Experimental and Clinical Basis for the Use of Statins in Patients With Ischemic and Nonischemic Cardiomyopathy

Journal of the American College of Cardiology

Volumn 51, Issue 4, 2008, Pages 415-426

  Ramasubbu, Kumudha ^a   Estep, Jerry ^a   White, Donna L ^b   Deswal, Anita ^a,b,c   Mann, Douglas L ^a  

^a Winters Ctr for Heart Failure Res   (United States)

^b Houston Center for Quality of Care and Utilization Studies   (United States)

^c MICHAEL E DEBAKEY VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATORVASTATIN; BISOPROLOL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PLACEBO; ROSUVASTATIN;

ANGIOGENESIS; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; CARDIOMYOPATHY; DEFIBRILLATOR; DRUG EFFECT; DRUG MEGADOSE; ENDOTHELIUM CELL; HEART LEFT VENTRICLE HYPERTROPHY; HEART VENTRICLE REMODELING; HUMAN; ISCHEMIC HEART DISEASE; PRIORITY JOURNAL; REVIEW; THERAPY EFFECT; TREATMENT OUTCOME; TREATMENT RESPONSE;

ANTI-ARRHYTHMIA AGENTS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; AUTONOMIC AGENTS; CARDIOMYOPATHIES; CYTOKINES; DRUG EVALUATION; ENDOTHELIUM, VASCULAR; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERTROPHY; LIPOPROTEINS; MYOCARDIAL ISCHEMIA; MYOCARDIUM; NEOVASCULARIZATION, PATHOLOGIC; NEUROTRANSMITTER AGENTS; SELENOPROTEINS; TREATMENT OUTCOME; UBIQUINONE; VENTRICULAR REMODELING;

EID: 38349150595     PISSN: 07351097     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jacc.2007.10.009     Document Type: Review

References (103)

