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Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid… Sandhu, Supna; Al-Sarraf, Ahmad; Taraboanta, Catalin; Frohlich, Jiri; Francis, Gordon A Sep 11, 2011

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RESEARCH Open AccessIncidence of pancreatitis, secondary causes, andtreatment of patients referred to a specialty lipidclinic with severe hypertriglyceridemia:a retrospective cohort studySupna Sandhu1, Ahmad Al-Sarraf2, Catalin Taraboanta1, Jiri Frohlich2 and Gordon A Francis1*AbstractBackground: Severe hypertriglyceridemia (HTG) is one cause of acute pancreatitis, yet the level of plasmatriglycerides likely to be responsible for inducing pancreatitis has not been clearly defined.Methods and Results: A retrospective cohort study was conducted on patients presenting non-acutely to theHealthy Heart Program Lipid Clinic at St. Paul’s Hospital with a TG level > 20 mM (1772 mg/dl) between 1986 and2007. Ninety-five patients with TG > 20 mM at the time of referral were identified, in who follow up data wasavailable for 84. Fifteen patients (15.8%), with a mean outpatient TG level of 38.1 mM, had a history of acutepancreatitis. Among 91 additional patients with less severe HTG, none had a history of pancreatitis when TG werebetween 10 and 20 mM. Among patients with TG > 20 mM on presentation, 8 (8.5%), with a mean TG level of67.8 mM, exhibited eruptive xanthomata. A diet high in carbohydrates and fats (79%) and obesity (47.6%) were thetwo most frequent secondary causes of HTG at initial visit. By 2009, among patients with follow up data 53%exhibited either pre-diabetes or overt Type 2 diabetes mellitus. Upon referral only 23 patients (24%) were receivinga fibrate as either monotherapy or part of combination lipid-lowering therapy. Following initial assessment by alipid specialist this rose to 84%, and remained at 67% at the last follow up visit.Conclusions: These results suggest hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitisunless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and fats, and obesity are the mainsecondary causes of HTG, and that fibrates are frequently overlooked as the drug of first choice for severe HTG.Keywords: Hypertriglyceridemia, triglycerides, pancreatitis, dysglycemia, diabetes, fibratesBackgroundHypertriglyceridemia (HTG), classically defined as fast-ing plasma triacylglycerols (triglycerides, TG) > 2.3 mMor 200 mg/dl, or 1.7 mM (150 mg/dl) in the definitionof metabolic syndrome [1], is a common laboratoryfinding. Severe hypertriglyceridemia, e.g., TG > 20 mM(1772 mg/dl), is much rarer and almost always causedby a combination of inherited and secondary factors[2,3]. Genetic disorders leading to hypertriglyceridemiainclude familial combined hyperlipidemia, familialhypertriglyceridemia, remnant removal disease (Type 3dyslipidemia), deficiencies of lipoprotein lipase or apoli-poprotein CII, and more recently characterized muta-tions including variants of apolipoprotein A5 [4,5]. Themost common secondary contributors to severe hyper-triglyceridemia include poorly controlled diabetes melli-tus, obesity, high fat and simple carbohydrate diet,excess alcohol consumption, hypothyroidism, and medi-cations including thiazide diuretics, b-blockers, oralestrogen, retinoids, and anti-retroviral agents [2,3].Patients with severe HTG may present with classicfindings such as abdominal pain or overt pancreatitis,eruptive or palmar xanthomas, lipemia retinalis, or they* Correspondence: gordon.francis@hli.ubc.ca1Department of Medicine, Healthy Heart Program Prevention Clinic, UBCJames Hogg Research Centre, Providence Heart + Lung Institute, St. Paul’sHospital, University of British Columbia, 1081 Burrard St., Vancouver, BC V6Z1Y6 CanadaFull list of author information is available at the end of the articleSandhu et al. Lipids in Health and Disease 2011, 10:157http://www.lipidworld.com/content/10/1/157© 2011 Sandhu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.may be asymptomatic [2,3]. The most significant com-plication of severe HTG is acute pancreatitis, which