAandmortality.•n=54,088(17,849men;36,239women)4.1yearfollow-up•3,819deathsPA,whichnormallyhasanegativerelationshipwithadiposity,hadthelargestimpactonsurvivalforthehealthstates,withthestrongestinverserelationshipbetweenBMIandmortality.•Sex:MenandwomenPAassessment:InterviewforPAmin/d,3groupsIncidenceofall-causemortalityandPAHongKong•Age:≥65yrProspectivecohort•Characteristics:ChineseeldersG1=NoneAdjustedHR(95%CI)G2=≤30min/d•G1=1.00(referent)G3=≥30min/d•G2=0.83(0.76-0.91)D&Bscore=13•G3=0.73(0.67-0.80)Trendp<0.001Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 52 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Sundquistetal2004[216]TostudytheassociationbetweenvaryinglevelsofPAandall-causemortalityintheelderly.•n=3,206(1,414men;1,792women)Baseline(1988-1989)andfollow-upin2000•1,806deathsEvenoccasionalPAdecreasestheriskofmortalityamongelderlypeople.•Sex:MenandwomenPAassessment:QuestionnaireforPA,5groupsAge-adjustedHR(95%CI)Sweden•Age:≥65yrMen•Characteristics:Non-institutionalizedelders•G1=1.00(referent)Prospectivecohort•G2=0.74(0.62-0.87)G1=none•G3=0.57(0.44-0.73)TheSwedishAnnualLevel-of-LivingSurvey(StatisticsSweden)G2=occasionally•G4=0.51(0.41-0.64)D&Bscore=12G3=onceperweek•G5=0.60(0.44-0.82)G4=twiceperweekWomenG5=vigorouslyatleasttwiceperweek•G1=1.00(referent)•G2=0.70(0.59-0.82)•G3=0.59(0.46-0.77)CoxproportionalHR•G4=0.47(0.35-0.62)•G5=0.54(0.31-0.94)MenandwomenMultivariateadjustment•G1=1.00(referent)•G2=0.72(0.64-0.81)•G3=0.60(0.50-0.71)•G4=0.50(0.42-0.59)•G5=0.60(0.46-0.79)Talbotetal2007[217]ToinvestigatehowchangesinLTPAaffectall-causemortality.•n=2,092(1,316men;776women)Baselinein1958formalesandin1978forfemalesandanaveragefollow-upof21.2±9.4yearsformenand10.2±5.6yearsforwomen•628deaths(538male;90female)Greaterdeclinesintotalandhigh-intensityLTPAareindependentpredictorsofall-causemortality.•Sex:MenandwomenUSA•Age:19-<90yrRR(95%CI)forstandarddeviationofrateofchangeinLTPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 53 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Prospectivecohort•Characteristics:Communityresidents,generallywithaboveaverageincome,higheducationandwithgoodorexcellentselfrelatedhealth(IfRRis<1thenaSDincreaseisassociatedwithdecreasemortality.IfRRis>1,thenaSDincreaseisassociatedwithincreaseinmortality)D&Bscore=13PAassessment:QuestionnaireforLTPA(METsmin/24h),3groupsTheBaltimoreLongitudinalStudyofAgingG1=lowG2=mediumMultivariateadjustmentG3=highMen<70yearsRateofchange(ROC)•G1=0.96(0.84-1.08)•G2=0.91(0.79-1.04)•G3=0.42(0.33-0.53)•ROClow=0.90(0.80-1.01)•ROCmed=1.01(0.90-1.14)•ROChigh=0.78(0.65-0.94)Men>70years•G1=0.95(0.82-1.10)•G2=0.89(0.76-1.05)•G3=0.78(0.62-0.97)•ROClow=1.07(0.93-1.24)•ROCmed=1.13(1.00-1.27)•ROChigh=0.91(0.75-1.12)Women<70years•G1=0.75(0.53-1.07)•G2=0.61(0.36-1.03)•G3=0.80(0.50-1.30)•ROClow=1.02(0.74-1.40)•ROCmed=1.38(0.86-2.28)•ROChigh=0.90(0.63-1.27)Women>70years•G1=0.85(0.63-1.15)•G2=0.78(0.39-1.59)•G3=0.62(0.32-1.22)•ROClow=1.10(0.85-1.42)•ROCmed=0.96(0.46-2.03)•ROChigh=0.70(0.40-1.22)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 54 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Trolle-Lagerrosetal2005[218]ToquantifytheeffectofPAonoverallmortalityinyoungerwomenandtoassesstheeffectofpastversuscurrentactivity.•n=99,09911.4yearfollow-up•1,313deathsCurrentPAsubstantiallyreducesmortalityamongwomen.TheassociationisobservedevenwithlowlevelsofPAandisaccentuatedwithincreasedPA.•Sex:Women•Age:30-49yrPAassessment:Questionnaireusinga5pointscale,5groupsIncidenceofall-causemortalityandPApastandcurrentSwedenandNorway•Characteristics:ParticipantsfromNorwayandoneregionofSwedenRetrospectivecohortG1=SedentaryAdjustedHR(95%CI)G2=LowPAatenrolmentG3=Moderate•G1=1.00(referent)D&Bscore=13G4=High•G2=0.78(0.61-1.00)G5=Vigorous•G3=0.62(0.49-0.78)•G4=0.58(0.44-0.75)•G5=0.46(0.33-0.65)Trendp<0.0001PAatage30yr•G1=1.00(referent)•G2=0.79(0.55-1.15)•G3=0.90(0.64-1.28)•G4=0.98(0.68-1.42)•G5=0.96(0.65-1.44)Trendp=0.22PAatage14yr•G1=1.00(referent)•G2=0.95(0.66-1.38)•G3=0.96(0.69-1.34)•G4=0.88(0.62-1.25)•G5=1.06(0.75-1.51)Trendp=0.62Villeneuveetal1998[219]ToexaminetherelationshipbetweenPF,PAandall-causemortality.•n=14,442(6,246men;8,196women)Baseline(1981)and7yearfollow-upRR(95%CI)byEE,multivariateadjustmentTherewasareductioninmortalityriskassociatedwithevenmodestparticipationinactivitiesoflowintensity.•Sex:MenandwomenCanada•Age:20-69yrPAassessment:QuestionnaireforEE(kcal/kg/day),5groupsLTPA,menWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 55 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)•Characteristics:AsymptomaticforCVD•G1=1.00(referent)Prospectivecohort•G2=0.81(0.59-1.11)•G3=0.79(0.54-1.13)CanadianFitnessSurveyG1=0-<0.5•G4=0.86(0.61-1.22)D&Bscore=11G2=0.5-<1.5•G5=0.82(0.65-1.04)*G3=1.5-<3.0G4=≥3.0NonvigorousLTPA,menG5=≥0.5•G1=1.00(referent)PFlevels:•G2=0.81(0.56-1.17)Recommended•G3=0.70(0.44-1.13)Minimum•G4=0.82(0.53-1.27)•G5=0.78(0.59-1.04)*UndesirableRefusalLTPA,womenMultivariatePoissonregressionanalysis•G1=1.00(referent)•G2=0.94(0.69-1.30)•G3=0.92(0.64-1.34)•G4=0.71(0.45-1.11)•G5=0.88(0.68-1.04)*NonvigorousLTPA,women•G1=1.00(referent)•G2=0.97(0.69-1.36)•G3=0.87(0.57-1.33)•G4=0.72(0.43-1.21)•G5=0.89(0.67-1.17)*RR(95%CI)byfitnesslevels,adjustedforage,sexandsmokingRecommended=1.00(referent)•Minimum=1.02(0.69-1.51)•Undesirable=1.52(0.72-3.18)•Refusal=1.04(0.45-2.39)WellerandCorey1998[220]TostudytherelationshipbetweenPAandmortalityinwomen.•n=6,620Baselineand7yearfollow-up•449deathsPAisinverselyassociatedwithriskofdeathinwomen.•Sex:Women•Age:≥;30yrOR(95%CI)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 56 of 220Table11:Studiesexaminingtherelationshipbetweenphysicalactivityandall-causemortality.(Continued)Canada•Characteristics:WithoutknownheartdiseasePAassessment:Questionnairesfor:EE(kcal/kg/d),quartiles•CanadianFitnessSurveyEE(kcal/kg/d)Prospectivecohort•Q1=1.00(referent)•Q2=0.91(0.66-1.25)Q1=lowest•Q3=0.94(0.72-1.23)D&Bscore=11Q2=•Q4=0.89(0.67-1.17)Q3=Q4=highestLTPAlevelsLTPA,3groups•G1=1.00(referent)G1=Sedentary•G2=0.63(0.46-0.86)G2=Mod•G3=0.76(0.59-0.98)G3=HighWalkingWalking,3groups•G1=1.00(referent)G1=<halfthetime•G2=0.64(0.49-0.82)G2=halfthetime•G3=0.64(0.47-0.86)G3=>halfthetimeYuetal2003[221]ToexaminetherelationshipbetweenLTPAandall-causemortality.•n=1,975Baselineand10yearfollow-up•252deathsThestudyfoundastronginverseassociationbetweenheavyLTPAandall-causemortality.UK•Sex:Men•Age:49-64yrAgeadjustedHR(95%CI)•Characteristics:WithoutahistoryofCHDatbaselinePAassessment:Questionnaire(MinnesotaLTPAindex,kcal/d),3group•G1=1.00(referent)•G2=0.73(0.54-0.99)Prospectivecohort•G3=0.74(0.55-1.04)Trendp=0.046D&Bscore=11G1=LighttonoactivityMultivariateadjustedG2=Moderateactivity•G1=1.00(referent)G3=Heavyactivity•G2=0.79(0.58-1.08)•G3=0.76(0.56-1.04)Trendp=0.083D&Bscore,DownsandBlackqualityscore;PF,physicalfitness;YR,years;RR,riskratio;95%CI,95%confidenceinterval;PA,physicalactivity;VO2peak,peakoxygenconsumption;HR,hazardratio;min/d,minutesperday;kcal/wk,kilocaloriesperweek;LTPA,leisure-timephysicalactivity;MET,metabolicequivalent;VO2max,maximaloxygenconsumption;OPA,occupationalphysicalactivity;CVD,cardiovasculardisease;hr/wk,hoursperweek;MPA,moderatephysicalactivity;kcal/kg/wk,kilocaloriesperkilogramperweek;kJ/wk,kilojoulesperweek;EE,energyexpenditure;G,groups;EE,energyexpenditure;BMI,bodymassindex;C,class;kg/m2,kilogrambymeterssquared;HR,heartrate;BPM,beatsperminute;MVPA,moderatetovigorousphysicalactivity;OR,oddsratio;Q,quartileorquintile;RCT,randomizedclinicaltrial;T,tertiles;TPA,totalphysicalactivity;VPA,vigorousphysicalactivity;mL/kg/min,millilitersperkilogramperminute.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 57 of 220definition of cardiovascular disease (n = 78), and other(n = 19). Therefore, a total of 49 articles were includedin the systematic review of the literature regarding therelationship between physical activity and the incidenceof cardiovascular disease.The majority of the studies included in our systematicreview were prospective cohort investigations (Table12). These studies involved a total of 726,474 partici-pants; averaging 12,313 participants per study (range680-88,393). There were a total of 34,815 reported casesof cardiovascular disease (ranging per study from 42-2,596). The total length of study follow-up for the pro-spective cohort studies averaged 14.1 yr (ranging from2-29 yr). The articles were published over a 32 yr periodranging from 1975 to 2007. These studies involved largesamples of men and women from regions throughoutthe world.Similar to the all-cause mortality data, the risk for car-diovascular disease demonstrates a graded inverse dose-response relationship to physical activity and fitness.The relative reduction in the incidence of cardiovasculardisease averages 33% (median risk reduction of 36%),with greater risk reductions in studies that employedobjective measures of aerobic fitness. It is not uncom-mon for studies to demonstrate a 50% or higher riskreduction when an objective measure of physical fitnesswas taken (Table 12). The importance of physical activ-ity may actually be underestimated owing to multivariatecontrol for many confounding factors (as discussed pre-viously) and the fact that effects of within-person varia-tion in physical activity are often not considered [55].The relative risk reduction appears to be similar formen and women, and also appear to extend to non-Caucasian populations [56]. Some evidence also existsindicating that small amounts of physical activity areassociated with lower cardiovascular-disease relatedmortality [57,58]. Similar to all-cause mortality, physicalactivity confers health benefits independent of otherknown risk factors [42,59]. Collectively, the level of evi-dence would be considered to be Level 2A based on thepresence of overwhelming evidence from observationaltrials. The quality of the investigations was generallyhigh with a mean (and median) Downs and Black scoreof 12 (range 9-14).QuintilesQ1 Q2 Q3 Q4 Q5Relative Risk0.00.40.50.60.70.80.91.0QuartilesQ1 Q2 Q3 Q4Tertiles3Q2Q1QMean Across Quintiles Mean Across Quartiles Mean Across Tertiles Figure 3 Mean relative risk reduction in all-cause mortality across physical activity/fitness categories.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 58 of 220ImplicationsResearch in the field began with the landmark work ofMorris and colleagues, which demonstrated that men inphysically demanding occupations (bus conductors andpostmen) had a significantly lower risk of heart diseasethan individuals who worked in less demanding jobs(bus drivers and office workers) [45]. Since thenconsiderable research has examined the relationshipbetween physical activity and the risk for cardiovasculardisease. In fact, several systematic reviews of the litera-ture have been developed regarding the role of habitualphysical activity in the primary and secondary preven-tion of cardiovascular disease [33,60-62]. The researchto date has been consistent and compelling, habitualphysical activity reduces markedly the risk for cardiovas-cular disease.Based on the available literature, there is compellingevidence that the recommendation of 30 min of moder-ate intensity exercise on most days of the week (equiva-lent to 4.2 MJ/wk or 1000 kcal/wk) reaches a thresholdassociated with significant reductions in cardiovascular-related mortality [32,63]. Brisk walking has also beenshown to be preferable to a slower pace [64]. However,weekly exercise volumes of less than 4.2 MJ (1000 kcal)may be cardio-protective [14,59,65-67]. For instance,Lee et al. (2001) found that as little as 1 hr/wk of walk-ing was associated with a 50% lower cardiovascular dis-ease mortality in one sample of women. Wisloff et al.[58] reported that a single weekly bout of self-reportedhigh intensity exercise was associated with a lower riskof cardiovascular death relative to those reporting noactivity in both men (RR = 0.61, 95% CI = 0.49-0.75),and women (RR = 0.49, 95% CI = 0.27-0.89). Moreover,no additional benefit was seen with higher durations orfrequency of exercise sessions [58]. The authors statedthat this evidence challenges “current recommendationsthat require at least 1000 kcal of caloric expenditure perweek to achieve exercise-induced protection against pre-mature cardiovascular death.” However, this research isin fact supportive of the Canadian guidelines whichrecognize the potential health benefits of low volumesof physical activity as reflected by the statement “Everylittle bit counts, but more is even better - everyone cando it!” It however should be noted that the statement“more is even better” is supported by a strong evidencebase.Recommendation #2For a reduced risk for cardiovascular disease-related events and mortality, it is recommended thatindividuals participate in 30 min or more of moder-ate to vigorous exercise on most days of the week.Greater health benefits appear to occur with highvolume and/or intensities of activity. Health benefitsmay also occur with as little as one hr of brisk walk-ing per week. [Level 2, Grade A]The Primary Prevention of StrokeStroke affects a significant proportion of Canadiansociety with approximately 50,000 new cases each year[68]. The relationship between physical activity and therisk for stroke is compelling, supporting at least a 25-Figure 4 Results of the Literature Search for CardiovascularDisease.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 59 of 220Table12Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsPaffenbargerandHale1975[47]ToevaluatetheroleofPAinreducingcoronarymortalityamonglongshoreman•n=6,35122yearsoffollowup,oruntilreachedtheageof75yrRR(95%CI)SuddendeathVPAisassociatedwithreducedriskofcoronarymortality,particularlysuddencardiacdeath.USA•Sex:Men•G1=1.00(referent)•Age:35-74yr•G2=3.5•Characteristics:LongshoremanPAassessment:Energyandoxygencostrequirementsoflongshoringjobs•G3=2.8ProspectivecohortDelayeddeath•G1=1.00(referent)D&Bscore=12•G2=1.4Activitylevel•G3=1.5G1=Heavy(5.2-7.5kcal/min)UnspecifieddeathG2=Moderate(2.4-5.0kcal/min)•G1=1.00(referent)G3=Light(1.5-2.0kcal/min)•G2=1.1•G3=1.6Outcomemeasure:DeathfromCHDMansonetal2002[56]TocomparetherolesofwalkingandvigorousexerciseinthepreventionofCVeventsinalarge,ethnicallydiversecohortofpostmenopausalwomen.•n=73,743Enrolmentfrom1994-98Clinicvisitforbaselinescreening,•NumberofNewCases:345BothwalkingandVPAareassociatedwithsubstantialreductionsintheincidenceofCHDevents.USA•Sex:Women•TotalNumberofCVDevents:1551•Age:50-79yr•Characteristics:Healthy,PostMenopausalAgeadjustedRR(95%CI)Totalexercise(MET-hr/wk)PAassessment:Questionnairefor:Totalexercise(MET-hr/wk)ProspectivecohortG1=0-2.4•G1=1.00(referent)•Women’sHealthInitiativeObservationalStudyG2=2.5-7.2•G2=0.73(0.53-0.99)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 60 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)G3=7.3-13.4•G3=0.69(0.51-0.95)D&Bscore=12G4=13.5-23.3•G4=0.68(0.50-0.93)G5=≥23.4•G5=0.47(0.33-0.67)p=<0.001Walking(MET-hr/wk)Walking(MET-hr/wk)•G1=1.00(referent)G1=None•G2=0.71(0.53-0.96)G2=0.1-2.5•G3=0.60(0.44-0.83)G3=2.6-5.0•G4=0.54(0.39-0.76)G4=5.1-10.0•G5=0.61(0.44-0.84)G5>10p=0.004TimeforVPA(min)VigorousexerciseG1=None•G1=1.00(referent)G2=1-60•G2=1.12(0.79-1.60)G3=61-100•G3=0.56(0.32-0.98)G4=101-150•G4=0.73(0.43-1.25)G5=>150•G5=0.58(0.34-0.99)p=0.008OutcomeMeasure:IncidenceofCVDandCHDWisloffetal2006[58]TostudytheassociationbetweentheamountandintensityofexerciseandCVDmortality.•n=56,072(27,143men;28,929women)Lengthoffollow-up:16±4yr•NumberofCases:1,603male,993femaleMenandwomenwhoexercisetoamoderatedegreeandspendlessthantherecommendedenergy(<1000kcal/wk)areatlowerriskofdyingfromheartdiseasethanthosewhoneverexercise.Norway•Sex:MenandwomenPAassessment:QuestionnaireforLTPA,4groupsMultivariateRR(95%CI)Prospectivecohort•Age:≥20yrMen•Characteristics:FreeformCVDMen•Q1=1.00(referent)Q1=None•Q2=0.66(0.50-0.87)D&Bscore=12•HUNTstudyQ2=1/wk>30minhigh•Q3=0.83(0.65-1.06)Q3=2-3/wk>30minhigh•Q4=0.77(0.59-1.01)Q4=≥4/wk>30minhighWomen •Q1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 61 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Women•Q2=0.63(0.31-1.29)Q1=None•Q3=0.66(0.32-1.34)Q2=1/wk≤30minlow•Q4=0.86(0.45-1.62)Q3=1/wk≤30minhighQ4=2-3/wk≤30minlowOutcomeMeasure:IschaemicheartdiseasemortalityCoxproportionalHRLeeetal2001[59]ToexaminetherelationshipbetweenPA(specificallywalking)andCHDamongwomen,includingthoseathighriskforCHD.•n=39,372RecruitmentofParticipants:Sept1992-May1995•NumberofCases:244EvenlighttomoderateactivityisassociatedwithlowerCHDratesinwomen.USAandPuertoRico•Sex:Women•Age:≥45yrMultivariateRR(95%CI)Timespentwalking•Characteristics:HealthyPAassessment:QuestionnairesDividedinto4or5groups:•G1=1.00(referent)•Women’sHealthStudy•G2=0.86(0.57-1.29)Aslittleas1hourofwalkingperweekpredictedlowerrisk.Prospectivecohort•G3=0.49(0.28-0.86)•G4=0.48(0.29-0.78)p=<0.001D&Bscore=12TimespentwalkingG1=NoregularwalkingWalkingpaceG2=1-59min/wk•G1=1.00(referent)G3=1.0-1.5h/wk•G2=0.56(0.32-0.97)G4=≥2.0h/wk•G3=0.71(0.47-1.05)Walkingpace(km/h)•G4=0.52(0.30-0.90)G1=Noregularwalkingp=0.02G2=3.2G3=3.2-4.7G4=≥4.8EE(kcal/wk)•Q1=1.00(referent)EE(kcal/wk)•Q2=0.79(0.56-1.12)G1=200•Q3=0.55(0.37-0.82)G2=200-599•Q4=0.75(0.50-1.12)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 62 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)G3=600-1499andp=0.03G4=1500ormoreEnergyexpendedVPA(kcal/wk)EnergyexpenditureforVPA(kcal/wk)•G1=1.00(referent)G1=Novigorous,<200kcal/wk•G2=0.65(0.46-0.91)G2=Novigorous,≥200kcal/wk•G3=1.18(0.79-1.78)•G4=0.96(0.60-1.55)•G5=0.63(0.38-1.04)G3=Vigorous,1-199kcal/wkG4=Vigorous,200-499kcal/wkG5=Vigorous,≥500kcal/wkPaffenbargeretal1993[67]ToanalyzechangesinthelifestyleofHarvardAlumniandtheassociationsofthesechangestomortality.•n=10,269Baselinemeasurein1962or1967withafollowupin1977AlumniwhoincreasedtheirPAindexto2000kcalormoreperweekhada17%lowerriskofdeathfromCHDthenthosewhoweresedentary(p=0.507)ModeratelyvigoroussportsactivitywasassociatedwithlowerratesofdeathfromCHDamongmiddleagedandoldermen•Sex:Men•Age:45-84yrUSA•Characteristics:Health,HarvardCollegeAlumniProspectivecohortPAassessment:Mailedquestionnairesincludedquestionsontype,duration,intensity,frequencyofPA.Menwhotookupmoderatetookupmoderatelyvigorousactivityhada41%lowerriskthanthosewhocontinuednottoengageinsuchactivity(p=0.044)D&Bscore=13OutcomeMeasure:CHDdeathsbetween1977and1985CoxproportionalhazardsmodelPoissonregressionmethodsTheMantelextensionoftheMantel-HaenszeltestHaapanenetal1997[77]ToexaminetheassociationbetweendurationandintensityofLTPAandtheriskofCHD.•n=2,840(1,500men;1,340women)LengthofFollow-up:10yrs•IncidentRates(per1000person-years)forCHD=108formenand75forwomen.TotalEEhadaninverseandindependentassociationwithriskofCHDinmiddleagedFinnishmenbutnotamongwomen.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 63 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Finland•Sex:MenandwomenPAassessment:QuestionnaireforLTPAEE(kcal/wk)MultivariateRR(95%CI)LTPAandCHDmortalityProspectivecohort•Age:35-63yrMen•Characteristics:HealthyMen•G1=1.98G1=0-1100•G2=1.33D&Bscore=13G2=1101-1900•G3=1.00(referent)G3=>1900WomenWomen•G1=1.25G1=0-900•G2=0.73G2=901-1500•G3=1.00(referent)G3=>1500OutcomeMeasure:CHDmortalityCoxproportionalHRBarengoetal2004[164]ToinvestigatewhethermoderateorhighLTPAareassociatedwithareducedCVDandall-causemortality,independentofCVDriskfactorsandotherformsofPAinmenandwomen.•n=31,677(15,853men;16,824women)20yearfollow-up•NumberofCases(Men):1,661ModerateandhighlevelsofLTPAandOPAareassociatedwithreducedCVDmortality.PAassessment:QuestionnaireforLTPAandOPA,3groups•NumberofCases(Women):778Finland•Sex:MenandwomenHR(95%CI)LTPA,menProspectivecohort•Age:30-59G1=Lowactivity•G1=1.00(referent)•Characteristics:Participantfromeasternandsouth-westernFinlandG2=Moderateactivity•G2=0.91(0.82-1.00)D&Bscore=14G3=Highactivity•G3=0.83(0.69-0.99)LTPA,women(referent)•G1=1.00•G2=0.83(0.71-0.96)•G3=0.89(0.68-1.18)OPA,men•G1=1.00(referent)•G2=0.75(0.64-0.87)•G3=0.77(0.69-0.87)OPA,womenWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 64 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)•G1=1.00(referent)•G2=0.73(0.60-0.88)•G3=0.77(0.65-0.91)Bijnenetal1998[166]TodescribetheassociationbetweenthePApatternofelderlymenandCHDmortality.•n=802LengthofFollow-up:10•NumberofCases:90PAdidnotshowaprotectiveeffectondeathfromCHD.•Sex:Men•Age:64-84yrPAassessment:Questionnaire,dividedinto3groupsRR(95%CI)Netherlands•Characteristics:FreefromSeriousIllness•G1=1.00(referent)•G2=0.63(0.38-1.05)ProspectivecohortG1=Lowest•G3=0.85(0.51-1.44)•Ethnicity:DutchG2=Middle•ZutphenElderlyStudyG3=HighestD&Bscore=13OutcomeMeasure:CHDMortalityCoxProportionalHRDavey-Smithetal2000[174]Toexaminetheassociationbetweentwomeasuresofphysicalactivity(LTPAandusualwalkingpace)withcausespecificmortality(CHD).•n=6,702LengthofFollow-up:25yrs•NumberofCases:955InverseassociationsofbothLTPAandwalkingpacewithmortalityfromCHDwereseen.•Sex:Men•Age:40-64yrRR(95%CI)bywalkingpaceEngland•WhitehallStudyPAassessment:QuestionnaireduringexaminationforwalkingpaceandLTPA•G1=1.45(0.9-2.2)•G2=1.30(1.1-1.6)Prospectivecohort•G3=1.00(referent)p<0.01D&Bscore=11WalkingpaceMultivariateRR(95%CI)byLTPAlevelG1=Slower•G1=1.24(1.0-1.5)G2=Same•G2=0.94(0.8-1.2)G3=Faster•G3=1.00p<0.05LTPAG1=InactiveWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 65 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)G2=ModerateG3=ActiveOutcomeMeasure:CHDMortalityCoxProportionalHREatonetal1995[175]TodeterminewhetherselfreportedPApredictsadecreasedriskofCHD.•n=8,463(LTPA),8,418(OPA)LengthofFollow-up:21yrs•NumberofCases:709BaselinelevelsofselfreportedLTPApredictedadecreasedrateofCHD.AgeadjustedRR(95%CI)byLTPAlevelUSA•Sex:MenPAassessment:Interview•G1=1.00(referent)•Age:40yr•G2=0.79(0.63-0.99)Prospectivecohort•Characteristics:Healthy,freeofCHDLTPA•G3=0.73(0.59-0.89)G1=Sedentary•G4=0.71(0.52-0.98)G2=LightD&Bscore=11Ethnicity:IsraeliG3=LightDailyAgeadjustedRR(95%CI)byOPAlevelG4=Heavy•G1=1.00(referent)•G2=0.99(0.75-1.18)OPA•G3=0.94(0.78-1.12)G1=Sitting•G4=0.87(0.67-1.10)G3=WalkingG4=PhysicalLabourOutcomeMeasure:CHDDeathCoxProportionalHRHillsdonetal2004[183]Toexaminewhetherashort,easilyadministeredmeasureofPAisassociatedwiththeriskofdeathfromallcausesandspecificcauses.•n=10,522(4,929men;5,593women)LengthofFollow-up:>10yrs•NumberofCases:155SelfreportedVPAisassociatedwiththeriskoffuturemortality.MultivariateRR(95%CI)byPAlevelUK•Sex:MenandwomenPAassessment:Questionnaire,3groups:•G1=1.00(referent)•G2=0.46(0.19-1.12)Prospectivecohort•Age:35-64yrG1=Never/<1time/month•G3=0.96(0.53-1.75)•Characteristics:nohistoryofchestpainG2=<2times/wkD&Bscore=11G3=≥2times/wkWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 66 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)OutcomeMeasure:IHDmortalityCoxproportionalHRLeonetal1997[199]TostudytherelationshipofPAtoCHDinawelldefinedpopulationataboveaverageriskforCHDovera16yrobservationperiod.•n=12,138Followupfor16yearsAgeAdjustedRR(95%CI)Arelativelysmallamount(10-36min/d)ofdailymoderateintensityLTPAcansignificantlyreduceprematuremortalityfromCHDinmiddleagedmenathighriskforCHD.USA•Sex:Men•G1=1.00(referent)•Age:35-57yrPAassessment:Questionnaireatbaseline(MinnesotaLTPAquestionnaire),divided/groupedintodecilesofLTPA(min/d)•G2=0.71(0.56-0.91)•Characteristics:FreeofCHDbutintheupper10-15%ofaCHDprobabilityriskscore•G3=0.75(0.59-0.96)•G4=0.69(0.54-0.96)ProspectivecohortMultivariateadjustedRR(95%CI)•G1=1.00(referent)D&Bscore=11G1=D1:(0-9min/d)•G2=0.75(0.54-0.96)MultipleriskfactorinterventiontrialG2=D2-4:(10-36min/d)•G3=0.81(0.64-1.04)G3=D5-7:(37-75min/d)•G4=0.75(0.59-0.96)G4=D8-10:(76-359min/d)OutcomeMeasure:CHDMortalityRosengrenetal1997[211]ToexaminethelongtermeffectofOPAandLTPAontheriskofdeathfromCHD.•n=7,142LengthofFollow-up:20yrsNumberofCases:684ThereappearstobeaprotectiveeffectofLTPAonCHD-relateddeath.•Sex:Men•Age:47-55yrMultivariateRR(95%CI)forLTPASweden•Characteristics:SwedishmenPAassessment:QuestionnaireforLTPA,3groups•G1=1.00(referent)•G2=0.84(0.71-1.00)Prospectivecohort•G3=0.84(0.73-0.96)G1=SedentaryG2=ModeratelyactiveWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 67 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)D&Bscore=13G3=RegularexerciseOutcomeMeasure:CHDdeathProportionalHRSchnohretal2006[214]TodescribetheassociationsbetweendifferentlevelsofLTPAandsubsequentcausesofdeath.•n=4,894(2,136men;2,758women)ParticipantsincludedinthestudywereonlythosewhosePAlevelsdidnotchangeover5years•NumberofCases:292Therewasaninverseandsignificantdose-responseassociationbetweenLTPAandCHD-relatedmortality.AdjustedRR(95%CI)WholegroupDenmark•Sex:Menandwomen•G1=1.00(referent)•G2=0.71(0.51-0.99)ProspectivecohortAge:20–79yrPAassessment:•G3=0.56(0.38-0.82)•Characteristics:HealthyQuestionnaireLTPAD&Bscore=12•CopenhagenCityHeartStudyG1=<4METSMenG2=4-6METS•G1=referentG3=>6METS•G2=survived4.9yrslonger•G3=survived6.8yrslongerCoxproportionalHRWomen •G1=referent•G2=survived5.5yrslonger•G3=survived6.4yrslongerWelleretal1998[220]ToexaminetherelationshipbetweenPAandmortality.•n=6,620LengthofFollow-up:7yrs•NumberofCases:109LTPAisinverselyassociatedwithriskoffatalMI.•Sex:Women•Age:≥30yrPAassessment:OR(95%CI)byLTPACanada•Characteristics:CanadianWomenQuestionnaire,4groupsforLTPA(kcal/kg/day)andnon-LTPA(kcal/kg/day)•Q1=1.00(referent)•Q2=0.61(0.07-1.19)Prospectivecohort•Q3=0.84(0.52-1.37)•Q4=0.63(0.36-1.09)D&Bscore=9LTPA(kcal/kg/day)OR(95%CI)bynon-LTPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 68 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Q1=≥0•Q1=1.00(referent)Q2=≥0.1•Q2=0.71(0.44-1.16)Q3=≥0.5•Q3=0.57(0.33-0.97)Q4=≥1.6•Q4=0.49(0.26-0.92)Non-LTPA(kcal/kg/day)Q1=≥0Q2=≥2.8Q3=≥5.9Q4=≥9.9OutcomeMeasure:FatalMILogisticregressionanalysisYuetal2003[221]ToexaminetheoptimalintensityofLTPAtodecreasetheriskofCHDmortalityinmiddleagedBritishmen.•n=1,97510yearfollow-up•NumberofCases:82StrongsignificantinverserelationshipbetweenheavyLTPAandCHDmortality.•Sex:MenPAassessment:Questionnaire(MinnesotaLTPAquestionnaire),3groupsMultivariateadjustedHR(95%CI)•Age:49-64yr•G1=1.00(referent)UK•Characteristics:Healthy,noprevioushistoryofCHD•G2=0.74(0.44-1.25)•G3=0.55(0.31-0.98)Prospectivecohortp=0.039Relationshipwasnotsignificantforlow-moderateintensityLTPAandOPA.•CaerphillycollaborativeheartstudyTotalactivitylevel(kcal/day)D&Bscore=11G1=0.0-161.6G2=161.8-395.3G3=395.5-2747.2CoxproportionalHRAltierietal2004[222]ToassessthepossibleprotectiveroleofPAonCHD.•n=985(507men;478women)PAassessment:QuestionnaireforOPA,dividedintoquartilesNumberofCases:507LTPAfrom15-19yrsaswellasOPAfrom30-39yrsbothhaveasignificantinverserelationshipwithriskofnonfatalacuteMI.OR(95%CI)forCHDandOPAItaly•Sex:MenandwomenQ1=lowest•Q1=1.00(referent)Q2•Q2=0.63(0.39-1.03)CaseControl•Age:<79yrQ3•Q3=0.56(0.35-0.90)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 69 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)•Characteristics:Case:PatientsadmittedtoHospitalwithnon-fatalAcuteMI.Controls:PatientsadmittedtohospitalforacuteconditionunrelatedtoknownorpotentialriskfactorsforacuteMIQ4=highest•Q4=0.57(0.34-0.95)D&Bscore=11p=0.045OutcomeMeasure:NonFatalacuteMIUnconditionallogisticregressionBattyetal2003[223]Toexaminetherelationshipbetweenphysicalactivityandthreemortalityendpointsinhealthypersons.•n=6,474LengthofFollow-up:25yr•NumberofCases:837Asuggestionthatthesymptomaticnatureofischemiaappearedtomodifytheaffectsof•Sex:Men•NumberofDropouts:158•Age:40-64yrPAassessment:QuestionnaireforLTPA,dividedinto3groups:UK•Characteristics:BritishcivilservantswhounderwentarestingECGHR(95%CI)forCHDandLTPA•G1=1.14(0.9-1.4)PAontotalandCHDmortality.ProspectivecohortG1=Inactive•G2=0.94(0.8-1.1)G2=Moderate•G3=1.00(referent)G3=ActiveD&Bscore=13OutcomeMeasure:CHDmortalityCoxProportionalHRChenandMillar[224]ToexaminethepotentialprotectiveeffectofLTPAontheincidenceofheartdiseaseanddepression.•n=15,670LengthofFollow-up:2yrs•100casesRegularandatleastMPAcanbebeneficialtohearthealth.•Sex:Menandwomen•Age:≥20yrPAassessment:EEfromselfadministeredquestionnaire,4groups(kcal/kg/day)AdjustedOR(95%CI)Canada•Characteristics:Healthyandfreefromheartdisease•G1=5.0(1.84-13.59)•G2=3.7(1.26-10.67)Prospectivecohort•G3=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 70 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)G1=Sedentary•G4=1.3(0.41-3.89)G2=Light(<1.5)D&Bscore=11NationalPopulationHealthSurveyG3=Moderate(1.5-2.9)G4=Active(≥3)OutcomeMeasure:CHDincidenceMultiplelogisticregressionConroyetal2005[225]Toexaminetherelationshipbetween1)PAduringyoungadulthoodandmiddleage,and2)PAduringeachtimeperiodandCHDduringmiddleageandolderwomen.•n=37,169LengthofFollow-up:9yrs•NumberofCases:477PAduringmiddleagepredictslowerriskofCHD•Sex:Women•Age:≥45yrMultivariateRR(95%CI)BaselinePAandincidenceofCHDUS•Characteristics:HealthywomenhealthprofessionalsPAassessment:QuestionnaireforEE(kcal/wk)andmonths/yr•Women’sHealthStudy•G1=1.00(referent)Cohortstudy•G2=0.62(0.48-0.80)•G3=0.61(0.48-0.79)D&Bscore=11BaselinePA(kcal/wk)•G4=0.61(0.46-0.81)G1=<200p=<0.001G2=200-599G3=600-1499PastPAandincidenceofCHDG4=≥1500•G1=1.00(referent)•G2=0.76(0.57-1.02)PastPA•G3=0.95(0.72-1.24)Monthsperyear•G4=1.04(0.78-1.39)G1=0•G5=0.81(0.58-1.14)G2=1-3G3=4-6G4=7-9G5=10-12OutcomeMeasure:IncidenceofCHDCoxproportionalhazardregressionWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 71 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Dornetal1999[226]Toexaminethelong-termrelationshipsbetweentotalPAandmortalityfromallcausesandCHDinthegeneralpopulation.•n=1,461(698men;763women)LengthofFollow-up:29years•NumberofCases:109men,81womenPAfavorablyinfluencesmortalityrisksinnon-obesemenandyoungerwomen.USA•Sex:MenandwomenPAassessment:QuestionnaireMultivariateRR(95%CI)forPAIinnon-obesemenProspectivecohort•Age:15-96yr•0.40(0.19-0.88)for1kcal/kg/h•Characteristics:OutcomeMeasure:CHDMultivariateRR(95%CI)forPAIinobesemenHealthy,freefromCHD,diabetes,andStroke.Mortality•1.86(0.86-4.03)for1kcal/kg/hD&Bscore=11CoxProportionalHazardRatioMultivariateRR(95%CI)forPAIinwomen<60yrs•Ethnicity:White.•0.42(0.11-1.52)for1kcal/kg/hMultivariateRR(95%CI)forPAIinwomen>60yrs•1.78(0.77-4.09)for1kcal/kg/hFolsometal1997[227]ToexaminetheassociationofPAatbaselinewithCHDincidence.•n=13,999(6,166men;7833women)LengthofFollow-up:4-7yrs•NumberofCases:223men,97women,Nosignificantrelationships.MultivariateRR(95%CI)LTPA,menUSA•Sex:MenandwomenPAassessment:Questionnaireduringhomeinterview,dividedintoquartilesofLTPAandsportsactivity•Q1=1.00(referent)Prospectivecohort•Age:45-64yr•Q2=1.08(0.75-1.55)•Characteristics:noCHDatbaseline•Q3=0.83(0.51-1.36)•Q4=0.89(0.59-1.35)D&Bscore=9Q1=Low•Ethnicity:BlackandnonBlackQ2LTPA,womenQ3•Q1=1.00(referent)•AtherosclerosisRiskinCommunitiesStudyQ4=High•Q2=0.74(0.42-1.31)•Q3=1.07(0.55-2.09)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 72 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)OutcomeMeasure:CHDincidencePoissonRegression•Q4=0.64(0.34-1.24)MultivariateRR(95%CI)Sports,men•Q1=1.00(referent)•Q2=1.15(0.79-1.68)•Q3=1.03(0.68-1.54)•Q4=0.83(0.56-1.23)Sports,women•Q1=1.00(referent)•Q2=0.99(0.58-1.67)•Q3=0.64(0.32-1.27)•Q4=0.72(0.37-1.38)Franssonetal2004[228]ToestimatetheinfluenceofLTPAandOPAonacuteMI.