- Author: Mary Ellen T Sweeney, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
Rule out secondary causes of hypertriglyceridemia, including diabetes mellitus (fasting or random glucose levels), hypothyroidism (thyroid-stimulating hormone [TSH] levels), chronic renal failure (urinalysis, creatinine, and microalbumin), alcohol abuse, hormone replacement therapy, and/or oral contraceptives.[37, 38]
Measure plasma lipid and lipoprotein levels while the patient is on a regular diet after an overnight fast. The Endocrine Society also recommends using fasting triglyceride levels over nonfasting triglyceride levels for the diagnosis of hypertriglyceridemia.
Abnormal lipoprotein patterns can often be identified after determining serum cholesterol and triglyceride levels and visual inspection of the plasma sample (stored at 4°C). In some cases, performing electrophoresis and ultracentrifugation of whole plasma specimens may be necessary to help establish a diagnosis.
If the diagnosis of eruptive xanthomas is in doubt, obtaining a biopsy of the suspicious lesions will reveal accumulations of fat (not cholesterol). A biopsy of cutaneous lesions suspected to be either planar or tuberous xanthomas will reveal cholesterol deposition.
Although some studies have shown that tests such as C-reactive protein (CRP) and total homocysteine levels have some predictive value in screening for vascular disease, and thus are emerging as nontraditional risk factors for coronary heart disease, further investigation is need to determine their value. Nonfasting triglyceride levels may reflect the level of atherogenic remnant lipoproteins and may even be stronger predictors of cardiovascular events than traditional fasting lipids.
Elevated triglycerides are determined by direct laboratory analysis of serum or plasma after a 10- to 12-hour fast. Determining which lipoprotein abnormality is the cause of hypertriglyceridemia is less straightforward.
Moderately elevated total cholesterol and triglyceride levels accompanied by the presence of palmar crease xanthomas confirm the diagnosis dysbetalipoproteinemia. Further laboratory workup may not be necessary.
Very low-density lipoproteins (VLDLs) are increased and chylomicrons are absent when triglyceride levels are elevated but below 1000 mg/dL. If triglyceride levels are above 1000 mg/dL, both VLDL and chylomicrons are usually present.
A standard lipid profile using the Friedewald equation to calculate the LDL cholesterol is not useful if the triglyceride level is more than 400-500 mg/dL. The excess cholesterol present in beta-VLDL is included in the LDL cholesterol value. If the triglycerides are elevated but less than 1000 mg/dL and the total cholesterol is elevated, the lipoprotein abnormality may be caused by either: (1) elevations of both low-density lipoprotein (LDL) and VLDL, which is type IIb or mixed hyperlipoproteinemia, or (2) increased remnant VLDL or intermediate-density lipoprotein (IDL), which is type III hyperlipidemia or dysbetahyperlipoproteinemia (total cholesterol levels, about 300-600 mg/dL; triglyceride levels, about 400-800 mg/dL). The 2 disorders may be distinguished by obtaining a direct LDL cholesterol analysis (enzymatic analysis), which is available at most commercial laboratories. If the direct LDL cholesterol is significantly lower than the calculated LDL cholesterol, a diagnosis of type IIIhyperlipoproteinemia is likely. Furthermore, if the cholesterol-to-triglyceride ratio in isolated VLDL is greater than 0.3, dysbetalipoproteinemia is likely (normal ratio, 0.2).
The only procedure that reliably distinguishes between a mixed hyperlipoproteinemia (increased LDL cholesterol and triglycerides) and type III hyperlipoproteinemia (increased IDL) is beta quantification (lipoprotein electrophoresis). This expensive analysis involves ultracentrifugation followed by electrophoresis. However, it is not performed by most commercial or hospital laboratories. Studies that can isolate and measure VLDL and IDL include density-gradient ultracentrifugation and nuclear magnetic resonance spectroscopy. These tests are reliable in helping diagnose dysbetalipoproteinemia, but they may be available only at lipid specialty laboratories.
