Abstract
Chronic heart failure (HF) represents an emerging epidemic since its prevalence is continuously increasing despite advances in treatment. Many recent clinical studies have clearly demonstrated that statin therapy is associated with improved outcomes in HF irrespective of aetiology (ischaemic or not) or baseline cholesterol levels. Indeed, most of the conducted large statin trials and trials in HF have demonstrated a positive effect of statins in HF patients. Furthermore, the use of statins in HF seems to be safe as none of the recent trials has resulted in worse outcomes for HF patients treated with statins. Potential mechanisms through which statins could benefit the failing myocardium include non-sterol effects of statins, as well as effects on nitric oxide and endothelial function, inflammation and adhesion molecules, apoptosis and myocardial remodelling and neurohormonal activation. This review discusses the pathophysiological basis of statin effects on HF and focuses on clinical data for the benefit from statin use in this setting. Until today there are no official recommendations in both the American and the European guidelines regarding the use of statins in HF patients, as the available data come from small observational or larger but retrospective, non-randomised studies. Therefore, HF patients should be treated according to current lipid guidelines. Large randomised clinical trials are underway and will further delineate the role of statin therapy in HF patients. Until more data are available, we could not recommend statin use to every patient with HF irrespective of HF aetiology and baseline cholesterol levels.
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Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJ (2001) More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 3:315–322
Uretsky BF, Thygesen K, Armstrong PW et al (2000) 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 102:611–616
Anker SD, von Haehling S (2004) Inflammatory mediators in chronic heart failure: an overview. Heart 90:464–470
Cleland JG, Loh H, Windram J (2004) Some current controversies in heart failure (2004–2005). Minerva Cardioangiol 52:465–477
Haramaki N, Ikeda H (2003) Statins for heart failure: a potential for new treatment. Cardiovasc Res 60:217–219
Laufs U, Bohm M (2005) Cardiac effects of statins-advancements and open questions. Cardiovasc Res 66:427–429
Nakagami H, Jensen KS, Liao JK (2003) A novel pleiotropic effect of statins: prevention of cardiac hypertrophy by cholesterol-independent mechanisms. Ann Med 35:398–403
von Haehling S, Anker SD (2005) Statins for heart failure: at the crossroads between cholesterol reduction and pleiotropism? Heart 91:1–2
Laws PE, Spark JI, Cowled PA, Fitridge RA (2004) The role of statins in vascular disease. Eur J Vasc Endovasc Surg 27:6–16
Liberopoulos EN, Daskalopoulou SS, Mikhailidis DP, Wierzbicki AS, Elisaf MS (2005) A review of the lipid-related effects of fluvastatin. Curr Med Res Opin 21:231–244
Pham M, Oka RK, Giacomini JC (2005) Statin therapy in heart failure. Curr Opin Lipidol 16:630–634
Wright DG, Lefer DJ (2005) Statin mediated protection of the ischemic myocardium. Vascul Pharmacol 42:265–270
Nakagami H, Liao JK (2004) Statins and myocardial hypertrophy. Coron Artery Dis 15:247–250
Ramasubbu K, Mann DL (2006) The emerging role of statins in the treatment of heart failure. J Am Coll Cardiol 47:342–344
Banach M, Drozdz J, Okonski P, Rysz J (2005) Immunological aspects of the statins’ function in patients with heart failure: a report from the Annual Conference of ESC – Heart Failure 2005. Cell Mol Immunol 2:433–437
van der Harst P, Voors AA, van Gilst WH, Bohm M, van Veldhuisen DJ (2006) Statins in the treatment of chronic heart failure: biological and clinical considerations. Cardiovasc Res 71:443–454
Fox KF, Cowie MR, Wood DA et al (2001) Coronary artery disease as the cause of incident heart failure in the population. Eur Heart J 22:228–236
