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Cardiac and vascular dynamics in persons of Aboriginal descent Foulds, Heather-Jean A 2014

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  CARDIAC AND VASCULAR DYNAMICS IN PERSONS OF ABORIGINAL DESCENT by Heather-Jean A. Foulds M.Sc., University of British Columbia, 2010 B.Sc., University of Northern British Columbia, 2007   A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate and Postdoctoral Studies (Experimental Medicine)  THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver)  July 2014  © Heather-Jean A. Foulds, 2014     ii  Abstract Introduction:  Aboriginal populations currently experience greater rates of cardiovascular disease, than non-Aboriginals.  Limited information regarding vascular and cardiac structure and function among this population are known, despite the close relationships of cardiac and vascular physiology to cardiovascular disease. Purposes:  Theses investigations evaluate cardiac and vascular dynamics of Aboriginal Canadians, directly compare vascular measures between Aboriginal and European adults and evaluate the cardiac and vascular responses to exercise among Aboriginal and European adults. Methods:  In the first investigation, 55 Aboriginal adults underwent a comprehensive vascular assessment.  In Study 2, 10 Aboriginal adults underwent a resting echocardiographic evaluation.  Study 3 compared the vascular status of 58 Aboriginal and 58 age- and sex-matched European adults.  Vascular measures were assessed pre and post-exercise among 12 Aboriginal adults and 12 age- and sex matched European adults in Study 4.  Pre and post-exercise cardiac assessments were performed on 12 Aboriginal and 12 age- and sex-matched European adults in Study 5.   Results:  In study 1, Aboriginal male and female adults (19-91 years) were found to have similar pulse wave velocity and intima-media thickness, with males having greater systolic blood pressure and small arterial compliance, and females having greater baroreceptor sensitivity.  Study 2 identified Aboriginal males having larger left ventricular mass, dimensions, and volumes, while females had greater vascular resistance.  In study 3, Aboriginal adults arterial compliance and baroreceptor sensitivity was identified as being more strongly associated with blood pressure compared to Europeans.  Additionally, only European hypertension (blood pressure  ≥140 mmHg systolic or ≥90 mmHg diastolic) rates were found to be associated with obesity (body mass index ≥30.0 kg·m-2).  Study 4 identified European adults as having greater reductions in blood pressure following exercise, with a lack of change among Aboriginal adults.  In study 5, Aboriginal and European adults were found to have similar cardiac functional responses to maximal aerobic exercise, including decreases in volumes and increases in arterial-ventricular coupling; however, only Aboriginal adults demonstrated decreases in volumes and compliance, and increases in elastance and stiffness following submaximal exercise.  Conclusion:  Differences in factors affecting blood pressure and blood pressure responses to exercise were identified between Aboriginal and European adults.    iii  Preface  The designing of this project was initiated by Heather-Jean Foulds.  Heather-Jean Foulds conducted and coordinated data collection and participant recruitment.  A large majority of data entry and data analysis, as well as all of the data editing and preparation was performed by Ms. Foulds.  All writing and statistical analysis of this thesis was conducted by Heather-Jean Foulds.  Heather-Jean Foulds was also responsible for writing the ethics for this project.   Dr. Darren Warburton provided funding for the research assistants, data collection, and analysis, and supervised the research portion of this program.  Dr. Warburton contributed substantially to the study development and provided expertise and interpretations.  Supervision, advice and guidance for this thesis were provided by Dr. Warburton.  Dr. Shannon Bredin also assisted with supervision of Aboriginal initiatives within the Cardiovascular Physiology and Rehabilitation Laboratory.  Drs. Ainslie, Shubair, and Devlin provided guidance and advice in the development and undertaking of this project.   Assistance with testing was provided by the Cardiovascular Physiology and Rehabilitation Laboratory students and undergraduate research assistants, including Willow Thickson, Carley Kennedy, and Amanda DeFaye. Ethical approval for this research was obtained through the University of British Columbia Clinical Research Ethics Board.  This research was conducted under ethics approval certificate H12-01084.   A version of Chapter Two from this thesis has been published as: Foulds HJA, Warburton DER (2014). The blood pressure and hypertension experience among North American Indigenous populations. Journal of Hypertension, 32(4) 724-734.  Heather-Jean Foulds was responsible for the manuscript preparation and statistical analysis, and was one of two reviewers to conduct the literature search.   Chapter four from this thesis has been prepared as a manuscript version to be published as: Foulds HJA, Bredin SSD, Warburton DER. The vascular health of Canadian Indigenous populations.  Heather-Jean Foulds was responsible for data collection and analysis, statistical analysis, and manuscript preparation. A version of chapter five from this thesis has been prepared as a manuscript to be published as: Foulds HJA, Bredin SSD, Warburton DER. The cardiac dynamics of Canadian  iv  Indigenous populations.  Heather-Jean Foulds was responsible for data collection and analysis, statistical analysis, and manuscript preparation. Chapter six from this thesis has also been prepared as a manuscript version for publication as: Foulds HJA, Bredin SSD, Warburton DER. Ethnic differences in vascular function and the relationship with blood pressure.  Heather-Jean Foulds was responsible for data collection and analysis, statistical analysis, and manuscript preparation. A version of chapter seven from this thesis has been published as: Foulds HJA, Bredin SSD, Warburton DER (2015). Ethnic differences in the vascular responses to aerobic exercise. Medicine and Science in Sports and Exercise, (in press).  Heather-Jean Foulds was responsible for data collection and analysis, statistical analysis, and manuscript preparation. Chapter eight from this thesis has also been prepared in manuscript form for publication as: Foulds HJA, Bredin SSD, Warburton DER. Ethnic differences in the cardiac responses to aerobic exercise.  Heather-Jean Foulds was responsible for data collection and analysis, statistical analysis, and manuscript preparation.      v  Table of Contents Abstract .................................................................................................................... ii Preface ..................................................................................................................... iii Table of Contents ..................................................................................................... v List of Tables .......................................................................................................... ix List of Figures ......................................................................................................... xi List of Symbols ...................................................................................................... xii List of Abbreviations ........................................................................................... xiii Acknowledgements.................................................................................................xv Dedication ............................................................................................................. xvi 1. Introduction ........................................................................................................ 1 2. Blood Pressure and Hypertension in North American Aboriginal Populations ............................................................................................................... 3 2.1 Introduction ................................................................................................................... 3 2.1 Methods......................................................................................................................... 4 2.2.1 Inclusion and Exclusion Criteria .................................................................... 4 2.2.2 Search Strategy .............................................................................................. 4 2.2.3 Study Selection and Data Extraction ............................................................. 4 2.2.4 Level of Evidence .......................................................................................... 7 2.2.5 Data Synthesis ................................................................................................ 7 2.3 Results ........................................................................................................................... 8 2.3.1 Hypertension Prevalence ............................................................................... 8 2.3.2 Mean Blood Pressures.................................................................................. 10 2.3.3 Blood Pressure and Hypertension Changes Over Time ............................... 14 2.3.4 Comparison to Reference Populations ......................................................... 16 2.4 Discussion ................................................................................................................... 18 2.5 Conclusion .................................................................................................................. 20 3. Literature Review, Objectives, and Hypotheses ...........................................21 3.1 Aboriginal Peoples ...................................................................................................... 21 3.1.1 Background .................................................................................................. 21 3.1.2 First Nations Peoples ................................................................................... 21 3.1.3 Métis Peoples ............................................................................................... 23 3.2 Cardiovascular Physiology and Disease ..................................................................... 24  vi  3.2.1 Vascular Physiology .................................................................................... 24 3.2.2 Cardiac Physiology ...................................................................................... 25 3.2.3 Cardiovascular Disease ................................................................................ 27 3.2.2 Aboriginal Health Disparities ...................................................................... 28 3.2.3 Ethnic Specific Criteria in Health ................................................................ 30 3.3 Vascular Dynamics ..................................................................................................... 30 3.3.1 Vascular Dynamics and Health .................................................................... 30 3.3.2 Ethnic Differences in Vascular Dynamics ................................................... 33 3.4 Cardiac Dynamics ....................................................................................................... 35 3.4.1 Cardiac Dynamics and Health ..................................................................... 35 3.4.2 Ethnic Differences in Cardiac Dynamics ..................................................... 36 3.5 Cardiovascular Responses to Exercise ........................................................................ 37 3.5.1 Exercise and Vascular Dynamics................................................................. 38 3.5.2 Exercise and Cardiac Dynamics .................................................................. 39 3.5.3 Ethnic Differences in Cardiovascular Responses to Exercise ..................... 40 3.6 Summary ..................................................................................................................... 41 3.7 Rationale, Objectives and Hypotheses ........................................................................ 42 3.7.1 Study 1: Vascular Health Status of Aboriginal Peoples .............................. 43 3.7.2 Study 2: Cardiac Dynamics of Aboriginal Peoples ..................................... 43 3.7.3 Study 3: Ethnic Differences in Vascular Measures and Relation of Vascular Measures with Blood Pressure .............................................................................. 44 3.7.4 Study 4: Ethnic Differences in the Vascular Responses to Exercise ........... 45 3.7.5 Study 5: Ethnic Differences in the Cardiac Responses to Exercise ............. 45 4. Vascular Health Status of Aboriginal Peoples ..............................................47 4.1 Introduction ................................................................................................................. 47 4.2 Methods....................................................................................................................... 47 4.2.1 Participants and Ethical Approval ............................................................... 47 4.2.2 Individual Characteristics and Blood Pressure ............................................ 48 4.2.3 Vascular Assessment ................................................................................... 49 4.2.4 Physical Fitness Measures ........................................................................... 51 4.2.5 Statistical Analyses ...................................................................................... 52 4.3 Results ......................................................................................................................... 52 4.4 Discussion ................................................................................................................... 58 4.5 Conclusion .................................................................................................................. 61 5. Cardiac Dynamics of Aboriginal Peoples ......................................................62 5.1 Introduction ................................................................................................................. 62 5.2 Methods....................................................................................................................... 62 5.2.1 Participants and Ethical Approval ............................................................... 62 5.2.2 Individual Characteristics, Blood Pressure, and Fitness Measures.............. 63 5.2.3 Echocardigraphy .......................................................................................... 63 5.2.4 Data Analysis ............................................................................................... 64 5.2.5 Statistical Analysis ....................................................................................... 65 5.3 Results ......................................................................................................................... 65 5.4 Discussion ................................................................................................................... 74  vii  5.5 Conclusion .................................................................................................................. 77 6. Ethnic Differences in Vascular Function and the Relationship with Blood Pressure ...................................................................................................................78 6.1 Introduction ................................................................................................................. 78 6.2 Methods....................................................................................................................... 79 6.3 Results ......................................................................................................................... 80 6.4 Discussion ................................................................................................................... 90 6.5 Conclusion .................................................................................................................. 95 7. Ethnic Differences in the Vascular Responses to Exercise ..........................96 7.1 Introduction ................................................................................................................. 96 7.2 Methods....................................................................................................................... 96 7.2.1 Participants and Ethical Approval ............................................................... 96 7.2.2 Experimental Procedure ............................................................................... 97 7.2.3 Aerobic Exercise .......................................................................................... 97 7.2.4 Statistical Analysis ....................................................................................... 97 7.3 Results ......................................................................................................................... 98 7.3.1 Baseline and Demographic Characteristics ................................................. 98 7.3.2 Vascular Responses to Exercise................................................................. 100 7.4 Discussion ................................................................................................................. 109 7.5 Conclusion ................................................................................................................ 112 8. Ethnic Differences in the Cardiac Responses to Exercise ..........................114 8.1 Introduction ............................................................................................................... 114 8.2 Methods..................................................................................................................... 114 8.2.1 Participants and Ethical Approval ............................................................. 114 8.2.2 Experimental Procedure ............................................................................. 115 8.2.3 Statistical Analysis ..................................................................................... 115 8.3 Results ....................................................................................................................... 116 8.3.1 Baseline and Demographic Characteristics ............................................... 116 8.3.2 Cardiac Responses to Exercise .................................................................. 118 8.3.3 Comparisons of Cardiac Responses to Maximal and Submaximal Exercise............................................................................................................................. 133 8.3.4 Correlations of VO2max with Cardiac Responses to Exercise .................. 136 8.4 Discussion ................................................................................................................. 140 8.5 Conclusion ................................................................................................................ 144 9. Conclusions .......................................................................................................145 9.1 Discussions and Conclusions .................................................................................... 145 9.2 Strengths and Limitations ......................................................................................... 146 9.2.1 Strengths .................................................................................................... 146 9.2.2 Limitations ................................................................................................. 147 9.3 Implications and Applications .................................................................................. 148 9.4 Future Research ........................................................................................................ 149  viii  References .............................................................................................................151     ix  List of Tables  Table 4.1 Characteristics and demographics of participants, by sex mean ± SD, n (%) ............. 53 Table 4.2 Health status and measures of participants, by sex mean ± SD, n (%) ........................ 54 Table 4.3 Vascular measures of Aboriginal participants, by sex mean ± SD, n (%) ................... 55 Table 5.1 Demographic characteristics of participants, by sex mean ± SD, n (%) ...................... 67 Table 5.2 Body composition and fitness characteristics of participants, by sex mean ± SD ....... 68 Table 5.3 Resting cardiac measurements of participants, by sex mean ± SD .............................. 69 Table 5.4 Cardiac function of participants, by sex mean ± SD .................................................... 70 Table 5.5 Cardiac elastance and mechanics of participants, by sex mean ± SD .......................... 71 Table 5.6 Cardiac structural correlates of aerobic fitness among Aboriginal participants .......... 72 Table 5.7 Cardiac functional correlates of aerobic fitness among Aboriginal participants ......... 72 Table 5.8 Cardiac functional correlates of aerobic fitness among Aboriginal participants ......... 73 Table 6.1 Characteristics and demographics of participants, by ethnic group mean ± SD, n (%)80 Table 6.2 Health status and measures of participants, by ethnic group mean ± SD, n (%) ......... 82 Table 6.3 Vascular measures of participants, by ethnic group mean ± SD .................................. 83 Table 6.4 Vascular measures of Male participants, by ethnic group mean ± SD ........................ 84 Table 6.5 Vascular measures of Female participants, by ethnic group mean ± SD ..................... 85 Table 6.6 Discrete correlates of hypertension rates among Aboriginal and European participants, n (%).............................................................................................................................................. 89 Table 6.7 Continuous correlates of hypertension rates among Aboriginal and European participants .................................................................................................................................... 90 Table 7.1 Demographic characteristics of participants, by ethnic group mean ± SD, n (%) ....... 99 Table 7.2 Body composition and fitness characteristics of participants, by ethnic group mean ± SD, n (%) .................................................................................................................................... 100 Table 7.3 Blood pressures of participants in response to exercise, by ethnic group mean ± SD102 Table 7.4 Vascular measures of participants in response to exercise, by ethnic group mean ± SD..................................................................................................................................................... 105 Table 7.5 Baroreflex response to exercise among Aboriginal and European participants, by ethnic group mean ± SD, n (%) .................................................................................................. 106 Table 7.6 The changes in vascular measures resulting from maximal and submaximal aerobic exercise, mean ± SD ................................................................................................................... 107 Table 7.7 The association of VO2max with changes in vascular measures following maximal and submaximal aerobic exercise ...................................................................................................... 108 Table 8.1 Demographic characteristics of participants, by ethnic group mean ± SD, n (%) ..... 117 Table 8.2 Body composition and fitness characteristics of participants, by ethnic group mean ± SD, n (%) .................................................................................................................................... 118 Table 8.3 Systolic dimension responses to exercise among Aboriginal and European participants, by ethnic group mean ± SD .................................................................................... 119  x  Table 8.4 Diastolic dimension responses to exercise among Aboriginal and European participants, by ethnic group mean ± SD .................................................................................... 121 Table 8.5 Systolic function response to exercise among Aboriginal and European participants, by ethnic group mean ± SD ........................................................................................................ 123 Table 8.6 Systolic function response to exercise among Aboriginal and European participants, by ethnic group mean ± SD ........................................................................................................ 125 Table 8.7 Left ventricular mass and arterial responses to exercise among Aboriginal and European participants, by ethnic group mean ± SD ................................................................... 127 Table 8.8 Diastolic function response to exercise among Aboriginal and European participants, by ethnic group mean ± SD ........................................................................................................ 128 Table 8.9 Elastance and arterial-ventricular coupling response to exercise among Aboriginal and European participants, by ethnic group mean ± SD ................................................................... 129 Table 8.10 Peak systolic strain and rotation response to exercise among Aboriginal and European participants, by ethnic group mean ± SD ................................................................... 130 Table 8.11 Peak systolic strain and rotation rates response to exercise among Aboriginal and European participants, by ethnic group mean ± SD ................................................................... 131 Table 8.12 Peak diastolic strain and rotation rates response to exercise among Aboriginal and European participants, by ethnic group mean ± SD ................................................................... 133 Table 8.13 The changes in cardiac structures and volumes resulting from maximal and submaximal aerobic exercise ...................................................................................................... 134 Table 8.14 The changes in cardiac function resulting from maximal and submaximal aerobic exercise, mean ± SD ................................................................................................................... 135 Table 8.15 The changes in rotation and strain resulting from maximal and submaximal aerobic exercise, mean ± SD ................................................................................................................... 136 Table 8.16 The association of VO2max with changes in cardiac structural measures following maximal and submaximal aerobic exercise ................................................................................ 137 Table 8.17 The association of VO2max with changes in cardiac functional measures following maximal and submaximal aerobic exercise ................................................................................ 139 Table 8.18 The association of VO2max with changes in cardiac rotation and strain measures following maximal and submaximal aerobic exercise ................................................................ 140     xi  List of Figures  Figure 2.1 Citations examined for systematic review .................................................................... 6 Figure 2.2 The prevalence of hypertension among Aboriginal populations in North American, by investigation and overall means, weighted for sample size ............................................................ 9 Figure 2.3 Systolic blood pressures among Aboriginal populations in North American, by investigation and overall means, weighted for sample sizes, standard deviations where available....................................................................................................................................................... 11 Figure 2.4 Diastolic blood pressures among Aboriginal populations in North American, by investigation and overall means, weighted for sample sizes, standard deviations where available....................................................................................................................................................... 13 Figure 2.5 Changes in hypertension rates (A), systolic (B) and diastolic (C) blood pressures over time among First Nations/American Indian, Inuit/Alaskan Native and overall Aboriginal populations in North American, including only samples with at least 400 individuals per average.  Asterisk (*) indicates significant change from Pre-1980, dagger (†) indicates significant change from 2000-present, p < 0.05 .......................................................................................................... 15 Figure 2.6 Direct comparisons of Aboriginal hypertension rates (A), systolic (B) and diastolic (C) blood pressures to non-Aboriginal population reference groups, including only articles which directly compare to reference samples, and comparisons with at least 400 individuals per ethnic group.  Asterisk (*) indicates significant difference from reference population, p < 0.05 ........... 17 Figure 3.1 The external common carotid artery with visible intima-media thickness ................. 31 Figure 4.1 The relationship between overall intima-media thickness and age among Aboriginal adult participants ........................................................................................................................... 56 Figure 4.2 The relationship between overall age and vascular measures of systolic blood pressure (A), diastolic blood pressure (B), central pulse wave velocity (C) and peripheral pulse wave velocity (D) among Aboriginal adult participants ............................................................... 57 Figure 4.3 The relationship between overall age and vascular measures of large arterial compliance (A), small arterial compliance (B), spectral method baroreceptor sensitivity (C) and sequence method baroreceptor sensitivity (D) among Aboriginal adult participants ................... 58 Figure 6.1 Ethnic differences in the relationship between mean arterial pressure and vascular measures of: large arterial compliance (A, p < 0.001), small arterial compliance (B, p < 0.001), spectral method baroreceptor sensitivity (C, p < 0.001*), sequence method baroreceptor sensitivity (D, p < 0.001), central pulse wave velocity (E, p = 0.16) and intima-media thickness (F, p = 0.09).  Asterisk (*) indicates a significant interaction between Aboriginal and European regression slopes. .......................................................................................................................... 87 Figure 7.1 Central (A) and peripheral (B) pulse wave velocity before (Pre) and after (Post) maximal and submaximal aerobic exercise among Aboriginal and European adults.  Asterisk (*) indicate significant difference from pre- to post, p < 0.05. Dagger (†) indicates significant difference in change from Aboriginal, p < 0.05. ........................................................................ 103    xii  List of Symbols  ≥  Greater than or equal to ≤  Less than or equal to >   Greater than <   Less than μ   Micro ±   Plus or minus %   Percent †  Footnote below ‡  Footnote below *  On table footnote below, on figure significant difference **  Footnote below $  Canadian dollars χ2  Chi-squared, distribution probability statistic, used to compare distribution    between groups     xiii  List of Abbreviations  beats   beats – contractions of the heart cm    centimetres – units of length measurement dyne   units of force measurement, equal to g·cm·s-2 g   gram – unit of mass measurement Hz   hertz - unit of frequency measurement in cycles per second kg    kilogram – unit of mass measurement L   litre – unit of volume measurement m   metre – unit of length measurement min   minutes – unit of time measurement mm   millimetre – unit of length measurement mmHg    millimetres of mercury – units of blood pressure measurement mL   millilitre – units of volume measurement mL∙mmHg-1  millilitres per millimetres of mercury – units of arterial compliance  measurement ms   millisecond – units of time measurement n.u.   normalized units rpm   Revolutions Per Minute s   seconds – unit of time measurement W   watts – units of power yr   years – unit of time measurement μm   micrometre - unit of length measurement °   degree of arc – unit of plane angle measurement °·s-1   degree of arc per second – unit of angular velocity measurement  A   Late Ventricular Diastolic Filling Velocity ANCOVA  Analysis of Covariance ANOVA  Analysis of variance BMI    Body Mass Index BPV   Blood Pressure Variability BRS   Baroreflex Sensitivity E   Early Ventricular Diastolic Filling Velocity E/A   Ratio of Early to Late Ventricular Filling Velocities E’   Mitral Annular Tissue Velocity EA   Arterial Elastance EAI   Arterial Elastance Indexed for Body Surface Area ELV   Ventricular Elastance ELVI   Ventricular Elastance Indexed for Body Surface Area HA   Alternative Hypothesis  xiv  H0   Null Hypothesis HRV   Heart Rate Variability IMT   Intima-Media Thickness N/A   Not Applicable NN   Normal-to-Normal PWV   Pulse Wave Velocity RMSSD  Root Mean Squared of Successive Differences SD   Standard Deviation SVI   Stroke Volume Indexed for Body Surface Area VO2max  Maximal Aerobic Capacity       xv  Acknowledgements  I would like to express my appreciation and thanks to Dr. Darren Warburton for his guidance, support, and assistance in the development and completion of this thesis.  I would also like to express my gratitude and thanks to the members of the Cardiovascular Physiology and Rehabilitation Laboratory for their assistance and guidance.  To my committee members Dr. Phil Ainslie, Dr. Mamdouh Shubair, and Dr. Angela Devlin, I thank you for your advice and guidance. Acknowledgements and thanks also to Willow Thickson, Carley Kennedy, Amanda De Faye, and all the volunteers who assisted with this project.  I would like to express my thanks to Allen McLean for his expertise and guidance in echocardiography.  I would like to express my thanks and appreciation to all the family and friends for their support and encouragement throughout this degree.  To Jeff, my parents, and brother, and all the friends and lab mates who have assisted me through this project, I owe you all a great deal of thanks.  Your encouragement, assistance, and guidance during this degree has been invaluable.  I would also like to thank the Natural Sciences and Engineering Research Council of Canada, Indspire, the National Aboriginal Achievement Foundation, the Foundation for the Advancement of Aboriginal Youth, the Canadian Institutes for Health Research, and the University of British Columbia for their financial support during the undertaking of this degree.  Special thanks also go to all the participants of this project, without whom this research would not be possible.      xvi  Dedication  To the ancestors and all those who came before me    1  1. Introduction Cardiovascular disease has a tremendous impact on Canadian society, as the leading cause of death, disability, and hospitalization (1-5).  In Canada, health care costs of cardiovascular disease exceed $18 billion (6).  Hypertension, defined as systolic blood pressure above 140 mmHg or diastolic blood pressure above 90 mmHg (7), affects a significant proportion of western population (8).  Further, elevated blood pressure strongly predicts cardiovascular disease and hypertension is known to be associated with increases in cardiovascular disease morbidity and mortality (9).   Canadian Aboriginal people, including First Nations, Métis, and Inuit,  are descendant from the first peoples inhabiting Canada prior to the arrival of Europeans (10, 11).  Currently, these peoples experience greater burdens of chronic health conditions relative to the non-Aboriginal population, including cardiovascular disease, diabetes, and obesity (12, 13).  This increased disease burden increases morbidity and mortality, and decreases quality of life and working years (4, 6, 14, 15).  Additionally, these greater disease burdens further compound the economic disparity and socio-economic position of Aboriginal people in Canada (16).  The ethnic-specific increased risk results from a combination of genetic predisposition and detrimental environmental, lifestyle, and socioeconomic factors (17). While it is well established that Aboriginal Canadians face unequal burdens of chronic health conditions, little is known about the vascular effects of these conditions, as much of the vascular assessments have been conducted in populations of European descent (18, 19).  Aboriginal populations have been reported to have lower blood pressures (18), and greater levels of physical activity than non-Aboriginals (20, 21).  As these factors are associated with reduced chronic health conditions, reports of healthier blood pressure and physical activity levels in Canadian Aboriginal populations is contradictory to the greater incidence of chronic health conditions in this group.  This suggests that other factors may contribute to the greater incidence of chronic health conditions in Aboriginal populations.  The objective of this thesis is to evaluate the cardiac and vascular dynamics of Aboriginal populations.  A review and analysis of prior blood pressure assessments of North American Indigenous populations is outlined in Chapter 2.  In Chapter 3 relevant background information is provided, from which five research questions were derived, with objectives and hypotheses targeting gaps in the current literature.   2  Specifically in Chapters 4 through 8, the findings of related research questions are discussed.  In Chapter 4, an investigation evaluating vascular measures of British Columbian Aboriginal populations is described. Chapter 5 addresses the question "What are the cardiac dynamics of Aboriginal populations?".  In Chapter 6 the question "How do vascular measures among Aboriginal and European populations compare, and how does blood pressure factor into these differences?" is evaluated.  Chapter 7 compares the vascular responses to maximal and submaximal exercise between Aboriginal and European populations.  Finally, Chapter 8 evaluates ethnic differences in the cardiac responses to maximal and submaximal exercise between Aboriginal and European populations.  The main body of this thesis is concluded in Chapter 9 with an integrated discussion, final thoughts and suggestions for future research in the field of Aboriginal cardiovascular health.       3  2. Blood Pressure and Hypertension in North American Aboriginal Populations1 2.1 Introduction Cardiovascular disease is the leading cause of death in Canada and the United States (1-3).  Elevated blood pressure is recognized as a strong predictor of cardiovascular disease (22) and hypertension, defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, is associated with substantial increase in cardiovascular disease morbidity and mortality (9).  Hypertension is known to affect a significant proportion of Western society (3, 23).  Recent statistics estimate this condition affects 29.2% of men and 24.8% of women worldwide (24).  While early detection and treatment of hypertension is paramount to the attenuation of risks and costs associated with hypertension and related co-morbidities, many Aboriginal populations in North America have more limited access to health care and health care screening (25-27).    Aboriginal populations of North American include Canadian Aboriginal [First Nations, Inuit, and Métis peoples (11)] and United States Native American [American Indian and Alaskan Native peoples (28)].  In recent decades, North American Aboriginal populations have been identified as experiencing elevated rates of cardiovascular disease, diabetes, obesity, and other chronic health conditions, relative to the non-Aboriginal populations (12, 29-34).  However, the blood pressure and hypertension experience among this population is less known.  The objective of this review is first to identify and summarize the blood pressure and hypertension profile of North American Aboriginal populations.  The secondary objective was to examine the change in blood pressure/hypertension among Aboriginal populations over time.  The final objective was to compare the experience of blood pressure and hypertension between Aboriginal and non-Aboriginal or European populations.  Considering the high rates of associated cardiovascular disease, diabetes, and obesity among Aboriginal populations, it was hypothesized that hypertension rates and average blood pressures would be increasing over time and be higher among Aboriginal populations compared to non-Aboriginal population reference groups.                                                   1 A version of Chapter 2 has been published. Foulds H.J.A., Warburton D.E.R. (2014). The blood pressure and hypertension experience among North American Indigenous populations. Journal of Hypertension, 32(4) 724-734.  4  2.1 Methods 2.2.1 Inclusion and Exclusion Criteria  A systematic, rigorous, and evidence-based approach was used in examining the blood pressure and hypertension experience among North American Aboriginal populations.  