Specialized lipid centers should be contacted if type IIb or III must be confirmed. In most clinical settings, however, distinguishing between these entities is rarely necessary, because the treatment of both conditions is essentially the same. Diet modification, exercise, and appropriate weight loss improve both. Type IIb and III also respond to the same medications—niacin and/or fibric acid derivatives. Therefore, no matter which diagnosis applies to a given patient, the treatment is the same.
The Endocrine Society does not recommend routinely measuring lipoprotein particle heterogeneity in patients with hypertriglyceridemia, suggesting that although apolipoprotein B (apo B) or lipoprotein(a) [Lp(a)] levels may be useful, results of other apolipoproteins are generally not clinically useful. However, apo E genotyping or phenotyping can be used to determine if the patient is homozygous for apo E-2, but this finding is not sufficient for the diagnosis of dysbetalipoproteinemia without clinical or lipid abnormalities consistent with the disorder.
If the triglyceride levels are greater than 1000 mg/dL and the presence of chylomicrons must be confirmed, the simplest and most cost-effective test involves overnight refrigeration of an upright tube of plasma or serum. If a creamy supernatant is seen the next day, chylomicrons are present. If the infranatant is cloudy, high levels of very low-density lipoprotein (VLDL) are present (type V hyperlipidemia). If the infranatant is clear, the VLDL content is normal and type I hypercholesterolemia (elevated chylomicrons only) should be suspected.
Type I hyperlipoproteinemia (pure hyperchylomicronemia)
To make a definitive diagnosis of type I hyperlipidemia, a deficiency of either lipoprotein lipase or apo C-II must be confirmed. The presence of lipoprotein lipase activity may be measured in plasma following intravenous heparin administration (50 IU of heparin per kg body weight) or by analysis of muscle or adipose tissue biopsy samples.
Defective or absent apo C-II must be determined at a lipid center that performs 1 of the 3 following assays: (1) gel electrophoresis, (2) radioimmunoassay, or (3) confirmation that lipoprotein lipase added to the patient's plasma is not active.
Nainggolan L. FDA Approves Epanova for Severe Hypertriglyceridemia. Medscape Medical News. Available at http://www.medscape.com/viewarticle/824748. Accessed: May 12, 2014.
Wu CW, Lin PY, Liu YF, Liu TC, Lin MW, Chen WM, et al. Central corneal mosaic opacities in Schnyder's crystalline dystrophy. Ophthalmology. 2005 Apr. 112(4):650-3. [Medline].
FREDRICKSON DS, LEES RS. A SYSTEM FOR PHENOTYPING HYPERLIPOPROTEINEMIA. Circulation. 1965 Mar. 31:321-7. [Medline].
Mahley RW, Rall SC Jr. Type III hyperlipoproteinemia (dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal metabolism. Scriver CR, Beaudet AR, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001. 2835-62.
Kane JP. Structure and function of the plasma lipoproteins and their receptors. Fuster V, Ross R, Topol EJ, eds. Atherosclerosis and Coronary Artery Disease. Philadelphia, Pa: Lippincott-Raven; 89-103. 1996: .
Mahley RW, Huang Y, Rall SC Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res. 1999 Nov. 40(11):1933-49. [Medline].
Smelt AH, de Beer F. Apolipoprotein E and familial dysbetalipoproteinemia: clinical, biochemical, and genetic aspects. Semin Vasc Med. 2004 Aug. 4(3):249-57. [Medline].
Huang Y, Schwendner SW, Rall SC Jr, Sanan DA, Mahley RW. Apolipoprotein E2 transgenic rabbits. Modulation of the type III hyperlipoproteinemic phenotype by estrogen and occurrence of spontaneous atherosclerosis. J Biol Chem. 1997 Sep 5. 272(36):22685-94. [Medline].
Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 1992 Oct 16. 258(5081):468-71. [Medline].
Corbo RM, Scacchi R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele?. Ann Hum Genet. 1999 Jul. 63:301-10. [Medline].
