Alexopoulos AS, Qamar A, Hutchins K, Crowley MJ, Batch BC, Guyton JR. Triglycerides: Emerging Targets in Diabetes Care? Review of Moderate Hypertriglyceridemia in Diabetes. Curr Diab Rep. 2019 Feb 26. 19 (4):13. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
FREDRICKSON DS, LEES RS. A SYSTEM FOR PHENOTYPING HYPERLIPOPROTEINEMIA. Circulation. 1965 Mar. 31:321-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Smelt AH, de Beer F. Apolipoprotein E and familial dysbetalipoproteinemia: clinical, biochemical, and genetic aspects. Semin Vasc Med. 2004 Aug. 4(3):249-57. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Feussner G, Piesch S, Dobmeyer J, Fischer C. Genetics of type III hyperlipoproteinemia. Genet Epidemiol. 1997. 14(3):283-97. [QxMD MEDLINE Link].
Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988 Jan-Feb. 8(1):1-21. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Goyal A, Cusick AS, Bansal P. Familial Hypertriglyceridemia. StatPearls. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].
Carrasquilla GD, Christiansen MR, Kilpelainen TO. The Genetic Basis of Hypertriglyceridemia. Curr Atheroscler Rep. 2021 Jun 19. 23 (8):39. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Pajukanta P, Porkka KV. Genetics of familial combined hyperlipidemia. Curr Atheroscler Rep. 1999 Jul. 1(1):79-86. [QxMD MEDLINE Link].
Kolovou GD, Anagnostopoulou KK, Kostakou PM, Bilianou H, Mikhailidis DP. Primary and secondary hypertriglyceridaemia. Curr Drug Targets. 2009 Apr. 10(4):336-43. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Sanchez RJ, Ge W, Wei W, Ponda MP, Rosenson RS. The association of triglyceride levels with the incidence of initial and recurrent acute pancreatitis. Lipids Health Dis. 2021 Jul 18. 20 (1):72. [QxMD MEDLINE Link]. [Full Text].
Zhang S, Du T, Li M, Lu H, Lin X, Yu X. Combined effect of obesity and uric acid on nonalcoholic fatty liver disease and hypertriglyceridemia. Medicine (Baltimore). 2017 Mar. 96 (12):e6381. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Sumner AE, Cowie CC. Ethnic differences in the ability of triglyceride levels to identify insulin resistance. Atherosclerosis. 2008 Feb. 196(2):696-703. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Saadatagah S, Pasha AK, Alhalabi L, et al. Coronary Heart Disease Risk Associated with Primary Isolated Hypertriglyceridemia; a Population-Based Study. J Am Heart Assoc. 2021 Jun. 10 (11):e019343. [QxMD MEDLINE Link]. [Full Text].
Fan W, Philip S, Granowitz C, Toth PP, Wong ND. Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey. J Clin Lipidol. 2019 Jan - Feb. 13 (1):100-8. [QxMD MEDLINE Link].
Pedersen SB, Langsted A, Nordestgaard BG. Nonfasting Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis. JAMA Intern Med. 2016 Dec 1. 176 (12):1834-42. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Brunzell JD, Bierman EL. Chylomicronemia syndrome. Interaction of genetic and acquired hypertriglyceridemia. Med Clin North Am. 1982 Mar. 66(2):455-68. [QxMD MEDLINE Link].
Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med. 1992. 37:249-73. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Fortson MR, Freedman SN, Webster PD 3rd. Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol. 1995 Dec. 90(12):2134-9. [QxMD MEDLINE Link].
Vipperla K, Somerville C, Furlan A, et al. Clinical Profile and Natural Course in a Large Cohort of Patients With Hypertriglyceridemia and Pancreatitis. J Clin Gastroenterol. 2016 Jun 17. [QxMD MEDLINE Link].
Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med. 2008 Jan. 121(1):10-2. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Rohrich RJ, Janis JE, Pownell PH. Xanthelasma palpebrarum: a review and current management principles. Plast Reconstr Surg. 2002 Oct. 110(5):1310-4. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link].
Haffner SM. Secondary prevention of coronary heart disease: the role of fibric acids. Circulation. 2000 Jul 4. 102(1):2-4. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
FDA. AbbVie Inc. et al; Withdrawal of Approval of Indications Related to the Coadministration With Statins in Applications for Niacin Extended-Release Tablets and Fenofibric Acid Delayed-Release Capsules. Federal Register. 2016 Apr 18. [Full Text].
Wending P. FDA Pulls Approval of Niacin, Fibrate in Combo with Statins. Medscape. 2016 Apr 15. [Full Text].
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. [QxMD MEDLINE Link].
Sica DA. Fibrate therapy and renal function. Curr Atheroscler Rep. 2009 Sep. 11(5):338-42. [QxMD MEDLINE Link].
Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol. 2008 Jun 24. 51(25):2375-84. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. 2008 Apr. 83(4):470-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Wendling P. No CVD Benefit With Omega-3 Fatty Acids. Medscape Medical News. Feb 2, 2018. [Full Text].
Aung T, Halsey J, Kromhout D, et al. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals. JAMA Cardiol. 2018 Mar 1. 3 (3):225-34. [QxMD MEDLINE Link]. [Full Text].
Kim HS, Kim H, Jeong YJ, et al. Comparative analysis of the efficacy of omega-3 fatty acids for hypertriglyceridaemia management in Korea. J Clin Pharm Ther. 2016 Jul 18. [QxMD MEDLINE Link].
Tatachar A, Pio M, Yeung D, et al. Over-the-counter fish oil use in a county hospital: medication use evaluation and efficacy analysis. J Clin Lipidol. 2015 May-Jun. 9 (3):326-33. [QxMD MEDLINE Link]. [Full Text].
Hilleman D, Smer A. Prescription Omega-3 Fatty Acid Products and Dietary Supplements Are Not Interchangeable. Manag Care. 2016 Jan. 25 (1):46-52. [QxMD MEDLINE Link]. [Full Text].
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.
Bhatt DL, Miller M, Brinton EA, et al. REDUCE-IT USA: Results from the 3,146 Patients Randomized in the United States. Circulation. 2019 Nov 11. [QxMD MEDLINE Link]. [Full Text].
Prescribing information: Omtryg. FDA. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204977s000lbl.pdf. 2014 Apr; Accessed: 2018 Jun 14.
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. [QxMD MEDLINE Link].
Nainggolan L. FDA Approves Epanova for Severe Hypertriglyceridemia. Medscape. Available at http://www.medscape.com/viewarticle/824748. May 7, 2014; Accessed: June 14, 2014.
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Jun JE, Jeong IK, Yu JM, et al. Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Diabetes Metab J. 2019 Jun 20. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24. 129 (25 Suppl 2):S1-45. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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.