Any studies reporting average blood pressures or hypertension rates among North American Aboriginal populations specifically were eligible for inclusion.  Investigations not reporting blood pressure or hypertension among North American Aboriginal populations specifically were excluded.  The inclusion criteria were also limited to articles published in the English language, while no restrictions on study design were implemented. 2.2.2 Search Strategy Electronic bibliographical database searches included:  MEDLINE (1950-October 2012 OVID Interface);  EMBASE (1980- October 2012, OVID Interface);   Cochrane Library (-October 2012, OVID Interface);  DARE (-October 2012, OVID Interface).   Broad Medical Subject Headings and text words were explored to identify keywords and phrases utilized in searches to identify appropriate citations.  Search results were downloaded onto an online research management system, Refworks (Bethesda, Maryland, USA).  2.2.3 Study Selection and Data Extraction  A multi-step process was used to screen all studies identified through the literature search.  This screening process was conducted as outlined on Figure 2.1.  Two individual reviewers independently conducted the screening process, with discrepancies addressed by consensus.  Duplicate citations were removed from the compiled list prior to title and abstract evaluations.  Full text versions of citations remaining after abstract screening were obtained for further screening.  Reasons for excluding full text citations were recorded.  Reviewers were not blinded to author or journal names during the screening process and study selection process.  Articles were also cross-referenced and articles from authors’ knowledge were added to identify missing citations.  Multiple publications of data from the same source study were removed, with  5  preference given to articles with the largest sample sizes and articles providing sufficient data to achieve all three analyses evaluated in this review.     6  Citations from electronic database search: MEDLINE 461   EMBASE 1038   Cochrane 30   DARE 9   ↓ Total with Duplicates Excluded (N = 1213) ↓ Citations Excluded after Scanning Titles                 (N = 613)  Total Abstracts Assessed for Eligibility after Scanning Titles (N = 600)   ↓ Citations Excluded after Assessing Abstracts               (N = 210)  Total Full Articles Assessed for Eligibility after Assessing Abstracts (N = 390)  ↓ Articles Excluded after Full Review (N = 275)      Reasons:     Duplicate publications of same data (N = 207) No Aboriginal specific data reported (N = 12) Review/Commentary/Letter to Editor/Study design  (N = 34) No blood pressures or hypertension rates  reported (N = 20) No sample sizes provided (N = 2) ↓ Articles Included (N =115) plus articles added from authors knowledge (N = 16) and articles added from referencing (N = 10) Total N = 141  Figure 2.1 Citations examined for systematic review   7  2.2.4 Level of Evidence  Objective and pre-determined criteria were used to establish level and grade of evidence (35).  Scores of 1 to 4 were used to evaluate levels of evidence, reflecting the study design, with 1 referring to randomized controlled investigations and 4 reflecting expert opinions.  Grades were used to evaluate the strength of findings, with grade A indicating consistent findings in support of the conclusion, grade B reflecting some support and grade C indicating inconclusive findings.  The Downs and Black scoring system was implemented to assess the quality of investigations (36).  Levels of evidence, strength of findings and quality of investigations were assessed independently by two reviewers, with consensus achieved through discussion as needed.      2.2.5 Data Synthesis  For the purposes of this dissertation, results were limited to adults (18 yr and older).  Investigations combining adolescents (12-17 yr) with adults included only the respective adult data wherever possible (n = 4), otherwise these investigations (n = 18) were evaluated as adults.  Hypertension was defined among adults as blood pressures of greater than or equal to 140 mmHg systolic and/or 90 mmHg diastolic or the use of anti-hypertensive medication (37).  Comparisons of current and past experiences of blood pressure and hypertension were conducted by comparing results obtained prior to 1980, with those from 1980-1989, 1990-1999 and 2000-2012.  Where the date of investigation could not be identified, the assessment was assumed to be 2 yr prior to the article publication date.  Where sample sizes of non-Aboriginal comparison groups could not be determined, these investigations were not used in the overall comparison.  Comparisons of blood pressures and hypertension rates between ethnic groups were conducted including only articles which directly compared Aboriginal populations to a reference sample.  Further, comparisons were only conducted where overall sample sizes exceeded 400 individuals.  Comparison of proportions was used to compare hypertension rates, while meta-analysis comparison of means was used to compare average blood pressures (MedCalc Version 12.7.0.0, Ostend, Belgium).    8  2.3 Results  A total of 1213 unique citations were examined, resulting in 141 articles included in the final evaluation (Figure 2.1), covering investigations published from 1937-2012.  Overall, 846,241 Aboriginal individuals (833,030 adults) were included in the final evaluation.  A total of 117 articles reported hypertension rates among Aboriginal populations, with 99 using the 140/90 mmHg definition.  Of the overall sample, 70 articles reported average blood pressure measures in this population.  As only 44 of these articles included standard deviations of systolic and/or diastolic blood pressure, overall standard deviations could not be determined.  A large proportion of articles reported among First Nations/American Indian populations, with 72 reporting hypertension prevalence and 44 reporting mean blood pressures.  Only a small number of articles reported among Inuit/Alaskan Native populations, with 10 reporting hypertension prevalence and 16 reporting mean blood pressures.  Further, only 2 articles could be identified outlining hypertension prevalence rates among Métis population, and none identifying mean blood pressures.  Due to this lack of literature among the Métis population, Métis specific analysis was not conducted.  Overall articles included were generally good quality (average 10.6 out of 15; range 3-14), and a range of grades from 1A to 3B.  2.3.1 Hypertension Prevalence  Figure 2.2 outlines the overall reported hypertension prevalence among Aboriginal populations at 23.4% (95% Confidence Interval = 23.3-23.5%; n = 734,769; 90 articles), with similar results among the respective subgroups.  Across increasing age categories, some changes in hypertension prevalence were observed, from to 37.2% (36.6-37.8%; n = 9771; 21 articles) among those 40 years and older to 43.5% (42.5-44.5%; n = 25,215; 15 articles) among those 50 years and older though 37.2% (33.8-38.0%; n = 2004, 10 articles) among those 60 years and older.  Overall Aboriginal males were found to have similar hypertension rates to that of women, at 23.6% (23.4-23.8%; n = 262,684; 37 articles) compared to 22.4% (22.2-22.5%; n = 299,268; 41 articles).    9  Aboriginal Hypertension Prevalence (%)0 20 40 60 80 100Overall AdultsAdults 40 years and olderAdults 50 years and olderAdults 60 years and olderMale AdultsFemale AdultsZhao et al. 2008Young et al. 1985Young et al. 1993Young et al. 1991Xu et al. 2012Welty et al. 2002Weiner et al. 2008Torrey et al. 1979Tom-Orme et al. 1988Thommasen et al. 2004Sugarman et al. 1990Sugarman et al. 1992Stidley et al. 2003Smith et al. 2009Sievers et al. 1967Sharlin et al. 1993Sewell et al. 2002Schulz et al. 1997Schraer et al. 1996Scavini et al. 2005Sawchuk et al. 2005Sawchuk et al. 2008Salsbury et al. 1937Rhoades et al. 2003Reid et al. 2010Redwood et al. 2008Razak et al. 2005Prosnitz et al. 1967Percy et al. 1997Oster et al. 2009Oser et al. 2005O'Connell et al. 2010Narva et al. 1996Murphy et al. 1997Muneta et al. 1993Moss et al. 2004Megill et al. 1989McIntyre et al. 1986Martens et al. 2011Macaulay et al. 1988Maberley et al. 2002Liu et al. 2006Levin et al. 2002Kunitz et al. 1986Kramer et al. 2009Johnson  et al. 1991John et al. 2003Jernigan et al. 2010Hsia et al. 2007Hoy et al. 1994Howard et al. 1996Hood et al. 1997Holm et al. 2010Hodge et al. 1995Hodge et al. 2011Hiratsuka et al. 2007Hirata-Dulas et al. 1996Hegele et al. 1999Heffernan et al. 1999Harwell et al. 2003Harjo et al. 2011Haffner et al. 2002Goldberg et al. 1991Goins et al. 2010Goins et al. 2006Gillum et al. 1983Gilliland et al. 2002Gerrard et al. 1991Fulmer et al. 1963Froese et al. 2008Fredy et al. 2005Franceschini et al. 2009Foulds et al. 2012Erber et al. 2010DeStefano et al. 1979Deprez et al. 1985De Simone et al. 2006de Courten et al. 1996Coulehan et al. 1990Cohen et al. 1953Chapleski et al. 1997Campos-Outcalt et al. 1995Bursac et al. 2003Bruce et al. 2008Bray et al. 2006Bjerregaard et al. 2003Basualdo et al. 1997Balluz et al. 2008Acton et al. 1993Acton et al. 1996American Indian/First NationsHypertension Prevalence (%)0 20 40 60 80 100Alaskan Native/InuitHypertension Prevlanence (%)0 20 40 60 80 100 Figure 2.2 The prevalence of hypertension among Aboriginal populations in North American, by investigation and overall means, weighted for sample size   10  2.3.2 Mean Blood Pressures  Similar measures of systolic blood pressures were found for all Aboriginal populations at 123.3 mmHg (n = 98,436; 34 articles) (Figure 2.3).  Increases in systolic blood pressure were observed across increasing age categories, from 127.5 mmHg (n = 15,786; 10 articles) among those 40 years and older, to 129.3 mmHg (n = 2290; 5 articles) among those 50 years and older, to 132.4 mmHg (n = 729; 4 articles) among those 60 years and older.  Sex specific systolic blood pressures were 2-4 mmHg greater among males.  Overall, Aboriginal systolic blood pressures compared at 125.5 mmHg (n = 17,410; 23 articles) among men and 122.7 mmHg (n = 22,744; 24 articles) among women.    11  Aboriginal SystolicBlood Pressure (mmHg)0 20 40 60 80 100120140160Overall AdultsAdults 40 years and olderAdults 50 years and olderAdults 60 years and olderMale AdultsFemale AdultsYoung et al. 1993Xu et al. 2012Witmer et al. 2004Weyer et al. 2000Welty et al. 2002Tom-Orme et al. 1988Tobe et al. 2006Tejero et al. 2010Strotz et al. 1973Stoddart et al. 2002Scott et al. 1958Schraer et al. 1996Rudnisky et al. 2012Rode et al. 1995Rhoades et al. 2003Redwood et al. 2010Razak et al. 2005Percy et al. 1997Murphy et al. 1997McIntyre et al. 1986Maberley et al. 2002Liu et al. 2006Ley et al. 2009Lee et al. 1992Lear et al. 2007Kellett et al. 2012Kaler et al. 2006Hoy et al. 1994Howard et al. 2008Howard et al. 1996Hood et al. 1997Hiratsuka et al. 2007Hegele et al. 1999Heath et al. 1991Harris et al. 2011Hanley et al. 2001Haffner et al. 2002Gillum et al. 1983Fredy et al. 2005Franceschini et al. 2009Foulds et al. 2012Finkelstein et al. 2004Ekoe et al. 1996Ebbesson et al. 2005DeStefano et al. 1979Daniel et al. 1999Chateau-Degat et al. 2011Chateau-Degat et al. 2010Campos-Outcalt et al. 1995Bray et al. 2006Bjerregaard et al. 2003Biery et al. 1997Allen et al. 2008Alfred et al. 1970American Indian/First Nations SystolicBlood Pressure (mmHg)0 20 40 60 80 100120140160Alaskan Native/Inuit Systolic Blood Pressure (mmHg)0 20 40 60 80 100120140160 Figure 2.3 Systolic blood pressures among Aboriginal populations in North American, by investigation and overall means, weighted for sample sizes, standard deviations where available  12   Diastolic blood pressures were similar across all groups (Figure 2.4).  Overall Aboriginal diastolic blood pressures were found to be 75.1 mmHg (n = 98,187; 53 articles), with First Nations/American Indians at 75.7 mmHg (n = 32,816; 35 articles) and Inuit/Alaskan Natives at 74.3 mmHg (n = 8,166; 16 articles).  Similar diastolic blood pressures were observed across increasing age categories of adults, from 76.5 mmHg (n = 15,786; 10 articles) among those 40 years and older, to 78.2 mmHg (n = 2290; 5 articles) among those 50 years and older, to 76.7 mmHg (n = 729; 4 articles) among those 60 years and older.  Differences in diastolic blood pressure between males and females were found to be 3-5 mmHg.  Overall Aboriginal diastolic blood pressures compared at 77.7 mmHg (n = 17,410; 23 articles) among men and 73.9 mmHg (n = 22,744; 24 articles) among women.    13  Aboriginal DiastolicBlood Pressures (mmHg)0 20 40 60 80 100Overall AdultsAdults 40 years and olderAdults 50 years and olderAdults 60 years and olderMale AdultsFemale AdultsYoung et al. 1993Xu et al. 2012Witmer et al. 2004Weyer et al. 2000Welty et al. 2002Tom-Orme et al. 1988Tobe et al. 2006Tejero et al. 2010Strotz et al. 1973Stoddart et al. 2002Scott et al. 1958Schraer et al. 1996Rudnisky et al. 2012Rode et al. 1995Rhoades et al. 2003Redwood et al. 2010Percy et al. 1997Murphy et al. 1997McIntyre et al. 1986Maberley et al. 2002Liu et al. 2006Ley et al. 2009Lee et al. 1992Lear et al. 2007Kellett et al. 2012Kaler et al. 2006Hoy et al. 1994Howard et al. 2008Howard et al. 1996Hood et al. 1997Hiratsuka et al. 2007Hegele et al. 1999Heath et al. 1991Harris et al. 2011Hanley et al. 2001Haffner et al. 2002Gillum et al. 1983Gilliland et al. 2002Fredy et al. 2005Franceschini et al. 2009Foulds et al. 2012Finkelstein et al. 2004Ekoe et al. 1996Ebbesson et al. 2005DeStefano et al. 1979Chateau-Degat et al. 2011Chateau-Degat et al. 2010Campos-Outcalt et al. 1995Bray et al. 2006Bjerregaard et al. 2003Biery et al. 1997Allen et al. 2008Alfred et al. 1970American Indian/First Nations DiastolicBlood Pressures (mmHg)0 20 40 60 80 100Alaskan Native/Inuit DiastolicBlood Pressures (mmHg)0 20 40 60 80 100 Figure 2.4 Diastolic blood pressures among Aboriginal populations in North American, by investigation and overall means, weighted for sample sizes, standard deviations where available  14  2.3.3 Blood Pressure and Hypertension Changes Over Time  Across the decades, changes in hypertension prevalence and mean systolic and diastolic blood pressures have occurred among Aboriginal populations (Figure 2.5).  Hypertension prevalence is greater compared to pre-1980 for all decades from 1980 onward among overall Aboriginal, First Nations/American Indian, and Inuit/Alaskan Native populations.  However, hypertension rates since 2000 are lower than rates during the 1990s, among overall Aboriginal populations (29.2% [n = 119,110; 34 articles] vs. 34.2% [n = 39,494; 38 articles]) and First Nations/American Indians (37.2% [n = 31,963; 26 articles] vs. 34.1% [n = 30,443; 19 articles]).  Among Inuit/Alaskan Native populations, high rates of hypertension were observed prior to the 1980s at 55.1% (n = 531; 2 articles), and have since decreased to 9.3% (n = 1,506; 6 articles) in the 1990s.   Mean levels of systolic and diastolic blood pressure have also changed over time (Figure 5).  Among the overall Aboriginal population, decreases in diastolic blood pressure have been observed since the 1980s, from 77.2 mmHg (n = 6,371; 26 articles) prior to 1980 to 74.3 mmHg (n = 17,226; 24 articles) since 1999.  There has also been an overall decrease in systolic blood pressure among the overall Aboriginal population from 123.4 mmHg (n = 6,371; 26 articles) prior to 1980 to 121.9 (n = 17,226; 24 articles) since 1999.  Overall, First Nations/American Indian populations systolic blood pressures since 1980 are higher than pre-1980: from 122.9 mmHg (n = 5,529; 25 articles) pre-1980 to 125.1 mmHg (n = 7,352; 14 articles) since 2000 though lower than the 1990s (125.7 mmHg [n = 18,590; 24 articles]).  Diastolic blood pressure, conversely, has decreased since 1980 and remained stable from 77.6 mmHg (n = 5,529; 25 articles) prior to 1980 to 75.4 mmHg (n = 7,352; 14 articles) since 2000.  Among the Inuit/Alaskan Native populations, increases in systolic and diastolic blood pressures have been observed since 1980.  Systolic blood pressure has increased from 118.8 mmHg (n = 1,311; 6 articles) in the 1980s to 120.9 mmHg (n = 3,559; 6 articles) since 1999.  Diastolic blood pressure has increased from 73.0 mmHg (n = 1,311; 6 articles) in the 1980s to 74.9 mmHg (n = 3559; 6 articles).    15  Hypertension Prevalence (%)0102030405060Pre-1980 1980-19891990-1999 2000-present Mean Systolic Blood Pressure (mmHg)020406080100120140Aboriginal GroupAboriginalFirst Nations/American IndianInuit/Alaskan NativeMean Diastolic Blood Pressure (mmHg)020406080100CBA********* ********* ****††††††††††† Figure 2.5 Changes in hypertension rates (A), systolic (B) and diastolic (C) blood pressures over time among First Nations/American Indian, Inuit/Alaskan Native and overall Aboriginal populations in North American, including only samples with at least 400 individuals per average.  Asterisk (*) indicates significant change from Pre-1980, dagger (†) indicates significant change from 2000-present, p < 0.05  16  2.3.4 Comparison to Reference Populations  From the 29 investigations reporting among both Aboriginal and reference populations, 11 reported specifically among First Nations/American Indian populations and three among multiple groups.  In comparison to non-Aboriginal population or other ethnic group reference samples, differences in hypertension rates were identified between Aboriginal populations and non-Aboriginal population reference groups (Figure 2.6).  Hypertension rates were found to be significantly lower among overall Aboriginal populations at 23.5% (23.4-23.6%; n = 571,163; 20 articles) compared to 31.2% (31.2-31.3%; n = 1,511,820) in reference groups.  These trends also continued among both Aboriginal men, at 23.2% (23.0-23.3%; n = 241,079; 5 articles) vs. 31.0% (30.7-31.4%; n = 86,319), and women, at 22.2% (22.0-22.4%; n = 267,298; 7 articles) vs. 32.0% (31.8-32.2%; n = 173,419). Similar measures of blood pressure were identified among all Aboriginal groups and their non-Aboriginal population counterparts (Figure 2.6).  Mean systolic and diastolic blood pressure identified was similar among Aboriginal and non-Aboriginal populations, respectively: with Aboriginal 123.0 mmHg (n = 3,709; 9 articles) vs. 124.9 mmHg (n = 14,836) and 74.5 mmHg (n = 3,413; 8 articles) vs. 75.2 mmHg (n = 14,515).  Within sexes, similar blood pressure measures were also identified among Aboriginal adults compared to their non-Aboriginal population counterparts, with males at 122.4/75.7 mmHg (n = 497; 5 articles) vs. 126.4/75.5 mmHg (n = 3,410) and females at 118.5/71.2 mmHg (n = 699; 4 articles) vs. 123.4/70.6 mmHg (n = 3,587).       17  Hypertension Prevalence (%)010203040Mean Systolic Blood Pressure (mmHg)020406080100120140Aboriginal GroupOverall AdultOverall Male AdultOverall Female Adult tOverall First Nations/American Indian AdultTOverall Inuit/Alaskan Native AdultuOverall Metis AdultMean Diastolic Blood Pressure (mmHg)020406080100Aboriginal GroupNon-Aboriginal Reference Group****** Figure 2.6 Direct comparisons of Aboriginal hypertension rates (A), systolic (B) and diastolic (C) blood pressures to non-Aboriginal population reference groups, including only articles which directly compare to reference samples, and comparisons with at least 400 individuals per ethnic group.  Asterisk (*) indicates significant difference from reference population, p < 0.05  18  2.4 Discussion This review is unique in examining blood pressure and hypertension among Aboriginal populations of North America.  Further, this investigation is able to examine within Aboriginal groups and across sexes.  This review adds to the knowledge of health markers and chronic health conditions among this population.  While much attention has been paid to obesity, diabetes, and cardiovascular disease experiences among this population, little focus has been placed on blood pressure and hypertension (29, 38-40).  The decreased levels of hypertension in recent years and the lower levels of hypertension and blood pressures compared to non-Aboriginal population reference groups highlights the important findings of this review.   Hypertension is known to be associated with numerous other chronic health conditions including stroke, diabetes, obesity, and cardiovascular disease (37, 41, 42).  North American Aboriginal populations are known to experience higher levels of obesity, diabetes, and cardiovascular disease relative to the non-Aboriginal population (12, 31, 32, 43).  However, the relationship between obesity and hypertension is known to differ across ethnicities (44), and blood pressure appears to be less affected by obesity among American Indian populations (45).  Numerous reports have identified low overall blood pressure measurements among Aboriginal populations, despite high rates of obesity and diabetes (46-49).  Further, blood pressures have been found to directly relate to an individual’s percentage of American Indian ancestry, where individuals with greater proportions of American Indian ancestry have lower blood pressures (45).  While blood pressure is known to increase with age (8, 45), the overall Canadian Aboriginal and United States Native American populations are younger than the overall Canadian and American populations, respectively (50, 51).  This age gap may in part account for the lower blood pressures observed among Aboriginal populations.  Conversely, North American Aboriginal populations have been found to have greater experience of stroke than the European American population (52-54).  Ethnic-specific hypertension definitions have also been proposed due to this health disparity among Aboriginal populations (55).  Further research is required to examine the co-existence of lower blood pressures and hypertension rates with higher rates of related chronic health conditions among Aboriginal populations.    The increase in hypertension rates and blood pressures among Aboriginal populations up to 1999 are expected as hypertension has also risen among the non-Aboriginal population with increased acculturation to western society (56).  In current western society, hypertension rates  19  are still increasing (57), while this review identified decreased rates of hypertension in recent years, among all Aboriginal populations.  These results may suggest Aboriginal populations are experiencing declines in hypertension rates from a peak in the 1990s and earlier.  However, as these overall rates are determined from meta-analysis of many separate studies, these time points may represent different samples, as such caution should be observed when interpreting these findings.     A large number of investigations reported blood pressure and hypertension rates among a general Aboriginal population, without reporting specifically among First Nations/American Indian, Inuit/Alaskan Native or Métis groups.  In North America, First Nations/American Indian and Inuit/Alaskan Native populations arise from two distinct genetic lineages (58-60).  In combining these two groups, data may not accurately represent either group, due to the vast differences in histories and cultures between them (61).  Future investigations should strive to report among individual groups specifically to reflect the distinct differences between these groups.  Further, these broad groupings represent distinct individual nations, each with their own culture, language, and history (18).  As such, general compiled averages may not relate specifically to each nation in North America.   This investigation is limited by a lack of available literature.  Specifically among the Inuit/Alaskan Native populations, only limited data were identified among current literature.  As a result of these limited studies, biologically implausible changes in rates were identified among the Inuit/Alaskan Native populations, i.e. reductions in hypertension rates from 55% to 9.3% over a single decade.  Similarly, the lower hypertension rate and diastolic blood pressure observed among those 50 years and older, compared to those 60 years and older, likely reflects small sample sizes and a lack of currently published literature.  This lack of available data limited the ability to determine hypertension rates and mean blood pressures across all groups and with both sexes represented.   This investigation compiled all available data from North American Aboriginal populations and combined averages into broad overall categories.  However, these individual populations represent distinct nations with genetic, phenotypic, historical, lifestyle, and dietary differences (18, 61).  As the same individual nations were not evaluated across decades, ages, and sexes, trends identified in this investigation may be influenced by genetic, phenotypic, lifestyle, dietary, and other historical differences between the populations utilized in this  20  analysis.  While this investigation is successful in evaluating overall hypertension rates and blood pressures among North American Aboriginal populations, these compilations are based on average data rather than individual measurements.  As such, this evaluation is not able to account for ethnic differences in risk factors affecting blood pressure.  Aboriginal populations are known to be more active than their non-Aboriginal population counterparts (20), and may engage in dietary and salt ingestion practices that differ from the reference populations (62, 63).  Future research should evaluate blood pressure and hypertension among Métis and Inuit/Alaskan Native populations and specifically report within sexes.   2.5 Conclusion Aboriginal populations appear to experience lower hypertension rates than their non-Aboriginal population counterparts and decreases in hypertension in recent years.  Further research is required to examine blood pressure and hypertension among Métis, Inuit/Alaskan Native populations.    21  3. Literature Review, Objectives, and Hypotheses 3.1 Aboriginal Peoples 3.1.1 Background  Aboriginal peoples have inhabited land throughout North America for more than 13,000 years (64).  First Nations and Inuit populations descend from two distinct lineages each arriving in North America in separate migrations (58-60).  Historically, North American Aboriginal populations reached upwards of 18 million people prior to the arrival of Europeans to North America, including a diverse range of cultures and lifestyles (64, 65).  Traditional subsistence methods included hunting, gathering, fishing, and farming (66).  Prior to the arrival of Europeans, Aboriginal peoples are thought to have led healthy, active lives (65). In 2011, there were approximately 1,400,685 Aboriginal people in Canada, characterized by 851, 560 First Nations people, 59,445 Inuit people, and 451,795 Métis people (67).  The Canadian Aboriginal population comprises 4.3% of the overall population, including 5.4% of the British Columbian population (67).  Within British Columbia, there are 232, 290 Aboriginal people representing 16.6% of the Canadian Aboriginal population (67).  The British Columbian Aboriginal population includes 155, 020 First Nations, or 18.2% of all First Nations peoples (67).  Métis people in British Columbia include 69, 475 individuals, comprising 15.4% of the Métis population in Canada (67).  Given the prevalence of the specific Aboriginal groups in British Columbia, the historical linkages between the First Nations and Métis populations (67-69), and the distinct genetic lineage of the First Nations and Inuit populations (58-60), this investigation focuses on cardiac and vascular dynamics specifically among the First Nations and Métis populations.   3.1.2 First Nations Peoples First Nations peoples are registered under the federal Indian Act of 1876 (70).   First Nations peoples consist of 617 distinct bands scattered throughout what is now Canada (71).  Within British Columbia, there are 198 First Nations bands (71) and more than 1500 reserves (72).  These bands are comprised of 30 historical and separate nations, each with their own language, politics, culture, territory, and comprised of a number of local communities (18).    22  From a population of approximately 250 000 people prior to the arrival of the Europeans, the British Columbian First Nations population was decimated to about 23 000 individuals by 1929 (72).  The majority of these losses were the result of diseases including small pox, tuberculosis, scarlet fever, influenza, and measles brought to the area by Europeans (72).  First Nations contact with Europeans was the result of fur trades, gold rushes, and finally, settlers (72).   British Columbian First Nations have survived several attacks on their culture, livelihood, and existence.  Beginning with disease outbreaks, decimation of the population began the assimilation of First Nations into western European society (72).  The residential school system in Canada was enacted with guidance of the Davin report of 1879 with a policy of assimilation to eradicate the “Indian problem” by “killing the Indian” in the child (73).  These schools were formed as a method to assimilate Aboriginal children into mainstream society (73).  Additionally, these institutions were used as a method of maintaining order and preventing violence among Aboriginal populations with increasing European settlements in western Canada as the Aboriginal children were effectively “hostages” of the Canadian government (73). From the onset of the gold rush, to settlement and joining of confederation, the influx of European and other settlers to British Columbia has threatened the First Nations access to land and traditional subsistence (72).  Colonial administration and attitudes permitted settlers to take control of much of the traditional territory, leading to breakdowns in traditional social relations (72).  Local First Nations economies broke down and Aboriginal people were confined to small plots of land with limited resources and poor sanitation (18). Due to historical trauma and forced acculturation, Native American and First Nations populations are impacted by disproportionately high stress levels (74, 75).  The attack on family interaction and culture in residential schools, coupled with the experiences of violence and abuse in daily life, led to further stress and disruption to First Nations peoples (72).  These colonization impacts are identified as critical health issues among Aboriginal populations, and have led to post-traumatic stress response across generations (76).  Historical trauma and colonization have been directly linked to increased prevalence of disease and poorer health and quality of life among First Nations populations (77, 78).   23  3.1.3 Métis Peoples   The Métis peoples in Canada represent a distinct group of individuals descending from both First Nations and European ancestors (79).  These individuals represent a distinct indigenous nation with their own distinct history and culture (79, 80).  The ancestral Métis population grew from marriages between Cree women and French fur traders, to include descendants of European fur traders of French, Scottish, and English descent, and First Nations women in the Red River colony during the seventeenth and eighteenth centuries (68, 69).   Following confederation, settling the west became a priority for Canada; a plan which required extinguishing the rights and title to the land of the region’s Indigenous peoples (81).  With the implementation of the Manitoba Act in 1870, the territory was transferred from the Hudson’s Bay Company to Canada (82).  In 1869-1870, the Métis set up a provisional government and successfully negotiated terms with the Dominion of Canada enabling the Dominion to take possession of the territory without unduly disposing the Métis inhabitants (82).  This transfer brought a large influx of European settlers to the region, eager for the land the Métis held (82).  In the Red River region where Métis settlements, culture and a cohesive community had become established, script in the form of land or monetary remuneration was enacted to extinguish the Aboriginal title of the Métis (81, 82).  However, these land grants were not granted until 1878-1880, by which time many of the Métis had already been displaced or had been convinced to sell their claims to speculators for greatly reduced prices (82). The classification of Métis is used in two contexts in Canada, representing two different definitions with conflicting memberships and eligibilities (68, 79).  One definition defines the term extending broadly to any individual of mixed Aboriginal and Euro-Canadian ancestry (83).  However, the Métis National Council describes Métis people specifically as the descendants of those with a homeland in western Canada who were disposed by the Canadian government from 1870 onward (80).  Additionally, Métis communities in other regions of the county, such as Labrador, outline a community of Métis evolving from Inuit or First Nations and European descent (84).  Throughout the literature, research investigating Métis use any one of these definitions.   The Métis population has nearly doubled in 10 years, partially due to increased tendency for individuals to identify as Métis (50).  This population is concentrated 87% in the western provinces or Ontario (50), with roughly 29-35% living in rural communities (26, 85) and 69%  24  living in urban centres (26).  Similar to other Aboriginal populations, the Métis are younger than the non-Aboriginal population, with a median age of 30 years, compared to 39 years (26, 50, 79). While Métis may be similar to First Nations, they maintain distinct differences.  Métis cultures encompass components of both First Nations and European cultures, religions, and languages (86).  First Nations populations typically hold specific land reserves, while Métis do not generally hold land rights in the form of reserves (86).  First Nations people are also entitled to government benefits such as Non-Insured Health Benefits through the Indian Act (86).  However, despite recent legal rulings qualifying Métis as Indians under the Indian Act, these benefits are not currently available to the Métis population (87). As Métis peoples descend from a mix of First Nations and European ancestors (79), and their socioeconomic, education, and health status markers often present intermediary to First Nations and European populations (88), these populations present a unique opportunity to evaluate the spectrum of epigenetic factors among First Nations and European populations.   3.2 Cardiovascular Physiology and Disease 3.2.1 Vascular Physiology Blood is transported from the heart to the body through the arterial system (89).  Throughout the body, arteries are composed of three layers of tissue (90).  A layer of connective tissue, blood vessels, and nerves make up the outermost layer of tunic adventitia (90).  The middle layer, or tunica media, varies between capacitance and conduit arteries (90).  Elastic capacitance arteries’ medial layer contains several sheets of elastic fibres (90, 91).  By contrast, muscular conduit arteries’ tunica media is comprised largely of smooth muscle cells (90, 91).  The inner layer of arteries, or tunica intima, lines the lumen of the blood vessel and is composed of a single layer of endothelial cells (90, 91).  To effectively maintain function in arterioles and capillaries, a steady flow of blood is required (92).  Blood is transported initially via pulsatile blood flow generated by contractions of the left ventricle (89, 92).  The initial pulsatile flow enters the large, elastic capacitance arteries proximal to the heart, which contain large proportions of elastic fibres (91, 93).  These elastic properties allow the large elastic arteries to buffer pulsatile flow by passively expanding during systole to store ejected blood and to undergo elastic recoil to continue blood flow to peripheral arteries during diastole (91-93).  Effectively, elastic capacitance arteries store about 60% of the  25  stroke volume during systole and drain it during diastole (92).  This action transforms pulsatile flow of capacitance arteries into the steady flow required in the conduit arteries, and is known as the “Windkessel function” (92). More distal conduit arteries contain larger proportions of smooth muscle within their walls, allowing for biomechanical and biochemical stimuli to alter vascular tone, in order to regulate blood flow throughout the body (90).  The ability of the arteries to buffer or cushion pulsatile flow is influenced by viscoelastic properties of arterial walls (92).  Compliance or distensibility of arteries represents the ability of an artery to regulate the radius of the vessel with the distending pressure within the artery (92).  With decreased arterial distensibility, a greater proportion of stroke volume is forwarded directly to the peripheral arterial system during systole (92).  This decreased buffering results in greater amplitude of arterial pulse wave and increased systolic blood pressure (92).  The diastolic blood pressure reached is influenced by the time between heart beats (heart rate) for blood to flow from the cushioning central arteries to the peripheral blood flow, and the resistance to blood flow (vascular resistance) of the arterial system (92).  Greater resistance to blood flow during diastole, due to increased peripheral resistance, results in greater systolic blood pressure, pulse pressure, and mean blood pressure (92).   Pressure waves along arteries are also determined by mechanical properties of arterial walls such a ventricular ejection, which pushes the pulse wave away from the heart at a limited speed (92).  Increased arterial stiffness increases this pulse wave velocity (PWV) (92).  Aging results in degrading of the tunica media including fractures and fragmentation of the elastic lamellae components, increased collagen and calcium components, and leads to decreased arterial distensibility and increased PWV (92).  Additionally, with aging, the large arteries and aorta undergo dilation and hypertrophy, further altering distensibility and PWV (92).   3.2.2 Cardiac Physiology The human heart consists of four chambers, with the left ventricle supplying the systemic circulation of blood (89).  Myocardium of the heart consists of multi-nucleated striated muscle (89).  These cells are arranged in an interconnected latticework fashion (89).  Two layers of myocardium surround the left ventricular wall (94, 95).  The superficial fibres run essentially vertically starting at the base, running to the apex and reflecting back to the base (94, 95).  Deep  26  fibres run essentially horizontally in the middle of the ventricular wall thicknesses in a progressive transverse fashion (94, 95).  Overall, the heart consists of a helicoid with two spiral turns of myocardium, arranged in layers of counter-wound helices (94, 96).  Configuration of myocardial layers equalizes stresses and strains across the ventricle and allows for optimal function of both active and passive tissue components (94).  The structure of the heart allows it to function both electrophysiologically and elastomechanically (94).   Blood is pushed from the heart into the arterial system through the aorta (89).  The average pressure created in the arterial system results from the output of blood from the heart (cardiac output) and the resistance to blood flow within the arterial system (peripheral resistance) (89).  Due to the arrangement of multi-nucleated myocardium, electrical signals can be transmitted throughout the heart, coordinating timing of myocardial contractions, resulting in effective contraction of the heart as a whole (94).  The sinoatrial node of the heart produces electrical impulses which are transmitted throughout the heart, causing calcium to be released (97).  Calcium is released into action potential ion channels, this resulting influx of calcium ions causes calcium-induced calcium release in the sarcoplasmic reticulum (98).  The binding of calcium then causes the release of actin and myosin contractile components from the troponin subunit (98).  This calcium binding causes a tropomyosin configuration change allowing actin and myosin to interact, generating force and muscle contraction (98).   During the cardiac cycle, phases of systole and diastole are recognized (98, 99).  Atrial systole begins with contraction of the atria causing an initial pressure increases in the ventricles while aortic valves remain closed (97-99).  As ventricular systole and contraction occur, the mitral valves are pushed closed (97).  Pressure within the ventricles continues to increase until the semilunar valves are pushed open, allowing for maximal contraction (97-99).  As the blood is pushed out of the ventricles, the pressure within the ventricles decreases (98, 99).  Diastole begins with relaxation of both the atria and ventricles (97).  The drop in ventricular pressure closes the aortic valve (98, 99).  This is followed by isovolumic relaxation, which allows the mitral valve to open, starting a period of early rapid filling once the pressure drops below atrial pressure (98, 99).  Diastasis follows when trans-mitral flow ends (98, 99).  At the end of diastole, atrial and ventricular pressures are returned to levels experienced prior to atrial contraction (98, 99).    27  3.2.3 Cardiovascular Disease Within Canada, the United States and Europe, a high prevalence of cardiovascular disease persists (100).  Common forms of cardiovascular disease include ischemic heart disease, myocardial infarction, cerebrovascular disease (stroke), angina pectoris, peripheral vascular disease, pulmonary embolism, hypertension, and congestive heart failure (4, 101-103).  Further, risk factors for cardiovascular disease such as obesity, diabetes, and metabolic syndrome are increasing in the developed world (100).  The continuum of events, leading to cardiovascular disease is predisposed by risk factor such as hypertension, dyslipidemia or diabetes, which lead to atherosclerosis and left ventricular hypertrophy (104, 105).   