Remme WJ (2000) Overview of the relationship between ischemia and congestive heart failure. Clin Cardiol 23:4–8
Pedersen TR, Olsson AG, Faergeman O et al (1998) Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 97:1453–1460
Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:7–22
Hong YJ, Jeong MH, Hyun DW et al (2005) Prognostic significance of simvastatin therapy in patients with ischemic heart failure who underwent percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 95:619–622
Spencer FA, Fonarow GC, Frederick PD et al (2004) Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction. Arch Intern Med 164:2162–2168
Casey PJ (1995) Protein lipidation in cell signaling. Science 268:221–225
Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420:629–635
Wang SM, Tsai YJ, Jiang MJ, Tseng YZ (1997) Studies on the function of RhoA protein in cardiac myofibrillogenesis. J Cell Biochem 66:43–53
Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279:509–514
Laufs U, Liao JK (2003) Isoprenoid metabolism and the pleiotropic effects of statins. Curr Atheroscler Rep 5:372–378
Laufs U, La Fata V, Plutzky J, Liao JK (1998) Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97:1129–1135
Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265–9269
Garg UC, Hassid A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83:1774–1777
Gauthier TW, Scalia R, Murohara T, Guo JP, Lefer AM (1995) Nitric oxide protects against leukocyte-endothelium interactions in the early stages of hypercholesterolemia. Arterioscler Thromb Vasc Biol 15:1652–1659
Laufs U, Liao JK (1998) Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 273:24266–24271
Kureishi Y, Luo Z, Shiojima I et al (2000) The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 6:1004–1010
Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J et al (1998) Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 101:2711–2719
Wollert KC, Fiedler B, Gambaryan S et al (2002) Gene transfer of cGMP-dependent protein kinase I enhances the antihypertrophic effects of nitric oxide in cardiomyocytes. Hypertension 39:87–92
Maack C, Kartes T, Kilter H et al (2003) Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation 108:1567–1574
Tiefenbacher CP, Friedrich S, Bleeke T, Vahl C, Chen X, Niroomand F (2004) ACE inhibitors and statins acutely improve endothelial dysfunction of human coronary arterioles. Am J Physiol Heart Circ Physiol 286:1425–1432
von Haehling S, Anker SD, Bassenge E (2003) Statins and the role of nitric oxide in chronic heart failure. Heart Fail Rev 8:99–106
Trochu JN, Mital S, Zhang X et al (2003) Preservation of NO production by statins in the treatment of heart failure. Cardiovasc Res 60:250–258
Niebauer J, Volk HD, Kemp M et al (1999) Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 353:1838–1842
Mann DL (2002) Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circ Res 91:988–998
Levine B, Kalman J, Mayer L, Fillit HM, Packer M (1990) Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323:236–241
Deswal A, Bozkurt B, Seta Y et al (1999) Safety and efficacy of a soluble P75 tumor necrosis factor receptor (Enbrel, etanercept) in patients with advanced heart failure. Circulation 99:3224–3226
Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT; Anti-TNF Therapy Against Congestive Heart Failure Investigators (2003) Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 107:3133–3140
Louis A, Cleland JGF, Crabbe S et al (2002) Clinical trial update. Eur J Heart Fail 3:381–387
Kaneko K, Kanda T, Yamauchi Y et al (1999) C-reactive protein in dilated cardiomyopathy. Cardiology 91:215–219
Kardys I, Knetsch AM, Bleumink GS et al (2006) C-reactive protein and risk of heart failure The Rotterdam Study. Am Heart J 152:514–520
Devaux B, Scholz D, Hirche A, Klovekorn WP, Schaper J (1997) Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure. Eur Heart J 18:470–479
Sola S, Mir MQ, Lerakis S, Tandon N, Khan BV (2006) Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 47:332–337
