Management of Hypertriglyceridemia: Common Questions and Answers
Am Fam Physician. 2020 Sep 15;102(6):347-354.
Author disclosure: No relevant financial affiliations.
Hypertriglyceridemia, defined as fasting serum triglyceride levels of 150 mg per dL or higher, is associated with increased risk of cardiovascular disease. Severely elevated triglyceride levels (500 mg per dL or higher) increase the risk of pancreatitis. Common risk factors for hypertriglyceridemia include obesity, metabolic syndrome, and type 2 diabetes mellitus. Less common risk factors include excessive alcohol use, physical inactivity, being overweight, use of certain medications, and genetic disorders. Management of high triglyceride levels (150 to 499 mg per dL) starts with dietary changes and physical activity to lower cardiovascular risk. Lowering carbohydrate intake (especially refined carbohydrates) and increasing fat (especially omega-3 fatty acids) and protein intake can lower triglyceride levels. Moderate- to high-intensity physical activity can lower triglyceride levels, as well as improve body composition and exercise capacity. Calculating a patient's 10-year risk of atherosclerotic cardiovascular disease is pertinent to determine the role of medications. Statins can be considered for patients with high triglyceride levels who have borderline (5% to 7.4%) or intermediate (7.5% to 19.9%) risk. For patients at high risk who continue to have high triglyceride levels despite statin use, high-dose icosapent (purified eicosapentaenoic acid) can reduce cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years). Fibrates, omega-3 fatty acids, or niacin should be considered for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis, although this has not been studied in clinical trials. For patients with acute pancreatitis associated with hypertriglyceridemia, insulin infusion and plasmapheresis should be considered if triglyceride levels remain at 1,000 mg per dL or higher despite conservative management of acute pancreatitis.
Hypertriglyceridemia is defined as fasting serum triglyceride levels of 150 mg per dL (1.69 mmol per L) or higher. Elevated triglyceride levels (150 to 499 mg per dL [1.69 to 5.64 mmol per L]) are associated with increased risk of cardiovascular disease (CVD), and severely elevated levels (500 mg per dL [5.65 mmol per L] or higher) are associated with increased risk of pancreatitis. (Table 1).1 This article answers commonly asked questions related to the management of hypertriglyceridemia.
WHAT'S NEW ON THIS TOPIC
Systematic reviews consistently do not support use of omega-3 fatty acids for the primary prevention of cardiovascular disease.
For patients with established cardiovascular disease and elevated triglyceride levels who are already on statins, icosapent (Vascepa) reduces cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years) but may not be cost-effective. Currently, treatment of 111 patients to prevent one cardiovascular death would cost approximately $1.8 million.
SORT: KEY RECOMMENDATIONS FOR PRACTICE
|Clinical recommendation||Evidence rating||Comments|
Weight loss and reduction of visceral adiposity through nutrition and an exercise program; consensus and disease-oriented evidence
Simple carbohydrates, including fructose, can increase fatty acid production in the liver; consensus and disease-oriented evidence
Risk increases with triglyceride levels of 1,000 mg per dL (11.30 mmol per L) or higher; consensus, standard practice, and expert opinion
Hypertriglyceridemia is a risk-enhancing factor for CVD; consensus and expert opinion
Patients randomized to icosapent, 4 g daily, had lower cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years); one large randomized controlled trial
CVD = cardiovascular disease.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.
SORT: KEY RECOMMENDATIONS FOR PRACTICE
|Clinical recommendation||Evidence rating||Comments|
Referencesshow all references
1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines [published correction appears in J Am Coll Cardiol. 2019; 73(24):3237–3241]. J Am Coll Cardiol. 2019;73(24):e285–e350....
2. Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2015;100(12):4685]. J Clin Endocrinol Metab. 2012;97(9):2969–2989.
3. Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–2333.
4. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140(12):e673–e691.
5. Christian JB, Bourgeois N, Snipes R, et al. Prevalence of severe (500 to 2,000 mg/dl) hypertriglyceridemia in United States adults. Am J Cardiol. 2011;107(6):891–897.
6. Ford ES, Li C, Zhao G, et al. Hypertriglyceridemia and its pharmacologic treatment among US adults. Arch Intern Med. 2009;169(6):572–578.
7. Araújo J, Cai J, Stevens J. Prevalence of optimal metabolic health in American adults: National Health and Nutrition Examination Survey 2009–2016. Metab Syndr Relat Disord. 2019;17(1):46–52.
8. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published corrections appear in J Am Coll Cardiol. 2019;74(10):1429–1430, and J Am Coll Cardiol. 2020;75(7):840]. J Am Coll Cardiol. 2019;74(10):e177–e232.
9. Zhang R, Deng L, Jin T, et al. Hypertriglyceridaemia-associated acute pancreatitis: diagnosis and impact on severity. HPB (Oxford). 2019;21(9):1240–1249.
10. Rosenzweig JL, Bakris GL, Berglund LF, et al. Primary prevention of ASCVD and T2DM in patients at metabolic risk: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(9):3939–3985.
11. Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.
12. Arsenault BJ, Rana JS, Stroes ES, et al. Beyond low-density lipoprotein cholesterol: respective contributions of non-high-density lipoprotein cholesterol levels, triglycerides, and the total cholesterol/high-density lipoprotein cholesterol ratio to coronary heart disease risk in apparently healthy men and women. J Am Coll Cardiol. 2009;55(1):35–41.