The development of cardiovascular disease begins with vascular changes at a subclinical level (106, 107).  These changes begin in childhood and evolve over decades (106).  Even in children, fatty streaks in large arteries are present (108, 109).  Fatty streaks progress to significant fibrous plaques and complicated lesions in the 30s and 40s (108, 110-112).  Fibrous plaques then undergo changes including hemorrhage, rupture, and thrombosis, leading to obstruction and clinically apparent cardiovascular disease (108).  Mechanical injury may also initiate the process of cardiovascular disease development (113, 114).  In response to mechanical injury, marked intimal thickening occurs within blood vessels, thought to reflect the start of atherosclerotic lesion development (113, 114).   Changes in vascular properties along this continuum include changes in dilation from fractures of load-bearing components of vasculature, and stiffening due to transferring stress to more rigid collagenous components of the arterial wall (107).  Vascular changes with aging, which increase PWV and decrease distensibility, are more pronounced in central arteries (92).  Increases in PWV and decreases in distensibility, leading to increased systolic blood pressure, increase fatigue on arterial walls and accelerate arterial damage (92).  The increased pressure on the arterial walls leads to increased arterial stiffness due to the pressure-volume relationship resulting from the smooth muscle cells, collagen, and elastin fibres of the arterial walls (92).   Alterations in cardiac and central function  also contribute to development of cardiovascular disease (107).  Arterial stiffening results in earlier return of the reflected wave, causing capacitance elastic artery release of stored blood to occur during systole (92).  This early return of blood results in increased systolic blood pressure, and decreased blood flow during diastole (92).  From a cardiac perspective, the consequences of this increased arterial stiffness  28  include reduced coronary perfusion and thus reduced subendocardial coronary blood supply (92).  Further, increased systolic blood pressure results in increased left ventricular afterload (92).  Increasing systolic blood pressure leads to left ventricular hypertrophy, which is associated with increased risk for coronary heart disease, sudden death, stroke, and other forms of cardiovascular disease (115).  In the progression of cardiac dysfunction, increases in left ventricular mass occur, followed by an increase in blood pressures beyond normal levels (116).  Increased haemodynamic loads lead to augmentation of muscle mass to bear the extra burden, achieved through hypertrophy of existing myocytes and parallel and series additions of sarcomeres, causing increased myocyte width (117).  Increases to wall thickness offset increases in pressure (117).  Specifically, increased systolic blood pressure increases systolic stress and left ventricular afterload (117).  Increased wall thickness offsets systolic stress of increased afterload, resulting in normalized ejection fraction (117).  Cardiovascular disease changes to cardiac structure including left ventricular wall thickness, are both associated with increased risk factors for cardiovascular disease such as hypertension, obesity, and diabetes, and independently associated with increased risks of cardiovascular disease morbidity and mortality (117).   3.2.2 Aboriginal Health Disparities Past Aboriginal populations were recognized as being tall and strong in comparison to Europeans, with historical populations healthier than current populations (65).  Records within the past 50 years report significantly higher physical fitness among Canadian Aboriginal populations in comparison to the non-Aboriginal population (118).  Evidence from skeletal remains of populations in the Western Hemisphere indicate North American Aboriginal peoples experienced some of the highest overall health indices (119).  Traditionally, diabetes and hypertension were rare in Aboriginal populations (120).   From 1950-1972, Aboriginal peoples experienced lower mortality from cardiovascular disease compared to European Canadians (121).  However, mortality rates from cardiovascular disease have steadily increased among Canadian Aboriginal peoples since the 1950s (121).  Aboriginal populations have also experienced increasing rates of diabetes since the 1950s and increasing rates of heart disease since the 1970s (122, 123).  Canadian Aboriginal populations have undergone a significant cultural shift over the past 60 years including a decrease in physical activity levels and alterations in diet (124).  Aboriginal peoples are often referred to as a  29  “population in transition” where the introduction of Western diet and sedentary activities have altered the traditional lifestyle of Canadian First Nations (43).   Canadian Aboriginal peoples currently experience poorer quality of life, and greater morbidity and mortality than the Canadian non-Aboriginal population (125).  Life expectance is lowest among Aboriginal peoples compared to any other group of Canadians (52).  Aboriginal peoples currently share disproportionate rates of physical disease and mental illness in Canada (39).  Rates of diabetes, obesity, and cardiovascular disease have reached epidemic proportions in many Aboriginal communities (43).  Mortality rates from cardiovascular disease among this population have risen dramatically in the past 30 years (126), and persist across all income levels (52).  Further, these rates have steadily increased while the non-Aboriginal population has experienced a steady decline in recent years (127).     Different ethnic groups experience different rates of pre-disposition to cardiovascular disease development (32).  Genetic variations associated with diabetes, plasma insulin concentrations and body mass index (BMI) have been found (FABP2 gene on chromosome 4q) (128).  Four cardiovascular disease genetic markers (AGT T235, FABP2 T54, PON R192 and APOE E4) are more prevalent among Aboriginal populations than European populations and are linked to differential phenotypic experiences of cardiovascular disease (129).  Aboriginal ethnicity is now recognized as an independent risk factor for cardiovascular disease, diabetes, and other related chronic health conditions, and is ranked higher than either weight or age (31, 32, 130).  This risk factor results from a combination of genetic factors, individual susceptibility, and environmental conditions (32).  Aboriginal populations often experience poorer cardiovascular disease risk factors including diabetes, BMI and waist circumference, and smoking (12, 131-138).  Ethnic differences in health measures are further exacerbated by differences in social determinants of health.  The income gap between Aboriginal Canadians and the Canadian population is about 30% (16, 139).  Further, education, and employment disparities between Aboriginal and non-Aboriginal Canadians leave Aboriginal Canadians at greater risk for cardiovascular disease (139).  Overall, Aboriginal Canadians experience poorer life expectancy and greater morbidity than their non-Aboriginal counterparts (139, 140).  Within the next few decades, rates of cardiovascular disease among Aboriginal Canadian populations are likely to continue increasing as more Aboriginal people move to a more “urban” lifestyle (141).   30  3.2.3 Ethnic Specific Criteria in Health In order to optimally identify individuals at risk of cardiovascular disease, ethnic-specific criteria are required (43, 142).  Recently, ethnic-specific criteria for BMI has been advocated with some ethnic groups encouraged to maintain lower BMI values (143).  Additionally, ethnic-specific waist circumference criteria in the diagnoses of metabolic syndrome have been advocated (144).  These criteria have been further supported as ethnic variations in proportions of visceral fat are found to vary between ethnic groups for the same BMI (145, 146).  Currently, other ethnic-specific definitions for cardiovascular disease and diabetes risk factors do not exist, despite ethnic-specific relationships between body composition and chronic health conditions such as hypertension and diabetes (44, 147).  However, ethnic-specific hypertension definitions have been previously suggested (55, 148). 3.3 Vascular Dynamics 3.3.1 Vascular Dynamics and Health Changes in vascular structure and function contribute to the development of cardiovascular disease.  Atherosclerotic lesion and plaque formation results from a complex combination of factors such as cholesterol, inflammation, and signalling molecules (149).  As the majority of these lesion growths progress outward, significant arterial remodelling results (149).  Vascular changes with atherosclerosis progression include both structural changes in lumen size (150) and functional changes such as decreased endothelial function (151).  Measurements of intima-media thickness (IMT) are one method of assessing vascular atherosclerotic progression (152).  Vascular changes leading to arterial stiffness and decreased arterial distensibility can be measured through PWV and arterial compliance, respectively (153).  Additionally, nervous system sympathetic and parasympathetic balance contributes to vascular tone and increased risk of cardiovascular disease (154, 155).  Measurements of heart rate variability (HRV) and baroreceptor sensitivity (BRS) can provide assessment of this nervous balance (156-160).  With the development of atherosclerosis and hyperplasia of the vascular walls, adaptive changes to the vascular walls occur (159).  These changes may also be adaptive in the media layer region (Figure 3.1), including remodelling in response to haemodynamic changes such as hypertension (159).  Chronic elevations in blood pressure are associated with thicker carotid artery walls (161).  Further, carotid and femoral artery walls are directly influenced by changes  31  in vascular tone (162).  Measuring the thickness of the intimal and medial layers of artery walls, IMT measurements, achieved through ultrasound imaging of the far wall of the artery, are a validated surrogate marker for atherosclerosis (152).  Carotid IMT measurements are associated with increased risk for adverse cerebral events independent of other risk factors (163-166), as well as increased risk of cardiac and peripheral vascular events (163, 164, 167-172).  Further, carotid IMT measurements among asymptomatic participants has predictive capacity similar to the risk stratification achieved through the Framingham Risk Score (173).  Figure 3.1 The external common carotid artery with visible intima-media thickness  The ability of an artery to expand and recoil with cardiac pulsation and relaxation is important for maintaining healthy and functional arteries (174).  Major artery stiffness is one of the main determining factors of vascular health (175).  Increased arterial stiffness is associated with increased risk of cardiovascular disease (153).  Pulse wave velocity is an increasingly important method, and most frequent method of evaluating arterial stiffness (153, 176).   32  Increased arterial stiffness (high PWV of ≥12 m∙s-1) has been associated with 5.4 greater odds of all cause mortality compared to normal stiffness (PWV ≤9.4 m∙s-1) (177).  Increased arterial stiffness is projected to precede the development of overt cardiovascular disease, serving as an early indicator or prediction mechanism (178).  Pulse pressure waveforms vary in different vessels of the same individual depending on elastic properties of the artery, which cause amplification of the wave as it travels from more elastic central arteries to more stiff peripheral arteries (179).  Additionally, pulse pressure wave forms depend on viscosity of the blood, wave reflections, and wave dispersion (179).  Measuring PWV requires determining the arrival of pulse wave at two sites, usually carotid and femoral for central assessments and carotid and radial for peripheral measurements (179).  Pulse wave velocity is known to increase with age, atherosclerosis, arteriosclerosis, and elevated blood pressure (176).  Subsequently, PWV is analysed after adjusting for blood pressure (176). Arterial distensibility is also an important determinant of vascular status (153).  Decreased arterial distensibility is associated with increased risk of cardiovascular disease (153).  Large artery distensibility is physiologically important for reducing impedance to systolic ejection and cardiac work, reducing PWV and improving coronary perfusion during diastole (180).  One method of determining arterial distensibility or arterial compliance is through applanation radial tonometric pulse wave analysis or pulse contour analysis, to calculate aortic pressure and pressure relationships with peripheral pressure values (153, 181).  Computerized “generalized transfer function” calculations allow calculation of central aortic pressure and waveforms from peripheral waveforms and peripheral blood pressures (179).  Pulse pressure within the central portions of the body is often not the same as pressures within peripheral limbs (176).  Pressure amplification represented in pulse pressure waveforms reflects both the initial starting pressure within the central portion of the body, and the arterial impedance in the subsequent arterial tree resulting in backward wave reflection (176).  By evaluating the pulse pressure waveform in the brachial or radial artery, an assessment of central and peripheral distensibility can be determined (176).  Arterial compliance is one method of evaluating the pulse pressure waveform using computerized general transfer function calculations.  Measurements of arterial compliance use the Windkessel model to allow evaluation of elasticity of large conduit arteries and small microcirculatory arteries (182, 183).  From these pulse pressure waveform analyses, estimates of systemic and total vascular resistance can also be  33  obtained (181).  Vascular resistance is a measure of vasomotor tone and reflects the non-pulsatile component of peripheral load (184).  This method of measurement is found to be reliable over short and intermediate observation periods, and reasonably agrees with invasive measurements (181).    Neurovascular autonomic activity, including activity of the cardiac vagal nerve serving the heart, influences cardiac activity/heart rate and risk of cardiovascular disease (157, 158).  Decreased activity of this nerve may occur through damage to the nerve from myocardial infarction or through alterations in the balance between sympathetic and parasympathetic nervous activity (157).  Measurements of cardiac autonomic activity can be achieved through HRV measurements, where high frequency power represents the parasympathetic component and low frequency power represents the sympathetic component (157, 185).  Changes in cardiac autonomic function, such as decreases in HRV and high frequency power, and increases in low frequency power are associated with increased cardiovascular morbidity and mortality (157, 186).  In maintaining adequate cardiovascular supply to the body, heart rate, blood pressure and sympathetic output to the blood vessels can be altered on a beat-by-beat basis (156).  One method of controlling these adjustments is through the baroreflex, a physiologic feedback control mechanism which prevents large fluctuations of and regulates short-term changes in blood pressure by adjusting cardiac output and peripheral vascular resistance (156, 159, 160).  Measuring the BRS non-invasively can be achieved by simultaneously recording spontaneous HRV and blood pressure on a beat-by-beat basis and evaluating using either spectral (frequency domain analysis) or sequence (time domain analysis) methods (156, 160).  Both BRS and HRV have been found to predict cardiovascular morbidity and mortality (154, 155).  Alterations in BRS have been associated with cardiovascular disease such as coronary artery disease, cardiac arrhythmias and myocardial infarctions (187).  Blood pressure variability (BPV) has also been linked to poor prognosis among those with hypertension or stroke (188). 3.3.2 Ethnic Differences in Vascular Dynamics  Ethnic differences in vascular measures have been reported among several ethnic groups including assessments across Canada and the United States.  Ethnicity has been proposed as an independent determinant of vascular measures such as arterial wave reflections (19).  Differences in age and sex-adjusted IMT have been reported between European, Asian, and South Asian  34  populations (189).  Chinese populations have also been found to have lower unadjusted carotid IMT compared to South Asian and European populations (190).  Similarly, African-Caribbean children demonstrate greater carotid IMT after adjusting for age and sex compared to White European children (191).  Ethnic differences in vascular measures such as vascular stiffness/PWV adjusted for blood pressure, and flow-mediated dilation have also been identified; however, many of these ethnic comparisons evaluate differences between European and African-American populations (192-194).  One study in Brazil identified differences in the prevalence of high PWV, after adjusting for age, sex, blood pressure, body mass index, waist-to-hip ratio and biochemical data, between ethnic groups including South American Amerindian populations (195).  The Amerindian population in Brazil demonstrated lower rates of vascular stiffness than other European, African, and mixed European-African ancestry (195).  Specifically among Aboriginal populations, some vascular measures have been evaluated.  The Strong Heart Study in the United States has evaluated IMT as a measure of atherosclerosis among 45-75 yr old American Indian adults.  Among adults free of hypertension or diabetes, IMT measurements of 0.72 ± 0.14 mm were identified, with measures of 0.75 ± 0.15 mm found among those with hypertension alone, 0.75 ± 0.16 mm among those with diabetes alone, and 0.76 ± 0.15 mm among those with both diabetes and hypertension (196).  Within Canada, a younger group of Oji-Cree First Nations adults (mean age 35-42 yr) have been evaluated, identifying age and sex-adjusted IMT measures of 818 ± 18 μm among those with metabolic syndrome and 746 ± 20 μm among those without (197).  Measures of arterial stiffness among Aboriginal populations have also been evaluated.  Augmentation index among the Strong Heart Study participants was identified as 4.58 ± 2.45 (198).  Limited information regarding the differences in vascular measures between Aboriginal and other ethnic groups exists.  A comparison of augmentation index between ethnic groups identified Native American Strong Heart Study participants as having lower, healthier augmentation index measures compared to British White, Chinese, and African-American populations (19).  However, this investigation did not directly compare these measurements, but rather consolidated and compared data from several independent investigations with varying methods for measuring augmentation index (19).  While arterial stiffness was directly compared between South American Amerindian and other European, African, and mixed ancestry groups in Brazil (195), Amerindian populations, similar to the Inuit, descend from a distinct lineage  35  from a separate wave of migration to North American from the American Indian/First Nations peoples (58-60).  3.4 Cardiac Dynamics 3.4.1 Cardiac Dynamics and Health  Cardiac output is determined by the volume of blood ejected from the heart each beat (stroke volume) and the rate of contraction of the heart (89).  Myocardial fibres are arranged in latticework fashion, resulting in movement and contractions in three directions: longitudinal, radial and circumferential (199, 200).  During cardiac contraction, myocyte contraction induces myocardial normal strains including shortening from base to apex (longitudinal), perpendicular to radial and to the long axis (circumferential) and perpendicular to epicardium and to longitudinal axis (radial thinning) (201).  Shear strains, such as transmural strains, are also produced within the myocardium due to the helical orientation of myofibres with subendocardial right-handed orientation and subepicardial left-handed orientation (202-204).  These shear strains include longitudinal-radial, circumferential-radial and circumferential-longitudinal components (202-204).  Torsion of the left ventricle results from opposing systolic rotation of the left ventricular apex and base caused by the helical arrangement of myofibres (205-212).  Left ventricular mechanics such as strain, rotation, and twist enhance the efficiency of left ventricular ejection and reduce myofibre stress during ventricular contractions (199, 213-215).  Because shear strains decrease before normal strains (204), “elastic recoil” occurs (205), causing rapid reductions of left ventricular pressure and leading to mitral valve opening and early filling (216, 217). Cardiac structure can be evaluated using echocardiography, including measures of left ventricular internal diameters at end systole and end diastole, wall thicknesses of posterior wall and interventricular septal wall, and left ventricular mass (218, 219).  Additional measurements include relative left ventricular wall thickness, left ventricular end-diastolic and end-systolic volumes, and left atrial dimensions (218, 220).  Measures of cardiac function through echocardiography include left ventricular ejection fraction, fractional shortening, and ratio of transmitral peak flow velocity during early left ventricular filling (218).  Additionally, measures of peak flow velocity during atrial filling (E/A ratio), atrial filling velocities (E), and early diastolic mitral annular tissue velocities (E’) can be determined using Tissue Doppler with  36  speckle-tracking (218, 220).  Cardiac motion during contraction can be measured using Tissue Doppler with speckle-tracking imaging and analysis (221).  These measurements include assessments of myocardial shortening (strain), rates of shortening (strain rates), tissue velocities, and tissue displacements (linear and angular) throughout the cardiac cycle (221).  Cardiac strains are determined as fractional changes in length compared to end-diastolic lengths (222).  Longitudinal strain rate is a robust measures of regional myocardial dysfunction as it is known to closely correlate with invasive markers of left ventricular contractility (223).  Advancements in these measurements also allow assessments of left ventricular function including rotation, torsion, and twist (224, 225).  Left ventricular twist is calculated from the maximal instantaneous difference in rotation between basal and apical levels in the short axis plane (226).  Torsion is determined by dividing twist by the longitudinal length between the two recorded short-axis levels (226).  During diastole the amount of twist occurring is recorded as untwist (226).   3.4.2 Ethnic Differences in Cardiac Dynamics  Ethnic-specific measurements of cardiac structure and function have been evaluated (227, 228).  African-American individuals have been found to have greater left ventricular wall thickness and greater left ventricular hypertrophy compared to their white counterparts (227, 228), as well a greater left ventricular wall mass (229).  Further, African-American women demonstrate higher prevalence of repolarization changes than white women (228).  The greater left ventricular wall thickness has also been identified among African-American individuals, despite similar resting blood pressure levels (230, 231).  The Strong Heart study in the United States American Indian population evaluated left ventricular structure and function (232), and left ventricular chamber volume and stroke volume (233) among Aboriginal populations.  Further, they identified left ventricular mass relations to demographic and haemodynamic variables among the American Indian population (234).  Increased left ventricular hypertrophy has also been associated with genotype differences in angiotensin 1-converting enzyme DD (235).  Altered allele frequencies for renin-angiotensin genes have also been identified among the Canadian First Nations (55).  Genetic contribution to left ventricular geometry is also supported by ethnic differences in frequencies of concentric hypertrophy left ventricular geometry (235).   37  Despite a multitude of investigations comparing cardiac structure and function among African-American and European populations, there are no investigations comparing cardiac structure or function between Aboriginal and other ethnic groups.   3.5 Cardiovascular Responses to Exercise  Physical activity includes any physical movements that result in energy expenditure (236).  Exercise is physical activity specifically to condition the body, improve health, maintain fitness or as therapy for restoring organs, bodily functions and/or deformities to a state of health (237).  Exercise training represents regular engagement in exercise in a routine manner.  An important component of a healthy lifestyle is exercise (180, 238).  Exercise and physical activity affect cardiovascular characteristics.  Exercise training may also have a larger effect on arterial remodelling of peripheral artery walls, compared to carotid or central artery walls (162).  Heart rate and systolic blood pressure are known to increase during aerobic exercise, proportional to the relative workload (239-241).  However, with exercise training, heart rate, and blood pressure required for the same workload can be decreased (239, 241-243).  During exercise, cardiac function increases; however, cardiac functional changes during exercise decline with age and cardiovascular disease progression (224, 244).  Cardiac function changes during exercise  may be more strongly related to aerobic capacity (224, 245).  As such, measurements of cardiac function during exercise may be predictive of future cardiovascular disease morbidity and mortality (225).  Maximal and near-maximal exercise stress-tests are prognostic for identifying cardiac arrhythmias and abnormalities among asymptomatic individuals with underlying cardiovascular disease (246).  Individuals demonstrating abnormal responses to maximal or near-maximal exercise are more likely to develop cardiovascular disease (246).  Further, the prediction of cardiovascular disease mortality from systolic blood pressure may be more accurate when evaluating systolic blood pressure during exercise rather than at rest (247-250).  Cardiovascular responses to exercise are also strong predictors of future cardiovascular disease mortality (251-253).  Changes in cardiac measures with exercise include left ventricular ejection fraction, regional wall motion, and left ventricular volumes (254).  In addition to maximal or near maximal exercise, submaximal exercise cardiovascular responses are also predictive of future cardiovascular disease events (252, 254).    38  3.5.1 Exercise and Vascular Dynamics Physical activity is found to be inversely related to IMT where higher levels of physical activity are related to attenuated progression of carotid IMT (162).  Low aerobic capacity has been associated with higher carotid IMT and increased presence of carotid plaques (255-258).  Exercise may reduce IMT through decreased inflammation, increased antioxidant presence or lower sympathetic nervous system activity at rest (162).  Greater intensity of exercise such as walking speeds correlate with lower carotid IMT measures (259-261).  Further, lower aerobic capacity represents the strongest predictor of an increase in carotid IMT over 4 years among middle-aged Finnish men (262).  Exercise provides sheer stress against arteries, which plays an important role in regulating large artery remodelling (263).  Systemic shear stress leads to adaptations in the artery wall in response to exercise training (162).  The development of carotid plaques links to the presence of low mean shear stress rates and oscillatory sheer stress (264, 265).  Conversely, exercise training is associated with lower arterial wall thickness (162).  Changes in lumen diameter and carotid IMT do not occur with an acute bout of exercise (266). Pulse wave velocity is known to be negatively correlated with physical activity levels, highlighting less arterial stiffness among more active individuals (267).  However, individuals participating in ultra-endurance events demonstrate greater PWV compared to normally active controls (268).  Changes in PWV following exercise are unclear.  Peripheral muscular artery stiffness is known to be reduced following acute maximal aerobic exercise (180), as well as post-resistance exercise (269).  However, following acute maximal sprint exercise, central PWV increases while peripheral decreases (270).  Participation in acute ultra-endurance exercise by contrast leads to increases in peripheral arterial stiffness though no changes in central arterial stiffness (268).  Moderate intensity aerobic exercise however, leads to reductions in both central and peripheral PWV (271). Exercise training promotes maintenance of a compliant arterial system (272, 273).  Exercise training is known to improve smaller muscular arteries (274) and the aorta (275), as well as systemic arterial compliance (272).  Further, increases in arterial compliance with exercise training are linearly related to changes in maximal aerobic capacity (VO2max) (272).  Though controversial, by contrast some evidence suggests high volume aerobic training may lead to decreases in arterial compliance compared to moderate levels of exercise training (276), and participation in acute ultra-endurance exercise also leads to reductions in arterial compliance  39  (277).  Participation in acute resistance exercise is also known to result in transient reductions in arterial compliance (278).  However, acute moderate aerobic exercise leads to increases in arterial compliance, which may be related to increased vasodilation (271).  In response to increasing exercise intensity or increasing aerobic capacity, arterial compliance may increase (279).  This increase is more pronounced among older individuals than younger individuals, and occurs at both maximal and submaximal exercise (279).  Systemic vascular resistance decreases during exercise due to vasodilation in active skeletal muscles (89).  Further, these reductions are known to be less apparent in populations with increased risk of cardiovascular disease, such as individuals with diabetes (280).   Regulation of cardiovascular function during and following exercise results largely from the autonomic nervous system (281).  The cardio-vagal baroreflex controls blood pressure oscillations through reflex changes in heart rate (187).  Artery wall changes in response to exercise also result from changes in vascular tone, especially when evaluating changes resulting from short term exercise (162).  Heart rate variability has been related to physical fitness (282-285), though with some controversy (286).  Overall, aging leads to impaired cardiac vagal function at rest, though poor physical fitness is associated with impaired vagal function during exercise (287).  Both chronic and acute exercise lead to improved BRS (288).  Acute changes in vagal tone directly influence the sensitivity of the cardio-vagal baroreflex (289).  While withdrawal of vagal innervation during exercise alters subsequent BRS values (290).  Acute exercise can lead to increases in sympathovagal tone immediately following exercise, due to the shift to increased sympathetic modulation (185).  Training at 100% of exercise intensity has resulted in poorer autonomic profiles, including both HRV and BRS, from baseline and compared to training 75% exercise intensity (291, 292). 3.5.2 Exercise and Cardiac Dynamics Habitual exercise training leads to physiological adaptations within the heart and specifically the left ventricle (213, 293).  Exercise training leads to an increase in resting and exercising stroke volume (294).  These cardiac improvements are associated with improved aerobic fitness (213, 293).  Exercise training leads to structural remodelling within the left ventricle and improvements in systolic and diastolic function (218, 295-298).  Left ventricular mechanics including strain and twist are also altered with exercise training, where highly trained  40  individuals experience reduced twist and strain, highlighting reduced stress and more efficient cardiac ejection (222, 293, 299).  Individuals with higher aerobic fitness demonstrate lower left ventricular apical rotation both at rest and during submaximal exercise, even in the absence of left ventricular structural changes (293). Due to increased sympathetic activity and circulating catecholamines during exercise, myocyte shortening and titin compression are greater (205).  These changes lead to decreases in end-systolic volume (205).  Elastic energy is stored in compressed titin due to left ventricular torsional deformation from helically oriented myofibers (199, 300, 301).  The greater compression of titin during exercise leads to greater force production, causing more rapid lengthening of myocytes and lowering of left ventricular chamber pressure (301, 302).  Additionally, base-to-apex intraventricular pressure gradients increase with exercise, leading to enhanced acceleration of blood across the mitral valve and enhanced left ventricular untwisting (205).  This enhanced left ventricular untwisting leads to more efficient left ventricular filling (205).  During exercise, cardiac output increases with increasing workloads, to meet the increasing metabolic demands of the body (89, 296, 303).  Cardiac output increases largely due to increases in heart rate due to decreases in parasympathetic modulation and increases in sympathetic modulation (296).  With increased exercising workload, increases in end diastolic volume and decreases in end systolic volume occur, leading to increases in stroke volume (296, 304).  Changes in ventricular volumes with exercise among healthy individuals also generally include increases in ejection fraction  (the proportion of blood ejected from the heart with beat) (241, 304).  Reductions in cardiac function following exercise have been termed “cardiac fatigue” or "exercise-induced cardiac fatigue" (305).  Evidence of transient cardiac impairment is identified following acute bouts of prolonged exercise more than three hours in duration (223, 306, 307).  Shorter duration or less intense exercise bouts have led to less consistent changes in cardiac function (308, 309).  Cardiac fatigue has not been identified following short duration exercise bouts of 5-18 minutes (310-312).  However, high intensity strenuous exercise as short as 30 s in duration has led to cardiac fatigue (313, 314).   3.5.3 Ethnic Differences in Cardiovascular Responses to Exercise Ethnic differences in cardiovascular responses to exercise have been previously investigated, largely among European and African-American populations.  Post-exercise blood  41  pressure reduction differences between ethnic groups have been reported, where African-American women do not experience reductions in blood pressure post-exercise (315).  In addition to greater resting PWV measures among African-American men, post-exercise heart rate and blood pressure-adjusted measurements of peripheral PWV were found to be larger among African-American men compared to European men, indicating a reduced response to exercise likely due to blunted vasodilation in response to adrenergic stimulation (193).  African-American individuals with heart failure have also been identified as having impaired vasodilation and vascular function following exercise, after adjusting for hypertension, compared to their non-African-American counterparts (194).  Further, ethnic differences in the vascular responses to resistance exercise have been identified between African-American and European populations (269).  Further, African-American men were found to have greater unadjusted arterial stiffness following resistance training compared to European men (269).   Cardiac responses to exercise training have also been found to vary across ethnic groups.  African/Afro-Caribbean athletes demonstrate more striking repolarization changes and greater magnitudes of left ventricular hypertrophy compared to Europeans after adjusting for age, and body composition (227, 228, 316).  Further, electrocardiography abnormalities identified through exercise testing more commonly occur among African descent populations than Europeans (228, 316).   Acute exercise testing among Canadian Aboriginal populations has only been reported in Canadian Inuit, with only measures of heart rate, blood pressure and aerobic capacity.  With acculturation of the Canadian arctic, Inuit populations demonstrated reductions in VO2max (317-320).  Furthermore, Aboriginal Inuit adults were found to have greater aerobic capacity than European Canadians (321).  While ethnic differences in the cardiovascular responses to exercise have been identified, cardiovascular responses including measures of cardiac and vascular function among Aboriginal populations have not been evaluated.  To date, no study has evaluated the temporal changes in stroke volume, cardiac output or blood pressure resulting from exercise in Aboriginal peoples.  3.6 Summary Aboriginal populations in North America currently experience greater burdens of cardiovascular disease, diabetes, and obesity.  Conversely, these populations demonstrate lower  42  measures of blood pressure and lower rates of hypertension than the non-Aboriginal population.  Limited assessments of vascular and cardiac dynamics have been conducted among Aboriginal populations, even fewer comparing and contrasting with other or non-Aboriginal populations.  Exercise and physical activity contribute to improved cardiovascular health and cardiac and vascular dynamics.  Though limited investigations have assessed the cardiovascular responses to exercise among Aboriginal populations.  Additionally, exercise testing is a method of evaluating cardiac and vascular dynamics and subclinical conditions.  However, exercise testing has not been conducted among First Nations/Métis Aboriginal individuals.   There is a clear need to further evaluate the co-existence of lower blood pressures with greater chronic health conditions among Aboriginal populations in Canada.  As obesity and diabetes are known to be associated with cardiovascular disease (100), and are prevalent among the Aboriginal population (12, 126, 189), the increased diabetes and obesity may contribute to cardiovascular disease development.  However, differences in body composition between Aboriginal and European populations with the same body mass index and waist circumference have not been identified (146, 322).  As body composition is similar between these ethnic groups, obesity likely does not account for the difference in trends between blood pressure and cardiovascular disease among Aboriginal populations.  The development of cardiovascular disease begins with subclinical changes.  Differences in the subclinical experience of cardiovascular disease development between Aboriginal and European populations may account for the greater prevalence of cardiovascular disease and lower blood pressure.  Additionally, differing cardiovascular responses to exercise may be further contributing to this condition through experiences during daily activity.  These experiences may support an ethnic specific hypertension definition for Aboriginal populations, where subclinical cardiovascular disease is developing at lower blood pressures relative to European populations.  Further research is required to evaluate the subclinical cardiovascular health of Aboriginal populations and the cardiovascular response to exercise and the relations to blood pressure.   3.7 Rationale, Objectives and Hypotheses In this section, five research questions forming the basis of this thesis are proposed to address current gaps in the literature regarding Aboriginal cardiovascular health and health disparities.  This research was conducted under the ethics approval Human Ethics – H12-01084.    43  3.7.1 Study 1: Vascular Health Status of Aboriginal Peoples Rationale  Vascular structure and function are important contributors to cardiovascular disease.  Subclinical assessments of vascular measures can provide indicators of atherosclerosis and developing vascular disease in the absence of overt cardiovascular disease (106, 107).  Ethnic differences in vascular measures have been identified (19).  However, few investigations have been conducted in Aboriginal populations with a lack of evaluation among Canadian Aboriginal populations.   Objective To evaluate vascular measures including PWV, IMT, arterial compliance, and BRS among Aboriginal adults in Canada including assessments between sexes and across the age range from 20-91 years. Hypotheses HA: Aboriginal males and older individuals will demonstrate greater PWV and IMT and lower BRS and arterial compliance compared to females and younger individuals, respectively.  H0: Vascular measures of PWV, IMT, arterial compliance, and BRS among a sample of Aboriginal adults will be similar between males and females, and across the age spectrum.  3.7.2 Study 2: Cardiac Dynamics of Aboriginal Peoples Rationale  Cardiac structure and function are indicators of cardiovascular status and risk of cardiovascular disease (229, 323).  Ethnic differences in cardiac structure have been identified among high level athletes (227, 228).  Few investigations have evaluated the cardiac structure and function among Aboriginal populations, solely in the United States (232, 233).  