maylead to pancreatic necrosis and death [2,6]. The inci-dence of classic signs and symptoms of HTG, includingpancreatitis, however, has not been determined inpatients presenting with severe HTG. In addition, thelevel of plasma triglycerides at which acute pancreatitiscan be ascribed specifically to the presence of HTG hasnot been reported.The purpose of this study was to determine the fre-quency of physical signs and symptoms of HTG includ-ing pancreatitis among patients with severe HTGreferred to a specialty lipid disorders clinic over a 21-year period. Specifically, our study attempted to deter-mine: (a) the frequency of classical signs and symptomsassociated with severe HTG; (b) the most common sec-ondary factors contributing to TG > 20 mM (1772 mg/dl); (c) differences in treatment for severe HTG betweenreferring physicians and lipid clinic specialists; and (d)changes in the lipid profile of patients with severe HTGfollowed at a specialty lipid clinic. Overall, we found anabsence of pancreatitis unless TG were > 20 mM, a rela-tively low incidence of classic clinical findings of HTGsuch as eruptive xanthomas, the presence of diabetes orpre-diabetes in the majority of HTG subjects, and a ten-dency of non-lipid specialists to overutilize statins andunderutilize fibrates as their first-line treatment forsevere HTG.ResultsPatient Demographics (Table 1)Between 1986 to 2007 the clinic saw a total of 95patients with TG ≥ 20 mM at the time of first referral.The mean age ± standard deviation was 54.2 ± 11.9years, with 70 patients (73.7%) being male and 75patients (78.9%) Caucasian.History of PancreatitisFifteen patients (15.8%) had a history of pancreatitisprior to referral to the clinic. Of these, the mean TGlevel at the time of non-acute presentation to the clinicwas 38.13 mM [median 30.91 mM (IQ 25.6 - 52.2)],with the lowest referral TG level associated with priorpancreatitis being 20.5 mM (1815 mg/dl). Peak TGlevels at the time of acute pancreatitis were not availablefor this analysis. Analysis of an additional cohort of 91patients with TG levels between 10 and 20 mM (886 -1771 mg/dl) at time of presentation to clinic revealed ahistory of pancreatitis in only 3 patients. In these 3,levels of TG at the time of acute pancreatitis were avail-able, and all were > 20 mM (1771 mg/dl). As such, weconclude that pancreatitis is unlikely to occur as a resultof hypertriglyceridemia unless TG are > 20 mM acutely.Prevalence of dysglycemia (Table 2)Thirty patients (31.6%) had a prior diagnosis of diabetesmellitus (DM). Of these, HbA1 c levels were not routi-nely available, however the majority (23/30) had poorcontrol, with a mean FBS of 9.97 ± 4.37 mM (179 ± 79mg/dL) at presentation to the clinic, and only 11 wereon antihyperglycemic medication. An additional 5patients (5.3%) were diagnosed with DM at their firstclinic visit. Four new diagnoses of DM were made dur-ing the follow up period. In the entire group with severehyperTG, 39 patients (41.0%) had a diagnosis of Type 2DM by 2009. An additional 11 patients (11.6%) hadimpaired fasting glucose, giving a total of 50 patients(52.6%) having impaired glucose metabolism. At the lat-est visit, 82% of patients with a diagnosis of DM weretaking antihyperglycemic medication.Other risk factors for hypertriglyceridemia and personal/family history of CVD (Table 3)Dietary assessment by clinic dietitians was performedusing three day food records plus a nutrient frequencyquestionnaire. Fat intake was considered high if >35%and carbohydrate intake high if >55% of total calories[7]. Seventy-five patients (78.9%) had a diet high in fatand carbohydrates based on these criteria. Forty-twopatients (49.4%) had no regular exercise. Alcohol con-sumption of >14 drinks/week or 7 - 14 drinks/weekwere recorded in 11 (11.6%) and 8 (8.4%) patients,respectively. Of the 15 (17.1%) patients previously diag-nosed with hypothyroidism, 5 were inadequatelyTable 1 Demographic Information for HTG Patients AtInitial Clinic Visitn/N %Mean Age (yrs) 54.2 +/- 11.9 95/95Gender Male 70/95 73.7Female 25/95 26.3Ethnicity Caucasian 75/95 