•n=4069(2,742men;1,327women)PAassessment:QuestionnaireforLTPA,5groups•NumberofCases:1,204men,550womenExerciseseemstoreducetheriskofMI.Sweden•Sex:MenandWomenG1=SeldomOR(95%CI)G2=SometimesCaseControl•Age:45-70yrG3=1×/wkLTPA,men•Characteristics:Cases:DiagnosedwithacuteMIG4=2-3×/wk•G1=1.00(referent)D&Bscore=12G5=>3×/wk•G2=0.76(0.61-0.95)•G3=0.67(0.51-0.88)•G4=0.63(0.49-0.83)•StockholmHeartEpidemiologyQuestionnairefortotalphysicalactivity,3groups•G5=0.53(0.38-0.73)G1=PassiveG2=SomewhatactiveLTPA,womenG3=Active•G1=1.00(referent)Questionnaireforsittingatwork,3groups•G2=0.69(0.49-0.98)•G3=0.38(0.25-0.58)G1=Lessthanhalfthetime•G4=0.62(0.38-1.01)G2=Abouthalfthetime•G5=0.31(0.15-0.66)G3=MorethanhalfthetimeTotalphysicalactivity,men•G1=1.00(referent)•G2=0.66(0.47-0.94)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 73 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)OutcomeMeasure:AcuteMI•G3=0.46(0.31-0.69)Totalphysicalactivity,womenConditionalandunconditionallogisticsregression•G1=1.00(referent)•G2=0.34(0.22-0.53)•G3=0.16(0.07-0.37)Sittingatwork,men•G1=1.00(referent)•G2=0.91(0.73-1.15)•G3=0.90(0.72-1.12)Sittingatwork,women•G1=1.00(referent)•G2=0.77(0.51-1.17)•G3=0.47(0.31-0.69)Franssonetal2006[229]ToevaluatewhetherLTPAcompensatesfortheincreasedriskofacuteMIassociatedwithoverweightandobesity.•n=4069(2,742men;1,327women)PAAssessment:QuestionnaireforLTPA,3groupsNumberofCases:1204men,550womenRegularLTPAseemstoprovideprotectionagainstMIandnon-fatalMI.MultivariateOR(95%CI)foracuteMISweden•Sex:MenandwomenG1=Verylittle/occasionalwalksLTPA,men•G1=1.00(referent)CaseControl•Age:45-70yrG2=Occasional/onceperweek•G2=0.70(0.58-0.84)•Characteristics:Cases:hadacuteMI•G3=0.57(0.46-0.71)D&Bscore=12G3=TwiceperweekormoreLTPA,women•G1=1.00(referent)Outcomemeasure:AcuteMI•G2=0.52(0.40-0.68)•G3=0.44(0.30-0.65)MultivariateOR(95%CI)fornon-fatalMIConditionalandunconditionallogisticsregressionLTPA,men•G1=1.00(referent)•G2=0.79(0.65-0.96)•G3=0.63(0.50-0.79)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 74 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)LTPA,women•G1=1.00(referent)•G2=0.64(0.48-0.86)•G3=0.58(0.39-0.87)Haapanen-Niemi2000[230]ToinvestigatetheindependentassociationsandthepossibleinteractionofBMILTPAandperceivedphysicalperformanceandfunctionalcapacitywiththeriskofmortality.•n=2,212(1,090men;1,122women)LengthofFollow-up:16yrs•NumberofCases:208allcausedeaths,54%ofthoseCVD.73%ofCVDdeathsduetoCHDIncreaseperceivedPFisassociatedwithareducedriskofCHDmortalityinmen.Finland•Sex:MenandwomenPAassessment:PostalSurveyMultivariateRR(95%CI)Prospectivecohort•Age:35-63yrTotalLTPAenergyexpenditure(kcal/wk)TotalLTPAEEindexandCHDmortality,men•Characteristics:Healthy•G1=1.00(referent)G1=High•G2=0.88(0.44-1.76)D&Bscore=13•Ethnicity:FinnishG2=Moderate•G3=1.70(0.90-3.21)G3=Lowp=0.056Perceivedphysicalfitnesscomparedtoage-matesMultivariateRR(95%CI)Perceivedphysicalfitness,menG1=Better•G1=1.00(referent)G2=Similar•G2=2.82(1.06-7.46)G3=Worse•G3=4.64(1.56-13.84)OutcomeMeasure:CHDmortalityp=0.011TotalLTPAEEindexandCHDmortality,womenCoxproportionalHR•G1=1.00(referent)•G2=0.43(0.16-1.16)•G3=1.17(0.51-2.68)p=0.046MultivariateRR(95%CI)Perceivedphysicalfitness,women •G1=1.00(referent)•G2=0.82(0.32-2.16)•G3=1.89(0.57-6.27)p=0.154Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 75 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Kanneletal1986[231]ToexaminetheroleoflowlevelsofOPAandLTPAinthedevelopmentofCVmorbidityandmortalityovertheshortandlongterm.•n=1,166LengthofFollow-up:24yrs•NumberofCases:220mortality,371morbidityRateofCHDMortalityandMorbiditydecreaseswithincreasedlevelofPAbutnoassociationwasfoundwithphysicaldemandofwork•Sex:Men•Age:45-65yrUSA•Characteristics:PAassessment:QuestionnaireduringexaminationCumulative24yearageadjustedrateper1000peopleProspectivecohort24hrPAindexforLTPACHDmortalityPAindex:•G1=255D&Bscore=11G1=<29•G2=184G2=30-34•G3=152G3=>34p<0.01Physicaldemandofwork24hrPAindexforLTPACHDincidenceG1=Sedentary•G1=414G2=Light•G2=353G3=Medium•G3=311G4=HeavyOutcomeMeasure:CHDmortalityandMorbidityPhysicaldemandofworkandCHDmortality•G1=216CoxproportionalHR•G2=209•G3=169•G4=170PhysicaldemandofworkandCHDincidence:•G1=355•G2=405•G3=307•G4=325Kaprioetal2000[232]ToexaminethecontributionofgeneticandotherfamilialfactorstotherelationshipbetweenLTPAandCHD.•n=8,205LengthofFollow-up:18yrs•NumberofCases:723LTPAcomparedtobeingsedentaryhelpspreventCHDinmen.•Sex:Men•Age:25-69yrMultivariateRR(95%CI)Finland•Characteristics:Samesextwinpairs,freeofCVDPAassessment:QuestionnaireforLTPA,3groups:•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 76 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)•G2=0.84(0.70-1.01)Prospectivecohort•G3=0.68(0.50-0.92)G1=Sedentaryp=0.010G2=OccasionalD&Bscore=12ExercisersG3=ConditioningExercisersOutcomeMeasure:HospitalizationordeathfromCHDPoissonregressionLakkaetal1994[233]ToinvestigatetheindependentassociationsofLTPAandmaximaloxygenuptakewiththeriskofacuteMI.•n=1,166Baselineexamination:1984-1989ConditioningLTPAandVO2maxhadaninverse,gradedandindependentassociationwiththerisk•Sex:Men•Age:42-61yrAdjustedRH(95%CI)byconditioningPAlevelFinland•Characteristics:HealthywithnormalECGPAassessment:QuestionnaireforconditioningPA(h/wk),3groups(h/wk)G1=<0.7•G1=1.00(referent)ProspectivecohortG2=0.7•G2=1.11(0.58-2.12)•KuopioIschaemicHeartDiseaseRiskFactorStudyG3=>2.2•G3=0.31(0.12-0.85)D&Bscore=13AdjustedRG(95%CI)byVO2max•G1=1.00PFassessment:VO2max(ml/kg/min)•G2=0.76(0.38-1.50)•G3=0.26(0.10-0.68)G1=<28.0G2=28.0-33.6G3=>33.6Outcomeevent:acuteMICoxproportionalHRWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 77 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Laukkanenatal2004[234]TodeterminewhetherVO2peakpredictsCVDmorbidityandmortalityinasampleofmenasrelatedtoconventionalriskfactors,medicationsorunderlyingchronicdisease.•1,294healthy;1,057unhealthyPFAssessment:VO2peak(ml/kg/min)measuredbyexercisetestwithanelectricallybrakedcycleergometer,dividedintoquartiles•NumberofCases:204CVdeaths,323non-fatalcoronaryeventsDose-responserelationshipbetweendirectlymeasuredPFandCVDdeathamonghealthymenatbaseline.Finland•Sex:MenHealthymenwithlowVO2peak(lowestquartile)hadanincreasedrisk•Age:42-60yrProspectivecohort•Characteristics:HealthyandnothealthyparticipantsQ1=<27.6AdjustedRR(95%CI)byPFquartileFatalMIQ2=27.6-32.2Unfitmenwithunfavorableriskprofilesaretheriskgroupthatwouldbenefitthemostfrompreventativemeasures.D&Bscore=11Q3=32.3-37.1•3.29(0.86-12.90)•KuopioIschaemicHeartDiseaseRiskFactorStudyQ4=>37.2Non-FatalMIOutcomeMeasure:IncidenceoffatalandnonfatalCVDduring13yearfollow-up•2.16(1.12-4.18)CoxproportionalHRLeeatal2000[235]ToinvestigatewhetherdifferentdurationsofexerciseepisodeareassociatedwithdifferentriskofCHD.•n=7,307Baselinesurveyin1988•NumberofCases:482LongerdurationsofPAboutsarenotassociatedwithdecreasedCHDriskcomparedwithshorterbouts,oncetotalEEistakenintoaccount.•Sex:MenUSA•Age:Mean66.1±7.5PAassessment:SurveyforEE(kJ/wk),dividedinto5groupsandepisodesofPA(min),dividedinto6groupsMultivariateadjustedRR(95%CI)byEE•G1=1.00(referent)•Characteristics:Healthy•G2=0.80(0.57-1.12)•G3=0.80(0.55-1.16)Prospectivecohort•HarvardAlumniStudy•G4=0.74(0.47-1.17)•G5=0.62(0.41-0.94)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 78 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)D&Bscore=12Energyexpenditure(kJ/wk)AslongasthetotalEEissimilar,morefrequentshorterboutsorlongerlessfrequentboutshaveanequivalentreductioninCHDrisk.G1=<4,200MultivariateadjustedRR(95%CI)bydurationofPAepisodeG2=4,200-8,399G3=8,400-12,599G4=12,600-16,799•G1=1.00(referent)G5=≥16,800•G2=1.15(0.70-1.87)•G3=1.01(0.68-1.51)•G4=1.11(0.67-1.84)DurationofPAepisode(min)•G5=1.18(0.77-1.80)G1=None•G6=1.25(0.83-1.87)G2=1-15G3=16-30G4=31-45G5=46-60G6=>60OutcomeMeasure:FatalandNonFatalCHDProportionalhazardsregressionLeeetal2003[236]Toinvestigatewhethermoderate-intensityexerciseisassociatedwithreducedCHD.•n=7,337PAassessment:Surveyratingusuallevelofexertionwhenexercising,dividedintotertiles•NumberofCases:551InverseassociationbetweenrelativeintensityofPAandtheriskofCHD.USA•Sex:MaleMultivariateadjustmentRR(95%CI)•Age:Mean66.1yr•T1=1.00(referent)•T2=0.87(0.70-1.09)•Characteristics:Healthy•T3=0.92(0.75-1.14)ProspectivecohortEnergyexpenditure(kcal/wk)HarvardAlumniStudyT1=<1000D&Bscore=13T2=1000-2499T3=≥2500CoxproportionalHRWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 79 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Lemaitreetal1999[237]Toinvestigatewhetherregularparticipationinmoderateintensityactivityconfersoverallprotectionfromsuddenprimarycardiacarrest.•n=355cases,503controlsPAassessment:Interview(withspouses)forLTPA,7groups•355casesParticipationinmoderateintensityLTPAwasassociatedwithadecreasedriskofprimarycardiacarrest.•Sex:MenandwomenRR(95%CI)USAG1=Noactivity•G1=1.00(referent)•Age:25-74yrG2=Gardeningonly≤60min/wk•G2=0.52(0.21-1.28)Casecontrol•Characteristics:Previouslyhealthypriortoprimarycardiacarrest.ControlSubjects:Individuallymatchedtocasepatientsonage(within7years)andsexataratioofabout2:1wererandomlyselectedfromcommunitybyrandom-digitdialingG3=Gardeningonly>60min/wk•G3=0.34(0.130.89)G4=Walking≤60min/wk•G4=0.45(0.17-1.19)D&Bscore=11G5=Walking>60min/wk•G5=0.27(0.11-0.67)G6=Moderateintensity•G6=0.31(0.13-0.74)LTPA(notwalkingorgardening)•G7=0.34(0.16-0.75)G7=HighintensityLTPALogisticregressionanalysisLemaitreetal1995[238]ToexaminewhetherLTPAdecreasestheriskofMIinpostmenopausalwomen.•n=1,193PAassessment:PhoneinterviewforLTPA,dividedintoquartilesofEE(meankcal/wk)•NumberofCases:268RiskofMIamongpostmenopausalwomenisdecreasedby50%withmodestLTenergyexpenditures,equivalentto30-45minofwalkingforexercisethreetimesperweek•Sex:Women•Age:Mean67yrMultivariateRR(95%CI)USA•Q1=1.00(referent)•Characteristics:PostmenopausalCases:Diagnosedwithnon-fatalMIControls:freefromMIQ1=71•Q2=0.52(0.34-0.80)CasecontrolQ2=472•Q3=0.40(0.26-0.63)Q3=1183•Q4=0.40(0.25-0.63)D&Bscore=11Q4=3576p=<0.001OutcomeMeasure:Diagnosedwithnon-fatalMILogisticregressionanalysisWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 80 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Lietal2006[239]ToexamineindependentandjointassociationsofPAandadipositywithCHDincidence.•n=88,393LengthofFollow-up:20yrs•NumberofCases:2,358PhysicalinactivityindependentlycontributestothedevelopmentofCHDinwomen.•Sex:Women•NumberofDropouts:<2%losttofollow-contributestothedevelopmentofCHDinwomen.USA•Age:34-59yrup•Characteristics:NursesPAassessment:QuestionnaireforLTPA(hr/wk),3groupsProspectivecohortMultivariateHR(95%CI)•Nurses’HealthStudy•G1=1.00(referent)G1=≥3.5•G2=1.34(1.18-1.51)D&Bscore=12G2=1-3.49•G3=1.43(1.26-1.63)G3=<1OutcomeMeasure:CHDincidenceCoxproportionalHRLemaitreetal1995[240]ToevaluatetheeffectofPAonMIoccurrence.•n=1,107(726controls,381cases)PAassessment:Questionnaire,3-5groupsdependingonvariableOR(95%CI),PAlevelwasinverselyassociatedwithoccurrenceofMIinbothsexes,althoughtheassociationpresentedasignificantlineartrendonlyforwomen;inmenitsuggestedau-shapedrelation.TotalPA,menPortugal•Sex:Menandwomen•G1=1.00(referent)TotalPA(METhr/day),men•G2=0.54(0.33-0.88)Casecontrol•Age:≥40yr•G3=0.34(0.20-0.59)•Characteristics:Case:AdmittedtoHospitalanddiagnosedwithfirstepisodeofMIControl:Healthy,nohistoryofCHDG1=28.3-32.1•G4=0.59(0.36-0.98)D&Bscore=12G2=32.2-33.3•G5=0.90(0.56-1.45)G3=33.4-36.5Trendp=0.827G4=36.6-40.3TotalPA,womenG5=40.4-83.1•Q1=1.00(referent)TotalPA(METhr/day),women•Q2=0.39(0.21-0.73)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 81 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Q1=28.9-32.7•Q3=0.33(0.17-0.64)Q2=32.8-34.1•Q4=0.22(0.11-0.47)Q3=34.2-37.8p=<0.001Q4=37.8-70.6Sportparticipation,menSportparticipation(METhr/day),men•G1=1.00(referent)G1=0.0•G2=0.36(0.19-0.69),G2=0.1-1.0•G3=0.72(0.41-1.26),G3=1.1-2.0•G4=0.42(0.23-0.76),G4=2.1-3.6•G5=0.31(0.16-0.62)G5=3.7-15.4p=<0.001Lovasietal2007[241]ToinvestigatetheshapeoftherelationshipbetweenLTPAandMIrisk.•n=4,094PAassessment:Telephoneinterview(MinnesotaLTPAQuestionnaire)•NumberofCases:697TimeengagedinLTPA,evennonstrenuousLTPAwasassociatedwithalowerriskofMI,andtheshapeofthisrelationshipwasnon-linear•Sex:MenandwomenAdjustedOR(95%CI)USA•Age:64±9yrLTPAandnonfatalCHD•Characteristics:GroupHealthCooperativeMembers•G1=1.00(referent)CasecontrolLTPA•G2=0.88(0.66-1.17)G1=None•G3=0.62(0.46-0.83)D&Bscore=11G2=<2•G4=0.61(0.45-0.82)G3=2-5•G5=0.59(0.44-0.80)G4=5-9G5=>9h/wkAdjustedRR(95%CI)StrenuousLTPAandnonFatalCHDStrenuousLTPA•G1=1.00(referent)G1=None•G2=0.76(0.59-0.99)G2=nonstrenuousLTPA•G3=0.53(0.40-0.70)G3=AnyStrenuousLTPAOutcomemeasure:nonfatalCHDLogisticregressionWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 82 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Mansonetal1999[242]Toassessthecomparativerolesofwalkingandvigorousexerciseinthepreventionofcoronaryeventsinwomen.•n=72,488PAassessment:•NumberofCases:645coronaryeventsBothwalkingandVPAareassociatedwithasubstantialreductionsinincidenceofCHD.RiskreductionsforeachweresimilarhentotalPAywassimilar.Walking3ormorehoursperweekcouldreducetheriskofCHDby30-40%.•Sex:WomenQuestionnairewithdetailedinformationonPA.•Age:40-65yrMultivariateRR(95%CI)bytotalPAscoreUSA•Characteristics:Healthy,noPrevioushistoryofCHD•G1=1.00(referent)•G2=0.88(0.71-1.10)ProspectivecohortTotalPAscore•G3=0.81(0.64-1.02)G1=1-2.0•G4=0.74(0.58-0.95)Nurses’HealthStudyG2=2.1-4.6•G5=0.66(0.51-0.86)D&Bscore=12G3=4.7-10.4p=0.002G4=10.5-21.7G5=>21.7MultivariateRR(95%CI)bywalkingactivity•G1=1.00(referent)Walking,inthosewhodidnotparticipateinVPA:(METhr/wk)•G2=0.78(0.57-1.06)G1=0.5•G3=0.88(0.65-1.21)G2=0.6-2.0•G4=0.70(0.51-0.95)G3=2.1-3.8•G5=0.65(0.47-0.91)G4=3.9-9.9p=0.02G5=≥10MultivariateRR(95%CI)bywalkingpace•1.00(referent)Walkingpace(mph)•0.75(0.59-0.96)G1=<2.0•0.64(0.47-0.88)G2=2.0-2.9G3=≥3.0Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 83 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Moraetal2007[243]ToinvestigatewhetherdifferencesinseveralCVriskfactorsmediatetheeffectofPAonreducedriskofCVD.•n=27,05510.9±1.6yroffollowup•NumberofCases:640ThereremainedaborderlinesignificantinverseassociationbetweenPAandriskofCHDafteradjustmentforallsetsofriskfactors.•Sex:Women•Age:≥45yrPAassessment:QuestionnairesatstudyentryforcategoriesofEEfromPA(kcal/wk),4groupsHR(95%CI),basicmodelUSA•Characteristics:Healthy•G1=1.00(referent)•G2=0.84(0.67-1.06)Prospectivecohort•Women’shealthstudy•G3=0.76(0.61-0.96)•G4=0.62(0.48-0.82)G1=<200p=0.001D&Bscore=13G2=200-599WhileallsetsofriskfactorsshouldsomemediationontheeffectofPAonCHDnonemadetherelationshipinsignificantG3=600-1499MultivariateadjustedHR(95%CI)G4=≥1500•G1=1.00(referent)•G2=0.71(0.58-0.87)Outcomemeasure:•G3=0.64(0.52-0.78)IncidenceofCVDand•G4=0.48(0.38-0.62)p=<0.001CoxproportionalHRO’Connoretal1995[244]ToexaminetheassociationbetweenintensityofexerciseandCHDrisk.•n=680(532menand148women)PAassessment:HomeinterviewforPA,dividedintoquartiles•NumberofCases:340SignificantinverseassociationbetweenPAlevelandtheriskofnonfatalMIinmen,whichpersistedafteradjustmentforotherriskfactors.AdjustedOR(95%CI)byPAlevel,men•Q1=1.00(referent)USA•Sex:MenandwomenQ1=Lowest•Q2=0.60(0.32-1.13)Q2•Q3=0.41(0.21-0.78)Casecontrol•Age:<76yrQ3•Q4=0.41(0.22-0.77)•Characteristics:Cases:DiagnosedMI(non-fatal),noprevioushistoryofCHD.Controls:nohistoryofCHD.Q4=Highestp=0.003D&Bscore=12OutcomeMeasure:non-fatalMIAdjustedOR(95%CI)byPAlevel,women•Q1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 84 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Moderate-vigoroussportsmenCut-pointskcal/wk•Q2=1.07(0.27-4.17)Q1=Lowest•Q3=2.02(0.56-7.38)Q2•Q4=1.29(0.31-5.35)Q3p=0.51Q4=HighestAdjustedOR(95%CI)bymoderate-vigoroussports,men•Q1=1.00(referent)Moderate-vigoroussportsWomen•Q2=1.12(0.60-2.10)Cut-pointskcal/wk•Q3=0.61(0.30-1.24)Q1=Lowest•Q4=0.43(0.20-0.92)Q2p=0.02Q3Q4=HighestAdjustedOR(95%CI)bymoderate-vigoroussports,womenLogisticregressionanalysis•Q1=1.00(referent)•Q2=1.31(0.37-4.66)•Q3=1.90(0.44-8.28)•Q4=0.35(0.07-1.84)p=0.62Rastogietal2004[245]ToexaminetherelationbetweenPAandCHDriskinIndia.•n=1,050PAassessment:QuestionnaireNumberofCases:350ObservedastronganddosedependentinverseassociationbetweenLTPAandnonfatalCHD.•Sex:MenandwomenMultivariateOR(95%CI)byLTPAUSA•Age:21-74yrLTPA(METmin/d)•G1=1.00(referent)•Characteristics:Cases:DiagnosedwithMI(nonfatal)Controls:non-cardiacpatientsG1=0•G2=0.96(0.59-1.55)CasecontrolG2=0-145•G3=0.44(0.27-0.71)D&Bscore=12G3=≥145p=0.001Sedentarytime(min/d)MultivariateOR(95%CI)bysedentarytimeG1=<70•G1=1.00(referent)G2=70-130•G2=1.15(0.68-1.95)G3=130-215•G3=1.04(0.61-1.76)G4=≥215•G4=1.88(1.09-3.21)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 85 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)p=0.02OutcomeMeasure:Non-fatalMIConditionallogisticregressionRodriguezetal1994[246]ToexaminetherelationshipbetweenPAand23yrincidenceofCHDmorbidityandmortality.•n=7,07423yearfollow-up•NumberofCases:789PAwasassociatedwithasignificantreductionintheriskofCHDmorbidityandmortality.•Sex:Men•Age:45-64yrPAassessment:QuestionnaireforPAindex,dividedintotertilesAgeadjustedRR(95%CI),CHDincidenceUSA•Characteristics:Japanese-AmericanlivinginOahu,Hawaiiin1965,<65yearstoreduceeffectofretirementonPAlevels•T1=1.00(referent)•T2=1.01(.86-1.19)ProspectivecohortT1=Low•T3=0.83(0.86-1.19)ThesedatasupportthehypothesisthatPAisassociatedwithafavorableprofileofCVDriskfactors.T2=ModerateT3=HighMultivariateadjustedRR(95%CI),CHDincidenceD&Bscore=11Coxproportionalregressionmodel•T1=1.00(referent)•T2=1.07(0.90-1.26)Thisstudydidnotshowadose-responserelationshipsincethemediumtertileofPAshowedincreasedratesofCHDcomparedtotheinactivegroup.•TheHonoluluHeartProgram•T3=0.95(0.80-1.14)AgeadjustedRR(95%CI),CHDmortality•T1=1.00(referent)•T2=1.12(0.88-1.44)•T3=0.74(0.56-0.97)MultivariateadjustedRR(95%CI)•T1=1.00(referent)•T2=1.19(0.93-1.53)•T3=0.85(0.65-1.13)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 86 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Rothenbacheretal2003[247]ToestimatetheriskforCHDassociatedwithLTPA.•n=791(312cases;479controls)PAassessment:InterviewNumberofCases:312LTPAshowedaclearinverseassociationwithriskofCHD.LTPA(h/wk)MultivariateOR(95%CI),LTPAGermany•Sex:MenandWomenG1=0WinterG2=<1•G1=1.00(referent)CasecontrolAge:40-68yrG3=1-2•G2=0.48(0.27-0.84)Characteristics:Cases:stableCHDdiagnosedwithin2years,norecentMI,Controls:nohistoryofCHD.G4=>2•G3=0.54(0.369-0.82)D&Bscore=12•G4=0.27(0.19-0.47)Workdayactivitybybike/foot,(min/workday)SummerG1=<15•G1=1.00(referent)G2=15-30•G2=0.85(0.47-1.53)G3=30-60•G3=0.60(0.38-0.95)G4=>60•G4=0.39(0.26-0.59)OutcomeMeasure:nonfatalCHDMultivariateOR(95%CI),workdayactivitybybike/footUnconditionallogisticregression,linearregressionmodel•G1=1.00(referent)•G2=0.53(0.30-0.93)•G3=0.36(0.21-0.62)•G4=0.58(0.36-0.94)SeccarecciaandMenotti1992[248]ToexaminetherelationshipbetweenOPAandtheriskofCHDdeath.•n=1,62125yearoffollow-up•189casesIncreaseinOPAisinverselyrelatedtoriskofCHDdeath.•Sex:Men•Age:40-59yrPAassessment:QuestionnaireforOPA(kcal/d),3groupsAgeStandardizedCHDanddeathsrates:•Characteristics:Healthy•G1=18.9±3.1Italy•G2=13.1±1.7G1=Sedentary,<2400•G3=11.0±0.9ProspectivecohortG2=Moderate,2400-3199D&Bscore=11G3=Heavy≥3200Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 87 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)IndicatorsofPFincludingHR,vitalcapacity,FEVin3/4ofsec,andcorrectedarmcircumference(minuscontributionoffat).EndPoint:FatalCHDSessoetal2000[249]ToexaminetheassociationofthequantityandintensityofPAwithCHDriskandtheimpactofothercoronaryriskfactors.•n=12,516PAassessment:QuestionnaireNumberofCases:2,135L-ShapedassociationbetweenPAandtheriskofCHD,withareductioninCHDriskofapproximately20%fortotalPAlevels>4200kJ/wk•Sex:Men•Age:39-88yrMultivariateHR(95%CI)USA•Characteristics:HealthyPAIndex(kJ/wk)•G1=1.00(referent)G1=<2100•G2=0.90(0.79-1.03)Prospectivecohort•HarvardAlumniG2=2100-4199•G3=0.81(0.71-0.92)StudyG3=4200-8399•G4=0.80(0.69-0.93)G4=8400-12599•G5=0.81(0.71-0.94)D&Bscore=12G5=>12600p=0.003SuggeststhatvigorousactivitiesareassociatedwithareducedriskofCHD,whereasmoderateorlightPAhasnoclearassociationwithriskofCHD.CoxproportionalHRSundquistetal2005[250]ToexaminethelongtermeffectofLTPAonincidentcasesofCHD.•n=5,196(2,645men,2,551women)PAassessment:QuestionnaireLevelsofPAAgeandsexadjustedRR(95%CI)PositivelongtermeffectofLTPAonCHDriskamongmenandwomen.•Q1=1.00(referent)Sweden•Sex:MenandwomenQ1=None•Q2=0.72(0.51-1.00)Q2=Occasionally•Q3=0.64(0.46-0.89)ProspectivecohortAge:35-74yrQ3=1-2timesperweek•Q4=0.46(0.29-0.74)•Characteristics:ThosenothospitalizedforCHDinthelast2yearsandthosewhoratetheirgeneralhealthaspoorwereexcludedQ4=Vigorous≥2timesperweekMultivariateadjustedRR(95%CI)D&Bscore=11OutcomeMeasure:FatalornonfatalCHD•Q1=1.00(referent)•Q2=0.76(0.55-1.07)•Q3=0.74(0.53-1.04)•Q4=0.59(0.37-0.95)CoxregressionmodelWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 88 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Talbotetal2002[251]ToexaminethecontributionsofLTPAandaerobicfitnesstotheriskofcoronaryeventsinhealthyyoungerandolderadults.•n=689Surveysbeganin1960andwerecompletedoneveryvisit•NumberofCases:63InyoungermenPFpredictsareducedriskofCHDbutnotLTPA.•Sex:Men•Age:Afteradjustingforcoronaryriskfactorstherewas:USA51.6±16.8yr•Characteristics:CommunitydwellingPAassessment:SurveyforLTPA(97activities)ateveryvisit.RR:0.53(p<0.001)andInoldermen,highintensityLTPAandPFappeartobeofsimilarimportanceinreducingCHDrisk.ProspectivecohortRR:0.61(p=0.024)inoldermen.D&Bscore=12•BaltimoreLongitudinalStudyofAgingPFassessment:TreadmillVO2maxtestonalternatevisitsTotalLTPAwasunrelatedtocoronaryriskineitheragegroup.With3levelsofLTPAintensitysubstitutedfortotalLTPA:Unpairedt-testsandchisquaretests.CoxProportionalhazardsAnalysisRR=0.39fortertile3vs.tertile1Tanasescuetal2002[252]Toassesstheamount,typeandintensityofPAinrelationtoriskofCHDinmen.•n=44,452PAassessment:Questionnaire•NumberofCases:1,700TotalPA,running,weighttraining,andwalkingwereassociatedwithareducedriskforCVD.•Sex:Men•Age:40-75yrAgeadjustedHR(95%CI)bytotalPAUSA•Characteristics:Healthprofessionals,nohistoryofCHDandingoodhealthTotalPA(METhr/wk)•Q1=1.00(referent)Q1=0-6.32•Q2=0.85(0.740.98)ProspectivecohortQ2=6.33-14.49•Q3=0.78(0.67-0.92)Q3=14.50-25.08•Q4=0.72(0.62-0.83)Theaverageexerciseintensitywasassociatedwithareducedrisk(independentoftotalPA).Q4=25.09-41.98•Q5=0.58(0.49-0.68)D&Bscore=11Q5=>41.99p=.001•HealthProfessionalsfollow-upstudyExerciseintensity(METs)AgeadjustedHR(95%CI)byexerciseintensityG1=Low-1-4•G1=.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 89 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)G2=Mod.-4-6•G2=0.94(0.83-1.04)G3=High6-12WalkingpaceindependentoftotalvolumeofPA(mph)•G3=0.83(0.72-0.97)p=0.02Q1=<2AgeadjustedHR(95%CI)bywalkingpaceQ2=2-3•Q1=1.00(referent)Q3=3-4•Q2=0.72(0.54-0.94)Q4=>4•Q3=0.61(0.45-0.81)•Q4=0.51(0.31-0.84)OutcomeMeasure:NonfatalMIorFatalCHDoccurringduringfollow-upp<0.001CoxproportionalHRVattenetal2006[253]Toinvestigatewhetherobesity-relatedCVmortalitycouldbemodifiedbyPA.•n=54,284(27,769men;26,515women)LengthofFollow-up:16years•NumberofCases:2,462IncreasedPAreducestheriskofdeathinwomen,butnotinmen.MultivariateHR(95%CI),menNorway•Sex:MenandwomenPAassessment:•Q1=1.00(referent)Questionnaire•Q2=1.01(0.89-1.16)ProspectivecohortAge:≥20yrDividedinto4groups•Q3=0.98(0.84-1.14)•Characteristics:FreefromCVDatbaselineQ1=High•Q4=1.18(1.00-1.38)Q2=Mediump=0.11D&Bscore=12Q3=Low•HUNTstudyQ4=NeverMultivariateHR(95%CI),womenOutcomeMeasure:Ischemicheartdiseasemortality•Q1=1.00(referent)•Q2=1.23(1.01-1.51)•Q3=1.54(1.24-1.91)•Q4=1.52(1.23-1.88)CoxproportionalHRp<0.001Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 90 of 220Table12:Studiesexaminingtherelationshipbetweenphysicalactivityandcardiovasculardisease.(Continued)Wagneretal2002[254]ToinvestigateiftheassociationbetweenPApatternsandincidenceofcoronaryeventscouldexplainthegradientinCHDobservedbetween2countries.•n=9,758LengthofFollow-up:5yrsNumberofCases:167hardCHD,154anginaeventsBeneficialeffectofLTPAEEonhardCHDincidenceinmiddleagedmen.•Sex:MenandwomenPAassessment:QuestionnaireforLTPA,3groups:NumberofDropouts:<2%Ireland/France•Age:50-59yr•Characteristics:HealthyatBaselineHR(95%CI),hardeventsProspectivecohortG1=Lowest•G1=1.00(referent)G2=Middle•G2=0.73(0.51-1.05)G3=Highest•G3=0.66(0.46-0.96)D&Bscore=12OutcomeMeasure:CHDhardeventsandAnginap=0.04HR(95%CI),angina•G1=1.00(referent)CoxproportionalHR•G2=0.83(0.55-1.25)•G3=1.28(0.88-1.86)p=0.10D&Bscore,DownsandBlackqualityscore;YR,years;G,groups;CHD,coronaryheartdisease;RR,riskratio;95%CI,95%confidenceinterval;PA,physicalactivity;VPA,vigorousphysicalactivity;CV,cardiovascular;MET,metabolicequivalent;kcal/wk,kilocaloriesperweek;Q,quartileorquintile;km/h,kilometersperhour;LTPA,leisure-timephysicalactivity;HR,hazardratio;OPA,occupationalphysicalactivity;kcal/kg/daykilocaloriesperkilogramperday;MI,myocardialinfarction;ECG,electrocardiogram;kcal/kg/hkilocaloriesperkilogramperhour;mph,milesperhour;CVD,cardiovasculardisease.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 91 of 22030% risk reduction in the most active individuals [31]. Infact, in a review of the literature Katzmarzyk and Jans-sen [20] reported that lack of physical activity carried arelative risk of 1.60 (95% CI = 1.42-1.80) for stroke,similar to or higher than that for coronary heart disease(1.45), hypertension (1.30), colon cancer (1.41), breastcancer (1.31), type 2 diabetes (1.50), and osteoporosis(1.59).In our systematic review of the literature, a total of1104 citations were identified during the electronic data-base search (Figure 5). Of these citations, 405 were iden-tified in MEDLINE, 183 in EMBASE, 227 in Cochrane,and 289 in the CINAHL/SportDiscus/PsychInfo search.A total of 13 duplicates were found, leaving a total of1091 unique citations. A total of 1011 articles wereexcluded after scanning, leaving a total of 80 articles forfull review. An additional 9 articles were retrievedthrough cross-referencing and the authors’ knowledge ofthe field. From these articles 64 were excluded after fullreview leaving 25 articles for inclusion in the systematicreview. The reasons for exclusion included non-experi-mental/weak design (poor execution introducing bias)(n = 16), did not contain three levels of physical activityor not possible to determine dose-response relationship(n = 14), reviews, summaries, meta-analyses (n = 17),dissertations, thesis, abstracts (n = 8), and other (n = 9).Therefore, a total of 25 articles were included in the sys-tematic review of the literature regarding the relation-ship between physical activity and the primaryprevention of stroke (Table 13).The data providing dose-response information is allobservational in nature, involving both case control andcohort investigations. These studies (predominantly pro-spective cohort designs) included a total of 479,336 par-ticipants; averaging 17,753 subjects per study (range428-73,265). There were a total of 12,361 reported casesof stroke (ranging per study from 32-2,863). The totallength of study follow-up for the prospective cohort stu-dies averaged 13.2 yr (ranging from 6-26 yr). The arti-cles were published over a 14 yr period ranging from1993 to 2007. These studies involved large samples ofmen and women from regions throughout the worldincluding studies from the USA (11), UK (2), Iceland(1), Denmark (2), Norway (4), Netherlands (1), Finland(2), Japan (1), Australia (1) and Greece (1). Very fewstudies [69,70] examined non-Caucasian participants.We found strong evidence that physical activity wasassociated with a reduced risk for stroke. The level of evi-dence was consistent with a Level 3A classification. Weobserved an average risk reduction of 31% across all stu-dies (median = 29%). In comparison to cardiovasculardisease, there was more variability in the risk reductionsin stroke in the highest activity/fitness group. The qual-ity of the investigations was also generally quite goodwith a mean (and median) Downs and Black score of 13(range 11-15).The risk reductions appear to be even greater in stu-dies that assessed physical fitness directly. For instance,in data from the Aerobics Center Longitudinal Study[71] the high fitness group (estimated peak METs =13.1) and the moderate fitness group (estimated peakMETs 10.5) had significantly lower risks of stroke mor-tality (68 and 63%, respectively) than the least fit men(estimated peak METs 8.5).A dose-response relationship did emerge when exam-ining the literature. However, as illustrated by othersthis was extremely variable amongst studies and variedFigure 5 Results of the Literature Search for Stroke.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 92 of 220Table13Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsWisloffetal2006[58]ToassessexerciseamountandintensityinrelationtosubsequentCVDmortality(includingstroke).•n=27,143men,28,929women16yearfollowupMultivariateadjustedRR(95%CI)MenBothhighandlow-intensityexercisemaybeassociatedwithareducedriskofstrokeinbothmenandwomen.Norway•Sex:MenandwomenPAAssessment:QuestionnaireG1=1.00(referent)•Age:≥20yrG2=0.90(0.70-1.17)•Characteristics:freefromCVDPAG3a=0.90(0.64-1.26)•HUNTStudyG1=NoneG3b=0.59(0.27-1.27)G2=<1/wkG3c=0.62(0.40-0.95)G3a=1/wk≤30minlowG3d=0.51(0.31-0.86)G3b=1/wk≤30minhighG4a=0.72(0.49-1.05)G3c=1/wk>30minlowG4b=0.63(0.31-1.30)ProspectivecohortG3d=1/wk>30minhighG4c=1.02(0.72-1.44)G4a=2-3/wk≤30minlowG4d=0.59(0.37-0.92)G4b=2-3/wk≤30minhighG5a=0.97(0.70-1.36)D&Bscore=12G4c=2-3/wk>30minlowG5b=0.68(0.27-1.66)G4d=2-3/wk>30minhighG5c=0.81(0.65-1.20)G5a=≥4/wk≤30minlowG5d=0.67(0.49-1.11)G5b=≥4/wk≤30minhighG5c=≥4wk>30minlowRR(95%CI)WomenG5d=≥4/wk>30minhighG1=1.00(referent)OutcomeMeasure:IHDmortalityG2=1.01(0.81-1.25)CoxproportionalHRG3a=0.88(0.68-1.15)G3b=0.98(0.46-2.10)G3c=0.63(0.42-0.94)G3d=1.00(0.50-1.98)G4a=0.91(0.70-1.17)G4b=1.44(0.78-2.65)G4c=0.62(0.44-0.88)G4d=0.77(0.36-1.66)G5a=0.74(0.56-0.99)G5b=0.40(0.10-1.62)G5c=0.63(0.45-0.89)G5d=0.51(0.21-1.26)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 93 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Abbottetal2003[69]Toexaminethewayinwhichriskfactoreffectsontheincidenceofthromboembolicandhemorrhagicstrokecanchangeoverabroadrangeofages.•n=7,5896,15and26yearfollowupIncidenceratesper1000ofstroke:TheprotectiveeffectofPAonreducingriskofstrokeincreasedwithage.USA•Sex:Men•G1=9.0(49)•Age:45-93yrPAassessment:UsingPAindexovera24hourperiodPAinformationcollectedatstudyenrolment1965-1968andupdatedatphysicalexaminationsthatoccurredat6,15and26yearsintofollow-up.•G2=17.8(124)Prospectivecohort•Characteristics:FreefromCHDandstrokeatenrolment;JapaneseancestrylivingontheislandofOahu,Hawaii.Groupedinto4agegroups,yr:•G3=33.4(112)D&Bscore=14•HonoluluHeartProgramG1=45-54•G4=48.1(111)G2=55-64Incidenceofstrokeeventincreasedwithadvancingagep<0.001G3=65-74Thereappearedtobeasmallprotectiveeffectwithineachagegroup.Inverserelationsincreasedwithage(p=0.046).TheprotectiveeffectofPAbecamesignificantinmen>77years(p=0.032)G4=75-93OutcomeMeasure:diagnosisoffatalandnonfatalstrokeduring26yearsoffollow-upCoxproportionalHRGilliumetal1996[70]Toexaminetherelationshipbetweenrecreationalandnon-recreationalPAandriskofstroke.•n=2,368men,2,713women11.6yearfollowupNumberofCases:249whitewomen,270whitemen,104blackSedentarybehaviourwasfoundtobeassociatedwithincreasedriskofstroke.USA•Sex:MenandwomenPAassessment:Questionnairedividedintotertiles:•Age:45-74yrT1=LowRR(95%CI)BlackmenandwomenRecreationalPAProspectivecohort•Ethnicity:BlackandwhiteT2=Medium•T1=1.33(0.67-2.63)D&Bscore=12•NHANESIT3=High•T2=1.33(0.63-2.79)•T3=1.00(referent)OutcomeMeasure:TotalStrokeNon-recreationalPACoxproportionalHR•T1=1.40(0.90-2.16)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 94 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)•T2=1.41(0.74-2.70)•T3=1.00(referent)RR(95%CI)Whitemenage45-64RecreationalPA•T1=1.24(0.63-2.41)•T2=1.17(0.61-2.27•T3=1.00(referent)Non-recreationalPA•T1=1.07(0.40-2.86)•T2=1.75(1.04-2.96)•T3=1.00(referent)RR(95%CI)Whitewomenage45-64RecreationalPA•T1=3.13(0.95-10.32)•T2=1.80(0.52-6.22)•T3=1.00(referent)Non-recreationalPA•T1=3.51(1.66-7.46)•T2=1.07(0.57-1.99)•T3=1.00(referent)RR(95%CI)Whitemenage65-74RecreationalPA•T1=1.29(0.58-1.88)•T2=0.86(0.58-1.28)•T3=1.00(referent)Non-recreational•T1=1.82(1.15-2.88)•T2=1.20(0.88-1.64)•T3=1.00(referent)RR(95%CI)Whitewomenage65-75RecreationalPA•T1=1.55(0.95-2.53)•T2=1.27(0.76-2.12)•T3=1.00(referent)Non-recreationalPA•T1=1.82(1.10-3.02)•T2=1.42(1.01-2.00)•T3=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 95 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)LeeandBlair2002[71]ToexaminetheassociationbetweenPFandstrokemortalityinmen.