Further, these investigations focus on older and middle-aged adults.  However, no investigations have evaluated ethnic differences in Aboriginal cardiac dynamics. Objective To evaluate cardiac measures including left ventricular dimensions and volumes, stroke volume, cardiac output, ejection fraction, fractional shortening, arterial-ventricular coupling,  44  strain, strain rates, and rotation among Aboriginal adults and to compare between males and females. Hypotheses HA: Male Aboriginal adults will demonstrate greater left ventricular dimensions and volumes, stroke volume, cardiac output, ejection fraction, fractional shortening, arterial-ventricular coupling, strain, strain rates, and rotation compared to female Aboriginal adults.   H0: Cardiac measures of left ventricular dimensions and volumes, stroke volume, cardiac output, ejection fraction, fractional shortening, arterial-ventricular coupling, strain, strain rates, and rotation among a sample of Aboriginal adults will be similar between males and females.  3.7.3 Study 3: Ethnic Differences in Vascular Measures and Relation of Vascular Measures with Blood Pressure Rationale  Aboriginal populations demonstrate lower blood pressure but, higher rates of cardiovascular disease relative to non-Aboriginal populations (12, 52).  Subclinical assessments of vascular measures can be early indicators of atherosclerosis and vascular disease (106, 107).  Ethnic differences in vascular measures have been identified (19).  However, no investigations have directly compared vascular measures among Aboriginal and European populations, or evaluated the role of blood pressure in vascular health status between these ethnic groups.     Objective To evaluate the ethnic differences in vascular measures of IMT, PWV, BRS, and arterial compliance among population level sample of adult Aboriginal and European adults in Canada and to evaluate the relationship of these measures to blood pressure among these ethnic groups. Hypotheses HA: Differences in vascular measures of IMT, BRS, PWV, and arterial compliance between Aboriginal and European adults will be identified, with differences between these measures and blood pressure identified between these ethnic groups. H0: Aboriginal adults will demonstrate similar IMT, BRS, PWV, and arterial compliance compared to European adults, with similar relationships between blood pressure and these vascular measures.  45  3.7.4 Study 4: Ethnic Differences in the Vascular Responses to Exercise Rationale  Exercise training is associated with lower IMT and PWV, and higher BRS and arterial compliance, and lower rates of cardiovascular disease (255-258).  Ethnic differences in vascular responses to exercise have been identified (193, 269).  However, these experience of Aboriginal adults has not been evaluated.    Objective To evaluate the ethnic differences in changes in PWV, arterial compliance, and BRS following maximal and submaximal aerobic exercise among Aboriginal and European Canadian adults. Hypotheses HA: Differences in vascular responses to maximal and submaximal aerobic exercise including BRS, PWV, and arterial compliance between Aboriginal and European adults will be identified. H0: Aboriginal and European adults will demonstrate similar PWV, BRS and arterial compliance changes resulting from maximal and submaximal aerobic exercise.   3.7.5 Study 5: Ethnic Differences in the Cardiac Responses to Exercise Rationale  Exercise training is associated with improved cardiac health and lower rates of cardiovascular disease (324-326).  Aboriginal individuals have been found to be more active than non-Aboriginals (20, 327).  Ethnic differences in cardiac responses to exercise have been identified (227, 228, 316).  However, these responses have not been evaluated among Aboriginal populations.    Objective To evaluate the ethnic differences in changes in cardiac functional measures including stroke volume, cardiac output, ejection fraction, strain and strain rates, arterial-ventricular coupling, and systolic and diastolic velocities following maximal and submaximal aerobic exercise among Aboriginal and European Canadian adults.   46   Hypotheses HA: Differences in cardiac responses to maximal and submaximal aerobic exercise including stroke volume, cardiac output, ejection fraction, strain and strain rates, arterial-ventricular coupling, and systolic and diastolic velocities between Aboriginal and European adults will be identified where greater changes following exercise would be identified among the Aboriginal adults. H0: Aboriginal and European adults will demonstrate similar stroke volume, cardiac output, ejection fraction, strain and strain rates, arterial-ventricular coupling, and systolic and diastolic velocities changes resulting from maximal and submaximal aerobic exercise.     47  4. Vascular Health Status of Aboriginal Peoples2 4.1 Introduction Cardiovascular disease begins with subclinical changes in the vascular system (106, 107).  Changes in vascular structure and function such as atherosclerosis progression, may include decreases in vessel lumen size, decreased endothelial function, increased arterial stiffening and decreased arterial distensibility (149-153).  Markers of subclinical cardiovascular disease can be evaluated through measurements of vascular structure and function and may be evident years prior to evidence of overt cardiovascular disease (107, 328).  Aboriginal populations currently experience greater burdens of cardiovascular disease (12, 131-138) and lower blood pressure (329-332).  However, limited information regarding vascular measures of Canadian Aboriginal adults exists.   This investigation aimed to evaluate the vascular health status among a sample of Aboriginal adults in British Columbia, Canada.  The objective was to evaluate vascular measures of IMT, BRS, PWV, and arterial compliance across both sexes of Aboriginal adults and across the age spectrum.  It was hypothesized that adult males, those of older age would demonstrate greater IMT and PWV, and lower BRS and arterial compliance compared to females and younger adults.   4.2 Methods 4.2.1 Participants and Ethical Approval From June 2012 to August 2013, Aboriginal adults,  ≥19 yr, from four communities around British Columbia, Canada underwent an assessment of vascular function.  From 66 Aboriginal adults recruited, 55 Aboriginal adults completed the vascular function assessment.  Participants represent a range of ages, from 20 to 91 yr.  Power calculations using G*Power 3.1.3 (333) based on previous investigations suggest sex differences can be detected with samples of PWV among 4 middle aged adults per group (334), IMT among 64 middle aged adults per group (335) and small arterial compliance among 23 young adults per group (336).  Ethics approval                                                  2 A version of Chapter 4 has been prepared for publication. Foulds H.J.A., Bredin S.S.D. Warburton D.E.R.. The vascular health status of a population of adult Canadian Indigenous peoples from British Columbia.   48  was obtained through the Clinical Research Ethics Board at the University of British Columbia and written informed consent was obtained from each participant prior to data collection.  Additionally, each Aboriginal community reviewed and approved the project prior to participation of members of their respective communities.  Participants were recruited through their local Indigenous communities by community and health leaders. Included individuals were adults at least 19 years of age who were ambulatory.  Excluded individuals were under 19 years of age or unable to perform 6 minutes of walking.  Testing was conducted within the local Aboriginal communities with the assistance of Aboriginal students and volunteers.  Participants were asked to refrain from caffeine, food intake, exercise and smoking for a minimum of 2 hours prior to the assessment, and refrain from alcohol intake for a minimum of 6 hours prior to the assessment.   4.2.2 Individual Characteristics and Blood Pressure Individual characteristics collected included age, sex, education level, income, employment, and self-reported health measures including diabetes, hypertension or other chronic health conditions as well as behaviours including smoking, drinking, and physical activity.  Education was assessed using a multiple choice questionnaire including less than 8th grade, some high school, high school diploma, vocational school or some college, college degree, or professional or graduate degree.  Education was then categorized as less than high school diploma, high school diploma, or more than high school.  Participants self-declared ethnicity and ancestral nations.  Aboriginal participants included all those who self-declared either First Nations or Métis ancestry, with no minimum blood quantum or status requirements.  Physical activity categories were determined using the Godin-Shephard Leisure Exercise Questionnaire (337, 338).  Anthropometric measures including height, body mass, and waist circumference were assessed (and BMI calculated) according the standardized protocols of Gledhill and Jamnik (339).  Measurements of height were determined using a Seca 214 portable height rod stadiometer (seca corp., Ontario, CA, USA) to the nearest 0.1 cm.  Height was measured from heels to the top of the head, with shoes removed while participants were at peak inhalation.  Body mass was recorded in kilograms (kg) to the nearest 0.2 kg using a Tanita BC-534 Innerscan Body Composition Monitor scale (Tanita Corporation of America, Inc., Illinois, USA) while participants wore light clothing with shoes, jackets, and heavy objects removed.  Waist  49  circumference was measured at the midpoint between the 12th rib and the iliac crest on the right side of the body using a flexible plastic tape to the nearest 0.1 cm.  Participants were instructed to cross their arms over their chest and waist circumference was measured at the end of exhalation.  Obesity classifications were determined using the World Health Organization principle cut-off points (143).  Abdominal obesity was determined at the World Health Organization level 2 ranges (men ≥102 cm, women ≥88 cm) (144).  These European obesity definitions were used for the Aboriginal population as they have been found to correlate with body fat measures (145, 146, 322).  Resting blood pressure was measured directly while participants were seated following five minutes of seated rest using three measurements, one minute apart, from an automated blood pressure measurement system (BP-TRU, VSM Medical, Vancouver, Canada).  The average of the second and third readings were used to determine seated resting blood pressure.  Standing blood pressure was determined immediately following rising from the seated position and determined using a single measurement.  Supine resting blood pressure was measured following five minutes of supine rest.  Hypertension was determined using the British Hypertension Society blood pressure measurement protocol as described above from seated measurements (340, 341).  Hypertension was defined as the use of anti-hypertension medication or average measurements of ≥140 mmHg systolic or ≥90 mmHg diastolic. 4.2.3 Vascular Assessment  Participants rested in a supine position for five minutes prior to the vascular assessment and remained supine throughout.  Arterial compliance was evaluated using supine resting measures of applanation tonometry (HDI/Pulsewave CR-2000 Cardiovascular Profiling System, Egan, Minnesota) on the right wrist with the appropriate sized blood pressure cuff and a rigid plastic wrist stabilizer.  This model evaluates diastolic pulse contour analysis, then incorporated into a modified Windkessel model of circulation.  The arterial tree is considered to be loaded by stroke volume during systole where diastolic decay contour is used to determine compliance, resistance and pressure changes of the isolated arterial system (342).  This system determines both large and small artery compliance where large artery is evaluating capacitance vessels and small artery represents small-oscillatory conductance vessels.  Large artery compliance is derived from more proximal artery segments and depends on arterial calibre.  Small artery  50  compliance is derived from the frequency and diastolic decay rate of pressure waves created at downstream of reflection, and is dependent on both elastic and geometric properties of the large arteries as well as pulse wave reflections (342).  Each measurement consists of a 30s segment recorded and analyzed.  Three of these measurements were averaged to determine arterial compliance and vascular resistance.    Pulse wave velocity and autonomic function were evaluated by collecting at least five minutes of beat-by-beat blood pressure data using finger photoplethysmography (Finapress, Ohmeda Inc., Englewood, CO) and pulse wave contours at the carotid and femoral arteries using infrared photoelectric sensors (ADInstruments), with three lead electrocardiography (I, II, III) on Chart software (Version 5.5.6).  Both central and peripheral pulse wave velocity (PWV) were determined by a single investigator from the pulse wave contours, with 30 consecutive cardiac cycles averaged to calculate the foot-to-foot pulse transit time between carotid and femoral (central PWV), and carotid and finger (peripheral PWV).  The shortest distances between the sites of pulse contour collection were measured to the nearest 0.5 cm using a standard flexible measuring tape.  The segmental distances were divided by the corresponding pulse transit time to calculate PWV, with a scaling factor of 0.8 used to correct the path length measured over the body surface area between carotid and femoral sites (343, 344). Autonomic function was evaluated through analysis of the entire length of collected beat-bye-beat blood pressure data, with a minimum of 180s of continuous cardiac cycles evaluated in the determination of heart rate variability (HRV), blood pressure variability (BPV) and baroreceptor sensitivity (BRS).  Offline power spectral evaluations of BRS, HRV, and BPV, as well as spontaneous baroreflex activity were conducted by the same investigator using Nevrokard BRS software (Version 6.1.0, Nevrokard Kiauta, d.o.o, Slovenia).  Heart rate and BPV analyses included both time and frequency domain measures, according to specifications by the Task Force of European Society of Cardiology and the North American Society of Pacing and Electrophysiology (185).  Power spectral analysis evaluated the harmonic components of RR interval and BP variabilities using a Fast Fournier transformation in the Hanning window. Low frequency was defined as components 0.04 to 0.15 Hz, while high frequency, synchronous with respiration and reflecting respiratory modulation of the sinoatrial node, was defined as components 0.15 to 0.40 Hz (185).  Power densities of spectral components were calculated in both absolute and normalized units, determined by dividing the low frequency or high frequency  51  by the total power, subtracting very low frequency (<0.04 Hz) and multiplying by 100 (185).  Spontaneous baroreflex activity was analysed through the sequence method.  Sequences were considered a baroreflex action if there were at least three consecutive cardiac beats of increased or decreased systolic arterial pressure with a parallel change in R-R interval exceeding a correlation coefficient of 0.85 (291). Each individual sequence was evaluated using linear regression (345).  A measure of the integrated BRS was obtained by averaging the slopes of all sequences evaluated (345).  These results were interpreted to represent the vagally-mediated baroreceptor-cardiac responses (291).   Intima-media thickness was measured using carotid ultrasonography.  Imaging was performed by a single investigator using Logic-e system equipped with a 9L-RS wide-band linear array transducer (GE Healthcare, Ltd., Horton, Norway).  The distal common carotid artery was imaged while participants lay in the supine position with slight hyperextension of the neck.  The common carotid artery, carotid bulb, and extra cranial internal and external carotid arteries were identified.  Two-dimensional five beat cine-loop clips of the common carotid artery within 1 cm of the carotid bulb were recorded in DICOM format.  Both left and right common carotid arteries were recorded at three imaging planes (anterior, lateral, and posterior) (346).  Offline measurements of far-wall IMT were obtained using commercially available software (EchoPac version 7.0, GE Medical).  Each beat was analyzed with electrocardiography used to time measurements at end diastole.  Care was taken not to include any evidence of carotid plaque in the IMT measurement, where plaque was defined as a focal structure encroaching into the arterial lumen of at least 0.5mm or a thickness more than 50% greater than the surrounding lumen (347).  Measurements per imaging plane were averaged, then each plane was averaged to obtain an overall right and left IMT.  An overall IMT measurement was determined as the average of right and left overall IMT measures.   4.2.4 Physical Fitness Measures Participants completed two repetitions of grip strength measures on each hand, according to standardized protocols (339).  The combined grip strength was determined as the sum of the greatest left and right measurements.  Participants also completed an aerobic fitness test, the six min walk test.  This test requires participants to walk as far as possible along a predetermined  52  track of known distance for six minutes (348, 349).  This test has been found to be an indicate marker of aerobic fitness, even among general healthy populations (350).  4.2.5 Statistical Analyses Statistical analyses were performed using Statistica 9.0 (Stats Soft, Tulsa, OK).  Continuous variables were reported as mean and standard deviation, while categorical and binary factors were reported as percentages and counts.  Normal distribution was tested, and as large arterial compliance was found not to be normally distributed, the natural log transformation was used for analysis.  Sex differences were evaluated using t-tests for independent samples for continuous variables and Pearson χ2 test for categorical variables.  Pulse wave velocity and IMT comparisons were performed using Analysis of Covariance (ANCOVA) to adjust for mean arterial pressure and age (342).  Regression was used to compare vascular measures across the age spectrum with Pearson’s Correlation Coefficient.  Multiple regression was used to compare IMT and PWV measures across the age spectrum, adjusting for sex and mean arterial pressure (PWV).  Significance was set at p < 0.05 for all analyses.  4.3 Results  A total of 55 Aboriginal adults were evaluated, including 26 males and 29 females.  As outlined on Table 4.1, men and women were of a similar age, with similar marital status.  However, trends were identified for men being less likely to have completed high school and less likely to have more than high school education.  Men were less likely to be employed.  A significant proportion of the Aboriginal population sampled earned less than $20 000 per year, similar across both sexes.  Men and women reported similar smoking and binge drinking behaviours with nearly 20% of the population considered to be smokers and a similar proportion engage in binge drinking more than once a month.      53  Table 4.1 Characteristics and demographics of participants, by sex mean ± SD, n (%)   Male (n = 26) Female (n = 29) Overall (n = 55) P value      Age (yr) 39 ± 20 38 ± 16 38 ± 18 0.85 First Nations, n (%) 16 (61.5) 20 (69.0) 36 (64.3) 0.57 Métis, n (%) 10 (38.5) 9 (31.0) 19 (33.9) 0.57 Single, n (%) 12 (46.2) 9 (31.0) 21 (37.5) 0.26 Married or common-law, n (%) 9 (34.6) 15 (51.7) 24 (42.9) 0.21 Divorced or separated, n (%) 4 (15.4) 5 (17.2) 9 (16.1) 0.86 Less than high school diploma, n (%) 3 (11.5) 0 (0.0) 3 (5.4) 0.06 High school diploma, n (%) 3 (11.5) 2 (6.9) 5 (8.9) 0.56 More than high school education, n (%) 20 (76.9) 27 (93.1) 47 (83.9) 0.09 Unemployed, n (%) 5 (19.2) 1 (3.4) 6 (10.7) 0.06 Employed, n (%) 18 (69.2) 27 (93.1) 45 (80.4) 0.02 Retired or homemaker, n (%) 3 (11.5) 1 (3.4) 4 (7.1) 0.26 Annual income  <$20 000 per year, n (%) 9 (34.6) 11 (37.9) 20 (35.7) 0.80 Smoker, n (%) 6 (23.1) 5 (17.2) 11 (19.6) 0.60 Binge drinker more than once a month, n (%) 7 (26.9) 5 (17.2) 12 (21.4) 0.39 Binge drinker ever, n (%) 15 (57.7) 16 (55.2) 31 (55.4) 0.85 Never binge drink, n (%) 11 (42.3) 13 (44.8) 24 (42.9) 0.85      SD, standard deviation  Men and women were found to have similar measures of seated blood pressure and heart rate (Table 4.2).  However, women were found to have significantly lower standing and supine systolic blood pressures.  Similar rates of hypertension were both reported and measured.  Less than four percent of both Aboriginal men and women reported taking anti-hypertension medication.  Men were found to be significantly taller, heavier, and have larger waist circumferences.  Body mass index was similar among both sexes, averaging in the overweight range.  Similar among both men and women, 20-30% of the population was found to be obese and 25-30% found to be abdominally obese.  None of the participants reported a history of cardiovascular disease or diabetes, while a small proportion reported a history of cardiovascular disease among primary family members.  Physical activity behaviour was similar among both men and women with a large majority reporting active lifestyles.  Men were found to have  54  significantly greater grip strength measures, while six min walk distances were similar across men and women.  Table 4.2 Health status and measures of participants, by sex mean ± SD, n (%)   Male (n = 26) Female (n = 29) Overall (n = 55) P value      Blood pressures (mmHg)      Seated systolic  122.3 ± 17.2 114.5 ± 16.8 118.2 ± 17.3 0.09  Seated diastolic  72.8 ± 9.5 72.2 ± 7.8 72.5 ± 8.5 0.79  Standing systolic  126.8 ± 14.6 112.9 ± 17.5 119.2 ± 17.5 0.02  Standing diastolic  83.3 ± 14.4 75.5 ± 10.3 79.1 ± 12.8 0.07  Supine systolic  126.7 ± 15.5 116.2 ± 14.7 121.3 ± 15.8 0.01  Supine diastolic  68.5 ± 9.4 65.3 ± 8.1 66.8 ± 8.8 0.19 Seated heart rate (beats·min-1) 68.1 ± 13.8 68.4 ± 9.4 68.3 ± 11.6 1.00 Hypertension (reported), n (%) 3 (11.5) 2 (6.9) 5 (8.9) 0.56 Hypertension (measured), n (%) 3 (11.5) 4 (13.8) 7 (12.5) 0.81 Use anti-hypertension medication, n (%) 1 (3.8) 1 (3.4) 2 (3.6) 0.94 Height (cm) 180.1 ± 7.1 163.3 ± 4.4 171.2 ± 10.2 <0.001 Body mass (kg) 95.3 ± 20.8 70.5 ± 17.1 82.2 ± 22.5 <0.001 BMI (kg·m-2) 29.6 ± 7.4 26.5 ± 6.8 28.0 ± 7.2 0.12 Waist circumference (cm) 97.9 ± 17.2 81.6 ± 14.7 89.4 ± 17.8 0.001 Cardiovascular disease, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Family history of cardiovascular disease *, n (%) 1 (3.8) 3 (10.3) 4 (7.1) 0.36 Diabetes, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Obesity, n (%) 8 (30.7) 6 (20.7) 14 (25.0) 0.40 Abdominal obesity, n (%) 8 (30.7) 8 (27.6) 16 (28.6) 0.80 Physically inactive, n (%) 3 (11.5) 5 (17.2) 8 (14.3) 0.56 Moderately active, n (%) 1 (3.8) 3 (10.3) 4 (7.1) 0.36 Physically active, n (%) 22 (84.6) 21 (72.4) 43 (76.8) 0.28 Combined grip strength (kg) 100.7 ± 16.9 62.6 ± 15.6 80.6 ± 25.0 <0.001 Six min walk distance (m) 634.3 ± 126.9 580.3 ± 119.4 605.8 ± 124.8 0.11           BMI, body mass index; SD, standard deviation; *primary family member prior to age 55 (male) or 65 (female)   Men and women were found to have similar IMT measurements, as outlined on Table 4.3.  Similar measures of central and peripheral PWV were identified across both sexes.  Men  55  were found to have significantly greater small and large arterial compliance.  Conversely, females were found to have greater spectral method BRS, down sequence BRS and overall sequence method BRS.  Heart rate variability and diastolic BPV were similar across both sexes; however, women were found to have lower systolic BPV mean normal-to-normal (NN) and low frequency power.   Table 4.3 Vascular measures of Aboriginal participants, by sex mean ± SD, n (%)   Male (n = 26) Female (n = 29) Overall (n = 55) P value      Right IMT (mm) 0.61 ± 0.14 0.55 ± 0.08 0.58 ± 0.11 0.11 Left IMT (mm) 0.60 ± 0.15 0.58 ± 0.10 0.59 ± 0.13 0.83 Overall IMT (mm) 0.61 ± 0.14 0.57 ± 0.08 0.59 ± 0.11 0.25 Central PWV (m∙s-1) 5.7 ± 2.5 5.1 ± 2.3 5.3 ± 2.4 0.61 Peripheral PWV (m∙s-1) 12.0 ± 4.0 12.4 ± 4.0 12.2 ± 4.0 0.74 Large arterial compliance  (mL∙mmHg-1 x 10) 19.1 ± 9.8 15.0 ± 5.9 17.0 ± 8.2 0.05 Small arterial compliance (mL∙mmHg-1 x 100) 8.9 ± 3.7 6.4 ± 2.3 7.6 ± 3.3 0.004 Spectral BRS (ms∙mmHg-1) 9.6 ± 6.8 16.9 ± 10.0 13.3 ± 9.3 0.01 Up Sequence BRS (ms∙mmHg-1) 18.8 ± 13.5 22.1 ± 11.3 20.4 ± 12.4 0.42 Down Sequence BRS (ms∙mmHg-1) 16.5 ± 9.0 26.9 ± 15.3 21.3 ± 13.2 0.01 All Sequence BRS (ms∙mmHg-1) 17.1 ± 10.7 24.6 ± 11.8 20.7 ± 11.7 0.04 HRV mean NN interval (ms) 980.9 ± 188.8 961.9 ± 121.5 971.0 ± 156.0 0.67 HRV SDNN (ms) 44.7 ± 28.4 46.0 ± 28.2 45.8 ± 28.0 0.97 HRV RMSSD (ms) 71.7 ± 61.2 64.2 ± 49.1 67.8 ± 54.8 0.63 HRV low frequency power (n.u.) 46.2 ± 21.8 41.3 ± 18.4 43.6 ± 20.0 0.42 HRV high frequency power (n.u.) 40.4 ± 21.8 49.0 ± 17.9 44.9 ± 20.1 0.15 HRV low frequency∙high frequency-1 1.8 ± 1.6 1.2 ± 1.3 1.5 ± 1.4 0.21 BPV mean NN systolic blood pressure (mmHg) 126.0 ± 21.4 110.2 ± 13.6 117.6 ± 19.2 0.004 BPV mean NN diastolic blood pressure (mmHg) 68.6 ± 12.0 67.0 ± 10.0 67.7 ± 10.8 0.62 BPV Systolic SDNN (mmHg) 3.6 ± 3.0 2.7 ± 1.9 3.1 ± 2.5 0.23 BPV Systolic RMSSD (mmHg) 5.3 ± 4.6 4.6 ± 3.9 4.9 ± 4.2 0.58 BPV low frequency Power (n.u.) 67.0 ± 16.8 52.8 ± 17.9 59.9 ± 18.6 0.01      BPV, blood pressure variability; BRS, baroreceptor sensitivity; HRV, heart rate variability; IMT, intima-media thickness; NN, normal to normal; PWV, pulse wave velocity; RMSSD, root mean squared of successive differences; SD, standard deviation  56    Across the age spectrum, a range of individuals were evaluated.  The Aboriginal adults evaluated represented a range of ages from 20 to 91 yr.  A significant relationship was identified between age and IMT (Figure 4-1).  Individuals of a younger age were found to have significantly lower IMT and older individuals found to have greater IMT measures, with 73% correlation between the two variables.   Age (years)0 20 40 60 80 100Overall Intima-Media Thickness (mm)0.40.50.60.70.80.91.01.1r=0.74, r2=0.53p<0.001 Figure 4.1 The relationship between overall intima-media thickness and age among Aboriginal adult participants   Systolic and diastolic blood pressures were found to significantly correlate with age, as outlined on Figure 4-2 A and B, respectively.  With increasing age, both systolic and diastolic blood pressure were found to increase among Aboriginal adults.  Both central (Figure 4-2 C) and peripheral (Figure 4-2 D) PWV were not found to be associated with age.  Very low correlation coefficients were identified among these measures with age.  57  0 20 40 60 80 100Systolic Blood Pressure (mmHg)801001201401601802000 20 40 60 80 100Diastolic Blood Pressure (mmHg)556065707580859095Age (years)0 20 40 60 80 100Central Pulse-Wave Velocity (m.s-1)02468101214Age (years)0 20 40 60 80 100Peripheral Pulse-Wave Velocity (m.s-1)681012141618202224r=0.48, r2=0.22p<0.001r=0.04, r2=-0.02p=0.79r=0.03, r2=-0.02p=0.86r=0.47, r2=0.21p<0.001ACDB Figure 4.2 The relationship between overall age and vascular measures of systolic blood pressure (A), diastolic blood pressure (B), central pulse wave velocity (C) and peripheral pulse wave velocity (D) among Aboriginal adult participants  Large artery compliance (Figure 4-3 A) and small artery compliance (Figure 4-3 B) were found to be negatively correlated to age.  Younger individuals were found to have greater arterial compliance, while older individuals demonstrated lower compliance.  Similarly, younger  58  individuals were found to have significantly greater BRS, as measured with either spectral (Figure 4-3 C) or sequence (Figure 4-3 D) method.   0 20 40 60 80 100Large Arterial Compliance (ms.mmHg-1 x 10)05101520253035400 20 40 60 80 100Small Arterial Compliance (ms.mmHg-1 x 100)024681012141618Age (years)0 20 40 60 80 100Spectral Baroreceptor Sensitivity (ms.mmHg-1)0510152025303540Age (years)0 20 40 60 80 100Sequence Baroreceptor Sensitivity (ms.mmHg-1)0102030405060r=-0.39, r2=0.14p=0.004r=-0.38, r2=0.12p=0.01r=-0.43, r2=0.43p=0.005r=-0.48, r2=0.21p<0.001AC DB Figure 4.3 The relationship between overall age and vascular measures of large arterial compliance (A), small arterial compliance (B), spectral method baroreceptor sensitivity (C) and sequence method baroreceptor sensitivity (D) among Aboriginal adult participants      4.4 Discussion Several investigations have assessed the health status of Aboriginal populations in Canada and the United States.  However, few include a comprehensive assessment of vascular  59  measures and subclinical atherosclerosis.  The present investigation is unique in identifying vascular health status of an Aboriginal population, including a broad age spectrum of relatively healthy adults.  To date, most vascular assessments among Aboriginal peoples have focused on older populations (196, 198, 351), or populations with a high rate of chronic health conditions (197).  As vascular measures can be used to determine preclinical atherosclerosis and subclinical cardiovascular disease, assessments of relatively healthy populations can indicate future cardiovascular disease experience and risk (92, 106, 107).   The participants in this investigation were generally healthy individuals, free of chronic health conditions.  In Canada, Aboriginal populations are younger than the non-Aboriginal population with a median age of 28 compared to 41 among the non-Aboriginal population (67).  This investigation sampled 64.3% First Nations individuals and 33.9% Métis, similar to the 60.8% First Nations and 32.2% Métis identified among Aboriginal populations in Canada (67).  By contrast, this sample has higher educational attainments, greater income, and higher employment rates than the 2006 Aboriginal National average (16).  The sampled population reported similar smoking rates to those sampled in larger provincial surveys (30).  Lower rates of hypertension, diabetes, obesity, and abdominal obesity were also identified among this sample, compared to previous samples of slightly older individuals (30).  The healthier status of the sampled population may have limited the variability in vascular measures identified as compared to the general Aboriginal population.   In this sample, Métis and First Nations were found to have statistically similar rates of hypertension, 21.1% and 8.3% respectively.  However, in a larger sample with approximately 130 individuals in each population, these differences may become statistically significant, consistent with the relationship between hypertension and percentage of Aboriginal ancestry previously reported (47).  Hypertension was not found to be related to body mass index, waist circumference or obesity, similar to findings among other Aboriginal populations (45, 47).   Intima-media thickness has previously been assessed among Aboriginal populations (196-198).  However, BRS, PWV and arterial compliance have not been reported among Aboriginal populations.  Pulse wave velocity measured in this sample are lower than reference population averages even for a younger population (343), though higher than those observed previously among ultra-marathon runners in the same laboratory (268).  Arterial compliance, evaluated using the same device, among this sample is higher compared to a middle aged female  60  population (352) and a population of older adults (353).  Baroreceptor sensitivity measures from this investigation are higher than those found for 30-40 year old samples of a reference group, though within the normal range for 20-40 year old samples (156).  The vascular measures obtained in this study are within the healthy ranges and consistent with trends of healthier measures among more active and younger individuals relatively free of chronic health conditions and demonstrating high rates of employment, educational attainments.  Sex differences in vascular measures have previously been identified.  These differences are expected as men have greater experiences of cardiovascular disease and lower life expectancy (354).  Men, regardless of ethnicity, are known to have greater IMT measures than women (355).  While this sample did not demonstrate statistically significant differences between men and women, the absolute mean IMT measures were greater among men than women.  Greater PWV have been identified among men as well (356), though these differences are lessened when adjusting for blood pressures (343).  This investigation did not identify sex differences in PWV after adjusting for mean arterial pressure.  Sex influences arterial pressure waveforms (357).  As arterial compliance is an analysis of arterial pressure waveforms (176), sex differences in arterial compliance also result.  This study identified sex differences in both small and large arterial compliance, with males maintaining higher values compared to females.  This poorer arterial compliance among women may be the result of greater systolic augmentation, due to lower stature (357).  Sex differences in BRS were also identified in this study, with differences in spontaneous BRS as well as down and overall sequence BRS.  Similar BRS values have previously been reported among males and females (156).  Overall, this relatively healthy population demonstrated limited sex differences.  The low rate of chronic health conditions and diabetes among this sample, coupled with the small sample size and large age range, likely influenced the limited sex differences identified.   Due to both increased exposure to risk factors over time, and progression of arterial dysfunction (92, 106), changes in vascular measures with age have been identified (108, 110-112).  Increases in IMT (347, 355) and PWV (343, 356) are found with increasing age.  Older individuals also have lower arterial compliance (353) and BRS (156) compared to younger individuals.  Overall, this investigation identified significant increases in IMT and blood pressures with age, and significant decreases in arterial compliance and BRS.  No changes in PWV were observed with age among this sample.  Increases in PWV with age are known to  61  occur more prominently at older decades of life (358).  As many of the participants in the present study were under 60 years of age, the influence of age on PWV may have been less apparent.    Hypertension was found to affect similar numbers of males and females, and First Nations and Métis.  Individuals with hypertension are known to have poorer vascular health, including increased IMT (351) and PWV (343), and decreased arterial compliance (359) and BRS (360).  As expected, in this investigation individuals with hypertension were found to have significantly greater IMT and PWV, and significantly lower BRS and arterial compliance.  These results were evident even with a hypertensive sample size of only seven individuals.   The inclusion of several markers of pre-clinical vascular disease provides information about several aspects of the progression.  By including markers which evaluate different components, a more comprehensive assessment can be achieved (361).  Arterial stiffening (PWV) and arterial thickening (IMT) are independent markers of increased cardiovascular disease risk (196, 362, 363).  The inclusion of several widely accepted markers of cardiovascular disease to evaluate vascular measures of Aboriginal populations, provides additional information regarding this high risk group not previously available.  This investigation is limited by the small sample size.  Having a small number of participants with a wide range of ages may reduce the statistical power of the investigation.  As this sample has lower rates of hypertension, diabetes, and higher education, employment, and income than other Aboriginal samples, these individuals may not represent the Aboriginal population as a whole.  Further, as the Aboriginal population in Canada is comprised of several distinct nations, each with their own culture and history, a single sample of individuals may not accurately reflect the whole sample (18, 61, 364).  Additionally, as this study included participants from a variety of nations, these results may not accurately reflect any of the individual groups sampled.    4.5 Conclusion  In conclusion, the Aboriginal population sampled was relatively healthy.  Males and females demonstrated similar vascular measures.  However, males were found to have greater systolic blood pressure and small arterial compliance, while females demonstrated greater BRS.  Arterial compliance and BRS were lower, and PWV and IMT greater among older individuals.     62  5. Cardiac Dynamics of Aboriginal Peoples3 5.1 Introduction Cardiovascular disease is a significant concern among Western society, and especially among Aboriginal populations (1, 2, 6, 30, 32).  With the development of cardiovascular disease, changes in cardiac structure and function occur, including reduced cardiac perfusion and reduced subendocardial coronary blood supply (92), increased left ventricular afterload and left ventricular hypertrophy (115, 328).  These changes in cardiac structure and function occur prior to clinical cardiovascular disease or with elevated blood pressure (116). Ethnic differences in cardiac structure and function have previously been identified among African-American populations (227, 228).  Cardiac structure and function have also been investigated among older adult American Indian populations (232-234).  In this United States population, left ventricular mass was found to be related to demographic and haemodynamic variables (234), and left ventricular hypertrophy associated with genotype differences in rennin-angiotensin genes (235). Assessments of cardiac structure and function have been investigated among these older Aboriginal populations; however, no investigations of Canadian Aboriginal populations, or of younger adult Aboriginal populations exist.  This investigation sought to evaluate cardiac measures including left ventricular dimensions and volumes, stroke volume, cardiac output, ejection fraction, fractional shortening, arterial-ventricular coupling, strain, strain rates, and rotation of a young, healthy adult Aboriginal population, and to compare between males and females.  This young, healthy population was hypothesized to have greater left ventricular dimensions and volumes, stroke volume, cardiac output, ejection fraction, fractional shortening, arterial-ventricular coupling, strain, strain rates, and rotation among males than females.     5.2 Methods 5.2.1 Participants and Ethical Approval From February to August 2013, Aboriginal adults,  ≥19 yr, were assessed for cardiac dynamics.  Participants represent a range of ages, from 21 to 31 yr.  From a recruited sample of                                                  3 A version of Chapter 5 has been prepared for publication. Foulds H.J.A., Bredin S.S.D. Warburton D.E.R.. The cardiac dynamics of Canadian Indigenous populations.   63  16 adults, a total of 10 Aboriginal adults completed the assessment of cardiac dynamics.  Power calculations using G*Power 3.1.3 (333) indicate sex differences in measures such as wall stress, left ventricular mass and ejection fraction/end diastolic volume can be determined with sample sizes of 4-12 per sex among young normally active adults, with 4 participants per sex required for wall stress, 9 participants per sex for left ventricular mass/BSA, and 12 participants required for ejection fraction/end diastolic volume (336).  Ethics approval was obtained through the Clinical Research Ethics Board at the University of British Columbia and written informed consent was obtained from each participant prior to data collection.  Additionally, Aboriginal elders from the community reviewed and approved the project prior to the study commencing.  Testing was conducted at the University of British Columbia Cardiovascular Physiology and Rehabilitation laboratory, with the assistance of Aboriginal students.  Participants were asked to refrain from caffeine, food intake, exercise and smoking for a minimum of 2 hours prior to the assessment, and refrain from alcohol intake for a minimum of 6 hours prior to the assessment.   5.2.2 Individual Characteristics, Blood Pressure, and Fitness Measures Individual characteristics, and blood pressure were evaluated as previously described in section 4.2.2.  Following the cardiac assessment, participants completed a maximal aerobic power test (VO2max).  Participants completed a VO2max test on a cycle ergometer (Ergometrics er800s, Ergoline, Bitz, Germany).  The progressive exercise test was performed at 80 rpm, beginning at 50 W.  The workload was increased by 25 W every two minutes until reaching the ventilatory threshold.  After the ventilatory threshold power output was increased by 25 W per min until exhaustion.  Heart rate and expired gas analysis (Ergocard, Medisoft, Sorinnes, Belgium) were recorded throughout rest, exercise and one minute post exercise.  Maximal aerobic capacity was determined as the highest aerobic output sustained over 15s.  The Physical fitness measures also included grip strength and six minute walk test as described in section 4.2.4.   5.2.3 Echocardigraphy  Cardiac measurements were obtained by a trained clinical echocardiography sonographer using a portable ultrasound unit (Vivid I, GE Healthcare, Wauwatosa, WI, USA), with simultaneous limb-lead electrocardiography and a 2.5-MHz phased-array transducer.  Participants were imaged in the left lateral decubitus position.  