78.9South Asian 12/95 12.6Chinese 4/95 4.2Other 4/95 4.2Table 2 Frequency of Diabetes and Elevated FastingBlood Sugar (FBS) in HTG Clinic Patientsn/N %At Initial Visit: Past DM Diagnosis 30/95 31.6FBS > 7 mM 23/30 76.7New DM Diagnosis 5/52 9.6At Interim: New DM Diagnosis 4/60 6.8At Latest Visit: Total DM 39/95 41.1Impaired Fasting Glucose 11/95 11.6Total with Dysglycemia 50/95 52.6Sandhu et al. Lipids in Health and Disease 2011, 10:157http://www.lipidworld.com/content/10/1/157Page 2 of 7controlled based on a TSH > 5 uIU/mL at presentation.No new diagnoses of hypothyroidism were made duringfollow up of this cohort. Twenty-four patients (25.3%)had smoked cigarettes within the past year. Sixteenpatients (16.9%) were on beta-blockers, 6 (6.4%) were onestrogen therapy, 4 (4.3%) were on anti-retroviral ther-apy, and 3 (3.2%) were on a thiazide diuretic. Twelvepatients (12.6%) had a personal history of coronaryartery disease and 5 (5.3%) of peripheral vascular dis-ease. Forty-seven patients (49.5%) indicated a history ofpremature vascular disease in first-degree relatives; only15 (15.8%) were aware of other family members havingdyslipidemia; however, this information was unknown tomany patients.Physical findings (Table 4)Obesity, defined as a body-mass-index > 30 kg/m2, waspresent in 45 patients (47.4%), 57% of whom were pre-viously diagnosed with diabetes. Overweight, as definedby a body-mass-index of 25-30 kg/m2 was present in anadditional 29.5%, with only 23% of the cohort having aBMI less than 25 kg/m2. Eight patients (8.5%) presentedwith eruptive xanthomas, occurring with a range of TGlevels of 20.5 - 171.9 mM, and a mean TG level of 67.8mM [median 51.2 mM (IQ 27.55 - 97.85)]. Of these 8patients, 2 were also felt to have lipemia retinalis (theonly 2 of the entire cohort in whom this was noted,occurring at TG levels of 25.6 and 54.3 mM), 5 wereobese, and 4 were diabetic. Three patients (3.2%) hadpalmar xanthomas. Corneal arcus was observed in 24patients (25.3%). Three patients had abdominal tender-ness at the initial visit, one of whom had a previous his-tory of pancreatitis, and 6 were noted to havehepatomegaly.Pre-Clinic and In-Clinic Treatment (Table 5)At the initial visit 23 patients (24.2%) were taking afibrate, with 17 on fibrate monotherapy, 4 on fibrate-sta-tin, 1 on fibrate-niacin, and 1 on fibrate-omega-3 fattyacids (fish oil). Sixteen patients (16.8%) were referredtaking statin monotherapy. Fifty-two patients (54.7%)were taking no hypolipidemic therapy, either due to lackof initiation or a history of lipid therapy intolerance. Allpatients received extensive dietary counseling andencouraged to limit dietary fats and simple carbohy-drates as well as alcohol consumption. After the initialvisit 80 patients (84.2%) were taking fibrate therapy,with 54 (56.8%) on fibrate monotherapy, 16 (16.8%) incombination with fish oil, 9 (9.5%) in combination witha statin, and 1 on fibrate-niacin combination. Eightpatients (8.4%) were placed on fish oil monotherapy,while one was left on statin monotherapy. At the lastvisit recorded (84 patients), 56 patients (66.7%)remained on fibrate therapy, with 31 patients (36.9%) onmonotherapy, 11 (13.1%) in combination with a statin, 4(4.8%) in combination with fish oil, and 1 in combina-tion with niacin. Six patients (7.1%) were on statinmonotherapy, 3 (3.6%) on fish oil monotherapy, and 2(2.4%) on niacin monotherapy. Of the remaining 25patients, 17 (20.2%) were on combination therapy with-out a fibrate, and 8 (9.5%) were on no treatment.Table 3 Frequency of Risk Factors in HTG Patients atInitial Clinic Visitn/N %High fat/sugar diet: 75/95 79Physical Exercise: >5/wk 13/85 15.33-5/wk 15/85 17.6< 3/wk 15/85 17.6none 42/85 49.4Alcohol Consumption: >14 drinks/wk 11/95 11.67-14 drinks/wk 8/95 8.41-7 drinks/wk 33/95 34.7none 43/95 45.3Diagnosed Hypothyroidism: 15/95 17.1with TSH>5 5/15 33.3Currently Smoking: 24/95 25.3Medications: B-blocker 16/95 16.9Estrogen 6/95 6.4Anti-retrovirals 4/95 4.3Thiazide diuretic 3/95 3.2Personal History: Premature CAD 12/95 12.6PVD 5/95 5.3Family History: Premature CVD 47/95 