Abstract
Hypercholesterolemia is a risk factor for coronary artery disease (CAD), CAD mortality, and incident heart failure (HF). Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been shown to reduce the risk of developing HF in patients with CAD. However, in patients with chronic established HF, hypercholesterolemia has not been associated with an increased risk of mortality. Several studies have demonstrated that higher lipid and lipoprotein levels, including total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides, are associated with significantly improved outcomes in HF of both ischemic and nonischemic etiologies. In light of the association between high cholesterol levels and improved survival in HF, statin or other lipid-lowering therapy in HF remains controversial. To date, large outcome trials of statin therapy in HF of multiple etiologies have not demonstrated mortality benefit.
Similar content being viewed by others
References and Recommended Reading
Lloyd-Jones D, Adams R, Carnethon M, et al.: Heart Disease and Stroke Statistics-2009 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009, 119:e21–e181
Pekkanen J, Linn S, Heiss G, et al.: Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med 1990, 322:1700–1707.
He J, Ogden LG, Bazzano LA, et al.: Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 2001, 161:996–1002.
Levy D, Larson MG, Vasan RS, et al.: The progression from hypertension to congestive heart failure. JAMA 1996, 275:1557–1562.
Adams JK, Fonarow GC, Emerman CL, et al.: Characteristics and outcomes of patients hospitalized for heart failure in the United States: Rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2005, 149:209–216.
Schocken DD, Benjamin EJ, Fonarow GC, et al.: Prevention of Heart Failure: A Scientific Statement From the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation 2008, 117:2544–2565.
Kannel WB, Belanger AJ: Epidemiology of heart failure. Am Heart J 1991, 121(3 Pt 1):951–957.
Kjekshus J, Pedersen TR, Olsson AG, et al.: The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail 1997, 3:249–254.
Pedersen TR: Coronary artery disease: the Scandinavian Simvastatin Survival Study experience. Am J Cardiol 1998, 82:53T–56T.
Scirica BM, Morrow DA, Cannon CP, et al.: Intensive statin therapy and the risk of hospitalization for heart failure after an acute coronary syndrome in the PROVE IT-TIMI 22 study. J Am Coll Cardiol 2006, 47:2326–2331.
Vredevoe DL, Woo MA, Doering LV, et al.: Skin test anergy in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1998, 82:323–328.
Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC: Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002, 8:216–224.
Rauchhaus M, Koloczek V, Volk HD, et al.: Inflammatory cytokines and the possible immunological role for lipoproteins in chronic heart failure. Int J Cardiol 2000, 76:125–133.
Rauchhaus M, Clark AL, Doehner W, et al.: The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 2003, 42:1933–1940.
Afsarmanesh N, Horwich TB, Fonarow GC: Total cholesterol levels and mortality risk in nonischemic systolic heart failure. Am Heart J 2006, 152:1077–1083.
Horwich TB, Hernandez AF, Dai D, et al.: Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure. Am Heart J 2008, 156:1170–1176.
Christ M, Klima T, Grimm W, et al.: Prognostic significance of serum cholesterol levels in patients with idiopathic dilated cardiomyopathy. Eur Heart J 2006, 27:691–699.
Kalantar-Zadeh K, Block G, Horwich T, Fonarow GC: Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J Am Coll Cardiol 2004, 43:1439–1444.
Horwich TB, Fonarow GC: Reverse epidemiology beyond dialysis patients: chronic heart failure, geriatrics, rheumatoid arthritis, COPD, and AIDS. Semin Dial 2007, 20:549–553.
Horwich TB, Kalantar-Zadeh K, MacLellan RW, Fonarow GC: Albumin levels predict survival in patients with systolic heart failure. Am Heart J 2008, 155:883–889.
Anker SD, Ponikowski P, Varney S, et al.: Wasting as independent risk factor for mortality in chronic heart failure. Lancet 1997, 349:1050–1053.
Deswal A, Petersen NJ, Feldman AM, et al.: Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 2001, 103:2055–2059.
May HT, Muhlestein JB, Carlquist JF, et al.: Relation of serum total cholesterol, C-reactive protein levels, and statin therapy to survival in heart failure. Am J Cardiol 2006, 98:653–658.
Rauchhaus M, Coats AJ, Anker SD: The endotoxin-lipoprotein hypothesis. Lancet 2000, 356:930–933.
Strey CH, Young JM, Molyneux SL, et al.: Endotheliumameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure. Atherosclerosis 2005, 179:201–206.
Takemoto M, Liao JK: Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol 2001, 21:1712–1719.
Uretsky BF, Thygesen K, Armstrong PW, et al.: Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. Circulation 2000, 102:611–616.
Gao L, Wang W, Li YL, et al.: Simvastatin therapy normalizes sympathetic neural control in experimental heart failure. roles of angiotensin ii type 1 receptors and NAD(P)H oxidase. Circulation 2005, 112:1763–1770
Patel R, Nagueh SF, Tsybouleva N, et al.: Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 2001, 104:317–324.
Horwich TB, MacLellan WR, Fonarow GC: Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol 2004, 43:642–648.
Go AS, Lee WY, Yang J, et al.: Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA 2006, 296:2105–2111.
Ray JG, Gong Y, Sykora K, Tu JV: Statin use and survival outcomes in elderly patients with heart failure. Arch Intern Med 2005, 165:62–67.
Fukuta H, Sane DC, Brucks S, Little WC: statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 2005, 112:357–363.
Node K, Fujita M, Kitakaze M, et al.: Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 2003, 108:839–843.
Sola S, Mir MQ, Lerakis S, et al.: Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 2006, 47:332–337.
Bleske BE, Nicklas JM, Bard RL, et al.: Neutral effect on markers of heart failure, inflammation, endothelial activation and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non-diabetic patients with non-ischemic cardiomyopathy and average low-density lipoprotein level. J Am Coll Cardiol 2006, 47:338–341.
Krum H, Ashton E, Reid C, et al.: Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, proinflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure. J Card Fail 2007, 13:1–7.
Kjekshus J, Apetrei E, Barrios V, et al.: Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007, 357:2248–2261.
GISSI-HF Investigators, Tavazzi L, Maggioni AP, et al.: Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008, 372:1231–1239.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Horwich, T. Low-density lipoprotein in the setting of congestive heart failure: Is lower really better?. Curr Atheroscler Rep 11, 343–349 (2009). https://doi.org/10.1007/s11883-009-0052-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11883-009-0052-4