Images of M-mode, two  64  dimensional, and Doppler echocardiography were obtained.  Conventional apical two- and four-chamber views were obtained in order to quantify left ventricular volumes, longitudinal strain and strain rate (365, 366).  From the four chamber view, left ventricular internal length was measured from the apex to the level of the mitral annulus.  Parasternal short-axis images at the level of the papillary muscle were also obtained to determine rotation and rotation rate, as well as radial and circumferential strain and strain rates.  M-mode images were used to determine left ventricular posterior wall thickness, internal diameter, end systolic diameter and left ventricular mass.  Doppler recordings included pulsed Doppler with the cursor placed at the tip of the mitral leaflets to quantify early (E)  and late (A) ventricular filling velocities, as well as tissue Doppler imaging of the septal and lateral mitral annular tissue velocity (E’).  Each image included recording at least three consecutive cardiac cycles.  The left ventricular apical cross-section was imaged as circular as possible, with a clear image quality and at the level of the real apex (367).  High strain rates (80-90 frames per second) were also used for all strain imaging.  5.2.4 Data Analysis Offline analysis was used to determine ventricular volumes, dimensions and functions, and tissue velocities (EchoPAC, GE Healthcare, v. 110.1.1).  For all measurements and calculations, an average of measures from at least three consecutive cardiac cycles were utilized.  Body surface area was calculated from height and weight (368).  The linear method and Simpson’s bi-plane method were used to determine left ventricular mass and volumes, respectively (366).  Left ventricular mass was also indexed for height2.7, as indexing for body surface area can underestimate risks among obese individuals (369, 370).  Stroke volume index (SVI) and cardiac output index were determined  by indexing stroke volume and cardiac output for body surface area.  Calculations of ejection fraction were performed by determining stroke volume as a percentage of end diastolic volume.  Ventricular diameters measured from the parasternal long axis window were used to determine fractional shortening, expressed as a percentage.  M-mode images of left ventricular were analyzed to determined left ventricular end systolic diameter and left ventricular systolic posterior wall thickness.  Non-invasive calculations of left ventricular end systolic wall stress were determined as 0.334 x systolic blood pressure x left ventricular end-systolic diameter / (left ventricular systolic posterior wall thickness  x (1 + left ventricular systolic posterior wall thickness/ left ventricular end systolic diameter)), as a  65  measure of afterload (371, 372).  Relative wall thickness was determined as twice the diastolic left ventricular posterior wall thickness/ left ventricular internal diameter (373).  Diastolic function was evaluated using E/A ratio to determine the proportion of filling occurring early in the cardiac cycle.  End-systolic pressure was determined as 0.9 x brachial systolic blood pressure (374).  Arterial elastance (EA) was determined as end systolic pressure/stroke volume.  Ventricular elastance (ELV) was calculated as end systolic pressure /end systolic volume.  Both EA and ELV were indexed for body surface area to calculate EAI and ELVI, respectively.  Arterial-ventricular coupling was determined as the ratio of EAI/ELVI.  Arterial stiffness, and its inverse, arterial compliance were determined, independent of left ventricular dimensions, as the ratios of pulse pressure to stroke volume and stroke volume to pulse pressure, as measures of systolic function (375). Speckle-tracking analysis was applied to the four chamber images in order to quantify longitudinal strain and strain rates.  Radial and circumferential strain and strain rates, as well as rotation and rotation rates were quantified through speckle-tracking analysis of parasternal short-axis images at the papillary muscle level.  This speckle-tracking analysis was conducted on the entire width of the myocardium and separately on the endocardial (innermost) and epicardial (outermost) layers of myocardium.   5.2.5 Statistical Analysis Statistical analyses were performed using Statistica 9.0 (Stats Soft, Tulsa, OK).  Continuous variables were reported as mean and standard deviation, while categorical and binary factors were reported as percentages and counts.  Sex differences were evaluated using t-tests for independent samples for continuous variables and Pearson χ2 test for categorical variables.  Regression was used to compare cardiac measures with aerobic fitness using Pearson’s Correlation Coefficient.  Significance was set at p < 0.05 for all analyses.  5.3 Results  Similar demographics were identified between male and female participants (Table 5.1).  Overall, participants were young adults, generally single, well-educated, and employed, though  66  incomes were largely below $20 000 per year.  Participants were also free of hypertension, diabetes, and cardiovascular disease.     67  Table 5.1 Demographic characteristics of participants, by sex mean ± SD, n (%)   Male (n = 6) Female (n = 4) Overall (n = 10) P value      Age (yr) 26 ± 3 23 ± 3 25 ± 3 0.10 First Nations, n (%) 2 (33.3) 3 (75.0) 5 (50.0) 0.24 Métis, n (%) 4 (66.7) 1 (25.0) 5 (50.0) 0.24 Single, n (%) 5 (83.3) 2 (50.0) 7 (70.0) 0.31 Married or common-law, n (%) 1 (16.7) 1 (25.0) 2 (20.0) 0.78 Divorced or separated, n (%) 0 (0.0) 1 (25.0) 1 (10.0) 0.24 Less than high school diploma, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 High school diploma, n (%) 3 (50.0) 0 (0.0) 3 (30.0) 0.11 More than high school education, n (%) 3 (50.0 4 (100.0) 7 (70.0) 0.11 Employed, n (%) 5 (83.3) 4 (100.0) 9 (90.0) 0.45 Annual income  <$20 000 per year, n (%) 4 (66.7) 4 (100.0) 8 (80.0) 0.24 Smoker, n (%) 2 (33.3) 0 (0.0) 2 (20.0) 0.24 Binge drinker more than once a month, n (%) 4 (66.7) 3 (75.0) 7 (70.0) 0.81 Binge drinker ever, n (%) 5 (83.3) 3 (75.0) 8 (80.0) 0.78 Never binge drink, n (%) 1 (16.7) 1 (25.0) 2 (20.0) 0.78 Hypertension (measured), n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Cardiovascular disease, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Family history of cardiovascular disease *, n (%) 0 (0.0) 1 (25.0) 1 (10.0) 0.24 Diabetes, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Ethnic identification score† 2.7 ± 0.9 3.5 ± 0.9 3.0 ± 0.9 0.18 Ethnic affirmation score† 3.0 ± 0.5 3.6 ± 0.7 2.9 ± 1.2 0.62 Cultural identity score† 2.9 ± 0.6 3.5 ± 0.8 2.8 ± 1.2 0.74      N/A, not applicable; SD, standard deviation; *primary family member prior to age 55 (male) or 65 (female); †from Multigroup Ethnic Identity Measure (376)     Male participants were found to be taller and heavier with greater BMI and waist circumferences than females (Table 5.2).  However, obesity and abdominal obesity were similar across sexes.  All participants reported active levels of physical activity.  Males demonstrated greater grip strength values; however, six min walk distances, VO2max, and maximal heart rate were similar across sexes.   Blood pressures and heart rate were similar across both sexes, and generally found to fall within the normal range.    68  Table 5.2 Body composition and fitness characteristics of participants, by sex mean ± SD   Male (n = 6) Female (n = 4) Overall (n = 10) P value      Height (cm) 181.1 ± 6.9 166.5 ± 5.4 175.2 ± 9.6 0.01 Body mass (kg) 88.3 ± 11.4 62.9 ± 6.2 78.1 ± 16.0 0.004 BMI (kg·m-2) 26.9 ± 2.7 22.7 ± 2 25.2 ± 3.2 0.03 Body surface area (m2) 2.1 ± 0.2  1.7 ± 0.1  1.9 ± 0.2 0.003 Waist circumference (cm) 93.8 ± 7.3 73.9 ± 5.1 85.8 ± 12.0 0.002 Overweight, n (%) 3 (50.0) 1 (25.0) 4 (40.0) 0.49 Obesity, n (%) 1 (16.7) 0 (0.0) 1 (10.0) 0.45 Abdominal obesity, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Physically inactive, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Moderately active, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 1.00 Physically active, n (%) 6 (100.0) 4 (100.0) 10 (100.0) 1.00 Combined grip strength (kg) 111.7 ± 16.1 79.5 ± 20.2 98.8 ± 23.6 0.02 Six min walk distance (m) 736.7 ± 146.9 683.3 ± 59.4 715.3 ± 118.0 0.52 Direct VO2max (mL·kg-1·min-1) 41.8 ± 5.2 47.0 ± 7.9 43.9 ± 6.5 0.24 Maximal heart rate (beats·min-1) 181.8 ± 17.9 189.0 ± 19.2 184.7 ± 17.7 0.56 Supine systolic blood pressure (mmHg) 118.2 ± 13.3 112.0 ± 5.4 115.7 ± 10.9 0.40 Supine diastolic blood pressure (mmHg) 63.3 ± 12.0 59.3 ± 5.5 61.7 ± 9.7 0.56 Supine heart rate (beats·min-1) 62.4 ± 9.9 59.5 ± 11.6 61.2 ± 10.1 0.68      BMI, body mass index; SD, standard deviation; VO2max, maximal aerobic capacity         Sex differences in left ventricular mass were identified, as outlined on Table 5.3, though these differences were not apparent after adjusting for body surface area or height.  Systolic and diastolic dimensions of left ventricular length and internal diameter were found to be similar across males and females.  However, significantly larger left ventricular posterior wall thicknesses and septal wall thicknesses were identified among the male participants, during both systole and diastole.  Diastolic relative wall thickness was found to be similar between males and females, as were end systolic and diastolic volumes.      69  Table 5.3 Resting cardiac measurements of participants, by sex mean ± SD   Male (n = 6) Female (n = 4) Overall (n = 10) P value      Left ventricular mass (g) 182.9 ± 37.6 117.4 ± 7.4 156.7 ± 44.1 0.01 Left ventricular mass/body surface area (g·m-2) 87.58 ± 17.25 69.24 ± 7.70 80.24 ± 16.57 0.08 Left ventricular mass/height2.7  (g·m-2.7) 36.9 ± 7.8 29.8 ± 3.5 34.0 ± 7.1 0.13      Systolic     Left ventricular length (cm) 6.8 ± 0.8 7.3 ± 0.5 7.0 ± 0.7  0.27 Left ventricular internal diameter (cm) 3.30 ± 0.40 3.06 ± 0.38 3.20 ± 0.39 0.37 Left ventricular posterior wall thickness (cm) 1.57 ± 0.14 1.16 ± 0.34 1.41 ± 0.31 0.03 Septal wall thickness (cm) 1.59 ± 0.24 1.11 ± 0.17 1.40 ± 0.32 0.01 End systolic volume (mL) 72.3 ± 16.8 55.4 ± 13.4 65.6 ± 17.1  0.13      Diastolic     Left ventricular length (cm) 9.3 ± 0.7 9.2 ± 0.5 9.3 ± 0.6  0.68 Left ventricular internal diameter (cm) 4.86 ± 0.34 4.56 ± 0.19 4.74 ± 0.32 0.15 Left ventricular posterior wall thickness (cm) 0.99 ± 0.15 0.78 ± 0.09 0.91 ± 0.16 0.04 Septal wall thickness (cm) 1.05 ± 0.20 0.80 ± 0.11 0.95 ± 0.21 0.05 Relative wall thickness 0.41 ± 0.08 0.34 ± 0.05 0.38 ± 0.07  0.16 End diastolic volume (mL) 169.3 ± 33.5 131.3 ± 22.8 154.1 ± 36.0  0.10      SD, standard deviation         Cardiac output was found to be significantly greater among Aboriginal males, compared to females (Table 5.4).  A trend was identified for greater stroke volume among males.  However, systolic functional measurements were found to be similar across sexes, including SVI and cardiac output indexed for body surface area, ejection fraction, wall stress, velocities, and arterial stiffness and small arterial compliance.  Trends for greater systolic functional measurements of fractional shortening, systolic blood pressure/end systolic volume and ejection fraction/end diastolic volume among female participants were demonstrated.  Diastolic velocities and velocity ratios were also similar between males and females.     70  Table 5.4 Cardiac function of participants, by sex mean ± SD   Male (n = 6) Female (n = 4) Overall (n = 10) P value      Systolic     Stroke volume (mL) 97.0 ± 19.8 75.9 ± 10.7 88.6 ± 19.4  0.09 SVI (mL·m-2) 46.5 ± 9.0 44.4 ± 4.5 45.7 ± 7.2  0.69 Cardiac output (L·min-1) 5.9 ± 0.7 4.4 ± 0.6 5.3 ± 1.0  0.01 Cardiac output index (L·min-1·m-2) 2.8 ± 0.3 2.6 ± 0.4 2.7 ± 0.3 0.35 Ejection fraction (mL) 57.4 ± 1.3 58.2 ± 4.2 57.7 ± 2.7  0.67 Fractional shortening (%) 16.6 ± 4.8 21.0 ± 4.5 18.3 ± 5.0  0.19 Wall stress (kdyne·cm-2) 124.2 ± 29.2 144.5 ± 38.5 132.4 ± 32.8  0.37 Systolic blood pressure/end systolic volume (mmHg·mL-1) 1.53 ± 0.34 1.99 ± 0.55 1.71 ± 0.47 0.14 Ejection fraction/end diastolic volume  0.35 ± 0.09 0.46 ± 0.13 0.40 ± 0.11 0.16 E’ septal (m·s-1) 0.23 ± 0.03 0.22 ± 0.02 0.22 ± 0.03  0.80 E’ lateral (m·s-1) 0.24 ± 0.04 0.24 ± 0.00 0.24 ± 0.03  0.91 Pulse pressure/SVI (mmHg· m2·mL-1) 1.23 ± 0.31 1.19 ± 0.04 1.21 ± 0.23  0.79 SVI/pulse pressure (mL·mmHg-1·m-2) 0.85 ± 0.17 0.84 ± 0.03 0.85 ± 0.13  0.97      Diastolic     E (m·s-1) 0.73 ± 0.13 0.79 ± 0.10 0.75 ± 0.12 0.49 A (m·s-1) 0.33 ± 0.08 0.30 ± 0.08 0.32 ± 0.08 0.64 E/A  2.38 ± 0.72 2.71 ± 0.40 2.51 ± 0.61 0.44 E/E’ septal  3.26 ± 0.55 3.57 ± 0.29 3.38 ± 0.47 0.80 E/E’ lateral  3.07 ± 0.38 3.32 ± 0.41 3.17 ± 0.39  0.36      A, late ventricular diastolic filling velocity; E, early ventricular diastolic filling velocity; E’, mitral annular tissue velocity; SD, standard deviation; SVI, stroke volume indexed for body surface area          Arterial and ventricular elastance were found to be similar among male and female participants, as outlined on Table 5.5.  However, after indexing for body surface area, trends were identified for females having greater elastance values.  Arterial-ventricular coupling was similar between males and females.  Systemic vascular resistance trends suggested females may have greater resistances.  Strain in all three directions, longitudinal, radial, and circumferential,  71  as well as diastolic and systolic strain rates were similar between males and females.  Rotation and rotational velocity were also similar between sexes. Table 5.5 Cardiac elastance and mechanics of participants, by sex mean ± SD   Male (n = 6) Female (n = 4) Overall (n = 10) P value      Elastance     EA (mmHg·mL-1)  1.15 ± 0.37 1.35 ± 0.18 1.23 ± 0.31 0.36 EAI (mmHg·mL-1·m-2)  0.55 ± 0.17 0.80 ± 0.15 0.65 ± 0.20 0.05 ELV (mmHg·mL-1)  1.56 ± 0.49 1.91 ± 0.53 1.70 ± 0.51 0.31 ELVI (mmHg·mL-1·m-2)  0.75 ± 0.24 1.14 ± 0.40 0.91 ± 0.34 0.09 EAI/ELVI  0.74 ± 0.04 0.73 ± 0.12 0.74 ± 0.08 0.75 Systemic vascular resistance (mmHg·min·L-1)  13.93 ± 2.61 17.51 ± 2.20 15.36 ± 2.97 0.05      Peak (systole)     Rotation  (°) 4.36 ± 2.75 2.70 ± 2.50 3.70 ± 2.65 0.36 Rotation velocity (°·s-1) 41.84 ± 23.43 48.34 ± 20.96 44.43 ± 21.51 0.67 Longitudinal strain (%)  -18.37 ± 1.53 -18.82 ± 1.89 -18.55 ± 1.60 0.69 Longitudinal strain rate (s-1)  -1.02 ± 0.20 -0.99 ± 0.11 -1.01 ± 0.16 0.80 Radial strain (%)  24.98 ± 10.16 24.24 ± 13.17 24.68 ± 10.74 0.92 Radial strain rate (s-1)  1.37 ± 0.35 1.43 ± 0.35 1.39 ± 0.30 0.80 Circumferential strain (%)  -12.61 ± 3.55 -13.78 ± 2.97 -13.08 ± 3.21 0.60 Circumferential strain rate (s-1)  -0.82 ± 0.22 -0.86 ± 0.22 -0.84 ± 0.21 0.79      Peak (diastole)     Rotation velocity (°·s-1) -32.98 ± 12.70 -42.62 ± 15.87 -36.83 ± 14.08 0.32 Longitudinal strain rate (s-1)  1.40 ± 0.14 1.40 ± 0.22 1.40 ± 0.16 0.99 Radial strain rate (s-1)  -1.35 ± 0.48 -1.51 ± 0.79 -1.42 ± 0.58 0.69 Circumferential strain rate (s-1)  0.78 ± 0.36 1.02 ± 0.29 0.88 ± 0.34 0.29      EA , arterial elastance; EAI, arterial elastance indexed for body surface area; ELV, ventricular elastance; ELVI, ventricular elastance indexed for body surface area; SD, standard deviation         Left ventricular mass was not found to correlate with aerobic fitness in this population (Table 5.6).  Systolic left ventricular posterior wall thickness and internal diameter also did not correlate with aerobic fitness measures.  However, systolic left ventricular septal wall thickness and left ventricular end systolic volume were found to correlate with 6 min walk test distances, but not VO2max, and there was a trend for left ventricular length to correlate with 6 min walk  72  test distances (p = 0.07).  Diastolic left ventricular length, internal diameter, and relative wall thicknesses did not correlate with aerobic fitness.  However, left ventricular end diastolic volume positively correlated with 6 min walk test distances.   Table 5.6 Cardiac structural correlates of aerobic fitness among Aboriginal participants   VO2max 6 min Walk Test Correlate Β SE P value Β SE P value        Left ventricular mass (g) -0.30 0.30 0.34 0.37 0.29 0.24 Left ventricular mass/body surface area (g·m-2) -0.20 0.31 0.53 0.30 0.30 0.35 Left ventricular mass/height2.7 (g·m-2.7) -0.18 0.31 0.58 0.36 0.30 0.25        Systolic       Left ventricular length (cm) 0.16 0.31 0.61 0.54 0.27 0.07 Left ventricular internal diameter (cm) -0.29 0.30 0.35 0.04 0.32 0.90 Left ventricular posterior wall thickness (cm) -0.40 0.29 0.20 0.32 0.30 0.32 Septal wall thickness (cm) -0.33 0.30 0.29 0.61 0.25 0.04 End systolic volume (mL) 0.30 0.30 0.34 0.64 0.24 0.03        Diastolic       Left ventricular length (cm) 0.01 0.32 0.98 0.47 0.28 0.12 Left ventricular internal diameter (cm) -0.17 0.31 0.60 -0.02 0.32 0.96 Left ventricular posterior wall thickness (cm) -0.50 0.27 0.10 0.39 0.29 0.21 Septal wall thickness (cm) -0.07 0.32 0.82 0.50 0.27 0.10 Relative wall thickness -0.46 0.28 0.13 0.45 0.28 0.14 End diastolic volume (mL) 0.21 0.31 0.51 0.64 0.24 0.03  SD, standard deviation; VO2max, maximal aerobic capacity   In general, cardiac functional and mechanical measures were not found to correlate with aerobic fitness measures, as outlined on Table 5.7.  However, stroke volume was found to correlate with 6 min walk test distances, and SVI (p = 0.07) and ejection fraction/end diastolic volume (p = 0.10) demonstrate trends  for correlations with 6 min walk test distances.  Significant correlations with VO2max were not identified, though trends with ejection fraction (p = 0.08) and arterial-ventricular coupling (p = 0.07) were identified.   Table 5.7 Cardiac functional correlates of aerobic fitness among Aboriginal participants  73    VO2max 6 min Walk Test Correlate Β SE P value Β SE P value        Stroke volume (mL) -0.12 0.31 0.70 0.63 0.25 0.03 SVI (mL·m-2)  0.17 0.31 0.59 0.54 0.27 0.07 Cardiac output (L·min-1)  -0.34 0.30 0.28 0.45 0.28 0.14 Cardiac output index (L·min-1·m-2)  -0.10 0.31 0.76 0.29 0.30 0.36 Ejection fraction (mL)  0.53 0.27 0.08 -0.27 0.30 0.39 Fractional shortening (%)  0.47 0.28 0.12 -0.24 0.31 0.45 Wall stress (kdyne·cm-2)  0.08 0.32 0.80 -0.24 0.31 0.45 Systolic blood pressure/end systolic volume (mmHg·mL-1)  0.23 0.31 0.47 -0.49 0.28 0.11 Ejection fraction/end diastolic volume   0.21 0.31 0.52 -0.49 0.28 0.10 E’ septal (m·s-1)  0.11 0.31 0.73 0.29 0.30 0.37 E’ lateral (m·s-1)  0.21 0.31 0.51 0.12 0.31 0.71 Pulse pressure/SVI (mmHg· m2·mL-1)  -0.19 0.31 0.55 -0.42 0.29 0.17 SVI/pulse pressure (mL·mmHg-1·m-2)  0.07 0.32 0.84 0.54 0.27 0.07 E (m·s-1)  0.01 0.32 0.98 0.38 0.29 0.22 A (m·s-1)  0.30 0.30 0.34 0.004 0.32 0.99 E/A   0.31 0.30 0.33 0.21 0.31 0.51 E/E’ septal   0.06 0.32 0.87 0.17 0.31 0.58 E/E’ lateral   0.21 0.31 0.51 0.25 0.31 0.43 EA (mmHg·mL-1)  0.16 0.31 0.62 -0.47 0.28 0.13 EAI (mmHg·mL-1·m-2)  0.06 0.32 0.84 -0.48 0.28 0.11 ELV (mmHg·mL-1)  0.06 0.32 0.84 -0.47 0.28 0.12 ELVI (mmHg·mL-1·m-2)  0.20 0.31 0.53 -0.45 0.28 0.14 EAI/ELVI  -0.55 0.26 0.07 0.27 0.30 0.40 Systemic vascular resistance (mmHg·min·L-1)  -0.01 0.32 0.98 -0.32 0.30 0.30  A, late ventricular diastolic filling velocity; E, early ventricular diastolic filling velocity; E’, mitral annular tissue velocity; EA , arterial elastance; EAI, arterial elastance indexed for body surface area; ELV, ventricular elastance; ELVI, ventricular elastance indexed for body surface area; SD, standard deviation; SE, standard error; SVI, stroke volume indexed for body surface area; VO2max, maximal aerobic capacity  Cardiac rotations were not found to correlate with aerobic fitness measures.  Systolic strains and strain rates, as well as diastolic strains and strain rates were not found to correlate with aerobic fitness measures. Table 5.8 Cardiac functional correlates of aerobic fitness among Aboriginal participants  74    VO2max 6 min Walk Test Correlate Β SE P value Β SE P value        Peak (systole)       Rotation  (°) -0.54 0.30 0.10 0.03 0.35 0.94 Rotation velocity (°·s-1) -0.47 0.31 0.17 -0.12 0.35 0.74 Longitudinal strain (%)  -0.40 0.29 0.19 0.12 0.31 0.72 Longitudinal strain rate (s-1)  -0.48 0.28 0.11 0.28 0.30 0.37 Radial strain (%)  0.23 0.34 0.52 -0.19 0.35 0.59 Radial strain rate (s-1)  0.45 0.32 0.19 -0.35 0.33 0.32 Circumferential strain (%)  0.51 0.30 0.13 -0.08 0.35 0.83 Circumferential strain rate (s-1)  0.43 0.32 0.21 0.11 0.35 0.77        Peak (diastole)       Rotation velocity (°·s-1) 0.22 0.35 0.54 0.25 0.34 0.47 Longitudinal strain rate (s-1)  0.26 0.31 0.42 -0.09 0.32 0.79 Radial strain rate (s-1)  0.22 0.34 0.54 0.49 0.31 0.15 Circumferential strain rate (s-1)  -0.42 0.32 0.23 -0.13 0.35 0.71  SE, standard error; VO2max, maximal aerobic capacity   5.4 Discussion  This investigation evaluated cardiac structure and function at rest among a young, healthy sample of Aboriginal adults.  Previous cardiac assessments among Aboriginal adults have been limited to middle aged and older individuals in the Strong Heart Study, with particular attention to those with hypertension, diabetes, and other chronic health conditions (232, 234, 235, 370, 373).  Further, this investigation is the first to evaluate cardiac strain and elastance among Aboriginal populations.  Maximal aerobic capacity was not found to be related to resting cardiac measures, though stroke volume, end systolic volume, end diastolic volume, and systolic left ventricular posterior wall thickness were related to 6 min walk distances.     The population sampled in this investigation were healthy, young adults, free of chronic health conditions.  In comparison to the general Canadian Aboriginal population, the participants of this study were younger, with a mean age of 25 years, compared to the median 28 years in Canada (67).  This study also included a greater proportion of Métis individuals (50%), compared to the Canadian average (32.3%) (67).  Participants in this investigation also reported  75  greater educational attainments, employment, and lower chronic health conditions than the general Canadian Aboriginal population (12, 16, 29).  The younger, healthier status of participants in this investigation likely resulted in lower indications of left ventricular hypertrophy and heart failure.  However, as cardiovascular disease risk factors develop prior to the appearance of overt cardiovascular disease, indications of left ventricular hypertrophy may appear at a young, healthy age (116, 117, 328).    Normative measures of cardiac structure and function among Aboriginal adults are available based on a middle-aged sample from the Strong Heart Study of American Indians in the United States (232, 373, 377-381).  Ejection fractions identified in this investigation fall within the healthy range identified for Aboriginal adults (377).  Measures of E/A in this investigation were generally greater than two, which corresponds to a healthy range among young adults (378).  In comparison to Aboriginal adults with E/A above 1.5, this sample demonstrated greater relative wall thicknesses, smaller left ventricular mass, with similar ejection fraction (379).  By contrast, in relation to Aboriginal adults free of hypertension and diabetes, the Aboriginal adults evaluated in this investigation demonstrated larger left ventricular mass, stroke volume, cardiac output, similar dimensions and fractional shortening, and lower vascular resistance and arterial stiffness (232).  Aboriginal adults evaluated in this investigation demonstrate left ventricular mass, dimensions, and wall stress similar to middle-aged Aboriginal adults free of chronic heart failure, though greater peak E velocity, lower peak A velocity, and much greater E/A than all middle-aged Aboriginal adults evaluated (380).  Aboriginal males in this investigation demonstrated greater left ventricular mass, stroke volume, peak E velocity, and E/A ratios than both non-obese and obese middle-aged Aboriginal males in a previous investigation, though similar relative wall thicknesses and lower peak A velocity (381).  Female Aboriginal adults in this investigation demonstrate greater stroke volume and peak E velocity, lower left ventricular mass, peak A velocity, and E/A ratios, and similar relative wall thicknesses to middle-aged Female Aboriginal adults in a previous investigation (381).  Left ventricular dimensions and mass of female Aboriginal participants in this investigation are similar to that of middle-aged Aboriginal females with normal left ventricular functional status (373).  Conversely, male Aboriginal adults in this investigation demonstrated left ventricular mass, and dimensions similar to middle-aged Aboriginal males with mild left ventricular dysfunction, though more favourable ejection fraction, wall stress, and pulse pressure/SVI than middle-aged  76  Aboriginal adults with normal left ventricular function (373).  Overall, these results indicate this sample of Aboriginal adults demonstrate similar cardiac structure and function to other Aboriginal adults of similar health status, with higher measures of peak E velocity and E/A, with lower peak A velocity, likely due to the younger age of participants in this investigation.  Sex differences identified in this investigation are consistent with previous findings among young, healthy adults.  Left ventricular mass was found to be significantly different between males and females in a previous investigation of healthy, active adults (336).  Cote et al. also identified similar sex differences in arterial elastance (336), identifying greater arterial impedance among males (382).  These findings are similar to the trends identified in this investigation, where both arterial and ventricular elastance measures as well as arterial-ventricular coupling may be greater among females, indicating Aboriginal males may have greater ventricular impedance.  Aboriginal adults have previously been found to have sex differences in stroke volume, SVI, left ventricular mass, and left ventricular mass indexed for body surface area or height, similar to sex differences and trends identified in this investigation (381).  Cardiac assessments among Aboriginal adults have previously identified sex differences in ejection fraction (373, 377), which were not identified among this sample.  Similarly, male and female Aboriginal adults in this investigation were found to have similar relative wall thicknesses, peak E and A velocities, and E/A ratios; however, these measures have previously been found to be different between Aboriginal male and female adults (381).  While it is possible the small sample size in this investigation prevented the identification of sex differences in ejection fraction, peak E and A velocities, and E/A ratios, the measures identified were similar between males and females.  Subsequently, these sex differences may not have appeared as the individuals evaluated in this investigation are at least 30 years younger than any previous investigation among Aboriginal adults.    Measures of cardiac structure and function were not found to be related to VO2max.  The lack of associations in this investigation is the result of resting cardiac assessments utilized.  Correlations between resting measures of cardiac function and exercise performance may not be identified (245, 383).  Correlations with aerobic fitness may be more evident with measures of cardiac function during exercise.  Measures of cardiac function during aerobic exercise are  77  known to be associated with aerobic capacity and may help in estimating long term prognosis (224, 225, 245).  This investigation adds to the existing literature evaluating middle-aged and older Aboriginal adults.  As cardiovascular disease progression begins prior to the appearance of overt disease age (116, 117, 328), the evaluation of younger, apparently healthy individuals is important for understanding the disease progression and risk development among this high risk population.  Longitudinal strain is known to be a correlate of left ventricular contractility, and indicates regional myocardial dysfunction (223).  Further, elastance and arterial-ventricular coupling provide insight into the interaction between the arterial system and the left ventricular, evaluating stroke work and energetic efficiency (384).  The inclusion of these measures adds to current understanding of cardiac function among Aboriginal populations.    This investigation is limited by the small sample size.  A larger sample size would likely identify relationships between cardiac structure and function and VO2max.  As this sample is young and free of chronic health conditions, these results may not represent the Aboriginal population as a whole, or the young adult Aboriginal population as a whole.  However, these individuals demonstrated similar results to healthy middle-aged Aboriginal adults, suggesting these results are consistent with other Aboriginal samples free of chronic health conditions.  As Aboriginal populations consist of many distinct nations, each with their own cultural history, language, and beliefs, a single sample of individuals may not accurately reflect the whole sample (18, 61, 364).  Further, as this study included individuals from several different nations, including both First Nations and Métis individuals, the results may not accurately reflect any of the individual groups sampled.     5.5 Conclusion  Aboriginal adults were found to have healthy cardiac structure and function.  Sex differences in left ventricular mass and dimensions, stroke volume, and elastance were identified.  Resting measures of cardiac structure and function were not found to be related to VO2max; however, cardiac function measures during exercise or immediately post-exercise may provide greater insight into the effects of aerobic fitness on cardiac function.   78  6. Ethnic Differences in Vascular Function and the Relationship with Blood Pressure4  6.1 Introduction A significant proportion of Western society experiences hypertension, with estimates of 24.8-29.2% of the population affected (3, 23, 24).  Hypertension is a strong predictor of cardiovascular disease and is associated with vascular disease and cardiovascular disease progression (159, 161).  Further, hypertension is known to be associated with subclinical vascular markers of cardiovascular disease, including intima-media thickness (IMT), pulse wave velocity (PWV), barorceptor sensitivity (BRS), and arterial compliance (343, 351, 359, 360). Cardiovascular disease disproportionately affects Aboriginal populations in Canada and the United States (12, 50, 364).  Conversely, Aboriginal populations in North America experience lower blood pressures and hypertension rates than their non-Aboriginal peers (329-332).  Despite these apparently conflicting experiences, vascular measures and subclinical vascular disease progression have never been directly compared between Aboriginal and non-Aboriginal populations.  The only available investigation comparing vascular measures among ethnic groups including Aboriginal identified a lower augmentation index among Aboriginal populations, and thus less progression of cardiovascular disease among this population compared to other groups (19).    This investigation aimed to evaluate vascular measures of IMT, BRS, arterial compliance, and PWV among a sample of Aboriginal and European adults in British Columbia, Canada.  The objective was to compare IMT, BRS, arterial compliance, and PWV across both ethnic groups and to compare the relationships between these measures and mean arterial blood pressure between ethnic groups.  It was hypothesized  that differences in IMT, BRS, arterial compliance, and PWV between Aboriginal and European adults would be identified, and the relationships between these measures and mean arterial blood pressure would also vary with ethnicity.                                                    4 A version of Chapter 6 has been prepared for publication. Foulds H.J.A., Bredin S.S.D. Warburton D.E.R.. Ethnic differences in vascular function and the relationship with blood pressure.   79  6.2 Methods From June 2012 to August 2013, 58 Aboriginal adults, and 58 age and sex matched European adults,  ≥19 yr, from four communities around British Columbia, Canada underwent an assessment of vascular measures.  Participants represent a range of ages, from 19 to 91 yr.  Power calculations using G*Power 3.1.3 (333) from previous investigations have identified ethnic differences in IMT with samples of 45 middle aged adults per ethnic group (385), and differences in PWV with samples of 3 young adults per ethnic group (269).  Ethics approval was obtained through the Clinical Research Ethics Board at the University of British Columbia and written informed consent was obtained from each participant prior to data collection.  Additionally, each Aboriginal community reviewed and approved the project prior to participation of members of their respective communities.  Testing was conducted within the local Aboriginal communities with the assistance of Aboriginal students and volunteers.   Individual characteristics and blood pressure were assessed as described in section 4.2.2.  Participants then completed a vascular assessment as outlined in section 4.2.3.  Physical fitness measures as described in 4.2.4 were also completed.   Statistical analyses were performed using Statistica 9.0 (Stats Soft, Tulsa, OK).  Continuous variables were reported as mean and standard deviation, while categorical and binary factors were reported as percentages and counts.  Normal distribution was tested, and as large arterial compliance was found not to be normally distributed, the natural log transformation was used for analysis.  Differences between ethnic groups were evaluated using t-tests for independent samples for continuous variables and Pearson χ2 test for categorical variables.  Pulse wave velocity and IMT comparisons were performed using ANCOVA to adjust for mean arterial pressure, age, and where appropriate, sex (342).  Regression was used to compare vascular measures across the blood pressure spectrum.  Differences in the regression slopes of vascular measures and blood pressure between ethnic groups were evaluated using ANCOVA slope by slope analysis.  Regression analysis of IMT and PWV were adjusted for age, sex and mean arterial pressure.  Discrete correlates of hypertension rates were compared across correlate groups and across ethnic groups using t-tests for independent samples.  Continuous correlates of hypertension rates were compared within ethnic group using regression and between ethnic groups using slope by slope ANCOVA analysis.  Significance was set at p < 0.05 for all analyses.   80  6.3 Results  Characteristics and demographic information about participants, by ethnic group, are outlined in Table 6.1.  Participants of Aboriginal and European descent were of similar ages.  Similar proportions of each group were single or married/common-law, however, greater proportions of Aboriginal participants were divorced or separated.  The prevalence rates of participants with only high school education or more than high school education were similar, though trends suggest Aboriginal participants may have greater proportions of individuals with less than high school education.  Employment status and the proportion of individuals with incomes less than $20 000 per year were similar across both groups, though a trend for greater proportion of European participants being retired or homemakers may exist.  Binge drinking habits were similar across both groups, however, Aboriginal participants reported significantly greater smoking rates.   Table 6.1 Characteristics and demographics of participants, by ethnic group mean ± SD, n (%)   Aboriginal      (n = 58) European         (n = 58) P value     Age (years) 39 ± 18 42 ± 18 0.37 Female, n (%) 31 (53.4) 31 (53.4) 1.00 Single, n (%) 22 (37.9) 21 (36.2) 0.85 Married or common-law, n (%) 25 (43.1) 32 (55.2) 0.20 Divorced or separated, n (%) 10 (17.2) 3 (5.2) 0.04 Less than high school diploma, n (%) 3 (5.2) 0 (0.0) 0.08 High school diploma, n (%) 5 (8.6) 9 (15.5) 0.26 More than high school education, n (%) 50 (86.2) 49 (84.5) 0.80 Unemployed, n (%) 7 (12.1) 6 (10.3) 0.77 Employed, n (%) 47 (81.0) 41 (70.7) 0.20 Retired or homemaker, n (%) 4 (6.9) 11 (19.0) 0.05 Annual income less than $20 000 per year, n (%) 21 (36.2) 15 (25.9) 0.23 Smoker, n (%) 12 (20.7) 1 (1.7) 0.001 Binge drink more than once a month, n (%) 10 (17.2) 7 (12.1) 0.44 Binge drink ever, n (%) 33 (56.9) 35 (60.3) 0.71 Never binge drink, n (%) 25 (43.1) 23 (39.7) 0.71     SD, standard deviation   81   Across Aboriginal and European ethnic groups, similar health status and health measures were observed (Table 6.2).  Blood pressures, including seated, standing, and supine were similar across both groups.  Measured hypertension rates and use of anti-hypertension medication were also similar across both groups, though trends suggest hypertension awareness may have been lower among the Aboriginal group.  Both groups were of a similar height, body mass, BMI, waist circumference, and obesity and abdominal obesity prevalence.  Rates of cardiovascular disease, family history of cardiovascular disease and diabetes were also similar between Aboriginal and European participants.  Physical activity levels were similar across both ethnicities, as were grip strength and six min walk distances.     82  Table 6.2 Health status and measures of participants, by ethnic group mean ± SD, n (%)   Aboriginal           (n = 58) European         (n = 58) P value     Seated systolic blood pressure (mmHg) 118.6 ± 17.1 117.2 ± 21.0 0.69 Seated diastolic blood pressure (mmHg) 72.2 ± 8.6 70.9 ± 10.7 0.48 Seated heart rate (beats·min-1) 68.0 ± 11.4 69.6 ± 11.7 0.47 Standing systolic blood pressure (mmHg) 118.6 ± 17.2 121.0 ± 17.8 0.53 Standing diastolic blood pressure (mmHg) 78.9 ± 12.4 79.0 ± 10.6 0.97 Supine systolic blood pressure (mmHg) 121.7 ± 16.0 121.1 ± 16.5 0.85 Supine diastolic blood pressure (mmHg) 66.8 ± 8.8 67.9 ± 11.0 0.54 Hypertension (reported), n (%) 5 (8.6) 12 (20.7) 0.07 Hypertension (measured), n (%) 8 (13.8) 12 (20.7) 0.33 Use anti-hypertension medication, n (%) 2 (3.4) 6 (10.3) 0.15 Borderline hypertension, n (%)* 40 (69.0) 34 (58.6) 0.76 Height (cm) 171.1 ± 10.5 171.3 ± 8.0 0.93 Body mass (kg) 82.0 ± 22.0 79.0 ± 18.6 0.43 BMI (kg·m-2) 27.9 ± 7.0 27.0 ± 6.1 0.43 Waist circumference (cm) 89.6 ± 17.5 88.8 ± 16.0 0.81 Cardiovascular disease, n (%) 0 (0.0) 1 (1.7) 0.32 Family history of cardiovascular disease **, n (%) 5 (8.6) 7 (12.1) 0.55 Diabetes, n (%) 1 (1.7) 3 (5.2) 0.31 Obesity, n (%) 15 (25.9) 13 (22.4) 0.67 Abdominal obesity, n (%) 18 (31.0) 18 (31.0) 1.00 Physically inactive, n (%) 8 (13.8) 6 (10.3) 0.57 Moderately active, n (%) 4 (6.9) 6 (10.3) 0.51 Physically active, n (%) 46 (79.3) 46 (79.3) 1.00 Combined grip strength (kg) 80.8 ± 25.1 77.2 ± 25.1 0.44 Six min walk distance (m) 608.1 ± 123.1 591.4 ± 106.2 0.43         BMI, body mass index; SD, standard deviation; * systolic blood pressure >130 mmHg or diastolic blood pressure >85 mmHg ; **primary family member prior to age 55 (male) or 65 (female)   Vascular measures were largely similar across both groups, as outlined in Table 6.3.  Similar mean IMT measures were recorded between Aboriginal and European participants.  Arterial compliance and PWV measures were also similar between the two groups.  Average BRS measures were similar across both groups.  Similar HRV was observed across both ethnic groups, with the exception of low frequency:high frequency ratios, and possibly HRV SDNN,  83  which were greater among European populations.  Mean NN and BPV low frequency power were similar between Aboriginal and European populations, though Aboriginal populations had significantly greater systolic SDNN and RMSSD. Table 6.3 Vascular measures of participants, by ethnic group mean ± SD   Aboriginal     (n = 58) European        (n = 58) P value     Right IMT (mm) 0.58 ± 0.11 0.61 ± 0.13 0.32 Left IMT (mm) 0.59 ± 0.12 0.61 ± 0.11 0.65 Overall IMT (mm) 0.59 ± 0.11 0.61 ± 0.11 0.44 Central PWV (m·s-1) 5.3 ± 2.4 6.2 ± 3.4 0.22 Peripheral PWV (m·s-1) 12.1 ± 4.0 12.9 ± 4.8 0.37 Large arterial compliance (mL·mmHg-1 x 10) 16.1 ± 6.4 17.5 ± 6.6 0.26 Small arterial compliance (mL·mmHg-1 x 100) 7.5 ± 3.3 8.0 ± 3.4 0.49 Spectral BRS (ms·mmHg-1) 13.3 ± 9.0 11.9 ± 5.4 0.38 Up Sequence BRS (ms·mmHg-1) 19.5 ± 12.4 19.9 ± 11.1 0.46 Down Sequence BRS (ms·mmHg-1) 20.1 ± 13.1 18.4 ± 10.6 0.16 All Sequence BRS (ms·mmHg-1) 19.9 ± 11.7 19.4 ± 10.4 0.85 HRV mean NN interval (ms) 971.6 ± 154.2 1011.8 ± 162.5 0.19 HRV SDNN (ms) 45.0 ± 27.9 45.5 ± 35.9 0.07 HRV RMSSD (ms) 67.5 ± 54.9 67.1 ± 53.4 0.84 HRV low frequency power (n.u.) 43.9 ± 21.2 43.8 ± 21.5 0.91 HRV high frequency power (n.u.) 44.1 ± 20.9 46.3 ± 21.2 0.93 HRV low frequency·high frequency-1 1.6 ± 1.6 1.7 ± 2.4 0.01 BPV mean NN systolic blood pressure (mmHg) 117.8 ± 19.1 120.1 ± 20.2 0.55 BPV mean NN diastolic blood pressure (mmHg) 67.5 ± 10.7 69.5 ± 12.6 0.38 BPV Systolic SDNN (mmHg) 3.1 ± 2.5 2.9 ± 1.8 0.03 BPV Systolic RMSSD (mmHg) 4.9 ± 4.1 4.4 ± 2.9 0.02 BPV low frequency power (n.u.) 60.2 ± 19.0 58.3 ± 22.2 0.29     BPV, blood pressure variability; BRS, baroreceptor sensitivity; HRV, heart rate variability; IMT, intima-media thickness; NN, normal to normal; PWV, pulse wave velocity; RMSSD, root mean squared of successive differences; SD, standard deviation   Differences in vascular measures between males of Aboriginal and European descent were generally not observed (Table 6.4).  A trend was identified where European males may have demonstrated greater central pulse wave velocity than Aboriginal males.  Measures of  84  seated resting blood pressure, IMT, arterial compliance, BRS, HRV, and BPV were similar between both groups.   