49.5Dyslipidemia 15/95 15.8CAD = Coronary Artery Disease; PVD = Peripheral Vascular Disease;CVD = Cardiovascular Disease; TSH = Thyroid Stimulating HormoneTable 4 Frequency of Clinical Findings in HTG Patientsn/N %Body Mass Index: > 30 kg/m2 45/95 47.425-30 kg/m2 28/95 29.5< 25 kg/m2 22/95 23.2Dermatological: Eruptive Xanthomas 8/95 8.5Palmar Xanthomas 3/95 3.2Ophthamalogical: Corneal Arcus 24/95 25.3Lipemia Retinalis 2/95 2.1Gastrointestinal: Abdominal tenderness 3/95 3.2Hepatomegaly 6/95 6.3Sandhu et al. Lipids in Health and Disease 2011, 10:157http://www.lipidworld.com/content/10/1/157Page 3 of 7Laboratory and Anthropometric Values of Patients fromInitial to Latest Visit (Table 6)Triglyceride levels decreased from a mean of 35.04 ±21.89 mM (3104 ± 1939 mg/dl) at the initial visit to8.07 ± 8.71 mM (715 ± 772 mg/dl) at the latest visit(Figure 1). Total cholesterol (TC) dropped from 12.8 ±6.37 mM (495 ± 247 mg/dl) to 6.72 ± 2.73 mM (260 ±106 mg/dl), and TC to high density lipoprotein choles-terol (HDL-C) ratio from 22.7 ± 25.59 to 6.70 ± 3.19(Figure 1). No statistically significant changes weredetected for HDL-C. Average BMI was unchanged fromfirst to the latest visit.DiscussionClinical findings in patients with severe HTGThe incidence of clinical findings including pancreatitisand physical stigmata in patients with severe HTG havenot previously been documented. Other studies havereported average acute levels of plasma TG in patientswith TG-induced pancreatitis of 51.8 mM [8] and 50.5mM [9], but did not define a lower limit of plasma TGat which HTG could be identified as the likely cause ofthe pancreatitis. A key finding of this study is that acutepancreatitis as a consequence of HTG occurs relativelyinfrequently, and rarely if ever unless TG levels aregreater than 20 mM (1772 mg/dl). In this study a his-tory of pancreatitis was present in 15.8% of individualsreferred with TG > 20 mM, occurring in patients with aminimum non-acute TG level of 20.5 mM (1816 mg/dl)and a mean non-acute TG level of 38.1 mM (3376 mg/dl). Of 91 patients seen in our clinic with non-acute TGlevels between 10-20 mM, none had a history of pan-creatitis unless their TG were > 20 mM acutely. Erup-tive xanthomas were found in only 8.5% of patients, at aminimum TG level of 20.5 mM (1816 mg/dl) and anaverage TG level of 67.8 mM (6007 mg/dl), even higherthan that required to induce pancreatitis. However, thelevel of TG did not accurately predict whether patientswould develop these signs. For instance, pancreatitis wasobserved in 2 patients with TG levels of 20-21 mM, andonly in 1 out of 5 patients who had TG>70 mM. It islikely that factors other than the TG level may contri-bute to the development of pancreatitis and other physi-cal characteristics observed in HTG patients. Furtherstudies with a greater sample size and possibly knowl-edge of the underlying genetic traits are needed to bet-ter elucidate such relationships. Lipemia retinalis was aninfrequent finding in our study. While it was uncertainwhether this was assessed at the time of non-acute pre-sentation in all patients, it appears that this finding ispresent mainly in very severe HTG and more likely tobe seen in the acute versus non-acute HTG setting.Chylomicronemia syndrome, defined as TG > 1000mg/dl (11.3 mM) plus one of either eruptive xanthomas,lipemia retinalis, or abdominal pain/pancreatitis, had apreviously quoted incidence rate of 1.7/10000 patientsTable 5 Prevalence of Lipid-lowering Medications in Clinic HTG PatientsUpon Arrival* Clinic Treatment* Latest Visit**n (%) n (%) n (%)Monotherapy: Fibrate 17 (17.9) 54 (56.8) 31 (36.9)Statin 16 (16.8) 1 (1.1) 6 (7.1)Fish Oil 1 (1.1) 8 (8.4) 3 (3.6)Niacin 1 (1.1) 0 2 (2.4)Resin 1 (1.1) 0 1 (1.2)Combination: Fibrate/Statin 4 (4.2) 9 (9.5) 11 (13.1)Fibrate/Niacin/Fish Oil 1 (1.1) 1 (1.1) 1 (1.2)Fibrate/Fish Oil 1 (1.1) 16 (16.8) 4 (4.8)Other 0 2 (2.2) 17 (20.2)* N = 95, ** N = 84Table 6 Laboratory Values and Anthropometry of HTG Patients from Initial to Latest VisitInitial Visit (mM) Latest Visit (mM) Paired t - testLaboratory: Triglycerides 35.04 ± 21.89 8.07 ± 