Conraads VM, Bosmans JM, Schuerwegh AJ et al (2005) Effect of short-term treatment with pravastatin on cytokines and cytokine receptors in patients with chronic heart failure due to ischemic and nonischemic disease. J Heart Lung Transplant 24:1114–1117
Mozaffarian D, Minami E, Letterer RA et al (2005) The effects of atorvastatin (10 mg) on systemic inflammation in heart failure. Am J Cardiol 96:1699–1704
Tousoulis D, Antoniades C, Vassiliadou C et al (2005) Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure. Eur J Heart Fail 7:1126–1132
Kang PM, Izumo S (2000) Apoptosis and heart failure: a critical review of the literature. Circ Res 86:1107–1113
Nakaya R, Uzui H, Shimizu H et al (2005) Pravastatin suppresses the increase in matrix metalloproteinase-2 levels after acute myocardial infarction. Int J Cardiol 105:67–73
Hayashidani S, Tsutsui H, Shiomi T et al (2002) Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 105:868–873
van der Harst P, Voors AA, van Gilst WH, van Veldhuisen DJ (2005) Statins and autonomic function in chronic heart failure. Cardiovasc Drugs Ther 19:167–168
Tsouli SG, Liberopoulos EN, Kiortsis DN, Mikhailidis DP, Elisaf MS (2006) Combined treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a review of the current evidence. J Cardiovasc Pharmacol Ther 11:1–15
Liberopoulos EN, Elisaf MS (2005) Clinical use of Nebivolol in the treatment of chronic heart failure. Hellenic J Cardiol 46:208–211
Bonaduce D, Petretta M, Marciano F et al (1999) Independent and incremental prognostic value of heart rate variability in patients with chronic heart failure. Am Heart J 138:273–284
Hamaad A, Sosin M, Lip GY, MacFadyen RJ (2005) Short-term adjuvant atorvastatin improves frequency domain indices of heart rate variability in stable systolic heart failure. Cardiovasc Drugs Ther 19:183–187
Vrtovec B, Okrajsek R, Golicnik A, Ferjan M, Starc V, Radovancevic B (2005) Atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTc interval duration in patients with advanced chronic heart failure. J Card Fail 11:684–690
Katircibasi MT, Canatar T, Kocum HT et al (2005) Decreased heart rate recovery in patients with heart failure: effect of fluvastatin therapy. Int Heart J 46:845–854
Pliquett RU, Cornish KG, Peuler JD, Zucker IH (2003) Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation 107:2493
Milionis HJ, Liberopoulos EN, Achimastos A, Elisaf MS, Mikhailidis DP (2006) Statins: another class of antihypertensive agents? J Hum Hypertens 20:320–335
Liberopoulos EN, Daskalopoulou SS, Mikhailidis DP (2005) Early statin therapy in patients with acute coronary syndrome. Hellenic J Cardiol 46:5–8
Korantzopoulos P, Kokkoris S (2004) The antioxidant effects of statins may extend beyond atherosclerosis: potential benefits for atrial fibrillation and heart failure. Atherosclerosis 175:187
Vyas AK, Guo H, Moss AJ et al (2006) Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. J Am Coll Cardiol 47:769–773
Hanna IR, Heeke B, Bush H et al (2006) Lipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction. Heart Rhythm 3:881–886
Ganotakis ES, Mikhailidis DP, Vardas PE (2006) Atrial fibrillation, inflammation and statins. Hellenic J Cardiol 47:51–53
Hillege HL, Nitsch D, Pfeffer MA et al (2006) Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113:671–678
Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ (2005) ADHERE Scientific Advisory Committee, Study Group, and Investigators Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA 293:572–580
Luthi JC, Flanders WD, Burnier M, Burnand B, McClellan WM (2006) Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients. BMC Nephrol 7:3
Ljungman S, Laragh JH, Cody RJ (1990) Role of the kidney in congestive heart failure. Relationship of cardiac index to kidney function. Drugs 39:10–21
Athyros VG, Mikhailidis DP, Papageorgiou AA et al (2004) The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol 57:728–734
Elisaf M, Mikhailidis DP (2002) Statins and renal function. Angiology 53:493–502
Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf MS (2006) The effect of cholesterol-lowering treatment on renal function. Am J Kidney Dis 47:561