Table 6.4 Vascular measures of Male participants, by ethnic group mean ± SD   Aboriginal     (n = 27) European        (n = 27) P value     Systolic blood pressure (mmHg) 122.1 ± 16.9 121.7 ± 19.5 0.94 Diastolic blood pressure (mmHg) 72.5 ± 9.4 72.9 ± 11.9 0.87 Hypertensive, n (%) 3 (11.1) 7 (25.9) 0.17 Right IMT (mm) 0.61 ± 0.13 0.61 ± 0.15 0.54 Left IMT (mm) 0.60 ± 0.15 0.61 ± 0.11 0.71 Overall IMT (mm) 0.61 ± 0.13 0.61 ± 0.13 0.53 Central PWV (m·s-1) 5.6 ± 2.5 7.4 ± 3.6 0.07 Peripheral PWV (m·s-1) 11.8 ± 4.1 13.4 ± 5.2 0.30 Large arterial compliance (mL·mmHg-1 x 10) 17.7 ± 6.5 17.6 ± 6.2 0.95 Small arterial compliance (mL·mmHg-1 x 100) 8.9 ± 3.7 8.6 ± 4.1 0.77 Spectral BRS (ms·mmHg-1) 10.0 ± 6.6 12.8 ± 5.1 0.12 Up Sequence BRS (ms·mmHg-1) 17.9 ± 13.2 18.7 ± 10.0 0.81 Down Sequence BRS (ms·mmHg-1) 16.0 ± 8.7 18.2 ± 9.1 0.41 All Sequence BRS (ms·mmHg-1) 16.9 ± 10.5 19.3 ± 9.5 0.42 HRV mean NN interval (ms) 979.8 ± 184.9 1022.4 ± 166.6 0.40 HRV SDNN (ms) 44.9 ± 28.1 39.0 ± 23.7 0.43 HRV RMSSD (ms) 70.3 ± 60.3 57.7 ± 40.8 0.39 HRV low frequency power (n.u.) 47.5 ± 22.7 48.8 ± 23.9 0.85 HRV high frequency power (n.u.) 38.8 ± 22.7 42.0 ± 22.5 0.63 HRV low frequency·high frequency-1 2.0 ± 1.8 2.4 ± 3.3 0.58 BPV mean NN systolic blood pressure (mmHg) 125.7 ± 21.0 126.5 ± 23.4 0.89 BPV mean NN diastolic blood pressure (mmHg) 68.1 ± 11.9 72.7 ± 14.5 0.25 BPV Systolic SDNN (mmHg) 3.6 ± 3.0 2.5 ± 1.1 0.11 BPV Systolic RMSSD (mmHg) 5.1 ± 4.5 3.7 ± 2.3 0.17 BPV low frequency power (n.u.) 69.1 ± 16.4 66.1 ± 19.8 0.59     BPV, blood pressure variability; BRS, baroreceptor sensitivity; HRV, heart rate variability; IMT, intima-media thickness; NN, normal to normal; PWV, pulse wave velocity; RMSSD, root mean squared of successive differences; SD, standard deviation   Female Aboriginal and European participants demonstrated similar vascular measures (Table 6.5), with the exception of IMT.  Overall IMT and right IMT were found to be greater among European females compared to Aboriginal females.  Seated resting blood pressure,  85  central and peripheral PWV, BPV, and HRV were found to be similar among both groups.  Large arterial compliance was similar between both ethnicities, though a trend suggests European females may have demonstrated greater small arterial compliance.  Spectral BRS was significantly greater among Aboriginal females, while sequence measures of BRS were similar across both groups.   Table 6.5 Vascular measures of Female participants, by ethnic group mean ± SD   Aboriginal     (n = 31) European        (n = 31) P value     Systolic blood pressure (mmHg) 115.5 ± 16.9 113.2 ± 21.7 0.64 Diastolic blood pressure (mmHg) 71.9 ± 7.9 69.1 ± 9.4 0.21 Hypertensive, n (%) 5 (16.1) 5 (16.1) 1.00 Right IMT (mm) 0.56 ± 0.08 0.61 ± 0.10 0.004 Left IMT (mm) 0.59 ± 0.10 0.60 ± 0.11 0.29 Overall IMT (mm) 0.57 ± 0.08 0.61 ± 0.10 0.03 Central PWV (m·s-1) 5.1 ± 2.3 5.0 ± 2.7 0.88 Peripheral PWV (m·s-1) 12.3 ± 3.9 12.5 ± 4.5 0.84 Large arterial compliance (mL·mmHg-1 x 10) 14.6 ± 6.0 17.3 ± 7.0 0.11 Small arterial compliance (mL·mmHg-1 x 100) 6.3 ± 2.3 7.4 ± 2.5 0.08 Spectral BRS (ms·mmHg-1) 16.1 ± 9.9 11.2 ± 5.7 0.03 Up Sequence BRS (ms·mmHg-1) 21.3 ± 11.5 21.1 ± 12.1 0.96 Down Sequence BRS (ms·mmHg-1) 24.9 ± 15.7 18.6 ± 12.1 0.14 All Sequence BRS (ms·mmHg-1) 23.0 ± 12.4 19.5 ± 11.4 0.32 HRV mean NN interval (ms) 964.2 ± 123.5 1003.1 ± 161.4 0.31 HRV SDNN (ms) 45.1 ± 28.1 50.8 ± 43.3 0.56 HRV RMSSD (ms) 65.1 ± 50.6 75.0 ± 61.6 0.51 HRV low frequency power (n.u.) 41.0 ± 19.7 39.5 ± 18.7 0.78 HRV high frequency power (n.u.) 48.5 ± 18.7 50.0 ± 19.7 0.78 HRV low frequency·high frequency-1 1.3 ± 1.3 1.0 ± 0.8 0.37 BPV mean NN systolic blood pressure (mmHg) 111.1 ± 14.6 114.6 ± 15.5 0.39 BPV mean NN diastolic blood pressure (mmHg) 67.0 ± 9.8 66.9 ± 10.1 0.95 BPV Systolic SDNN (mmHg) 2.7 ± 1.9 3.3 ± 2.2 0.35 BPV Systolic RMSSD (mmHg) 4.6 ± 3.8 5.0 ± 3.3 0.72 BPV low frequency power (n.u.) 52.0 ± 17.7 51.6 ± 22.3 0.94     BPV, blood pressure variability; BRS, baroreceptor sensitivity; HRV, heart rate variability; IMT, intima-media thickness; NN, normal to normal; PWV, pulse wave velocity; RMSSD, root mean squared of successive differences; SD, standard deviation   86  The relationships between vascular measures and blood pressures were different between Aboriginal and European participants.  Among Aboriginal and European populations, both small (Figure 6-1 A) and large (Figure 6-1 B) arterial compliance demonstrated significant negative relationships where lower arterial compliance was associated with greater mean arterial pressures.  However, the relationship with small arterial compliance was stronger among the Aboriginal population while the relationship with large arterial compliance was stronger among the European population.  Significantly different relationships were identified among both spectral (Figure 6-1 C) and sequence method (Figure 6-1 D) BRS between Aboriginal and European populations.  Aboriginal populations demonstrated significant negative relationships between BRS and mean arterial pressure where greater BRS values were observed among those with lower mean arterial pressures.  Conversely, no significant relationship could be determined between spectral BRS and mean arterial pressure among the European population.  An interaction was identified for the relationships between spectral BRS and mean arterial pressure between Aboriginal and European adults.  Neither Aboriginal nor European populations demonstrated relationships between central PWV and mean arterial pressure (Figure 6-1 E).  While significantly positive relationships were demonstrated between overall mean IMT and mean arterial pressure (Figure 6-1 F) among Aboriginal and European populations, the relationship was not found to be different between Aboriginal and European adults.  Overall, both ethnic groups demonstrated relationships between vascular measures and mean arterial pressures.  However, these relationships were more significant and stronger among the Aboriginal population.   87  Large Arterial Compliance (ms.mmHg-1 x 10)0510152025303540Small Arterial Compliance (ms.mmHg-1 x 100)02468101214161820AboriginalEuropeanAboriginal RegressionEuropean RegressionSequence Baroreceptor Sensitivity (ms.mmHg-1)0102030405060Spectral Baroreceptor Sensitivity (ms.mmHg-1)010203040Mean Arterial Pressure (mmHg)60 80 100 120Intima-Media Thicness (mm)0.40.50.60.70.80.91.01.1Mean Arterial Pressure (mmHg)60 80 100 120Central Pulse-Wave Velocity (m.s-1)024681012141618r=-0.42, r2=0.16, p=0.001r=0.64, r2=0.40, p<0.001r=0.40, r2=0.15, p=0.003r=0.19, r2=0.02,p=0.16r=0.16, r2=0.01, p=0.25r=-0.49, r2=0.22 p=0.001r=-0.26, r2=0.05, p=0.08r=-0.48, r2=0.21, p=0.001r=-0.11, r2=-0.01, p=0.44r=-0.39,r2=0.14, p=0.003r=-0.30, r2=0.07, p=0.02r=-0.52,r2=0.26,  p<0.001BDFECA Figure 6.1 Ethnic differences in the relationship between mean arterial pressure and vascular measures of: large arterial compliance (A, p < 0.001), small arterial compliance (B, p < 0.001), spectral method baroreceptor sensitivity (C, p < 0.001*), sequence method baroreceptor sensitivity (D, p < 0.001), central pulse wave velocity (E, p = 0.16) and intima-media thickness (F, p = 0.09).  Asterisk (*) indicates a significant interaction between Aboriginal and European regression slopes.   88   In comparing discrete correlates of hypertension, differences in hypertension rates were observed between categories (Table 6.6).  Individuals who are not married or in common-law relationships and those who earn less than $20 000 annually were found to have significantly lower rates of hypertension than their counterparts, among both Aboriginal and European populations.  Educational status and employment status were not found to influence rates of hypertension among either group.  Similar relationships of physical activity and binge drinking behaviour were observed between Aboriginal and European populations, where Aboriginal populations at least moderately active and European populations who binge drink demonstrate significantly lower hypertension rates than their counterparts.  European populations who are at least moderately active and Aboriginal populations who binge drink may also experience significantly lower hypertension rates.  Differential associations with hypertension rates were found among obesity and abdominal obesity categories between Aboriginal and European populations.  Among European populations, obesity and abdominal obesity were found to be significantly associated with increased rates of hypertension.  However, this relationship was not observed among the Aboriginal population.      89  Table 6.6 Discrete correlates of hypertension rates among Aboriginal and European participants, n (%)   Aboriginal European P value†   n Hypertension Rate n Hypertension Rate       Not obese 43 4 (9.3) 45 6 (13.3) 0.56 Obese 15 4 (26.7) 13 6 (46.2) 0.30 P value  0.10  0.01        Not abdominally obese 40 4 (10.0) 40 4 (10.0) 1.00 Abdominally obese 18 4 (22.2) 18 8 (44.4) 0.17 P value  0.22  0.002        Moderately active or active 50 5 (10.0) 52 9 (17.3) 0.29 Physically inactive 8 3 (37.5) 6 3 (50.0) 0.67 P value  0.04  0.06        More than high school 50 6 (12.0) 49 9 (18.4) 0.38 High school or less 8 2 (25.0) 9 3 (33.3) 0.73 P value  0.33  0.32        Employed 47 5 (10.6) 41 6 (14.6) 0.58 Not employed 11 3 (27.3) 17 6 (35.3) 0.67 P value  0.16  0.08        Married or common-law 25 8 (32.0) 32 11 (34.4) 0.85 Not married or common-law 33 0 (0.0) 26 1 (3.8) 0.26 P value  <0.001  0.004        Annual income $20 000 or more 37 8 (21.6) 43 12 (27.9) 0.52 Annual income <$20 000 21 0 (0.0) 15 0 (0.0) 1.00 P value  0.02  0.02        Never binge drink 25 6 (24.0) 23 9 (39.1) 0.27 Binge drink ever 33 2 (6.1) 35 3 (8.6) 0.70 P value  0.05  0.004        SD, standard deviation; †between ethnic groups     90  The relationships between continuous correlates and hypertension rates varied between Aboriginal and European populations (Table 6.7).  Age was found to be a significant predictor of hypertension among both Aboriginal and European participants, while trends for physical activity scores as predictors of hypertension were identified for both groups.  By contrast, BMI and waist circumference were significant predictors of hypertension among European populations, but did not demonstrate a relationship with hypertension among Aboriginal populations.  Conversely, ethnic identity, ethnic affinity, and cultural identity were found to be significantly associated with hypertension among Aboriginal populations, but not European populations.   Table 6.7 Continuous correlates of hypertension rates among Aboriginal and European participants   Aboriginal     (n = 58) European     (n = 58)  P value† Correlate Β SE P value Β SE P value         Age (yr) 0.01 0.002 <0.001 0.01 0.003 0.001 <0.001 BMI (kg·m-2) 0.003 0.01 0.62 0.04 0.01 <0.001 <0.001 Waist circumference (cm) 0.003 0.003 0.23 0.01 0.003 <0.001 <0.001 Godin-Shephard physical activity score‡ -0.002 0.001 0.08 -0.003 0.002 0.06 0.03 Ethnic identity score -0.14 0.04 0.003 -0.05 0.07 0.51 0.02 Ethnic affinity score -0.11 0.05 0.02 -0.02 0.06 0.78 0.11 Cultural identity score -0.13 0.05 0.01 -0.03 0.07 0.65 0.04         BMI, body mass index; SE, standard error; †between ethnic groups; ‡(337)  6.4 Discussion  This investigation is unique in evaluating the vascular status and hypertension experience among Aboriginal and European populations, including a comprehensive analysis of influencing factors.  Aboriginal populations have been identified as having greater experience of cardiovascular disease, and greater prevalence of risk factors including diabetes and obesity (12, 29, 126, 189, 386).  Conversely, Aboriginal populations have also been found to have lower rates of hypertension than their non-Aboriginal peers (329-332).  Subsequently, understanding the vascular status and hypertension experience among this population is important for maintaining the health of Aboriginal populations and reducing ethnic and cultural inequalities.     91  As participants were recruited through similar methods, and come from the same communities, the two comparison populations likely experience similar exposures and risk factors.  The lack of differences in characteristics, demographics, and health status measures further supports these populations as being similar.  In Canada, Aboriginal populations currently experience lower rates of education, employment, and lower income levels (16).  These two sample populations are largely similar in terms of education, income, and employment attainments.  Further, while Aboriginal populations are generally found to have greater experiences of obesity and diabetes (12, 29, 126, 189, 386), these two populations demonstrate similar rates of obesity, diabetes, and cardiovascular disease.  Overall, these two populations demonstrate similar health status and characteristics, thus minimizing the confounding variables influencing vascular measures and blood pressure.  Blood pressures were found to be similar between Aboriginal and European populations.  Hypertension rates of 20.7% among the European population are in line with 24.8-29.2% hypertension rates estimated worldwide (24).  This study identified the Aboriginal hypertension rate at 13.8%.  While not statistically lower than the European population, a 7% reduction in hypertension rates may be clinically relevant.  A larger sample size may have identified this hypertension rate as significantly lower than the European counterparts.  These potential differences in hypertension rates are consistent with previous literature of lower hypertension rates among North American Indigenous populations (329-332).   Vascular measures were found to be similar between Aboriginal and European populations, though some sex specific comparisons identified more favourable vascular measures among Aboriginal participants.  Measures of IMT from this investigation are lower than those identified among an American Indian population (198), even among those free of diabetes and obesity (196), and lower than a Canadian sample free of metabolic syndrome (197).  However, a similarly aged non-Aboriginal (European and South Asian) population was found to have lower IMT values than the means obtained in this investigation (347).  Overall, the IMT values obtained in this investigation are within normal ranges for a generally healthy population.  The PWV measures from this investigation were lower than reference population values even among the lowest age group, and those free of chronic health conditions (343).  However, these values are higher than those observed previously among ultra-marathon runners in the same laboratory (268).  Arterial compliance among this sample was higher compared to a middle aged  92  female population (352) and a population of older adults (353).  The PWV and arterial compliance values obtained in this study are within the normal ranges and consistent with trends of lower PWV among more active individuals, and higher arterial compliance among younger populations.  Baroreceptor sensitivity measures from this investigation are higher than those found for 30-40 year old reference samples, though within the normal range for 20-40 year old samples (156).  Overall, vascular measures from this investigation are generally healthier than that found in reference samples published in the literature.  These findings likely reflect the generally healthy status of participants and the low rates of diabetes, obesity, physical inactivity, and unemployment, and the high educational attainments of participants in this study.   The relationship between blood pressure and vascular measures was found to differ between Aboriginal and European populations.  In general, Aboriginal populations were found to have a stronger relationship between blood pressure and vascular measures.  Aboriginal populations have more favourable vascular measures at lower blood pressures, compared to their European counterparts, and poorer vascular measures at higher blood pressures.  At mean arterial pressures greater than approximately 100 mmHg, corresponding to a blood pressure of 135 mmHg systolic and 85 mmHg diastolic, Aboriginal populations demonstrate poorer vascular measures than their non-Aboriginal counterparts.  Subsequently, experiences of elevated blood pressures, even within the borderline hypertension range, may lead to increased vascular disease and subsequent cardiovascular disease among Aboriginal populations relative to their European counterparts.  As the population as a whole has experienced increased blood pressures over the past 50 years or so (37), there is likely a greater proportion of Aboriginal individuals with higher blood pressures now than in past years.  Subsequently, the poorer vascular experience among Aboriginal populations at borderline hypertension and higher blood pressures may contribute to the increased rates of cardiovascular disease currently experienced by this population (12, 29, 126, 189, 386). Ethnic differences in the relationship between vasculature and blood pressure may result from differences in environments.  Differences in the relationships between alleles and hypertension have previously been identified across generations within the same family (387).  As early nutrition, birth weight and environments have changed in recent decades, the epigenetic effects alter the relationships between alleles and hypertension (387).  Aboriginal populations in Canada currently experience poorer environmental factors including lower incomes,  93  employment, education and other health outcome measures (16, 61).  As such, the epigenetic effect of environment may cause the relationship between vasculature and blood pressure to be stronger among Aboriginal populations relative to Europeans.  Physiologically, the ethnic differences in these relationships may result from alterations in the sympathetic nervous system balance at rest.  Sympathetic nervous system balance among Aboriginal adults was significantly associated to blood pressure, as indicated by BRS.  Differences in sympathetic output could be resulting in chronic vasoconstriction, which is associated with inward remodelling of the vasculature and subsequent hypertension (388).  This remodelling would result in greater blood pressures, as well as greater vascular resistance and lower arterial compliance (388).   Alternatively, differences in sensitivity of nitric oxide between the two ethnic groups would vary the sensitivity of the vasculature to vasodilate in response to increased pressures.  Ethnic differences in nitric oxide receptors have been identified, which may alter the sensitivity of endothelium to respond to nitric oxide, leading to differences in cardiovascular disease outcomes (389-391). Among non-Aboriginal populations including South Asian, East Asian and European populations, obesity is known to be associated with hypertension (41, 44, 392).  These trends are identified among the European participants of this investigation where obesity and abdominal obesity, BMI, and waist circumference are associated with increased hypertension rates.  Conversely, these relationships were not identified among the Aboriginal participants.  These results are consistent with American Indian populations where reduced relationships between blood pressure and obesity have been identified (45, 47).  Despite greater experiences of obesity among the current Aboriginal populations (29, 189), these experiences do not appear to be influencing the blood pressures of this population.  This differential relationship may reflect ethnic differences in the renin-angiotensin aldosterone system (393), as previously identified among Canadian Aboriginal populations in the Sandy Lake area (55).  The renin-angiotensin aldosterone system is directly linked with adipocytes, where large dysfunctional adipocytes produce angiotensinogen, and visceral adipose tissue produces greater angiotensinogen than subcutaneous adipose tissue (394).  Angiotensinogen leads to vasoconstriction, increasing blood pressure and resistance (394).  Further, Angiotensin II influences the development of large dysfunctional adipocytes (394).  Genetic variations reducing the active effect of angiotensin II on developing adipocytes would lead to lower rates of hypertension in obese individuals as fewer  94  metabolically active large, dysfunctional adipocytes would be developed.  Similarly, ethnic variations causing decreased angiotensinogen production in adipocytes would reduce the effect of obesity on hypertension.   The association between hypertension rates and marital status and low income are likely influenced by the age of participants.  As a number of younger adults participated in this investigation, these individuals likely represent a large proportion of the single participants, those who make less than $20 000 annually and those who binge drink (395-397).  Conversely, the young age of these individuals is likely associated with lower blood pressure and hypertension rates, thus creating the trend for lower blood pressures among those who are single, who have lower annual incomes and those who binge drink.   Ethnic identity, ethnic affinity, and cultural identity were found to be related to hypertension rates among Aboriginal populations, but not European.  These findings may result from the disproportionately high stress loads experienced by Aboriginal populations due to historical trauma and forced acculturation (74, 75).  Further, blood pressure and hypertension have previously been linked to experiences of racism and anger inhibition (398-401).  Stronger scores for ethnic identity reflect individuals who feel they belong to their ethnic group, have a sense of pride in their ethnic identity, have a secure sense of belonging to their ethnic group and have positive attitudes towards their ethnic group (402).  The historical trauma, intergenerational trauma and racial discrimination faced by Aboriginal populations may be reflected in these ethnic identity scores (61, 76, 403).  As such, Aboriginal individuals who are facing these traumas may experience greater stress and subsequent greater blood pressure (74, 75, 404).  However, as personal and family histories of residential school and foster care experiences, as well as histories of mental illness or other trauma were not evaluated directly in this investigation.  As such, the association of cultural identity scores cannot be directly linked to historical trauma. This investigation is limited by the sample size.  A larger sample size may have identified significant differences between Aboriginal and European populations in measures of BRS or PWV.  Because this sample of participants is largely healthy and relatively free of chronic health conditions, the results obtained in this investigation may not reflect the non-Aboriginal population.  Conversely, the utilization of a fairly healthy population with similar education, employment, marital, and income experiences may reduce some of the confounding factors in  95  evaluating blood pressure and vascular measures.  As Aboriginal populations represent many distinct nations with their own history, culture, and background, results from one nation may not reflect the experiences of another nation (18, 61, 364).  Further, as this investigation combines samples from several locations, the findings may not perfectly reflect any one of the individual locations.   6.5 Conclusion  Aboriginal and European adults of similar age, sex, demographics, and health status experience similar vascular health status.  However, vascular health status is more strongly associated with mean arterial pressure among Aboriginal populations.  Aboriginal participants demonstrated associations of hypertension rates with cultural identity, while European participants demonstrated associations of hypertension rate with obesity.    96  7. Ethnic Differences in the Vascular Responses to Exercise5 7.1 Introduction Physical activity is an important component of maintaining health and preventing cardiovascular disease (259, 405, 406).  Vascular measures including IMT, BRS, PWV, and arterial compliance are also known to be influenced by physical activity (89, 162, 267, 272, 273, 280, 288).  Ethnic differences in vascular blood pressure and PWV responses to exercise have been identified among European and African-American populations (193, 194, 269, 315).   While ethnic differences in vascular responses to exercise have been identified among African-American populations, Aboriginal populations have not been investigated.  This investigation evaluated the vascular responses to maximal and submaximal aerobic exercise among a sample of Aboriginal and European adults in British Columbia, Canada.  The objective was to compare the vascular BRS, PWV, and arterial compliance responses to exercise among Aboriginal and European age- and sex-matched adults.  It was hypothesized that Aboriginal adults would demonstrate greater changes in vascular measures of BRS, PWV, and arterial compliance following exercise.    7.2 Methods 7.2.1 Participants and Ethical Approval From February to August 2013, 12 Aboriginal adults and 12 age and sex matched European adults,  19-44 yr and free of chronic health conditions, underwent vascular assessments pre and post maximal and submaximal aerobic exercise.  Based on power calculations with G*Power 3.1.3 (333) from previous ethnic comparisons of PWV and blood pressure among young healthy adults, changes resulting from aerobic exercise, ethnic differences can be detected with sample sizes of 12 per group (193).  Ethics approval was obtained through the Clinical Research Ethics Board at the University of British Columbia and written informed consent was obtained from each participant prior to data collection.  Additionally, Aboriginal elders from the community reviewed and approved the project prior to the study commencing.  Testing was                                                  5 A version of Chapter 7 has been published. Foulds H.J.A., Bredin S.S.D. Warburton D.E.R Ethnic differences in the vascular responses to aerobic exercise. Medicine and Science in Sports and Exercise, in press.  97  conducted at the University of British Columbia Cardiovascular Physiology and Rehabilitation laboratory, with the assistance of Aboriginal students.   7.2.2 Experimental Procedure Individual characteristics and baseline measures were collected on the first day of the investigation as outlined in section 4.2.2 upon arrival at the testing location.  The second day of testing included identical measures of body mass and blood pressures.  On both days, following five minutes of supine rest, vascular pre-exercise measurements, were obtained as described in section 4.2.3.  Each testing day consisted of an aerobic exercise session, which was followed by identical vascular assessment and blood pressure measures.  On the second day of testing, following the post-exercise vascular assessment, participants completed the physical fitness measures outlined in section 4.2.4. 7.2.3 Aerobic Exercise On the first day of testing, participants completed a maximal aerobic power test (VO2max) on a cycle ergometer (Ergometrics er800s, Ergoline, Bitz, Germany).  The progressive exercise test was performed at 80 rpm, beginning at 50 W.  The workload was increased by 25 W every two minutes until reaching the ventilatory threshold.  After the ventilatory threshold, power output was increased by 25 W per minute until exhaustion.  Heart rate and expired gas analysis (Ergocard, Medisoft, Sorinnes, Belgium) were recorded throughout rest, exercise, and one minute post exercise.  Maximal aerobic capacity was determined as the highest aerobic output sustained over 15s.   On the second day of exercise, participants completed 30 min of seated cycling on the same ergometer at 60% of VO2max, with identical heart rate and expired gas analysis throughout.  Following both sets of exercise, participants repeated vascular assessments and seated and standing blood pressure measures.   7.2.4 Statistical Analysis Statistical analyses were performed using Statistica 9.0 (Stats Soft, Tulsa, OK).  Characteristics were reported as mean and standard deviation for continuous variables and as percentages and counts for categorical and binary factors.  Baseline differences between ethnic groups were evaluated using t-tests for independent samples for continuous variables and  98  Pearson χ2 test for categorical variables.  Pulse wave velocity comparisons were performed using ANCOVA to adjust for mean arterial pressure (342).  Repeated measure analysis of variance (ANOVA), with Fisher’s least significant difference post-hoc analysis was used to identify differences in responses to exercise between Aboriginal and European adults.  Differences in the PWV response to exercise between ethnic groups were evaluated using ANCOVA analysis of post-exercise measures adjusted for pre-exercise measures, mean arterial pressure and heart rate (193).  Differences in the responses to maximal and submaximal exercise were evaluated through paired t-tests of the changes from pre to post-exercise.  Analysis of changes in vascular measures with exercise  in relation to fitness levels were conducted using Pearson’s Correlations of the changes in vascular measures with VO2max.  Significance was set at p < 0.05 for all analyses.   7.3 Results 7.3.1 Baseline and Demographic Characteristics Twelve Aboriginal adults and twelve age- and sex-matched European adults underwent vascular assessments pre and post-maximal aerobic exercise.  Only 11 Aboriginal individuals returned for a submaximal aerobic exercise session with pre and post-exercise vascular assessments, as such only 11 individuals of each ethnic group are included in the submaximal assessment.  As outlined on Table 7.1, participants of each ethnic group were of a similar age, sex , and marital status.  Aboriginal participants included half First Nations and half Métis individuals.  All participants had completed at least high school education, though a trend suggests European participants may have been more likely to have more than high school education.  The majority of participants from each ethnic group were married.  Aboriginal participants were more likely to be smokers, while binge drinking behaviours were similar across both groups.  Only one participant was found to be hypertensive, while no participants reported personal histories of cardiovascular disease or diabetes.  Family history of cardiovascular disease among primary family members was low among both group.  Significant differences in ethnic and cultural identity scores were identified between Aboriginal and European participants.  Aboriginal participants reported greater ethnic identification, ethnic affirmation, and cultural identity compared to their European counterparts.      99  Table 7.1 Demographic characteristics of participants, by ethnic group mean ± SD, n (%)   Aboriginal (n = 12) European (n = 12) P value     Age (yr) 26 ± 6 25 ± 7 0.68 First Nations, n (%) 6 (50.0) N/A  Métis, n (%) 6 (50.0) N/A  Female, n (%) 4 (33.3) 4 (33.3) 1.00 Single, n (%) 8 (66.7) 9 (75.0) 0.67 Married or common-law, n (%) 2 (16.7) 3 (25.0) 0.63 Divorced or separated, n (%) 2 (16.7) 0 (0.0) 0.15 Less than high school diploma, n (%) 0 (0.0) 0 (0.0) 1.00 High school diploma, n (%) 3 (25.0) 0 (0.0) 0.07 More than high school education, n (%) 9 (75.0) 12 (100.0) 0.07 Employed, n (%) 10 (83.3) 10 (83.3) 1.00 Annual income  <$20 000 per year, n (%) 9 (75.0) 5 (41.7) 0.11 Smoker, n (%) 4 (33.3) 0 (0.0) 0.03 Binge drinker more than once a month, n (%) 9 (75.0) 7 (58.3) 0.41 Binge drinker ever, n (%) 10 (83.3) 12 (100.0) 0.15 Never binge drink, n (%) 2 (16.7) 0 (0.0) 0.15 Hypertension (measured), n (%) 0 (0.0) 1 (8.3) 0.33 Cardiovascular disease, n (%) 0 (0.0) 0 (0.0) 1.00 Family history of cardiovascular disease *, n (%) 1 (8.3) 1 (8.3) 1.00 Diabetes, n (%) 0 (0.0) 0 (0.0) 1.00 Ethnic identification score† 2.9 ± 0.9 2.2 ± 0.4 0.02 Ethnic affirmation score† 3.2 ± 0.6 2.7 ± 0.4 0.03 Cultural identity score† 3.1 ± 0.7 2.6 ± 0.5 0.05     N/A, not applicable; SD, standard deviation; *primary family member prior to age 55 (male) or 65 (female); †from Multigroup Ethnic Identity Measure (376)         Physical body composition and fitness measures were found to be similar among Aboriginal and European participants (Table 7.2).  Participants were found to be of similar height, body mass, BMI, and waist circumference.  Body mass of participants, both overall and among each ethnic group, was not found to change between the two testing days.  Similar proportions of participants were found to be obese or overweight, with only 58.3% of participants of each ethnic group demonstrating normal body mass.  Based on self-reported physical activity levels, all participants were found to be physically active.  Physical fitness measures were also similar across both ethnic groups, including grip strength, six min walk  100  distance and VO2max.  Maximal heart rate were also found to be similar between Aboriginal and European participants.   Table 7.2 Body composition and fitness characteristics of participants, by ethnic group mean ± SD, n (%)   Aboriginal (n = 12) European (n = 12) P value     Height (cm) 177.3 ± 10.0 174.6 ± 8.4 0.48 Pre maximal exercise body mass (kg) 79.4 ± 14.8 73.3 ± 10.6 0.26 Pre submaximal exercise body mass (kg) 79.4 ± 15.8 73.4 ± 10.5 0.29 BMI (kg·m-2) 25.0 ± 2.9 24.0 ± 2.5 0.35 Waist circumference (cm) 85.8 ± 11.3 79.5 ± 7.2 0.12 Overweight, n (%) 4 (33.3) 5 (41.7) 0.69 Obesity, n (%) 1 (8.3) 0 (0.0) 0.33 Abdominal obesity, n (%) 0 (0.0) 0 (0.0) 1.00 Physically inactive, n (%) 0 (0.0) 0 (0.0) 1.00 Moderately active, n (%) 0 (0.0) 0 (0.0) 1.00 Physically active, n (%) 12 (100.0) 12 (100.0) 1.00 Combined grip strength (kg) 101.5 ± 22.3 97.4 ± 25.5 0.68 Six min walk distance (m) 711.7 ± 109.9 652.5 ± 124.8 0.23 VO2max (mL·kg-1·min-1) 43.6 ± 6 47.8 ± 10 0.22 Maximal heart rate (beats·min-1) 181.6 ± 19.2 180.1 ± 7.3 0.80     BMI, body mass index; SD, standard deviation; VO2max, maximal aerobic capacity        7.3.2 Vascular Responses to Exercise  Prior to both maximal and submaximal exercise, resting blood pressures were generally similar between Aboriginal and European participants (Table 7.3).  Following maximal aerobic exercise, Aboriginal participants demonstrated greater seated diastolic blood pressures, while European participants demonstrated lower standing systolic blood pressures and possibly lower supine systolic blood pressures.  Systolic blood pressure responses following maximal aerobic exercise were similar between Aboriginal and European participants. However, trends suggest diastolic blood pressure responses to maximal aerobic exercise, including seated and supine measures may have been different between groups, with European participants experiencing a decrease in diastolic blood pressure and Aboriginal participants experiencing an increase.  In response to submaximal exercise, Aboriginal blood pressures did not change, while European  101  systolic blood pressures (seated and standing) decreased.  In general, no significant differences in the blood pressure responses to submaximal exercise were identified between ethnic groups, though seated systolic blood pressure responses demonstrated a trend for ethnic differneces, with European populations experiencing a greater decrease post-submaximal exercise.      102  Table 7.3 Blood pressures of participants in response to exercise, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Seated systolic blood pressure (mmHg)     Pre-Exercise Post-Exercise 107.2 ± 8.1  117.5 ± 16.4  0.07 114.5 ± 13.7  116.6 ± 11.3  0.70 110.9 ± 13.5  114.3 ± 13.9   113.2 ± 15.6  109.3 ± 11.9   P value 0.40 0.48 0.28 0.60 0.004 0.08        Seated diastolic blood pressure (mmHg)     Pre-Exercise Post-Exercise 65.6 ± 7.6  68.2 ± 9.7  0.21 71.2 ± 11.5  66.3 ± 8.4  0.67 72.3 ± 13.6  71.2 ± 14.3   69.8 ± 8.6  66.4 ± 7.7   P value 0.04 0.65 0.07 0.13 0.94 0.30        Standing systolic blood pressure (mmHg)     Pre-Exercise Post-Exercise 119.3 ± 14.9  126.5 ± 16.3  0.30 118.5 ± 14.1  120.9 ± 13.5  0.70 116.6 ± 15.0  113.9 ± 20.5   118.6 ± 17.9  113.7 ± 13.3   P value 0.59 0.02 0.17 0.96 0.04 0.12        Standing diastolic blood pressure (mmHg)     Pre-Exercise Post-Exercise 78.1 ± 18.5  82.8 ± 12.2  0.43 83.2 ± 12.3  76.3 ± 7.7  0.14 80.1 ± 9.5  77.7 ± 15.8   77.9 ± 13.2  76.4 ± 9.1   P value 0.61 0.20 0.20 0.12 0.98 0.26        Supine systolic blood pressure (mmHg)     Pre-Exercise Post-Exercise 116.5 ± 10.0  120.4 ± 10.3  0.35 118.5 ± 13.0  119.6 ± 8.9  0.82 116.6 ± 12.4  119.2 ± 7.6   119.5 ± 13.6  119.3 ± 8.3   P value 0.41 0.08 0.56 0.34 0.96 0.65        Supine diastolic blood pressure (mmHg)     Pre-Exercise Post-Exercise 62.0 ± 9.2  68.3 ± 11.1  0.10 63.7 ± 9.3  64.3 ± 5.3  0.85 64.0 ± 9.9  64.0 ± 5.7   65.3 ± 11.5  64.4 ± 5.9   P value 0.34 0.70 0.07 0.70 0.57 0.52        SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise   Following maximal exercise, central PWV (Figure 7-1A) and peripheral PWV (Figure 7-1B) were found to be similar.  Among both European and Aboriginal participants, no changes in   103  PWV were identified following submaximal aerobic exercise.  Pre-exercise measures of central and peripheral PWV were also similar between the two ethnic groups.Pre-Maximal Post-Maximal N.a.N. Pre-SubmaximalPost-SubmaximalPeripheral Pulse-Wave Velocity (m.s-1)0510152025Central Pulse-Wave Velocity (m.s-1)23456789Aboriginal European AB Figure 7.1 Central (A) and peripheral (B) pulse wave velocity before (Pre) and after (Post) maximal and submaximal aerobic exercise among Aboriginal and European adults.  Asterisk (*) indicate significant difference from pre- to post, p < 0.05. Dagger (†) indicates significant difference in change from Aboriginal, p < 0.05.    104   Changes in IMT were not observed with either maximal or submaximal exercise among Aboriginal or European participants (Table 7.4).  Further, pre-exercise measures of right and left IMT were similar between the two groups.  Both large and small artery compliance were found to be similar between Aboriginal and European participants prior to exercise.  Large and small artery compliance were also not found to change following either maximal or submaximal exercise among either ethnic group, and both ethnic groups demonstrated similar arterial compliance responses to exercise.  Prior to both maximal and submaximal exercise, Aboriginal and European participants demonstrated similar total and systemic vascular resistance.  Following maximal exercise, both Aboriginal and European participants demonstrated reductions in both total and systemic vascular resistance.  These ethnic groups experienced similar changes in total vascular resistance, while trends suggested European participants may have experienced greater systemic vascular resistance reductions resulting from maximal aerobic exercise.  Following submaximal exercise, total vascular resistance was not found to change among either ethnic group.  However, while Aboriginal participants experienced no change in systemic vascular resistance following submaximal exercise, European participants experienced a decrease.  Overall, the responses of total and systemic vascular resistance to submaximal exercise were found to be similar between Aboriginal and European participants.      105  Table 7.4 Vascular measures of participants in response to exercise, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Overall IMT (mm)      Pre-Exercise Post-Exercise 0.53 ± 0.07 0.52 ± 0.06  0.15 0.49 ± 0.03 5 0.50 ± 0.02 0 0.91 Post-Exercise 0.51 ± 0.04  0.52 ± 0.03   0.49 ± 0.04  0.50 ± 0.04   P valu  0.33 0.67 0.32 0.81 0.69 0.91        Large arterial compliance (mL·mmHg-1 x 10)    Pre-Exercise Post-Exercise 19.5 ± 3.0  19.7 ± 5.4  0.94 21.4 ± 7.6  17.9 ± 3.6  0.17 Post-Exercise 21.8 ± 8.2  21.5 ± 10.1   19.6 ± 4.6  18.1 ± 6.5   P valu  0.33 0.46 0.86 0.39 0.91 0.49        Small arterial compliance (mL·mmHg-1 x 100)    Pre-Exercise Post-Exercise 9.5 ± 2.7  9.0 ± 2.1  0.79 9.0 ± 2.8  10.1 ± 3.1  0.39 Post-Exercise 10.1 ± 3.9  10.3 ± 5.8   9.6 ± 3.3  9.2 ± 3.5   P valu  0.58 0.30 0.73 0.42 0.25 0.17        Total vascular resistance (dyne·s·cm-5)     Pre-Exercise Post-Exercise 105.0 ± 14.6  123.0 ± 28.4  0.14 105.4 ± 30.3  124.5 ± 25.3  0.16 Post-Exercise 82.8 ± 33.6  89.3 ± 36.2   95.6 ± 27.7  113.7 ± 39.6   P valu  0.02 0.001 0.37 0.32 0.27 0.94        Systemic vascular resistance (dyne∙s∙cm-5)    Pre-Exercise Post-Exercise 1070.3 ± 111.6  1237.5 ± 177.0  0.02 1088.4 ± 167.8  1177.8 ± 198.2  0.24 Post-Exercise 980.8 ± 158.0  1038.8 ± 205.5   1056.2 ± 134.4  1080.2 ± 193.7   P valu  0.04 <0.001 0.07 0.29 0.004 0.14        IMT, intima-media thickness; SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise   Baroreceptor sensitivity responses to exercise are outlined on Table 7.5.  Prior to maximal exercise, similar measures of spectral, up sequence and overall sequence BRS were observed between Aboriginal and European participants.  However, European participants were found to have greater down sequence BRS.  Following maximal exercise, both Aboriginal and European participants experienced reductions in all measures of BRS.  These reductions in BRS following maximal exercise were similar among both ethnic groups.  Prior to submaximal exercise, Aboriginal participants demonstrated significantly lower measures of BRS than their  106  European counterparts including spectral, up sequence, down sequence and overall sequence methods.  Following submaximal exercise, European participants experienced significant reductions in all measures of BRS, while Aboriginal participants did not experience a change in BRS.  