8.7 p < 0.0001TC 12.8 ± 6.37 6.72 ± 2.73 p < 0.0001TC/HDL-C 22.7 ± 25.59 6.70 ± 3.19 p < 0.0001HDL-C 0.87 ± 1.05 1.05 ± 0.31 p = 0.224Systolic BP 126.91 ± 18.12 128.11 ± 19.96 p = 0.634Diastolic BP 80.46 ± 10.05 80.46 ± 10.05 p < 0.05Anthropometric: BMI 29.61 ± 5.17 29.55 ± 6.27 p = 0.917TC = Total Cholesterol; HDL-C = High Density Lipoprotein Cholesterol; BP = Blood Pressure; BMI = Body Mass IndexSandhu et al. Lipids in Health and Disease 2011, 10:157http://www.lipidworld.com/content/10/1/157Page 4 of 7(< 0.02%) [10]. Recent increases in obesity and DMrates, however, have led to a potential increase in thisincidence. In our high risk patient population, 23patients (24.2%) met the criteria for this syndrome.Secondary contributors to severe HTGIn addition to inherited causes of HTG that wereundoubtedly present in most if not all the patients inthis cohort, the most common secondary factors predis-posing to HTG were a high fat and carbohydrate diet,physical inactivity and obesity. In 53% of the cohort, andconcomitant with these other factors in many cases, dys-glycemia was present in the form of pre-diabetes orovert Type 2 diabetes mellitus. Two previous studiesfound similarly high levels of diabetes, 72% [8] and 43%[9], in acute HTG-induced pancreatitis. The negativeimpact of metabolic syndrome, dysglycemia and abdom-inal obesity on triglyceride levels is well documented[1,3,11]. Insulin resistance and diabetes are associatedwith an increase in plasma TG for multiple reasons,including reduced insulin-dependent inhibition of lipoly-sis in adipocytes, increased TG and VLDL productionby the liver, and impaired insulin-dependent activationof lipoprotein lipase and hydrolysis of TG-rich lipopro-teins [3,12].Although known to contribute to HTG, the incidenceof uncontrolled DM and hypothyroidism has not beenwell characterized in previous studies. The majority ofpatients (77%) with DM at first presentation to theclinic had poor glycemic control. Diagnosed hypothyr-oidism was present in 17.1% of patients, with a signifi-cant number of these (33.3%) having evidence ofinadequate thyroid hormone replacement (TSH > 5uIU/mL). The high incidence of such comorbiditieshighlights the importance of controlling these factors toprevent severe HTG. All told, 100% of our patients hadat least one secondary factor contributing to their HTG.Although genetic testing is not currently available forFigure 1 Triglycerides, Total Cholesterol, and Total Cholesterol:HDL-C Ratio at Initial and Latest Clinic Visit in HTG Patients. *,significant difference between means, p < 0.001 (two tail; pair student t-test).Sandhu et al. Lipids in Health and Disease 2011, 10:157http://www.lipidworld.com/content/10/1/157Page 5 of 7familial combined hyperlipidemia and is not routinelyavailable for many other inherited causes of HTG, ourassumption is that in most if not all of our patients acombination of primary genetic plus secondary causescontributed to their severe HTG. In any patient withTG levels >3-4 mM, it should be assumed there is alikely underlying inherited cause of HTG present, aggra-vated further by one or more secondary factors.Lipid Lowering TherapyAt initial visit, almost as many patients were being trea-ted by their referring physician with statin monotherapyas fibrate monotherapy, the recommended first linetreatment for severe HTG. Lipid specialists, on theother hand, treated most patients with fibrate mono-therapy. It has been well documented that fibrates arethe most efficacious first line pharmacotherapy forHTG, and typically lower TG very rapidly and effectively[3,11,13]. Adjuncts to this include lifestyle modifications,such as following a low fat and low simple carbohydratediet, avoiding alcohol, control of blood sugars, and fishoil Ω-3 fatty acid) supplementation [3,14]. Fish oil dosesof at least 2 g in doses divided two or three times dailyare needed to have any major TG-lowering effect, anddoses of up to 12 g daily can be used. Niacin (nicotinicacid) is also a potent TG-lowering agent. It is not practi-cal to use in the acute setting, however, where reducingthe