1. Laufs U., and Liao J.K. Isoprenoid metabolism and the pleiotropic effects of statins. Curr Atheroscler Rep 5 (2003) 372-378
2. Liao J.K. Isoprenoids as mediators of the biological effects of statins. J Clin Invest 110 (2002) 285-288
3. Hanada T., and Yoshimura A. Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev 13 (2002) 413-421
4. Delerive P., De Bosscher K., Besnard S., et al. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 274 (1999) 32048-32054
5. Brown J.H., Del Re D.P., and Sussman M.A. The Rac and Rho hall of fame: a decade of hypertrophic signaling hits. Circ Res 98 (2006) 730-742
6. Laufs U., Kilter H., Konkol C., Wassmann S., Bohm M., and Nickenig G. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res 53 (2002) 911-920
7. Francis S.E., Holden H., Holt C.M., and Duff G.W. Interleukin-1 in myocardium and coronary arteries of patients with dilated cardiomyopathy. J Mol Cell Cardiol 30 (1998) 215-223
8. Torre-Amione G., Kapadia S., Benedict C., Oral H., Young J.B., and Mann D.L. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 27 (1996) 1201-1206
9. Levine B., Kalman J., Mayer L., Fillit H.M., and Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323 (1990) 236-241
10. Bleske B.E., Nicklas J.M., Bard R.L., 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 nonischemic cardiomyopathy and average low-density lipoprotein level. J Am Coll Cardiol 47 (2006) 338-341
11. Sola S., Mir M.Q., Lerakis S., Tandon N., and Khan B.V. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 47 (2006) 332-337
12. Mozaffarian D., Minami E., Letterer R.A., Lawler R.L., McDonald G.B., and Levy W.C. The effects of atorvastatin (10 mg) on systemic inflammation in heart failure. Am J Cardiol 96 (2005) 1699-1704
13. Tousoulis D., Antoniades C., Vassiliadou C., et al. 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 (2005) 1126-1132
14. Krum H., and Tonkin A. The Rosuvastatin Impact on Ventricular Remodeling, Cytokines and Neurohormones (UNIVERSE) Study. (abstr). J Am Coll Cardiol 47 (2006) 61A-62A
15. 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, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure. J Card Fail 13 (2007) 1-7
16. Bevilacqua M.P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol 11 (1993) 767-804
17. Chung H.K., Lee I.K., Kang H., et al. Statin inhibits interferon-gamma-induced expression of intercellular adhesion molecule-1 (ICAM-1) in vascular endothelial and smooth muscle cells. Exp Mol Med 34 (2002) 451-461
18. Kwak B., Mulhaupt F., Myit S., and Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 6 (2000) 1399-1402
19. Keith M., Geranmayegan A., Sole M.J., et al. Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol 31 (1998) 1352-1356
20. Mellin V., Isabelle M., Oudot A., et al. Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure. Eur Heart J 26 (2005) 1544-1550
21. Heymes C., Bendall J.K., Ratajczak P., et al. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol 41 (2003) 2164-2171
22. Takemoto M., Node K., Nakagami H., et al. Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 108 (2001) 1429-1437
23. Chen M.S., Xu F.P., Wang Y.Z., et al. Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis. J Mol Cell Cardiol 37 (2004) 889-896
24. Ichihara S., Noda A., Nagata K., et al. Pravastatin increases survival and suppresses an increase in myocardial matrix metalloproteinase activity in a rat model of heart failure. Cardiovasc Res 69 (2006) 726-735
25. Habibi J., Whaley-Connell A., Qazi M.A., et al. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, decreases cardiac oxidative stress and remodeling in Ren2 transgenic rats. Endocrinology 148 (2007) 2181-2188
26. Maack C., Kartes T., Kilter H., et al. 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 (2003) 1567-1574
27. Drexler H., Hayoz D., Munzel T., Just H., Zelis R., and Brunner H.R. Endothelial function in congestive heart failure. Am Heart J 126 (1993) 761-764
28. Landmesser U., Spiekermann S., Dikalov S., et al. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 106 (2002) 3073-3078
29. Diodati J.G., Dakak N., Gilligan D.M., and Quyyumi A.A. Effect of atherosclerosis on endothelium-dependent inhibition of platelet activation in humans. Circulation 98 (1998) 17-24
30. Hambrecht R., Fiehn E., Weigl C., et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98 (1998) 2709-2715
31. Scherrer-Crosbie M., Ullrich R., Bloch K.D., et al. Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice. Circulation 104 (2001) 1286-1291
32. Laufs U. Beyond lipid-lowering: effects of statins on endothelial nitric oxide. Eur J Clin Pharmacol 58 (2003) 719-731
33. Dimmeler S., Fleming I., Fisslthaler B., Hermann C., Busse R., and Zeiher A.M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399 (1999) 601-605
34. Sun W., Lee T.S., Zhu M., et al. Statins activate AMP-activated protein kinase in vitro and in vivo. Circulation 114 (2006) 2655-2662
35. Rikitake Y., and Liao J.K. Rho GTPases, statins, and nitric oxide. Circ Res 97 (2005) 1232-1235
36. Bates K., Ruggeroli C.E., Goldman S., and Gaballa M.A. Simvastatin restores endothelial NO-mediated vasorelaxation in large arteries after myocardial infarction. Am J Physiol Heart Circ Physiol 283 (2002) H768-H775