Ezekowitz J, McAlister FA, Humphries KH et al (2004) The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427 patients with heart failure and coronary artery disease. J Am Coll Cardiol 44:1587–1592
Ochiai ME, Barretto AC, Oliveira MT Jr, Munhoz RT, Morgado PC, Ramires JA (2005) Uric acid renal excretion and renal insufficiency in decompensated severe heart failure. Eur J Heart Fail 7:468–474
Roch-Ramel F, Guisan B, Diezi J (1997) Effects of uricosuric and antiuricosuric agents on urate transport in human brush-border membrane vesicles. J Pharmacol Exp Ther 280:839–845
Bakhtiiarov ZA (1989) Changes in xanthine oxidase activity in patients with circulatory failure. Ter Arkh 61:68–69
Terada LS, Guidot DM, Leff JA et al (1992) Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. Proc Natl Acad Sci USA 89:3362–3366
Leyva F, Anker S, Swan JW et al (1997) Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure. Eur Heart J 18:858–865
Leyva F, Anker SD, Godsland IF et al (1998) Uric acid in chronic heart failure: a marker of chronic inflammation. Eur Heart J 19:1814–1822
Anker SD, Doehner W, Rauchhaus M et al (2003) Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation 107:1991–1997
Cengel A, Turkoglu S, Turfan M, Boyaci B (2005) Serum uric acid levels as a predictor of in-hospital death in patients hospitalized for decompensated heart failure. Acta Cardiol 60:489–492
Hare JM, Johnson RJ (2003) Uric acid predicts clinical outcomes in heart failure: insights regarding the role of xanthine oxidase and uric acid in disease pathophysiology. Circulation 107:1951–1953
Athyros VG, Elisaf M, Papageorgiou AA et al (2004) Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Am J Kidney Dis 43:589–599
Milionis HJ, Kakafika AI, Tsouli SG et al (2004) Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia. Am Heart J 148:635–640
Tsouli SG, Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf MS (2006) Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander? Metabolism 55:1293–1301
Taegtmeyer H, McNulty P, Young ME (2002) Adaptation and maladaptation of the heart in diabetes: Part I: general concepts. Circulation 105:1727–1733
Kenchaiah S, Evans JC, Levy D et al (2002) Obesity and the risk of heart failure. N Engl J Med 347:305–313
He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK (2001) Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 161:996–1002
Krumholz HM, Chen YT, Wang Y, Vaccarino V, Radford MJ, Horwitz RI (2000) Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J 139:72–77
Shindler DM, Kostis JB, Yusuf S et al (1996) Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry. Am J Cardiol 77:1017–1020
Liberopoulos EN, Tsouli S, Mikhailidis DP, Elisaf MS (2006) Preventing type 2 diabetes in high risk patients: an overview of lifestyle and pharmacological measures. Curr Drug Targets 7:211–228
Liberopoulos EN, Athyros VG, Elisaf MS, Mikhailidis DP (2005) New-onset diabetes after transplantation. Lancet 365:1766
Freeman DJ, Norrie J, Sattar N et al (2001) Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 103:357–362
Ingelsson E, Arnlov J, Lind L, Sundstrom J (2006) The metabolic syndrome and risk for heart failure in middle-aged men. Heart 92:1409–1413
Liberopoulos EN, Mikhailidis DP, Elisaf MS (2005) Diagnosis and management of the metabolic syndrome in obesity. Obes Rev 6:283–296
Kjekshus J, Pedersen TR, Olsson AG, Faergeman O, Pyorala K (1997) The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail 3:249–254
LaRosa JC, Grundy SM, Waters DD et al (2005) Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 352:1425–1435
Pedersen TR, Faergeman O, Kastelein JJ et al (2005) High-dose atorvastatin vs. usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 294:2437–2445
Schwartz GG, Olsson AG, Ezekowitz MD et al (2001) Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 285:1711–1718
de Lemos JA, Blazing MA, Wiviott SD et al (2004) Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 292:1307–1316
