Zahra Raza, MD; Ashwini Kamath Mulki, MD; Linda Contillo Garufi, MD, MEd; : Grant M. Greenberg, MD, MHSA, MA Department of Family A strategic approach ­Medicine, Lehigh Valley Health Network, Allentown, PA This review, and the at-a-glance tables that follow, detail

Ashwini.KamathMulki@ indications and strategies for the treatment of adults with lvhn.org hypertriglyceridemia. The authors reported no potential conflict of interest relevant to this article.

CASE 1 u PRACTICE Tyler M, age 40, otherwise healthy, and with a body mass index RECOMMENDATIONS (BMI) of 30, presents to your office for his annual physical ex- ❯ Evaluate patients for amination. He does not have a history of alcohol or tobacco use. ­hypertriglyceridemia when Mr. M’s obesity raises concern about metabolic syndrome, they have a ­comorbid ­condition (eg, type 2 diabetes,­ which warrants evaluation for hypertriglyceridemia (HTG). You obesity, ­hypothyroidism, offer him lipid testing to estimate his risk of atherosclerotic car- metabolic syndrome, diovascular disease (ASCVD). alcoholism). B The only abnormal value on the lipid panel is a triglyceride ❯ Do not require fasting status (TG) level of 264 mg/dL (normal, < 175 mg/dL). Mr. M’s 10-yr when evaluating triglycerides­ ASCVD risk is determined to be < 5%. in a lipid panel. B What, if any, intervention would be triggered by the find- ing of moderate HTG? ❯ Make therapeutic lifestyle changes first-line treatment u for hypertriglyceridemia. C CASE 2 Alicia F, age 30, with a BMI of 28 and ASCVD risk < 7.5%, comes ❯ Prescribe fibrates for severe to the clinic for evaluation of anxiety and insomnia. She reports ­hypertriglyceridemia to eating a high-carbohydrate diet and drinking 3 to 5 alcoholic reduce the risk and recurrence­ beverages nightly to help her sleep. of pancreatitis. A Ms. F’s daily alcohol use prompts evaluation for HTG. Re- ❯ Prescribe a statin and an sults show a TG level of 1300 mg/dL and a high-density lipopro- omega-3 fatty acid (fish oil) tein (HDL) level of 25 mg/dL (healthy HDL levels: adult females, to lower the triglyceride level ≥ 50 mg/dL; adult males, ≥ 40 mg/dL). Other test results are nor- and thus reduce resulting ­atherogenicity when the risk of mal, except for elevated transaminase levels (just under twice atherosclerotic ­cardiovascular normal). disease is > 7.5%. B What, if any, action would be prompted by the patient’s severe HTG and below-normal HDL level? Strength of recommendation (SOR) A Good-quality patient-oriented evidence B Inconsistent or limited-quality How HTG is defined: patient-oriented evidence Causes, cutoffs, signs  C Consensus, usual practice, opinion, disease-oriented HTG is most commonly caused by obesity and a sedentary life- evidence, case series style; certain associated comorbid medical conditions can also be a precipitant (TABLE 11,2). Because the condition is a result of polygenic phenotypic expression, even a genetically low-risk

180 THE JOURNAL OF FAMILY PRACTICE | MAY 2020 | VOL 69, NO 4 Even a genetically low- risk patient can present with hypertriglyceridemia when exposed to certain medical conditions and environmental causes.

patient can present with HTG when exposed lipid profile is ordered to evaluate the risk of to certain medical conditions and environ- ASCVD. (Of note, for people older than 20 mental causes. years, the US Preventive Services Task Force Primary HTG (genetic or familial) is rare. no longer addresses the question, “Which Genetic testing may be considered for patients population should be screened for dyslipid- with TG > 1000 mg/dL (severely elevated emia?” Instead, current recommendations TG = 500 to 1999 mg/dL, measured in fast- answer the question, “For which population ing state*) or a family history of early ASCVD should statin therapy be prescribed?”5) (TABLE 11,2).2,3 ❚ Effect on ASCVD risk assessment. TG Typically, HTG is asymptomatic. Xan- levels are known to vary, depending on fast- thelasmas, , and lipemia retinalis ing or nonfasting status, with lower levels re- are found in hereditary disorders of elevated ported when fasting. An elevated TG level can TGs. Occasionally, HTG manifests as chylo- lead to inaccurate calculation of LDL when micronemia syndrome, characterized by re- using the Friedewald formula6: current abdominal pain, nausea, vomiting, and, in severe HTG, pancreatitis.3 LDL = total cholesterol – (triglycerides/5) – HDL Fine points of TG measurement The purpose of testing lipids in a fasting state Triglycerides are a component of a complete (> 9 hours) is to minimize the effects of an

