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hyperlipidemia

Hyperlipidemia: Excessive quantity of fat (cholesterol &/or triglycerides) in the blood. Etiology: 1) primary hyperlipidemia - genetic disorders of lipoprotein metabolism 2) secondary hyperlipidemia a) excess dietary intact of fat, calories, alcohol b) concurrent illnesses - obesity* - hypothyroidism - nephrotic syndrome - uremia - cholestasis, obstructive liver disease - primary biliary cirrhosis - alcoholism [1] - diabetes mellitus type 2 (insulin resistance)* - renal failure* c) pharmacologic agents - corticosteroids - thiazide diuretics - beta-blockers* - estrogens, oral contraceptives - alcohol - amiodarone - cyclosporine - retinoids* - antiretroviral protease inhibitors d) smoking [1] e) combinations of 1,2,3, & 4 * increased serum triglycerides & decreased HDL cholesterol Epidemiology: - 7% of adults have LDL cholesterol level > 190 mg/dL [11] Clinical manifestations: 1) generally asymptomatic until symptoms secondary to atherosclerosis occur a) angina pectoris b) claudication c) symptoms of TIA or stroke 2) elevation of triglyceride > 1000 mg/dL may cause symptoms of pancreatitis 3) xanthomas may occur on extensor tendons 4) periorbital xanthelasmas may occur in familial cases Laboratory: - fasting lipid panel a) non HDL cholesterol = total cholesterol - HDL cholesterol 1] useful for serum triglycerides > 200 mg/dL 2] target = target LDL cholesterol + 30 [1] b) see management for goals of therapy - laboratory tests that have no impact on mortality [1] a) serum C-reactive protein b) serum lipoprotein c) serum apolipoprotein B d) serum homocysteine - gene testing* for familial hypercholesterolemia - gene mutations for familial hypercholesterolemia in < 2% of patients with LDL cholesterol level > 190 mg/dL [13] * genetic testing for familial hypercholesterolemia - LDLR gene mutations - APOB gene+LDLR gene mutations - APOB+LDLR+PCSK9 gene mutations Management: === goals of therapy === 1) target LDL cholesterol depends upon a) presence of CAD: < 100 mg/dL b) 2 or more cardiovascular risk factors: < 130 mg/dL c) < 2 cardiovascular risk factors: < 160 mg/dL [1] 2) no target for treating low HDL cholesterol [1] === diet is primary therapy === 1) total fat < 30% of calories, < 10% saturated fat 2) limit carbohydrates [1] 3) cholesterol < 300 mg/day 4) lower LDL & HDL cholesterol 5) may not affect HDL cholesterol / total cholesterol [2] 6) plant-based diet may have additional benefit [2] 7) Mediterranean-style diet, fish-oil (2.2 g/day of w-3 polyunsaturated fat) & red yeast rice-extract (2.4-3.6 g/day) as effective as 40 mg simvastatin/day in lowering LDL cholesterol [4] 8) viscous fibers (oats, barley, beans)* 9) limit alcohol consumption === aerobic exercise === 1) 20 to 30 minutes 3 times/week 2) fitness lowers mortality in hyperlipidemic patients, regardless of statin use 3) moderate fitness (5.1-7.0 METS) lowers mortality as much as statin use [6] === pharmacologic agents === 1) hypercholesterolemia a) HMG CoA reductase inhibitors (statins) 1st line [1] - beneficial effects on LDL cholesterol, HDL cholesterol, serum triglycerides (see LDL cholesterol for intensity of therapy) - ezetimibe 10 mg 1st add to statin therapy [10] - PCSK9 inhibitor evolocumab or alirocumab - alternative addition to statin therapy [10] - recommended if risk factors, on maximum statin & ezetimibe therapy & LDL-cholesterol > 130 mg/dL [1] b) bile acid sequestrant 1] affect (lowers) mainly LDL cholesterol 2] cholestyramine (Questran) 4 g QD - TID 3] no evidence of cardiovascular benefit when added to statin [1] c) nicotinic acid 1-3 g TID 1] beneficial effects on LDL cholesterol, HDL cholesterol, serum triglycerides 2] better for hypertriglyceridemia than statins [1] 3] no benefit as adjunct to statin therapy for patients with low HDL cholesterol & high serum triglycerides [5] d) Probucol (Lorelco) 500 mg PO BID e) estrogen replacement therapy f) red yeast rice (Monascus purpureus, Xue Zhi Kang)* - can lower LDL cholesterol 35-43 gm/dL - marked variation among different commercial products g) psyllium* (5% reduction in LDL cholesterol) [8] 2) hypertriglyceridemia a) fibrates are 1st line - gemfibrozil (Lopid) 600 mg PO BID b) nicotinic acid (second choice) c) statins 3) caution in treating hyperlipidemia in patients with schizophrenia - increased serum cholesterol & serum triglycerides are associated with better cognitive function in patients with schizophrenia [9] * GRS8 states evidence stronger to support effectiveness of viscous fibers (oats, barley, beans, psyllium) than for red yeast rice [8] despite lesser effect on LDL cholesterol (apparently because of variation among different commercial products of red yeast rice)