These two ethnic groups were found to experience different effects of submaximal exercise on all measures of BRS. Table 7.5 Baroreflex response to exercise among Aboriginal and European participants, by ethnic group mean ± SD, n (%)  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Spectral BRS (ms·mmHg-1)     Pre-Exercise Post-Exercise 15.2 ± 8.6  16.2 ± 6.4  0.46 9.2 ± 4.3  15.8 ± 8.3  0.01 6.8 ± 4.7  6.8 ± 4.0   11.5 ± 6.7  8.9 ± 5.7   P value <0.001 <0.001 0.47 0.41 0.01 0.02        Up sequence BRS (ms·mmHg-1)     Pre-Exercise Post-Exercise 23.0 ± 12.4  27.1 ± 10.8  0.31 15.5 ± 6.0 27.9 ± 10.4  0.003 10.8 ± 5.1  13.3 ± 11.6   12.9 ± 5.0  15.5 ± 8.9   P value 0.003 0.002 0.77 0.57 0.001 0.04        Down sequence BRS (ms·mmHg-1)     Pre-Exercise Post-Exercise 19.9 ± 9.2  24.3 ± 11.5  0.03 12.3 ± 6.8  25.6 ± 10.9  0.003 8.7 ± 3.6  10.3 ± 5.7   13.8 ± 9.3  15.3 ± 10.0   P value 0.01 <0.001 0.19 0.85 0.01 0.045        Overall sequence BRS (ms·mmHg-1)     Pre-Exercise Post-Exercise 22.2 ± 10.3  27.0 ± 10.9  0.13 14.6 ± 5.4  26.2 ± 10.5  0.004 9.7 ± 4.0  11.8 ± 8.3   16.5 ± 11.0  15.4 ± 9.4   P value 0.001 <0.001 0.40 0.48 0.01 0.02        BRS, baroreceptor sensitivity; SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise  Comparisons of changes in vascular measures between maximal and submaximal aerobic exercise are outlined on Table 7.6.  In general, maximal and submaximal exercise elicited similar changes in vascular measures.  Similar effects of maximal and submaximal aerobic exercise on blood pressures, PWV, IMT, and arterial compliance were identified.  Total vascular resistance  107  and systemic vascular resistance were found to decrease more greatly following maximal aerobic exercise, as compared to submaximal exercise.  Down and overall sequence BRS changes were also found to be greater following maximal aerobic exercise, though up sequence BRS responded similarly to each exercise stimulus. Table 7.6 The changes in vascular measures resulting from maximal and submaximal aerobic exercise, mean ± SD   Maximal Aerobic Exercise (n = 22) Submaximal Aerobic Exercise (n = 22) P value     Seated systolic blood pressure (mmHg) 0.7 ± 15.0 -4.3 ± 8.1 0.13 Seated diastolic blood pressure (mmHg) 1.8 ± 11.3 1.6 ± 6.4 0.92 Standing systolic blood pressure (mmHg) -8.6 ± 17.8 -3.5 ± 11.0 0.21 Standing diastolic blood pressure (mmHg) -0.4 ± 13.6 -2.6 ± 10.8 0.56 Supine systolic blood pressure (mmHg) -1.1 ± 5.8 0.3 ± 6.1 0.44 Supine diastolic blood pressure (mmHg) -1.7 ± 8.6 0.8 ± 5.4 0.26 Central PWV (m·s-1) 0.01 ± 2.2 -0.7 ± 2.5 0.22 Peripheral PWV (m·s-1) -0.1 ± 4.4 -0.7 ± 7.8 0.67 Right IMT (mm) -0.01 ± 0.10 0.002 ± 0.02 0.71 Left IMT (mm) -0.02 ± 0.08 0.004 ± 0.03 0.21 Overall IMT (mm) -0.01 ± 0.07 0.003 ± 0.02 0.33 Large arterial compliance (mL·mmHg-1 x 10) 2.3 ± 8.3 -0.8 ± 6.5 0.14 Small arterial compliance (mL·mmHg-1 x 100) 1.1 ± 4.2 -0.1 ± 2.8 0.18 Total vascular resistance (dyne·s·cm-5) -28.7 ± 31.8 -10.3 ± 31.1 0.049 Systemic vascular resistance (dyne·s·cm-5) -163.3 ± 135.9 -64.9 ± 102.2 0.002 Spectral BRS (ms·mmHg-1) -8.8 ± 5.5 -2.8 ± 9.9 0.07 Up sequence BRS (ms·mmHg-1) -13.9 ± 13.5 -10.2 ± 10.8 0.26 Down sequence BRS (ms·mmHg-1) -13.2 ± 10.5 -8.1 ± 10.7 0.0499 Overall sequence BRS (ms·mmHg-1) -16.2 ± 9.9 -6.7 ± 12.5 0.01     BRS, baroreceptor sensitivity; IMT, intima-media thickness; PWV, pulse wave velocity; SD, standard deviation         Correlations of aerobic fitness with changes in vascular measures are outlined on Table 7.7.  In general, the vascular response to aerobic exercise was not found to be related to VO2max.  Central PWV and supine systolic blood pressure responses to maximal exercise were found to be related to fitness where individuals with higher fitness experienced lower reductions in these  108  vascular measures.  In response to submaximal aerobic exercise, seated and standing systolic blood pressure were found to be related to fitness, where those with lower fitness experienced greater reductions in these systolic blood pressure measures post-exercise.  Table 7.7 The association of VO2max with changes in vascular measures following maximal and submaximal aerobic exercise   Maximal Aerobic Exercise    (n = 24) Submaximal Aerobic Exercise     (n = 22) Correlate Β SE P value β SE P value        Seated systolic blood pressure (mmHg) 0.11 0.39 0.79 -0.52 0.18 0.01 Seated diastolic blood pressure (mmHg) -0.33 0.27 0.25 -0.27 0.16 0.11 Standing systolic blood pressure (mmHg) -0.22 0.44 0.62 -0.85 0.22 0.001 Standing diastolic blood pressure (mmHg) 0.15 0.35 0.66 -0.40 0.28 0.16 Supine systolic blood pressure (mmHg) -0.35 0.13 0.01 -0.02 0.16 0.93 Supine diastolic blood pressure (mmHg) -0.37 0.21 0.09 -0.01 0.14 0.95 Central PWV (m·s-1) -0.12 0.05 0.02 -0.02 0.07 0.78 Peripheral PWV (m·s-1) -0.08 0.12 0.51 -0.06 0.21 0.79 Right IMT (mm) 0.001 0.002 0.57 0.001 0.001 0.13 Left IMT (mm) 0.001 0.002 0.79 0.001 0.001 0.27 Overall IMT (mm) 0.0005 0.002 0.79 0.001 0.001 0.09 Large arterial compliance  (mL·mmHg-1 x 10) -0.29 0.19 0.15 0.06 0.17 0.73 Small arterial compliance  (mL·mmHg-1 x 100) -0.12 0.10 0.23 -0.07 0.07 0.37 Total vascular resistance (dyne·s·cm-5) 0.63 0.76 0.42 0.27 0.83 0.75 Systemic vascular resistance  (dyne·s·cm-5) -1.56 3.71 0.68 -1.22 2.71 0.66 Spectral BRS (ms·mmHg-1) -0.10 0.15 0.54 0.14 0.27 0.60 Up sequence BRS (ms·mmHg-1) 0.41 0.35 0.25 0.005 0.34 0.99 Down sequence BRS (ms·mmHg-1) -0.13 0.26 0.62 0.18 0.38 0.65 Overall sequence BRS (ms·mmHg-1) -0.26 0.25 0.32 -0.04 0.40 0.92        BRS, baroreceptor sensitivity; IMT, intima-media thickness; PWV, pulse wave velocity; SD, standard deviation   109  7.4 Discussion This investigation was unique in evaluating the vascular responses to exercise among Aboriginal populations.  Healthy Aboriginal and European adults were identified as demonstrating similar vascular responses to aerobic exercise including both maximal and submaximal intensities.  These vascular responses were generally limited to decreases in vascular resistance and BRS post-exercise.  However, reductions in blood pressures were limited to European participants.  Overall, maximal and submaximal aerobic exercise produced similar vascular responses.  However, maximal aerobic exercise was more beneficial for reducing total and systemic vascular resistance, and caused greater reductions in BRS measures.  Additionally, while BRS responses to maximal exercise were similar among the two groups, responses to submaximal exercise differed with Europeans experiencing declines and Aboriginal participants experiencing increases.  In this healthy, adult population, aerobic fitness measured through VO2max was not found to be related to the degree of vascular response to maximal or submaximal aerobic exercise.  Vascular responses to exercise were observed for measures such as BRS and vascular resistance, which are influenced by the autonomic nervous system (281, 407).  During exercise, increases in sympathetic neural activity (407) and blood pressure (408) occur, along with decreases in total vascular resistance (281).  Subsequently, following exercise, the reduction in sympathetic input and increases in parasympathetic input, lead to reductions in heart rate, while blood pressures and vascular resistance are reduced below resting levels (281).  By contrast, more structural based vascular measures such as IMT, did not change with exercise.  This is expected, as arterial remodelling can take several weeks, thus changes do not occur following an acute bout of exercise (266).  In this investigation, intermediary vascular measures which are influenced by both structure and function, including PWV and arterial compliance, were not found to change following aerobic exercise.  Central PWV was found to remain unchanged following aerobic exercise in a similar investigation (193).  However, conflicting responses of central and peripheral PWV have been identified following acute exercise sessions (180, 193, 270, 271).  Similarly, conflicting responses of arterial compliance to acute exercise have been identified (276-278).  While transient changes in both arterial compliance and PWV may occur following exercise, this investigation did not identify changes.  As this population consisted of healthy, young adults, participants may have recovered from any changes in PWV or arterial  110  compliance prior to the post-exercise assessment.  Alternatively, as this population demonstrated healthy levels of PWV and arterial compliance prior to exercise, they may not have experienced significant changes as a result of exercise.   Aboriginal populations experience lower blood pressures and hypertension rates than European populations (332), though significantly greater rates of diabetes, cardiovascular disease and obesity than European populations (12, 126, 189).  Limited ethnic comparisons of vascular measures among Aboriginal populations have identified healthier levels of arterial augmentation index among Aboriginal populations, compared to other ethnic groups including European, Chinese, African-American and Hispanic (19).  Despite similar baseline levels of vascular measures such as peripheral PWV, healthy African-American adult males have demonstrated reduced responses to aerobic exercise compared to European males (193).  Consequently, ethnic differences in vascular responses to exercise may exist among Aboriginal populations, and may contribute to the disparities in blood pressure and cardiovascular disease trends among this population.  This investigation observed similar changes in vascular measures between European and Aboriginal participants.  However, blood pressure responses were only observed among the European population, and trends of ethnic differences in the blood pressure responses to exercise were also identified.  A possible reduced response of blood pressure to exercise may contribute to the increased cardiovascular disease experience among Aboriginal individuals, despite lower or similar resting blood pressures.  African-American populations have reduced vasodilation and heightened vasoconstriction in response to adrenergic stimulation, and reduced PWV response to exercise (193, 409, 410).  The reduced blood pressure response to exercise among Aboriginal populations, may indicate similar reductions in vasodilation properties.  As daily life includes periods of activity and energy expenditure, these blunted responses to exercise may lead to higher average daily blood pressure, despite lower resting blood pressures.  Greater average daily blood pressures may contribute to increased vascular dysfunction and increased experience of cardiovascular disease.  A lack of reduction in blood pressure following exercise may also exist because of the low blood pressures Aboriginal adults demonstrated prior to exercise.  Reductions in blood pressures post-exercise are known to occur more consistently among individuals with hypertension (411).  As the Aboriginal participants were free of hypertension, lower blood pressures may not be expected.  Additionally, a lack of reduction in blood pressure post-exercise may be beneficial among this population by reducing the risk of orthostatic hypotension (412).  111  Ethnic differences in the vascular resistance and blood pressure responses to exercise may be related to the resting levels of sympathetic balance, vascular resistance and blood pressure.   The sympathetic nervous system causes vasoconstriction, which increases vascular resistance and blood pressure, while blood pressure and vascular resistance are also affected by local vasoconstriction and vasodilation mechanisms such as nitric oxide (342).  Prior to exercise, Aboriginal adults demonstrated systolic blood pressures an average of 4mmHg lower than European adults (not statistically different).  Following exercise, European adults decreased systolic blood pressure an average of 5 mmHg, with no changes among the Aboriginal adults (not statistically different).  Post-exercise, Aboriginal and European adults demonstrated similar average systolic blood pressures.  These findings suggest Aboriginal adults experience a lower sympathetic input at rest.  In order to maintain circulation during diastole and maintain brain blood flow, a minimum level of sympathetic nervous input is required (413).  Following exercise of greater than 60% VO2max, heart rate variability is known to be decreased (287), as observed among both ethnic groups.  However, recovery post-exercise is known to vary with exercise intensity and duration (414, 415), and ethnic differences in autonomic function are known to exist (416), including ethnic differences in recovery of autonomic function post-exercise (417).  Differences in the recovery of sympathetic balance post-exercise may have resulted in Aboriginal adults recovering from exercise changes in BRS prior to the assessment, thus resulting in no changes detected.  Further, ethnic differences in nitric oxide receptors (389-391) may have altered the vasoconstriction response and thus resulted in different vascular resistance and blood pressure observations. Maximal and submaximal exercise elicited similar vascular responses, though greater reductions in vascular resistance and BRS were observed with maximal exercise.  These differences are expected given the significant impact and direct relationship of sympathetic input on these measures (281, 407, 408).  Aerobic exercise was found to reduce vascular resistance.  Reductions in vascular resistance can lead to reduced risks of cardiovascular disease events (418-420).  These results support the inclusion of regular physical activity to reduce cardiovascular disease risks.  In general, individuals of both higher and lower fitness were found to experience similar benefits of aerobic exercise, with the exception of systolic blood pressure and central PWV.  Individuals with greater blood pressures pre-exercise, experienced greater reductions in blood  112  pressure post-exercise.  Given the association of PWV with blood pressure, the corresponding association among central PWV is expected.  As this population consisted of relatively healthy individuals with average or above average rates of aerobic capacity, the range and variability may be small, and thus, these relationships were not identified.   Improvements in vascular resistance were only evident following maximal exercise among Aboriginal adults.  Further research is needed to determine if submaximal exercise intensities greater than 60% will produce vascular responses among Aboriginal adults.  Given the vascular responses to exercise among Aboriginal adults only occurred following maximal exercise, exercise training programs for Aboriginal adults should therefore incorporate greater intensity of maximal or near-maximal aerobic exercise to achieve greater health benefits of reduced vascular resistance.  Interval training is known to produce greater benefits than traditional continuous aerobic exercise training (421, 422).  By incorporating intervals of 3-5 min duration at maximal or near-maximal exercise, interspersed with 2-5 min duration of active rest, for a target 30 min per day, on 2-5 days per week, improvements in health outcomes can be achieved (421, 422).  The benefits of this type of exercise training for both young and older individuals (421, 422), combined with the reductions in vascular resistance among Aboriginal adults with greater intensity exercise, make this type of exercise a recommended training and health strategy for this population.   The small sample size of this investigation limits the strength of this investigation, though this sample size is consistent with other ethnic comparisons of vascular exercise responses (193, 269).  Additionally, as this investigation evaluated young, healthy populations, these results may not translate to older or less healthy individuals.  Future studies should employ larger samples and investigate the responses among older individuals and a range of individuals including those with lower aerobic capacity and poorer vascular measures.  Endothelial function may also vary between ethnic groups, influencing the vascular measures and trends observed in this investigation, further research should also include endothelial function assessments.   7.5 Conclusion Aboriginal and European healthy adults demonstrated similar vascular structural and functional responses to aerobic exercise.  However, some differences in blood pressure and vascular resistance responses were observed.  Only European adults demonstrated reductions in  113  blood pressure following exercise.  Additionally, in response to submaximal exercise, reductions in BRS were only observed among the European adults.     114  8. Ethnic Differences in the Cardiac Responses to Exercise6 8.1 Introduction Regular physical activity is known to reduce risks of overall mortality and risks of cardiovascular disease (406, 423, 424).  Exercise also leads to changes within the heart including increased stroke volume, structure remodelling of the left ventricular and improvements in systolic and diastolic function (218, 293-298).  Ethnic differences in cardiac structure and function have previously been identified among African-American populations, with African/Afro-Caribbean athletes demonstrating more striking repolarization changes and greater magnitudes of left ventricular hypertrophy than their European counterparts (227, 228, 316).  Cardiac structure and function have also been investigated among older adult American Indian populations, though not compared to other ethnic groups (232-235).  Assessments of exercise responses among Aboriginal populations have thus far been limited to blood pressure, heart rate and aerobic capacity assessments of Canadian Inuit populations (321).   This investigation aimed to compare Aboriginal and European adults’ responses of stroke volume, cardiac output, ejection fraction, strain and strain rates, arterial-ventricular coupling, and systolic and diastolic velocities following maximal and submaximal aerobic exercise.  Aboriginal populations were hypothesized to have greater responses to maximal and submaximal exercise than the European population.    8.2 Methods 8.2.1 Participants and Ethical Approval From February to August 2013, 12 Aboriginal adults and 12 age and sex matched European adults,  19-44 yr and free of chronic health conditions, underwent cardiac assessments pre and post maximal and sumbaximal aerobic exercise.  Based on power calculations using G*Power 3.1.3 (333) from previous results among young normally active adults, changes in cardiac measures such as E’ septal, E and diastolic longitudinal strain rate following maximal exercise can be identified with 11-18 participants per group (336).  Ethics approval was obtained                                                  6 A version of Chapter 8 has been prepared for publication. Foulds H.J.A., Bredin S.S.D. Warburton D.E.R Ethnic differences in the cardiac responses to aerobic exercise.   115  through the Clinical Research Ethics Board at the University of British Columbia and written informed consent was obtained from each participant prior to data collection.  Additionally, Aboriginal elders from the community reviewed and approved the project prior to the study commencing.  Testing was conducted at the University of British Columbia Cardiovascular Physiology and Rehabilitation laboratory, with the assistance of Aboriginal students.  Participants in this investigation included individuals also participating in the investigation outlined in Chapter 7. 8.2.2 Experimental Procedure Individual characteristics and baseline measures were collected on the first day of the investigation as outlined in section 4.2.2 upon arrival at the testing location.  The second day of testing included identical measures of body mass and blood pressures.  On both days, following five minutes of supine rest, echocardiaphy pre-exercise measurements, were obtained as described in section 5.2.3.  Each testing day consisted of an aerobic exercise session, as described in section 7.2.3.  Following the aerobic exercise session, identical echocardiography and blood pressure measures were obtained.  On the second day of testing, following the post-exercise vascular assessment, participants completed the physical fitness measures outlined in section 4.2.4. Data analysis of echocardiography measures was completed as described in section 5.2.3. 8.2.3 Statistical Analysis Statistical analyses were performed using Statistica 9.0 (Stats Soft, Tulsa, OK).  Characteristics were reported as mean and standard deviation for continuous variables and as percentages and counts for categorical and binary factors.  Baseline differences between ethnic groups were evaluated using t-tests for independent samples for continuous variables and Pearson χ2 test for categorical variables.  Repeated measure analysis of variance (ANOVA), with Fisher’s least significant difference post-hoc analysis was used to identify differences in responses to exercise between Aboriginal and European adults.  Differences in the responses to maximal and submaximal exercise were evaluated through paired t-tests of the changes from pre to post-exercise.  Analysis of changes in vascular measures with exercise in relation to fitness levels were conducted using Pearson’s Correlations of the changes in vascular measures with VO2max.  Significance was set at p < 0.05 for all analyses.   116  8.3 Results 8.3.1 Baseline and Demographic Characteristics Twelve Aboriginal adults and twelve age- and sex-matched European adults underwent cardiac assessments pre and post-maximal aerobic exercise.  Only 11 Aboriginal individuals returned for a submaximal aerobic exercise session with pre and post-exercise cardiac assessments, as such only 11 individuals of each ethnic group are included in the submaximal assessment.  As outlined on Table 8.1, participants of each ethnic group were of a similar age, sex, and marital status.  Aboriginal participants included half First Nations and half Métis individuals.  All participants had completed at least high school education, though a trend suggests European participants may have been more likely to have more than high school education.  The majority of participants from each ethnic group were married.  Aboriginal participants were more likely to be smokers, while binge drinking behaviours were similar across both groups.  Only one participant was found to be hypertensive, while no participants reported personal histories of cardiovascular disease or diabetes.  Family history of cardiovascular disease among primary family members was generally not reported among either group.  Significant differences in ethnic and cultural identity scores were identified between Aboriginal and European participants.  Aboriginal participants reported greater ethnic identification, ethnic affirmation, and cultural identity compared to their European counterparts.      117  Table 8.1 Demographic characteristics of participants, by ethnic group mean ± SD, n (%)   Aboriginal (n = 12) European (n = 12) P value     Age (yr) 26 ± 6 25 ± 7 0.68 First Nations, n (%) 6 (50.0) N/A  Métis, n (%) 6 (50.0) N/A  Female, n (%) 4 (33.3) 4 (33.3) 1.00 Single, n (%) 8 (66.7) 9 (75.0) 0.67 Married or common-law, n (%) 2 (16.7) 3 (25.0) 0.63 Divorced or separated, n (%) 2 (16.7) 0 (0.0) 0.15 Less than high school diploma, n (%) 0 (0.0) 0 (0.0) 1.00 High school diploma, n (%) 3 (25.0) 0 (0.0) 0.07 More than high school education, n (%) 9 (75.0) 12 (100.0) 0.07 Employed, n (%) 10 (83.3) 10 (83.3) 1.00 Annual income  <$20 000 per year, n (%) 9 (75.0) 5 (41.7) 0.11 Smoker, n (%) 4 (33.3) 0 (0.0) 0.03 Binge drinker more than once a month, n (%) 9 (75.0) 7 (58.3) 0.41 Binge drinker ever, n (%) 10 (83.3) 12 (100.0) 0.15 Never binge drink, n (%) 2 (16.7) 0 (0.0) 0.15 Hypertension (measured), n (%) 0 (0.0) 1 (8.3) 0.33 Cardiovascular disease, n (%) 0 (0.0) 0 (0.0) 1.00 Family history of cardiovascular disease *, n (%) 1 (8.3) 1 (8.3) 1.00 Diabetes, n (%) 0 (0.0) 0 (0.0) 1.00 Ethnic identification score† 2.9 ± 0.9 2.2 ± 0.4 0.02 Ethnic affirmation score† 3.2 ± 0.6 2.7 ± 0.4 0.03 Cultural identity score† 3.1 ± 0.7 2.6 ± 0.5 0.05     N/A, not applicable; SD, standard deviation; *primary family member prior to age 55 (male) or 65 (female); †from Multigroup Ethnic Identity Measure (376)         Physical body composition and fitness measures were found to be similar among Aboriginal and European participants (Table 8.2).  Participants were found to be of similar height, body mass, BMI, and waist circumference.  Body mass of participants, both overall and among each ethnic group, was not found to change between the two testing days.  Similar proportions of participants were found to be obese or overweight, with only 58.3% of participants of each ethnic group demonstrating normal body mass.  Based on self-reported physical activity levels, all participants were found to be physically active.  Physical fitness measures were also similar across both ethnic groups, including grip strength, six min walk  118  distance and VO2max.  Maximal heart rate were also found to be similar between Aboriginal and European participants.  European and Aboriginal participants demonstrated similar resting supine blood pressures and heart rates. Table 8.2 Body composition and fitness characteristics of participants, by ethnic group mean ± SD, n (%)   Aboriginal (n = 12) European (n = 12) P value     Height (cm) 177.3 ± 10.0 174.6 ± 8.4 0.48 Pre maximal exercise body mass (kg) 79.4 ± 14.8 73.3 ± 10.6 0.26 Pre submaximal exercise body mass (kg) 79.4 ± 15.8 73.4 ± 10.5 0.29 BMI (kg·m-2) 25.0 ± 2.9 24.0 ± 2.5 0.35 Waist circumference (cm) 85.8 ± 11.3 79.5 ± 7.2 0.12 Overweight, n (%) 4 (33.3) 5 (41.7) 0.69 Obesity, n (%) 1 (8.3) 0 (0.0) 0.33 Abdominal obesity, n (%) 0 (0.0) 0 (0.0) 1.00 Physically inactive, n (%) 0 (0.0) 0 (0.0) 1.00 Moderately active, n (%) 0 (0.0) 0 (0.0) 1.00 Physically active, n (%) 12 (100.0) 12 (100.0) 1.00 Combined grip strength (kg) 101.5 ± 22.3 97.4 ± 25.5 0.68 Six min walk distance (m) 711.7 ± 109.9 652.5 ± 124.8 0.23 VO2max (mL·kg-1·min-1) 43.6 ± 6 47.8 ± 10 0.22 Maximal heart rate (beats·min-1) 181.6 ± 19.2 180.1 ± 7.3 0.80 Supine systolic blood pressure (mmHg) 116.5 ± 10.0 120.4 ± 10.3 0.34 Supine diastolic blood pressure (mmHg) 62.0 ± 9.2 68.3 ± 11.1 0.14 Supine heart rate (beats·min-1) 67.5 ± 19.3 61.6 ± 7.8 0.34     BMI, body mass index; SD, standard deviation; VO2max, maximal aerobic capacity        8.3.2 Cardiac Responses to Exercise  Prior to both maximal and submaximal exercise, resting systolic left ventricular dimensions and volume were similar between Aboriginal and European adults (Table 8.3).  Following maximal aerobic exercise, similar among both ethnic groups, these dimensions were not found to change.  Following submaximal aerobic exercise, European and possibly Aboriginal adults were found to have lower left ventricular posterior wall thicknesses.  End systolic volumes were found to change differentially between the two ethnic groups following submaximal  119  aerobic exercise, where Aboriginal adults demonstrated significantly lower end systolic volume post-exercise, while European end systolic volume remained unchanged.   Table 8.3 Systolic dimension responses to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Left ventricular length (cm)      Pre-Exercise Post-Exercise 6.6 ± 0.4 7.0 ± 0.7 0.10 7.1 ± 0.9  6.7 ± 0.5  0.21 6.7 ± 0.5 6.9 ± 0.7  6.8 ± 0.9  6.6 ± 0.6   P value 0.63 0.32 0.81 0.10 0.23 0.73        Left ventricular internal diameter (cm)     Pre-Exercise Post-Exercise 3.29 ± 0.39 3.29 ± 0.45 1.00 3.26 ± 0.67  3.11 ± 0.38  0.51 3.17 ± 0.58 3.16 ± 0.50  3.27 ± 0.61  3.09 ± 0.47   P value 0.26 0.37 0.97 0.95 0.58 0.70        Left ventricular posterior wall thickness (cm)     Pre-Exercise Post-Exercise 1.53 ± 0.23 1.46 ± 0.32 0.59 1.50 ± 0.19  1.58 ± 0.31  0.50 1.47 ± 0.33 1.41 ± 0.35  1.32 ± 0.29  1.48 ± 0.26   P value 0.42 0.43 0.93 0.08 0.045 0.28        Septal wall thickness (cm)     Pre-Exercise Post-Exercise 1.34 ± 0.22 1.39 ± 0.29 0.68 1.33 ± 0.19  1.36 ± 0.24  0.72 1.30 ± 0.24 1.33 ± 0.25  1.37 ± 0.25  1.38 ± 0.19   P value 0.35 0.50 0.96 0.36 0.75 0.88        End systolic volume (mL)     Pre-Exercise Post-Exercise 64.0 ± 11.8 68.5 ± 17.0 0.46 66.5 ± 19.5 62.3 ± 8.9  0.52 64.2 ± 10.5 68.4 ± 22.1  61.9 ± 17.2  64.3 ± 11.3   P value 0.97 0.93 0.92 0.04 0.23 0.04        SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise   Prior to aerobic exercise, left ventricular diastolic dimensions and volume were generally similar between European and Aboriginal adults, as outlined on Table 8.4.  Prior to maximal exercise, Aboriginal adults were found to have smaller left ventricular lengths than European  120  adults, however these differences were not observed prior to submaximal exercise.  Following maximal exercise, European adults demonstrated decreases in left ventricular internal diameter and end diastolic volume.   A trend suggests these changes may also have occurred among the Aboriginal adults.  In response to submaximal exercise, ethnic differences in the diastolic responses were identified, where Aboriginal adults demonstrated reduced end diastolic volume, in comparison to unchanged end diastolic volume among European adults.    121  Table 8.4 Diastolic dimension responses to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Left ventricular length (cm)      Pre-Exercise Post-Exercise 8.8 ± 0.7 9.4 ± 0.6 0.04 9.4 ± 0.7  9.0 ± 0.7  0.27 8.8 ± 0.6 9.3 ± 0.9  9.0 ± 0.9  8.8 ± 0.8   P value 0.56 0.78 0.65 0.08 0.11 0.80        Left ventricular internal diameter (cm)     Pre-Exercise Post-Exercise 4.94 ± 0.43 4.83 ± 0.38 0.49 4.89 ± 0.51  4.87 ± 0.44  0.91 4.66 ± 0.58 4.71 ± 0.41  4.80 ± 0.56  4.72 ± 0.64   P value 0.07 0.02 0.20 0.20 0.28 0.66        Left ventricular posterior wall thickness (cm)     Pre-Exercise Post-Exercise 0.96 ± 0.13 0.95 ± 0.20 0.84 0.90 ± 0.12  0.97 ± 0.23  0.41 0.96 ± 0.17 0.97 ± 0.19  0.88 ± 0.15  1.04 ± 0.18   P value 0.69 1.00 0.79 0.50 0.26 0.04        Septal wall thickness (cm)     Pre-Exercise Post-Exercise 0.92 ± 0.17 0.96 ± 0.19 0.58 0.89 ± 0.17  0.94 ± 0.17  0.46 0.94 ± 0.15 0.97 ± 0.15  0.91 ± 0.17  0.96 ± 0.11   P value 0.86 0.57 0.91 0.48 0.67 0.84        Relative wall thickness      Pre-Exercise Post-Exercise 0.39 ± 0.04 0.39 ± 0.08 0.87 0.37 ± 0.04  0.40 ± 0.09  0.34 0.42 ± 0.07 0.41 ± 0.08  0.37 ± 0.08  0.45 ± 0.10   P value 0.33 0.21 0.81 0.98 0.18 0.10       End diastolic volume (mL)      Pre-Exercise Post-Exercise 154.4 ± 28.1 160.3 ± 36.2 0.66 154.8 ± 40.6  149.4 ± 22.4  0.71 143.4 ± 21.6 147.7 ± 43.4  136.5 ± 33.0  147.1 ± 27.0   P value 0.06 0.02 0.90 0.01 0.81 0.04        SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise     122  Table 8.5 outlines the changes in systolic function in response to maximal and submaximal exercise among Aboriginal and European adults.  Both ethnic groups demonstrated similar systolic function prior to exercise on both occasions.  In response to maximal aerobic exercise, both Aboriginal and European adults demonstrated similar declines in stroke volume, SVI, and ejection fraction, with increases in cardiac output and body surface area indexed cardiac output.  Following submaximal exercise, both Aboriginal and European adults demonstrated reduced ejection fraction.  However, ethnic differences in the stroke volume and SVI responses to submaximal exercise were identified, where significant declines in stroke volume and SVI following submaximal exercise could only be identified among Aboriginal adults.      123  Table 8.5 Systolic function response to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Stroke volume (mL)      Pre-Exercise Post-Exercise 90.4 ± 18.0 91.8 ± 19.6 0.86 88.2 ± 21.6   87.1 ± 15.4  0.89 79.1 ± 12.0 79.3 ± 21.6  74.5 ± 16.4  82.8 ± 16.6   P value 0.01 0.001 0.84 0.003 0.30 0.049        Cardiac output (L·min-1)      Pre-Exercise Post-Exercise 5.0 ± 1.0 5.6 ± 1.1 0.21 5.5 ± 1.2  5.1 ± 1.1  0.47 6.3 ± 1.3 6.5 ± 1.9  5.3 ± 1.0  5.6 ± 1.3   P value 0.03 0.002 0.43 0.68 0.12 0.27        Cardiac output index (L·min-1·m-2)     Pre-Exercise Post-Exercise 2.7 ± 0.5 2.8 ± 0.4 0.35 2.8 ± 0.5  2.7 ± 0.5  0.71 3.3 ± 0.5 3.3 ± 0.8  2.7 ± 0.4  3.0 ± 0.4   P value 0.04 0.002 0.43 0.63 0.12 0.14        SVI (mL·m-2)      Pre-Exercise Post-Exercise 48.1 ± 7.9 46.6 ± 7.1 0.63 44.9 ± 8.7  46.4 ± 6.1  0.63 42.1 ± 5.3 40.0 ± 8.3  38.0 ± 6.5  44.0 ± 6.5   P value 0.005 0.001 0.58 0.002 0.28 0.03        Ejection fraction (mL)      Pre-Exercise Post-Exercise 58.5 ± 3.0 57.5 ± 2.5 0.39 57.4 ± 2.9  58.2 ± 3.2  0.55 55.3 ± 2.4 54.0 ± 2.4  55.0 ± 2.7  56.2 ± 2.8   P value <0.001 0.001 0.38 <0.001 0.02 0.37        Fractional shortening (%)      Pre-Exercise Post-Exercise 18.6 ± 3.4 17.7 ± 4.8 0.62 18.0 ± 4.8  19.9 ± 3.4  0.29 17.4 ± 4.9 19.6 ± 4.3  19.3 ± 4.3  20.5 ± 3.5   P value 0.16 0.46 0.16 0.31 0.76 0.77        SVI, stroke volume indexed for body surface area; SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise   Further changes in systolic function following aerobic exercise among Aboriginal and European adults are outlined on table 8.6.  Aboriginal and European adults demonstrated similar  124  systolic function measures prior to either exercise session.  Following maximal aerobic exercise, no changes in wall stress, systolic blood pressure/end systolic volume, ejection fraction/end diastolic volume, E’ septal or E’ lateral were identified among either ethnic group.  However, following submaximal exercise, ethnic differences in the responses of systolic blood pressure/end systolic volume and possibly ejection fraction/end diastolic volume were identified, where European adults demonstrated decreases in systolic blood pressure/end systolic volume while Aboriginal adults demonstrated no changes, and Aboriginal adults were the only group demonstrating increases in ejection fraction/end diastolic volume following submaximal exercise.     125  Table 8.6 Systolic function response to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Wall stress (kdyne·cm-2)      Pre-Exercise Post-Exercise 127.9 ± 13.6 131.6 ± 30.7 0.70 129.0 ± 38.3  120.6 ± 14.4  0.50 130.7 ± 30.3 132.8 ± 35.5  144.7 ± 41.7  124.8 ± 19.5   P value 0.89 0.74 0.95 0.14 0.16 0.22        Systolic blood pressure/end systolic volume (mmHg·mL-1)   Pre-Exercise Post-Exercise 1.88 ± 0.33 1.66 ± 0.44 0.19 1.85 ± 0.55  1.90 ± 0.30  0.79 1.82 ± 0.32 1.76 ± 0.52  1.95 ± 0.58  1.74 ± 0.33   P value 0.24 0.52 0.36 0.24 0.05 0.03        Ejection fraction/end diastolic volume     Pre-Exercise Post-Exercise 0.39 ± 0.08 0.38 ± 0.11 0.78 0.40 ± 0.14  0.40 ± 0.06  0.93 0.39 ± 0.07 0.40 ± 0.12  0.43 ± 0.13  0.39 ± 0.08   P value 0.32 0.80 0.55 0.03 0.63 0.07        E’ septal (m·s-1)      Pre-Exercise Post-Exercise 0.22 ± 0.03 0.22 ± 0.03 0.59 0.22 ± 0.04  0.22 ± 0.03  0.60 0.23 ± 0.04 0.22 ± 0.03  0.22 ± 0.03  0.21 ± 0.04   P value 0.77 0.35 0.39 0.97 0.78 0.66        E’ lateral (m·s-1)      Pre-Exercise Post-Exercise 0.25 ± 0.04 0.24 ± 0.03 0.31 0.23 ± 0.03  0.25 ± 0.03  0.13 0.24 ± 0.03 0.24 ± 0.03  0.22 ± 0.03  0.23 ± 0.03   P value 0.96 0.57 0.82 0.45 0.08 0.78        E’, mitral annular tissue velocity; SD, standard deviation; SVI, stroke volume indexed for body surface area; †difference between ethnic groups, upper at baseline, lower in response to exercise   Table 8.7 outlines the responses of left ventricular mass and cardiac arterial measures in response to aerobic exercise.  Similar measures of left ventricular mass and indicators of arterial stiffness and compliance were identified among Aboriginal and European adults prior to exercise.  However, systemic vascular resistance was found to be higher among Aboriginal   126  adults prior to maximal exercise.  Following maximal aerobic exercise, European adults demonstrated reductions in left ventricular mass, while Aboriginal adults left ventricular mass was found to remain unchanged.  Both ethnic groups demonstrated increases in arterial stiffness (pulse pressure/SVI) and decreases in arterial compliance (SVI/pulse pressure).  In response to submaximal exercise, European adults demonstrated no changes in left ventricular mass or arterial responses.  However, Aboriginal adults demonstrated increase in arterial stiffness and decreases in arterial compliance, and these differences may represent significant ethnic variations in the responses to exercise.      127  Table 8.7 Left ventricular mass and arterial responses to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Left ventricular mass (g)      Pre Post-Exercise 173.0 ± 49.6 168.6 ± 48.8 0.83 158.8 ± 46.0  172.7 ± 58.5  0.54 Post 159.8 ± 51.9 163.3 ± 38.6  153.2 ± 46.7  171.7 ± 48.4   P valu 0.55 0.04 0.48 0.39 0.52 0.42        Left ventricular mass/body surface area (g·m-2)    Pre Post-Exercise 90.87 ± 20.87 84.86 ± 18.46 0.46 79.72 ± 14.81  90.90 ± 25.38  0.22 Post 83.99 ± 23.53 82.46 ± 13.54  77.27 ± 17.08  90.69 ± 20.68   P valu 0.57 0.03 0.51 0.42 0.57 0.30        Left ventricular mass/height2.7 (g·m-2.7)     Pre Post-Exercise 37.8 ± 8.3 35.3 ± 7.1 0.44 33.5 ± 5.6  37.6 ± 10.1  0.25 Post 35.0 ± 9.7 34.3 ± 4.9  32.4 ± 6.3  37.5 ± 7.9   P valu 0.57 0.03 0.53 0.39 0.54 0.26        Pulse pressure/SVI (mmHg·m2·mL-1)     Pre Post-Exercise 1.10 ± 0.25 1.19 ± 0.21 0.35 1.27 ± 0.31  1.20 ± 0.19  0.56 Post 1.32 ± 0.17 1.36 ± 0.26  1.46 ± 0.27  1.26 ± 0.18   P valu 0.001 0.001 0.84 0.02 0.55 0.06        SVI/pulse pressure (mL·mmHg-1·m-2)     Pre Post-Exercise 0.99 ± 0.44 0.86 ± 0.12 0.31 0.82 ± 0.16  0.85 ± 0.14  0.66 Post 0.77 ± 0.10 0.76 ± 0.15  0.71 ± 0.12  0.81 ± 0.10   P valu 0.007 0.08 0.69 0.01 0.81 0.047        Systemic vascular resistance (mmHg·min·L-1)    Pre Post-Exercise 17.69 ± 3.76 14.80 ± 3.05 0.05 15.62 ± 3.60  16.85 ± 3.28  0.41 Post 13.57 ± 2.70 13.51 ± 3.66  15.98 ± 2.79  15.36 ± 3.22   P valu 0.07 0.001 0.13 0.65 0.08 0.22        SVI, stroke volume indexed for body surface area; SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise   As outlined on table 8.8, diastolic function was similar between Aboriginal and European adults prior to exercise.  In response to maximal aerobic exercise, no significant changes in these  128  measures were identified.  However, in response to submaximal exercise, both Aboriginal and European adults were found to have significantly reduced E and E/E’ septal.   Table 8.8 Diastolic function response to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        E (m·s-1)      Pre-Exercise Post-Exercise 0.72 ± 0.15 0.76 ± 0.11 0.52 0.72 ± 0.15  0.75 ± 0.14 0.62 0.70 ± 0.11 0.74 ± 0.15  0.65 ± 0.10  0.68 ± 0.15   P value 0.66 0.30 0.61 0.01 0.002 0.94        A (m·s-1)      Pre-Exercise Post-Exercise 0.28 ± 0.06 0.33 ± 0.08 0.10 0.31 ± 0.07  0.30 ± 0.06  0.80 0.28 ± 0.10 0.31 ± 0.12  0.28 ± 0.09  0.29 ± 0.09   P value 0.61 0.94 0.57 0.49 0.37 0.91        E/A       Pre-Exercise Post-Exercise 2.70 ± 0.71 2.41 ± 0.60 0.28 2.52 ± 0.84  2.66 ± 0.84  0.71 2.70 ± 0.69 2.72 ± 0.92  2.50 ± 0.62  2.68 ± 1.34   P value 0.40 0.99 0.94 0.93 0.97 0.81        E/E’ septal       Pre-Exercise Post-Exercise 3.37 ± 0.59 3.44 ± 0.52 0.74 3.27 ± 0.62  3.50 ± 0.45  0.60 3.15 ± 0.66 3.42 ± 0.72  2.97 ± 0.49  3.25 ± 0.68   P value 0.89 0.25 0.39 0.02 0.06 0.63        E/E’ lateral       Pre-Exercise Post-Exercise 2.96 ± 0.63 3.20 ± 0.46 0.31 0.23 ± 0.03  0.25 ± 0.03  0.13 2.91 ± 0.41 3.16 ± 0.75  2.93 ± 0.41  2.92 ± 0.34   P value 0.78 0.73 0.69 0.09 0.28 0.68        A, late ventricular diastolic filling velocity; E, early ventricular diastolic filling velocity; E’, mitral annular tissue velocity; SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise   Table 8.9 outlines the changes in elastance and arterial-ventricular coupling in response to aerobic exercise among Aboriginal and European adults.  Prior to exercise, Aboriginal and European adults demonstrated similar elastance measures.  Following maximal aerobic exercise,  129  both Aboriginal and European adults demonstrated significant increases in EA, EAI and arterial-ventricular coupling (EAI/ELVI).  Following submaximal exercise, ethnic differences in the elastance responses were identified, where only Aboriginal adults demonstrated significant increases in EA.  However, both Aboriginal and European adults demonstrated significant increases in arterial-ventricular coupling following submaximal exercise. Table 8.9 Elastance and arterial-ventricular coupling response to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        EA (mmHg·mL-1)      Pre-Exercise Post-Exercise 1.23 ± 0.19 1.19 ± 0.30 0.79 1.28 ± 0.35  1.26 ± 0.17  0.89 1.38 ± 0.19 1.41 ± 0.35  1.50 ± 0.36  1.33 ± 0.22   P value 0.004 0.001 0.39 0.002 0.29 0.06        EAI (mmHg·mL-1·m-2)      Pre-Exercise Post-Exercise 0.66 ± 0.14 0.62 ± 0.19 0.56 0.67 ± 0.24  0.68 ± 0.14  0.87 0.74 ± 0.15 0.74 ± 0.25  0.79 ± 0.24  0.73 ± 0.18   P value 0.004 0.001 0.29 0.003 0.25 0.12        ELV (mmHg·mL-1)      Pre-Exercise Post-Exercise 1.74 ± 0.30 1.63 ± 0.49 0.54 1.75 ± 0.65  1.75 ± 0.22  0.99 1.71 ± 0.30 1.68 ± 0.52  1.85 ± 0.52  1.71 ± 0.28   P value 0.52 0.69 0.54 0.24 0.30 0.11        ELVI (mmHg·mL-1·m-2)      Pre-Exercise Post-Exercise 0.94 ± 0.24 0.86 ± 0.34 0.49 0.93 ± 0.45  0.95 ± 0.19  0.90 0.93 ± 0.23 0.88 ± 0.35  0.98 ± 0.37  0.93 ± 0.23   P value 0.48 0.67 0.50 0.34 0.37 0.23        EAI/ELVI      Pre-Exercise Post-Exercise 0.71 ± 0.09 0.74 ± 0.07 0.41 0.75 ± 0.09  0.72 ± 0.10  0.56 0.81 ± 0.08 0.85 ± 0.08  0.82 ± 0.09  0.78 ± 0.09   P value <0.001 0.001 0.37 <0.001 0.01 0.36        EA , arterial elastance; EAI, arterial elastance indexed for body surface area; ELV, ventricular elastance; ELVI, ventricular elastance indexed for body surface area; SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise    130   Rotation and strain were similar between Aboriginal and European adults prior to exercise (Table 8.10).  Following maximal exercise, no differences in responses between groups were identified.  However rotation was found to increase among the Aboriginal group, following maximal exercise.  In response to submaximal exercise, similar responses between Aboriginal and European populations were identified.  