IMAGE: ©ALICIA BUELOW lipid profile, which also includes total cho- elevated TG level on the calculated LDL. In lesterol, calculated low-density lipoprotein severe HTG, beta-quantitation by ultracen- (LDL-C), and HDL.4 As in both case vignettes, trifugation and electrophoresis can be per- detection of HTG is often incidental, when a formed to determine the LDL level directly. ❚ Advantage of nonfasting measure- *In comparison, a normal level of triglycerides is < 175 ment. When LDL-C is not a concern, there is, mg/dL; a moderately elevated level, measured in a fasting or nonfasting state, 175-499 mg/dL; and a very in fact, value in measuring TGs in the nonfast- severely elevated level, ≥ 2000 mg/dL.2 ing state. Why? Because a nonfasting TG level

MDEDGE.COM/FAMILYMEDICINE VOL 69, NO 4 | MAY 2020 | THE JOURNAL OF FAMILY PRACTICE 181 TABLE 1 Causes of hypertriglyceridemia1,2

Primary Secondary • Familial chylomicronemia (and related • Chronic kidney disease and nephrotic disorders) syndrome • Familial combined • Chronic liver disease • Familial dysbetalipoproteinemia • Drug-inducedb • Familial hypertriglyceridemiaa • Excessive alcohol consumption • Familial hypoalphalipoproteinemia • Hypothyroidism • Primary genetic susceptibility • Metabolic syndromec • Obesity • Poorly controlled type 2 diabetes mellitus • Other disorders - Glycogen storage disease - Multiple myeloma - Systemic lupus erythematosus aCommon (5% to 10% of cases); likely polygenic; often not expressed until adulthood because of environmental Studies have factors, obesity, or stress. found a higher bIncluding antipsychotics, beta-blockers, corticosteroids, estrogens, immunosuppressants, protease inhibitors, ASCVD risk in tamoxifen, and thiazides. cAbdominal obesity, increased level of triglycerides, decreased level of high-density lipoprotein, hypertension, and the setting of elevated fasting level of glucose (ie, insulin resistance). an elevated postprandial triglyceride level is a better indicator of a patient’s average TG reduce both the risk and recurrence of pan- accompanied by status: Studies have found a higher ASCVD creatitis12,13; given that the postprandial TG a low HDL level. risk in the setting of an elevated postprandial level can change rapidly from severe to very TG level accompanied by a low HDL level.7 severe (> 2000 mg/dL), multiple guidelines The Copenhagen City Heart Study identi- recommend pharmacotherapy to a TG goal fied postprandial HTG as an independent risk of < 500-1000 mg/dL.1,9,13,14 factor for atherogenicity, even in the setting of ❚ An ASCVD risk–HTG connection? a normal fasting TG level.8 American Associa- In the population already at higher risk of tion of Clinical Endocrinologists and American ASCVD (> 7.5%), HTG is recognized as a College of Endocrinology guidelines endorse risk-enhancing factor because of its athero- testing the nonfasting TG level when the fast- genic potential (TABLE 22); however, there is ing TG level is elevated in a lipid profile; if insufficient evidence that TGs have a role the nonfasting TG level is > 500 mg/dL, evalu- as an independent risk factor for ASCVD. In ation for secondary causes is warranted9,10 a population-based study of 58,000 people, (TABLE 11,2). 40 to 65 years of age, conducted at Copen- In a practical sense, therefore, offering hagen [Denmark] University Hospital, inves- patients nonfasting lipid testing allows more tigators found that those who did not meet people to obtain access to timely care. criteria for statin treatment and who had a ❚ Pancreatitis. Acute pancreatitis com- TG level > 264 mg/dL had a 10-year risk of a monly prompts an evaluation for HTG. The major adverse cardiovascular event similar risk of acute pancreatitis in the general popu- to that of people who did meet criteria for lation is 0.04%, but that risk increases to 8% statin therapy.15 to 31% for a person with HTG.11 Incidence The FIELD (Fenofibrate Intervention and when the TG level is > 500 mg/dL is thought Event Lowering in Diabetes) and AIM-HIGH to be increased because chylomicrons, acting (Atherothrombosis Intervention in Metabolic as a TG carrier in the bloodstream, are re- Syndrome with Low HDL/High Triglycerides sponsible for pancreatitis.3 Treating HTG can and Impact on Global Health Outcomes)