•n=16,878Baselinemedicalevaluationbetween1971and1994withaveragefollowupperiodof10yearsAverageestimatedmaximalMETsModerateandhighlevelsofPFwereassociatedwithlowerriskofstrokemortalityinmen.•Sex:Men•T1=8.5MET•Age:40-87yrs•T2=10.5METUSA•AerobicsCenterLongitudinalStudy•T3=13.1METProspectivecohortPFassessment:Maximalexercisetolerancetest,dividedintotertilesRR(95%CI)adjustedforageandexamyear•T1=1.00(referent)D&Bscore=13T1=Low•T2=0.35(0.16-0.77)T2=Moderate•T3=0.28(0.11-0.71)T3=HighTrendp=0.005CoxproportionalHRHuetal2000[72]ToexaminetheassociationbetweenPAandriskoftotalstrokeandstrokesub-typesinwomen.•n=72,488Baselinemeasurementin1986withfollow-upquestionnairein1988and1992•407casesofstroke(258ischemicstrokes,67subarachnoidhemorrhages,42intracerebralhemorrhages,and40strokesofunknowntype)PA,includingmoderate-intensityexercisesuchaswalking,isassociatedwithasubstantialreductioninriskoftotalandischemicstrokeinadose-responsemanner.•Sex:Women•Age:40-65yrUSA•Characteristics:NursesProspectivecohort•Nurses’HealthStudyPAassessment:QuestionnairefortotalPA(METh/wk),dividedintoquintiles,walkingactivity(METh/wk),dividedintoquintilesandwalkingpaceMultivariateRR(95%CI)fortotalstrokebytotalPAlevel•Q1=1.00(referent)D&Bscore=13•Q2=0.98•Q3=0.82•Q4=0.74•Q5=0.66TotalPA(METh/wk)p=0.005Q1=0-2.0Q2=2.1-4.6MultivariateRR(95%CI)forischemicStrokebytotalPAlevelQ3=4.7-10.4Q4=10.5-21.7Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 96 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)•Q1=1.00(referent)Q5=>21.7•Q2=0.87Walkingactivity(METh/wk)•Q3=0.83Q1=0.5•Q4=0.76Q2=0.6-2.0•Q5=0.52Q3=2.1-3.8p=0.003Q4=3.9-10Q5=10MultivariateRR(95%CI)fortotalstrokebywalkingactivityWalkingpace(mph)•Q1=1.00(referent)G1<2.0•Q2=0.76G2=2-2.9•Q3=0.78G33.0•Q4=0.70•Q5=0.66Outcomemeasure:Strokeincidencep=0.01MultivariateRR(95%CI)forischemicstrokebywalkingactivityPooledlogisticregressionCoxproportionalHR•Q1=1.00(referent)•Q2=0.77•Q3=0.75•Q4=0.69•Q5=0.60p=0.02MultivariateRR(95%CI)fortotalstrokebyusualWalkingPace•G1=1.00(referent)•G2=0.81•G3=0.49p<0.001MultivariateRR(95%CI)forischemicstrokebyusualwalkingpace•G1=1.00(referent)•G2=0.71•G3=0.47p<0.001Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 97 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Leeetal1999[74]Toexaminetheassociationbetweenexerciseandstrokerisk.•n=21,82311.1yearfollowupNumberofCases:533VPAisassociatedwithadecreasedriskofstrokeinmen.•Sex:Men•Age:40-84yrPAassessment:QuestionnaireforfrequencyofVPA,dividedinto4groupsMultivariateRR1(95%CI)fortotalstrokebyVPAUSA•G1=1.00(referent)Prospectivecohort•G2=0.79(0.61-1.03)InverseassociationwithPAseemedtobemediatedthroughbeneficialeffectsonbodyweight,BP,cholesterolandglucosetolerance.G1<1time/week•G3=0.80(0.65-0.99)G2=1time/week•G4=0.79(0.61-1.03)D&Bscore=13G3=2-4times/weekp=0.04G4≥5times/weekRR2(95%CI)fortotalstrokebyVPA•G1=1.00(referent)RR1=adjustedforsmoking,alcoholconsumption,historyofanginaandparentalhistoryofMIat<60years•G2=0.81(0.61-1.07)•G3=0.88(0.70-1.10)•G4=0.86(0.65-1.13)p=0.25RR2(95%CI)forischemicstrokebyRR2=adjustedforalloftheaboveplus,BMI,historyof,hypertension,highcholesterolanddiabetesVPA•G1=1.00(referent)•G2=0.90(0.66-1.22)•G3=0.95(0.74-1.22)•G4=0.97(0.71-1.32)OutcomeMeasure:TotalStroke(IschemicandHemorrhagic)p=0.81RR2(95%CI)forhemorrhagicstrokebyVPACoxproportionalHR•G1=1.00(referent)•G2=0.54(0.25-1.13)•G3=0.71(0.41-1.23)•G4=0.54(0.26-1.15)p=0.10Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 98 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Bijnenetal1998[166]TodescribetheassociationbetweenthePApatternsofelderlymenandstrokemortality.•n=80210yearfollowupNumberofCases:47Nosignificantfinding•Sex:Men•Age:64-84yrPAassessment:MultivariateadjustedRR(95%CI)Denmark•Characteristics:NotallfreefrompreviousstrokeQuestionnaireforLTPA,dividedintotertiles•T1=1.00(referent)•T2=0.65(0.33-1.25)ProspectivecohortT1=Lowest•T3=0.55(0.24-1.26)T2p=0.12T3=HighestD&Bscore=15OutcomeMeasure:StrokeMortalityCoxproportionalHRSchnohretal2006[214]TodescribetheassociationbetweendifferentlevelsofLTPAandsubsequentcausesofdeath(stroke).•n=2136men,2,758women5yearfollowupRR(95%CI),univariateAlthoughRRforofdeathfromstrokewasbelow1forbothmoderateandhighcomparedwithlowPA,thisassociationdidnotreachthelevelofstatisticalsignificance.•G1=1.00(referent)•Sex:MenandwomenPAassessment:•G2=0.64(0.39-1.05)Copenhagen•Age:20–79yrQuestionnaireforLTPA,•G3=0.70(0.41-1.21)•Characteristics:Healthy,PAleveldidnotchangebetween2examinations,5yearsapartdividedinto3groupsTrendp=0.4ProspectivecohortG1=LowPA(<4METS)G2=ModeratePA(4-6RR(95%CI),multivariate:METS)•G1=1.00(referent)D&Bscore=13G3=HighPA(>6METS)•G2=0.67(0.40-1.12)•CopenhagenCityHeartStudy•G3=0.76(0.43-1.34)MultivariateAnalysisKaplan-MeierPlotsTrendp=0.6Linear,LogisticalandCoxRegression.Vattenetal2006[253]Toinvestigatewhetherobesity-relatedCVmortalitycouldbemodifiedbyPA.•n=26,515men,27,769women16yearfollowupNumberofCases:994women,771menLowerlevelsofTPAareassociatedwithanincreasedriskofstroke.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 99 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)•Sex:MenandwomenPAassessment:QuestionnairefortotalamountofPA,dividedinto4groupsNorway•Age:20yrMultivariateHR(95%CI),men•Characteristics:FreefromCVDatbaseline•Q1=1.00(referent)Prospectivecohort•Q2=1.05(0.85-1.30)•HUNTstudyG1=High•Q3=1.21(0.95-1.54)G2=medium•Q4=1.35(1.05-1.74)D&Bscore=14G3=lowp=0.009G4=neverMultivariateHR(95%CI),womenOutcomeMeasure:Strokemortality•Q1=1.00(referent)•Q2=1.16(0.93-1.45)•Q3=1.45(1.14-1.86)CoxproportionalHR•Q4=1.45(1.14-1.83)p<0.001Agnarssonetal1999[255]ToexaminetheassociationofLTPAandpulmonaryfunctionwiththeriskofstroke.•n=4,484LengthofFollow-up:10.6±3.6yearsNumberofCases:249ApparentprotectiveeffectofregularcontinuedLTPAinmiddleagemenontheriskofischemicstroke.•Sex:Men•Age:45-80AdjustedforageandsmokingRR(95%CI)fortotalstrokebyLTPAlevelIceland•Characteristics:nohistoryofStrokePAassessment:QuestionnaireforLTPA(h/wk)andtypeofactivity(intensity),eachdividedinto3groupsProspectivecohort•ReykjavikStudy•G1=1.00(referent)•G2=0.84(0.63-1.13)•G3=0.73(0.40-1.35)D&Bscore=13LTPAsummer/winterG1=noneAdjustedforageandsmokingRR(95%CI)forischemicstrokebyLTPAlevelG2=≤5h/wkG3=≥6h/wk•G1=1.00(referent)TypeofActivity•G2=0.72(0.51-1.01)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 100 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)G1=none•G3=0.78(0.41-1.48)G2=lowintensityG3=highIntensityRR(95%CI)fortotalstrokebytypeofactivityOutcomeMeasure:TotalandischemicStroke•G1=1.0,0(referent)•G2=0.75(0.53-1.08)•G3=1.10(0.78-1.57)CoxproportionalHRRR(95%CI)forischemicstrokebytypeofactivity•G1=1.00(referent)•G2=0.72(0.44-1.07)•G3=0.96(0.64-1.44)Ellekjaeretal2000[256]ToexaminetheassociationbetweendifferentlevelsofLTPAandstrokemortalityinmiddle-agedandelderlywomen.•n=14,101Baseline1984-1986:2selfadministeredquestionnairesandclinicalmeasurementsincludedinthescreeningprogram.Numberofcases:457Thisstudydemonstratesaconsistent,negativeassociationbetweenPAandstrokemortalityinwomen.•Sex:Women•Age:50yrMultivariateRR(95%CI),allagegroupsNorway•Characteristics:freefromstrokeatbaseline•G1=1.00(referent)Prospectivecohort•G2=0.77PAassessment:QuestionnaireforLTPA,dividedinto3groups•G3=0.52D&Bscore=14MultivariateRR(95%CI),age50–69yearsG1=lowThemostactivewomenhadapprox.50%lowerriskofdeathfromstrokecomparetoinactivewomen.G2=medium•G1=1.00(referent)G3=high•G2=0.57•G3=0.42OutcomeMeasure:Deathfromstrokep=0.0021MultivariateRR(95%CI),age70-79yearsWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 101 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)CoxproportionalHR•G1=1.00(referent)•G2=0.79•G3=0.56p=0.0093MultivariateRR(95%CI),age80-101years •G1=1.00(referent)•G2=0.91•G3=0.57p=0.1089Evensonetal1999[257]ToexaminetherelationshipbetweenPAandischemicstrokerisk.•n=14,5757.2yearfollowupNumberofCases:189PAwasweaklyassociatedwithareducedriskofischemicstrokeamongmiddleagedadults.•Sex:MenandwomenNumberofDropouts:0%•Age:45-64yrPAassessment:Questionnaire(Baeckequestionnaire)USA•AtherosclerosisRiskinCommunitiesStudySport,IncidenceofIschemicStrokeProspectivecohortMultivariateadjustedRR(95%CI)bysportOutcomeMeasure:IschemicStroke•Q1=1.00(referent)D&Bscore=14•Q3=0.83(0.52-1.32)MultivariatePoissonandCoxproportionalHRMultivariateadjustedRR(95%CI)byLTPA•Q1=1.00(referent)•Q2=•Q3=0.89(0.57-1.37)MultivariateadjustedRR(95%CI)byOPA•Q1=1.00(referent)•Q2=•Q3=0.69(0.47-1.00)Haheimetal1993[258]Todeterminetheriskfactorsofstrokeincidenceandmortality.•n=14,403BaselineScreeningfromMay1972-December1973.HR(95%CI)forstrokeincidenceIncreasedLTPAisassociatedwithareducedriskofstrokeincidencebutnotmortality.•Sex:Men•G1=1.00(referent)•Age:40-49yr•G2=0.64(0.38-1.08)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 102 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)NorwayPAassessment:QuestionnaireforLTPA,dividedintogroups•G3=0.36(0.15-0.80)ProspectivecohortHR(95%CI)forstrokemortalityG1=Sedentary•G1=1.00,(referent)G2=Moderate•G2=0.82(0.33-2.35)D&Bscore=14G3=IntermediateorGreat•G3=0.29(0.03-1.51)OutcomeMeasure:Incidenceofstrokemorbidityandmortalityuntilstudyenddate,December31,1984.CoxproportionalHRHuetal2005[259]ToassesstherelationshipofdifferenttypesofPAwithtotalandtype-specificstrokerisk.•n=47,721PAassessement:MailedquestionnaireforLTPA,OPAandcommutingPA,dividedintogroupsasfollows:RR(95%CI)byLTPA,menAhighlevelofLTPAreducestheriskofallsubtypesofstroke.Dailyactivecommutingalsoreducestheriskofischemicstroke.•Sex:Menandwomen•G1=1.00(referent)•G2=0.83Finland•Age:25-64•G3=0.72•Characteristics:Healthyatbaselinep<0.001ProspectivecohortLTPAlevels:RR(95%CI)byLTPA,womenG1=Low•G1=1.00(referent)D&Bscore=13G2=Moderate•G2=0.86G3=High•G3=0.75p=0.007OPA:G1=LightRR(95%CI)byLTPA,menandwomenG2=ModerateG3=Hard•G1=1.00(referent)•G2=0.85CommutingPA:G1=Motorizedornowork,•G3=0.73G2=walkingorcycling1-29minG3=walkingorcycling≥30min.p<0.001RR(95%CI)byOPA,men•NotsignificantWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 103 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)OutcomeMeasure:Incidenceoffatalornon-fatalstrokeoccurringduringfollow-upuntilendof2003.Meanfollow-upof19years.RR(95%CI)byOPA,women•NotsignificantRR(95%CI)byOPA,menandwomen •G1=1.00(referent)Coxproportionalhazard•G2=0.90•G3=0.87p=0.007RR(95%CI)bycommutingPA,men•G1=1.00(referent)•G2=0.91•G3=0.85p=0.047RR(95%CI)bycommutingPA,women •G1=1.00(referent)•G2=0.86•G3=0.85p=0.018RR(95%CI)bycommutingPA,menandwomen•G1=1.00(referent)•G2=0.89•G3=0.85p=0.002Kielyetal1994[260]ToexaminetheinfluenceofincreasedPAonstrokeriskinmembersoftheFraminghamstudycohort.•n=1,897men2,299womenBaselinemeasurementin1954-1955andfollowupineither1968-1969or1971-1972MultivariateadjustedRR(95%CI)atfirstexamination,men(meanage50years)MediumandhighlevelsofPAamongmenareprotectiveagainststrokerelativetolowlevels.•Sex:MenandwomenUSA•G1=1.00(referent)•Age:28-62yr•G2=0.90(0.62-1.31)p=0.59Prospectivecohort•Characteristics:FreefromstrokePAassessment:Questionnaireformetabolicworkdoneduringatypical24hrperiod,dividedinto3groups•G3=0.84(0.59-1.18)p=0.31Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 104 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)MultivariateadjustedRR(95%CI)atfirstexamination,women(meanage50years)ProtectiveeffectofPAwasslightlylessforhighlevelsofPAcomparedtomediumlevelsforoldermen.D&Bscore=12G1=Low•G1=1.00(referent)G2=Medium•G2=1.21(0.89-1.63)p=0.23G3=High•G3=0.89(0.60-1.31)p=0.54OutcomeMeasure:Incidenceofstroke,asdefinedbythefirstoccurrenceofatherothromboticbraininfarctions,cerebralembolismorothertypeofstroke,during32yearsoffollow-up.MultivariateadjustedRR(95%CI)atsecondexamination,men(meanage63years)•G1=1.00(referent)•G2=0.41(0.24-0.89)p=0.0007•G3=0.53(0.34-0.84)p=0.007MultivariateadjustedRR(95%CI)atsecondexamination,women(meanage64years)CoxproportionalHR•G1=1.00(referent)•G2=0.97(0.64-1.47)p=0.67•G3=1.21(0.75-1.96)p=0.43Krarupetal2007[261]TocomparethereportedlevelofPAperformedduringtheweekprecedinganischemicstrokewiththatofcommunitycontrols.•n=127cases301controlsPAassessment:UnivariateOR(95%CI)Strokepatientsarelessphysicallyactiveintheweekprecedinganischemicstrokewhencomparedtoageandsex-matchedcontrols.IncreasingPASEscorewasinversly,log-linearlyandsignificantlyassociatedwithORforischemicstroke.QuestionnaireaboutPA1weekpriortostroke(cases)and1weekpriortoquestionnaire(controls),dividedintoPASEscoresandquartilesPASEScore•Sex:Menandwomen•Q1=1.00(referent)Denmark•Q2=0.51(0.28-0.95)•Age:≥40yr•Q3=0.27(0.14-0.54)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 105 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Casecontrol•Characteristics:Case:StrokePatients(20%hadhistoryofStroke),Controls:4%hadhistoryofstroke•Q4=0.08(0.03-0.20)D&Bscore=14Q1=0-49MultivariateOR(95%CI)PASEScoreQ2=50-99Q3=100-149•Q1=1.00(referent)Q4=150+•Q2=0.53(0.26-1.08)•Q3=0.27(0.12-0.59)Outcomemeasure:Ischemicstroke•Q4=0.09(0.03-0.25)ChisquaredKruskal-WallisStatisticsMultivariateconditionallogisticregressionKurletal2003[262]ToexaminetherelationshipofPFwithsubsequentincidenceofstroke.AlsotocomparePFwithconventionalriskfactorsasapredictorforfuturestroke.•n=2,011BaselineexaminationsconductedbetweenMarch1984andDecember1989withaveragefollowupperiodof11yearsMultivariateHR(95%CI),anystrokeLowPFwasassociatedwithanincreasedriskofanystrokeandischemicstroke.•Sex:Men•Q1=1.00(referent)•Age:42,48,54or60yrs•Q2=1.39(0.70-2.77)Finland•Q3=1.32(0.66-2.65)•Characteristics:Freefromstrokeorpulmonarydisease•KuopioIschaemicHeartDiseaseRiskFactorStudy•Q4=2.30(1.18-4.06)ProspectivecohortTrendp=0.01PFassessment:Maximalexercisetestoncycleergometer.VO2max(ml/kg/min)dividedintoquartilesMultivariateHR(95%CI),ischemicstrokeD&Bscore=14•Q1=1.00(referent)•Q2=1.28(0.56-2.94)•Q3=1.64(0.74-3.65)Q1=>35.3•Q4=2.40(1.09-5.25)Q2=30.3-35.3Trendp=0.01Q3=25.2-30.2Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 106 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Q4=<25.2OutcomeMeasure:StrokeincidenceCoxproportionalHRMyintetal2006[263]ToexaminetheassociationbetweenacombinationofOPAandLTPAwithriskofsubsequentstroke.•n=22,602BaselinemeasurementinModelA:Usedall4categoriesofPAHigherlevelsofPAassessedusingasinglesimplepragmatictoolbasedonbothOPAandLTPAisassociatedwithreducedstrokerisk.•Sex:Men1993-1997HR(95%CI),menandwomen•Age:40-79yr•G1=1.00(referent)UK•Characteristics:HealthyatbaselinePAassessment:QuestionnaireforPA(includesLTPAandOPA)dividedinto4groups•G2=0.78(0.61-1.00)•G3=0.66(0.49-0.91)Prospectivecohort•EuropeanProspectiveInvestigationinCancer-Norfolk•G4=0.70(0.49-0.99)p=0.024D&Bscore=11G1=InactiveHR(95%CI),menG2=moderatelyinactive•G1=1.00(referent)G3=moderatelyactive•G2=0.75(0.52-1.09)G4=active•G3=0.55(0.35-0.86)•G4=0.67(0.43-1.05)OutcomeMeasure:Incidenceoffatalandnonfatalstroke.p=0.41Womennotsignificantp=0.50CoxproportionalHRModelB:Used3categoriesofPA(G3andG4combinedcombined)HR(95%CI),menandwomen•G1=1.00(referent)•G2=0.78(0.61-1.00)•G3=0.68(0.52-0.88)p=0.009HR(95%CI),men•G1=1.00(referent)•G2=0.75(0.52-1.09),•G3=0.61(0.43-0.86)p=0.019Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 107 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Womennotsignificantp=0.34Nodaetal2005[264]ToexaminetheimpactofexerciseonCVD(stroke)mortalityinAsianpopulations.•n=31,023men,42,242women9.7yearfollowupNumberofCases:186men,141womenPAthroughwalkingandsportsparticipationmayreducetheriskofmortalityfromischemicstroke•Sex:MenandwomenPAassessment:QuestionnaireforPA(walkingandsportsparticipation(h/day),dividedintoquartiles:NumberofDropouts:3.4%Japan•Age:40-79yr•Ethnicity:AsianMultivariateadjustedHR(95%CI)bydurationofwalkingPA,menProspectivecohort•Q1=1.03(0.63-1.69)Q1=<0.5•Q2=1.00(referent)D&Bscore=13Q2=0.5•Q3=0.56(0.35-0.91)Q3=0.6-0.9•Q4=0.71(0.49-1.02)Q4=>1.0MultivariateadjustedHR(95%CI)bydurationofwalkingPA,womenOutcomeMeasure:Deathfromischemicstroke•Q1=1.38(0.82-2.33)•Q2=1.00(referent)CoxproportionalHR•Q3=0.56(0.32-0.97)•Q4=0.73(0.48-1.13)MultivariateadjustedHR(95%CI)bysportPA,men•Q1=1.34(0.86-2.08)•Q2=1.00(referent)•Q3=1.22(0.66-2.25)•Q4=0.84(0.45-1.57)MultivariateadjustedHR(95%CI)bysportPA,women•Q1=1.07(0.64-1.77)•Q2=1.00(referent)•Q3=0.62(0.25-1.58)•Q4=0.73(0.31-1.70)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 108 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Paganini-HillandBarreto2001[265]Toidentifyriskfactorsandpreventativemeasuresforstrokeinelderlymenandwomen.•n=4,722men,8,532womenBaselinesurveyin1981-1982.MultivariateadjustedRR(95%CI)fortotalhemorrhagicocclusionbyexercise,menEmphasizedroleoflifestylemodificationintheprimarypreventionofstroke.•Sex:MenandwomenPAassessment:Questionnaireonamountofhoursperdayofexercise•Q1=1.00(referent)USAAge:44-101yr•Q2=0.88•Characteristics:noprevioushistoryofstroke.ResidenceofaretirementcommunityinSouthernCaliforniaQ3=0.83ProspectivecohortG1=<0.5G2=<0.1MultivariateadjustedRR(95%CI)fortotalhemorrhagicocclusionbyexercise,womenG3=1+D&Bscore=13OutcomeMeasure:IncidenceofhemorrhagicocclusionstrokesupuntilDecember31,1998.•Q1=1.00(referent)•Q2=0.91•Q3=0.85PoissonRegression40yearfollowupPitsavosetal2004[266]ToinvestigatetheinteractionbetweenPAinmenwithLVHonstrokemortality.•n=489Numberofcases:67PAreducedtheriskofstrokeinmenwithoutLVH.•Sex:MenPAassessment:QuestionnaireRR(95%CI)USA•Age:40-59yr•G1=1.00(referent)•Characteristics:ThosewithoutLVHG1=Sedentary•G2=0.64(0.45-0.91)ProspectivecohortG2=Moderate•G3=0.72(0.51-1.02)•CorfuCohort(Greece)fromSevenCountriesStudyG3=HardD&Bscore=12OutcomeMeasure:StrokemortalityCoxproportionalHRWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 109 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)Saccoetal1998[267]ToinvestigatetheassociationbetweenLTPAandischemicstroke.•n=369case,678controlCaseSubjectswererecruitedduringhospitalization,selfreferralorfrommonitoringnonhospitalizedstroke.Controlswereeligibleiftheyhadneverbeendiagnosedwithstrokeandwere>39years.LTPAwasrelatedtoadecreasedoccurrenceofischemicstrokeinelderly,multiethnic,urbansubjects.•Sex:MenandwomenOR(95%CI)fordurationofLTPAandstrokeUSA•Age:>39yr•G1=1.00(referent)Casecontrol•Characteristics:CaseSubjects:DiagnosedwithfirstcerebralinfarctionafterJuly1,1993.ControlSubjects:Neverdiagnosedwithstroke•G2=0.42•G3=0.35D&Bscore=14•G4=0.31PAassessment:QuestionnaireDividedintodurationofLTPA(h/wk)•NorthernManhattanStrokeStudyG1=0G2=<2G3=2-<5G4=≥5MultivariateconditionallogisticregressionBaselinedatacollectionfrom1982-1983inEastBoston(MA),NewHaven(CT)andIowaandWashingtoncounties(IA).Simonsicketal1993[268]ToexaminetheassociationbetweenrecreationalPAamongphysicallycapableolderadultsandincidenceofselectedchronicdiseasesandmortalityover3and6years.•n=1,815After3yearsIowaNoconsistentrelationshipbetweenPAandstrokewasfoundafter3or6yearsacrossall3populationcohorts.•Sex:Menandwomen•Age:≥65yrsOR(95%CI)StrokeandactivitylevelWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 110 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)USA•Characteristics:Physicallycapabletodoheavyworkaroundthehouse,walkupanddownaflightofstairsandwalkahalfmilewithouthelp.•T1=0.22(0.08-0.61)•T2=1.05(0.60-1.84)Prospectivecohort•T3=1.00(Referent)PAassessment:QuestionnaireNewHavenD&Bscore=12T1=HighOR(95%CI)StrokeandactivitylevelT2=Moderateand•T1=1.06(0.38-2.95)T3=Inactive•T2=1.26(0.54-2.92)•EstablishedPopulationsforEpidemiologicStudiesoftheElderly•T3=1.00(Referent)OutcomeMeasure:Strokeincidenceduring3and6yearfollow-ups.EastBostonOR(95%CI)Strokeandactivitylevel•T1=0.59(0.17-1.95)LogisticRegression•T2=1.08(0.52-2.27)•T3=1.00(Referent)After6yearsIowaOR(95%CI)Strokeandactivitylevel•T1=0.56(0.31-1.00)•T2=0.97(0.64-1.48)•T3=1.00(Referent)NewHavenOR(95%CI)Strokeandactivitylevel•T1=1.05(0.52-2.12)•T2=1.29(0.72-2.32)•T3=1.00(Referent)EastBostonOR(95%CI)Strokeandactivitylevel•T1=1.21(0.56-2.61)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 111 of 220Table13:Studiesexaminingtherelationshipbetweenphysicalactivityandstroke.(Continued)•T2=1.73(0.98-3.06)•T3=1.00(Referent)Thriftetal2002[269]Toexaminewhetherintracerebralhemorrhageisassociatedwithdynamicorstaticexercise.•n=662PAassessment:Interview,dividedinto3groups:frequencyofvigorousactivityNumberofCases:331Findingsnotsignificantaftermultivariateanalysis.•Sex:Menandwomen•Age:18-80yrMultivariateOR(95%CI)byfrequencyofVPAAustralia•Characteristics:Cases:firstepisodeofintracerebralhemorrhageControls:NeighboursofcasesG1=Never•G1=1.00(referent)CasecontrolG2=Rarely•G2=0.68(0.36-1.27)G3=Onceormorepermonth•G3=0.66(0.39-1.11)D&Bscore=14p=0.094OPAlevelMultivariateOR(95%CI)byOPAlevelG1=Sedentary•G1=1.00(referent)G2=Lighttomoderate•G2=0.94(0.59-1.48),p=0.773G3=Heavy•G3=1.18(0.57-2.46),p=0.650OutcomeMeasure:IntracerebralhemorrhageMultiplelogisticregressionD&Bscore,DownsandBlackqualityscore;YR,years;wk,week;CVD,cardiovasculardisease;G,groups;PA,physicalactivity;CHD,coronaryheartdisease;RR,riskratio;95%CI,95%confidenceinterval;T,tertile;PF,physicalfitness;MET,metabolicequivalent;Q,quartileorquintile;OPA,occupationalphysicalactivity;LTPA,leisure-timephysicalactivity;HR,hazardratio;VPA,vigorousphysicalactivity;LVH,leftventricularhypertrophy.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 112 of 220according to the type of stroke (ischemic or haemorrha-gic) [52]. For instance, 12 studies (46%) revealed a dose-response relationship in one or more measures of occu-pational and/or leisure-time physical activity and therisk for stroke. It is difficult to determine the minimaland optimal physical activity dosage for the preventionof stroke. Brisk walking has been associated with alower risk of total and ischemic stroke [72]. In the Har-vard Alumni study, the risk of stroke was lower at aweekly energy expenditure of 4.2-8.4 MJ/wk (1000-1999kcal/wk) (RR = 0.76 (95% CI, 0.59 to 0.98)). Withexpenditures of 8.4-12.6 MJ/wk (2000-2999 kcal/wk) theRR dropped to 0.54 (0.38 to 0. 76) [73]. Thus, therecommended daily expenditure of Canada’s physicalactivity guidelines is sufficient to reduce the risk forstroke. Further research is required to clearly determinethe risk reductions at exercise volumes less than 4.2 MJ/wk (1000 kcal/wk).In summary, the results of these studies (taken as awhole) indicate that occupation- and leisure time-relatedphysical activity are inversely related to the risk forstroke. Both physically active men and women have alower risk of stroke, and it appears that this benefit maybe present for both ischemic and haemorrhagic stroke[74]. The relationship between physical activity andstroke appears to be consistent between men andwomen. Unfortunately, relatively limited data exists innon-Caucasian populations.Recommendation #3For a reduced risk of stroke, it is recommended thatindividuals should participate in 30 min or more ofmoderate to vigorous exercise on most days of theweek. Brisk walking appears to be protective againstthe development of stroke. It remains to be deter-mined whether lower volumes of physical activitylead to a reduced risk for stroke. [Level 3, Grade A]Primary Prevention of HypertensionA total of 6287 citations were identified during the elec-tronic database search (Figure 6). Of these citations,4054 were identified in MEDLINE, 1360 in EMBASE,253 in Cochrane, and 620 in the CINAHL/SportDiscus/PsychInfo search. A total of 40 duplicates were found,leaving a total of 6247 unique citations. A total of 6167articles were excluded after scanning, leaving a total of80 articles for full review. An additional five articleswere found through cross-referencing and the reviewers’personal files. From these articles 72 were excluded afterfull review for the following reasons: weak design (n =4), did not contain three levels of physical activity ornot possible to determine dose-response relationship (n= 19), reviews, summaries, meta-analyses (n = 8), notdealing with hypertension (n = 2), only reported onchanges in blood pressure (n = 27), clinical population(n = 7), and other (n = 6). Therefore, a total of 12 arti-cles were included in the systematic review of the litera-ture regarding the relationship between physical activityand the primary prevention of hypertension. The major-ity of the literature examining the dose-response (for atleast three levels of physical activity/fitness) involvedprospective cohort analyses (83%).As shown in Table 14, 12 investigations examined thedose-response (i.e., three or more levels) relationshipbetween physical activity and the incidence of hyperten-sion. This involved a total of 112,636 participants, aver-aging 10,240 subjects per study (range 1,243-41,837).Figure 6 Results of the Literature Search for Hypertension.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 113 of 220Table14Studiesexaminingtherelationshipbetweenphysicalactivityandhypertension.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsRankinenetal2007[75]ToinvestigatethecontributionsofDNAsequencevariationincandidategenes,PFandBMI,aswellastheirinteractionstotheincidenceofhypertension.•n=629cases;605controls10yearfollowupPFshowedthestrongestassociationwithHTNriskamongallsubjectsaswellassex-specificmodels.Each1-METincrementinPFwasassociatedwith19%(12-14%),16%(9-22%),32%(17-45%)riskreductioninallsubjects,menandwomenrespectively.PFisasignificantpredictoroftheriskofhypertension.USA•Sex:MenandwomenAllsubjectsrequiredtohave2clinicvisitsatleast2yearsapart.Casecontrol•Age:Case:43.3(9.2)yrControl:42.7(8.9)yrPFassessment:treadmilltest(Blakeprotocol)D&Bscore=13•Characteristics:HealthywithBP134/86mmHgorlessattheirfirstclinicvisit.Cases:thosewhodevelopedhypertensionduringthefollow-upperiod.ControlswerethosewhodidnotdevelophypertensionOutcomemeasure:Incidenceofhypertensionduringfollow-up.IncidentcasesofhypertensionweredefinedasphysiciandiagnosedhypertensionwithmedicationorSBP≥140mmHgand/ofDBP≥90mmHgt-testsandchi-squaretestsLogisticregressionmodellingWhendividedintoquartilesonthebasisofsexspecificMETcut-offs,thethirdandfourthquartileshada58%(41-71%)and63%(47-75%)lowerriskofhypertensioncomparedtothe1stquartile.Pereiraetal1999[76]ToexaminePAandincidenthypertensioninmenandwomen.•n=7,459PAAssessment:Questionnaireforleisure,sportandworkindex,dividedintoquartilesWhiteMenThereisaninverseassociationbetweenPAandincidenthypertensioninWhitemiddleagedmen.Whitemeninthehighestquartilesofsportandleisureactivityhadstatisticallysignificantreductionsintheoddsofdevelopinghypertensionof23and34%respectively,comparedtomeninthelowerquartiles.USA•Sex:MenandwomenQ1=LowestLeisureIndexModel1Prospectivecohort•Age:45-65yrQ2•Q1=1.00(referent)D&Bscore=12•Characteristics:Nohistoryofangina,MI,evidenceofMI,angioplastyorotherCVsurgeryorhypertensionQ3•Q2=0.95(0.70-1.28)•AtherosclerosisRiskinCommunitiesStudyQ4=Highest•Q3=0.83(0.63-1.09)Model1adjustedfor:Age,education,baselineBPandstudycentre•Q4=0.64(0.46-0.89)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 114 of 220Table14:Studiesexaminingtherelationshipbetweenphysicalactivityandhypertension.(Continued)Model2adjustedfor:Covariatesinmodel1andsmoking,alcoholconsumption,parentalhistoryofhypertension,energy,sodium,potassiumandcaffeineintake,BMI,waisttohipratio,menopausalstatusandhormoneuseTrendp=0.01OutcomeMeasure:IncidenceofhypertensionasdefinedasaSBP140mmHgand/oraDBP90mmHgoruseofantihypertensivemedications.LeisureIndexModel2UnconditionallogisticregressionOrthogonalpolynomialcoefficients•Q1=1.00(referent)•Q2=0.99(0.72-1.35)•Q3=0.86(0.65-1.13)•Q4=0.66(0.47-0.94)Trendp=0.01WomenSportIndexModel1•Q1=1.00(referent)•Q2=1.26(0.78-2.05)•Q3=1.06(0.61-1.84)•Q4=1.92(1.12-3.29)Trendp=0.04MenSportIndexModel1•Q1=1.00(referent)•Q2=1.23(0.91-1.66)•Q3=0.92(0.70-1.22)•Q4=0.74(0.54-1.02)Trendp=0.02SportIndexModel2•Q1=1.00(referent)•Q2=1.26(0.93-1.71)•Q3=0.95(0.71-1.26)•Q4=0.77(0.55-1.08)Trendp=0.05Haapanenetal1997[77]ToassesstheassociationbetweenPAandhypertension.•n=732men;796women10yearfollowup(1980baseline)AgeadjustedincidenceratesofhypertensionTotalenergyexpenditureHighasreferent:IncreasedEEduringLTPAandincreasedintensityoftheseactivitieswereassociatedwithreducedriskforincidenthypertension(ageadjusted)inmenbutnotwomen.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 115 of 220Table14:Studiesexaminingtherelationshipbetweenphysicalactivityandhypertension.(Continued)Finland•Sex:MenandwomenPAassessement:QuestionnaireforEE(kcal/wk),dividedintotertilesProspectivecohort•Age:35-65yearsMaleMale:D&Bscore=11•Characteristics:Freeofhypertensionatbaseline.ExcludedthoseunabletoparticipateinregularPAduetopoorhealthT1=Low=0-1100•T1=1.00(referent)T2=Medium=1101-1900•T2=1.66T3=High>1900•T3=1.73Trendp=0.021FemaleFemale:T1=Low=0-900•T1=1.00(referent)T2=Medium=901-1500•T2=0.94T3=High=>1500•T3=1.16Outcomemeasure:IncidenceofhypertensionthroughselfreporteddiagnosisanddeathcertificatesTrendp=0.648CoxproportionalHRPaffenbargeretal1983[78]ToexaminetherelationshipofstudentandalumnusPApatternsandothercharacteristicswithincidenthypertension.•n=14,998PAAssessment:QuestionnaireforPAbasedonnumberofstairsascended,blockswalkedandhoursperweekoflightandvigoroussportsplay,yardworketc.Therewasnosignificantlyreducedriskforhypertensioninmenwhoclimbed50plusstairsperday(comparedto<50stairs);whowalked5plusblocksperday(comparedto<5blocks);orwhoplayedlightsports(comparedtothosewhodidnot).Contemporaryvigorousexercisewasinverselyrelatedtohypertensionrisk.USA•Sex:MenProspectivecohort•Age:35-74yrOutcomemeasure:DiagnosisofhypertensionbyphysiciansusingcriteriaofSBP>160mmHgand/orDBP>95mmHgThe59%ofmenwhodidengageinvigoroussportswereat35%greaterriskofhypertensionthanthe41%whodidnot.RR=1.35Trendp=<0.001D&Bscore=12•Characteristics:freeofhypertensionHarvardAlumniStudyMultivariateestimatesAlumnionthelowsideofthephysicalactivityindex(<2000kcal/wk)hada30%increasedriskofhypertensionthenthose≥2000kcal/wk.RR=1.30Trendp=0.004Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 116 of 220Table14:Studiesexaminingtherelationshipbetweenphysicalactivityandhypertension.(Continued)Paffenbargeretal1997[79]Toinvestigatethequantityandintensityofenergyexpenditurerequiredtodelayhypertensionandpreventprematuredeath.•n=6,390PAAssessment:Questionnaireforweeklysportsplay,dividedintotertilesRR(95%CI)Lackofvigoroussportsplayindependentlyincreasedtheriskofdevelopinghypertension.USA•Sex:MenT1=None•T1=1.00(referent)Prospectivecohort•Age:45-84yrT2=LightOnly(<4.5METs)•T2=1.04(0.77-1.40)D&Bscore=12•Characteristics:Freeofhypertension,CHD,diabetes,COPDandpotentiallymalignantcancerin1977T3=Moderatelyvigorous(≥4.5METs)•T3=0.77(0.62-0.96)•HarvardAlumniStudyOutcomemeasure:IncidenthypertensionTrendp=0.004Huetal2004[81]TodiscoverwhetherregularPAcanreducetheriskofhypertensioninnormalweightandoverweightmenandwomen.•n=8,302men;9,139women11yearfollowupMultivariateadjustedHR(95%CI),menRegularPAcanreducetheriskofhypertension.TheprotectiveeffectofPAwasobservedinbothsexesregardlessoflevelofobesity.Finland•Sex:MenandwomenPAassessement:QuestionnaireforOPA,LTPAandcommutingPA,dividedintotertiles•T1=1.00(referent)ProspectivecohortAge:25-64yrT1=Low•T2=0.63D&Bscore=13Characteristics:HealthyandfreeofhypertensionatbaselineT2=Medium•T3=0.59T3=HighTrendp=<0.001OutcomeMeasure:IncidenceofdrugtreatedhypertensionMultivariateadjustedHR(95%CI),womenCoxproportionalHR•T1=1.00•T2=0.82•T3=0.71Trendp=0.005Guetal2007[82]Todeterminethe8-yearincidenceofHTNanditsriskfactorsamongChineseadults.