Interactions

disease interactions

Related

hyperlipoproteinemia (HLP)

Specific

hypercholesterolemia hypertriglyceridemia lecithin-cholesterol acyltransferase [LCAT] deficiency (Norum disease)

General

chronic metabolic disease lipid disorder (dyslipidemia)

Figures/Diagrams

Figures/diagrams/slides/tables related to hyperlipidemia Dyslipoproteinemias

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2018, 2021.
  2. Journal Watch 25(12):97, 2005 Gardner CD, Coulston A, Chatterjee L, Rigby A, Spiller G, Farquhar JW. The effect of a plant-based diet on plasma lipids in hypercholesterolemic adults: a randomized trial. Ann Intern Med. 2005 May 3;142(9):725-33. Summary for patients in: Ann Intern Med. 2005 May 3;142(9):I35. PMID: 15867404
  3. Prescriber's Letter 14(1): 2007 Intensive LDL Reduction: What's the Evidence? Detail-Document#: 230107 (subscription needed) http://www.prescribersletter.com
  4. Becker DJ et al. Simvastatin vs therapeutic lifestyle changes and supplements: Randomized primary prevention trial. Mayo Clin Proc 2008 Jul; 83:758. PMID: 18613992
  5. 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 - Prescriber's Letter 18(7): 2011 Niacin Plus Statin to Reduce Cardiovascular Risk: AIM-HIGH Study Detail-Document#: 270701 (subscription needed) http://www.prescribersletter.com - The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011 Nov 15 PMID: 22085343 http://www.nejm.org/doi/full/10.1056/NEJMoa1107579
  6. Kokkinos PF et al. Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: A cohort study. Lancet 2012 Nov 28 PMID: 23199849
  7. Stone NJ et al 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk on Adults. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. Nov 12, 2013 PMID: 24222016 http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a - Stone NJ et al Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults: Synopsis of the 2013 ACC/AHA Cholesterol Guideline. Ann Intern Med. Published online 28 January 2014 PMID: 24474185 http://annals.org/article.aspx?articleid=1818923
  8. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  9. Brooks M Hyperlipidemia: Bad for the Heart, Good for the Brain? Medscape News from the American Psychiatric Association (APA) 2015 Annual Meeting http://www.medscape.com/viewarticle/844814
  10. Lloyd-Jones DM et al 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. J Am Coll Cardiol. April 2016 PMID: 27046161 Free Article http://content.onlinejacc.org/article.aspx?articleID=2510936#tab1
  11. Watson KE How Many Patients with Severe Hypercholesterolemia Have FH? NEJM Journal Watch. April 19, 2016 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Khera AV et al. Diagnostic yield of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol 2016 Apr 3 PMID: 27050191
  12. Roth EM, McKenney JM, Hanotin C, et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012;367(20):1891-1900 PMID: 23113833 Free Article
  13. 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. Circulation. 2019 Jun 18;139(25):e1082-e1143. PMID: 30586774 - 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: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1046-e1081. PMID: 30565953 - Forman DE, Stone NJ, Grundy SM. Treating Hypercholesterolemia in Older Adults. JAMA. 2019 Aug 20;322(7):695. No abstract available. PMID: 31429891