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TABLE 2 Risk factors and risk-enhancing factors for atherosclerotic cardiovascular disease2 Risk factors Risk-enhancing factors • Age • Parental history of cardiovascular disease - Men > 45 y • Family history of stroke - Women > 55 y • Metabolic syndrome, with or without diabetes • Male gender • Chronic kidney disease • Race (eg, African American) • Inflammatory disorder • Diabetes • Hypertriglyceridemia • Hypertension • Ankle–brachial index < 0.9 • Prior cardiovascular event • Elevated level of C-reactive protein (on high-sensitivity • Smoking testing) • Elevated level of low-density lipoprotein • Elevated levels of lipoproteins and apolipoprotein B • Low (< 40 mg/dL) level of high-density lipoprotein • Early menopause • Stages 3 and 4 chronic kidney diseasea • Preeclampsia • Polycystic ovary syndromea • High-risk ethnic group (eg, South Asian) • Evidence of coronary artery calcificationa aNewly identified risk factor. studies, among others, have failed to show a sociated with an increase in ischemic significant reduction in coronary events by stroke events.17 treating HTG.10 That said, it’s worth considering the find- ings of other trials: Treatment • In the PROVE IT-TIMI 22 (Pravastatin Therapeutic lifestyle changes or Atorvastatin Evaluation and Infec- Changes in lifestyle are the foundation of man- tion Therapy–Thrombolysis in Myocar- agement of, and recommended first-line treat- dial Infarction 22) trial, an overall 28% ment for, all patients with HTG. Patients with a reduction in endpoint events (myo- moderately elevated TG level (175-499 mg/dL, cardial infarction, acute coronary syn- measured in a fasting or nonfasting state) can drome) was seen with high-intensity be treated with therapeutic lifestyle changes statin therapy, compared to moderate- alone1,2; a trial of 3 to 6 months (see specific intensity therapy.10 However, there was interventions below) is recommended before a sizeable residual risk identified that considering adding medications.10 was theorized by investigators to be ❚ Weight loss. There is a strong asso- associated with high non-HDL lipo- ciation between BMI > 30 and HTG. Visceral proteins, including TGs. adiposity is a much more significant risk • A 2016 study in Israel, in which 22 than subcutaneous adipose tissue. Although years of data on 15,355 patients with weight loss to an ideal range is recommend- established ASCVD were studied, ed, even a 10% to 15% reduction in an obese revealed that elevated TGs are asso- patient can reduce the TG level by 20%. A ciated with an increased long-term combination of moderate-intensity exercise mortality risk that is independent of and healthy eating habits appears to assist the HDL level.16 best with this intervention.18 • A cross-sectional study, nested in the ❚ Exercise. Thirty minutes a day of mod- prospective Copenhagen City Heart erate-intensity exercise is associated with Study, demonstrated that HTG is as- a significant drop in postprandial TG. This

MDEDGE.COM/FAMILYMEDICINE VOL 69, NO 4 | MAY 2020 | THE JOURNAL OF FAMILY PRACTICE 183 TABLE 3 Agents in your arsenal to treat hypertriglyceridemia4,13,18,23 Class or name Mechanism of action Reduction in TG level Adverse effects of medication Statins Increase lipoprotein lipase 10%-15% Dizziness ­activity to clear TG from Tachycardia plasma Myalgia Elevated LFT Fibrates Inhibit secretion of TG from 30%-50% Dyspepsia liver and reduce blood TG Gallstones levels Myopathy Activate lipoprotein lipase to stimulate clearance of TG from plasma Omega-3 ethyl esters Same as for fibrates (see 20%-50% Fishy taste above) Burping Bleeding diathesis Hyperglycemia Ezetimibe23,a Decreases cholesterol 5%-10%18 Bloating ­absorption from small Abnormal bleeding ­intestine Constipation Blocks release of free fatty 10%-30% Elevated LFT acid from adipose tissue Flushing Reduces rate of secretion of Gout very-low-density lipoprotein particles Hyperglycemia Macular edema Peptic ulcer disease HDL, high-density lipoprotein; LDL, low-density lipoprotein; LFT, liver function tests; TG, triglycerides. aIndicated, in combination with fenofibrate, as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL, apolipoprotein B, and non-HDL cholesterol in patients with mixed hyperlipidemia.18,23