risk of pancreatitis is the main priority, given thetime needed to titrate the niacin dose to therapeuticlevels (≥ 1000 mg daily). In most cases, apart fromhomozygous lipoprotein lipase or apolipoprotein CIIdeficiency, use of a fibrate in combination with a low fatand carbohydrate diet and improvement in blood sugarcontrol is highly efficacious in reducing severe HTG tomore moderate levels, as seen in our cohort. While sta-tins have some TG-lowering effect, ranging from 20 -28% at higher doses of newer statins [15], they are noteffective enough in this regard to remove the risk ofpancreatitis in patients with severe HTG, and shouldnot be used on their own as first line agents. The discre-pancy between treatments initiated by referring physi-cians and lipid specialists needs to be addressed,perhaps by an education series focused on lipid treat-ment. By doing so, it is possible that more patientswould be able to achieve marked TG reduction withoutlipid clinic referrals.In patients with severe HTG and persistent elevationof apolipoprotein B100 or LDL-C following initiation ofTG-lowering therapy, treatment with combined fibrate/statin may be indicated. Although the recent ACCORDLipid trial did not find additional benefit of adding feno-fibrate to a statin in terms of cardiovascular event ratein patients with type 2 diabetes [16], it may be necessaryto continue fibrate therapy long term in severe HTGpatients who also require a statin, in order to maintainTG levels out of the range of risk for pancreatitis. Whilewe did not observe pancreatitis in anyone with TGlevels < 20 mM, due to the volatile nature of TG eleva-tion when secondary factors are not well controlled, werecommend attempting to lower TG levels to not morethan a maximum of 6-8 mM in order to reduce the riskof TG rising into pancreatitis range acutely.ConclusionsThis is the first cohort in which incidence rates of clini-cal findings in patients with severe HTG have beenquantified. The classic findings of pancreatitis and erup-tive xanthomas occurred in a relatively small percentageof patients, and not unless TG were > 20 mM (1772mg/dl). Patients with extreme HTG have a combinationof primary and secondary factors contributing to theirHTG. Lifestyle changes (low fat and simple carbohydratediet, increased exercise) and a reduction in comorbid-ities (uncontrolled DM and hypothyroidism) are criticalaspects of managing HTG in conjunction with pharma-cotherapy using fibrates and omega-3 fatty acid supple-ments. Fibrates remain the treatment of choice forsevere HTG, with statins lacking sufficient TG-loweringeffect to remove the risk of pancreatitis.MethodsA retrospective chart review was conducted in theHealthy Heart Program Lipid (now Prevention) Clinic atSt. Paul’s Hospital, Vancouver, Canada. Patients seen inthe clinic between the years of 1986 and 2007 withplasma triglyceride levels greater than 20 mM uponreferral were included in the study. Patients were identi-fied either by individual chart review, or after 1999 byscan of an electronic clinic database. In total, 95 patientsmet this inclusion criterion; of those, 84 patientsreturned for at least one follow up visit, and manypatients have been followed intermittently for severalyears. Data extracted from the chart from the patient’sinitial visit and most recent follow up visit for the cur-rent study included: demographics (age, gender, ethnicbackground); history of pancreatitis; presence ofincreased fasting glucose or diagnosis of diabetes atinitial or follow up visit; other historical features includ-ing secondary factors potentially contributing to the pre-sence of HTG (dietary carbohydrates and fats, level ofphysical activity, alcohol consumption, hypothyroidism,current smoking, and medications potentially raising TGincluding thiazide diuretics, b-blockers, oral estrogen,and anti-retroviral agents), history of cardiovascular dis-ease, and family history of premature vascular disease orknown dyslipidemia; physical findings including bodymass index, dermatologic findings including eruptive orpalmar xanthomas, eye findings including