Feussner G, Piesch S, Dobmeyer J, Fischer C. Genetics of type III hyperlipoproteinemia. Genet Epidemiol. 1997. 14(3):283-97. [Medline].
Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988 Jan-Feb. 8(1):1-21. [Medline].
Hassing HC, Surendran RP, Mooij HL, Stroes ES, Nieuwdorp M, Dallinga-Thie GM. Pathophysiology of hypertriglyceridemia. Biochim Biophys Acta. 2012 May. 1821(5):826-32. [Medline].
Executive Summary of The 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). JAMA. 2001 May 16. 285(19):2486-97. [Medline].
Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011 May 24. 123(20):2292-333. [Medline].
Pajukanta P, Porkka KV. Genetics of familial combined hyperlipidemia. Curr Atheroscler Rep. 1999 Jul. 1(1):79-86. [Medline].
Kolovou GD, Anagnostopoulou KK, Kostakou PM, Bilianou H, Mikhailidis DP. Primary and secondary hypertriglyceridaemia. Curr Drug Targets. 2009 Apr. 10(4):336-43. [Medline].
Pilia G, Chen WM, Scuteri A, Orrú M, Albai G, Dei M, et al. Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet. 2006 Aug 25. 2(8):e132. [Medline]. [Full Text].
Willer CJ, Mohlke KL. Finding genes and variants for lipid levels after genome-wide association analysis. Curr Opin Lipidol. 2012 Apr. 23(2):98-103. [Medline]. [Full Text].
Johansen CT, Wang J, Lanktree MB, Cao H, McIntyre AD, Ban MR, et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet. 2010 Aug. 42(8):684-7. [Medline]. [Full Text].
Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet. 2009 Jan. 41(1):56-65. [Medline]. [Full Text].
Hiramatsu M, Oguri M, Kato K, Horibe H, Fujimaki T, Watanabe S, et al. Synergistic effects of genetic variants of APOA5 and BTN2A1 on dyslipidemia or metabolic syndrome. Int J Mol Med. 2012 Jul. 30(1):185-92. [Medline].
Shen GQ, Li L, Wang QK. Genetic variant R952Q in LRP8 is associated with increased plasma triglyceride levels in patients with early-onset CAD and MI. Ann Hum Genet. 2012 May. 76(3):193-9. [Medline].
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16. 287(3):356-9. [Medline].
Sumner AE, Cowie CC. Ethnic differences in the ability of triglyceride levels to identify insulin resistance. Atherosclerosis. 2008 Feb. 196(2):696-703. [Medline].
Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Münster study. Am J Cardiol. 1992 Sep 15. 70(7):733-7. [Medline].
Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986 Nov 28. 256(20):2823-8. [Medline].
Athyros VG, Giouleme OI, Nikolaidis NL, Vasiliadis TV, Bouloukos VI, Kontopoulos AG, et al. Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis. J Clin Gastroenterol. 2002 Apr. 34(4):472-5. [Medline].
Brunzell JD, Bierman EL. Chylomicronemia syndrome. Interaction of genetic and acquired hypertriglyceridemia. Med Clin North Am. 1982 Mar. 66(2):455-68. [Medline].
Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med. 1992. 37:249-73. [Medline].
US Preventive Services Task Force. Screening for lipid disorders in adults: U.S. Preventive Services Task Force recommendation statement. Rockville, Md: Agency for Healthcare Research and Quality; 2008.
Jellinger PS, Smith DA, Mehta AE, Ganda O, Handelsman Y, Rodbard HW, et al. American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012 Mar-Apr. 18 Suppl 1:1-78. [Medline].
Fortson MR, Freedman SN, Webster PD 3rd. Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol. 1995 Dec. 90(12):2134-9. [Medline].
Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med. 2008 Jan. 121(1):10-2. [Medline].