benefit can last as long as 3 days, suggesting leafy green vegetables, fruits, cereals, nuts, a goal of at least 3 days a week of an active and legumes; moderate intake of fish and lifestyle. Such a program can include inter- other meat, dairy products, and red wine; and mittent aerobics or mild resistance exercise.19 low intake of eggs and sugars.) The American ❚ Healthy eating habits. The difference Heart Association recommends 2 servings of between a low-fat, high-carbohydrate diet and fatty fish a week for its omega-3 oil benefit of a high-fat, low-carbohydrate diet is less impor- reducing ASCVD risk. Working with a regis- tant than the overall benefit of weight loss from tered dietician to assist with lipid lowering either of these diets. Complex carbohydrates can produce better results than physician- are recommended over simple carbohydrates. only instruction on healthy eating.9 A low-carbohydrate diet in a patient with dia- ❚ Alcohol consumption. Complete cessa- betes has been demonstrated to improve the tion or moderation of alcohol consumption (1 TG level, irrespective of weight change.20 drink a day/women and 2 drinks a day/men*) A Mediterranean diet can reduce the TG level by 10% to 15%, and is recommended *One “standard” alcoholic drink is considered to 14 contain approximately 0.16 fluid ounces (14 g) of pure over a low-fat diet. (This diet generally in- alcohol; however, the amount of alcohol in any drink cludes a high intake of extra virgin olive oil; can vary widely.21

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TABLE 4 Strategies for when and how to treat HTG in adults2,9 Age Severity Intervention All patients > 20 y Moderate HTGa; Therapeutic lifestyle changes risk of ­ASCVD < 7.5% Management of secondary causes Consideration of the role of medications that can contribute to HTG 40-75 y Moderate HTGa; Therapeutic lifestyle changes risk of ­ASCVD ≥ 7.5% Management of secondary causes Initiation (or intensification) of statin therapy All patients > 20 y Severe HTGb; Therapeutic lifestyle changes risk of ASCVD < 7.5% Evaluation and management of primary and secondary causes Fibrate therapy 40-75 y Severe HTGb; Therapeutic lifestyle changes risk of ASCVD ≥ 7.5% Evaluation and management of primary and secondary causes The risk of acute Initiation (or intensification) of statin therapy pancreatitis in the Fibrate therapy general population ASCVD, atherosclerotic cardiovascular disease; HTG, hypertriglyceridemia. is 0.04%, but that a175-499 mg/dL, measured in a fasting or nonfasting state. risk increases to b≥ 500 mg/dL , measured in a fasting or nonfasting state. 8% to 31% for a person with hyper- triglyceridemia. is recommended to improve HTG. Among risk.2 If the TG level remains elevated (> 500 secondary factors, alcohol is commonly the mg/dL) after statin therapy is maximized, an cause of an unusually high elevation of the additional agent can be added—ie, a fibrate TG level.14 or fish oil (see below). ❚ Smoking cessation. Smoking increases ❚ Fibrates. If a fibrate is used as an add-on the postprandial TG level.10 Complete ces- to a statin, fenofibrate is preferred over gemfi- sation for just 1 year can reduce a person’s brozil because it presents less risk of the severe ASCVD risk by approximately 50%. However, myopathy that can develop when taken with in a clinical trial,22 smoking cessation did not a statin.13 Despite the effectiveness of fibrates significantly decrease the TG level—possibly in reducing the TG level, these drugs have not because of the counterbalancing effect of been shown to reduce overall mortality.24 The weight gain following cessation. evidence on improved cardiovascular out- comes is subgroup-specific (ie, prevention of Medical therapy a second myocardial infarction in the setting In addition to lifestyle modification, medica- of optimal statin use and elevated non-HDL tions are recommended to reduce atherogenic lipoproteins).12 A study demonstrated that potential in patients with moderate or severe gemfibrozil reduced the incidence of transient HTG and an ASCVD risk > 7.5% (TABLE 34,13,18,23 ischemic attack and stroke in a subgroup of and TABLE 42,9). Before initiating medical thera- male US veterans who had coronary artery py, we recommend that you engage in shared disease and a low HDL level.25 decision-making with patients to (1) delineate ❚ Fish oil. The omega-3 ethyl esters eicos- treatment goals and (2) describe the risks and apentaenoic acid (EPA) and docosahexae- benefits of medications for HTG.2 noic acid (DHA), available as EPA alone or in ❚ Statins. These agents are recommend- combination with DHA, do not interact with ed first-line therapy for reducing ASCVD statins and are tolerated well. They reduce