37. Trochu J.N., Mital S., Zhang X., et al. Preservation of NO production by statins in the treatment of heart failure. Cardiovasc Res 60 (2003) 250-258
38. 10 reductions in chronic heart failure. Atherosclerosis 179 (2005) 201-206
39. Michowitz Y., Goldstein E., Wexler D., Sheps D., Keren G., and George J. Circulating endothelial progenitor cells and clinical outcome in patients with congestive heart failure. Heart 93 (2007) 1046-1050
40. Orlic D., Kajstura J., Chimenti S., et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A 98 (2001) 10344-10349
41. Assmus B., Urbich C., Aicher A., et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ Res 92 (2003) 1049-1055
42. Dimmeler S., Aicher A., Vasa M., et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 108 (2001) 391-397
43. Dimmeler S., Dernbach E., and Zeiher A.M. Phosphorylation of the endothelial nitric oxide synthase at ser-1177 is required for VEGF-induced endothelial cell migration. FEBS Lett 477 (2000) 258-262
44. Alsheikh-Ali A.A., Maddukuri P.V., Han H., and Karas R.H. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol 50 (2007) 409-418
45. Mann D.L. Mechanisms and models in heart failure: a combinatorial approach. Circulation 100 (1999) 999-1008
46. Clerk A., and Sugden P.H. Small guanine nucleotide-binding proteins and myocardial hypertrophy. Circ Res 86 (2000) 1019-1023
47. Hattori T., Shimokawa H., Higashi M., et al. Long-term inhibition of Rho-kinase suppresses left ventricular remodeling after myocardial infarction in mice. Circulation 109 (2004) 2234-2239
48. Kobayashi N., Horinaka S., Mita S., et al. Critical role of Rho-kinase pathway for cardiac performance and remodeling in failing rat hearts. Cardiovasc Res 55 (2002) 757-767
49. 2α formation. J Cardiovasc Pharmacol 40 (2002) 868-874
50. Indolfi C., Di Lorenzo E., Perrino C., et al. Hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation. Circulation 106 (2002) 2118-2124
51. Martin J., Denver R., Bailey M., and Krum H. In vitro inhibitory effects of atorvastatin on cardiac fibroblasts: implications for ventricular remodeling. Clin Exp Pharmacol Physiol 32 (2005) 697-701
52. Saka M., Obata K., Ichihara S., et al. Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure. J Cardiovasc Pharmacol 47 (2006) 770-779
53. Node K., Fujita M., Kitakaze M., Hori M., and Liao J.K. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 108 (2003) 839-843
54. Strehlow K., Wassmann S., Bohm M., and Nickenig G. Angiotensin AT1 receptor over-expression in hypercholesterolaemia. Ann Med 32 (2000) 386-389
55. van der Harst P., Wagenaar L.J., Buikema H., et al. Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease. Am J Cardiol 96 (2005) 1361-1364
56. Nickenig G., Baumer A.T., Temur Y., Kebben D., Jockenhovel F., and Bohm M. Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation 100 (1999) 2131-2134
57. Horiuchi M., Cui T.X., Li Z., Li J.M., Nakagami H., and Iwai M. Fluvastatin enhances the inhibitory effects of a selective angiotensin II type 1 receptor blocker, valsartan, on vascular neointimal formation. Circulation 107 (2003) 106-112
58. Saijonmaa O., Nyman T., Stewen P., and Fyhrquist F. Atorvastatin completely inhibits VEGF-induced ACE upregulation in human endothelial cells. Am J Physiol Heart Circ Physiol 286 (2004) H2096-H2102
59. Ito M., Adachi T., Pimentel D.R., Ido Y., and Colucci W.S. Statins inhibit beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes via a Rac1-dependent mechanism. Circulation 110 (2004) 412-418
60. Cygankiewicz I., Zareba W., Vazquez R., et al. Relation of heart rate turbulence to severity of heart failure. Am J Cardiol 98 (2006) 1635-1640
61. Nolan J., Batin P.D., Andrews R., et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation 98 (1998) 1510-1516
62. Owlya R., Vollenweider L., Trueb L., et al. Cardiovascular and sympathetic effects of nitric oxide inhibition at rest and during static exercise in humans. Circulation 96 (1997) 3897-3903
63. Pliquett R.U., Cornish K.G., Peuler J.D., and Zucker I.H. Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation 107 (2003) 2493-2498
64. Vrtovec B., Okrajsek R., Golicnik A., Ferjan M., Starc V., and Radovancevic B. 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 (2005) 684-690
65. Hanna I.R., Heeke B., Bush H., et al. Lipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction. Heart Rhythm 3 (2006) 881-886
66. Vyas A.K., Guo H., Moss A.J., et al., MADIT-II Research Group. Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. J Am Coll Cardiol 47 (2006) 769-773
67. Goldberger J.J., Subacius H., Schaechter A., et al., DEFINITE Investigators. Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 48 (2006) 1228-1233
68. Tamargo J., Caballero R., Gomez R., Nunez L., Vaquero M., and Delpon E. Lipid-lowering therapy with statins, a new approach to antiarrhythmic therapy. Pharmacol Ther 114 (2007) 107-126
69. Adam O., Frost G., Custodis F., et al. Role of Rac1 GTPase activation in atrial fibrillation. J Am Coll Cardiol 50 (2007) 359-367
70. Rauchhaus M., Coats A.J., and Anker S.D. The endotoxin-lipoprotein hypothesis. Lancet 356 (2000) 930-933