Pandhi D, Gupta P, Singal A, Tondon A, Sharma S, Madhu SV. Xanthelasma palpebrarum: a marker of premature atherosclerosis (risk of atherosclerosis in xanthelasma). Postgrad Med J. 2012 Apr. 88(1038):198-204. [Medline].
Rohrich RJ, Janis JE, Pownell PH. Xanthelasma palpebrarum: a review and current management principles. Plast Reconstr Surg. 2002 Oct. 110(5):1310-4. [Medline].
Institute for Clinical Systems Improvement. Lipid management in adults. Bloomington, Minn: Institute for Clinical Systems Improvement; 2009.
Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Sep. 97(9):2969-89. [Medline]. [Full Text].
Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007 Jul 18. 298(3):309-16. [Medline].
Haffner SM. Secondary prevention of coronary heart disease: the role of fibric acids. Circulation. 2000 Jul 4. 102(1):2-4. [Medline].
University of Michigan Health System. Screening and management of lipids. Ann Arbor, Mich: University of Michigan Health System; 2009.
Klop B, Wouter Jukema J, Rabelink TJ, Castro Cabezas M. A physician's guide for the management of hypertriglyceridemia: the etiology of hypertriglyceridemia determines treatment strategy. Panminerva Med. 2012 Jun. 54(2):91-103. [Medline].
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. A summary of implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Arterioscler Thromb Vasc Biol. 2004 Aug. 24(8):1329-30. [Medline].
Shimabukuro M, Higa M, Tanaka H, Shimabukuro T, Yamakawa K, Masuzaki H. Distinct effects of pitavastatin and atorvastatin on lipoprotein subclasses in patients with Type 2 diabetes mellitus. Diabet Med. 2011 Jul. 28(7):856-64. [Medline].
Hadfield SG, Horara S, Starr BJ, Yazdgerdi S, Marks D, Bhatnagar D, et al. Family tracing to identify patients with familial hypercholesterolaemia: the second audit of the Department of Health Familial Hypercholesterolaemia Cascade Testing Project. Ann Clin Biochem. 2009 Jan. 46:24-32. [Medline].
Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DC, Liem AH, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008 Nov 11. 337:a2423. [Medline]. [Full Text].
van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagné C, Shi G, et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol. 2008 Oct 21. 52(17):1421-9. [Medline].
Schaap-Fogler M, Schurr D, Schaap T, Leitersdorf E, Rund D. Long-term plasma exchange for severe refractory hypertriglyceridemia: a decade of experience demonstrates safety and efficacy. J Clin Apher. 2009. 24(6):254-8. [Medline].
US Food and Drug Administration. Safety: statins and HIV or hepatitis C drugs: drug safety communication - interaction increases risk of muscle injury. Posted: March 1, 2012. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm294294.htm. Accessed: November 1, 2013.
US Food and Drug Administration. Safety: statin drugs - drug safety. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm293670.htm. Accessed: November 1, 2013.
US Food and Drug Administration. Safety: Zocor (simvastatin): label change - new restrictions, contraindications, and dose limitations. Posted: June 8, 2011. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258384.htm. Accessed: November 1, 2013.
Maki KC, Bays HE, Dicklin MR. Treatment options for the management of hypertriglyceridemia: strategies based on the best-available evidence. J Clin Lipidol. 2012 Sep-Oct. 6(5):413-26. [Medline].
Mohiuddin SM, Pepine CJ, Kelly MT, Buttler SM, Setze CM, Sleep DJ, et al. Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: a phase 3, randomized, controlled study. Am Heart J. 2009 Jan. 157(1):195-203. [Medline].
Wu J, Song Y, Li H, Chen J. Rhabdomyolysis associated with fibrate therapy: review of 76 published cases and a new case report. Eur J Clin Pharmacol. 2009 Dec. 65(12):1169-74. [Medline].
Abourbih S, Filion KB, Joseph L, Schiffrin EL, Rinfret S, Poirier P, et al. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med. 2009 Oct. 122(10):962.e1-8. [Medline].