•n=10,525BaselineExaminationin1991with8yearfollowupRR(95%CI),menIncreasingPAhasthepotentialtoreduceincidenceofhypertension.China•Sex:MenandwomenPAassessment:Questionnaireadministeredbytrainedstaff,dividedintogroups•G1=1.00(referent)ProspectivecohortAge:≥40yrG1=Low•G2=1.12(0.86-1.46)D&Bscore=13Characteristics:Healthyandfreefromhypertensionatbaseline.G2=Medium•G3=1.27(1.10-1.47)G3=HighRR(95%CI),womenWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 117 of 220Table14:Studiesexaminingtherelationshipbetweenphysicalactivityandhypertension.(Continued)Outcomemeasure:HTNasdefinedatSBP≥140mmHgand/orDBP≥90mmHgorcurrentuseofantihypertensivemedication•G1=1.00(referent)t-tests,chisquaredtests,Cochran-Armitagemodeling,ModifiedPoissonapproach•G2=1.14(0.98-1.34)•G3=1.22(1.02-1.45)Hayashietal1999[83]ToinvestigatetheassociationofthedurationofthewalktoworkandLTPAwiththeriskforhypertension.•n=6,017PAassessment:QuestionnaireonhealthrelatedbehavioursandexerciseWalktimetoworkRR(95%CI)Frequencywalktimetowork(minutesThedurationofwalktoworkwasassociatedwithadecreasedriskofhypertensionevenafteradjustment.Japan•Sex:MenT1=0-10min•T1=1.00(referent)RegularPA(atleastonceweekly)wasinverselyrelatedtotheriskofincidenthypertensionProspectivecohort•Age:35-60yrT2=11-20min•T2=0.65(0.47-0.90)D&Bscore=12•Characteristics:FreefromHTNatbaseline.AllemployeesatgascompanyinOsakaJapan.Allhadsedentaryjobs.T3=≥21min•T3=0.72(0.59-0.88)Outcomemeasure:Diagnosedwithhypertension(asdefinedbyaSBP≥160mmHg,aDBP≥95mmHg,oruseofantihypertensivemedication)Trendp=<0.001CoxproportionalHRNakanishietal2005[84]ToexaminetherelationshipofoverallPAtotheriskofdevelopinghypertensioninnormotensiveJapanesemaleofficeworkersovera7yearobservationperiod.•n=2,5487yearfollowupMultivariateadjustedRR(95%CI)byPAlevelonlyTherateofriseinbothSBPandDBPineachfollow-upyeardecreasedwithhigherEEandthattheriskofdevelopinghypertensiondecreasedinadosedependentmannerwithhigherdailylifeactivitylevel.Japan•Sex:MenQ1=1.00(referent)Analysisstratifiedbythepresenceoforabsenceofariskfactorshowedthenegativeassociationofdailylifeactivitywiththeriskofdevelopinghypertensionformenatbothlowandhighrisk.Thistendencywasalsoobservedamongmeninall3categoriesofnormotension.Prospectivecohort•Age:35-59yrPAassessment:1-dayactivityrecordandreportedthetypeandfrequencyonaweeklybasisofLTPA,dividedintoquartiles(kcal/kg/d)Q2=0.84(0.72-0.98)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 118 of 220Table14:Studiesexaminingtherelationshipbetweenphysicalactivityandhypertension.(Continued)D&Bscore=12•CharacteristicsHealthyatbaseline.NohypertensionorCHD.AllofficeworkersforaJapanesecompany•Q1=<33.3•Q3=0.75(0.63-0.88)•Q2=33.3-36.9•Q4=0.54(0.45-0.64)•Q3=37.0-40.3Trendp=<0.001•Q4=40.4MultivariateadjustedRR(95%CI)byPAlevel,lownormalBP3categoriesofnormotensiveBPLowNormal:SBP<120,DBP<80Normal:SBP120-130,DBP80-85HighNormal:SBP130-139DBP85-89•Q1=1.00(referent)3categoriesofnormotensiveBPLowNormal:SBP<120,DBP<80Normal:SBP120-130,DBP80-85HighNormal:SBP130-139DBP85-89•Q2=0.70(0.47-1.05)Coxproportionalhazardmodel•Q3=0.55(0.37-0.83)•Q4=0.43(0.28-0.65)Trendp=<0.001MultivariateadjustedRR(95%CI)byPAlevel,normalBP •Q1=1.00(referent)•Q2=0.89(0.68-1.16)•Q3=0.69(0.52-0.91)•Q4=0.50(0.37-0.68)Trendp=<0.001MultivariateadjustedRR(95%CI)byPAlevel,highnormalBP•Q1=1.00(referent)•Q2=0.86(0.69-1.07)•Q3=0.88(0.69-1.11)•Q4=0.60(0.46-0.78)Trendp=0.001Foyetal2006[85]ToexaminewhetherinsulinresistanceisassociatedwiththeeffectofvigorousormoderatePAonbaselineBP.•n=1,599Baselineexaminationin1992-1993UnadjustedOR(95%CI)ParticipantswhomeetorexceedcurrentcaloricexpenditurerecommendationsforVPAdemonstratesignificantlylesshypertensionthandosedentaryorunderactiveindividuals.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 119 of 220Table14:Studiesexaminingtherelationshipbetweenphysicalactivityandhypertension.(Continued)USA•Sex:MenandwomenPAassessment:VPAoverthepastyearwasdeterminedviaa1-yearrecallofphysicalactivity(kcal/d),dividedinto3groups•T1=1.00(referent)Crosssectional•Age:40-69yr•T1=O•T2=0.69(0.53-0.88)D&Bscore=12•Characteristics:Communitydwellingadults•T2=1-149kcal/day•T3=0.57(0.45-0.74)•InsulinResistanceAtherosclerosisStudy•T3=>150kcal/day•Trendp=<0.001AdjustedOR(95%CI)•T1=1.00(referent)•T2=0.82(0.62-1.09)•T3=0.73(0.55-0.98)Trendp=0.004Folsometal1990[270]Toexaminetherelationshipbetweenfatdistributionandthe2-yrincidenceofhypertensionandstroke.•n=41,837Baselinemailedsurveyin1986:Paassessment:QuestionnaireforLTPA•978casesHighPAreducedtheriskofhypertensiononlybeforeadjustingforotherfactors.USA•Sex:WomenT1=LowAgeAdjustedRR(95%CI)Prospectivecohort•Age:55-69years(yr)T2=Medium•T1=1.00(referent)D&Bscore=12•Characteristics:AllfreeofHTNatbaselineT3=High•T2=0.9(0.7-1.1)Mantel-Haenszelmethod•T3=0.7(0.6-0.9)MultiplelogisticregressionLevensteinetal2001[271]ToexaminetheeffectsofavarietyofpsychosocialfactorsonthedevelopmentofHTNinmenandwomeninthegeneralpopulation.•n=1,031men,1,326womenQuestionnairesin1965and1974,cohortfolloweduntil1994LTPApredictorofhypertensionOR(95%CI)RiskofHTNwasreducedwithincreasesinLTPAinwomen.USA•Sex:MenandwomenPAassessment:LTPAratedonascaleof0-16pointsandanalysedasacontinuousvariable•AllSubjects:0.94(0.91-0.97)Prospectivecohort•Characteristics:FreeofhypertensionatbaselineOutcomemeasure:Incidenceofhypertension(definedasthosewhoaretakingantihypertensivemedications)•Women:0.90(0.87-0.94)D&Bscore=13•AlamedacohortstudyLogisticregressionanalysis•Men:0.98(0.94-1.02)D&Bscore,DownsandBlackqualityscore;YR,years;PF,physicalfitness;BMI,bodymassindex;MET,metabolicequivalent;PA,physicalactivity;MI,myocardialinfarction;G,groups;Q,quartileorquintile;95%CI,confidenceinterval;SBP,systolicbloodpressure;DBP,diastolicbloodpressure;EE,energyexpenditure;kcal/wk,kilocaloriesperweek;T,tertile;RR,riskratio;HR,hazardratio;CHD,coronaryheartdisease;COPD,chronicobstructivepulmonarydisease;OPA,occupationalphysicalactivity;LTPA,leisure-timephysicalactivity;BP,bloodpressure;kcal/day,kilocaloriesperday.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 120 of 220There were a total of 11,441 reported cases of hyperten-sion (ranging per study from 118-2,936). The totallength of study follow-up averaged 8.6 yr (ranging from0-16 yr). The articles were published over a 24 yr periodranging from 1983 to 2007.All studies reviewed demonstrated positive effects ofphysical activity on the risk for hypertension. Of thesestudies all (7; 58%) revealed an inverse and graded rela-tionship between hypertension and at least one measureof physical activity or fitness. Across all studies, whencomparing the most active/fit group versus the leastactive/fit group we found an average RR of 0.68 (median= 0.70, range 0.37 to 0.90). Therefore, we observed thatphysical activity/fitness was associated with an averagerisk reduction of 32% for hypertension. It should benoted that the study [75] demonstrating the largest riskreduction (63%) evaluated cardiorespiratory fitnessdirectly during a maximal treadmill test. This supportsresearch (as discussed previously) which indicates thatphysical fitness is a better predictor of chronic diseasethan physical activity [6,18,19,32,33]. Taken as a whole,the level of evidence can be classified as Level 3A. Thequality of studies was generally good with a mean Downsand Black score of 11 (median = 11, range = 10-12).Five studies showed variable results (i.e., no clearlydefined dose-response) while generally supporting theinverse relationship between physical activity/fitness andhypertension [76-80]. The variability in the responseappears to be the result of different activity/fitness clas-sifications and/or differing subject populations. Forinstance, some studies revealed that the dose-responserelationships differed between genders and/or ethnicities[76,77]. Pereira et al. [76] revealed a 30% reduction inthe risk for hypertension in the most active white men.There were graded dose-response relationships betweenindices of both leisure and sport activities in the whitemen.However, there was a lack of association between phy-sical activity and hypertension in white women and Afri-can American men and women. Similarly, Haapenen etal. [77] revealed a stronger association in men than inwomen. However, it should be noted clearly that otherstudies included in this systematic review evaluatedwomen demonstrating a graded response [81]. More-over, several studies were conducted with non-Cauca-sian populations and demonstrated a dose-dependentbenefit [82-85]. In fact, data was obtained from variedregions of the world including USA (7), Japan (2), China(1), and Finland (1). Therefore, there is evidence to sug-gest that the protective effects of physical activity withrespect to hypertension are transferable to women andnon-Caucasian populations. However, further research isclearly warranted that examines the relationshipbetween physical activity and hypertension in persons ofdifferent ethnicities. Moreover, further research isneeded to determine the effects of impact of socio-eco-nomic status on the observed relationships.Some studies have indicated that vigorous activity isrequired to reduce the risk for hypertension. Forinstance, Paffenbarger [78] revealed that HarvardAlumni who did not engage in vigorous sports playwere at a 35% higher risk for developing hypertension.However, there was no difference in the risk for hyper-tension in men who climbed >50 stairs per day, walkedmore than 5 city blocks daily, or engaged in light sportsonly. Similarly, the Paffenbarger and Lee [79] studyrevealed that moderately vigorous sports play was asso-ciated with a lower risk for hypertension, but physicalactivity (kcal/wk), walking distance (km/wk) and theamount of stairs climbed (floors/wk) were not signifi-cant predictors of the risk for hypertension. Collectively,this research group concluded that these findings high-lighted the importance of the intensity of effort.However, it should be noted that many of the studiesin our systematic review observed the protective effectwith moderate intensity physical activities. Findingsfrom randomized controlled trials have also providedstrong evidence that moderate intensity aerobic exerciseis sufficient to reduce blood pressure and the risk forhypertension, particularly in at risk individuals [86,87].The American College of Sports Medicine [88] recentlyadvocated that to prevent hypertension, individualsshould exercise on most, and preferably all, days of theweek at a moderate intensity, for 30 min or more perday (continuous or accumulated). They also recom-mended supplementing endurance type activities withresistance exercise. This is supported by research indi-cating that moderate intensity resistance training canreduce blood pressure [89]. Collectively, this researchand our current summary of the dose-response litera-ture indicates that physical activity levels that are of amoderate to vigorous intensity are sufficient to lead tomarked reductions in the risk for hypertension.ImplicationsThe impact of hypertension on North American societyis enormous. In the US, 31% of non-institutionalizedadults over the ages of 20 are currently thought to havehypertension [90]. In Canada, approximately 20% ofadults report a diagnosis of hypertension including over4 million Canadians [91-93]. It has been estimated thata 55 yr old Canadian with normal blood pressure has agreater than 90% chance of developing hypertensionbefore the age of 80 yr [92]. The primary prevention ofhypertension is of paramount importance to theattenuation of the risks and costs associated with hyper-tension and related comorbidities.There is clear evidence that routine physical activityand/or increased physical fitness reduce greatly the riskWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 121 of 220for hypertension in both normotensive and hypertensiveindividuals [18,19]. Extensive research has been con-ducted in the area including numerous prospective trialsand various randomized controlled trials. Numerousreviews of the literature (of epidemiological and rando-mized controlled trials) have supported an inverse rela-tionship between physical activity/fitness and in theincidence of hypertension [20,87,89,94-102]. In a recentsystematic review of the prospective literature, Katzmar-zyk and Janssen (2004) calculated that physically inactiveindividuals were at a 30% higher risk for hypertension(RR = 1.30 (95% CI = 1.16-1.46)) with a populationattributable risk of 13.8% in Canada [20]. Acute bouts ofexercise have also been shown to lead to transientchanges in blood pressure that are potentially of healthbenefit [98]. For instance, blood pressure is oftenreduced after a single exercise session for 12-22 hr[88,103].It is clear that routine physical activity is effective inboth the primary and secondary prevention of hyperten-sion. However, the optimal dosage of physical activity/exercise remains somewhat unclear. Our review of theliterature examined critically the relationship betweenmultiple levels of physical activity/fitness and the inci-dence of hypertension (in individuals without diagnosedhypertension). As identified above this evidence wascompelling supporting the protective effects of habitualphysical activity in the primary prevention ofhypertension.Recommendation #4For a reduced risk for hypertension, it is recom-mended that individuals should participate in 30min or more of moderate to vigorous exercise on mostdays of the week. [Level 3, Grade A]Primary Prevention of Colon and Breast CancerColon CancerIn our systematic search of the colon cancer literature, atotal of 252 citations were identified during the electro-nic database search (Figure 7). Of these citations, 83were identified in MEDLINE, 44 in EMBASE, 25 inCochrane, and 100 in the CINAHL/SportDiscus/Psy-chInfo search. A total of 15 duplicates were found, leav-ing a total of 237 unique citations. A total of 164articles were excluded after screening, leaving a total of73 articles for full review. From these articles 47 wereexcluded after full-text review leaving 26 articles forinclusion, and an additional 7 articles were added fromthe authors’ personal files. The reasons for exclusionincluded non-experimental/weak design (n = 8), reviews,summaries, meta-analyses (n = 13), editorial/comment(n = 3), not dealing specifically with colon cancer (n =4), did not contain three levels of physical activity ornot possible to determine dose-response relationship(n = 9), and other (n = 10). Therefore, a total of 33 arti-cles were included in the systematic review of the litera-ture regarding the relationship between physical activityand the primary prevention of colon cancer.These studies involved a total of 1,433,103 partici-pants; averaging 43,427 participants per study (range142-413,044). There were a total of 17,959 reportedcases of colon cancer (ranging per study from 93-1,993).The total length of study follow-up for the prospectivecohort studies averaged 10.7 yr (ranging from 4-26 yr).The articles were published over a 23 yr period rangingfrom 1985 to 2008. These studies involved large samplesof men and women from regions throughout the world.A dose-dependency of this relationship was present inthe majority of the studies. When comparing the mostFigure 7 Results of the Literature Search for Colon Cancer.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 122 of 220active/fit group versus the least active/fit group wefound a mean risk reduction of 30% (median = 32%)across all studies. The most compelling literature wasthat which evaluated the relationship between moder-ate-to-vigorous leisure time physical activity. Based onthe literature reviewed and the volume of activityassessed it would appear that Canada’s guidelines forphysical activity are sufficient to lower the risk for thedevelopment of colon cancer in asymptomatic adults.The level of evidence would be considered to be Level2A. The studies were generally of a higher quality with amean Downs and Black score of 13 (median = 14, range= 11-15).It should be noted that there was considerable varia-bility in the findings and conclusions of the studies(Table 15). As discussed later, the literature was furtherconfounded by the fact that the relative risks associatedwith physical activity were often controlled (throughmultivariate analyses) for various potential confoundingfactors, which may actually inappropriately decrease thelevel of risk reduction associated with physical activity[31]. Moreover, similar to other chronic conditions thisliterature was limited greatly by the lack of consistentphysical activity assessment and description. In manyinstances, it was difficult to determine the actual abso-lute volume and/or intensity of activity for each categoryof comparison. However, despite these limitations theresults of these studies (taken as a whole) indicate thatboth occupation- and leisure time-related physical activ-ity are inversely related to the risk of colon cancer.Breast CancerAs reviewed eloquently by others, the epidemiologicalevidence relating physical activity to a decreased inci-dence of breast cancer is persuasive. A recent systematicreview of the literature found that more than 60 obser-vational trials have examined the relationship betweenphysical activity and breast cancer [31]. Previous reviewsof the literature have revealed compelling and consistentfindings indicating that habitual physical activity is asso-ciated with a reduced risk for breast cancer rangingfrom 20-80% [31,104].Various investigations have attempted to evaluate thedose-response relationship between physical activity andthe incidence of breast cancer (Table 16). Despite thevolume of evidence available questions still remainregarding the minimal and optimal volume of exerciserequired to reduce the risk for breast cancer. As dis-cussed by others [31,104] the findings are as varied asthe investigations.In our systematic search of the literature, a total of571 citations were identified during the electronic data-base search (Figure 8). Of these citations, 228 were iden-tified in MEDLINE, 89 in EMBASE, 56 in Cochrane,and 198 in the CINAHL/SportDiscus/PsychInfo search.A total of 46 duplicates were found, leaving a total of571 unique citations. A total of 411 articles wereexcluded after scanning, leaving a total of 114 articlesfor full review. From these articles 77 were excludedafter full review leaving 37 articles for inclusion in thesystematic review. An additional 6 articles were foundthrough the reviewers’ personal files. The reasons forexclusion included not containing three levels of physi-cal activity or not possible to determine dose-responserelationship (n = 1), reviews, summaries, meta-analyses(n = 20), report (n = 5), editorial/comment (n = 21), nota research article (N = 11), not dealing specifically withbreast cancer (n = 4), not relevant (n = 5), not primaryprevention (n = 3), and other (n = 10). Therefore, atotal of 43 articles were included in the systematicreview of the literature regarding the relationshipbetween physical activity and the primary prevention ofbreast cancer.The data providing dose-response information is allobservational in nature, involving both case control andcohort investigations. These studies involved a total of1,861,707 participants averaging 44,326 subjects perstudy (range 526-680,000). There were a total of 80,247reported cases of breast cancer (ranging per study from109-17,986). The total length of study follow-up for theprospective cohort studies averaged 10.5 yr (rangingfrom 4-31 yr). The articles were published over a 14 yrperiod ranging from 1993-2007. These studies involvedlarge samples of men and women from regions through-out the world.The literature with respect to the primary preventionof breast cancer is as compelling as that found withrespect to colon cancer. There is strong evidence thatroutine physical activity is associated with a reduced riskfor the development of breast cancer. However, this lit-erature is also confounded by many shortcomings (simi-lar to other cancer literature) including considerablevariability in the statistical analyses employed, the physi-cal activity measurement tools used, and the experimen-tal designs.The overall risk reduction for breast cancer for indivi-duals that are habitually physically active (at or aboveCanada’s guidelines for physical activity) is thought toapproximate 20-40% [31,105]. In our analyses, we foundvery similar findings. When comparing the most activegroup versus the least active group we found a mean(and median) risk reduction of 20% across all studies.The level of evidence would be considered to be Level2A. Generally, the articles were of high quality with amean Downs and Black score of 13 (median = 13, range= 9-14).A dose-dependency of this relationship is also gener-ally present in the majority of the studies. For instance,greater than 50% studies revealed a dose-responseWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 123 of 220Table15Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsHouetal2004[272]ToexaminetheeffectofvariousformsofPAoncoloncancerrisk,withparticularattentiontocommutingPA.•n=931case,1,552controlPAassessment:Interviewforthefollowingvariables•Numberofcases:931RegularfrequentPAoveralongperiodoftimereducesriskofCC.China•Sex:MenandwomenMultivariateOR(95%CI)byOPA,men•G1=1.00(referent)Casecontrol•Age:30-74yrOPA(kJ/min)•G2=1.23(0.93-1.64)D&Bscore=14•Characteristics:Case:diagnosedwithCC.controls:selectedrandomlyfromresidentsofurbanShanghai.G1=<8•G3=0.81(0.59-1.19)G2=8-12p=0.10G3=>12CommutingPA(METhr/wk)MultivariateOR(95%CI)byOPA,womenG1=<48.3•G1=1.00(referent)G2=48.3-94.3•G2=0.96(0.69-1.16)G3=>94.3•G3=0.64(0.39-1.02)p=0.009LTPA(METhr/wk)MultivariateOR(95%CI)CommutingPA,menG1=<9.2•G1=1.00(referent)G2=9.2-13.6•G2=1.11(0.31-1.23)G3=>13.6•G3=0.52(0.27-0.87)OutcomeMeasure:incidentCCp<0.001MultiplelogisticregressionMultivariateOR(95%CI)CommutingPA,women•G1=1.00(referent)•G2=0.87(0.42-1.52)•G3=0.56(0.21-0.91)p=0.007MultivariateOR(95%CI)LTPA,men•G1=1.00(referent)•G2=1.17(0.13-1.95)•G3=0.72(0.41-1.07)p=0.06Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 124 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)MultivariateOR(95%CI)LTPA,women •G1=1.00(referent)•G2=1.03(0.41-1.59)•G3=0.84(0.13-2.25)p=0.15Boutron-Ruaultetal2001[273]Todeterminewhichstepoftheadenoma-carcinomapathwaywasinfluencedbyOPAandrecreationalPA.•n=480PAassessment:Questionnaireandclassifiedinto3groupsNumberofcases:171AsedentarylifestylewasassociatedwithahighriskofCC.France•Sex:MenandwomenG1=LowAgeandgenderadjustedOR(95%CI),OPACasecontrol•Age:30-79yearsG2=Medium•G1=1.00(referent)D&Bscore=13•Characteristics:Caseshad1st diagnosisofcolorectaladenoma,controlswerepolypfree.G3=High•G2=1.3(0.8-2.0)•G3=0.5(0.3-0.9)p=0.005OutcomeMeasure:IncidentCCMultiplelogisticregressionAgeandgenderadjustedOR(95%CI),LTPA•G1=1.00(referent)•G2=0.7(0.4-1.1)•G3=0.3(0.2-0.5)p=<0.0001AgeandgenderadjustedOR(95%CI),GlobalPA•G1=1.00(referent)•G2=0.8(0.5-1.2)•G3=0.3(0.2-0.6)p=0.0003Brownsonetal1991[274]Toinvestigatetherisksof16cancertypesinrelationtoOPA.•n=17,147PAassessment:Medicalrecordsandclassifiedinto3groups:Numberofcases:1,838OPAisinverselyrelatedtoriskofCC.•Sex:MenMultivariateOR(95%CI)USA•Age:≥20yrOPAG1=1.00(referent)•Characteristics:White,workingG1=Low-Activityrequired<20%oftimeG2=1.2(1.0-1.5)CasecontrollG2=Moderate-Activityrequired20-80%oftimeG3=1.1(1.0-1.3)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 125 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)D&Bscore=15G3=High-Activityrequired>80%oftimep=0.05OutcomeMeasure:CCMaximumlikelihoodestimatesCaltonetal2006[275]ToexaminetherelationshipbetweenPAandcoloncancerriskinwomen.•n=31,78311yearfollowupNumberofcases:243ResultsdonotsupportthehypothesisthatPAisrelatedtoalowerincidenceofCCinwomen.USA•Sex:WomenPAAssessment:Questionnaire/Phoneinterviewsforthefollowingvariables,dividedinto4or5groupsProspectivecohort•Age:61.1yrMultivariateRR(95%CI),TPAD&Bscore=12•Characteristics:Freefromcanceratbaseline•G1=1.00(referent)•G2=1.45(0.98-2.15)•G3=1.16(0.77-1.75)•G4=1.27(0.84-1.91)•G5=1.15(0.76-1.75)p=0.77TPA(METh/d)G1=34.0-48.5MultivariateRR(95%CI),MPAG2=48.51-54.3•G1=1.00(referent)G3=54.31-59.0•G2=1.23(0.82-1.83)G4=59.1-64.9•G3=1.47(0.99-2.21)G5=65.0-98.1•G4=0.94(0.61-1.46)•G5=1.07(0.70-1.62)MPA(h/d)p=0.80G1=0-3.0G2=3.01-5.0G3=5.01-6.70MultivariateRR(95%CI),VPAG4=6.71-8.14•Q1=1.00(referent)G5=8.15-18.0•Q2=1.19(0.85-1.66)•Q3=0.87(0.59-1.29)VPA(h/d)•Q4=1.10(0.78-1.55)Q1=0p=0.80Q2=0.1-1.0Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 126 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Q3=1.1-2.0Q4=2.1-14.0OutcomeMeasure:IncidenceofCCCoxproportionalHRChaoetal2004[276]ToexaminehowthecharacteristicsofrecreationalPAaffectitsassociationwithcoloncancerincidenceamongolder.•n=151,174(70,403men;80,771women)7yearfollowupNumberofcases:940IncreasedamountsoftimespentinrecreationalPAisassociatedwithsubstantiallylowerriskofCC.USA•Sex:MenandwomenPAassessment:QuestionnaireforthefollowingvariablesMultivariateRR(95%CI)byrecreationalPA,menProspectivecohort•Age:mean63yr•G1=1.00(referent)D&Bscore=12•CancerpreventionstudyIINutritionCohort•G2=0.91(0.69-1.19)RecreationalPA(h/wk)•G3=0.72(0.52-1.01)G1=None•G4=0.86(0.64-1.15)G2=<2•G5=0.77(0.54-1.08)G3=2-3•G6=0.58(0.39-0.87)G4=4-6p=0.007G5=7G6=≥8MultivariateRR(95%CI)byrecreationalPA,womenRecreational(METh/wk)•G1=1.00(referent)G1=None•G2=1.01(0.70-1.44)G2=<7,7-13•G3=1.01(0.68-1.49)G3=14-23•G4=0.97(0.66-1.43)G4=24-29•G5=1.03(0.65-1.65)G5=≥30•G6=0.65(0.39-1.11)p=0.14Walking(h/wk)Q1=NoneQ2=<4MultivariateRR(95%CI)byrecreationalPA,menandwomenQ3=4-6•G1=1.00(referent)Q4=≥7•G2=0.94(0.75-1.16)•G3=0.83(0.65-1.07)Walkingplusother•G4=0.89(0.71-1.12)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 127 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)activities(h/wk)•G5=0.85(0.64-1.12)Q1=None•G6=0.60(0.44-0.83)Q2=<4p=0.002Q3=4-6Q4=≥7MultivariateRR(95%CI)byMETh/wkmenOutcomeMeasure:IncidenceofCC•G1=1.00(referent)•G2=0.90(0.68-1.18)CoxproportionalHR•G3=0.83(0.59-1.16)•G4=0.75(0.55-1.01)•G5=0.86(0.63-1.19)•G6=0.60(0.41-0.87)p=0.005MultivariateRR(95%CI)byMETh/wkwomen•G1=1.00(referent)•G2=1.02(0.71-1.46)•G3=0.98(0.65-1.47)•G4=1.0(0.68-1.47)•G5=0.94(0.60-1.48)•G6=0.77(0.48-1.24)p=0.15MultivariateRR(95%CI)byMETh/wkmenandwomen•G1=1.00(referent)•G2=0.93(0.75-1.16)•G3=0.88(0.68-1.13)•G4=0.84(0.66-1.06)•G5=0.89(0.68-1.15)•G6=0.65(0.49-0.87)p=0.002MultivariateRR(95%CI)bywalking,Men•Q1=1.00(referent)•Q2=0.87(0.66-1.15)•Q3=0.83(0.60-1.16)•Q4=0.88(0.61-1.25)p=0.34Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 128 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)MultivariateRR(95%CI)bywalking,women •Q1=1.00(referent)•Q2=1.00(0.70-1.44)•Q3=1.08(0.71-1.63)•Q4=1.18(0.71-1.95)p=0.41MultivariateRR(95%CI)bywalkingplusotheractivities,men•Q1=1.00(referent)•Q2=0.73(0.53-1.02)•Q3=0.85(0.58-1.24)•Q4=0.53(0.36-0.78)p=0.02MultivariateRR(95%CI)bywalkingplusotheractivities,women•Q1=1.00(referent)•Q2=0.99(0.67-1.47)•Q3=0.72(0.43-1.19)•Q4=0.59(0.36-0.98)p=0.07Colbertetal2001[277]ToexaminetheassociationbetweenOPAandLTPAandcoloncancerinmalesmokers.•n=29,13312yearfollow-upNumberofcases:152OPAisprotectiveagainstCCinadose-responsemanner.USA•Sex:MenProspectivecohort•Age:50-69yrPAassessment:InterviewforOPAandLTPAMultivariateRR(95%CI)byOPAD&Bscore=13•Characteristics:Smokers•G1=0.61(0.39-0.98)•Alpha-Tocopherol,Beta-CaroteneCancerPreventionStudy•G2=1.00(referent)•G3=0.60(0.34-1.04)OPA•G4=0.45(0.26-0.78)G1=Non-workerp=0.003G2=SedentaryG3=LightMultivariateRR(95%CI),byLTPAG4=Moderate•G1=1.00(referent)•G2=0.82(0.59-1.13)LTPAG1=SedentaryG2=ActiveWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 129 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)OutcomeMeasure:incidentCCCoxproportionalHRDosemecietal1993[278]ToexamineassociationsbetweenPAandcancersitesamongworkersinTurkey.•n=6,236(3,486casesinmenand379casesinwomen;2,127controlmenand244controlwomen)PAassessment:StanfordOccupationalClassificationcodesystem.Numberofcases:93OccupationalEEisinverselyrelatedtoriskofCC.Turkey•93casesforCCMultivariateOR(95%CI)bytotaloccupationalEECasecontrol•Sex:Menandwomen•G1=1.6(0.9-2.8)•Age:notindicatedTotalOccupationalEE(kj/min)•G2=1.1(0.6-2.0)D&Bscore=13•Characteristics:AllhospitalizedCases:DiagnosedwithCC.Controls:includedsubjectsdiagnosedasnon-cancersandcancerswhichthereisnosuggestionofanassociationwithPA.G1=<8•G3=1.0(referent)G2=8-12p=0.04G3=>12Whenadjustedforsocioeconomicstatusp=0.03Sittingtimeatwork(h/d)Levels:MultivariateOR(95%CI)bysittingtimeatworkG1=<2•G1=1.00(referent)G2=2-6•G2=1.5(0.9-2.5)G3=>6•G3=1.5(0.8-3.0)p=0.03OutcomeMeasure:IncidentCCWhenadjustedforsocioeconomicstatusp=0.03MaximumlikelihoodestimatesFriedenreichetal2006[279]ToinvestigatetheroleofPAinthedevelopmentofcoloncancer.•n=413,0444yearfollow-upMultivariateRR(95%CI),TPAInverseassociationbetweenPAandriskofCC,particularlyforrightsidedtumours.•Sex:MenandwomenPAassessment:modifiedBaeckeQuestionnaire•Q1=1.00(referent)UK•Age:35-70yr•Q2=0.92(0.76-1.12)•Characteristics:Freeofcanceratbaseline•Q3=0.86(0.70-1.04)Prospectivecohort•EuropeanProspectiveInvestigationintoNutritionandCancer.(EPIC)TPA•Q4=0.78(0.59-1.03)Q1=Inactivep=0.04Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 130 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)D&Bscore=14Q2=ModeratelyinactiveMultivariateRR(95%CI),TPAandrightsidedCCQ3=Moderatelyactive•Q1=1.00(referent)Q4=Active•Q2=1.79(0.59-1.06)HouseholdPA(MET-h/wk)•Q3=0.64(0.47-0.86)Q1=<19.5•Q4=0.65(0.43-1.00)Q2=19.5-39.6p=0.004Q3=39.6-73.9Q4=≥73.9MultivariateRR(95%CI),householdPAandrightsidedCC•Q1=1.00(referent)•Q2=0.97(0.75-1.27)OutcomeMeasure:IncidentCC•Q3=0.84(0.64-1.12)•Q4=0.74(0.54-1.02)p=0.05CoxproportionalHRGiovannuccietal1995[280]ToexaminetheassociationbetweenPAandcoloncancer.•n=47,7236yearfollow-upMultivariateRR(95%CI)AmoderatelevelofPAwasrelatedtoasubstantiallylowerriskofCCinthiscohortofmiddleagetoelderlymen.•Sex:Men•G1=1.00(referent)•Age:40-75yrPAassessment:Questionnaire•G2=0.73(0.48-1.10)USA•Characteristics:Healthprofessionals•G3=0.94(0.63-1.39)•G4=0.78(0.51-1.20)Prospectivecohort•HealthProfessionalsFollow-upStudyOutcomeMeasure:Incidenceofcoloncancer•G5=0.53(0.32-0.88)p=0.03D&Bscore=12Mantel-HaeszelestimatorandlogisticregressionIsomuraetal2006[281]ToexaminetherelationshipofOPA,LTPA,commuting,houseworkandshoppingwithcolorectalcancerrisk.