Longitudinal strain was found to decrease among the Aboriginal population, while no other changes resulted from submaximal exercise.  Table 8.10 Peak systolic strain and rotation response to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Rotation (°)     Pre Post-Exercise 3.61 ± 2.44  3.59 ± 1.79  0.98 4.32 ± 2.46  3.22 ± 1.80  0.30 Post 5.09 ± 1.83  4.12 ± 1.58   4.18 ± 2.63  4.64 ± 2.82   P valu 0.03 0.41 0.30 0.87 0.11 0.21        Longitudinal strain (%)     Pre Post-Exercise -18.58 ± 1.69  -18.58 ± 1.69  0.58 -18.98 ± 1.62  -19.82 ± 2.23  0.32 Post -17.95 ± 3.21  -17.95 ± 3.21   -16.82 ± 2.31  -18.75 ± 3.07   P valu 0.50 0.50 0.69 0.002 0.21 0.22        Radial strain (%)     Pre Post-Exercise 25.77 ± 10.33  29.04 ± 10.94  0.45 31.48 ± 14.47  31.44 ± 8.46  0.99 Post 32.69 ± 11.72  37.39 ± 9.42   32.40 ± 13.41  29.65 ± 13.16   P valu 0.11 0.06 0.81 0.78 0.58 0.55        Circumferential strain (%)     Pre Post-Exercise -12.50 ± 3.22  -12.73 ± 1.74  0.87 -13.36 ± 2.57  -12.30 ± 1.83  0.39 Post -13.67 ± 4.02  -13.95 ± 3.70   -12.35 ± 3.88  -12.70 ± 2.84   P valu 0.37 0.35 0.98 0.36 0.71 0.37        SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise  Aboriginal and European adults were generally found to have similar systolic rotation and strain rates prior to exercise, as outlined in Table 8.11.  Changes in systolic rotation and strain rates resulting from both maximal and submaximal exercise were similar between the two  131  groups.  Following maximal exercise, Aboriginal adults experienced increases in systolic rotation rates and radial strain rates, and decreases in longitudinal and circumferential strain rates.  The European group demonstrated similar increases in radial strain rates following maximal exercise, with possible increases in rotation rates and decreases in circumferential strain rates.  Following submaximal exercise, European adults demonstrated increases in systolic rotation rates and decreases in longitudinal strain rates.    Table 8.11 Peak systolic strain and rotation rates response to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Rotation rate (°·s-1)     Pre Post-Exercise 43.59± 19.67  47.86 ± 15.63  0.61 55.54 ± 30.97  47.57 ± 17.10  0.50 Post 67.75 ± 26.32  60.17 ± 19.02   68.14 ± 29.49  66.34 ± 29.66   P valu 0.002 0.08 0.29 0.14 0.03 0.60        Longitudinal strain rate  (s-1)     Pre Post-Exercise -0.99 ± 0.16  -1.02 ± 0.12  0.61 -1.02 ± 0.14  -1.09 ± 0.13  0.28 Post -1.16 ± 0.21  -1.13 ± 0.20   -1.08 ± 0.24  -1.26 ± 0.33   P valu 0.03 0.13 0.65 0.44 0.04 0.31        Radial strain rate (s-1)     Pre Post-Exercise 1.38 ± 0.28  1.34 ± 0.29  0.80 2.26 ± 2.08  1.44 ± 0.27  0.09 Post 1.97 ± 0.41  1.88 ± 0.55   1.75 ± 0.51  1.57 ± 0.41   P valu 0.002 0.004 0.84 0.25 0.77 0.30        Circumferential strain rate (s-1)     Pre Post-Exercise -0.80 ± 0.22  -0.79 ± 0.16  0.96 -0.85 ± 0.18  -0.79 ± 0.22  0.60 Post -1.08 ± 0.40  -1.01 ± 0.43   -1.06 ± 0.48  -0.88 ± 0.21   P valu 0.02 0.08 0.69 0.05 0.37 0.42        SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise  Diastolic rotation and strain rates were found to be similar between Aboriginal and European adults prior to exercise, as outlined on Table 8.12.  Aboriginal and European adults demonstrated similar responses to both maximal and submaximal exercise.  Maximal exercise  132  was found to elicit decreases in diastolic rotation among both ethnic groups, as well as decreases in radial strain rates and increases in circumferential strain rates among the Aboriginal adults.  Submaximal exercise was found to elicit decreases in diastolic rotation rates and longitudinal strain rates among the Aboriginal adults, with possible decreases in radial strain rates among the Aboriginal adults and rotation rates among the European adults.      133  Table 8.12 Peak diastolic strain and rotation rates response to exercise among Aboriginal and European participants, by ethnic group mean ± SD  Maximal Aerobic Exercise Submaximal Aerobic Exercise   Aboriginal (n = 12) European (n = 12) P value† Aboriginal (n = 11) European  (n = 11) P value†        Rotation  rate (°·s-1)     Pre Post-Exercise -36.37 ± 12.78  -47.02 ± 12.33  0.08 -48.19 ± 19.53  -36.08 ± 11.31  0.17 Post -58.85 ± 16.73  -64.17 ± 14.35   -65.82 ± 30.18  -47.68 ± 15.88   P valu<0.001 0.002 0.46 0.01 0.06 0.48        Longitudinal strain rate (s-1)     Pre Post-Exercise 1.40 ± 0.15  1.48 ± 0.32  0.41 1.35 ± 0.21  1.52 ± 0.31  0.14 Post 1.40 ± 0.33  1.37 ± 0.31   1.12 ± 0.26  1.45 ± 0.40   P valu0.96 0.18 0.49 0.01 0.44 0.12        Radial strain rate (s-1)     Pre Post-Exercise -1.40 ± 0.53  -1.49 ± 0.39  0.96 -1.56 ± 0.62  -1.41 ± 0.44  0.54 Post -1.92 ± 0.38  -1.71 ± 0.44   -1.90 ± 0.71  -1.43 ± 0.49   P valu0.02 0.53 0.21 0.09 0.90 0.26        Circumferential strain rate (s-1)     Pre Post-Exercise 0.83 ± 0.34  0.96 ± 0.26  0.48 0.96 ± 0.24  0.83 ± 0.22  0.27 Post 1.32 ± 0.66  1.14 ± 0.49   0.97 ± 0.38  0.86 ± 0.24   P valu0.01 0.32 0.21 0.94 0.80 0.90        SD, standard deviation; †difference between ethnic groups, upper at baseline, lower in response to exercise  8.3.3 Comparisons of Cardiac Responses to Maximal and Submaximal Exercise Table 8.13 outlines the changes in left ventricular mass, and systolic and diastolic dimensions and volumes following maximal and submaximal exercise.  Similar changes in left ventricular mass, systolic and diastolic dimensions and systolic and diastolic volumes were identified following maximal and submaximal exercise.  134  Table 8.13 The changes in cardiac structures and volumes resulting from maximal and submaximal aerobic exercise   Maximal Aerobic Exercise (n = 22) Submaximal Aerobic Exercise (n = 22) P value     Left ventricular mass (g) -7.4 ± 24.7 -3.3 ± 21.2 0.60 Left ventricular mass/body surface area (g·m-L) -3.74 ± 11.91 -1.33 ± 10.44 0.54 Left ventricular mass/height2.7 (g·m-2.7) -1.6 ± 5.0 -0.6 ± 4.3 0.56     Systolic    Left ventricular length (cm) 0.0 ± 0.8 -0.3 ± 0.5 0.11 Left ventricular internal diameter (cm) -0.17 ± 0.4 0.00 ± 0.33 0.20 Left ventricular posterior wall thickness (cm) -0.04 ± 0.23 -0.14 ± 0.24 0.23 Septal wall thickness (cm) -0.03 ± 0.19 0.03 ± 0.14 0.34 End systolic volume (mL) 1.1 ± 8.4 -1.3 ± 7.3 0.31     Diastolic    Left ventricular length (cm) -0.1 ± 0.7 -0.3 ± 0.5 0.12 Left ventricular internal diameter (cm) -0.20 ± 0.31 -0.12 ± 0.31 0.39 Left ventricular posterior wall thickness (cm) 0.01 ± 0.13 0.02 ± 0.15 0.82 Septal wall thickness (cm) 0.03 ± 0.14 0.02 ± 0.10 0.86 Relative wall thickness 0.02 ± 0.07 0.02 ± 0.09 0.93 End diastolic volume (mL) -10.2 ± 17.4 -10.3 ± 18.4 0.97     SD, standard deviation       Changes in systolic and diastolic function and elastance in response to maximal and submaximal exercise are outlined on Table 8.14.  Maximal and submaximal exercise produced similar responses of stroke volume, SVI, fractional shortening, systolic and diastolic function, and strain.  However, greater changes in cardiac output, cardiac output indexed for body surface area, and ejection fraction were identified following maximal exercise.  Cardiac arterial stiffness and compliance were similarly influenced by maximal and submaximal exercise; however, systemic vascular resistance was more greatly influenced by maximal aerobic exercise.     135  Table 8.14 The changes in cardiac function resulting from maximal and submaximal aerobic exercise, mean ± SD   Maximal Aerobic Exercise (n = 22) Submaximal Aerobic Exercise (n = 22) P value    Stroke volume (mL) -11.2 ± 11 -9 ± 12 0.50 SVI (mL·m-2)  -6 ± 5.7 -4.7 ± 6.1 0.44 Cardiac output (L·min-1)  1.1 ± 1.2 0.2 ± 1.1 0.01 Cardiac output index (L·min-1·m-2)  0.5 ± 0.6 0.1 ± 0.6 0.01 Ejection fraction (mL)  -3.5 ± 2.4 -2.2 ± 1.9 0.001 Fractional shortening (%)  0.8 ± 4.8 0.9 ± 4.3 0.93 Wall stress (kdyne·cm-2)  0.1 ± 27.4 10 ± 24.8 0.27 Systolic blood pressure/end systolic volume (mmHg·mL-1)  0 ± 0.31 -0.03 ± 0.28 0.68 Ejection fraction/end diastolic volume   0.01 ± 0.05 0.01 ± 0.04 0.56 E’ septal (m·s-1)  0.01 ± 0.03 0 ± 0.03 0.51 E’ lateral (m·s-1)  0 ± 0.03 -0.01 ± 0.03 0.39 Pulse pressure/SVI (mmHg· m2·mL-1)  0.18 ± 0.2 0.12 ± 0.25 0.36 SVI/pulse pressure (mL·mmHg-1·m-2)  -0.15 ± 0.3 -0.08 ± 0.15 0.31 E (m·s-1)  -0.03 ± 0.1 -0.08 ± 0.07 0.05 A (m·s-1)  -0.01 ± 0.12 -0.02 ± 0.08 0.70 E/A   0.12 ± 0.87 -0.01 ± 0.93 0.64 E/E’ septal   -0.14 ± 0.66 -0.34 ± 0.42 0.22 E/E’ lateral   -0.04 ± 0.48 -0.16 ± 0.36 0.38 EA (mmHg·mL-1)  0.16 ± 0.16 0.15 ± 0.2 0.78 EAI (mmHg·mL-1·m-2)  0.09 ± 0.09 0.08 ± 0.1 0.66 ELV (mmHg·mL-1)  -0.02 ± 0.21 0.03 ± 0.22 0.34 ELVI (mmHg·mL-1·m-2)  -0.01 ± 0.12 0.01 ± 0.12 0.40 EAI/ELVI  0.11 ± 0.08 0.07 ± 0.06 0.002 Systemic vascular resistance (mmHg·min·L-1)  -2.84 ± 3 -0.56 ± 2.87 0.003     A, late ventricular diastolic filling velocity; E, early ventricular diastolic filling velocity; E’, mitral annular tissue velocity; EA , arterial elastance; EAI, arterial elastance indexed for body surface area; ELV, ventricular elastance; ELVI, ventricular elastance indexed for body surface area; SD, standard deviation; SVI, stroke volume indexed for body surface area       Changes in rotation and strain in response to maximal and submaximal exercise are outlined on Table 8.15.  Maximal and submaximal exercise produced similar responses of rotation, rotation rates, and systolic circumferential and longitudinal strain and strain rates.   136  Similar diastolic rotation velocity, and longitudinal and radial strain rate responses to maximal and submaximal exercise were also demonstrated.  However, greater increases in systolic radial strain and strain rate, and diastolic circumferential strain rate resulted from maximal exercise.   Table 8.15 The changes in rotation and strain resulting from maximal and submaximal aerobic exercise, mean ± SD   Maximal Aerobic Exercise (n = 22) Submaximal Aerobic Exercise (n = 22) P value    Peak (systole)    Rotation  (°) 1.01 ± 2.19 0.59 ± 2.73 0.56 Rotation velocity (°·s-1) 18.23 ± 23.75 14.38 ± 25.99 0.60 Longitudinal strain (%)  0.74 ± 3.09 1.61 ± 2.26 0.37 Longitudinal strain rate (s-1)  -0.11 ± 0.22 -0.12 ± 0.24 0.97 Radial strain (%)  7.63 ± 14.02 -0.40 ± 9.93 0.03 Radial strain rate (s-1)  0.56 ± 0.57 -0.18 ± 1.37 0.02 Circumferential strain (%)  -1.20 ± 4.31 0.28 ± 3.40 0.20 Circumferential strain rate (s-1)  -0.25 ± 0.39 -0.14 ± 0.32 0.28     Peak (diastole)    Rotation velocity (°·s-1) -19.67 ± 16.34 -13.40 ± 19.01 0.23 Longitudinal strain rate (s-1)  -0.06 ± 0.3 -0.15 ± 0.27 0.27 Radial strain rate (s-1)  -0.37 ± 0.57 -0.17 ± 0.61 0.23 Circumferential strain rate (s-1)  0.34 ± 0.61 0.02 ± 0.39 0.04     SD, standard deviation     8.3.4 Correlations of VO2max with Cardiac Responses to Exercise Correlations of VO2max with changes in left ventricular mass, and systolic and diastolic dimensions and volumes resulting from aerobic exercise are outlined on Table 8.16.  Maximal aerobic capacity was not found to correlate with changes in left ventricular mass following exercise.  Changes in systolic and diastolic dimensions and volumes following aerobic exercise were also not found to correlate with VO2max.      137  Table 8.16 The association of VO2max with changes in cardiac structural measures following maximal and submaximal aerobic exercise   VO2max Association with Changes Following Maximal Aerobic Exercise     (n = 24) VO2max Association with Changes Following Submaximal Aerobic Exercise      (n = 22) Correlate Β SE P value Β SE P value        Left ventricular mass (g) -0.01 0.21 0.97 0.18 0.22 0.42 Left ventricular mass/body surface area (g·m-2) -0.02 0.21 0.92 0.18 0.22 0.42 Left ventricular mass/height2.7 (g·m-2.7) -0.01 0.21 0.94 0.17 0.22 0.45        Systolic       Left ventricular length (cm) 0.14 0.21 0.51 0.12 0.22 0.59 Left ventricular internal diameter (cm) -0.17 0.21 0.44 0.41 0.20 0.05 Left ventricular posterior wall thickness (cm) 0.21 0.21 0.31 -0.25 0.22 0.26 Septal wall thickness (cm) 0.26 0.21 0.23 -0.16 0.22 0.47 End systolic volume (mL) -0.20 0.21 0.36 0.40 0.21 0.07        Diastolic       Left ventricular length (cm) -0.04 0.21 0.85 0.09 0.22 0.71 Left ventricular internal diameter (cm) -0.14 0.21 0.50 0.25 0.22 0.26 Left ventricular posterior wall thickness (cm) 0.01 0.21 0.96 -0.05 0.22 0.82 Septal wall thickness (cm) 0.11 0.21 0.59 0.01 0.22 0.95 Relative wall thickness 0.04 0.21 0.84 -0.09 0.22 0.69 End diastolic volume (mL) -0.37 0.20 0.08 0.37 0.21 0.09  SD, standard deviation; VO2max, maximal aerobic capacity   In general, cardiac functional and mechanical measures were not found to correlate with VO2max, as outlined on Table 8.17.  Changes in cardiac output, and cardiac output indexed for body surface area, as well as stroke volume and SVI following maximal aerobic exercise were found to negatively correlate with VO2max.  Accordingly, individuals with greater VO2max, were found to have lower increases in stroke volume, SVI, cardiac output, and cardiac output indexed for body surface area following maximal aerobic exercise.  Trends also suggest  138  individuals with greater VO2max may also demonstrate less change in ejection fraction and greater change in arterial-ventricular coupling following maximal aerobic exercise.  In response to submaximal exercise, correlations between VO2max and changes in systolic blood pressure/end systolic volume were identified where individuals with greater VO2max may experience less change in systolic blood pressure/end systolic volume following submaximal aerobic exercise.  This trend may also exist for changes in  ejection fraction/end diastolic volume following submaximal aerobic exercise.       139  Table 8.17 The association of VO2max with changes in cardiac functional measures following maximal and submaximal aerobic exercise   Maximal Exercise     (n = 24) Submaximal  Exercise      (n = 22) Correlate with VO2max Β SE P value Β SE P value        Stroke volume (mL) -0.44 0.19 0.03 0.33 0.21 0.13 SVI (mL·m-2)  -0.47 0.19 0.02 0.32 0.21 0.14 Cardiac output (L·min-1)  -0.45 0.19 0.03 0.05 0.22 0.81 Cardiac output index (L·min-1·m-2)  -0.42 0.19 0.04 0.09 0.22 0.68 Ejection fraction (mL)  -0.38 0.20 0.07 0.04 0.22 0.85 Fractional shortening (%)  -0.06 0.21 0.78 -0.07 0.22 0.77 Wall stress (kdyne·cm-2)  -0.31 0.20 0.14 0.29 0.21 0.19 Systolic blood pressure/end systolic volume (mmHg·mL-1)  0.09 0.21 0.69 -0.55 0.19 0.01 Ejection fraction/end diastolic volume   0.14 0.21 0.51 -0.39 0.21 0.07 E’ septal (m·s-1)  0.02 0.21 0.92 0.05 0.24 0.85 E’ lateral (m·s-1)  0.03 0.21 0.89 -0.23 0.22 0.31 Pulse pressure/SVI (mmHg· m2·mL-1)  0.34 0.20 0.11 -0.26 0.22 0.24 SVI/pulse pressure (mL·mmHg-1·m-2)  -0.33 0.20 0.11 0.23 0.22 0.31 E (m·s-1)  -0.01 0.21 0.95 -0.17 0.23 0.46 A (m·s-1)  -0.05 0.21 0.82 0.08 0.23 0.74 E/A   -0.008 0.21 0.97 -0.08 0.23 0.74 E/E’ septal   -0.01 0.21 0.95 -0.18 0.23 0.45 E/E’ lateral   -0.04 0.21 0.87 0.12 0.23 0.61 EA (mmHg·mL-1)  0.24 0.21 0.26 -0.34 0.21 0.12 EAI (mmHg·mL-1·m-2)  0.24 0.21 0.25 -0.32 0.21 0.14 ELV (mmHg·mL-1)  -0.09 0.21 0.68 -0.33 0.21 0.14 ELVI (mmHg·mL-1·m-2)  -0.11 0.21 0.62 -0.31 0.21 0.16 EAI/ELVI  0.38 0.20 0.06 -0.07 0.22 0.76 Systemic vascular resistance (mmHg·min·L-1)  0.15 0.21 0.50 -0.11 0.22 0.62  A, late ventricular diastolic filling velocity; E, early ventricular diastolic filling velocity; E’, mitral annular tissue velocity; EA , arterial elastance; EAI, arterial elastance indexed for body surface area; ELV, ventricular elastance; ELVI, ventricular elastance indexed for body surface area; SD, standard deviation; SVI, stroke volume indexed for body surface area; VO2max, maximal aerobic capacity  In general, cardiac rotation and strain measures were not found to correlate with VO2max, as outlined on Table 8.18.  Changes in rotation and strain measures following maximal  140  aerobic exercise were not found to correlate with maximal aerobic capacity.  Following submaximal exercise, the changes in circumferential and radial strain resulting from submaximal exercise, may be related to maximal aerobic capacity, where individuals with greater maximal aerobic capacity may experience less change in radial strain and greater change in circumferential strain compared to their less fit counterparts.   Table 8.18 The association of VO2max with changes in cardiac rotation and strain measures following maximal and submaximal aerobic exercise   Maximal Exercise     (n = 24) Submaximal  Exercise      (n = 22) Correlate with VO2max Β SE P value Β SE P value        Peak (systole)       Rotation  (°) 0.03 0.21 0.88 0.01 0.21 0.97 Rotation velocity (°·s-1) -0.32 0.20 0.13 -0.14 0.21 0.51 Longitudinal strain (%)  0.28 0.20 0.18 -0.33 0.21 0.13 Longitudinal strain rate (s-1)  0.25 0.21 0.23 -0.19 0.22 0.40 Radial strain (%)  -0.04 0.21 0.86 -0.36 0.20 0.09 Radial strain rate (s-1)  -0.34 0.20 0.11 0.18 0.21 0.39 Circumferential strain (%)  -0.01 0.21 0.98 0.39 0.20 0.06 Circumferential strain rate (s-1)  0.05 0.21 0.83 0.27 0.21 0.21        Peak (diastole)       Rotation velocity (°·s-1) -0.11 0.21 0.61 0.14 0.21 0.50 Longitudinal strain rate (s-1)  -0.31 0.20 0.14 0.17 0.22 0.46 Radial strain rate (s-1)  -0.07 0.21 0.73 0.13 0.21 0.54 Circumferential strain rate (s-1)  -0.06 0.21 0.79 -0.32 0.20 0.13  SD, standard deviation  8.4 Discussion  This is the first investigation to evaluate cardiac structure and function in response to aerobic exercise among Aboriginal populations.  Healthy, young Aboriginal and European adults were found to experience similar cardiac responses to maximal aerobic exercise.  However, differences in responses to submaximal exercise were identified, where Aboriginal adults demonstrated responses to 60% of maximal aerobic capacity, including decreases in end diastolic volume, stroke volume, and compliance, with increases in elastance and stiffness, while these  141  changes were not observed among the European adults.  Among asymptomatic individuals, maximal and near-maximal exercise are prognostic for identifying underlying cardiovascular disease or risk of developing cardiovascular disease (246).  As cardiovascular responses to exercise are greater predictors of future cardiovascular disease mortality than many traditional risk factors, including hypertension, cholesterol, and smoking (251), and Aboriginal populations experience greater cardiovascular disease and many cardiovascular disease risk factors than non-Aboriginal populations, including European, East Asian and South Asian (12, 126, 189), evaluating the cardiovascular response to exercise among this population is important to understand the underlying cardiovascular disease experience and risks.    With exercise, physiological demands, including blood flow to working muscles, increase (425).  In order to meet these needs, cardiac function increases during exercise (425).  Changes in cardiac function with maximal and submaximal exercise have previously been reported, including systolic left ventricular posterior wall thickness and diastolic left ventricular internal diameter (426).  These results were also observed among both Aboriginal and European adults in response to aerobic exercise, as well as increases in ejection fraction.  Increases in ejection fraction with exercise have been identified among older and younger adults, with greater increases among younger adults (427).  Cardiac output and stroke volume are also known to increase from rest with exercise, as observed in the present investigation (428).  Cardiac measures including fractional shortening, wall stress, ejection fraction/end diastolic volume, peak E' septal velocity, peak E' lateral velocity, ventricular elastance, arterial-ventricular coupling and longitudinal strain have also been reported to change following maximal aerobic exercise in a healthy, young, active adult population (336).  In the current investigation, changes in arterial-ventricular coupling, peak E velocity, and peak E/E' septal velocity were observed following submaximal exercise.  However, changes in fractional shortening, wall stress, and peak E' velocities were not observed in the current investigation.  The increased arterial elastance and arterial-ventricular coupling observed in the present investigation are consistent with findings from previous exercise assessments (427).  Arterial compliance and vascular resistance are known to decrease, and arterial stiffness is known to increase with exercise, as identified in the present investigation (428).    Maximal and submaximal exercise were found to have differential influences on cardiac function.  The greater increase in cardiac output and decrease in ejection fraction with maximal  142  exercise are expected.  As exercise intensity increases, physiological needs increase accordingly (425).  Maximal and submaximal exercise utilize different aerobic capacities and present different physiological demands, thus cardiac function responses to maximal and submaximal exercise to varying degrees, according to the relative intensity (425).  Increased cardiac output and decreased ejection fraction have previously been reported with increasing exercise intensity (425, 427).  Further, greater declines in arterial-ventricular coupling with maximal exercise compared to submaximal exercise have been previously reported (427), similar to the findings in this investigation.  Greater decreases in arterial stiffness, and greater increases in arterial compliance and vascular resistance are known to occur with maximal aerobic exercise compared to submaximal exercise (428).  The present investigation identified greater reductions in vascular resistance following maximal aerobic exercise compared to submaximal exercise, though arterial compliance and stiffness changes were not found to be statistically different.    Ethnic differences in cardiac function were identified among cardiac responses to submaximal exercise, including end systolic volume, end diastolic volume, diastolic left ventricular posterior wall thickness, stroke volume, SVI, systolic blood pressure/end systolic volume, arterial compliance, and arterial stiffness.  Aboriginal adults were found to demonstrate the expected changes in cardiac measures following submaximal exercise.  However, these changes were not identified among the European population.  As these changes are expected, based on previous investigations (336, 427, 428), both ethnic groups would be expected to demonstrate these responses to submaximal exercise.  The ethnic difference in these results may suggest the Aboriginal adults were not able to recover as quickly as the European adults, or the European adults were not sufficiently stimulated by the 60% of aerobic capacity.  These results may indicate greater risks of cardiac dysfunction among Aboriginal adults, as a greater response was produced at a similar intensity among individuals of similar aerobic capacity.  Ethnic differences in cardiac strain, myocardial rate of contractile function, a measure of left ventricular performance (429).  Poorer systolic and diastolic myocardial function are associated with hypertrophic remodeling .  Subtle alterations in left ventricular function may indicate early signs of myocardial pathology preceding left ventricular structural changes with cardiovascular disease development (429).  While differences in cardiac structure and function were generally not identified at rest, cardiac responses to exercise can provide additional information regarding subclinical cardiovascular disease development.  Individuals who are asymptomatic at rest may  143  demonstrate symptoms of cardiovascular disease post-exercise (246).  Similarly, while ethnic differences were not apparent at rest, ethnic differences in cardiac responses to submaximal exercise may reflect ethnic differences in cardiac performance and early signs of myocardial pathology.     Changes in measures of cardiac structure and function in response to aerobic exercise were not found to be related to VO2max.  This finding is consistent with previous identifications of a lack of correlation between aerobic capacity and resting cardiac measures (383).  Measurements of cardiac function during exercise may be more closely related to aerobic capacity (224, 245), rather than resting measures.  Measures of cardiac function during exercise may provide more clinically relevant information, as asymptomatic individuals may demonstrate cardiac function abnormalities during exercise (224, 245).    This investigation is the first to evaluate cardiac structure and function in response to exercise among Aboriginal populations.  Inclusions of both maximal and submaximal exercise, are a strength of this investigation, as both maximal and submaximal cardiovascular responses to exercise are predictive of future cardiovascular disease events (252, 254).  Further, as individuals regularly include physical activity within their daily life (180, 238), understanding how the heart responds to this activity among an 'at risk' population is important for understanding future risk.   This investigation evaluated individuals of two distinct ethnic groups, with matched age, sex, aerobic fitness, body composition, and physical activity.  As these influencing factors were similar between the two groups, this investigation is more strongly able to evaluate ethnic differences directly.   This investigation is limited by the small sample size.  A larger sample size may have more consistently identified significant changes resulting from exercise.  Many measures were identified with trends of change with exercise (p < 0.10), and these changes may have been statistically significant with a larger sample size.  This sample of young adults free of chronic health conditions may not represent the Aboriginal population as a whole.  However, these individuals demonstrated similar baseline measures to healthy middle-aged Aboriginal adults, suggesting these results are consistent with other Aboriginal samples free of chronic health conditions.  As Aboriginal populations consist of many distinct nations, each with their own cultural history, language, and beliefs, a single sample of individuals may not accurately reflect the whole sample (18, 61, 364).  Further, as this study included individuals from several different  144  nations, including both First Nations and Métis individuals, the results may not accurately reflect any of the individual groups sampled.    8.5 Conclusion  Aerobic exercise elicited changes in cardiac function among both Aboriginal and European adults.  Aboriginal and European adults demonstrated similar cardiac functional responses to maximal exercise.  However, submaximal exercise was found to produce changes in left ventricular volumes, elastance and stiffness among Aboriginal participants, but not among European adults.       145  9. Conclusions 9.1 Discussions and Conclusions This series of investigations has produced new insight into the cardiovascular disease risks among Aboriginal populations.  Specifically, Aboriginal men were found to have greater systolic blood pressures and small arterial compliance, though lower BRS compared to females.  Aboriginal females were found to have lower left ventricular mass and dimensions, end diastolic volume, stroke volume, and cardiac output, and greater systemic vascular resistance.  This investigation identified greater increases in IMT and PWV, and decreases in arterial compliance and BRS among Aboriginal adults compared to Europeans with increasing mean arterial pressure.  Aboriginal adults were found to experience these poorer outcome measures at a blood pressure correlating to above 135 mmHg systolic and 85 mmHg diastolic.  Further, hypertension was not found to correlate to measures of body composition among Aboriginal adults, contrary to correlations among European adults.  In response to exercise, only European adults were found to experience decreases in blood pressures.  Further, Europeans demonstrated decreases in BRS following submaximal aerobic exercise, while no changes were observed among Aboriginal adults.  While similar cardiac functional responses to maximal aerobic exercise were experienced between Aboriginal and European adults, only Aboriginal adults were found to have decreased end diastolic volume, stroke volume, compliance, and increased stiffness and elastance following submaximal exercise.   Previous investigations have evaluated older individuals and have not compared directly to other ethnic groups.  This is also the first investigation to evaluate the response to exercise among Aboriginal populations using modern cardiac and vascular measures.  The inclusion of a large age range in the vascular assessment also adds to the Aboriginal literature which largely assesses older individuals and those with chronic health conditions.  In this series of investigations, Aboriginal adults were identified as experiencing greater risks of cardiovascular disease through several investigations.  While this investigation identified Aboriginal and European adults as having similar mean blood pressures, vascular and cardiac measures, different relationships between blood pressure and vascular measures were identified as well as some different responses to exercise.  Aboriginal individuals with higher blood pressures were identified as having greater risks of cardiovascular disease than Europeans with similar blood  146  pressure.  In response to exercise, Aboriginal participants did not experience reductions in blood pressure post-exercise as observed among the European adults.  Aboriginal adults were also found to have a lack of BRS and systemic vascular resistance response to submaximal exercise.  Cardiac responses to maximal exercise were found to be similar among Aboriginal and European adults; however, Aboriginal adults demonstrated changes in response to submaximal exercise not identified among European adults.  Collectively, these results suggest Aboriginal adults may experience greater risks and progression of cardiovascular disease than European adults. Associations between hypertension and obesity were identified among European adults, but were absent among Aboriginal adults.  As obesity is known to be an important contributor to hypertension, the absence of this relationship among Aboriginal populations may account for the lower rates of hypertension identified among this population, despite greater experiences of cardiovascular disease, diabetes, obesity, and other chronic health conditions.  These results suggest cardiovascular disease risk experience and development may occur differently among Aboriginal populations.  As Aboriginal adults demonstrate lower BRS and arterial compliance, with greater PWV and IMT at the same blood pressure, compared to Europeans, greater cardiovascular disease progression may also be occurring among Aboriginal adults.  Consequently, cardiovascular disease risks should be evaluated among all Aboriginal adults, in addition to those individuals with obesity; Aboriginal adults who appear healthy should also be monitored for blood pressure increases and development of subclinical cardiovascular disease.  Further research may be needed to better understand the progression of cardiovascular disease development within this population. This investigation identified correlations between vascular measures and cultural identity measures among Aboriginal adults.  In perspective of the historical trauma and multi-generational stress response experienced by many Aboriginal individuals, these results may indicate a link between these traumas and biological markers of hypertension.  This finding may highlights the larger picture implications of cultural and historical influences on physiological responses and physical health risks.  Care must be taken to ensure medical treatment and interventions are performed in a safe and culturally appropriate manner. 9.2 Strengths and Limitations 9.2.1 Strengths   147  The inclusion of individuals across a wide spectrum of ages, from several locations around the province provides a more broad picture of the vascular status of Aboriginal populations.  Further, the inclusion of a number of vascular measures, evaluating distinct properties of vascular structure and function, allowed for a more broad picture to be evaluated.  This investigation utilized vascular measures not previously assessed in Aboriginal populations.  While several investigations have evaluated cardiac structure and function among Aboriginal adults, this is the only investigation to evaluate elastance, strain and arterial-ventricular coupling.  Additionally, this investigation evaluated the responses to both maximal and submaximal exercise among this population, a physiological stressor not previously examined in this population.   This investigation directly compared individuals of Aboriginal and European descent, directly comparing individuals of similar age, body size, aerobic fitness, income, and education.  The direct ethnic comparison utilized in this investigation allowed for the major covariates known to exist between Aboriginal and European populations have been eliminated, resulting in more direct comparison of vascular and cardiac measures.  Direct comparisons of vascular measures between Aboriginal and other ethnic groups have not previously been investigated beyond traditional measures of blood pressure.   9.2.2 Limitations  This series of investigations is limited by the small sample size of participants.  In particular, the small sample size of participants in the cardiac and exercise investigations may have limited the ability to identify ethnic differences in cardiac measures and cardiac and vascular responses to exercise.  While limited cardiac differences were identified between ethnic groups, a larger sample size may have allowed greater evaluations, including comparisons of cardiac hypertrophy and relationships between cardiac measurements and blood pressures.  The inclusion of additional vascular measures, including endothelial function (flow-mediated dilatation) and augmentation index, was limited by constraints of participant time, research personal and facility coordination.  While a number of vascular measures were included in this investigation, the addition of flow-mediated dilatation would have added additional characteristics and responses, evaluating another aspect of vascular function.  While limited information regarding vascular dynamics of Aboriginal populations exists, the only comparison  148  between ethnic groups to include Aboriginal populations utilized augmentation index.  Thus the exclusion of augmentation index in this series of investigations prevents directly evaluating the findings in previous work.  9.3 Implications and Applications The identification of differential relationships between blood pressure and vascular measures among Aboriginal and European adults identifies Aboriginal adults with elevated blood pressures as experiencing greater risks of cardiovascular disease than their European counterparts.  The implications of this finding suggest blood pressure control and cardiovascular disease risk management should be more aggressively pursued among Aboriginal adults with elevated blood pressures.  Further, as mean arterial pressures corresponding to high-normal blood pressure ranges (130-130 mmHg systolic or 80-89 mmHg diastolic) among Aboriginal adults were found to be associated with greater IMT and PWV, and lower arterial compliance and BRS compared to European adults with hypertension, treatment and control of blood pressure among Aboriginal adults may be needed beginning at high-normal blood pressure ranges.  Maximal exercise was found to decrease the vascular resistance of Aboriginal adults, while submaximal exercise may be less effective.  These decreases in vascular resistance may reduce blood pressures and risks of cardiovascular disease.  As such, greater intensities of exercise may be more beneficial among this population.  Aboriginal adults should be encouraged to engage in regular physical activity, striving for intensities greater than 60% of VO2max.   Exercise programs for Aboriginal adults may be more effective when utilizing higher intensity interval training.  As Aboriginal adults experienced vascular responses to maximal exercise, with a lack of response to submaximal exercise, greater intensity training programs may be more effective for maintaining lower vascular resistance and reducing subclinical cardiovascular disease development and progression.  Interval training provides the benefits of high intensity exercise while allowing individuals to exercise for greater durations than attempting to sustain a single maximal session, resulting in benefits of both high intensity exercise and sufficient duration of exercise.  Exercise programs for Aboriginal adults should aim to incorporate interval training as the main aerobic training component, including intervals of 2-5 minutes of maximal or near-maximal aerobic exercise, interspersed with intervals of 2-5 minutes  149  of active rest.  Aboriginal adults should incorporate aerobic interval training on 2-3 days per week.   Among Aboriginal adults, a correlation between cultural identity measures and hypertension was identified.  These results highlight the importance of recognizing historical trauma and multi-generational stress response in addressing physical health among Aboriginal populations.  In reducing the mortality and morbidity gap between Aboriginal populations and the non-Aboriginal population, a wider approach may be required, beyond traditional medications and prescriptions.  These findings also highlight the importance of culturally appropriate strategies to address health disparities, including ownership, implication, and initiation of strategies from within Aboriginal communities.  9.4 Future Research  The greater IMT and PWV, and lower arterial compliance and BRS at higher blood pressures identified among Aboriginal populations may translate into greater experiences of cardiac hypertrophy an risks of chronic heart failure at lower blood pressures than observed among European populations.  This investigation identified changes in BRS and vascular resistance resulting from exercise, but no differences in PWV and arterial compliance.  These findings may suggest a neurovascular difference between Aboriginal and European adults.  In order to further evaluate the possible impacts of neurovascular properties, future studies should evaluate flow-mediated dilatation to evaluate endothelial function, and Doppler blood flow to evaluate neurovascular responses.    While evaluating vascular and cardiac responses to aerobic exercise, future investigations should attempt to measure cardiac function during aerobic exercise.  As cardiac measures during aerobic exercise are a better indicator of fitness, these measures may further expand on the Aboriginal specific experience of cardiac function during activity.  The employment of cardiac measures during exercise will provide better understandings of how the heart is responding to exercise and increases in exercise intensity, which influence and indicate the development of cardiac dysfunction.  Additionally, to progression of recovery of end diastolic volume, stroke volume, stiffness, compliance, and elastance among Aboriginal and European adults should be evaluated to determine if cardiac recovery from exercise longer among Aboriginal adults, potentially demonstrating greater risks of cardiovascular disease.   150   Additional research is required to assess the adequate intensity of aerobic exercise required to elicit vascular responses among Aboriginal adults.  Further research is needed to understand the benefits of interval training for Aboriginal adults.  Future research should investigate whether a submaximal intensity greater than 60% is sufficient to produce vascular responses, or whether interval training incorporating intervals of maximal or near-maximal exercise are more effective.  Interval training interventions are required to assess benefits of cardiac and vascular dynamics, as well as traditional risk factors such as lipids, blood glucose, blood pressure and body composition.  More information is needed to understand the ideal balance of intervals and rest, the duration of intervals and rest, the weekly frequency of exercise, and the duration of exercise programs required to significantly and sustainably improve CVD risks among Aboriginal adults.  Longitudinal investigations of the progression of cardiovascular disease among Aboriginal populations will provide a better understanding of the development of cardiovascular disease and its risk factors.  A better understanding of the implications of obesity and hypertension on this disease may also be determined from longitudinal research following individuals starting prior to the development of cardiovascular disease, hypertension or obesity.  Further, longitudinal research would help inform researchers and clinicians on the development of cardiovascular disease in relation to blood pressure.  In longitudinal monitoring, increases in blood pressure over time and blood pressure ranges could be directly linked to stages of cardiovascular disease progression.  Awareness of cardiovascular disease progression and corresponding blood pressures may allow for identifying increased risks of subclinical cardiovascular disease development and advise treatment strategies through blood pressure monitoring.  The sample sizes in these investigations were small.  Future research should be employed to further these findings using a larger sample size.  Additionally, the participants evaluated pre and post exercise were young and healthy adults.  Further research should evaluate the cardiac and vascular responses to exercise across a spectrum of ages and health statuses.      151  References 1. 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