Sica DA. Fibrate therapy and renal function. Curr Atheroscler Rep. 2009 Sep. 11(5):338-42. [Medline].
Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol. 2008 Jun 24. 51(25):2375-84. [Medline].
Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986 Dec. 8(6):1245-55. [Medline].
McKenney JM, McCormick LS, Weiss S, Koren M, Kafonek S, Black DM. A randomized trial of the effects of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. Collaborative Atorvastatin Study Group. Am J Med. 1998 Feb. 104(2):137-43. [Medline].
Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. 2008 Apr. 83(4):470-8. [Medline].
Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, et al. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009 Sep. 54(3):196-203. [Medline].
Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol. 2009 Aug 11. 54(7):585-94. [Medline].
Egert S, Kannenberg F, Somoza V, Erbersdobler HF, Wahrburg U. Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr 2009;139:861-68.
Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis 2006;189:19-30.
Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. 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 Cardiol. 2011 Sep 1. 108(5):682-90. [Medline].
Kastelein JJ, Maki KC, Susekov A, Ezhov M, Nordestgaard BG, Machielse BN, et al. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. J Clin Lipidol. 2014 Jan-Feb. 8(1):94-106. [Medline].
Fletcher B, Berra K, Ades P, Braun LT, Burke LE, Durstine JL, et al. Managing abnormal blood lipids: a collaborative approach. Circulation. 2005 Nov 15. 112(20):3184-209. [Medline].
Hsia SH, Connelly PW, Hegele RA. Successful outcome in severe pregnancy-associated hyperlipemia: a case report and literature review. Am J Med Sci. 1995 Apr. 309(4):213-8. [Medline].
Kuklina EV, Yoon PW, Keenan NL. Trends in high levels of low-density lipoprotein cholesterol in the United States, 1999-2006. JAMA. 2009 Nov 18. 302(19):2104-10. [Medline].
Hudgins LC, Kleinman B, Scheuer A, White S, Gordon BR. Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia. Am J Cardiol. 2008 Nov 1. 102(9):1199-204. [Medline].
Foran SE, Flood JG, Lewandrowski KB. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish?. Arch Pathol Lab Med. 2003 Dec. 127(12):1603-5. [Medline].
Pharmacist's Letter. 2010; 26(1): 260101. Available at http://pharmacistsletter.therapeuticresearch.com/. Accessed: October 11, 2013.
Pharmacist's Letter. 2012; 28(6): 280606. Available at http://pharmacistsletter.therapeuticresearch.com/. Accessed: October 11, 2013.
|Type||Serum Elevation||Lipoprotein Elevation|
|I||Cholesterol and triglycerides||Chylomicrons|
|IIb||Cholesterol and triglycerides||LDL, VLDL|
|III||Cholesterol and triglycerides||IDL|
|V||Cholesterol and triglycerides||VLDL, chylomicrons|
|IDL = intermediate-density lipoprotein; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein.
Source: Fredrickson DS, Lees RS. A system for phenotyping hyperlipidaemia. Circulation. Mar 1965;31:321-7.
|Classification||TG level, mg/dL|
|Normal triglyceride level||< 150|
|Borderline-high triglyceride level||150-199|
|High triglyceride level||200-499|
|Very high triglyceride level||>500|
|Source: National Cholesterol Education Program. Executive summary of the 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). JAMA. May 16 2001;285(19):2486-97.|
|CHD and CHD risk equivalent, diabetes mellitus, and the following:||10-year risk for CHD >20%||< 100||< 130|
|Two or more risk factors and the following:||10-year risk < 20%||< 130||< 160|
|0-1 risk factor||< 160||< 190|
|CHD = coronary heart disease; LDL = low-density lipoprotein; HDL = high-density lipoprotein.
