What should we do about Hypertriglyceridemia in Coronary Artery Disease Patients?
- 403 Downloads
Triglycerides are routinely obtained with standard lipid testing, but their role in cardiovascular risk is controversial. An excess of triglycerides is commonly encountered in patients with the metabolic syndrome or diabetes, and represents an excess burden of small, dense low-density lipoproteins (LDLs), which confers additive risk for cardiovascular disease. Current guidelines prioritize LDL targets first, but treatment of triglycerides once LDL targets are achieved bears consideration. Beyond lifestyle modification, potential pharmacologic therapies include statins, fibrates, niacin, omega-3 fatty acids and antidiabetic drugs. There are few trials to date comparing these agents directly in the management of hypertriglyceridemia, but available data seems to demonstrate that the greatest benefit of triglyceride lowering is experienced in a subgroup of patients with an atherogenic lipid profile (elevated triglycerides, low high-density lipoprotein (HDL), elevated small, dense LDL particles). Here, we discuss the current understanding of how triglyceride elevations impart cardiovascular risk, current therapies and the data supporting their use, and ongoing studies to elucidate the degree to which treatment of triglycerides modifies risk of future cardiovascular events.
KeywordsTriglycerides Cardiovascular disease Fibrates Omega-3 fish oil Niacin
J. Berger: none; E. Gianos: consultancy for Amarin; A. Singh: none; A. Schwartzbard: payment for development of educational presentations from Takeda, Merck, and Gilead; H. Weintraub: consultancy for Abbott Pharma, Payment for development of educational presentations for Abbott, AstraZeneca, Kowa, Takeda, Daiichi Sankyo, Boehringer, Novartis, travel/accommodations expenses covered or reimbursed by Amarin Corporation.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 2.Labossiere R, Goldberg I. Management of Hypertriglyceridemia. In: Davidson M, editor. In: Therapeutic Lipidology. Totowa: Humana Press; 2007. p. 201–20.Google Scholar
- 13.Emerging Risk Factor’s Collaboration. Major Lipids, Apolipoproteins and Risk of Vascular Disease JAMA 2009;302: 1993–2000.Google Scholar
- 15.Faergeman O, Holme I, Fayya R, et al. Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease. Am J Cardiol. 2009;104:459–63.PubMedCrossRefGoogle Scholar
- 16.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–3421.Google Scholar
- 17.Standards of Medical Care in Diabetes—2011. Diab Care 2011;34:S11-S61.Google Scholar
- 21.Pieke B, von Eckardstein A, Gülbahçe E, et al. Treatment of hypertriglyceridemia by two diets rich either in unsaturated fatty acids or in carbohydrates: effects on lipoprotein subclasses, lipolytic enzymes, lipid transfer proteins, insulin and leptin. Int J Obes Relat Metab Disord. 2000;24:1286–96.PubMedCrossRefGoogle Scholar
- 25.The Stroke Prevention by Aggressive Reductioni n Cholesterol Levels (SPARCL) Investigators. High-Dose Atorvastatin after Stroke or Transient Ischemic Attack. NEJM 2006;355:549–559.Google Scholar
- 26.Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.Google Scholar
- 33.Rubens HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. NEJM. 1999;341:410–8.CrossRefGoogle Scholar
- 34.Otvos JD, Collins D, Freedman DS, et al. Low Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events And Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation. 2006;113:1556–63.PubMedCrossRefGoogle Scholar
- 39.Scott R, O’Brien R, Fulcher G. Effects of Fenofibrate Treatment on Cardiovascular Disease Risk in 9,795 Individuals With Type 2 Diabetes and Various Components of the Metabolic Syndrome: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32:493–8.PubMedCrossRefGoogle Scholar
- 40.•Otvos, J. The surprising AIM-HIGH results are not surprising when viewed through a particle lens. J Clin Lipid 2011;5: 368–70.Google Scholar
- 41.Vaijinath SK, Kashyap L. Mechanism of Action of Niacin. Am J Card. 2008;101:S20–6.Google Scholar
- 44.Canner PL, Berrge KG, Wenger NK, et al. Fifteen year Mortality in Coronary Drug Project Patients: long-term benefit with niacin. JACC 1986;1245.Google Scholar
- 45.•The AIM-HIGH investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. NEJM 2011;365:2255–2267. Widely publicized clinical trial of niacin versus placebo to raise low HDL in patients with established cardiovascular disease, which was stopped early due to lack of efficacy.Google Scholar
- 46.HPS2-THRIVE: A Randomized Trial of the Long-term Clinical Effects of Raising HDL Cholesterol With Extended Release Niacin/Laropiprant. http://clinicaltrials.gov/ct2/show/NCT00461630. Accessed August 2012.
- 47.Armitage, Jane. HPS2-THRIVE: Treatment of HDL to Reduce the Incidence of Vascular Events. Presented at the European Society of Cardiology 2012 Congress. Munich, Germany. August 25–29, 2012.Google Scholar
- 48.Grundy DM, Vega GL, McGovern ME, et al. Diabetes Multicenter Research Group: Efficacy, safety and tolerability of once daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial. Arch Intern Med. 2002;162:1568.PubMedCrossRefGoogle Scholar
- 52.GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354: 447–455.Google Scholar
- 55.•Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Patients With Very High Triglyceride Levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] Trial). Am J Card. 2011;108:682–90. Initial published results of AMR101 (now Vascepa), a new purified EPA-only omega 3 fish oil for use in moderate to severe hypertriglyceridemia.PubMedCrossRefGoogle Scholar
- 56.•Ballantyne CM, Bays HE, Kastelein JJ, et al. Efficacy and Safety of Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Statin Treated Patients with Persistent High Triglycerides (from the ANCHOR Study). Am J Card. Epub July 23, 2012. Followup study of Vascepa, with results demonstrating greater triglyceride-lowering with high potency statins as well as potential reductions in LDL.Google Scholar
- 57.A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. (REDUCE-IT) (http://clinicaltrials.gov/ct2/show/NCT01492361. Accessed August 2012.