MDEDGE.COM/FAMILYMEDICINE VOL 69, NO 4 | MAY 2020 | THE JOURNAL OF FAMILY PRACTICE 185 hypertriglyceridemia by 20% to 50%.13 off alcohol; add relaxation exercises Eicosapentaenoic acid, EPA plus DHA, before bedtime; do aerobic exercise 30 and icosapent ethyl, an ethyl ester product minutes a day, 3 times a week; decrease containing EPA without DHA, are approved dietary carbohydrates daily by cutting by the US Food and Drug Administration for portion size in half; and increase intake HTG > 500 mg/dL, at a dosage of 2000 mg of fresh vegetables and lean protein. twice daily. In the REDUCE-IT trial, adding • Treatment with fenofibrate to reduce icosapent ethyl, 2 g twice daily, to a statin in the risk of pancreatitis. Ms. F begins a patients with HTG was associated with fewer trial. Six months into treatment, she ischemic events, compared to placebo.23,26 has reduced her BMI to 24 and the TG Fish oil formulations can inhibit plate- level has fallen to < 500 mg/dL. Ms. F let aggregation and increase bleeding time also reports that she is sleeping well, in otherwise healthy people; however, such believes that she is able to manage her episodes are minor and nonfatal. Patients on infrequent anxiety, and is now in a rou- anticoagulation or an antiplatelet medication tine that feels sustainable. should be monitored periodically for bleeding You congratulate Ms. F on her success events, although recommendations on how to and support her decision to undertake a tri- monitor aren’t specified in a recent advisory al of discontinuing fenofibrate, after shared by the American Heart Association.23 decision-making about the risks and potential There is a strong DHA was thought to increase the LDL-C benefits of doing so. association levels and, by doing so, potentially counter- ­between a BMI balance benefit,23,27 but most studies have Summing up: > 30 and hyper- failed to reproduce this effect.28 Instead, stud- Management of HTG triglyceridemia. ies have shown minimal elevation of LDL-C Keep these treatment strategy highlights in when DHA is used to treat HTG.23,27 mind: ❚ Niacin. At a dosage of 500-2000 mg/dL, • Lifestyle modification with a low-fat, niacin lowers the TG level by 10% to 30%. It low-carbohydrate diet, avoidance of al- also increases HDL by 10% to 40% and lowers cohol, and moderate-intensity exercise LDL by 5% to 20%.13 is the mainstay of HTG management. ❚ Considerations in pancreatitis. For • The latest evidence supports that (1) management of recurrent pancreatitis in HTG is a risk-enhancing factor for patients with HTG, lifestyle modification re- ­ASCVD and (2) statin therapy is rec- mains the mainstay of treatment. When med- ommended for patients who have ication is considered for persistent severe HTG and an ASCVD risk > 7.5%. HTG, fibrates have evidence of primary and • When the TG level remains elevated secondary prevention of pancreatitis.11 When despite statin therapy and lifestyle a patient is intolerant of fibrates, consider changes, an omega-3 ethyl ester can a different option to reduce the TG level— be used as an adjunct for additional eg, fish oil supplementation. atherogenic risk reduction. • For severe HTG, a regimen of thera- CASE 1 u peutic lifestyle changes plus a fibrate is ❚ Recommendation for Mr. M: Therapeutic recommended to reduce the risk and lifestyle changes to address moderate HTG. recurrence of pancreatitis.1,24 JFP Because Mr. M’s 10-yr ASCVD risk is < 5%, CORRESPONDENCE statin therapy is not indicated for risk reduc- Ashwini Kamath Mulki, MD, Family Health Center, tion. With a fasting TG value < 500 mg/dL, he is 1730 Chew Street, Allentown, PA 18104; [email protected]. not considered at increased risk of pancreatitis.