•n=1545(778cases,767controls)PAassessment:Questionnaireandinterviewforthefollowingvariables•Numberofcases:778AddstotheevidencethatPAconfersdecreasedriskofCC,especiallyofdistalCCinbothmenandwomen.Japan•Sex:MenandwomenMultivariateOR(95%CI)forallCCbyOPA,men•G1=1.00(referent)Casecontrol•Age:20-74yrOPA,men•G2=0.9(0.6-1.4)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 131 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)•Characteristics:FreefromcanceratbaselineG1=Sedentary•G3=0.7(0.4-1.0)D&Bscore=12G2=Moderatep=0.06.G3=Hard•FukuokacolorectalcancerstudyMultivariateOR(95%CI)forproximalOPA,womenCCbyOPA,menG1=Sedentary•G1=1.00(referent)G2=Active•G2=1.2(0.6-2.2)•G3=0.7(0.4-1.4)Totalnon-OPA,men(MET-h/wk)p=0.45G1=0.0MultivariateOR(95%CI)fordistalCCbyOPA,menG2=0.1-15.9•G1=1.00(referent)G3=16.0•G2=0.8(0.4-1.4)•G3=0.6(0.4-1.0)p=0.047Totalnon-OPAwomen(METhr/wk)G1=0.0G2=0.1-15.9G3=16.0MultivariateOR(95%CI)forallCCbynon-OPA,menModerateorhardnon-OPA,men(METhr/wk)•G1=1.00(referent)G1=0.0•G2=0.9(0.6-1.4)G2=0.1-14.9•G3=0.8(0.5-1.2)G3=≥15.0p=0.22MultivariateOR(95%CI)forproximalCCbynon-OPA,menModerateorhardnon-OPA,women(METhr/wk)•G1=1.00(referent)G1=0.0•G2=1.2(0.6-2.1)G2=0.1-14.9•G3=0.9(0.5-1.7)G3=15.0p=0.69OutcomeMeasure:IncidentCCMultivariateOR(95%CI)fordistalCCbynon-OPA,men•G1=1.00(referent)Multiplelogisticregressionanalysis•G2=0.8(0.5-1.3)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 132 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •G3=0.7(0.4-1.1)p=0.19MultivariateOR(95%CI)forallCCbynon-OPA,women•G1=1.00(referent)•G2=0.9(0.5-1.5)•G3=0.8(0.5-1.4)p=0.45MultivariateOR(95%CI)forproximalCCbynon-OPA,women•G1=1.00(referent)•G2=1.5(0.7-3.3)•G3=1.6(0.7-3.6)p=0.41MultivariateOR(95%CI)fordistalCCbynon-OPA,women•G1=1.00(referent)•G2=0.7(0.4-1.3)•G3=0.6(0.3-1.1)p=0.12MultivariateOR(95%CI)forallCCbymoderateorhardnon-OPA,men•G1=1.00(referent)•G2=0.8(0.6-1.2)•G3=0.8(0.5-1.1)p=0.24MultivariateOR(95%CI)forproximalCCbymoderateorhardnon-OPA,men•G1=1.00(referent)•G2=1.1(0.6-2.1)•G3=1.0(0.6-1.8)p=0.99MultivariateOR(95%CI)fordistalCCbymoderateorhardnon-OPA,men•G1=1.00(referent)•G2=0.7(0.4-1.1)•G3=0.7(0.4-1.0)p=0.12Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 133 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)MultivariateOR(95%CI)forallCCbymoderateorhardnon-OPA,women •G1=1.00(referent)•G2=1.0(0.6-1.6),•G3=0.8(0.5-1.4)p=0.35MultivariateOR(95%CI)forproximalCCbymoderateorhardnon-OPA,women •G1=1.00(referent)•G2=1.3(0.6-2.5)•G3=1.3(0.6-2.7)p=0.59MultivariateOR(95%CI)fordistalCCbymoderateorhardnon-OPA,women •G1=1.00(referent)•G2=0.8(0.5-1.5)•G3=0.5(0.3-1.1)p=0.41Johnsenatel2006[282]ToinvestigatetheeffectsofOPAoncoloncancerincidence.•n=54,478(28,356men,26,122women)7.6yearfollow-up•Numberofcases:140women,157menNosupportforthehypothesisthatOPAmeasuredbyMET-scoremaybeassociatedwithalowerriskofCC.•Sex:MenandwomenPAassessment:QuestionnaireforOPAbyMETscore,4groups•Numberofdropouts:<0.8%Denmark•Age:50-64yrMultivariateRR(95%CI),menProspectivecohort•Characteristics:FreeofCanceratbaselineQ1=Sitting•Q1=1.00(referent)•Diet,CancerandHealthStudyQ2=Standing•Q2=1.11(0.69-1.77)Q3=Manual•Q3=1.17(0.77-1.79)D&Bscore=13Q4=Notworking•Q4=0.95(0.58-1.55)OutcomeMeasure:IncidenceofcoloncancerMultivariateRR(95%CI),women•Q1=1.00(referent)•Q2=1.15(0.68-1.93)•Q3=1.34(0.83-2.16)CoxproportionalHR•Q4=0.96(0.60-1.53)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 134 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Larsenetal2006[283]ToexaminetherelationshipbetweenPAandcolorectalcancer.•n=6,961PAassessment:Questionnaire(scoredfrom2-12),dividedintoquartiles:Numberofcases:108Inactivitywasnotasignificantriskfactorforadvancedcolonicneoplasia.•Sex:MenandwomenRR(95%CI)Norway•Age:50-64•Q1=1.00(referent)•Characteristics:Nohistoryofcolorectalsurgery,radiotherapy,cardiopulmonarydisease,anticoagulanttherapy,coronaryepisode.Q1=2-4•Q2=0.61(0.32-1.16)Cross-sectionalevaluationwithinarandomizedcontrolledtrialQ2=5•Q3=0.75(0.45-1.26)Q3=6•Q4=0.56(0.34-0.92)Q4=7-12p=0.04OutcomeMeasure:PositivetestforcolonicneoplasiaMultivariateRR(95%CI)D&Bscore=13•Q1=1.00(referent)•Q2=0.64(0.33-1.25)•Q3=0.82(0.47-1.43)Multivariatelogisticregressionanalysis•Q4=0.67(0.39-1.16)p=0.23Larssonetal2006[284]ToinvestigatetheassociationbetweenPAandcolorectalcancer.•n=45,9067.1yearfollow-upNumberofcases:309(133proximal,138distal)ResultssupportaroleofPAinreducingtheriskofCC.•Sex:Men•Age:45-79yrPAassessment:QuestionnaireforthefollowingvariablesSweden•Characteristics:FreeofcanceratbaselineMultivariateHR(95%CI)byLTPA•Q1=1.00(referent)Prospectivecohort•Q2=0.66(0.43-1.02)LTPA(min/day)•Q3=0.68(0.46-1.01)Q1=<10•Q4=0.56(0.37-0.83)D&Bscore=14Q2=10-29p=0.01Q3=30-59Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 135 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Q4=≥60MultivariateHR(95%CI)byhome/houseworkPAHome/houseworkPA(h/day)•Q1=1.00(referent)•Q2=0.75(0.58-0.97)Q1=none•Q3=0.75(0.58-0.97)Q2=<1•Q4=0.68(0.48-0.96)Q3=1-2p=0.01Q4=≥3IncidenceofProximalCC(h/day)MultivariateHR(95%CI)fordistalCCbyLTPAG1=<1•Q1=1.00(referent)G2=1-2G3=≥3•Q2=0.51(0.28-0.93)•Q3=0.50(0.29-0.87)•Q4=0.40(0.22-0.70)p=0.01OutcomeMeasure:IncidentCCMultivariateHR(95%CI)forproximalCCbyhome/houseworkPACoxproportionalHR•G1=1.00(referent)•G2=0.78(0.53-1.14)•G3=0.50(0.29-0.89)p=0.02LeeandPaffenbarger1994[285]TopredictcancerriskusingprospectiveassessmentsofPA.•n=17,60726yearfollow-up•Numberofcases:280Foundatrend,ofborderlinestatisticalsignificancetowarddecreasingCCriskwithincreasingPA.•Sex:Men•Numberofdropouts:14%•Age:30-79yrPAassessment:QuestionnaireforPAlevel(kcal/wk)USA•Characteristics:HealthyatbaselineMultivariateRR(95%CI),ModelA:PAin1962/1966andupdatedin1977•HarvardCollegeAlumni•G1=1.00(referent)ProspectivecohortG1=<1000•G2=1.07(0.81-1.42)G2=1000-2499•G3=1.08(0.81-1.46)G3=≥2500p=0.58D&Bscore=13Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 136 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)OutcomeMeasure:IncidenceoffatalandnonfatalCCMultivariateRR(95%CI),ModelB:PAinboth1962/1966and1977•G1=1.00(referent)•G2=0.75(0.42-1.35)CoxproportionalHR•G3=0.94(0.54-1.64)p=0.76Leeetal1997[286]ToinvestigatewhetherPAalterstheriskofdevelopingCCinmen.•n=20,61410.9yearfollow-upNumberofcases:217DatadoesnotsupportthehypothesisthatPAisrelatedinverselytoriskofdevelopingCC.•Sex:Men•Age:40-84yrsPAassessment:QuestionnaireforthefollowingvariablesMultivariateRR(95%CI),frequencyofUSA•Characteristics:Physicians,freeofcanceratbaselinePAatbaseline•G1=1.00(referent)Prospectivecohort•G2=1.1(0.7-1.7)FrequencyofPAatbaseline(times/week)•G3=1.2(0.8-1.6)PhysiciansHealthStudy•G4=1.1(0.7-1.6)D&Bscore=15G1=<1p=0.6G2=1G3=2-4RR(95%CI),frequencyofPAatbaselineand36monthsG4=5+•G1=1.00(referent)FrequencyofPAatbaselineand36months•G2=1.2(0.5-2.7)G1=1/<1•G3=1.4(0.9-2.3)G2=<1/1+•G4=1.3(0.9-2.0)G3=1+/<1G4=1+/1+OutcomeMeasure:Incidenceoffatalandnon-fatalCCCoxproportionalHRWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 137 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Leeetal2007[287]ToexaminetheassociationbetweenPAandtheriskofdevelopingCRCinJapanesemenandwomen.•n=65,0226yearfollow-upNumberofcases:154proximalCC,166distalCCPAmaypreventCCamongJapanesemen.•Sex:MenandwomenJapan•Age:40-69yrMultivariateRR(95%CI)forCCmen•CharacteristicsPAassessment:QuestionnaireforPAlevel(medianMEThr/d)•Q1=1.00(referent)Prospectivecohort•Ethnicity:JapaneseQ1=28.25•Q2=0.87(0.61-1.26)Q2=33.25•Q3=0.62(0.41-0.95)Q3=35.25•Q4=0.58(0.39-0.87)D&Bscore=13Q4=43.75p=0.006OutcomeMeasure:IncidenceofCCMultivariateRR(95%CI)forproximalCCmenCoxproportionalHR•Q1=1.00(referent)•Q2=0.89(0.52-1.51)•Q3=0.44(0.22-0.86)•Q4=0.29(0.14-0.60)p<0.001MultivariateRR(95%CI)fordistalCCMen•Q1=1.00(referent)•Q2=0.92(0.54-1.54)•Q3=0.75(0.42-1.33)•Q4=0.89(0.53-1.51)p=0.685PAlevelandincidenceofCCwomenTotalCC•Q1=1.00(referent)•Q2=1.03(0.65-1.64)•Q3=0.91(0.57-1.47)•Q4=0.89(0.54-1.49)p=0.610ProximalCCwomen•Q1=1.00(referent)•Q2=1.14(0.61-2.12)•Q3=1.01(0.53-1.89)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 138 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •Q4=0.55(0.24-1.26)p=0.151DistalCCwomen•Q1=1.00(referent)•Q2=1.09(0.52-2.29)•Q3=0.77(0.34-1.74)•Q4=1.37(0.66-2.85)p=0.401Longneckeretal1995[288]ToexaminetherelationshipbetweenOPAandvigorousLTPAandtheriskofcanceroftherightcolonandrectum.•n=242rectalcancerand703controlsPAassessment:InterviewforvigorousLTPAandOPA(codedandself-reported),dividedintogroups:Numberofcases:163TheamountoftimespentatvigorousLTPAwasassociatedwithadecreasedriskofcanceroftherightcolon.•Sex:MenRR(95%CI)byvigorousLTPAUSA•Age:≥31yr•G1=1.00(referent)•Characteristics:Case:Diagnosedwithadenocarcinomaoftherightcolonorrectum.Controls:Bothcommunityandhospital.Nohistoryoflargebowelcancer.•G2=0.73(0.23-2.29)Casecontrol•G3=0.47(0.16-1.36)VigorousLTPA(h/wk)•G4=0.60(0.35-1.00)D&Bscore=14G1=0p=0.03G2=≤0.5G3=1MultivariateOR(95%CI)byvigorousG4=>1LTPA•G1=1.00(referent)CodedlifetimeOPA•G2=0.81(0.26-2.54)G1=Sedentary•G3=0.36(0.11-1.14)G2=lightwork•G4=0.57(0.33-0.97)G3=moderatep=0.06G4=heavySelfreportedlifetimeMultivariateOR(95%CI)bycodedlifetimeOPAOPAG1=Sedentary•G1=1.00(referent)G2=lightwork•G2=0.79(0.39-1.61)G3=morethanlightwork•G3=0.79(0.36-1.74)•G4=0.99(0.30-3.22)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 139 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)p=0.42OutcomeMeasure:DiagnosedwithCCMultivariateOR(95%CI)byselfreportedlifetimeOPAConditionalLogisticRegression•G1=1.00(referent)•G2=0.85(0.41-1.76)•G3=0.68(0.31-1.52)p=0.15Maietal2007[289]ToexamineindetailtherelationshipbetweenrecreationalPAandinvasiveCCamongwomen.•n=120,1477yearfollow-upNumberofcases:395ModestinverseassociationbetweenrecreationalPAandCC.•Sex:Women•Age:22-84yrPAassessment:QuestionnaireRR(95%CI)byMPAoverpast3yearsUSA•Characteristics:nopriorhistoryofCC•G1=1.00(referent)•G2=0.95(0.72-1.24)ProspectivecohortMPAoverpast3yrs(h/wk/yr)•G3=0.78(0.62-0.97)•CaliforniaTeachersStudyp=0.02G1=0-0.50D&Bscore=15G2=0.51-1.99RR(95%CI)bystrenuous+moderate(lifetime)PA:G3=≥2.00•G1=1.00(referent)•G2=0.79(0.56-1.11)Strenuous+Moderate(lifetime)PA(h/wk/yr)•G3=0.64(0.44-0.93)p=0.04G1=0.0-0.50G2=0.51-3.99G3=≥4.00OutcomeMeasure:IncidenceofinvasiveadenocarcinomaofthecolonCoxproportionalHRMartinezetal1997[290]ToexaminewhetherLTPAcouldsignificantlyinfluencetheriskofCCinwomen.•n=89,4486yearfollow-upNumberofcases:212SignificantinverseassociationbetweenLTPAandincidenceofCCinwomen.•Sex:WomenWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 140 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)•Age:30-55yrPAassessment:QuestionnaireforLTPAMultivariateRR(95%CI)forallCCUSA•Characteristics:Nurses,freefromcanceratbaseline•G1=1.00(referent)G1=<2•G2=0.71(0.44-1.15)ProspectiveG2=2-4•G3=0.78(0.50-1.20)cohortG3=5-10•G4=0.67(0.42-1.07)G4=11-21•G5=0.54(0.33-0.90)D&Bscore=14G5=>21p=0.03OutcomeMeasure:IncidenceofCCMultivariateRR(95%CI)fordistalCC•G1=1.00(referent)•G2=0.92(0.48-1.79)Mantel-HaenszelEstimatorandlogisticregressionmodels•G3=0.81(0.43-1.55)•G4=0.71(0.36-1.41)•G5=0.31(0.12-0.77)p=0.01MultivariateRR(95%CI)forproximalCC•G1=1.00(referent)•G2=0.54(0.23-1.22)•G3=0.79(0.40-1.56)•G4=0.62(0.30-1.32)•G5=0.77(0.38-1.58)p=0.67Nilsenetal2008[291]TostudytheseparateassociationsofrecreationalPAwiththeincidenceof,andmortalityfromcancerintheascending,transverse,descendingandsigmoidsegmentsofthecolon.•n=59,36917yearfollow-upNumberofcases:736StronginverseassociationsbetweenrecreationalPAandriskofcancermorbidityandmortalityofthetransverseandsigmoidcolonbutnoassociationforcancerintheascendinganddescendingcolon.•Sex:MenandwomenPAassessment:QuestionnaireforfrequencyanddurationofrecreationalPAHR(95%CI)byfrequencyofrecreationalPA,menNorway•Age:notindicated•G1=1.00(referent)Prospectivecohort•Characteristics:Freefromcanceratbaseline•G2=0.84(0.60-1.19)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 141 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)•Nord-TrondelagHealthStudy•G3=0.82(0.58-1.17)•G4=0.81(0.57-1.15)D&Bscore=14FrequencyofRecreationalPA(timesperweek)•G5=0.77(0.54-1.09)G1=nonep=0.18G2=<1HR(95%CI)byfrequencyofG3=1recreationalPA,womenG4=2-3•G1=1.00(referent)G5=≥4•G2=0.91(0.66-1.25)•G3=0.79(0.57-1.09)DurationofrecreationalPA(minperexercise)•G4=0.66(0.47-0.92)•G5=0.99(0.72-1.36)G1=nonep=0.35G2=<15G3=15-30HR(95%CI)bydurationofrecreationalG4=31-60PA,menG5=>60•G1=1.00(referent)•G2=1.07(0.71-1.60)IntensityofrecreationalPA•G3=0.80(0.57-1.12)•G4=0.68(0.48-0.97)G1=none•G5=0.74(0.50-1.08)G2=Lowp=0.02G3=Moderate/HighHR(95%CI)bydurationofrecreationalPA,womenSummaryscoreforrecreationalPA•G1=1.00(referent)G1=None•G2=0.85(0.59-1.23)G2=Low•G3=0.81(0.60-1.09)G3=High•G4=0.73(0.53-1.01)Bysubsite-specific(transversecolon,decendingcolon,sigmoidcolon)CC•G5=0.84(0.53-1.34)p=0.10HR(95%CI)byintensityofrecreationalPA,menLevelsofRECPA:Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 142 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)G1=None•G1=1.00(referent)G2=<1x/wk•G2=0.83(0.62-1.12)G3=lowscore•G3=0.74(0.52-1.06)G4=highscorep=0.11OutcomeMeasure:incidenceoffatalandnonfatalCCHR(95%CI)byintensityofrecreationalPA,womenCoxproportionalHR•G1=1.00(referent)•G2=0.77(0.59-1.01)•G3=0.89(0.60-1.32)p=0.33HR(95%CI)bysummaryscoreforrecreationalPA,men•G1=1.00(referent)•G2=0.85(0.62-1.16)•G3=0.69(0.48-0.98)p=0.06HR(95%CI)bysummaryscoreforrecreationalPA,women•G1=1.00(referent)•G2=0.86(0.64-1.01)•G3=0.72(0.53-0.98)p=0.03HR(95%CI)bytotalCCandrecreationalPA,incidence•G1=1.00(referent)•G2=0.88(0.70-1.12)•G3=0.87(0.70-*1.08)•G4=0.73(0.58-0.92)p=0.009HR(95%CI)bysubsitespecificCCandrecreationalPA,death•G1=1.00(referent)•G2=0.87(0.64-1.18)•G3=0.79(0.59-1.04)•G4=0.56(0.41-0.78)p<0.001HR(95%CI)fortransverseCCincidenceandrecreationalPA•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 143 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •G2=0.75(0.44-1.28)•G3=0.66(0.41-1.08)•G4=0.44(0.25-0.78)p=0.004HR(95%CI)fortransverseCCdeathandrecreationalPA•G1=1.00(referent)•G2=0.73(0.36-1.49)•G3=0.40(0.19-0.82)•G4=0.33(0.14-0.76)p=0.002HR(95%CI)forsigmoidCCincidenceandrecreationalPA•G1=1.00(referent)•G2=0.88(0.59-1.32)•G3=0.68(0.46-1.01)•G4=0.48(0.31-0.75)p<0.001HR(95%CI)forsigmoidCCdeathandrecreationalPA•G1=1.00(referent)•G2=0.78(0.45-1.35)•G3=0.51(0.30-0.87)•G4=0.29(0.15-0.56)p<0.001Schnohretal2005[292]ToassesstheassociationbetweenLTPAandincidenceofcancerinthegeneralpopulation.•n=28,259(15,043men,13,216women)14yearfollow-up•Numberofcases:215men,108womenForthemostactivemen,VPAwasassociatedwithanon-significantlowerriskofCC.DenmarkPAassessment:QuestionnaireforLTPAMultivariateRR(95%CI),men•Sex:MenandwomenG1=Low•G1=1.00(referent)ProspectivecohortG2=Moderate•G2=1.08(0.74-1.57)•Age:20-93yrG3=Vigorous•G3=0.72(0.47-1.11)D&Bscore=13•Characteristics:FreefromcanceratbaselineOutcomeMeasure:IncidenceofCCp=0.06MultivariateRR(95%CI),women•CopenhagenHeartStudy,TheCopenhagenCountyCentreofPreventiveMedicineandtheCopenhagenMaleStudy•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 144 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)CoxproportionalHR•G2=1.02(0.70-1.50)•G3=0.90(0.56-1.46)p=0.68Slatteryetal1988[293]ToassesstherelationshipofPAanddietwiththedevelopmentofCCinUtah.•n=229cases,384controlsPAassessment:Interviewforthefollowingvariables•Numberofcases:229PAshowsaninverserelationshipwithincidenceofCC.USA•Sex:MenandwomenMultivariateOR(95%CI)byTPA,menCasecontrol•Age:40-79yr•Q1=1.00(referent)•Characteristics:Case:DiagnosedwithCCControls:nohistoryofcancerTPA•Q2=1.19(0.67-2.13)Q1=Low•Q3=0.88(0.48-1.69)Q2•Q4=.70(0.38-1.29)D&Bscore=13Q3Q4=highMultivariateOR(95%CI)byTPA,womenIntensePA•Q1=1.00(referent)G1=none•Q2=0.97(0.56-1.69)G2=low•Q3=0.91(0.52-1.60)G3=high•Q4=0.48(0.27-0.87)Non-intensePAMultivariateOR(95%CI)byintensePA,menQ1=LowQ2•G1=1.00(referent)Q3•G2=0.83(0.40-1.75)Q4=high•G3=0.27(0.11-0.65)OutcomeMeasure:DiagnosedwithCCMultivariateOR(95%CI)byintensePA,womenMultiplelogisticregressionanalysis•G1=1.00(referent)•G2=0.55(0.23-1.34)MultivariateOR(95%CI)bynon-intensePA,men•Q1=1.00(referent)•Q2=1.40(0.76-2.57)•Q3=0.93(0.51-1.72)•Q4=1.25(0.68-2.29)MultivariateOR(95%CI)bynon-intensePA,women•Q1=1.00(referent)•Q2=1.09(0.62-1.90)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 145 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •Q3=0.94(0.53-1.66)•Q4=0.53(0.29-0.95)Slatteryetal1997[294]ToexaminetherelationshipbetweenweeklyPApatterns(source,durationandfrequency)andCC.•n=1,993cases,2,410controlsPAAssessment:Interview,adaptedCARDIAPAhistoryNumberofcases:1,993HighlevelofleisuretimeVPAduringthepast20yrswasassociatedwithareducedriskofCCinbothmenandwomen.ThesameassociationswerenotobservedwithleisuretimeMPA.USA•Sex:MenandwomenMultivariateOR(95%CI)byrecentleisuretimeVPA,menCasecontrol•Age:30-79yrRecentleisuretime•Q1=1.00(referent)•Characteristics:Cases:diagnosedwithfirstprimaryCC.Controls:nohistoryofCCVPA•Q2=0.80(0.64-1.01)Q1=None•Q3=0.84(0.66-1.05)D&Bscore=14Q2•Q4=0.69(0.55-0.87)Q3Q4=HighMultivariateOR(95%CI)byrecentleisuretimeVPA,womenThegreatestinverseassociationwasobservedwhenactivitieswereperformedforlongerperiodsoftimepersession.TheThreeCenteredDiet,ActivityandLifestyleColonCancerStudyLeisuretimeVPA•Q1=1.00(referent)Q1=Low•Q2=0.79(0.61-1.02)Q2•Q3=0.83(0.64-1.07)Q3•Q4=0.86(0.67-1.10)Q4=HighCurrentPA(min)MultivariateOR(95%CI)byleisuretimeVPA,menG1=<30G2=30-60•Q1=1.00(referent)G3=≥60•Q2=0.97(0.76-1.25)•Q3=0.86(0.67-1.09)LTPA(rankedbytimepersession)•Q4=0.61(0.47-0.79)Q1=NoneMultivariateOR(95%CI)byleisuretimeVPA,womenQ2=Low-<30minQ3=moderate-30-60min•Q1=1.00(referent)Q4=high->60min•Q2=0.75(0.59-0.95)•Q3=0.68(0.53-0.87)Numberofactivitysessionperweek•Q4=0.63(0.48-0.83)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 146 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)G1=NoneMultivariateOR(95%CI)bycurrentMPAtimeperweekG2=1G3=2-4•Q1=1.00(referent)G4=5-7•Q2=1.00(0.83-1.21)G5=>7•Q3=0.90(0.76-1.07)•Q4=0.92(0.77-1.10)OutcomeMeasure:DiagnosedwithCCMultivariateOR(95%CI)bycurrentVPAtimeperweekUnconditionalregressionmodels•Q1=1.00(referent)•Q2=0.90(0.73-1.12)•Q3=0.89(0.71-1.10)•Q4=0.83(0.69-0.98)MultivariateOR(95%CI)byleisuretimeMPAtimepersession•Q1=1.00(referent)•Q2=1.20(0.91-1.59)•Q3=1.09(0.83-1.42)•Q4=1.08(0.82-1.42)MultivariateOR(95%CI)byleisuretimeVPAtimepersession•Q1=1.00(referent)•Q2=0.86(0.74-0.99)•Q3=0.76(0.64-0.90)•Q4=0.68(0.52-0.87)MultivariateOR(95%CI)bynumberofMPAsessions/wk•G1=1.00(referent)•G2=1.02(0.79-1.30)•G3=0.86(0.72-1.02)•G4=0.91(0.81-1.14)•G5=1.02(0.82-1.27)MultivariateOR(95%CI)bynumberofVPAsessions/wk•G1=1.00(referent)•G2=0.72(0.56-0.92)•G3=0.87(0.73-1.03)•G4=1.00(0.81-1.25)•G5=0.84(0.61-1.15)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 147 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Slatteryetal1997[295]TodeterminehowphysicalinactivityinteractswithothercomponentsofenergybalanceindeterminingriskofCC.•n=1,993cases,2,410controlsPAAssessment:InterviewforlifetimeVPA(PAindex)Numberofcases:1,993TheseresultssupportpreviousfindingsthatphysicalinactiityisassociatedwithanincreasedriskofdevelopingCC.USA•Sex:MenandwomenQ1=10-12MultivariateOR(95%CI),men•Age:30-79yrQ2=7-9•Q1=1.00(referent)•Characteristics:Cases:diagnosedwithfirstprimaryCC.Controls:nohistoryofCCQ3=4-6•Q2=1.60(1.11-1.75)Casecontrol•TheThreeCenteredDiet,ActivityandLifestyleColonCancerStudyQ4=<4•Q3=1.59(1.26-2.01)D&Bscore=14•Q4=1.63(1.26-2.12)OutcomeMeasure:DiagnosedwithCCMultivariateOR(95%CI),women•Q1=1.00•Q2=1.14(0.86-1.52)Unconditionalregressionmodels•Q3=1.13(0.85-1.49•Q4=1.59(1.21-2.10)Takahashietal2007[296]ToinvestigatetheassociationbetweentimespentwalkingeachdayandtheriskofCRC.•n=20,519men,21,469women7yearfollow-up•Numberofcases:101Timespentwalkingperdaywasassociatedwithalowerriskofcoloncancerinmenbutnotinwomen.•Sex:MenandwomenPAassessment:Questionnairefortimespentwalking(h/day)•Numberofdropouts:3.5%Japan•Age:40-64yrMultivariateRR(95%CI),men•Characteristics:Freefromcanceratbaseline•G1=1.00(referent)ProspectivecohortG1=<0.5•G2=0.72(0.43-1.21)G2=0.5-1•G3=0.38(0.22-0.64)G3=>1p<0.001D&Bscore=12OutcomeMeasure:IncidenceofCCTimespentwalkingandincidenceofCCMultivariateRR(95%CI),womenCoxproportionalHR•G1=1.00•G2=2.68(0.94-7.68)•G3=1.79(0.64-4.96)p=0.42Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 148 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Tangetal1999[297]ToinvestigatetheassociationbetweenPA,waterintakeandriskofCRCinahospitalbasedcasecontrolledstudy.•n=163cases,163controlsPAassessment:Interview•Numberofcases:163FoundanegativeassociationbetweenLTPAandtheriskofCCamongmen.•Sex:MenandwomenMultivariateRR(95%CI),menTaiwanLTPAMETs•G1=1.00(referent)•Age:33-80yrG1=Sedentary•G2=2.22(0.68-7.21)Casecontrol•Characteristics:Cases:HospitalpatientsdiagnosedwithcolorectalcancerControls:Hospitalpatientsinhospitalforotherreasons,freeofCRC.G2=Moderate(<20MET)•G3=0.19(0.05-0.77)D&Bscore=14G3=Active(≥20MET)p=0.03MultivariateRR(95%CI),womenOutcomeMeasure:DiagnosisofCC•G1=1.00(referent)•G2=0.52(0.13-2.03)•G3=0.63(0.18-2.18)Conditionallogisticregressionanalysisp=0.48Tavanietal1999[298]ToinvestigatetherelationshipbetweenPAandriskofCCinbothsexesatdifferentages.•n=5,379(1,225casesand4,154controls)PAassessment:Questionnaireonactivityatworkandduringleisuretime•Numberofcases:537women,688menThestudyconfirmsthatOPAisprotectiveagainstCC.Italy•Sex:MenandwomenMultivariateOR(95%CI)forCCbyOPAatage15-19yr,menCasecontrol•Age:19-74yrG1=Highest•G1=1.00(referent)G2•G2=0.89(0.64-1.23)D&Bscore=13G3•G3=0.72(0.54-0.97)G4•G4=0.54(0.40-0.74)G5=Lowest•G5=0.47(0.31-0.71)p<0.01OPAat30-39yrsoldQ1=HighestMultivariateOR(95%CI)forCCbyOPAatage15-19yr,womenQ2•G1=1.00(referent)Q3•G2=0.73(0.55-0.96)Q4=Lowest•G3=0.91(0.69-1.21)OutcomeMeasure:DiagnosisofCC•G4=0.62(0.44-0.89)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 149 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)UnconditionalmultipleLogisticRegressionp<0.05MultivariateOR(95%CI)forCCbyOPAatage30-39yr,men•G1=1.00(referent)•G2=1.01(0.75-1.37)•G3=0.79(0.59-1.06)•G4=0.71(0.52-0.97)•G5=0.64(0.44-0.93)p<0.01MultivariateOR(95%CI)forCCbyOPAatage30-39yr,women•G1=1.00(referent)•G2=0.65(0.46-0.93)•G3=0.57(0.41-0.79)•G4=0.49(0.33-0.72)p<0.01MultivariateOR(95%CI)forCCbyOPAatage50-59yr,men•G1=1.00(referent)•G2=1.06(0.78-1.43)•G3=0.85(0.63-1.14)•G4=0.68(0.49-0.95)•G5=0.69(0.45-1.05)p<0.01MultivariateOR(95%CI)forCCbyOPAatage50-59yr,women•G1=1.00(referent)•G2=0.69(0.47-1.00)•G3=0.68(0.46-1.00)•G4=0.75(0.47-1.20)p=>0.05MultivariateOR(95%CI)forascendingCCbyOPAatage30-39yrNosignificantassociationsformenorwomenMultivariateOR(95%CI)fortransverseanddescendingCCbyOPAatage30-39yr,men•Q1=1.00(referent)•Q2=0.92(0.51-1.67)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 150 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •Q3=0.76(0.43-1.37)•Q4=0.46(0.24-0.87)p<0.05MultivariateOR(95%CI)fortransverseanddescendingCCbyOPAatage30-39yr,women•Q1=1.00(referent)•Q2=0.51(0.23-1.10)•Q3=0.39(0.19-0.80)•Q4=0.29(0.12-0.71)p<0.01MultivariateOR(95%CI)forsigmoidCCbyOPAatage30-39yr,men•Q1=1.00(referent)•Q2=1.02(0.65-1.57)•Q3=0.78(0.51-1.20)•Q4=0.54(0.34-0.85)p<0.01MultivariateOR(95%CI)forsigmoidCCbyOPAatage30-39yr,women•Q1=1.00(referent)•Q2=0.62(0.36-1.05)•Q3=0.71(0.44-1.15)•Q4=0.58(0.32-1.03)p>0.05Thuneetal1996[299]Toexaminetheassociationbetweenself-reportedOPAandLTPAandthesubsequentriskofCC.•n=81,516(53,242men,28,274women)16.3yearfollowupNumberofcases:236men,99womenAninversedose-responserelationshipbetweenTPAandriskofCCwasobservedinwomen.Inmenthisinversedose-responsewasfoundonlyforthose45yrsorolderatstudyentry.PAassessment:QuestionnaireforTPA(OPAplusrecreationalPA(combined)MultivariateRR(95%CI)fortotalCC,menNorway•Sex:MenandwomenG1=Sedentary•G1=1.00(referent)Prospectivecohort•Age:20-49yrG2=Moderate•G2=1.18(0.76-1.82)•Characteristics:FreefromcanceratbaselineG3=Active•G3=0.97(0.63-1.50)D&Bscore=14p=0.49Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 151 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)MultivariateRR(95%CI)fortotalCC,womenOutcomeMeasure:IncidenceofCC•G1=1.00(referent)CoxproportionalHR•G2=0.97(0.33-2.77)•G3=0.63(0.39-1.04)p=0.04MultivariateRR(95%CI)forproximalCC,men•G1=1.00(referent)•G2=1.16(0.57-2.34)•G3=0.96(0.47-1.93)p=0.64MultivariateRR(95%CI)forproximalCC,women•G1=1.00(referent)•G2=1.22(0.51-2.94)•G3=0.62(0.30-1.28)p=0.10MultivariateRR(95%CI)fordistalCC,men•G1=1.00(referent)•G2=1.29(0.72-2.33)•G3=0.99(0.55-1.80)p=0.53MultivariateRR(95%CI)fordistalCC,women •G1=1.00(referent)•G2=0.84(0.32-2.17)•G3=0.61(0.30-1.23)p=0.15MultivariateRR(95%CI)fortotalCC,men<45yrsatentry•G1=1.00(referent)•G2=2.02(0.78-5.21)•G3=2.23(0.88-5.66)p=0.13MultivariateRR(95%CI)fortotalCC,women<45yrsatentry•G1=1.00(referent)•G2=0.96(0.39-2.40)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 152 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •G3=0.62(0.31-1.23)p=0.13MultivariateRR(95%CI)fortotalCC,men≥45yrsatentry•G1=1.00(referent)•G2=0.96(0.59-1.58)•G3=0.66(0.40-1.10)p=0.04MultivariateRR(95%CI)fortotalCC,women≥45yrsatentry•G1=1.00(referent)•G2=0.99(0.41-2.39)•G3=0.66(0.33-1.33)p=0.19Venaetal1985[300]ToassesstherelationshipbetweenlifetimeOPAandtheriskofCC.•n=1,641(210cases,1,431control)PAassessment:Questionnaire•Numberofcases:210CCriskincreasedwithincreasingamountandproportionoftimeinjobsinvolvingonlysedentaryorlightwork.USA•Sex:MenNumberofworkyearsinjobswithsedentaryorlightwork(yr)OR(95%CI)bynumberofworkyearsinjobswithsedentaryorlightworkCasecontrol•Age:30-79yrG1=None•G1=1.00(referent)•Characteristics:Cases:admittedtohospital.DiagnosisofCCControls:Admittedtohospital.Diagnosedwithnon-neoplasticnon-digestivediseasesG2=1-20•G2=1.49D&Bscore=15G3=>20•G3=1.97OR(95%CI)byproportionofyearsinjobswithsedentaryorlightworkProportionofyearsinjobswithsedentaryorlightwork•G1=1.00(referent)•G2=1.53•G3=1.58G1=None•G4=2.10G2=0.01-0.50G3=0.41-0.99OR(95%CI)byproportionoflifeinjobswithsedentaryorlightworkG4=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 153 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •G1=1.00(referent)Proportionoflifeinjobswithsedentaryorlightwork•G2=1.66•G3=1.83G1=NoneG2=0.01-0.40G3=0.41-1.00OutcomeMeasure:diagnosedwithCCMultiplelogisticregressionVetteretal1992[301]ToinvestigatetheinfluenceofOPAontheriskofCCinadevelopingcountry.•n=87mencases,13womencases,371controlsPAassessment:QuestionnaireJobtitleandindustrynamesNumberofcases:87men,13womenThisstudypresentsaweakinverseassociationbetweenCCandPA.USA•Sex:MenandwomenOR(95%CI)SittingtimeandCCOnly2ofthe4measuresofactivityshowedevidenceofanincreasedCCriskforsedentaryjobs(timespentsittingandoccupationalEE)thoughneitherwasstatisticallysignificant.Casecontrol•Age:14-97yrLevels(Sittingtime,energyexpenditure•G1=1.00(referent)D&Bscore=11•Characteristics:Cases:DiagnosedwithCCControls:cancercasesotherthencolon,rectumandlungcancer.G1=High•G2=1.0(0.5-2.0)G2=Moderate•G3=1.5(0.7-2.9)G3=Sedentaryp=0.145OutcomeMeasure:DiagnosedwithCCOR(95%CI)EnergyExpenditureandCC•G1=1.00(referent)•G2=1.5(0.7-3.3)•G3=1.6(0.8-3.6)p=0.143Whiteetal1996[302]ToassesstherelationshipbetweenPAandCCamongmenandwomen.•n=871(251men,193womencases.233men&194womencontrols)PAassessment:Phoneinterview•Numberofcases:251men&193womenTheresultsofthisstudyshowmodestsupportthatrecreationalPAisassociatedwithareducedriskofCC.USATotalPA(episodes/wk)RR(95%CI)bytotalPA,menG1=0•G1=1.00(referent)Casecontrol•Sex:MenandwomenG2=<1•G2=0.81(0.45-1.44)G3=1-<2•G3=0.53(0.30-0.94)D&Bscore=14•Age:30-62yrG4=2-<4•G4=0.57(0.33-1.00)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 154 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)•Characteristics:Cases:DiagnosedwithCC,noprevioushistoryorCCorinflammatorybowelG5=≥4•G5=0.57(0.40-1.11)Moderate-highintensityPA(epsiodes/wk)p=0.03RR(95%CI)bytotalPA,womenG1=0•G1=1.00(referent)G2=<1•G2=1.17(0.57-2.40)G3=1-<2•G3=1.27(0.65-2.45)Controls:NohistoryofCCorinflammatorybowelG4=≥2•G4=0.59(0.34-1.04)•G5=1.09(0.61-1.97)HighintensityPA(episodes/wk)p=0.52G1=0RR(95%CI)bytotalPA,menandwomenG2=<1•G1=1.00(referent)G3=≥1•G2=0.94(0.60-1.47)METS/wk•G3=0.77(0.50-1.19)Q1=0•G4=0.57(0.39-0.85)Q2=<7.30Q3=7.30-17.88•G5=0.83(0.57-1.22)Q4=≥17.88p=0.04OutcomeMeasure:DiagnosedwithCCRR(95%CI)bymoderate-highintensityPA,men•G1=1.00(referent)Unconditionallogisticregression•G2=0.84(0.49-1.43)•Q3=0.75(0.42-1.36)•Q4=0.66(0.41-1.05)p=0.07RR(95%CI)bymoderate-highintensityPA,women•G1=1.00(referent)•G2=1.07(0.58-1.97)•G3=1.00(0.51-1.98)•G4=0.74(0.42-1.29)p=0.37RR(95%CI)bymoderate-highintensityPA,menandwomenWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 155 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •Q1=1.00(referent)•Q2=0.93(0.62-1.39)•Q3=0.86(0.55-1.34)•Q4=0.70(0.49-1.00)p=0.05RR(95%CI)byhighintensityPA,men•G1=1.00(referent)•G2=0.85(0.48-1.52)•G3=0.57(0.35-0.92)p=0.02RR(95%CI)byhighintensityPA,Women •G1=1.00(referent)•G2=1.02(0.51-2.04)•G3=0.74(0.43-1.28)p=0.31RR(95%CI)byhighintensityPA,menandwomen•G1=1.00(referent)•G2=0.93(0.59-1.44)•G3=0.64(0.45-0.92)p=0.02RR(95%CI)byMETs/wk,men•Q1=1.00(referent)•Q2=0.64(0.38-1.07)•Q3=0.59(0.37-0.96)•Q4=0.69(0.42-1.13)p=0.05RR(95%CI)byMETs/wk,women•Q1=1.00(referent)•Q2=0.87(0.51-1.49)•Q3=1.20(0.69-2.08)•Q4=0.74(0.41-1.34)p=0.62RR(95%CI)byMETs/wk,women•Q1=1.00(referent)•Q2=0.73(0.50-1.06)•Q3=0.80(0.56-1.16)•Q4=0.73(0.50-1.06)p=0.08Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 156 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Wolinetal2007[303]ToassesstherelationshipbetweenPAandriskofCCinwomen.•n=79,29516yearfollow-upNumberofcases:547(245distal,302proximal)Numberofdropouts:10%AsignificantinverseassociationexistsbetweenPA,includingmoderateintensity,suchaswalking,andriskofCCinwomenthatismorepronouncedfordistaltumours.•Sex:Women•Age:40-65yrPAassessment:QuestionnaireUSA•Characteristics:Nurses,nohistoryofCC,ulcerativecolitisandCrohn’sdiseaseProspectivecohortLevelofPAMultivariateRR(95%CI)fordistalCCbylevelofPAG1=<2•G1=1.00(referent)G2=2.1-4.5•G2=0.93(0.64-1.36)D&Bscore=14G3=4.6-10.3•G3=0.99(0.68-1.44)Nurses’HealthStudyG4=10.4-21.4•G4=0.87(0.59-1.29G5=≥21.5•G5=0.54(0.34-0.84)MPAorVPA(hr/wk)p=0.004G1=0MultivariateRR(95%CI)forproximalCCbylevelofPAnotsignificantp=0.77G2=<1G3=1-1.9G4=2-3.9G5=≥4MultivariateRR(95%CI)forallCCbyMPAorVPAOutcomeMeasure:FatalandnonfatalCC•G1=1.00(referent)•G2=0.85,(0.64-1.14)CoxproportionalHR•G3=0.74(0.53-1.04)•G4=0.56(0.33-0.94)p=0.01MultivariateRR(95%CI)fordistalCCbyMPAorVPA•G1=1.00(referent)•G2=1.10(0.73-1.66)•G3=0.63(0.36-1.10)•G4=0.51(0.22-1.17)p=0.04MultivariateRR(95%CI)forproximalCCbyMPAorVPAnotsignificantp=0.12Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 157 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued)Zhangetal2006[304]ToexaminetherelationshipbetweenLTPAandOPAandtheriskofCCbyanatomicsiteandtoevaluatetheirjointeffectontheriskofCC.•n=585cases2,172controlsPAassessment:QuestionnaireforthefollowingvariablesNumberofcases:585FoundasignificantinverseassociationbetweenreportedLTPAandriskofCCwithaslightlystrongerassociationfortherightcolonthantheleftinbothmenandwomen.USA•Sex:MenandwomenMultivariateOR(95%CI)bymoderate-strenuousLTPA,menandwomen•Age:40-85yrModerate-StrenuousLTPA•G1=1.00(referent)Casecontrol•Characteristics:Case:diagnosedwithCCControl:nohistoryofCC.G1=<1month•G2=0.7(0.5-1.1)G2=1-4months•G3=0.6(0.4-0.8)D&Bscore=15G3=≥2weeksp=0.003MultivariateOR(95%CI)bymoderate-strenuousLTPA,menThejointeffectofOPAandLTPAsuggestedthattheriskwaslowestforthosewithhighOPAandnon-OPA.•G1=1.00(referent)OutcomeMeasure:CC•G2=0.9(0.5-1.7)•G3=0.5(0.3-0.9)Unconditionallogisticregressionmodelsp=0.02MultivariateOR(95%CI)bymoderate-strenuousLTPA,women•G1=1.00(referent)•G3=0.5(0.3-1.0)•G3=0.6(0.4-0.9)p=0.02MultivariateOR(95%CI)bymoderate-strenuousLTPA,menandwomen •G1=1.00(referent)•G2=0.7(0.5-1.1)•G3=0.8(0.6-1.1)p=0.53MultivariateOR(95%CI)bymoderate-strenuousLTPA,men•G1=1.00(referent)•G2=0.9(0.5-1.5)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 158 of 220Table15:Studiesexaminingtherelationshipbetweenphysicalactivityandcoloncancer.(Continued) •G3=0.8(0.6-1.2)p=0.55MultivariateOR(95%CI)bymoderate-strenuousLTPA,women•G1=1.00(referent)•G2=0.6(0.3-1.1)•G3=0.8(0.5-1.2)p=0.62MultivariateOR(95%CI)bymoderate-strenuousLTPAandOPA,OPA-Low•G1=1.00(referent)•G2=0.5(0.3-0.9)•G3=0.8(0.5-1.2)p=0.41MultivariateOR(95%CI)bymoderate-strenuousLTPAandOPA,OPA-Medium•G1=0.7(0.5-1.1)•G2=0.7(0.4-1.3)•G3=0.5(0.3-0.8)p=0.04MultivariateOR(95%CI)bymoderate-strenuousLTPAandOPA,OPA-High•G1=0.9(0.5-1.6)•G2=0.6(0.3-1.3)•G3=0.5(0.3-0.8)D&Bscore,DownsandBlackqualityscore;YR,years;PA,physicalactivity;OPA,occupationalphysicalactivity;kJ/min,kilojoulesperminute;G,groups;MET,metabolicequivalent;HR,hazardratio;RR,riskratio;OR,oddsratio;95%CI,confidenceinterval;LTPA,leisure-timephysicalactivity;CC,coloncancer;TPA,totalphysicalactivity;MDA,moderatephysicalactivity;h/d,hoursperday;VPA,vigorousphysicalactivity;h/wk,hoursperweek.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 159 of 220Table16Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsRockhilletal1999[106]ToexaminetheeffectofPAontheriskforBC.