71. Turunen M., Olsson J., and Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 1660 (2004) 171-199
72. Hargreaves I.P. Ubiquinone: cholesterol's reclusive cousin. Ann Clin Biochem 40 (2003) 207-218
73. Appelkvist E.L., Edlund C., Low P., Schedin S., Kalen A., and Dallner G. Effects of inhibitors of hydroxymethylglutaryl coenzyme A reductase on coenzyme Q and dolichol biosynthesis. Clin Invest 71 Suppl (1993) S97-S102
74. Moosmann B., and Behl C. Selenoprotein synthesis and side-effects of statins. Lancet 363 (2004) 892-894
75. Kjekshus J., Pedersen T.R., Olsson A.G., Faergeman O., and Pyörälä K. The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail 3 (1997) 249-254
76. Segal R., Pitt B., Poole-Wilson P., et al. Effects of HMG-COA reductase inhibitors (statins) in patients with heart failure. (abstr). Eur J Heart Fail 2 Suppl 3 (2000) 96
77. Laufs U., Wassmann S., Schackmann S., Heeschen C., Bohm M., and Nickenig G. Beneficial effects of statins in patients with nonischemic heart failure. Z Kardiol 93 (2004) 103-108
78. Wojnicz R., Wilczek K., Nowalany-Kozielska E., et al. Usefulness of atorvastatin in patients with heart failure due to inflammatory dilated cardiomyopathy and elevated cholesterol levels. Am J Cardiol 97 (2006) 899-904
79. Foody J.M., Shah R., Galusha D., Masoudi F.A., Havranek E.P., and Krumholz H.M. Statins and mortality among elderly patients hospitalized with heart failure. Circulation 113 (2006) 1086-1092
80. Mozaffarian D., Nye R., and Levy W.C. Statin therapy is associated with lower mortality among patients with severe heart failure. Am J Cardiol 93 (2004) 1124-1129
81. Scirica B.M., Morrow D.A., Cannon C.P., 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 47 (2006) 2326-2331
82. Aronow W.S., and Ahn C. Frequency of congestive heart failure in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol ≥125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol 90 (2002) 147-149
83. Vrtovec B, Okrajsek R, Golicnik A, et al. Atorvastatin therapy decreases sudden cardiac death in patients with advanced chronic heart failure: a prospective study. Presented at: European Society of Cardiology Congress; Vienna, Austria: September 4, 2007.
84. Kjekshus J., Apetrei E., Barrios V., et al., CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 357 (2007) 2248-2261
85. Shepherd J., Blauw G.J., Murphy M.B., et al., PROSPER Study Group. 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 (2002) 1623-1630
86. Fukuta H., Sane D.C., Brucks S., and Little W.C. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 112 (2005) 357-363
87. Higgins J.P., and Thompson S.G. Quantifying heterogeneity in a meta-analysis. Stat Med 21 (2002) 1539-1558
88. Dersimonian R., and Laird N. Meta-analysis in clinical trials. Control Clin Trials 7 (1986) 177-188
89. Egger M., Davey Smith G., Schneider M., and Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 315 (1997) 629-634
90. Anker S.D., Clark A.L., Winkler R., et al. Statin use and survival in patients with chronic heart failure: results from two observational studies with 5200 patients. Int J Cardiol 112 (2006) 234-242
91. Folkeringa R.J., Van Kraaij D.J., Tieleman R.G., Nieman F.H.M., Pinto Y.M., and Crijns H.J.G.M. Statins associated with reduced mortality in patients admitted for congestive heart failure. J Card Fail 12 (2006) 134-138
92. Go A.S., Lee W.Y., Yang J., Lo J.C., and Gurwitz J.H. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA 296 (2006) 2105-2111
93. Horwich T.B., MacLellan W.R., and Fonarow G.C. Statin therapy is associated with improved survival in ischemic and nonischemic heart failure. J Am Coll Cardiol 43 (2004) 642-648
94. Krum H., Latini R., Maggioni A.P., et al. Statins and symptomatic chronic systolic heart failure: a post-hoc analysis of 5010 patients enrolled in Val-HeFT. Int J Cardiol 119 (2007) 48-53
95. Krum H., Bailey M., Meyer W., et al. Impact of statin therapy on clinical outcomes in chronic heart failure patients according to beta-blocker use: results of CIBIS II. Cardiology 108 (2007) 28-34
96. Ray J.G., Gong Y., Sykora K., and Tu J.V. Statin use and survival outcomes in elderly patients with heart failure. Arch Intern Med 165 (2005) 62-67
97. Dickinson M.G., Ip J.H., Olshansky B., et al., SCD-HeFT Investigators. Statin use was associated with reduced mortality in both ischemic and nonischemic cardiomyopathy and in patients with implantable defibrillators: mortality data and mechanistic insights from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Am Heart J 153 (2007) 573-578
98. Garg R., and Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 273 (1995) 1450-1456
99. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 353 (1999) 9-13
100. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353 (1999) 2001-2007
101. Packer M., Coats A.J.S., Fowler M.B., et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344 (2001) 1651-1658
102. Dargie H.J. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 357 (2001) 1385-1390
103. Tavazzi L., Tognoni G., Franzosi M.G., et al. 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 (2004) 635-641