Source: National Cholesterol Education Program. Executive summary of the 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). JAMA. May 16 2001;285(19):2486-97.
|Drug||Lipid Effects||Lipid Effects in Combination with Statin||Outcomes Data||Comments|
|Bezafibrate||LDL decrease: 9.6-25% (400 mg)
HDL increase: 15-24% (400 mg)
Triglyceride decrease: 25-43% (400 mg)
|Further LDL decrease: 1.1% (400 mg)
Further HDL increase: 22% (400 mg)
Further triglyceride decrease: 31.7% (400 mg)
|Secondary prevention: Prevents composite endpoint of MI and sudden death in a subgroup with triglycerides of 200 mg/dL or higher. No increase in non-CV death||First-line option for triglyceride >10 mmol/L
Option for triglyceride 5-10 mmol/L
Option for low HDL
Reversible increase in serum creatinine
Requires renal dose adjustment
Limited data with statins
|Ezetimibe||LDL decrease: 18% (10 mg/day)
HDL increase: 1% (10 mg/day)
Triglyceride decrease: 8%
|Further LDL decrease: 25%, as add-on
Further HDL increase: 3%, as add-on
Further triglyceride decrease: 14%, as add-on
|Prevention of CV events in post-acute coronary syndrome patient when added to statin showed a benefit of reducing the primary endpoint (composite of CV death, MI, unstable angina requiring rehospitalization, coronary revascularization or stroke) by 6.4% vs statin alone
In intermediate outcomes studies, ezetimibe did not reduce regression of carotid intima-media thickness (surrogate marker) when added to a statin
|Efficacy studied in combination with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin
Role as statin add-on to reduce LDL if HDL and triglyceride satisfactory
|Fenofibrate||LDL decrease: 20.6% (145 mg)
HDL increase: 11% (145 mg)
Triglyceride decrease: 23.5-50.6% (greatest drop in patients with highest triglycerides) (145 mg)
|Further LDL decrease: 0-6% (200 mg)
Further HDL increase: 13-17% (200 mg)
Further triglyceride decrease: 20-32% (200 mg)
|Prevention of CV events in type 2 diabetes: Did not reduce primary composite outcome (nonfatal MI or CV death). Improved outcomes included nonfatal MI (24% decrease), coronary revascularization (21% decrease), progression to albuminuria, and reduced laser treatments for retinopathy. Nonsignificant increase in risk of CV death.
As statin add-on, did not lower risk of non-fatal MI, nonfatal stroke, or CV death more than statin alone in patients with type 2 diabetes at high risk for CV disease
|First-line option for triglyceride >10 mmol/L (about 1000 mg/dL)
Option for triglyceride >500 mg/dL or 5-10 mmol/L
Option for low HDL
Preferred over gemfibrozil for use with statins
Requires renal dose adjustment
Associated with reversible increase in serum creatinine
|Gemfibrozil||LDL: No effect
HDL increase: 6% (1200 mg/day)
Triglyceride decrease: 33-50% (greatest drop in patients with highest triglycerides) (1200 mg/day)
|Further triglyceride decrease: 41%
Further HDL increase: 9%
|Primary prevention of coronary heart disease
Secondary prevention of cardiac events in men with low HDL
|First-line option for triglyceride >10 mmol/L (about 1000 mg/dL)
Option for triglyceride >500 mg/dL or 5-10 mmol/L
Option for low HDL
Requires renal dose adjustment
Avoid with statin
|Icosapent ethyl||LDL decrease: 5%
HDL decrease: 4%
Triglyceride decrease: 27%
|Further triglyceride decrease: 21.5% (4 g/day), 10.1% (2 g/day)
Further LDL decrease: 6.2% (4 g/day)
|A study, REDUCE IT, is underway to look at reduction in CV events with icosapent ethyl||Option for triglyceride >500 mg/dL
Safe for use with statins