•n=121,701PAassessment:Self-reportedLTPA,groupedintohr/wk3,137casesofBCWomenwhoengagedin7ormorehoursperweekofMVPAhada20%lowerriskofBC.Aninversedose-responserelationshipexistedbetweenPAandBCincidence.•Sex:Women•Age:30-55yrRR(95%CI)forBCandLTPAUSA•16-yrfollow-upG1=<1•Characteristics:FreeofBCG2=1.0-1.9•G1=1.00(referent)ProspectivecohortG3=2.0-3.9•G2=0.88(0.79-0.98)•ThenursesHealthStudyG4=4.0-6.9•G3=0.89(0.81-0.99)D&Bscore=13G5=≥7•G4=0.85(0.77-0.94)Multivariatepooledlogisticregression•G5=0.82(0.70-0.97)Trendp=0.004Sessoetal1998[107]ToexaminetheassociationbetweenPAandBCamongpostmenopausalwomen.•n=1,56631-yrfollow-up109casesofBCThereisaninverserelationshipbetweenPAandBCinpost-menopausalwomen.•Sex:WomenUSA•Age:45.5PAassessment:Questionnaireatbaseline,dividedintotertiles(kcal/wk)RR(95%CI)forBCandPA•Characteristics:FreeofBCProspectivecohort•T1=1.00(referent)T1=<500•T2=0.92(0.58-1.45)D&Bscore=14T2=500-999T3=≥1,000•T3=0.73(0.46-1.14)RR(95%CI),post-menopausalwomenonly•T1=1.00(referent)•T2=0.95(0.58-1.57)•T3=0.49(0.28-0.86)Dosemecietal1993[278]Toconductamultiple-sitecase-controlstudyof15cancerstoexamineassociationsbetweenPA,SES,andthesecancersitesamongworkers.•n=2,643controlgroupCases:obtainedfromanoncologicaltreatmentcenterfrom1979-198431menhadBCand241womenhadBCThisstudyshowsthesitting-timeindexshowedanelevatedriskoffemaleBCforsedentaryjobswithoutSESadjustment.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 160 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•n=2,127menandn=244women)•Sex:MenandwomenTurkey•Characteristics:Cases-diagnosedwithoneofthe15cancersbeingexamined.ControlGroup-subjectsdiagnosedwithnon-cancers,cancersofthebuccalcavity,esophagus,liver,bone,softtissue,brain,lymphomaandothercancersitesforwhichthereisnosuggestiononanassociationwithPAAdjustedSESOR(95%CI),menControls:pulledfromthesamehospitalasthecasesCasecontrol•G1=1.40(0.60-3.90)D&Bscore=12PAassessment:OPA(kJ/min)•G2=1.10(0.40-3.10)G1=<8•G3=1.00(referent)TheslightlyelevatedriskofmaleBCwasbasedonasmallnumberanddisappearedwhentheriskwasadjustedforSES.G2=8-12Trendp=0.34G3=>12AdjustedSESOR(95%CI),womenGart’smethodandMantel’schi-squaretest•G1=1.10(0.60-2.10)•G2=0.90(0.50-1.80)•G3=1.00(referent)Trendp=0.23Bernsteinetal1994[305]TodeterminewhetheryoungwomenwhoregularlyparticipateinPAduringtheirreproductiveyearshadareducedriskofBC.•n=1,090(545cases;545controls)PAassessment:QuestionnaireforoverallparticipationinPAaftermenarche(h/wk),PAwithin10yearsaftermenarche(h/wk),eachdividedinto5groups:AdjustedOR(95%CI)byPAaftermenarchePAmaysubstantiallyreduceawomen’slifetimeriskofBC.•Sex:Women•G1=1.00(referent)USA•Age:≤40yr•G2=0.95(0.64-1.41)•Characteristics:WhitewomenmatchedforageandparityCasecontrol•G3=0.65(0.45-0.96)D&Bscore=15G1=none•G4=0.80(0.54-1.17)G2=0.1-0.7G3=0.8-1.6•G5=0.42(0.27-0.64)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 161 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)G4=1.7-3.7G5=≥3.8Trendp=0.0001LogisticregressionAdjustedOR(95%CI)byPAwithin10yearsaftermenarche•None=1.00(referent)•0.1-1.2=0.93(0.63-1.38)•1.3-2.9=0.78(0.52-1.19)•3.0-5.5=0.69(0.45-1.05)•≥5.6=0.70(0.47-1.06)Trendp=0.027AdjustedOR(95%CI)byPAaftermenarche,nulliparouswomen •G1=1.00(referent)•G2=0.81(0.42-1.57)•G3=0.65(0.35-1.21)•G4=0.94(0.53-1.67)•G5=0.73(0.38-1.41)Trendp=0.43AdjustedOR(95%CI)byPAaftermenarche,parouswomen •G1=1.00(referent)•G2=1.06(0.65-1.74)•G3=0.65(0.40-1.06)•G4=0.70(0.42-1.18)•G5=0.38(0.16-0.50)Trendp<0.0001Bernsteinetal2005[306]ToexaminetherelationshipbetweenBCriskandlifetimeandtime-orage-specificmeasuresofLTPAamongwhiteandblackwomen.•n=9,187(4,538cases;4,649control)Cases:histologicallyconfirmedcasesofBC4,538casesofBCThisstudysupportsaninverseassociationbetweenPAandBCamongblackwomenandamongwhitewomen.•Sex:Women•Age:35-64MultivariateadjustedOR(95%CI)annualMETh/wk,WhiteparticipantsUSA•Ethnicity:White(includingHispanics)orBlackControls:random-digitdialingmethodsWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 162 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•Characteristics:CaseGroup:histologicallyconfirmedcasesofinvasiveBCCasecontrol•ControlGroup:healthy•G1=1.00(referent)PAassessment:•G2=0.84(0.71-0.99)D&Bscore=13QuestionnaireforlifetimePA(METh/wk),dividedinto5groups•G3=0.89(0.75-1.04)G1=Inactive•G4=0.82(0.69-0.97)Therelationshipappearstobesimilarbetweenblackandwhitewomen.G2=≤2.2•G5=0.81(0.69-0.96)G3=2.3-6.6Trendp=0.09G4=6.7-15.1G5=≥15.2UnconditionallogisticregressionmodelingMultivariateadjustedOR(95%CI)annualMETh/wk,Blackparticipants•G1=1.00(referent)•G2=1.11(0.91-1.35)•G3=0.83(0.67-1.03)•G4=0.79(0.63-0.99)•G5=0.77(0.62-0.95)Trendp=0.003Carpenteretal.1999[307]ToexaminewhetherlifetimeexerciseactivityisrelatedtoBCriskinpost-menopausalwomen.•n=2,027(1,123case;904control)Cases:diagnosedwithprimaryinvasiveorinsituBC1,123casesofBCStrenuousexerciseappearstoreduceBCriskamongpost-menopausalwomenwhodonotgainsizableamountsofweightduringadulthood.•Sex:WomenMultivariateadjustedOR(95%CI)USA•Age:55-64yr•Ethnicity:White(includingHispanic)Controls:individuallymatchedtoeachcasepatientbasedonbirthdateandrace•G1=1.00(referent)Casecontrol•Characteristics:post-menopausal,English-speaking,borninUSA,CanadaorWesternEurope•G2=0.88(0.72-1.07)D&Bscore=15•G3=0.55(0.37-0.83)PAassessment:QuestionnaireforlifetimePA(METhr/wk),dividedinto3groupsTrendp=0.01G1=noactivityG2=0.1-17.59Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 163 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)G3=≥17.6ConditionallogisticregressionCarpenteretal2003[308]Toexaminetheeffectsofobesityandlifetimeexercisepatternsonpost-menopausalBCriskaccordingtofamilyhistory.•n=3,511(casesn=1,883,controls)n=1,628PAassessment:InterviewforthefollowingPAvariables1,883casesofBCExerciseindependentofbodysizeseemedtoexertaprotectiveeffectprimarilyamongwomenwithanegativefamilyhistory.•Sex:WomenAdjustedOR(95%CI)bylifetimeexercisebetweenmenarcheandreferencedate(METhr/wk)USA•Age:55-72•Characteristics:PostmenopausalWomenLifetimeexercisebetweenmenarcheandreferencedate(METhr/wk)CasecontrolD&Bscore=15G1=0•G1=1.00(referent)G2=0.1-3.74•G2=0.85(0.71-1.03)G3=3.75-8.74G4=8.75-17.59•G3=0.87(0.69-1.10)G5=≥17.60•G4=1.02(0.79-1.30)Averageexerciseactivityin10yearspriortoreferencedate(METhr/wk)•G5=0.66(0.48-0.90)G1=0Trendp=0.07G2=0.1-6.9G3=7.0-13.9AdjustedOR(95%CI)byaverageexerciseactivityin10yearspriortoreferencedate(METhr/wk)G4=14.0-24.4G5=≥24.5•G1=1.00(referent)•G2=0.93(0.71-1.22)•G3=0.92(0.70-1.19)•G4=0.86(0.65-1.11)•G5=0.75(0.55-1.02)Trendp=0.05Changetal2006[309]Toaddresstheindependentandcombinedeffectsofenergyintake,BMI,andPAonBCincidenceinwomen.•n=27,5419.3yearfollow-up(median4.9yr)764womendevelopedBCThestudysuggeststhatenergyintake,BMIandphysicalinactivityareeachindependentlyandpositivelyassociatedwithBCrisk.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 164 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•Sex:WomenUSA•Age:55-74•Characteristics:nohistoryofanycancer(nonmelanomaskincancerpatientswereincludedinthetrial)PAassessment:QuestionnaireforvigorousPA(h/wk),dividedinto6groupsMultivariateadjustedRR(95%CI)Prospectivecohort•Prostate,Lung,colorectal,andOvarianCancerScreeningTrialG1=0G2=<1•G1=1.00(referent)D&Bscore=13G3=1•G2=0.89(0.69-1.15)G4=2•G3=0.96(0.73-1.26)G5=3•G4=0.90(0.70-1.16)G6=≥4•G5=1.02(0.79-1.30)•G6=0.78(0.61-0.99)CoxproportionalHRTrendp=0.153Colditzetal2003[310]ToevaluatetherelationshipbetweenPAandriskofpre-menopausalBCbytypeofactivityandwithinsubgroupsofadiposityandoralcontraceptiveuse.•n=110,468PAassessment:Selfreporton8activities(walkingorhiking,jogging(>10minmile),running,Biking,racquetsports,lapswimming,calisthenics/aerobicsotheraerobicactivities)tocalculateMETscores(METhrwk),dividedinto5groups:Totalcasesdiagnosedn=849Thesedataamongpre-menopausalwomensuggestthatthereisnooverallassociationbetweenPAandriskofBC.ThefindingsalsosuggestthattheeffectofPAcouldbesubstantiallymodifiedbytheunderlyingdegreeofadiposity.•Sex:WomenUSA•Age:25-42•Characteristics:pre-menopausal,nohistoryofcancerotherthannonmelanomaskincancerMultivariateadjustedRR(95%CI)Prospectivecohort•G1=1.00(referent)D&Bscore=12•G2=1.05(0.82-1.34)•G3=0.96(0.75-1.23)G1=<3•G4=1.05(0.80-1.37)G2=3-8.9G3=9-17.9•G5=1.07(0.84-1.36)G4=18-26.9G5=≥27Trendp=0.69CoxproportionalHRCooganetal1997[311]ToevaluatetheeffectofOPAonBCrisk.•n=11,646(4,863casesand6,783controls).PAassessment:TelephoneinterviewtoestimateOPA,dividedintotertiles:4,863casesofBCTherewasevidenceofagradedinverserelationshipbetweentheintensityofworkrelatedactivityandtheincidenceofBC.OR(95%CI)USA•Sex:WomenT1=Sedentary•T1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 165 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•Age:<74yrT2=Mediumactivityjobs•T2=0.86(0.77-0.97)CasecontrolT3=Heavyjobs•T3=0.82(0.63-1.08)D&Bscore=14LogisticregressionmodelsCooganandAschengrau1999[312]ToevaluatetheeffectofOPAonBCrisk.•n=903(233case;670control)PAassessment:TelephoneinterviewtoestimateOPA,dividedintotertiles:233casesofBCTherewasnoevidencethatholdingajobofmedium/heavyactivityreducedBC.•Sex:WomenOR(95%CI)•Age:<50-80+T1=Exclusivelysedentary•T1=1.00(referent)USA•Ethnicity:White,BlackorOtherT2=Exclusivelylight•T2=1.20(0.70-1.90)•Characteristics:musthaveworkedoutsidethehome.Cases:AllincidentcasesofBCreportedtotheMassachusettsCancerRegistryfrom1983to1986wereeligibleT3=Exclusivelymediumorheavy•T3=0.90(0.40-1.90)ThestudywaslimitedbyOPAmisclassificationandbythelackofinformationonLTPA.CasecontrolTrendp=0.63D&Bscore=14Miettinen’stest-basedmethodandFisher’sexactmethodDallaletal2007[313]ToexaminetherelationshipbetweenLTPAandinvasiveandinsituBCamongwomen.•n=110,5996.6yrfollow-up2,649casesofinvasiveTheresultssupportaprotectiveroleofstrenuouslong-termexerciseactivityagainstinvasiveandinsituBCandsuggestdifferingeffectsbyhormonereceptorstatus.•Sex:WomenBCUSA•Age:20-79PAassessment:Self-reportedparticipationinmoderateandstrenuousactivitiestoestimateannualstrenuousphysicalactivity(hr/wk),dividedintoquintiles593casesofinsituBC•Ethnicity:White,Black,Hispanic,Asian,AmericanIndianorotherProspectivecohort•Characteristics:CaliforniaresidentatbaselineandnohistoryofBCMultivariateadjustedRR(95%CI)forinvasiveBCD&Bscore=12•CaliforniaTeachersStudycohort•Q1=1.00(referent)•Q2=0.93(0.85-1.02)Q1=0.00-0.50Q2=0.51-2.00•Q3=0.88(0.78-0.99)Q3=2.01-3.50Q4=3.51-5.00•Q4=1.02(0.88-1.18)Q5=>5•Q5=0.80(0.69-0.94)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 166 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)CoxproportionalHRTrendp=0.02MultivariateadjustedRR(95%CI)forinsituBC•Q1=1.00(referent)•Q2=0.96(0.79-1.17)•Q3=0.86(0.67-1.11)•Q4=0.95(0.70-1.30)•Q5=0.69(0.48-0.98)Trendp=0.40Dirxetal2001[314]ToevaluatetherelationshipbetweenPAandBCriskwithspecificemphasisoninteractionwithotheraspectsofenergybalance.•n=62,5377.3yrfollow-up1,208casesofincidentBCThecurrentstudysupportsthehypothesesthatPAisrelatedinverselytoBCriskinpostmenopausalwomen.•Sex:WomenNetherlands•Age:55-69PAassessment:QuestionnairefortotalrecreationalPA(min/day),dividedintoquartiles•Characteristics:healthy,postmenopausalMultivariateadjustedRR(95%CI)Casestudy•Q1=1.00(referent)D&Bscore=11Q1=<30•Q2=0.84(0.67-1.07)Q2=30-60Q3=61-90•Q3=0.78(0.60-1.00)Q4=>90•Q4=0.76(0.58-0.99)ExponentiallydistributedfailuretimeregressionmodelsTrendp=0.003Dornetal2003[315]ToexaminetheassociationsbetweenLTPAandOPAacrossthelifespanandpre-andpost-menopausalBC.•n=1,550(740case;810control)Cases:womendiagnosedandhistologicallyconfirmedwithBC740casesofBCThestudysupportsthehypothesisthatstrenuousLTPAisassociatedwithareducedriskofBCriskinbothpre-andpostmenopausalwomenUSA•Sex:WomenMultivariateadjustedOR(95%CI),pre-menopausal•Age:40-85Casecontrol•Characteristics:CaseGroup–histologicallyconfirmedincidenceofBC.ControlGroup–healthyControls:randomlyselectedandfrequencymatchedonageandcountywiththecases.•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 167 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)D&Bscore=13•G2=0.94(0.64-1.38)•G3=0.73(0.44-1.22)PAassessment:QuestionnaireforlifetimestrenuousPA(hr/yr)•G4=1.07(0.57-2.02)Trendp=0.82G1=0G2=1-273G3=274-545MultivariateadjustedOR(95%CI),post-menopausalG4=>546Logisticregression•G1=1.00(referent)•G2=0.85(0.61-1.19)•G3=0.73(0.45-1.17)•G4=0.78(0.47-1.29)Trendp=0.19Drake2001[316]ToevaluatePAasapredictorofBCanddescribeBCriskfactorsinthissample.•n=4,520PAassessment:Self-reportoftype,intensity,durationandfrequencyofwalking,jogging,biking,stationarybiking,swimming,dancing,racketsports,stretching,participatinginotherexercise,calisthenics,weight-liftingandtreadmillexercises,dividedintogroups150incidentcasesofbreastcancerIncreasedfrequencyofaspecificPA(jogging)wasfoundtohaveanimportantprotectiveroleinBCincidence.•Sex:WomenUSA•Age:21-86•Characteristics:nodiagnosisofBCatentryOR(95%CI)forBCandPAProspectivecohortD&Bscore=11•AerobicCenterLongitudinalStudyActivitytype•G1=1.32•G2=1.08•G3=1.35Trendp=0.05G1=Aerobic(job,bike,aerobicdance)G2=Moderate(golf,walk)G3=WeighttrainingChi-squareWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 168 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Friedenreichetal2001[317]ToexaminethetypeanddoseofPAandthetimeperiodsinlifewhenPAmaybespecificallyassociatedwithBCrisk.•n=2,470(1,233case;1,237control)Cases:insituandinvasivecasesofBCfrom1995-19971,233casesofBCThisstudyprovidesevidencethatlifetimePAreducesriskofpost-menopausalBC.Canada•Sex:WomenOR(95%CI),pre-menopausalCaseControl•Age:≤80Controls:matchedtocasesonageandplaceofresidence•Q1=1.00(referent)•Characteristics:CaseGroup-Albertaresidents,Englishspeaking,capableofcompletinganin-personinterview.ControlGroup–nohistoryofcancerdiagnosesexcludingnonmelanomaskincancer•Q2=1.15(0.78-1.70)D&Bscore=13PAassessment:QuestionnaireforlifetimePA(METhr/wk/yr),dividedintoquartilesbymenopausalstatus•Q3=1.15(0.78-1.69)Pre-menopausal•Q4=1.07(0.72-1.61)Q1=<86.6Trendp=0.50Q2=86.6-108.3OR(95%CI),post-menopausalQ3=108.3-134.9•Q1=1.00(referent)Q4=≥134.9•Q2=0.73(0.55-0.98)Post-menopausal•Q3=0.75(0.56-1.00)Q1=<104.8•Q4=0.70(0.52-0.94)Q2=104.8-128.1Trendp=0.003Q3=128.1-160.9Q4=≥160.9LogisticregressionFriedenreichetal2001[318]Toexaminetheinfluenceoffrequency,duration,andintensityofPAonriskofBCandtocompareBCrisksassociatedwithself-reportedversusassignedintensityofPA.•n=2,470(1,233case;1,237control)Cases:insituandinvasivecasesofBC1,233casesofBCThisstudyfoundthatmoderate-intensityactivitieswerethemajorcontributorstothedecreaseinBCriskfoundinthisstudy.Canada•Sex:WomenMultivariateadjustedOR(95%CI),pre-menopausalCasecontrol•Age:≤80Controls:matchedtocasesonageandplaceofresidence•Q1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 169 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)D&Bscore=13•Characteristics:CaseGroup–residentofAlberta,Englishspeakingandabletocompleteanin-personinterview.ControlGroup–freeofanycancerdiagnosisexcludingnonmelanomaskincancerPAassessment:QuestionnaireforlifetimePAquestionnaire(METhr/wk/yr),dividedintoquartiles•Q2=1.19(0.80-1.76)Q1=<28.8•Q3=1.33(0.90-1.96)Q2=28.8-35.4•Q4=1.07(0.71-1.62)Q3=35.4-42.7Trendp=0.52Q4=≥42.7MultivariateadjustedOR(95%CI),post-MenopausalLogisticregression•Q1=1.00(referent)•Q2=0.85(0.64-1.14)•Q3=0.83(0.62-1.10)•Q4=0.69(0.51-0.93)Trendp=0.006FriedenreichandRohan1995[319]TodescribetheassociationbetweenLTPAandBC.•n=902(451case;451control)Cases:firstdiagnosisofBCin1982and1984AdjustedOR(95%CI),pre-menopausalThisstudyfoundsomeevidence(ofborderlinestatisticalsignificance)thatrecreationalPAisassociatedwithdecreasedriskofBC.Australia•Sex:Women•Q1=1.00(referent)Casecontrol•Age:20-74yrControls:Randomlyselectedfromtheelectoralroll,matchedondateofbirthtoeachcase•Q2=0.77(0.36-1.65)D&Bscore=13•Characteristics:AustralianwomenPAassessment:SelfreportedPA(kcal/wk),dividedintoquartiles•Q3=0.48(0.22-1.03)Q1=0•Q4=0.60(0.30-1.17)Q2=1-2,000Trendp=0.09Q3=2000-4000AdjustedOR(95%CI),post-menopausalQ4=>4000•Q1=1.00(referent)Logisticregressionmodels•Q2=0.74(0.46-1.18)•Q3=0.88(0.53-1.48)•Q4=0.73(0.44-1.20)Trendp=0.32Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 170 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Gammonetal1998[320]ToexaminetheassociationbetweenLTPAandBCamongyoungwomen.•n=3,173(1,668case;1,505control)Cases:womendiagnosedwithBCbetween1990-19921,668casesofBCThestudy’sdatadoesnotsupportthehypothesisofareducedriskofBCamongyoungwomenwithincreasedrecreationalPAinadolescence,youngadulthoodorduringtheyearpriortotheinterview,orwiththeaveragePAoverthethreetimeperiodsUSA•Sex:WomenMultivariateadjustedOR(95%CI)Casecontrol•Age:<45Controls:werematchedtocasesbyagegroupandgeographiccenter•Q1=1.00(referent)D&Bscore=13•Characteristics:CaseGroup–diagnosedwithinvasiveorinsituBC.ControlGroup-healthyPAassessment:QuestionnnaireforrecreationalPA,forages12-13yr,age20yrand1yearpriortotheinterview.DividedintoquartilesMETscore•Q2=0.79(0.63-0.98)Q1=1.62-18.07•Q3=0.98(0.79-1.22)Q2=18.08-30.00•Q4=1.01(0.81-1.25)Q3=30.01-42.95Trendp=0.42Q4=42.96-98.00LogisticregressionGillilandetal2001[321]ToinvestigatetherelationshipofPAwithBCriskinHispanicandnon-HispanicWhitewomen•n=1,556(712case;844control)Cases:diagnosedwithBCbetween1992-1994712casesofBCHispanicandnon-HispanicwomenwithhighPAduringnon-OPAwereatsubstantiallyreducedriskofBC.USA•Sex:WomenCasecontrol•Age:between35-74atdiagnosisControls:matchedonethnicity,ageandsevenhealthplanningdistrictsAdjustedOR(95%CI),pre-menopausalHispanicD&Bscore=13•Ethnicity:Hispanicandnon-HispanicWhitePAassessment:Self-reportednon-OPA(METhr/wkscore)•G1=1.00(referent)•Characteristics:CaseGroup–diagnosedwithinsituorinvasiveBCandresidentsofNewMexicoattimeofdiagnosis.ControlGroup–healthyG1=<25•G2=1.17(0.53-2.55)G2=25-50•G3=0.49(0.22-1.07)G3=50-80•G4=0.29(0.12-0.72)G4=≥80Trendp<0.001LogisticregressionAdjustedOR(95%CI),pre-menopausalnon-Hispanic•G1=1.00(referent)•G2=1.35(0.64-2.85)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 171 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•G3=1.44(0.67-3.10)•G4=1.13(0.49-2.61)Trendp=0.741AdjustedOR(95%CI),post-menopausalHispanic•G1=1.00(referent)•G2=0.74(0.40-1.36)•G3=0.37(0.18-0.75)•G4=0.38(0.18-0.77)Trendp=0.002AdjustedOR(95%CI),post-menopausalnon-Hispanic•G1=1.00(referent)•G2=0.45(0.26-0.78)•G3=0.49(0.28-0.86)•G4=0.45(0.24-0.85)Trendp=0.019Hsingetal1998[322]Toevaluatetheroleofselecteddemographic,lifestyle,andanthropometricfactorsintheriskformaleBC.•n=690(178case;512control)Cases:selectedfrom18,733decedentsincludedinthe1986NMFSconductedbytheUS178casesofBCThisstudysuggeststhatobesityincreasestheriskofmaleBC,possiblythroughhormonalmechanisms,whiledietaryfactors,PAandSESindicatorsalsodeservefurtherinvestigation.USA•Sex:MenNationalCenterforHealthStatistics(NCHS)AdjustedOR(95%CI)•Age:25-74•G1=1.00(referent)Casecontrol•Ethnicity:BlackandWhite•G2=0.60(0.30-1.10)D&Bscore=12•Characteristics:CaseGroup–deceased.ControlGroup–dying(ordeceased)ofcausesotherthanBCControls:selectedfrommaledecedentsdyingofcausesotherthanBC•G3=1.30(0.80-2.00)PAassessment:Questionnaire(frequencyandintensity),dividedintogroupsG1=RegularG2=IrregularG3=HardlyanyLogisticregressionanalysisHuetal1997[323]Tostudybreastcancerfocusingonbreast-feeing,bodyweight,andPAaswellasreproductivehistoriesonpre-andpost-menopausalJapanesewomen.•n=526(157case;369control)Cases:HistologicallyconfirmedcasesofBCfrom1989-1993.157casesofBCReducedriskofpre-menopausalBCwasassociatedwithhighEEinPAduringteenageyears,althoughthetrendwasnotstatisticallysignificant.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 172 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Japan•Sex:WomenUnadjustedRR(95%CI),pre-menopausalCasecontrol•Age:26-75•G1=1.00(referent)D&Bscore=13•Characteristics:CaseGroup–histologicallyconfirmedcasesofBCandresidentofGifuprefectureattimeofdiagnosis.ControlGroup–nobreastdiseaseorhormone-related(ovarian,endometrialandthyroid)cancersControls:individualswhohadthescreeningtestforBCduringthesameperiod•G2=0.74(0.38-1.44)PAassessment:QuestionnaireforTPA(kcal/wk),dividedintogroups•G3=1.01(0.54-1.87)G1=0Trendp=0.876G2=1-649UnadjustedRR(95%CI),post-menopausal:G3=≥650•G1=1.00(referent)•G2=1.53(0.69-3.54)Logisticregressionmodels•G3=1.39(0.61-3.13)Johnetal2003[324]ToexamineBCriskinrelationtolifetimehistoriesofMPAandVPAincludingLTPA,transportationhouseholdandoutdoorchores,andOPAinamultiethnicpopulation.•n=2,870(1,277case;1,593control)Cases:diagnosedbetween1995-19981,277casesofBCThisstudysupportspreviousreportsofareducedriskofBCinphysicallyactivewomen.USA•Sex:WomenMultivariateadjustedOR(95%CI),pre-menopausalLatinasCasecontrol•Age:35-79•G1=1.00(referent)D&Bscore=12•Ethnicity:Latina,African-AmericanandWhiteControls:randomlyselectedaccordingrace/ethnicityandagedistributionofcases•G2=0.84(0.49-1.45)PAassessment:In-personinterviewforlifetimePA(hr/wk),dividedintogroups•G3=0.73(0.42-1.28)Pre-menopausalMultivariateadjustedOR(95%CI),pre-menopausalAfricanAmericansG1=<9.1•G1=1.00(referent)G2=9.1-20.7•G2=1.00(0.55-1.84)G3=≥20.7•G3=0.68(0.35-1.34)Post-menopausalG1=<9.6G2=9.6-21.6G3=≥21.7Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 173 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)LogisticregressionmodelingMultivariateadjustedOR(95%CI),pre-menopausalWhites •G1=1.00(referent)•G2=0.82(0.42-1.58)•G3=0.76(0.36-1.61)MultivariateadjustedOR(95%CI),post-menopausalLatinas •G1=1.00(referent)•G2=0.82(0.55-1.24)•G3=0.81(0.54-1.22)MultivariateadjustedOR(95%CI),post-menopausalAfricanAmericans•G1=1.00(referent)•G2=0.78(0.52-1.17)•G3=0.71(0.47-1.07)MultivariateadjustedOR(95%CI),post-menopausalWhites •G1=1.00(referent)•G2=0.94(0.64-1.37)•G3=0.91(0.60-1.41)Kruk2007[325]ToexaminetheassociationbetweenalltypesofPAandBCriskamongPolishwomen.•n=590(268case;322control)PAassessment:QuestionnaireforlifetimePA(METhr/wk/yr),dividedintogroups268casesofBCTheresultsofthisstudyprovideevidenceofaninverseassociationbetweenPAandtheriskofBC.Poland•Sex:WomenG1=<110MultivariateadjustedOR(95%CI),pre-menopausalCasecontrol•Age:35-75yrG2=110-150•G1=1.00(referent)D&Bscore=13•Characteristics:Polishwomen.Cases:identifiedfromtheSzczecinRegionalCancerRegistry.Controls:matchedonageandplaceofresidenceG3=>150•G2=0.45(0.14-1.44)Logisticregressionanalysis•G3=0.44(0.14-1.37)Trendp=0.42MultivariateadjustedOR(95%CI),post-menopausal•G1=1.00(referent)•G2=0.60(0.33-1.09)•G3=0.31(0.21-0.70)Trendp=0.002Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 174 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Kruk2007[326]ToexaminetherelationshipbetweenLTPAandBCrisk.•n=822(casesn=257,controln=565PAassessment:QuestionnaireforLTPA(METs),dividedintogroupsAdjustedOR(95%CI)ThefindingsprovidefurthersupporttothehypothesisthatincreasedLTPAthroughoutlifeisassociatedwithadecreasedriskofBC.Poland•Sex:WomenG1=Low•G1=1.00(referent)Casecontrol•Age:35-93yrG2=Medium•G2=0.57(0.36-0.89)D&Bscore=13G3=High•G3=0.22(0.14-0.35)Trendp<0.0001Lahmannetal2007[327]ToexaminetheassociationofPAwithpre-andpost-menopausalBCrisk.•n=218,169Baselineand6.4yearfollow-up3,423casesofBCIncreasingPAreducesBCrisk.Europe(9countries)•Sex:WomenMultivariateadjustedHR(95%CI)byTPA,pre-menopausalProspectivecohort•Age:20-80•Q1=1.00(referent)D&Bscore=12•TheEuropeanProspectiveInvestigationintoCancerandnutritionstudyPAassessment:InterviewsandquestionnaireforTPAandrecreationalPA,eachdividedintoquartiles•Q2=1.02(0.84-1.24)TPAIndex•Q3=0.84(0.68-1.04)Q1=Inactive•Q4=1.02(0.77-1.36)Q2=ModeratelyinactiveTrendp=0.267Q3=ModeratelyactiveMultivariateadjustedHR(95%CI)byTPA,Post-menopausalQ4=Active•Q1=1.00(referent)RecreationalPA(METhr/wk)•Q2=0.89(0.79-1.00)Q1=<14•Q3=0.84(0.74-0.96)Q2=14-24•Q4=0.92(0.76-1.12)Q3=25-42Trendp=0.06Q4=>42MultivariateadjustedHR(95%CI)byrecreationalPA,pre-menopausalCoxproportionalindex•Q1=1.00(referent)•Q2=0.91(0.75-1.10)•Q3=0.95(0.78-1.14)•Q4=0.94(0.76-1.15)Trendp=0.580MultivariateadjustedHR(95%CI)byrecreationalPA,post-menopausalWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 175 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•Q1=1.00(referent)•Q2=1.05(0.94-1.17)•Q3=0.92(0.83-1.03)•Q4=0.96(0.85-1.08)Trendp=0.176Leeetal2001[328]ToexaminetheassociationbetweenPAandBCrisk.•n=39,322Baselineand4yearfollow-up411casesofBCThedatasuggestthatPAduringmiddleageandolderisnotuniformlyassociatedwithdecreasedBCrisk.Amongpost-menopausalwomenonly,higherlevelsofPAmaydecreasetheriskofBC.USA•Sex:Women•Age:≥45yrMultivariateadjustedRR(95%CI)byPA,allwomenProspectivecohort•Characteristics:HealthywomenPAassessment:Questionnaire•Q1=1.00(referent)D&Bscore=12Women’sHealthStudyPA(kJ/wk),dividedintoquartiles•Q2=1.04(0.77-1.40)Q1=<840•Q3=0.86(0.64-1.17)Q2=840-2519•Q4=0.80(0.58-1.12)Q3=2520-6299Trendp=0.11Q4=≥6300MultivariateadjustedRR(95%CI)byPA,post-menopausalonlyVPA(kJ/wk),dividedintoquintiles•Q1=1.00(referent)Q1=none•Q2=0.97(0.68-1.39)Q2=1-839•Q3=0.78(0.54-1.12)Q3=840-2099•Q4=0.67(0.44-1.02)Q4=2100-4199Trendp=0.03Q5=≥4200MultivariateadjustedRR(95%CI)byVPA,allwomenProportionalhazardregression•Q1=1.00(referent)•Q2=1.02(0.70-1.48)•Q3=1.11(0.78-1.58)•Q4=0.97(0.66-1.44)•Q5=0.98(0.69-1.40)Trendp=0.98MultivariateadjustedRR(95%CI)byVPA,post-menopausalonly•Q1=1.00(referent)•Q2=0.93(0.57-1.50)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 176 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•Q3=0.91(0.57-1.47)•Q4=0.93(0.57-1.50)•Q5=0.76(0.47-1.24)Trendp=0.29Magnussonetal2005[329]Toreporttherelationshipbetweenpre-menopausalBC,bodyfatnessatage10yearsandinadulthood,andsportsparticipationduringpuberty,lateadolescenceandearlyadulthoodfromthreerelatedcase-controlstudies.•n=3,108(1,560cases;1,548controls)PAassessment:Interviewforsportsparticipation(h/wkinthefollowingagecategories(12-14yr,16-18yr,20-30yr,12-30yr,aroundageofdiagnosis)AdjustedRR(95%CI),12-14yrAninverseassociationbetweenbodyfatnessbutnotPAatayoungageandtheriskofBCinpre-menopausalwomen.UK•Sex:Women•G1=1.00(referent)Casecontrol•Age:Study1=36yr,study2=36-45yr,study3=46-54yr•G2=1.04(0.93-1.17)D&Bscore=13•Characteristics:Whitewomenwithnopreviousmalignancy,mentalhandicaporillnessSportsparticipation(h/wk)•G3=1.03(0.93-1.14)G1=0-1Trendp=0.95G2=2-3AdjustedRR(95%CI),16-18yrG3=≥4•G1=1.00(referent)•G2=0.95(0.83-1.09)•G3=0.89(0.79-1.02)Trendp=0.20AdjustedRR(95%CI),20-30yr•G1=1.00(referent)•G2=0.90(0.76-1.08)•G3=1.01(0.81-1.26)Trendp=0.73AdjustedRR(95%CI),12-30yr•G1=1.00(referent)•G2=0.99(0.89-1.11)•G3=1.01(0.88-1.16)Trendp=0.94AdjustedRR(95%CI),aroundageofdiagnosis•G1=1.00(referent)•G2=0.84(0.71-1.00)•G3=1.06(0.86-1.32)Trendp=0.82Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 177 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Malinetal2005[330]ToevaluateapatternofbehavioralexposuresindicatingpositiveenergybalancewouldbeassociatedwithincreasedBCrisk.•n=3,015(1,459cases;1,556control)PAassessment:QuestionnaireforPA(METhr/d/yr),dividedintogroupsOR(95%CI)ThestudysuggeststhatpromotionofbehavioralpatternsthatoptimizeenergybalancemaybeaviableoptionforBCprevention.China•Sex:WomenG1=0•G1=1.86(1.44-2.41)Casecontrol•Age:Mean~47yrG2=0.1-2.92•G2=1.33(0.96-1.83)D&Bscore=12•Characteristics:ResidentsofurbanShanghaiG3=>2.92•G3=1.00(referent)ShanghaiBreastCancerStudyMargolisetal2005[331]TostudytheassociationbetweenPAandincidentinvasiveBC.•n=99,504Baselineand9.1yearfollow-up1,166casesofBCNoevidenceofaprotectiveeffectofPAonBCriskwasfound.Norway/Sweden•Sex:WomenProspectivecohort•Age:30-49(mean41yr)PAassessment:QuestionnaireforPAusinga5pointscaleandforcompetitivePA(yearsofparticipation),eachdividedintogroupsMultivariateadjustedRR(95%CI)byPAlevel,atenrollmentD&Bscore=13•TheNorwegian-SwedishWomen’sLifestyleandHealthStudyPAlevel(5pointscale)•G1=1.00(referent)G1=None•G2=1.35(0.96-1.90)G2=Low•G3=1.26(0.91-1.74)G3=Moderate•G4=1.19(0.85-1.67)G4=High•G5=1.24(0.85-1.82)G5=VigorousTrendp=0.85CompetitivePA(years)MultivariateadjustedRR(95%CI)byPAlevel,atage30G1=None•G1=1.00(referent)G2=1-4•G2=1.03(0.64-1.66)G3≥5•G3=1.16(0.74-1.81)•G4=1.06(0.67-1.68)•G5=1.20(0.77-1.95)Trendp=0.60MultivariateadjustedRR(95%CI)byPAlevel,atage14•G1=1.00(referent)•G2=0.93(0.62-1.39)•G3=0.94(0.65-1.35)•G4=1.07(0.73-1.55)•G5=1.05(0.72-1.54)Trendp=0.14Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 178 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)MultivariateadjustedRR(95%CI)byyearsofcompetitivePA•G1=1.00(referent)•G2=1.21(0.95-1.54)•G3=0.95(0.75-1.19)Trendp=0.96McTiernanetal1996[332]ToinvestigatetherelationshipbetweenLTPAandBC.•n=1,029(casesn=537,controlsn=492)PAassessment:Questionnaire(MinnesotaLTPAQuestionnaire)forLTPA(hr/wk),dividedintogroupsAdjustedOR(95%CI)byLTPAduringadulthood,allagesandmenopausalstatusTheresultsindicateaweaknegativeassociationbetweenPAandriskofBCinmiddle-agedwomen.USA•Sex:WomenG1=None•G1=1.00(referent)Casecontrol•Age:50-64G2=0.1-1.5•G2=1.1(0.7-1.6)D&Bscore=13G3=1.6-2.5•G3=0.7(0.4-1.1)G4=2.6-3.5•G4=0.7(0.4-1.1)G5=3.6-5.0•G5=0.6(0.4-0.9)G6=>5•G6=1.1(0.7-1.6)CalculatedcategoriesofEE(totaltimexintensitycode)Trendp=0.29G1=LowestAdjustedOR(95%CI)byLTPAduringadulthood,aged≥55yr,post-menopausalonlyG6=Highest•G1=1.00(referent)•G2=0.8(0.5-1.3)•G3=0.5(0.3-0.9)•G4=0.6(0.4-1.1)•G5=0.4(0.2-0.8)•G6=0.8(0.5-1.3)Trendp=0.03AdjustedOR(95%CI)bycategoryoftotalEEinadulthood,allagesandmenopausalstatus•G1=1.00(referent)•G2=1.2(0.8-2.0)•G3=0.9(0.6-1.3)•G4=0.6(0.4-0.9)•G5=0.9(0.6-1.5)•G6=0.9(0.6-1.4)Trendp=0.25Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 179 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)AdjustedOR(95%CI)bycategoryoftotalEEinadulthood,aged≥55yr,post-menopausalonly•G1=1.00(referent)•G2=0.8(0.4-1.4)•G3=0.7(0.4-1.2)•G4=0.5(0.3-0.8)•G5=0.8(0.5-1.3)•G6=0.6(0.4-1.0)Trendp=0.009McTiernanetal2003[333]ToexaminetheassociationbetweencurrentandpastLTPAandincidenceofBCinpost-menopausalwomen.•n=74,171Baselineandmeanfollow-upof4.7years1,780casesofBCIncreasedPAisassociatedwithreducedriskforBCinpost-menopausalwomen.USA•Sex:WomenPAassessment:QuestionnaireforTPA(METhr/wk),moderateorstrenuousPA(hr/wk)andstrenuousPA(hr/wk),eachdividedintogroupsAdjustedRR(95%CI)byTPALongerdurationprovidesthemostbenefithoweverneednotbestrenuous.Prospectivecohort•Age:50-79TPA(METhr/wk)•G1=1.00(referent)D&Bscore=13•Characteristics:WomenfromtheWomen’sHealthInitiativeObservationalStudyG1=none•G2=0.90(0.77-1.07)G2=0-5.0•G3=0.82(0.68-0.97)G3=5.1-10.0•G4=0.89(0.76-1.00)G4=10.1-20.0•G5=0.83(0.70-0.98)G5=20.1-40•G6=0.78(0.62-1.00)G6=≥40.0Trendp=0.03ModerateorstrenuousPA(hr/wk)AdjustedRR(95%CI)byTPA,G1=noneBMI≤24.13G2=≤1•G1=1.00(referent)G3=1.1-2.0•G2=0.78(0.57-1.10)G4=2.1-3.0•G3=0.70(0.51-0.97)G5=3.1-4.0•G4=0.80(0.60-1.10)G6=4.1-7.0•G5=0.68(0.51-0.92)G7=>7.0•G6=0.63(0.43-0.93)StrenuousPA(hr/wk)Trendp=0.03G1=noneAdjustedRR(95%CI)byTPA,BMI24.14-28.44G2=≤1.0•G1=referentWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 180 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)G3=1.1-2.0•G2=0.72(0.53-0.98)G4=2.1-4.0•G3=0.78(0.57-1.10)G5=>4.0•G4=0.77(0.58-1.00)Coxproportionalhazardratio•G5=0.85(0.64-1.10)•G6=0.78(0.52-1.20)Trendp=0.74AdjustedRR(95%CI)byTPA,BMI>28.44•G1=1.00(referent)•G2=1.10(0.88-1.50)•G3=0.90(0.67-1.20)•G4=1.00(0.79-1.30)•G5=0.89(0.65-1.20)•G6=0.94(0.57-1.60)Trendp=0.30AdjustedRR(95%CI)bycurrentmoderateorstrenuousPA•G1=1.00(referent)•G2=0.92(0.78-1.10)•G3=0.91(0.79-1.10)•G4=0.94(0.81-1.10)•G5=0.99(0.83-1.20)•G6=0.91(0.78-1.10)•G7=0.79(0.63-0.99)Trendp=0.12AdjustedRR(95%CI)bycurrentstrenuousPA•G1=1.00(referent)•G2=0.94(0.80-1.10)•G3=0.95(0.80-1.10)•G4=0.93(0.78-1.10)•G5=0.91(0.67-1.20)Trendp=0.25NavarroSilveraetal2006[334]TostudytheindependentandcombinedassociationsofVPA,energyconsumptionandBMIwithriskofsubsequentBC.