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Eruptive xanthomas on the back of a patient admitted with a triglyceride level of 4600 mg/dL and acute pancreatitis.
Close-up of eruptive xanthomas.
Composition of triglyceride (TG)-rich lipoproteins. IDL = intermediate-density lipoprotein; VLDL = very low-density lipoprotein.
Lipoprotein lipase (LPL) releases free fatty acids (FFAs) from chylomicrons (chylo) and produces chylomicron remnants that are small enough to take part in the atherosclerotic process. Chol = cholesterol; TGs, TGS = triglycerides.
Once very low-density lipoprotein (VLDL) has been metabolized by lipoprotein lipase, VLDL remnants in the form of intermediate-density lipoprotein (IDL) can be metabolized by hepatic lipase, producing low-density lipoprotein (LDL), or they can be taken up by the LDL receptor via either apolipoprotein B (apo B) or apo E. Chol = cholesterol; TGs = triglycerides.

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Table 1. Fredrickson Classification of Hyperlipidemia

Type	Serum Elevation	Lipoprotein Elevation
I	Cholesterol and triglycerides	Chylomicrons
IIa	Cholesterol	LDL
IIb	Cholesterol and triglycerides	LDL, VLDL
III	Cholesterol and triglycerides	IDL
IV	Triglycerides	VLDL
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.^[3]

Table 2. Classification of Triglycerides

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.^[14]

Table 3. Classification of LDL Cholesterol and Non-HDL Cholesterol

Classification		LDL Goal, mg/dL	Non-HDL Goal, mg/dL
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
Two or more risk factors and the following:	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.^[14]

Table 4. Fibric Acid Agents, Omega Acid Ethyl Esters, and Niacin Drug Characteristics ^[91]

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.

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

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)

Secondary CV risk prevention; REDUCE-IT trial showed primary endpoint (major CV events) occurred in 24.7% of placebo compared with 18.2% of icosapent ethyl treated patients (p = 0.000001) ^[80]

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

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

Table 5. Statin Drug Characteristics ^[92]

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

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Author

Mary Ellen T Sweeney, MD Associate Professor of Medicine (Endocrinology, Diabetes, and Metabolism), Department of Medicine, Emory University School of Medicine; Physician, Division of Endocrinology, Veterans Administration Medical Center; Physician, Lipid Metabolism Clinic, Emory Healthcare, The Emory Clinic

Mary Ellen T Sweeney, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, National Lipid Association

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Acknowledgements

Steve Charles, MD Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians and Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong

Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society

Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Other; Topcon Medical Lasers Consulting fee Consulting

Karen E Friday, MD, FACP Clinical Core Director of Tulane Xavier National Center of Excellence, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Tulane University School of Medicine

Karen E Friday, MD, FACP is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Heart Association, American Society for Clinical Nutrition, and Endocrine Society

Disclosure: AstraZeneca own AstraZeneca stock None; Merck own Merck stock None; Schering Plough own Schering Plough stock None; Medco Health own Medco Health stock None

Robert A Gabbay, MD, PhD Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity

Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society

Disclosure: Novo Nordisk Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R. Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America

Disclosure: Nothing to disclose.

Romesh Khardori, MD, PhD Professor and Director, Division of Endocrinology, Metabolism, and Molecular Medicine, Southern Illinois University School of Medicine

Romesh Khardori, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society of Andrology, Endocrine Society, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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