CASE 2 u References ❚ Recommendations for Ms. F: 1. Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treat- ment of hypertriglyceridemia: an Endocrine Society clinical prac- • Therapeutic lifestyle changes to ad- tice guideline. J Clin Endocrinol Metab. 2012;97:2969-2989. dress severe HTG. Ms. F agrees to wean 2. Grundy SM, Stone NJ, Bailey AL, et al. AHA/ACC/AACVPR/

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AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guide- 16. Klempfner R, Erez A, Sagit B-Z, et al. Elevated triglyceride level line on the Management of Blood Cholesterol. A report of the is independently associated with increased all-cause mortal- American College of Cardiology/American Heart Association ity in patients with established coronary heart disease: twenty- Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. two-year follow-up of the Bezafibrate Infarction Prevention 2019;73:e285-e350. Study and Registry. Circ Cardiovasc Qual Outcomes. 2016;9: 3. Brahm A, Hegele RA. Hypertriglyceridemia. Nutrients. 100-108. 2013;5:981-1001. 17. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, et al. Nonfasting tri- 4. Expert Panel on Detection, Evaluation, and Treatment of High glycerides and risk of ischemic stroke in the general population. Blood Cholesterol in Adults. Executive Summary of the Third JAMA. 2008;300:2142-2152. Report of the National Cholesterol Education Program (NCEP) 18. Miller M, Stone NJ, Ballantyne C, et al; American Heart Asso- Expert Panel on Detection, Evaluation, and Treatment of High ciation Clinical Lipidology, Thrombosis, and Prevention Com- Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. mittee of the Council on Nutrition, Physical Activity, and Me- 2001;285:2486-2497. tabolism; Council on Arteriosclerosis, Thrombosis and Vascular 5. US Preventive Services Task Force. Final recommendation state- Biology; Council on Cardiovascular Nursing; Council on the Kid- ment. Statin use for the primary prevention of cardiovascular ney in Cardiovascular Disease. Triglycerides and cardiovascular disease in adults: preventive medication. November 13, 2016. disease. Circulation. 2011;123:2292-2333. www.uspreventiveservicestaskforce.org/Page/Document/­ 19. Graham TE. Exercise, postprandial triacylglyceridemia, and car- UpdateSummaryFinal/statin-use-in-adults-preventive-­ diovascular disease risk. Can J Appl Physiol. 2004;29:781-799. medication. Accessed April 24, 2020. 20. Meng Y, Bai H, Wang S, et al. Efficacy of low carbohydrate diet for 6. Fukuyama N, Homma K, Wakana N, et al. Validation of the Frie- type 2 diabetes mellitus management: a systematic review and dewald equation for evaluation of plasma LDL-cholesterol. J Clin meta-analysis of randomized controlled trials. Diabetes Res Clin Biochem Nutr. 2007;43:1-5. Pract. 2017;131:124-131. 7. Scherer DJ, Nicholls SJ. Lowering triglycerides to modify cardio- 21. What is a standard drink? National Institute on Alcohol Abuse vascular risk: Will icosapent deliver? Vasc Health Risk Manag. and Alcoholism Web site. www.niaaa.nih.gov/what-standard- 2015;11:203. drink. Accessed April 24, 2020. 8. Nordestgaard BG, Benn M, Schnohr P, et al. Nonfasting triglyc- 22. Gepner AD, Piper ME, Johnson HM, et al. Effects of smoking and erides and risk of myocardial infarction, ischemic heart disease, smoking cessation on lipids and lipoproteins: outcomes from a and death in men and women. JAMA. 2007;298:299-308. randomized clinical trial. Am Heart J. 2011;161:145-151. 9. Jellinger PS. American Association of Clinical Endocrinologists/ 23. Skulas-Ray AC, Wilson PWF, Harris WS, et al; American Heart As- American College of Endocrinology Management of Dyslipid- sociation Council on Arteriosclerosis, Thrombosis and Vascular emia and Prevention of Cardiovascular Disease Clinical Practice Biology; Council on Lifestyle and Cardiometabolic Health; Coun- Guidelines. Diabetes Spectr. 2018;31:234-245. cil on Cardiovascular Disease in the Young; Council on Cardio- 10. Malhotra G, Sethi A, Arora R. Hypertriglyceridemia and cardio- vascular and Stroke Nursing; and Council on Clinical Cardiology. vascular outcomes. Am J Therapeut. 2016;23:e862-e870. 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