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group (1998) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 339:1349–1357
Athyros VG, Papageorgiou AA, Mercouris BR et al (2002) Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Curr Med Res Opin 18:220–228
Spencer FA, Allegrone J, Goldberg R et al (2004) The GRACE Study. Association of statin therapy with outcomes of acute coronary syndromes: The GRACE Study. Ann Intern Med 140:857–866
Scirica BM, Morrow DA, Cannon CP et al (2006) 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 47:2326–2331
Anderssen SA, Hjelstuena AK, Hjermanna I, Bjerkana K, Holmea I (2005) Fluvastatin and lifestyle modification for reduction of carotid intima-media thickness and left ventricular mass progression in drug-treated hypertensives. Atherosclerosis 178:387–397
Sacks FM, Pfeffer MA, Moye LA et al (1996) The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 335:1001–1009
Heart Protection Study Collaborative Group (2005) The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomised placebo-controlled trial [ISRCTN48489393]. BMC Med 3:6
Shepherd J, Blauw GJ, Murphy MB et al (2002) PROspective Study of Pravastatin in the Elderly at Risk Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360:1623–1630
Koren MJ, Hunninghake DB; ALLIANCE Investigators (2004) Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. J Am Coll Cardiol 44:1772–1779
Heart Protection Study Collaborative Group (2007) N-terminal pro-B-type natriuretic peptide, vascular disease risk, and cholesterol reduction among 20,536 patients in the MRC/BHF Heart Protection Study. J Am Coll Cardiol 49:311–319
Khush KK, Waters DD, Bittner V et al (2007) Effect of high-dose atorvastatin on hospitalizations for heart failure subgroup analysis of the treating to new targets (TNT) Study. Circulation 115:576–583
Horwich TB, MacLellan WR, Fonarow GC (2004) Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol 43:642–648
Mozaffarian D, Nye R, Levy WC (2004) Statin therapy is associated with lower mortality among patients with severe heart failure. Am J Cardiol 93:1124–1129
Folkeringa RJ, Van Kraaij DJ, Tieleman RG, Nieman FH, Pinto YM, Crijns HJ (2006) Statins associated with reduced mortality in patients admitted for congestive heart failure. J Card Fail 12:134–138
Fukuta H, Sane DC, Brucks S, Little WC (2005) Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 112:357–363
Sola S, Mir MQ, Rajagopalan S, Helmy T, Tandon N, Khan BV (2005) Statin therapy is associated with improved cardiovascular outcomes and levels of inflammatory markers in patients with heart failure. J Card Fail 11:607–612
Sola S, Mir MQ, Lerakis S, Tandon N, Khan BV (2006) Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 47:332–337
Ray JG, Gong Y, Sykora K, Tu JV (2005) Statin use and survival outcomes in elderly patients with heart failure. Arch Intern Med 165:62–67
Foody JM, Shah R, Galusha D, Masoudi FA, Havranek EP, Krumholz HM (2006) Statins and mortality among elderly patients hospitalized with heart failure. Circulation 113:1086–1092
Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH (2006) Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA 296:2105–2111
Hognestad A, Dickstein K, Myhre E, Snapinn S, Kjekshus J; OPTIMAAL Investigators (2004) Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure. Am J Cardiol 93:603–606
Sakamoto T, Kojima S, Ogawa H et al (2006) Multicenter study for aggressive lipid-lowering strategy by HMG-CoA reductase inhibitors in patients with acute myocardial infarction investigators. Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese. Am J Cardiol 97:1165–1171
Saab FA, Eagle KA, Kline-Rogers E, Fang J, Otten R, Mukherjee D; Michigan Cardiovascular Outcomes Research and Reporting Program of the University of Michigan Cardiovascular Center (2004) Comparison of outcomes in acute coronary syndrome in patients receiving statins within 24 hours of onset versus at later times. Am J Cardiol 94:1166–1168