Use caution with fish or shellfish allergy
|Niacin||LDL decrease: 14-17% (Niaspan 2 g/day); 12% (niacin immediate-release 1.5 g/day and Niaspan 1.5 g/day)
HDL increase: 22-26% (2 g/day Niaspan); 17% (niacin immediate release 1.5 g/day); 20-22% (Niaspan 1.5 g/day)
Triglyceride decrease: 20-50%
|Further LDL decrease: 1-5% (Niaspan 1 g/day); 10% (Niaspan 2 g/day)
Further HDL increase: 24% (Niaspan 2 g/day); 15-17% (Niaspan 1 g/day)
Further triglyceride decrease: 24% (Niaspan 2 g/day); 12-22% (Niaspan 1 g/day)
|Secondary MI prevention; in combination with a resin, slows progression or promotes regression of atherosclerosis; reduces mortality
As statin add-on, reduces carotid intima-media thickness (surrogate marker) compared with ezetimibe as statin add-on in patients with lower HDL
No CV event benefit from niacin plus statin versus statin alone in patients with well-controlled LDL, low HDL, and high triglycerides
|Option for triglyceride >500 mg/dL (about 5 mmol/L)
Raises HDL more than any other agent
Dose-dependent risk of hyperglycemia (especially in patients with type 2 diabetes) and liver toxicity
May increase risk of statin myopathy
|Omega-3 ethyl esters||LDL increase: 44.5% (4 g/day)
HDL increase: 9.1% (4 g/day)
Triglyceride decrease: 45% (4 g/day)
|LDL increase: 0.7% (4 g/day)
Further HDL increase: 3.4% (4 g/day)
Further triglyceride decrease: 29.5% (4 g/day)
|Secondary prevention: Reduces cardiovascular death; sudden death; and combined endpoint of death, nonfatal MI, and nonfatal stroke
Secondary prevention in patients with, or at risk for, type 2 diabetes: did not reduce CV events
|Option for triglyceride >500 mg/dL (about 5 mmol/L)
Safe for use with statins
Associated with an increase in risk for recurrence of symptomatic atrial fibrillation or flutter within first 3 months of therapy
Use with caution with fish or shellfish allergy
|Drug||Potency (average LDL decrease)||Renal Considerations||Liver Function Monitoring|
|Atorvastatin||10 mg: 35-39%
20 mg: 43%
40 mg: 50%
80 mg: 55-60%
|No dose adjustment necessary for reduced renal function||Check liver function tests at baseline and when clinically indicated|
|Fluvastatin||20 mg: 22%
40 mg: 25%
80 mg: 35%
(as XL product)
|In severe renal impairment, use daily doses >40 mg with caution||Check liver function tests at baseline and when clinically indicated|
|Lovastatin||10 mg: 21%
20 mg: 24-27%
40 mg: 30-31%
80 mg: 40-42%
(as 40 mg BID)
|If CrCl < 30 mL/min, use daily doses over 20 mg with caution||Check liver function tests at baseline and when clinically indicated|
|Pitavastatin||1 mg: 31-32%
2 mg: 36-39%
4 mg: 41-45%
|For glomerular filtration rate 15-59 mL/min/1.73 m2, including hemodialysis, initial daily dose is 1 mg, not to exceed 2 mg/day||Check liver function tests at baseline and when clinically indicated|
|Pravastatin||10 mg: 22%
20 mg: 32%
40 mg: 34%
80 mg: 37%
|In significant renal impairment, start with 10 mg/day||Check liver function tests at baseline and when clinically indicated|
|Rosuvastatin||5 mg: 45%
10 mg: 46-52%
20 mg: 47-55%
40 mg: 55-63%
|If CrCl < 30 mL/min/1.73 m2 (but not on hemodialysis), starting dose is 5 mg/day, not exceed 10 mg/day
Rosuvastatin levels in hemodialysis patients are about 50% higher than levels in normal renal function
|Check liver function tests at baseline and when clinically indicated|
|Simvastatin||5 mg: 26%
10 mg: 30%
20 mg: 38%
40 mg: 29-41%
80 mg: 36-47%
|In severe renal impairment, starting dose is 5 mg daily with close monitoring||Check liver function tests at baseline and when clinically indicated|