•n=40,318inanalysis(49,613priortoexclusion)Baselineand16.4yearfollow-up1,673casesofBCfromthe40,318includedintheanalysis(2,545casesfromtotalpriortoexclusion)TheresultsofthestudysuggestthatBCriskmayvaryaccordingtovariouscombinationsofthecomponentsofenergybalance.Canada•Sex:WomenPAassessment:QuestionnaireforVPA(min/d),dividedintogroupsAdjustedHR(95%CI)byVPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 181 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Prospectivecohort•Age:40-59G1=none•G1=1.00(referent)D&Bscore=13•Characteristics:CanadianwomenwithnohistoryofBCG2=Any•G2=0.98(0.85-1.13)•NationalBreastScreeningStudy(NBSS)G3=0-30•G3=1.06(0.88-1.27)G4=30-60•G4=0.98(0.83-1.16)G5>60•G5=0.93(0.78-1.10)CoxproportionalhazardratioTrendp=0.38AdjustedHR(95%CI)byVPA,pre-menopausal•G1=1.00(referent)•G2=0.91(0.75-1.10)•G3=1.02(0.80-1.31)•G4=0.88(0.70-1.11)•G5=0.87(0.68-1.09)Trendp=0.23AdjustedHR(95%CI)byVPA,post-menopausal•G1=1.00(referent)•G2=1.06(0.87-1.30)•G3=1.08(0.81-1.42)•G4=1.11(0.87-1.41)•G5=1.00(0.78-1.29)Trendp=0.96Pateletal2003[335]ToexaminetheassociationbetweenvariousmeasuresofPAandpost-menopausalBCrisk.•n=72,608Baselineand5yearfollow-up1,520casesofbreastcancerThestudyshowsalowerriskofpost-menopausalBCisassociatedwithregularPA.USA•Sex:WomenPAassessment:QuestionnaireforLTPA(METshr/wk)atvarioustimesduringlife,dividedintogroupsAdjustedRR(95%CI),LTPAatstudyentryProspectivecohort•Age:50-74G1=none•G1=0.86(0.70-1.04)D&Bscore=14•Characteristics:PostmenopausalwomenG2=0.1-6.9•G2=1.00(referent)•TheAmericanCancerSocietyCancerPreventionStudyII(CPS-II)NutritionalCohortG3=7.0-17.5•G3=0.92(0.81-1.04)G4=17.6-31.5•G4=0.94(0.81-1.09)G5=31.6-42.0•G5=0.77(0.56-1.06)G6=>42.0•G6=0.71(0.49-1.02)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 182 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)LTPAat10yearspriortostudy,calculatedMETscoreandcategorizedintogroups:Trendp=0.08(amongactivewomenp=0.03)NoneAdjustedRR(95%CI),LTPAatage40yrSlight•G1=1.03(0.88-1.21)Moderate•G2=1.00(referent)Heavy•G3=1.05(0.92-1.20)Coxproportionalhazardratio•G4=1.01(0.87-1.18)•G5=1.16(0.92-1.46)•G6=0.79(0.61-1.03)Trendp=0.31(amongactivewomenp=0.36)AdjustedRR(95%CI),LTPAat10yearspriortostudyentry •None=0.80(0.51-1.25)•Slight=1.00(referent)•Moderate=0.93(0.83-1.04)•Heavy=0.87(0.68-1.13)Trendp=0.32(amongactivewomen,trendp=0.16)Pateletal2003[336]ToevaluatetheassociationbetweenlifetimeLTPAandBCrisk.•n=1,183(casesn=616)n=567,controlsn=616)PAassessment:Calendarreportingforlifetimeexerciceactivity(METh/wk),dividedintogroupsAdjustedOR(95%CI)ThefindingssuggestthatPAmaymodifytheriskofinsituBCparticularlyinwomenwithoutafamilyhistoryofBC.USA•Sex:WomenG1=None•G1=1.00(referent)Casecontrol•Age:35-64G2=0.0-3.0•G2=0.70(0.48-1.03)D&Bscore=14•Characteristics:WhiteandBlackwomenG3=3.0-8.0•G3=0.65(0.44-0.96)G4=8.0-16.0•G4=0.61(0.41-0.92)G5=16.0-32.0•G5=0.63(0.40-0.98)G6=>32.0•G6=0.65(0.39-1.08)UnconditionallogisticalregressioinTrendp=0.27(amongexercisersonlyp=0.81)Rintalaetal2002[337]ToobtainanestimateofBCincidenceinassociationwithself-ratedOPA.•n=680,000PAassessment:Self-reportedOPAin5classes(1=low,5=high)17,986casesofBCTheresultssupportthehypothesisthatOPA,ifhighenough,markedlyreducedBCrisk.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 183 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Finland•Sex:WomenClass1=JobssittingandlighthandtasksAdjustedRR(95%CI),age25-39yearsProspectivecohort•Age:Womenbornin1930-1969Class2=Handlingofheavieritems(conveyorbelt)•C1+2=1.00(referent)D&Bscore=11•Characteristics:FinishwomenClass3=Jobsinvolvingbodymotion•C3=0.99(0.85-1.17)Class4=Jobsinvolvingwalkingupstairsorlongdistances,bendingandcarrying•C4=0.90(0.76-1.07)Class5=Sameasclass4exceptheavytaskswereperformedformostoftheday•C5=0.68(0.51-1.93)PoissonregressionmodelsTrendAdjustedRR(95%CI),age40-54years•C1+2=1.00(referent)•C3=1.02(0.94-1.11)•C4=0.99(0.91-1.09)•C5=0.84(0.70-1.00)TrendAdjustedRR(95%CI),age≥55years•C1+2=1.00(referent)•C3=1.01(0.96-1.07)•C4=1.04(0.98-1.11)•C5=0.82(0.71-0.94)TrendRockhilletal1998[338]ToexaminetheassociationbetweenPAattwodifferenttimesinlifeandBCrisk.•n=372Baselineand6yearfollow-up372casesofBCThefindingsdonotsupportalinkbetweenPAinlateadolescenceorintherecentpastandBCriskamongyoungadultwomen.USA•Sex:WomenPAassessment:QuestionnaireforMVPA(h/wk)MultivariateadjustedRR(95%CI)Prospectivecohort•Age:25-42G1=<1•G1=1.00(referent)D&Bscore=12•Characteristics:NursesG2=1.0-1.9•G2=1.1(0.8-1.4)•TheNursesHealthStudyG3=2.0-3.9•G3=1.1(0.8-1.4)G4=4.0-6.9•G4=1.0(0.7-1.4)G5=≥7•G5=1.1(0.8-1.5)LogisticregressionWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 184 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)Slatteryetal2007[339]ToevaluatetheBCriskassociatedwithTPAandVPAatages15,30and50yearsandthereferentyearpriortodiagnosis/selection.•n=4,850Non-Hispanicwhite:n=3,128(casesn=1,527controlsn=1601);HispanicAmericanIndian:n=1,722(casesn=798,controlsn=924)PAassessment:QuestionnaireforTPA(activityscore)andlifetimeVPA(h/wk)1527casesofBC(non-Hispanicwhite;798casesofBC(HispanicAmericanIndian)ThedatasuggestthatPAisimportantinreducingriskofBCinnon-HispanicwhiteandHispanicAmericanIndianwomen.USA•Sex:WomenTPAscoreCasecontrol•Age:<50yrG1=0-3D&Bscore=12•Characteristics:Non-HispanicwhiteandHispanicAmericanIndianG2=4-6OR(95%CI)byTPAscore,non-HispanicwhiteG3=7-9•G1=1.00(referent)G4=10-12•G2=0.78(0.52-1.17)LifetimeVPA•G3=0.84(0.57-1.22)G1=None•G4=0.70(0.44-1.12)G2=<1.0Trendp=0.26G3=1.0-2.9OR(95%CI)byTPAscore,HispanicAmericanIndianG4=≥3.0•G1=1.00(referent)Multivariablelogisticregression•G2=1.49(0.98-2.26)•G3=1.21(0.80-1.84)•G4=0.97(0.53-1.76)Trendp=0.90OR(95%CI)bylifetimeVPA,non-Hispanicwhite•G1=1.00(referent)•G2=0.66(0.36-1.23)•G3=0.73(0.40-1.34)•G4=0.69(0.37-1.27)Trendp=0.68OR(95%CI)bylifetimeVPA,HispanicAmericanIndian•G1=1.00(referent)•G2=1.15(0.67-1.96)•G3=1.19(0.70-2.03)•G4=1.09(0.62-1.90)Trendp=0.84Spragueetal2007[340]ToinvestigatetherelationshipbetweenLTPAandstrenuousOPAandBCrisk.•n=15,710(1,689casesinsitu;6,391invasiveand7,630controls)PAassessment:QuestionnaireforlifetimeTPA(hr/wkandMEThr/wk),dividedintogroupsAdjustedOR(95%CI)forinsituBCbylifetimeTPA(hr/wk)Theresultsprovidefurtherevidencethatformostwomen,PAmayreducetheriskofinvasiveBC.USA•Sex:WomenLifetimetotalPA(hr/wk)•G1=1.00(referent)Casecontrol•Age:20-69G1=0•G2=0.92(0.72-1.19)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 185 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)D&Bscore=13•TheCollaborativeBreastCancerStudyG2=0.1-15.0•G3=0.83(0.62-1.13)G3=15.1-30.0•G4=0.86(0.59-1.24)G4=>30.0Trendp=0.22METhr/wkAdjustedOR(95%CI)forinsituBCbylifetimeTPA(METhr/wk)G1=0.0•G1=1.00(referent)G2=0.1-62.5•G2=0.93(0.72-1.20)G3=62.6-125.0•G3=0.82(0.61-1.10)G4=>125.0•G4=0.82(0.57-1.17)Trendp=0.10AdjustedOR(95%CI)forinvasiveBCbylifetimeTPA(hr/wk) •G1=1.00(referent)•G2=0.88(0.76-1.03)•G3=0.87(0.73-1.05)•G4=0.85(0.67-1.07)Trendp=0.22AdjustedOR(95%CI)forinvasiveBCbylifetimeTPA(METhr/wk)•G1=1.00(referent)•G2=0.89(0.76-1.04)•G3=0.82(0.68-0.99)•G4=0.88(0.71-1.09)Trendp=0.12Steindorfetal2003[341]ToclarifytherelationshipbetweenPAandBCrisk.•n=1,246(360cases;886controls)PAassessment:ComputerassistedtelephoneinterviewforTPA(METhr/wk)atvariousages360casesofBCThedatadonotsuggestaninverseassociationbetweenPAandBCriskinpre-menopausalwomen.Germany•Sex:WomenTPAatage12-19yrMultivariateadjustedOR(95%CI)byTPAatage12-19yrCasecontrol•Age:Mean.cases41.9yr;controls42.5yrG1=13.0-55.7•G1=1.00(referent)D&Bscore=13G2=55.8-88.7•G2=1.07(0.75-1.52)G3=88.8-134.0•G3=1.00(0.70-1.42)G4=134.1-695.9•G4=0.73(0.50-1.07)TPAatage20-30yrTrendp=0.44Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 186 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)G1=6.4-69.0MultivariateadjustedOR(95%CI)byTPAatage20-30yrG2=69.1-109.0•G1=1.00(referent)G3=109.1-160.4•G2=0.95(0.67-1.37)G4=160.5-728.8•G3=0.85(0.59-1.23)TPAatage12-30yr(both)•G4=0.96(0.67-1.39)G1=17.2-70.4Trendp=0.32G2=70.5-104.0MultivariateadjustedOR(95%CI)byTPAatage12-30yrG3=104.1-145.5•G1=1.00(referent)G4=145.6-564.4•G2=0.97(0.68-1.38)Logisticregression•G3=0.68(0.46-0.99)G4=0.94(0.65-1.35)Trendp=0.29Tehardetal2006[342]Toinvestigatethetype,duration,frequencyandintensityofPArequiredtoreducetheriskofBC.•n=90,509Baselineandfollow-upevery2yearsfor12years3,424casesofBCBCriskwasreduced,especiallywithVPA.France•Sex:WomenPAassessment:QuestionnaireforvariousPAvariables,alldividedintogroupsMultivariateadjustedRR(95%CI)byTPAProspectivecohort•Age:40-65TPA(METhr/wk)•G1=1.00(referent)D&Bscore=13•Characteristics:FrenchwomeninsuredwithMutuelleGeneraledel’EducationNationaleG1=<28.3•G2=1.05(0.93-1.17)•E3NCohortStudyG2=28.3-41.8•G3=0.94(0.83-1.05)G3=41.8-57.8•G4=0.90(0.80-1.02)Trendp<0.05G4=≥57.8MultivariateadjustedRR(95%CI)bytotalrecreationalPATotalrecreationalPA(METhr/wk)•G1=1.00(referent)G1=Inactive•G2=0.82(0.71-0.93)G2=<16.0•G3=0.94(0.84-1.06)G3=16.0-22.3•G4=0.88(0.79-0.98)G4=22.3-33.8•G5=0.81(0.72-0.92)G5=≥33.8=0.81Trendp<0.01Walking(min/d)MultivariateadjustedRR(95%CI)bywalkingdurationG1=<500•G1=1.00(referent)G2=500-2000•G2=1.03(0.95-1.11)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 187 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)G3=>2000•G3=0.91(0.81-1.02)MPA(hr/wk)Trendp=0.45G1=InactiveMultivariateadjustedRRG2=0(95%CI)byMPAG3=1-4•G1=1.00(referent)G4=5-13•G2=0.80(0.60-1.05)G5=14•G3=0.87(0.79-0.94)VPA(hr/wk)•G4=0.86(0.74-0.99)G1=Inactive•G5=0.89(0.65-1.24)G2=0Trendp<0.01G3=1-2MultivariateadjustedRR(95%CI)byVPAG4=3-4•G1=1.00(referent)G5=5•G2=0.90(0.81-0.99)Coxproportionalhazardratio•G3=0.88(0.79-0.97)•G4=0.82(0.71-0.95)•G5=0.62(0.49-0.78)Trendp<0.0001Thuneetal1997[343]ToinvestigatewhethereverydayexerciseisrelatedtotheriskofBC.•n=25,624Baselineandmeanfollow-upof14years351casesofBC(110pre-menopausaland251post-menopausalwomen)LTPAandOPAareassociatedwithareducedriskofBC.Norway•Sex:WomenPAassessment:Self-reportedLTPAandOPA,dividedintogroups•G1=1.00(referent)AdjustedRR(95%CI)byLTPAProspectivecohort•Age:20-54LTPA•G2=0.93(0.71-1.22)D&Bscore=14G1=Sedentary•G3=0.63(0.42-0.95)G2=ModerateTrendp=0.04G3=RegularexerciseOPAAdjustedRR(95%CI)byLTPA,pre-menopausalG1=Sedentary•G1=1.00(referent)G2=Walking•G2=0.77(0.46-1.27)G3=Lifting•G3=0.53(0.25-1.14)G4=HeavymanuallaborTrendp=0.10DuringworkAdjustedRR(95%CI)byLTPA,post-menopausalPre-menopausal•G1=1.00(referent)G1=Sedentary•G2=1.00(0.72-1.39)G2=Walking•G3=0.67(0.41-1.10)G3=LiftingorheavymanuallaborTrendp=0.15AdjustedRR(95%CI)byOPAWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 188 of 220Table16:Studiesexaminingtherelationshipbetweenphysicalactivityandbreastcancer.(Continued)•G1=1.00(referent)•G2=0.84(0.63-1.12)•G3=0.74(0.52-1.06)•G4=0.48(0.25-0.92)Trendp=0.02AdjustedRR(95%CI)byOPA,pre-menopausal•G1=1.00(referent)•G2=0.82(0.50-1.34)•G3=0.48(0.24-0.95)Trendp=0.03AdjustedRR(95%CI)byOPA,post-menopausal•G1=1.00(referent)•G2=0.87(0.61-1.24)•G3=0.78(0.52-1.18)Trendp=0.24Zhengetal1993[344]ToassesstheroleofOPAintheriskofBC.•n=3,783(BC=2,736)PAassessment:InterviewforOPA,dividedintogroups2,736casesofBCWomenwithlowOPAhadanincreasedriskofBC;theincidenceofBCwasreducedinwomenwithhigh-activityjobs.China•Sex:WomenG1=LowStandardizedincidenceratiosD&Bscore=9•Age:30G2=Moderate•G1=131G3=High•G2=95•G3=79D&Bscore,DownsandBlackqualityscore;YR,years;PA,physicalactivity;BC,breastcancer;LTPA,leisure-timephysicalactivity;g,group;HR,hazardratio;RR,riskratio;OR,oddsratio;95%CI,confidenceinterval;T,tertile;MET,metabolicequivalent;MET/wk,metabolicequivalentperweek;OPA,occupationalphysicalactivity;METh/wk/yr,metabolicequivalentperhourperweekperyear;kcal/wk,kilocaloriesperweek;TPA,totalphysicalactivity;VPA,vigorousphysicalactivity.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 189 of 220relationship in one or more measures of occupationaland/or leisure-time physical activity and the risk forbreast cancer. Moreover, the majority of studies demon-strated the greatest risk reduction at the highest activitylevel. With respect to the minimal and optimal volumeof exercise required, Lee [105] stated that 30-60 min/day of moderate-to-vigorous physical activity is requiredto decrease the risk for breast cancer. This belief isstrongly supported by the literature. However, othershave shown significant risk reductions at lower exercisevolumes. For instance, Rockhill et al. [106] showed sig-nificant reductions (12% or greater) in the risk for breastcancer in women who accumulated at least 1 hr ofmoderate or vigorous physical activity per week.Similarly, Sesso et al. (1998) revealed that there was an8% reduction in the risk for breast cancer with a rela-tively small energy expenditure of 500-999 kcal/wk.Further risk reductions were observed with higherenergy expenditures (= 1000 kcal/wk = 51% reductionin the risk). As discussed above, Monninkhof et al.revealed a 6% decrease in breast cancer risk for eachadditional hour of physical activity per week [104].Taken as a whole, it would therefore appear that Cana-da’s guidelines for physical activity are more than appro-priate for reducing the risk for breast cancer. Furtherresearch however is required to determine the minimalvolume of exercise that is effective in the primary pre-vention of breast cancer.ImplicationsThere is a preponderance of data linking physical inac-tivity to site-specific cancers, particularly of the breastand colon [31,104-109]. The protective effects of physi-cal activity also appear with other forms of cancer (suchas endometrial cancer) [110]. In an important review ofthe literature Lee revealed that physically active womenhave a 20-30% lower risk of breast cancer, and physicallyactive men and women have a 30-40% lower risk ofcolon cancer [105]. A more recent systematic review ofthe literature revealed a 20-80% lower risk of breast can-cer in post-menopausal women [104], with a weakerassociation in pre-menopausal women. Considering datafrom both pre- and post-menopausal women theauthors demonstrated that physically active individualshad a 15-20% lower risk of breast cancer. Monninkhofet al. also reported a 6% lower risk of breast cancer foreach additional hour of physical activity per week [104].This level of risk reduction was also supported by theU.S. Department of Health and Human Services duringits recent evaluation of the literature [31].Our current reviews of the literature support previouswork in the field including the finding of a dose-response relationship between physical activity and can-cers of the breast and colon [104,105,109]. It wouldappear that 30-60 min/day of moderate-to-vigorous phy-sical activity is associated with a lower risk of breast andcolon cancer.Recommendation #5For a reduced risk for site specific cancers (such ascolon cancer and breast cancer), it is recommendedthat individuals should participate in 30 min ormore of moderate to vigorous exercise on most daysof the week. [Level 2, Grade A]Primary Prevention of Type 2 DiabetesIn comparison to other chronic conditions, there is rela-tively limited literature examining the relationshipbetween multiple levels of physical activity/fitness andthe incidence of type 2 diabetes. All of the literatureFigure 8 Results of the Literature Search for Breast Cancer.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 190 of 220examining the dose-response (for at least three levels ofphysical activity/fitness) involved prospective cohortanalyses. A total of 3655 citations were identified duringthe electronic database search (Figure 9). Of these cita-tions, 2038 were identified in MEDLINE, 1116 inEMBASE, 118 in Cochrane, and 372 in the CINAHL/SportDiscus/PsychInfo search. A total of 614 duplicateswere found, leaving a total of 3041 unique citations. Atotal of 2865 articles were excluded after scanning, leav-ing a total of 176 articles for full review. From thesearticles 156 were excluded after full review leaving 20articles for inclusion in the systematic review of the lit-erature regarding the relationship between physicalactivity and type 2 diabetes. The reasons for exclusionincluded non-experimental/weak design (N = 18), threelevels of physical activity not reported (N = 16), reviews,summaries, or meta-analyses (N = 41), not related totype 2 diabetes (N = 71), and other (N = 10).As shown in Table 17, 20 investigations examined thedose-response (i.e., three or more levels) relationshipbetween physical activity and the incidence of type 2diabetes. This involved a total of 624,952 subjects, aver-aging 32,892 subjects per study (range 1,543-87,907).There were a total of 19,325 cases of type 2 diabetes(ranging per study from 78-4,030). The total length offollow-up averaged 9.3 yr (ranging from 3 -16.8 yr). Thearticles were published over a 16 yr period ranging from1991 to 2007.Of these studies 100% revealed an inverse relationshipbetween type 2 diabetes and levels of physical activity orfitness. When comparing the most active/fit group ver-sus the least active/fit group we found an average riskreduction of 42% (median = 44%). Therefore in our ana-lyses the most physically active/fit had a 42% lower riskof developing type 2 diabetes. The majority (84%) ofthese studies revealed incremental reductions in the riskfor type 2 diabetes with increasing activity/fitness levels.Therefore, the health benefits with respect to type 2 dia-betes prevention appear to continue across the physicalactivity/fitness continuum. Similar to other clinical con-ditions, the dose-response relationship is such that smallchanges in activity levels yield marked reductions in therisk for type 2 diabetes. The health benefits of exerciseappear to be particularly prevalent in individuals at highrisk for developing type 2 diabetes (e.g., those with ahigh body mass index, the metabolic syndrome, a his-tory of hypertension and/or a family history of type 2diabetes). The level of evidence relating physical activityto the primary prevention of type 2 diabetes would beconsidered to be Level 2A. The quality of the investiga-tions was generally high with a mean (and median)Downs and Black score of 13 (range 11-14).As with other conditions is it difficult to separate theeffects of volume and intensity of exercise. However,small changes in activity levels clearly can have a largeeffect on the risk for and incidence of type 2 diabetes.For instance, Hu and coworkers [111] revealed thatnurses (n = 68,497) who engaged in 1 hr/day of briskwalking had 24% less obesity and 34% less type 2 dia-betes (over a 6-year follow-up). These authors estimatedthat approximately 30% of new cases of obesity and 43%of new cases of type 2 diabetes could be prevented byadopting an active lifestyle including less than 10 hr/wkof television watching and ≥ 30 min/d of brisk walking.Similarly, over a 5-year period, male physicians whoFigure 9 Results of the Literature Search for Diabetes.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 191 of 220Table17Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsHaapanenetal1997[77]ToexaminetheassociationofPAandtheriskofCHD,hypertensionandT2D.•n=1,340men,1,500women10yrfollow-upNumberofcases:118LTPAhasapreventiveeffectonT2D.•Age:35-63yrPAassessment:Self-reportedAge-adjustedRR(95%CI),menFinlandLTPA(kcal/wk),dividedintogroups•G1=1.54(0.83-2.84)•G2=1.21(0.63-2.31)Prospectivecohort•G3=1.00(referent)p=0.374MenD&Bscore=14G1=0-1100Age-adjustedRR(95%CI),womenG2=1101-1900•G1=2.64(1.28-5.44)G3=>1900•G2=1.17(0.50-2.70)•G3=1.00(referent)Women(kcal/wk)p<0.006G1=0-900G2=901-1500G3=>1500CoxproportionalHRHuetal2003[111]Toexaminetherelationshipbetweensedentarybehaviours(particularlyprolongedtelevisionwatching)andriskofobesityandT2Dinwomen.•n=68,497(diabetesspecificanalyses)6yrfollow-upNumberofcases:1515Sedentarybehaviours(especiallytelevisionwatching)areassociatedwithanincreasedriskforobesityandT2D.USA•n=50,277(obesityspecificanalyses)PAassessment:Self-reportedPAandsedentarybehaviourEach2-h/dincrementinTVwatchingwasassociatedwitha23%(95%CI,17%-30%)increaseinobesityanda14%(95%CI,5%-23%)increaseinriskofT2DProspectivecohort•Age:30-55yrOutcomemeasure:onsetofobesityandT2DEach2-h/dincrementinsittingatworkwasassociatedwitha5%(95%CI,0%-10%)increaseinobesityanda7%(95%CI,0%-16%)increaseinT2DLighttomoderatePAwasassociatedwithasignificantlylowerriskforobesityandT2D.D&Bscore=13•Sex:WomenMultivariateanalysesadjustingforage,smoking,dietaryfactors,andothercovariatesStandingorwalkingaroundathome(2h/d)wasassociatedwitha9%(95%CI,6%-12%)reductioninobesityanda12%(95%CI,7%-16%)reductioninT2DWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 192 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)•Characteristics:Each1hourperdayofbriskwalkingwasassociatedwitha24%(95%CI,19%-29%)reductioninobesityanda34%(95%CI,27%-41%)reductioninT2DFreeofT2D,CVD,orcanceratbaseline•Nurses’HealthStudyMansonetal1992[112]ToexaminetheassociationbetweenregularexerciseandthesubsequentdevelopmentofT2D.•n=21,2715yrfollow-upNumberofcases:285ExerciseappearstoreducethedevelopmentofT2DevenafteradjustingforBMI.•Sex:MenPAassessment:QuestionnaireFprVPA(enoughtodevelopsweat)•Age:40-84yrTheage-adjustedincidenceofT2D:USA•Characteristics:•369casesper100,000person-yearsinmenwhoengagedinVPAlessthanonceweekly•214casesper100,000person-yearsinthoseexercisingatleastfivetimesperweek(ptrend<0.001)Freeofdiagnoseddiabetes,CVDandcanceratbaselineProspectivecohortD&Bscore=14Exercisefrequency(times/wk)G1=<WeeklyG2=AtleastweeklyAge-adjustedRR(95%CI)byexercisefrequencyTimesperweekG1=0•G1=1.00(referent)G2=1•G2=0.64(0.51-0.82)G3=2-4G4=>5Age-adjustedRR(95%CI)byexercisefrequency•G1=1.00(referent)Outcomemeasure:IncidenceT2D•G2=0.77(0.55-1.07)•G3=0.62(0.46-0.82)•G4=0.58(0.40-0.84)Age-andBMI-adjustedRR(95%CI)byexercisefrequency•G1=1.00(referent)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 193 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)•G2=0.71(0.56-0.91)Age-andBMI-adjustedRR(95%CI)byexercisefrequency•G1=1.00(referent)•G2=0.78(0.56-1.09)•G3=0.68(0.51-0.90)•G4=0.71(0.49-1.03)Huetal.2001[114]ToexaminetherelationshipbetweendietaryandlifestylefactorsinrelationtotheriskforT2D.•n=84,94116yrfollow-upNumberofcases:3300ThemajorityofT2Dcouldbepreventedthroughhealthyliving.•Sex:Women•Age:40-75yrPAassessment:QuestionnaireForPA(h/wk),dividedintogroupsMultivariate-adjustedRR(95%)USA•Characteristics:participantshadnohistoryofdiabetes,CVD,orcancer.•Q1=1.00(referent)•Q2=0.89(0.77-1.02)Retrospectivecohort•Q3=0.87(0.75-1.00)Q1=<0.5•Q4=0.83(0.71-0.96)Q2=0.5–1.9•Q5=0.71(0.56–0.90)D&Bscore=13Nurses’HealthStudyQ3=2.0–3.9Q4=4.0–6.9Q5=≥7.0Outcomemeasure:IncidenceofT2DCoxregressionSatoetal2007[116]ToexaminetherelationshipbetweenwalkingtoworkandthedevelopmentofT2D.•n=8,5764yrfollow-upNumberofcases:878ThedurationofawalktoworkisanindependentpredictoroftheriskforT2D.•Sex:Men•Age:40–55yrPAassessment:Fortimespentwalkingtowork,dividedintotertilesOR(95%CI)Japan•KansaiHealthcareStudy•T1=1.00(referent)•T2=0.86(0.70-1.06)ProspectivecohortT1=0-10min•T3=0.73(0.58-0.92)T2=11-20minSignificantdifferencewasseenbetween≤10minand≤20minonly(p=0.007)T3=≥20minWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 194 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)D&Bscore=14Outcomemeasure:IncidenceofT2DHuGetal2003[117]ToexaminetherelationshipofOPA,commutingandLTPAwiththeincidenceofT2D.•n=14,290PAassessment:QuestionnaireForOPA,LTPAandcommutingPAMultivariateadjustedHR(95%Cl)forOPA,menModerateandhighOPA,commutingPAorLTPAsignificantlyreducesriskofT2Dinmiddleagedadults.•Sex:Menandwomen•G1=1.00(referent)Finland•Age:35-64yr•G2=0.67(0.44-1.01)•Characteristic:OPA•G3=0.73(0.52-1.02)ProspectivecohortAsymptomaticforstroke,CHD,ordiabetesatbaseline.G1=Light(sitting)G2=Moderate(standing,walking)MultivariateadjustedHR(95%Cl)forOPA,womenD&Bscore=12G3=Active(walking,lifting)•G1=1.00(referent)•G2=0.72(0.46-1.12)•G3=0.78(0.52-1.18)CommutingPA(min/d)G1=NoneMultivariateadjustedHR(95%Cl)forOPA,menandwomenG2=1-29G3=≥30G1=1.00(referent)G2=0.70(0.52-0.96)LTPAG3=0.74(0.57-0.95)•G1=Low(inactive)•G2=Moderate(walking,cycling>4hr/wk)MultivariateadjustedHR(95%Cl)forcommutingPA,men•G3=High(running,jogging>3hr/wk)•G1=1.00(referent)•G2=1.00(0.71-1.42)Outcomemeasure:incidenceofT2D•G3=0.75(0.46-1.23)MultivariateadjustedHR(95%Cl)forcommutingPA,womenCoxproportionalHR•G1=1.00(referent)•G2=0.94(0.63-1.42)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 195 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)•G3=0.57(0.34-0.96)MultivariateadjustedHR(95%Cl)forcommutingPA,menandwomen•G1=1.00(referent)•G2=0.96(0.74-1.25)•G3=0.64(0.45-0.92)MultivariateadjustedHR(95%Cl)forLTPA,men•G1=1.00(referent)•G2=0.78(0.57-1.06)•G3=0.84(0.52-1.37)MultivariateadjustedHR(95%Cl)forLTPA,women•G1=1.00(referent)•G2=0.81(0.58-1.15)•G3=0.85(0.43-1.66)MultivariateadjustedHR(95%Cl)forLTPA,menandwomen•G1=1.00(referent)•G2=0.81(0.64-1.20)•G3=0.84(0.57-1.25)Hsiaetal2005[118]USAToevaluatetherelationshipbetweenPAandtheincidenceofT2Dinalarge,diversegroupofolderwomen.•n=87,907PAassessment:Questionnaireforfrequencyanddurationof4walkingspeedsand3otheractivitiesclassifiedbyintensity(light,moderate,strenuous)Numberofcases:2,271ThereisastronginverserelationshipbetweenPAandT2D.ThereisastrongerrelationshipbetweenPAandT2DinCaucasianwomenthaninminoritywomen.Thismaybeexplainedbylesspreciseriskestimatesinminoritywomen.•Sex:Women•Age:White63.8±7.3,AfricanAmerican61.9±7.3,Hispanic60.5±7.1,Asian/PacificIslander63.7±7.6,AmericanIndian61.5±8.0MultivariateadjustedHR(95%CI)bywalking,Caucasian•Q1=1.00(referent)Prospectivecohort•Q2=0.85(0.74-0.87)•Q3=0.87(0.75-1.01)•Q4=0.75(0.64-0.89)D&Bscore=11Q1=Low•Q5=0.74,(0.62-0.89)Q2=Trendp<0.001Q3=Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 196 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)Q4=MultivariateadjustedHR(95%CI)byTPA,CaucasianQ5=High•Ethnicity:Whiten=74,240;AfricanAmericann=6,465;Hispanicn=3,231;Asian/PacificIslander2,445;AmericanIndiann=327•Q1=1.00(referent)CoxproportionalHR•Q2=0.88(0.76-1.01)•Q3=0.74(0.64-0.87)•Q4=0.80(0.68-0.94)•Q5=0.67(0.56-0.81)Trendp=0.002•Characteristics:participantshadnohistoryofdiabetes,werenotonanyantidiabeticmedications•Women’sHealthInitiativeWannametheeetal2000[120]ToexaminetheroleofcomponentsoftheinsulinresistancesyndromeintherelationshipbetweenPAandtheincidenceofT2DandCHD.•n=5,15916.8yrfollow-upNumberofcases:196TherelationshipbetweenPAandT2Dappearstobemediatedbyseruminsulinandcomponentsoftheinsulinresistancesyndrome.However,thesefactorsdonotappeartoexplaintheinverserelationshipbetweenPAandT2D.•Sex:Men•Age:40-59yrPAassessment:QuestionnaireforTPAPhysicalactivitygroupswereidentifiedandscored:MultivariateadjustedRR(95%CI)England,WalesandScotland•Characteristics:Nohistoryofheartdisease,diabetesorstrokeQ1=1.00(referent)Q2=0.66(0.42-1.02)Q3=0.65(0.41-1.03)ProspectivecohortQ4=0.48(0.28-0.83)Q1=NoneQ5=0.46(0.27-0.79)Q2=Occasionalp<0.005D&Bscore=14Q3=LightQ4=ModerateWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 197 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)Q5=Moderatelyvigorous/vigorousMPA(sportingactivityonceaweekorfrequentlighter-intensityactivitiessuchaswalking,gardening,do-ityourselfprojects)aresufficienttoproduceasignificantreductioninriskofbothCHDandT2D.Themenwereclassifiedaccordingtocurrentsmokingstatus,alcoholconsumption,andsocialclassCoxproportionalHRMansonetal1991[121]ToexaminetheassociationbetweenregularVPAandtheincidenceofT2D.•n=87,2538yrfollow-upNumberofcases:1303WomenwhoengageinVPAatleastonceperweekhadreducedadjustedRRofT2DRR=0.66(0.6-0.75)PAispromisingintheprimarypreventionofT2D.•Sex:Women•Age:34-59yrPAassessment:USA•Characteristics:Freeofdiagnoseddiabetes,cardiovasculardiseaseandcancerQuestionnaireFrequencyofweeklyexercise(0-+4)ProspectivecohortThereductioninriskremainedsignificantafteradjustmentforBMIRR=0.84(0.75-0.95)D&Bscore=13Analysisalsorestrictedtothefirst2yraftertheassessmentofPAlevelandtosymptomaticdiabetesWhenanalysiswasrestrictedtothefirst2yearsafterascertainmentofPAlevelandtosymptomaticdiseaseastheoutcome,theage-adjustedRRofthosewhoexercisedwas0.50,andageandbody-massindexadjustedRRwas0.69(0.48-1.0)Multivariateadjustmentsforage,body-massindex,familyhistoryofdiabetes,andothervariablesdidnotalterthereducedriskfoundwithexerciseMultivariateanalysisFamilyhistoryofdiabetesdidnotmodifytheeffectofexercise,andriskreductionwithexercisewasevidentamongbothobeseandnon-obesewomenWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 198 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)Helmrichetal1994[122]ToexaminetherelationshipbetweenPAandthedevelopmentofT2D.•n=5,99098,524man-yearsoffollow-up(1962-1976)Numberofcases:202IncreasedPAiseffectiveinpreventingT2D.•Sex:Men•Age:39-68yrRR(95%CI)byblockswalkedperdayUSA•Characteristics:healthy,asymptomaticPAassessment:QuestionnaireforLTPA(walking,stairclimbing,sportsetc;kcal/wk)Blockswalked/dayTheprotectivebenefitisespeciallypronouncedinthoseindividualswhohavethehighestriskofdisease.•T1=1.00(referent)FurtherreviewofthedatareportedbyHelmichetal.1991•T2=1.30UniversityofPennsylvaniaAlumniHealthStudy•T3=0.92p=0.80LTPA(kcal/wk)kcalwereassignedtoeachactivityandaddedtogetherLTPAwasinverselyrelatedtothedevelopmentofT2DProspectivecohortSamefindingstothatreportedin1991D&Bscore=14Lowest<500Highest≥3500Blockswalked/dayT1=<5T2=5-14T3=≥15CoxproportionalHRHelmrichetal1991[123]ToexaminetheRelationshipbetweenPAandtheSubsequentdevelopmentofT2D.•n=5,99098,524man-yearsoffollow-up(1962-1976)Numberofcases:202IncreasedPAiseffectiveinpreventingT2D.•Sex:Men•Age:39-68yrLTPAwasinverselyrelatedtothedevelopmentoftype2diabetesUSA•Characteristics:healthy,asymptomaticPAassessment:QuestionnaireforLTPAkcal/wk:stairsclimbed/dayandblockswalked/day,dividedintogroupsTheprotectivebenefitisespeciallypronouncedinthoseindividualswhohavethehighestriskofdisease.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 199 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)ProspectivecohortRR(95%CI)bysportsplayed•UniversityofPennsylvaniaAlumniHealthStudy•G1=1.00(referent)•G2=0.90D&Bscore=13•G3=0.69•G4=0.65AllactivitiesLTPATrendp=0.02Q1=<500Q2=500-999RR(95%CI)byFlightsofstairsclimbed/dayQ3=1000-1499Q4=1500-1999•T1=<5=1.00(referent)Q5=2000-2499•T2=0.78Q6=2500-2999•T3=0.75Q7=3000-3499Trendp=0.07Q8=≥3500RR(95%CI)byBlockswalked/daySportsplayed•T1=1.00(referent0G1=None•T2=1.31G2=ModerateG3=Vigorous•T3=0.93Trendp=0.80G4=ModerateandVigorousAgeadjustedRR(95%CI)byallactivitiesStairsclimbedperdayT1=<5•Q1=1.00(referent)T2=5-14•Q2=0.94T3=≥15•Q3=0.79•Q4=0.78Blockswalkedperday•Q5=0.68T1=<5•Q6=0.90Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 200 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)T2=5-14•Q7=0.86T3=≥15•Q8=0.52p=0.01fortrendCoxproportionalHRAgeadjustedRR(95%CI)byallactivitiesexceptvigoroussports•Q1=1.00(referent)•Q2=0.97•Q3=0.87•Q4=0.92•Q5=0.75•Q6=1.29•Q7=1.03•Q8=0.48Trendp=0.07AgeadjustedRR(95%CI)byvigoroussportsonly•Q1=1.00(referent)•Q2=0.69•Q3=N/A•Q4=0.53•Q5=0.86•Q6=0.56•Q7=0.40•Q8=0.46Trendp=0.05Weietal1999[124]TodeterminewhetherPFisassociatedwithriskforimpairedfastingglucoseandT2D.•n=8,6336yrfollow-upNumberofcases:149HighPFisassociatedwithareducedriskforimpairedfastingglucoseandT2D.USA•Sex:Men•Age:43.5yrPFassessment:Maximaltreadmillexercisetest(METs),dividedinto3groups593patientsdevelopedimpairedfastingglucose•Characteristics:Non-diabeticmenOR(95%CI)fordevelopingglucoseintoleranceProspectivecohortT1=Low•T1=1.9(1.5–2.4)T2=Moderate•T2=1.5(1.2–1.8)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 201 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)T3=High•T3=1.00(referent)D&Bscore=12Outcomemeasure:IncidenceofimpairedfastingglucoseandT2DOR(95%CI)fordevelopingT2D•T1=3.7(2.4–5.8)•T2=1.7(1.1–2.7)•T3=1.00(referent)Statistics:GLMKatzmarzyketal2007[126]Toexaminetherelationshipsamongadiposity,PA,PFandthedevelopmentofT2DinadiversesampleofCanadians.