Node K, Fujita M, Kitakaze M, Hori M, Liao JK (2003) Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 108:839–843
Wojnicz R, Wilczek K, Nowalany-Kozielska E et al (2006) Usefulness of atorvastatin in patients with heart failure due to inflammatory dilated cardiomyopathy and elevated cholesterol levels. Am J Cardiol 97:899–904
Yamada T, Node K, Mine T et al (2006) Atorvastatin therapy associated with improvement in left ventricular remodelling in a case of idiopathic dilated cardiomyopathy. Am J Med Sci 332:361–363
Laufs U, Wassmann S, Schackmann S, Heeschen C, Bohm M, Nickenig G (2004) Beneficial effects of statins in patients with non-ischemic heart failure. Z Kardiol 93:103–108
Kjekshus J, Dunselman P, Blideskog M et al (2005) A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): study design and baseline characteristics. Eur J Heart Fail 7:1059–1069
Tavazzi L, Tognoni G, Franzosi MG et al (2004) Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail 6:635–641
Rauchhaus M, Coats AJ, Anker SD (2000) The endotoxin-lipoprotein hypothesis. Lancet 356:930–933
Rauchhaus M, Clark AL, Doehner W et al (2003) The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 42:1933–1940
de Lorgeril M, Salen P, Bontemps L, Belichard P, Geyssant A, Itti R (1999) Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients. J Cardiovasc Pharmacol 33:473–478
Mortensen SA (2003) Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of “Q-symbio”-a multinational trial. Biofactors 18:79–89
Sander S, Coleman CI, Patel AA, Kluger J, White CM (2006) The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail 12:464–472
Mortensen SA, Leth A, Agner E, Rohde M (1997) Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med 18:137–144
Berman M, Erman A, Ben-Gal T et al (2004) Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. Clin Cardiol 27:295–299
Strey CH, Young JM, Molyneux SL et al (2005) Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure. Atherosclerosis 179:201–206
Stoll LL, McCormick ML, Denning GM, Weintraub NL (2005) Antioxidant effects of statins. Timely Top Med Cardiovasc Dis 9:1
Richartz BM, Radovancevic B, Frazier OH, Vaughn WK, Taegtmeyer H (1998) Low serum cholesterol levels predict high perioperative mortality in patients supported by a left-ventricular assist system. Cardiology 89:184–188
Horwich TB, Hamilton MA, MacLellan WR, Fonarow GC (2002) Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 8:216–224
Bleske BE, Nicklas JM, Bard RL et al (2006) 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 47:338–341
Tousoulis D, Antoniades C, Bosinakou E et al (2005) Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure. Atherosclerosis 178:359–363
Smith SC Jr, Allen J, Blair SN et al (2006) AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 113:2363–2372
Swedberg K, Cleland J, Dargie H et al (2005) Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 26:1115–1140
Daskalopoulou SS, Mikhailidis DP (2006) Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis and absorption with simvastatin plus ezetimibe. Curr Med Res Opin 22:511–528
Landmesser U, Bahlmann F, Mueller M et al (2005) Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation 111:2356–2363
Expert panel on detection, evaluation and treatment of high blood cholesterol in adults, executive summary of the third report of the National Cholesterol Education Program (NCEP) (Adult Treatment Panel III). JAMA (2001) 285:2486–2497
Grundy SM, Cleeman JI, Bairey CN et al (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110:227–229
De Backer G, Ambrosioni E, Borch-Johnsen K et al (2003) European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 24:1601–1610
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Tsouli, S.G., Liberopoulos, E.N., Goudevenos, J.A. et al. Should a statin be prescribed to every patient with heart failure?. Heart Fail Rev 13, 211–225 (2008). https://doi.org/10.1007/s10741-007-9041-2
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DOI: https://doi.org/10.1007/s10741-007-9041-2