13. Kajikawa M, Maruhashi T, Kishimoto S, et al. Target of triglycerides as residual risk for cardiovascular events in patients with coronary artery disease - post hoc analysis of the FMD-J Study A. Circ J. 2019;83(5):1064–1071.
14. Deng LH, Xue P, Xia Q, et al. Effect of admission hypertriglyceridemia on the episodes of severe acute pancreatitis. World J Gastroenterol. 2008;14(28):4558–4561.
15. Scherer J, Singh VP, Pitchumoni CS, et al. Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol. 2014;48(3):195–203.
16. LeFevre ML. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults with cardiovascular risk factors: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(8):587–593.
17. Schwarz JM, Linfoot P, Dare D, et al. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr. 2003;77(1):43–50.
18. Mensink RP, Zock PL, Kester AD, et al. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77(5):1146–1155.
19. Cao Y, Mauger DT, Pelkman CL, et al. Effects of moderate (MF) versus lower fat (LF) diets on lipids and lipoproteins: a meta-analysis of clinical trials in subjects with and without diabetes. J Clin Lipidol. 2009;3(1):19–32.
20. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188.
21. Softic S, Cohen DE, Kahn CR. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig Dis Sci. 2016;61(5):1282–1293.
22. Evans RA, Frese M, Romero J, et al. Fructose replacement of glucose or sucrose in food or beverages lowers postprandial glucose and insulin without raising triglycerides: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106(2):506–518.
23. Chung M, Ma J, Patel K, et al. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014;100(3):833–849.
24. Chapman MJ, Ginsberg HN, Amarenco P, et al.; European Atherosclerosis Society Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32(11):1345–1361.
25. Rees K, Takeda A, Martin N, et al. Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2019;(3):CD009825.
26. Estruch R, Ros E, Salas-Salvadó J, et al.; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378(25):e34.
27. Appel LJ, Sacks FM, Carey VJ, et al.; OmniHeart Collaborative Research Group. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005;294(19):2455–2464.
28. Hyde PN, Sapper TN, Crabtree CD, et al. Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss. JCI Insight. 2019;4(12).
29. Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013;93(3):993–1017.
30. Wewege MA, Thom JM, Rye KA, et al. Aerobic, resistance or combined training: a systematic review and meta-analysis of exercise to reduce cardiovascular risk in adults with metabolic syndrome. Atherosclerosis. 2018;274:162–171.
31. Ostman C, Smart NA, Morcos D, et al. The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis. Cardiovasc Diabetol. 2017;16(1):110.
32. Mann S, Beedie C, Jimenez A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports Med. 2014;44(2):211–221.
33. Kelley GA, Kelley KS. Impact of progressive resistance training on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. Prev Med. 2009;48(1):9–19.
34. Gordon B, Chen S, Durstine JL. The effects of exercise training on the traditional lipid profile and beyond. Curr Sports Med Rep. 2014;13(4):253–259.
35. Campbell WW, Kraus WE, Powell KE, et al.; 2018 physical activity guidelines advisory committee. High-intensity interval training for cardiometabolic disease prevention. Med Sci Sports Exerc. 2019;51(6):1220–1226.
36. Ginsberg HN, Elam MB, Lovato LC, et al.; ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus [published correction appears in N Engl J Med. 2010;362(18):1748]. N Engl J Med. 2010;362(17):1563–1574.
37. Boden WE, Probstfield JL, Anderson T, et al.; AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy [published correction appears in N Engl J Med. 2012; 367(2):189]. N Engl J Med. 2011;365(24):2255–2267.
38. Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;(7):CD003177.
39. Bhatt DL, Steg PG, Miller M, et al.; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22.
40. Oh RC, Lanier JB. Management of hypertriglyceridemia. Am Fam Physician. 2007;75(9):1365–1371. Accessed April 14, 2020. https://www.aafp.org/afp/2007/0501/p1365.html
41. The NNT. Statins given for 5 years for heart disease prevention (with known heart disease). Accessed April 18, 2020. https://www.thennt.com/nnt/statins-for-heart-disease-prevention-with-known-heart-disease
42. Goodrx.com. Vascepa. Accessed March 3, 2020 (zip code: 66211). https://www.goodrx.com/vascepa
43. Schandelmaier S, Briel M, Saccilotto R, et al. Niacin for primary and secondary prevention of cardiovascular events. Cochrane Database Syst Rev. 2017;(6):CD009744.
44. Simons-Linares CR, Jang S, Sanaka M, et al. The triad of diabetes ketoacidosis, hypertriglyceridemia and acute pancreatitis. How does it affect mortality and morbidity?: A 10-year analysis of the National Inpatient Sample. Medicine (Baltimore). 2019;98(7):e14378.
45. Lindkvist B, Appelros S, Regnér S, et al. A prospective cohort study on risk of acute pancreatitis related to serum triglycerides, cholesterol and fasting glucose. Pancreatology. 2012;12(4):317–324.
46. Chaudhary A, Iqbal U, Anwar H, et al. Acute pancreatitis secondary to severe hypertriglyceridemia: management of severe hypertriglyceridemia in emergency setting. Gastroenterology Res. 2017;10(3):190–192.
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