Circulation. 2003;108:839-843
Published online before print July 28, 2003, doi: 10.1161/01.CIR.0000084539.58092.DE
Published online before print July 28, 2003, doi: 10.1161/01.CIR.0000084539.58092.DE
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(Circulation. 2003;108:839.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Short-Term Statin Therapy Improves Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy
From the Cardiovascular Division (K.N.), Department of Medicine, Saga Medical School, Saga, Japan; Department of Internal Medicine and Therapeutics (M.F., M.H.), Osaka University Graduate School of Medicine, Osaka, Japan; Division of Cardiology (M.K.), National Cardiovascular Center, Osaka, Japan; and Cardiovascular Division (J.K.L.), Department of Medicine, Brigham & Women’s Hospital and Harvard Medical School, Boston, Mass.
Correspondence and reprint requests to James K. Liao, MD, Brigham & Women’s Hospital, 65 Landsdowne St, Room 275, Cambridge, MA 02139 (e-mail jliao{at}rics.bwh.harvard.edu), or Koichi Node, MD, PhD, Cardiovascular Division, Department of Medicine, Saga University School of Medicine, 5-1-1 Nabeshima, Saga, 849-8501 Japan (e-mail nodekoi@post.saga-med.ac.jp).
Received November 12, 2001; de novo received April 24, 2003; accepted May 6, 2003.
Background— Chronic heart failure is associated with inflammation and neurohormonal imbalance. The 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, exert anti-inflammatory and vascular protective effects. We hypothesized that short-term statin therapy may have beneficial effects in patients with nonischemic heart failure.
Methods and Results— Sixty-three patients with symptomatic, nonischemic, dilated cardiomyopathy were randomly divided into 2 groups. One group received simvastatin (n=24), and the other group received placebo (n=27). The initial dose of simvastatin was 5 mg/d, which was increased to 10 mg/d after 4 weeks. After 14 weeks, patients receiving simvastatin exhibited a modest reduction in serum cholesterol level compared with patients receiving placebo (130±13 versus 148±18, P<0.05). Patients treated with simvastatin had a lower New York Heart Association functional class compared with patients receiving placebo (2.04±0.06 versus 2.32±0.05, P<0.01). This corresponded to improved left ventricular ejection fraction in the simvastatin group (34±3 to 41±4%, P<0.05) but not in the placebo group. Furthermore, plasma concentrations of tumor necrosis factor-
, interleukin-6, and brain natriuretic peptide were significantly lower in the simvastatin group compared with the placebo group.
Conclusions— Short-term statin therapy improves cardiac function, neurohormonal imbalance, and symptoms associated with idiopathic dilated cardiomyopathy. These findings suggest that statins may have therapeutic benefits in patients with heart failure irrespective of serum cholesterol levels or atherosclerotic heart disease.
Key Words: heart failure • statins • cholesterol • endothelium • inflammation
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
U. Landmesser, F. Bahlmann, M. Mueller, S. Spiekermann, N. Kirchhoff, S. Schulz, C. Manes, D. Fischer, K. de Groot, D. Fliser, et al. Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans Circulation, May 10, 2005; 111(18): 2356 - 2363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
P. B. Massion, C. Dessy, F. Desjardins, M. Pelat, X. Havaux, C. Belge, P. Moulin, Y. Guiot, O. Feron, S. Janssens, et al. Cardiomyocyte-Restricted Overexpression of Endothelial Nitric Oxide Synthase (NOS3) Attenuates {beta}-Adrenergic Stimulation and Reinforces Vagal Inhibition of Cardiac Contraction Circulation, October 26, 2004; 110(17): 2666 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, N. Engberding, F. H. Bahlmann, A. Schaefer, A. Wiencke, A. Heineke, S. Spiekermann, D. Hilfiker-Kleiner, C. Templin, D. Kotlarz, et al. Statin-Induced Improvement of Endothelial Progenitor Cell Mobilization, Myocardial Neovascularization, Left Ventricular Function, and Survival After Experimental Myocardial Infarction Requires Endothelial Nitric Oxide Synthase Circulation, October 5, 2004; 110(14): 1933 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
A. E. Tsirka, K. Trinkaus, S.-C. Chen, S. E. Lipshultz, J. A. Towbin, S. D. Colan, V. Exil, A. W. Strauss, and C. E. Canter Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation J. Am. Coll. Cardiol., July 21, 2004; 44(2): 391 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Sacks High-Intensity Statin Treatment for Coronary Heart Disease JAMA, March 3, 2004; 291(9): 1132 - 1134. [Full Text] [PDF]
|
|
|
|
 |
|
 F.M Sacks Do statins play a role in the early management of the acute coronary syndrome? Eur. Heart J. Suppl., March 1, 2004; 6(suppl_A): A32 - A36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
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