•n=1,543(709menand834women)6yrfollow-upNumberofcases:78(37inmen,41inwomen)AdiposityandPFareimportantpredictorsofthedevelopmentofT2D.Canada•Sex:MenandwomenPFassessment:QuestionnairePAwasassociatedwith23%loweroddsofdevelopingdiabetesandmaximalMETswasalsoassociatedwithsignificantlyloweroddsofdevelopingdiabetes(OR=0.28)Prospectivecohort•Age:36.8-37.5PAassessment:LTPAQuestionnaireD&Bscore=13•Characteristics:Freeofdiabetesatbaseline•CanadianPhysicalActivityLongitudinalStudyBurchfieletal1995[345]ToexaminetherelationshipbetweenPAandT2D.•n=6,8156yrfollow-upNumberofcases:391PAisassociatedinverselyandindependentlywithincidentT2D.USA•Sex:Men(Japanese-American)PAassessment:QuestionnairePAindex(basedonintensityanddurationofactivity)Theage-adjusted6-yearcumulativeincidenceofdiabetesdecreasedprogressivelywithincreasingquintileofphysicalactivityfrom73.8to34.3per1,000(p<0.0001,trend)•Age:45-68yrLevelsofactivity:Prospectivecohort•Characteristics:FreeofdiabetesatentryQ1=Basal-SleepingrecliningD&Bscore=13•TheHonoluluHeartProgramQ2=SedentaryQ3=Slight-CasualwalkingQ4=Moderate–GardeningQ5=Heavy-Lifting,shovelingOutcomemeasure:Self-reportedT2D(clinicallyrecognized)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 202 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)Dziuraetal2004[346]TodeterminetheprospectiverelationbetweenreportsofhabitualPA,3-yearchangeinbodyweight,andthesubsequentriskofT2Dinanoldercohort.•n=2,135PAassessment:Questionnairefor4typesofactivities(walking,gardening/housework,physicalexercises,activesportsorswimming)andfrequencyofparticipationmeasuredwithaPAscore:118casesofT2DObservationofaninverserelationshipbetweenreportedPAandrateofT2DM.USA•Sex:MenandwomenIncidentdensityofT2D=6.6/1000personyears•Age:≥65yrProspectivecohort•Ethnicity:83%White,15%AfricanAmerican,2%Non-whiteDiabetes(n=118)PAscore:2.17±1.7‘Some’PA:78%SubjectsreportingsomePAatbaselineexperiencedarateofT2Dover50%lowerrelativetothosereportingnoPA.D&Bscore=12•Characteristics:HealthyasymptomaticNever(score0)Sometimes(score1)Often(score2)Non-Diabetes(n=2017)PAscore:2.34±1.7‘Some’PA:84%PearsonproductmomentcorrelationcoefficientandCoxproportionalHRHuetal.1999[347]Toquantifythedose-responserelationshipbetweentotalPAandincidenceofT2Dinwomen.•n=70,1028yroffollow-upNumberofcases:1419IncreasedPAisassociatedwithsubstantialreductioninriskofT2DincludingPAofmoderateintensityandduration.USA•Sex:WomenPAassessment:QuestionnaireforTPA(METhr/wk)andVPA(6METs)Multivariate-adjustedRR(95%CI)ofbyTPA•Age:40-65yr•Q1=1.0(referent)ProspectivecohortToexaminethehealthbenefitsofwalkingincomparisontomorevigorousactivity.•Characteristics:participantshadnohistoryofdiabetes,CVD,orcancerTPA(METhr/wk)•Q2=0.77(0.66-0.90)D&Bscore=12Nurses’HealthStudyQ1=0-2.0•Q3=0.75(0.65-0.88)Q2=2.1-4.6•Q4=0.62(0.52-0.73)Q3=4.7-10.4•Q5=0.54(0.45-0.64)Q4=10.5-21.7Trendp<0.001•Q5=≥21.8METscoreMultivariate-adjustedRR(95%CI)amongwomenwhodidnotperformvigorousexercise(MET’s):Q1=≤0.5•Q1=1.0(referent)Q2=0.6-2.0•Q2=0.91(0.75-1.09)Q3=2.1-3.8•Q3=0.73(0.59-0.90)Q4=3.9-9.9•Q4=0.69(0.56-0.86)Q5=≥10.0•Q5=0.58(0.46-0.73)Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 203 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)Outcomemeasures:Trendp<0.001IncidenceofT2DHuetal2001[348]ToexaminetheroleofprolongedtelevisionwatchingontheriskforT2D.•n=37,91810yearfollow-upNumberofcases:1058IncreasingPAisassociatedwithasignificantreductioninriskforT2D,whereasasedentarylifestyleindicatedbyprolongedTVwatchingisrelateddirectlytoincreasedrisk.USA•Sex:Men•Age:40-75yrPAassessment:QuestionnaireforPA(METhr/wk)andTVwatching(h/wk),eachdividedintoquintilesMultivariate-adjustedRR(95%CI)byPAProspectivecohort•Characteristics:participantshadnohistoryofdiabetes,CVD,orcancerQ1=0-5.9•Q1=1.00(referent)D&Bscore=11•HealthProfessionals’Follow-upStudyQ2=6.0-13.7•Q2=0.78(0.66–0.93)Q3=13.8-24.2•Q3=0.65(0.54–0.78)Q4=24.3-40.8•Q4=0.58(0.48–0.70)Q5=≥40.9•Q5=0.51(0.41–0.63)Trendp<0.001Timespentwatchingtelevisionperweek(h/wk)Multivariate-adjustedRR(95%CI)byTVtimeQ1=0-1•Q1=1.00(referent)Q2=2-10•Q2=1.66(1.15-2.39)Q3=11-20•Q3=1.64(1.12-2.41)Q4=21-40•Q4=2.16(1.45-3.22)Q5=>40•Q5=2.87(1.46-5.65)Trendp<0.001Ranaetal2007[349]ToexaminetheindividualandcombinedassociationofobesityandphysicalinactivitywiththeincidenceofT2D.•n=68,90716yrfollow-upNumberofcases:4,030ThisstudyfoundthatobesityandphysicalinactivityindependentlycontributedtothedevelopmentofT2D.USA•Sex:WomenProspectivecohort•Age:30-55yearsagerangein1976(note:1986wasthebaselineyearforthestudy)PAassessment:Questionnaireforaverageamountoftime/weekMEThoursperweekspentinMVPA(≥3METs),dividedintoquintilesMultivariate-adjustedRR(95%CI)byMVPA:ThebenefitsofPAwerenotlimitedtoleanwomen;amongthosewhowereoverweightandobese,physicallyactivewomentendedtobeatlowerriskforT2Dthansedentarywomen.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 204 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)D&Bscore=12•Characteristics:Nohistoryofdiabetes,CVDorcancerQ1=<2.1•Q1=2.37(2.15–2.16)•Nurses’HealthStudyQ2=2.1-4.6•Q2=1.92(1.73–2.13)Q3=4.7-10.4•Q3=1.48(1.34–1.64)Q4=10.5-21.7•Q4=1.40(1.26–1.55)Q5=≥21.8•Q5=1.00(referent)Trendp<0.001CoxproportionalHRSawadaetal2003[350]ToexaminetheassociationbetweenPFandtheincidenceofT2D.•n=4,74714yrfollow-upNumberofcases:280LowPFisassociatedwithahigherriskforthedevelopmentofT2D.Japan•Sex:Men•Age:20-40yrPFassessment:Maximalaerobicpowerestimateml/kg/minusingasubmaximalcycleergometertest,dividedintoquartilesAge-adjustedRR(95%CI)Prospectivecohort•Characteristics:Freeofdiabetes,CVD,hypertensin,tuberculosis,andgastrointestinaldiseaseatbaselineQ1=32.4±3.1•Q1=1.00(referent)D&Bscore=13Q2=38.0±2.5•Q2=0.56(0.42–0.75)Q3=42.4±3.0•Q3=0.35(0.25–0.50)Q4=51.1±6.2•Q4=0.25(0.17–0.37)Trendp<0.001Outcomemeasure:IncidenceofT2DMultivariateadjustedRR(95%CI)•Q1=1.00(referent)•Q2=0.78(0.58–1.05)•Q3=0.63(0.45–0.89)•Q4=0.56(0.37–0.84)Trendp=0.001CoxproportionalHRWeinsteinetal2004[351]ToexaminetherelativecontributionsandjointassociationofPAandBMIwithT2D.•n=37,8786.9yearfollowupNumberofcases:1,361AlthoughBMIandphysicalinactivityareindependentpredictorsofincidentdiabetes,themagnitudeoftheassociationwithBMIwasgreaterthanwithPAincombinedanalyses.ThesefindingsunderscorethecriticalimportanceofadiposityasadeterminantofT2D.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 205 of 220Table17:Therelationshipbetweenphysicalactivityandthedevelopmentoftype2diabetes.(Continued)USA•Sex:WomenPAassessment:Questionnaireforwalkingperweek(h/wk)andTPA(kcal/wk),dividedintogroupsandquartilesrespectivelyMultivariate-adjustedHR(95%CI)bytimespentwalking•Age:45+years•G1=1.00(referent)Prospectivecohort•Healthcareprofessionals•G2=0.95(0.82-1.10)D&Bscore=12•Characteristics:NohistoryofCVD,cancerordiabetes•G3=0.87(0.73-1.02)•G4=0.66(0.54-0.81)•G5=0.89(0.73-1.09)Walkingperweek(h/wk)Trendp=0.004G1=nowalkingMultivariate-adjustedHR(95%CI)byTPAG2=<1•Q1=1.00(referent)G3=1-1.5•Q2=0.91(0.79-1.06)G4=2-3•Q3=0.86(0.74-1.01)G5=≥4•Q4=0.82(0.70-0.97)TPA(kcal/wk)Trendp=0.01Q1<200Q2=200-599Q3=600-1,499Q4≥1500CoxproportionalHRD&Bscore,DownsandBlackqualityscore;YR,years;PA,physicalactivity;CHD,coronaryheartdisease;T2D,type2diabetes;LTPA,leisure-timephysicalactivity;g,group;kcal/wk,kilocaloriesperweek;HR,hazardratio;RR,riskratio;OR,oddsratio;95%CI,confidenceinterval;CVD,cardiovasculardisease;OPA,occupationalphysicalactivity;PF,physicalfitness;MET,metabolicequivalent;MET/wk,metabolicequivalentperweek.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 206 of 220exercised vigorously at least once weekly had a 29%lower incidence of type 2 diabetes than individuals whodid not exercise regularly [112]. These authors alsorevealed that physical activity that was sufficient tocause sweating was associated with a lower incidence oftype 2 diabetes. Other research has also demonstratedthat moderate-to-vigorous physical activity (≥ 5.5 METsfor at least 40 min per week) and/or aerobic fitnesslevels above 31 mL·kg-1·min-1 are associated with alower risk of type 2 diabetes in middle-aged men [113]with the effect being the greatest in high-risk indivi-duals. Therefore, it would appear that Canada’s recom-mendations for physical activity are sufficient to reducethe risk for type 2 diabetes.In 2001, Hu et al. [114] reported very interesting andcompelling research regarding the role of lifestyle factorsin the development of type 2 diabetes. Using data fromthe Nurses’ Health Study, they defined a low-risk groupaccording to five lifestyle factors including BMI, ahealthy diet, the participation in moderate-to-vigorousphysical activity for at least 30 min per day, no currentsmoking, and the consumption of an average of at leastone-half serving of an alcoholic beverage per day. Theyrevealed that the women in the low risk group had a RRfor type 2 diabetes of only 0.09 (CI 0.05-0.17) in com-parison to the rest of the cohort. They also found that91% of the cases of type 2 diabetes in this cohort (CI83-95%) could be attributed to the five lifestyle factors.This research provided compelling evidence that themajority of type 2 diabetes could be prevented throughhealthy living [115].As reviewed in Table 17 there is evidence that leisure-time, occupational and commuting-related leisure timeactivities significantly reduce the risk for the develop-ment of type 2 diabetes. For instance, a recent study bySato and colleagues [116] revealed that the walking dis-tance to work was directly related to the incidence oftype 2 diabetes in 8,576 Japanese men followed for 4years. The risk reduction was approximately 27% in theparticipants who walked to work for ≥21 min comparedto those who did so for ≥10 min. These findings aresimilar to that found by Hu et al. who reported thatmoderate occupational, commuting and leisure-timephysical activities all had a significant inverse relation-ship to risk in middle-aged men and women [117].Although ethnicity is often not reported in the currentresearch, the studies examined in our systematic reviewcame from a variety of countries and regions. Data wasobtained from studies from the USA, Canada, UK,Japan, and Finland. For instance, Hsia et al. (2005) con-ducted a prospective 5-year study of 87,907 post-meno-pausal women, finding a strong graded inverserelationship between physical activity and type 2 dia-betes. The relationship was stronger in “Caucasian” thanin minority (African-American, Hispanic or Asian)women. The authors postulated this finding mightreflect less precise risk assessments in minority women[118]. As we have outlined previously, further researchis clearly warranted that examines the relationshipbetween physical activity and type 2 diabetes in personsof different ethnicities. Moreover, further research isneeded to determine the effects of socio-economic sta-tus on the observed relationships. Nonetheless, theresearch is compelling, habitual physical activity appearsto be highly effective in the primary prevention of type2 diabetes.ImplicationsIn 1992, the consensus panel from the InternationalConference on Physical Activity, Fitness and Health(held in Toronto, Canada) [17] indicated that physicalactivity can effectively reduce the risk for, and incidenceof, type 2 diabetes. Over 15 years later, the research iscompelling; habitual physical activity is an effective pri-mary preventative strategy against the development oftype 2 diabetes [111-113,118-123]. As shown in our ana-lyses, numerous observational studies have revealed thatregular physical activity is associated with a lower riskof developing type 2 diabetes [111-113,118-123]. More-over, increased aerobic fitness is inversely associatedwith the risk of type 2 diabetes [113,124]. It is alsoapparent that both aerobic and resistance type activitiesreduce the risk for type 2 diabetes [125,126].Although it is difficult to determine the dose-responsebetween physical activity and type 2 diabetes in themajority of the current randomized controlled trials,these trials have revealed important findings. Influentialexercise and/or lifestyle intervention trials have demon-strated clearly the health benefits of physical activity/exercise in the prevention of type 2 diabetes. Forinstance, in the Diabetes Prevention Program (US),3,234 high-risk participants were randomly assigned toone of three groups: a) a placebo control, b) metformindrug therapy (850 mg twice daily), and c) a lifestyleintervention. The authors revealed that the lifestyleintervention (including physical activity for at least 150minutes per week) was more effective than metformin(alone) (respective reductions in incidence 58% and31%) [127]. Similarly, Tuomilehto et al. (2001) con-ducted a randomized controlled trial with middle-aged,overweight subjects with impaired glucose tolerance(172 males and 350 females). The authors reported asignificant reduction in the incidence of type 2 diabetesin the intervention group (which received advice regard-ing moderate intensity exercise (30 min/day) and dietarycontrol). The lifestyle intervention reduced the risk oftype 2 diabetes by approximately 54% in women and63% in men [128]. In a review of the literature, William-son et al. revealed modest weight loss via diet andWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 207 of 220physical activity reduced the incidence of type 2 diabetesin high risk individuals by 40-60% over a 3-4 year period[129]. Collectively, the epidemiological and randomizedcontrolled trials provide compelling evidence supportingthe role of habitual physical activity in the primary pre-vention of type 2 diabetes.Recommendation #6For a reduced risk for type 2 diabetes, it is recom-mended that individuals should participate in 30min or more of moderate to vigorous exercise on mostdays of the week. [Level 2, Grade A]Primary Prevention of OsteoporosisThe protective effects of physical activity and exercisetraining on bone health are well documented. In fact,the relationship between indicators of bone health (suchas bone mineral density or bone mineral content) andphysical activity have been evaluated extensively (seeTable 18). Numerous exercise intervention trials haverevealed that aerobic and resistance activities have abeneficial effect on bone mineral density across the life-span [16]. In fact, several systematic reviews of the lit-erature [130-135] and major consensus statements [136]have shown clearly the potential benefits of both aerobicand resistance training on bone health (particularly inpost-menopausal women). It has been estimated thatexercise interventions prevent or reverse at least 1% ofbone loss per year in the lumbar spine and the femoralneck of pre- and post-menopausal women [130,137].Exercise has also been shown to significantly reducethe risk and/or number of falls in comparison to inac-tive controls [138-142]. Moreover, fracture risk and/orincidence has been shown to be reduced in active indivi-duals [143-145]. Case-control studies of older personswho suffered a hip fracture have revealed that theseindividuals had significantly lower physical activity levelsthroughout adulthood [136,146]. Observational studieshave also revealed an inverse relationship between theincidence of fractures and physical activity [147-149].For instance, Joakimsen et al. revealed lower fracturerates in individuals who performed more weight-bearingactivities [148]. Similarly, Kujala et al. [147] in a 21-yearprospective study revealed that intense activity was asso-ciated with a lower incidence of hip fracture (HazardRatio = 0.38, 95% CI = 0.16-0.91). Feskanich et al.(2002) also revealed that moderate physical activity wasinversely related to the risk of hip fracture in postmeno-pausal women [149]. In a review of observational trials,Katzmarzyk and Janssen [20] revealed that the fracturerisk was markedly higher in habitually inactive indivi-duals (RR = 1.59 (95% CI = 1.40-1.80)) with a popula-tion attributable risk of 24% in Canada.There is clear evidence that exercise training is of ben-efit for bone health and accordingly reduces the risk forosteoporosis. However, remarkably limited research hasactually examined the relationship between routine phy-sical activity and the prevalence and/or incidence ofosteoporosis (Figure 10). In our systematic search of theosteoporosis literature, a total of 3655 citations wereidentified during the electronic database search (Figure7). Of these citations, 1888 were identified in MEDLINE,236 in EMBASE, 82 in Cochrane, and 481 in theCINAHL/SportDiscus/PsychInfo search. A total of 276duplicates were found, leaving a total of 2411 uniquecitations. A total of 2059 articles were excluded afterscreening, leaving a total of 352 articles for full review.From these articles all 352 were excluded after full-textreview. The reasons for exclusion included non-experi-mental/weak design (n = 87), did not contain threelevels of physical activity or not possible to determinedose-response relationship (n = 38), reviews, summaries,meta-analyses (n = 39), not dealing specifically withosteoporosis (n = 21), only on change in bone mineraldensity (N = 123), clinical population (N = 10), bonemetabolism (N = 13), fractures (N = 3), population < 18yrs (N = 11), and other (N = 7). An additional 2 articleswere found through the authors’ knowledge of the field.As identified in our systematic search, the majority ofthe literature has dealt with the relationship betweenphysical activity and indicators of bone health and/orthe incidence of fractures. However, a recent observa-tional trial [150] has provided evidence supporting theability of physical activity to reduce the incidence ofosteoporosis. For instance, Robitaille et al. revealed adose-response relationship between physical activitylevel and the prevalence of reported osteoporosis in8073 women aged ≥ 20 yr in the National Health andNutrition Examination Survey, 1999-2004 [150]. Thoseperforming no physical activity were at a higher riskthan those who engaged in moderate (<30 MET hr/wk)and high (>30 MET hr/wk) levels of physical activity.There was a dose-response relationship with the highestphysical activity group having the lowest prevalence ofosteoporosis. Similarly, Keramat et al. [151] in a case-control investigation revealed that physical activity wasprotective against the development of osteoporosis.At this time it is difficult to define clearly the actualdose-response required to cause a reduction in the inci-dence of osteoporosis. It is clear that bone adaptations toexercise are load dependent and site specific [9,10,16,152].As such, physical activities that involve significantly load-ing/impact are often advocated for the prevention ofosteoporosis. It is has been shown that running 15-20miles per week is associated with bone mineral accrual ormaintenance. Longer distances however may be associatedwith reduced bone mineral density [136].Feskanich et al. reported that the risk of hip fracturewas lowered by 6% for each increase of 3 MET-hoursWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 208 of 220Table18Studiesexaminingtherelationshipbetweenphysicalactivityandosteoporosis.PublicationCountryStudyDesignQualityScoreObjectivePopulationMethodsOutcomeCommentsandConclusionsRobitailleetal2008[150]Toassesstherelationshipbetweenthephysician-diagnosisedosteoporosisandfamilyhistoryandexaminewhetherosteoporosisriskfactorsaccountforthisrelationship.•n=8,073PAassessment:Questionnaire.LevelofPAwasexpressedinMET(hr/wk)PrevalenceofreportedosteoporosisinUSwomenbyPAlevelPrevalenceofosteoporosisdeclineswithincreasingPAinadose-responsemanner.•Sex:Women•Age:≥20yrsUSA•Characteristics:Americanwomen•Study:NHANES(1999-2004)G1=0PAlevel(%prevalence)Cross-sectionalG2=<30•G1=11.0(9.8-12.4)G3=≥30•G2=7.1(6.0-8.4)D&Bscore=10•G3=3.9(2.8-5.4)Musclestrengtheningactivitieswereexpressedinfrequency/wkTimes/weekp<0.001PAlevel(ageadjusted)•G1=8.9(7.7-10.1)G1=0•G2=8.4(7.3-9.7)G2=<2•G3=6.2(4.4-8.5)G3=≥2p<0.01Criteriafordiagnosisofosteoporosis:Self-reportedphysiciandiagnosedMusclestrengthening(%prevalence)•G1=8.1(7.2-9.1)Chi-square•G2=3.1(1.7-5.5)•G3=7.4(5.8-9.4)p<0.001Musclestrengthening(ageadjusted)•G1=7.8(6.9-8.7)•G2=6.7(3.8-11.8)•G3=9.5(7.6-11.9)p<0.05Keramatetal2008[151]ToassessriskfactorsforosteoporosisinpostmenopausalwomenfromselectedBMDcentersinIranandIndia.•Irann=363;178case,185controlStudyperiod2002–2005OR(95%CI)ofosteoporosisinexercisersvs.non-exercisers.Iran(ageadjusted)ExercisewasshownasprotectivefactorinbothcountriesanditremainedsignificantafteradjustmentforageweightandheightinIran.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 209 of 220Table18:Studiesexaminingtherelationshipbetweenphysicalactivityandosteoporosis.(Continued)•Indian=354;203case,151controlPAassessment:Questionnaire.PAwascategorizedasexercises,otherexercises(e.g.,swimming,aerobics,weighttraining)andwalkingIranandIndia•Sex:Women•Exercises=0.4(0.2-0.7)Casecontrol•Age:IranCase=58.2(7.1)yr;IranControl=55.7(6.0)yr;IndiaCase=58.9(8.1)yr;IndiaControl=56.4(7.5)yrBMDassessment:DEXA•Otherexercises=0.4(0.2-0.6)•Characteristics:CaseshadBMD>2.5SDbelowaverageofyoungnormalbonedensityinL1-L4spineregionand/ortotalfemoralregion.ControlshadBMD<1SDbelownormalMultinominallogisticregression•RegularWalking=0.5(0.3-0.8)D&Bscore=11WalkingandotherexerciseswereshownasprotectivefactorsinIraniansubjects.Iran(age,weight,heightadjusted)•Exercises=0.4(0.2-0.7)•Otherexercises=0.3(0.2-0.6)•RegularWalking=0.4(0.2-0.8)India(ageadjusted)•Exercises=0.4(0.3-0.9)•Otherexercises=NS•RegularWalking=NSIndia(age,weight,heightadjusted)•Exercises=NS•Ethnicity:IndianandIranian•Otherexercises=NS•RegularWalking=0.4(0.2-0.8)D&Bscore,DownsandBlackqualityscore;YR,years;MET/wk,metabolicequivalentperweek;G,groups;PA,physicalactivity;BMD,bonemineraldensity;SD,standarddeviation;DEXA,dualenergyx-rayabsorptiometry;NS,notsignificant.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 210 of 220per week of activity (or 1 hr/wk of walking at an averagepace) [149]. There was a linear reduction with increas-ing physical activity level. Walking for at least 4 hr/wkwas also associated with a 41% lower risk of hip fracturecompared to less than 1 hr/wk [149]. The work of Robi-taille et al. also indicated that moderate levels of physi-cal activity are sufficient to reduce the prevalence ofosteoporosis [150].In summary, there is preliminary evidence to indicatethat the current Canadian physical activity guidelines aresufficient to maintain and/improve bone health. However,further research is clearly required, in particular researchthat examines the relationship between physical activityand the incidence of osteoporosis in both men andwomen from varied ethnic backgrounds. Currently, thelevel of evidence would be considered to be at a Level 3A.The quality of the investigations was generally low with amean (and median) Downs and Black score of 11.Recommendation #7For a reduced risk for osteoporosis, it is recom-mended that individuals should participate in loadbearing activities for 30 min or more on most days ofthe week. [Level 3, Grade A]Other ConsiderationsMusculoskeletal Fitness and HealthIn the present analyses, all indices of physical activity/fitness were incorporated into our systematic reviews.Although the majority of the data is related to aerobicactivities, it should be noted that many of these activitiesalso had a significant musculoskeletal component.Moreover, direct measurements of musculoskeletal fit-ness were included in various studies included in ourreview. Although there is limited information available(in comparison to aerobic activities) there is compellingevidence that musculoskeletal fitness is also positivelyassociated with health status [9,10,16].Warburton and colleagues [9,10] in two reviews of theliterature reported that enhanced musculoskeletal fitnessis associated positively with glucose homeostasis, bonehealth, functional independence, mobility, psychologicalwell-being, and overall quality of life and negativelyassociated with fall risk, morbidity and premature mor-tality. They also reported that interventions that increasemusculoskeletal fitness also have a significant positiveeffect on the health status of the individuals with a lowmusculoskeletal reserve (e.g., the frail elderly).In an evaluation of the current literature some keyfindings emerge. Grip strength has particularly beenshown to be inversely related to premature mortalityand/or morbidity (e.g., functional limitations) [153-156].Rantanen et al. (1998) reported that those individualswith the lowest grip strength had a higher rate of mortal-ity at a younger age (over a 27- year period) than theircounterparts with higher muscular strength. Further-more, they revealed that those with a faster rate ofdecline in muscular strength (>1.5% per year) or a verylow grip strength (<21 kg) had a greater incidence ofchronic diseases, such as type 2 diabetes, stroke, arthritis,coronary heart disease, and pulmonary disorders. It wasshown that those in the lowest grip strength tertile hadan 8-fold increased risk for disability. Individuals withhigh muscular strength have also been shown to developless functional limitations in comparison to their coun-terparts with lower strength over a 5-year period [157].Figure 10 Results of the Literature Search for Osteoporosis.Warburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 211 of 220Katzmarzyk and colleagues [126,154,158] in Canadahave also demonstrated a positive relationship betweenmusculoskeletal fitness and health status. For instance,Katzmarzyk and Craig (2002) revealed that there was asignificantly higher risk of premature mortality in thelower quartile of sit-ups in both men (RR = 2.72) andwomen (RR = 2.26). Grip strength was also predictive ofmortality in men (RR = 1.49), but not women. In arecent study, Mason et al. revealed that musculoskeletalfitness was a significant predictor of weight gain over a20-year period [158]. Importantly, they also reportedthat individuals with low musculoskeletal fitness had78% greater odds of significant weight gain (≥ 10 kg)compared to those with high musculoskeletal fitness.These studies provide direct support for the inclusion ofresistance and flexibility training in Canada’s physicalactivity guidelines for adults [3,159].Recommendation #8For improved health status and reduced risk forchronic disease and disability, it is recommendedthat individuals should include daily activities thattax the musculoskeletal system [Level 2, Grade A]LimitationsIt is important to note that for each chronic condition,the methods used to determine the relationship betweenphysical activity and the specific clinical outcome wereoften quite varied. For instance, early work in the fieldgenerally controlled for few confounding variables (suchas age). In comparison, current literature often controlsfor a myriad of potential confounding variables. Thesediscrepancies make the comparison of the relative riskreductions between studies and across clinical condi-tions more difficult. Moreover, the multivariate analyses(controlling for various potential confounding factors)may inappropriately decrease the level of risk reductionassociated with physical activity and the clinical end-point [31]. This is owing to the fact that some of thehealth benefits associated with physical activity may bemediated through these variables [31].There was often considerable variability in the findingsand major conclusions of the studies examined. Oftenthe available literature was limited by the lack of a clearstandard for assessing physical activity. In manyinstances, it was extremely difficult to determine theactual dosage of physical activity used to group the par-ticipants. This lack of clarity makes it very difficult toclearly define the dose-response relationship betweenphysical activity and various chronic conditions.ConclusionsThere is incontrovertible evidence that regular exerciseis an effective preventative strategy against prematuremortality, cardiovascular disease, stroke, hypertension,colon cancer, breast cancer, and type 2 diabetes. Thereis also compelling indirect evidence to support theprotective effects of physical activity with respect toosteoporosis. In many instances the dose-responserelationship is linear with further health benefits withincreasing levels of activity. The current Canadian phy-sical activity guidelines for adults are sufficient toreduce the risk for multiple chronic diseases simulta-neously. The acknowledgement that every bit of exer-cise counts towards health benefits (with greaterbenefits at higher energy expenditures) is consistentwith the literature and a reasonable message to pro-mote to the general population. However, furtherinvestigation is likely required to evaluate the relation-ship between physical activity and health status innon-Caucasian populations.AcknowledgementsProduction of this paper has been made possible through a financialcontribution from the Public Health Agency of Canada. The views expressedherein do not necessarily represent the views of the Public Health Agencyof Canada. The leadership and administrative assistance was provided by theCanadian Society for Exercise Physiology (CSEP). Dr. Warburton is supportedby a Canadian Institutes of Health Research New Investigator award and aMichael Smith Foundation for Health Research Clinical Scholar award. Weare indebted to the work conducted by the staff from the CSEP Health &Fitness Program of BC and Physical Activity Support Line (PAL; http://www.physicalactivityline.com) in the systematic review of the literature and thedevelopment of tables for this manuscript and the companion paper byPaterson and Warburton [160].Author details1Cardiovascular Physiology and Rehabilitation Laboratory, University of BritishColumbia, Vancouver, Canada. 2Experimental Medicine Program, Faculty ofMedicine, University of British Columbia, Vancouver, Canada. 3Cognitive andFunctional Learning Laboratory, University of British Columbia, Vancouver,Canada.Authors’ contributionsDW was responsible for the conceptualization and design of the systematicreview, the generation of the systematic review terms, oversaw the datacollection, evaluated each article included in the review, and wasresponsible for creating and revising the manuscript. SC was involved in thedata collection, the critical review of the articles, the creation of the tablescontained in the article and the revision of the manuscript. AI assisted withthe data collection, the critical review of the articles, and the creation andthe revision of tables in the manuscript. LN assisted with the generation ofthe systematic review terms, the retrieval of articles, and the generation andrevision of the tables. SB was involved in the conceptualization and designof the systematic review, the generation of the systematic review terms,oversaw the data collection, the review of the articles, and was responsiblefor creating and revising the manuscript. All authors have read andapproved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Received: 24 July 2009 Accepted: 11 May 2010 Published: 11 May 2010References1. Bouchard C, Shephard RJ: Physical activity fitness and health: the modeland key concepts. 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JAMA 2004, 292:1188-1194.doi:10.1186/1479-5868-7-39Cite this article as: Warburton et al.: A systematic review of theevidence for Canada’s Physical Activity Guidelines for Adults.International Journal of Behavioral Nutrition and Physical Activity 2010 7:39.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitWarburton et al. International Journal of Behavioral Nutrition and Physical Activity 2010, 7:39http://www.ijbnpa.org/content/7/1/39Page 220 of 220

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