corneal arcusSandhu et al. Lipids in Health and Disease 2011, 10:157http://www.lipidworld.com/content/10/1/157Page 6 of 7and lipemia retinalis, and abdominal findings includingepigastric tenderness and hepatomegaly. Use of lipid-lowering therapies including fibrates (gemfibrozil orfenofibrate), statins (simvastatin, pravastatin, atorvastatinor rosuvastatin), niacin, omega-3 fatty acids (fish oils),and bile acid binding resins were recorded. Total choles-terol, triglyceride levels, HDL-cholesterol (HDL-C) andtotal cholesterol:HDL-C ratio were recorded for theinitial and follow up visits. This study was approved bythe Institutional Ethics Review Board for Human Stu-dies, Providence Health Care Research Institute, Van-couver, BC, Canada.Statistical AnalysisThe cohort’s characteristics were expressed as mean andstandard deviation for continuous variables. Frequencyof findings was used for dichotomous traits. Means werecompared using a paired Students t test, when normalitywas confirmed, two tailed - 95% CI with a p value <0.05 considered statistically significant. Data analysis wasperformed using SPSS v12.0 (SPSS Inc., Chicago, IL).AcknowledgementsThis study was funded by a Faculty of Medicine Summer Studentship Awardto SS, and by CIHR operating grant MOP-12660 to GAF.Author details1Department of Medicine, Healthy Heart Program Prevention Clinic, UBCJames Hogg Research Centre, Providence Heart + Lung Institute, St. Paul’sHospital, University of British Columbia, 1081 Burrard St., Vancouver, BC V6Z1Y6 Canada. 2Department of Pathology and Laboratory Medicine, HealthyHeart Program Prevention Clinic, UBC James Hogg Research Centre,Providence Heart + Lung Institute, St. Paul’s Hospital, University of BritishColumbia, 1081 Burrard St., Vancouver, BC V6Z 1Y6 Canada.Authors’ contributionsSS participated in the collection and analysis of data and writing of themanuscript. AA-S and CT participated in the data collection and analysis. JFparticipated in conception of the study, supervision, data analysis andmanuscript editing. GF participated in conception and oversight of thestudy, supervision, data analysis and manuscript preparation. All authors readand approved the final version of the manuscript.Competing interestsThe authors declare that they have no competing interests.Received: 18 July 2011 Accepted: 11 September 2011Published: 11 September 2011References1. Alberti KG, Zimmet P, Shaw J: The metabolic syndrome–a new worldwidedefinition. Lancet 2005, 366:1059-1062.2. Brunzell JD, Deeb SS: Familial lipoprotein lipase deficiency, apo CIIdeficiency and hepatic lipase deficiency. In The Metabolic and MolecularBases of Inherited Disease.. 8 edition. Edited by: Scriver CR, Beaudet AL, SlyWS, Valle D. New York: McGraw-Hill; 2001:2789-2816.3. Yuan G, Al-Shali KZ, Hegele RA: Hypertriglyceridemia: its etiology, effectsand treatment. 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Barter PJ, Rye KA: Cardioprotective properties of fibrates: which fibrate,which patients, what mechanism? Circulation 2006, 113:1553-1555.14. Oh R: Practical applications of fish oil (Omega-3 fatty acids) in primarycare. J Am Board Fam Pract 2005, 18:28-36.15. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA,Blasetto JW: Comparison of the efficacy and safety of rosuvastatin versusatorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).Am J Cardiol 2003, 92:152-160.16. Ginsberg HN, Elam MB, Lovato LC, Crouse JR, Leiter LA, Linz P,Friedewald WT, Buse JB, Gerstein HC, Probstfield J, et al: Effects ofcombination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010,362:1563-1574.doi:10.1186/1476-511X-10-157Cite this article as: Sandhu et al.: Incidence of pancreatitis, secondarycauses, and treatment of patients referred to a specialty lipid clinic withsevere hypertriglyceridemia: a retrospective cohort study. Lipids inHealth and Disease 2011 10:157.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitSandhu et al. Lipids in Health and Disease 2011, 10:157http://www.lipidworld.com/content/10/1/157Page 7 of 7


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