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hypertriglyceridemia

Elevated triglycerides in serum. Etiology: 1) hyperlipoproteinemias I, IIb, IV, V 2) diseases/disorders a) hypothyroidism b) nephrotic syndrome c) glycogen storage diseases d) diabetes mellitus 3) extremely high triglyceride concentrations are common in acute pancreatitis 4) non-fasting state 5) medications - estrogens, tamoxifen, retinoids, HIV1 antiretroviral agents [19] Epidemiology: - affects 31% of adults in the United States [7] Pathology: - associated with low levels of HDL cholesterol & high levels of small, dense LDL particles Genetics: - susceptibility associated with Tyr-985 in ORP1 (homozygous) [11] Laboratory: - diagnosis should be based on fasting serum triglycerides [10] - serum lipase may be very high when associated with acute pancreatitis [19] Complications: 1) uncertain independent association with: [2,3,4] a) coronary artery disease b) ischemic stroke, transient ischemic attack 2) hypercoagulability [5] 3) acute pancreatitis (levels > 1000-2000 mg/dL) [19,20] Management: 1) assessment & control of associated disorders [8,10] a) glycemic control in patients with diabetes mellitus (1st line) [19] b) use of statins in patients with - elevated serum LDL cholesterol - cardiovascular disease - coronary artery disease - peripheral arterial disease 2) non pharmacologic therapy first line for patients without associated treatable disorders with serum triglycerides < 500 mg/dL [8] a) aerobic exercise b) weight reduction c) avoid excess alcohol d) fish oil of no benefit [10] - icosapent ethyl use controversial (conflicting reports) - MKSAP19 [10] supports use for patients > 50 years, with diabetes mellitus & additional cardiovascular risk factor 3) pharmacologic therapy (serum triglyceride > 500 mg/dL) [7] a) no good treatments for severe hypertriglyceridemia b) fibrates 1] first line for patients with serum triglycerides > 500 mg/dL [7,8.10] 2] not much benefit of fibrate with serum triglyceride < 500 mg/dL (see Field study) 3] fenofibrate lowers serum triglycerides, but does not favorably affect adverse cardiovascular events when added to simvastatin [6] (see ACCORD study) 4] ref [10] claims cardiovascular risk benefit of fibrates (MKSAP19) 5] refs [7,8] not as favorable as ref [10] regarding fibrates reducing cardiovascular risk 6] no good evidence that fibrates reduce risk of pancreatitis [7] 7] fenofibrate may unfavorably affect GFR [6] c) nicotinic acid - of no outcome benefit when added to statin [9] d) prescription omega-3 fatty acids are an effective & safe [16] - EPA with or without DHA at 4 grams a day. - icosapent ethyl provides additional cardiovascular risk reduction beyond statins [15] - krill oil-derived omega-3 formulation reduces plasma triglycerides in patients with severe hypertriglyceridemia [17] 4) avoid estrogen-containing contraceptives - use progestin only contraceptive - depot medroxyprogesterone acetate [19] 5) screening [10] a) all adults should be screened at least every 5 years with serum triglycerides as part of a lipid panel

Related

diabetes mellitus glycogen storage disease (glycogenosis) hyperlipoproteinemia (HLP) hypothyroidism nephrotic syndrome pancreatitis triglyceride in serum

Useful

Field study

Specific

familial hypertriglyceridemia

General

hyperlipidemia

Database Correlations

OMIM 145750

References

  1. UpToDate 13.3 http://www.utdol.com
  2. Avins AL et al Do triglycerides provide meaningful information about heart disease risk? Arch Intern Med 2000 160:1937
  3. Garber AM & Avins AL, Triglyceride concentration in coronary heart disease. Not yet proved of value as a screening test. BMJ 1994; 309:2
  4. Cullen P Evidence that triglycerides are an independent coronary heart disease risk factor Am J Cardiol 2000; 86:943
  5. Simpson HCR et al Hypertriglyceridaemia and hypercoagulability Lancet 1983; 1:786
  6. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1563-74 PMID: 20228404 http://dx.doi.org/10.1056/NEJMoa1001282
  7. Miller M et al Triglycerides and Cardiovascular Disease A Scientific Statement From the American Heart Association Circulation 2011 May 24 ; 123:2292 PMID: 21502576 http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3182160726v1
  8. Prescriber's Letter 18(6): 2011 Strategies for Lowering Triglycerides Detail-Document#: 270606 (subscription needed) http://www.prescribersletter.com
  9. NIH News: Thursday, May 26, 2011 NIH stops clinical trial on combination cholesterol treatment Lack of efficacy in reducing cardiovascular events prompts decision http://www.nih.gov/news/health/may2011/nhlbi-26.htm
  10. Medical Knowledge Self Assessment Program (MKSAP) 16,19 American College of Physicians, Philadelphia 2012, 2019 - McCullough PA, Ahmed AB, Zughaib MT, Glanz ED, Di Loreto MJ Treatment of hypertriglyceridemia with fibric acid derivatives: impact on lipid subfractions and translation into a reduction in cardiovascular events. Rev Cardiovasc Med. 2011;12(4):173-85 PMID: 22249508
  11. OMIM :accession 145750
  12. Berglund L et al Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline J Clin Endocrin & Metab 2012 97(9):2969-2989 PMID: 22962670 http://jcem.endojournals.org/content/97/9/2969.abstract (corresponding NGC guideline withdrawn Feb 2018)
  13. Hansel B, Giral P Severe Hypertriglyceridemia: How Should It Be Managed? Medscape Diabetes & Endocrinology. March 1, 2016 http://www.medscape.com/viewarticle/859410
  14. NEJM Knowledge+. Question of the Week. Jan 24, 2017 http://knowledgeplus.nejm.org/question-of-week/835/ - Berenson AB, Rahman M, Wilkinson G. Effect of injectable and oral contraceptives on serum lipids. Obstet Gynecol. 2009 Oct;114(4):786-94. PMID: 19888036 Free PMC Article
  15. Bhatt DL, Steg PG, Miller M et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2018 Nov 10; PMID: 30415628 https://www.nejm.org/doi/10.1056/NEJMoa1812792
  16. 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, Aug 19, 2019 PMID: 31422671 https://www.ahajournals.org/doi/10.1161/CIR.0000000000000709
  17. Mozaffarian D, Maki KC, Bays HE et al Effectiveness of a Novel omega-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia. A Randomized Clinical Trial. JAMA Netw Open. 2022;5(1):e2141898. PMID: 34989797 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787655
  18. Bosworth T Triglyceride Lowering Fails to Show CV Benefit in Large Fibrate Trial. Twenty-Five Percent Reduction Has No Effect. Medscape. Nov 5, 2022 https://www.medscape.com/viewarticle/983610
  19. NEJM Knowledge+ Endocrinology
  20. Carr RA, Rejowski BJ, Cote GA et al Systematic review of hypertriglyceridemia-induced acute pancreatitis: A more virulent etiology? Pancreatology. 2016 Jul-Aug;16(4):469-76. PMID: 27012480 Review.