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(Circulation. 1999;100:230-235.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (P.M.R., M.A.P., F.S., E.B.), and the Children's Hospital Medical Center (N.R.), Boston, Mass.
Correspondence to Dr Paul M. Ridker, Cardiovascular Diseases, Brigham and Womens' Hospital, 75 Francis St, Boston, MA 02115. E-mail pridker{at}rics.bwh.harvard.edu
BackgroundElevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that reduces cardiovascular risk, might alter levels of this inflammatory parameter.
Methods and ResultsCRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-up. Overall, CRP levels at baseline and at 5 years were highly correlated (r=0.60, P<0.001). However, among those allocated to placebo, median CRP levels and the mean change in CRP tended to increase over time (median change, +4.2%; P=0.2 and mean change, +0.07 mg/dL; P=0.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocated to pravastatin (median change, -17.4%; P=0.004 and mean change, -0.07 mg/dL; P=0.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP levels (difference, -21.6%; P=0.007), mean CRP levels (difference, -37.8%; P=0.002), and absolute mean change in CRP (difference, -0.137 mg/dL; P=0.003). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships.
ConclusionsAmong survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent.
Key Words: myocardial infarction proteins pravastatin atherosclerosis
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H. Lorenz, C. Junger, K. Seidl, A. Gitt, S. Schneider, R. Schiele, H. Wienbergen, R. Winkler, M. Gottwik, W. Delius, et al. Do statins influence the prognostic impact of non-sustained ventricular tachycardia after ST-elevation myocardial infarction? Eur. Heart J., June 1, 2005; 26(11): 1078 - 1085. [Abstract] [Full Text] [PDF] |
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P. M. Ridker, D. A. Morrow, L. M. Rose, N. Rifai, C. P. Cannon, and E. Braunwald Relative Efficacy of Atorvastatin 80 mg and Pravastatin 40 mg in Achieving the Dual Goals of Low-Density Lipoprotein Cholesterol <70 mg/dl and C-Reactive Protein <2 mg/l: An Analysis of the PROVE-IT TIMI-22 Trial J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1644 - 1648. [Abstract] [Full Text] [PDF] |
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W. Li, T. Asagami, H. Matsushita, K.-H. Lee, and P. S. Tsao Rosuvastatin Attenuates Monocyte-Endothelial Cell Interactions and Vascular Free Radical Production in Hypercholesterolemic Mice J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 557 - 562. [Abstract] [Full Text] [PDF] |
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R. A.H. Stewart, H. D. White, A. C. Kirby, S. R. Heritier, R. J. Simes, P. J. Nestel, M. J. West, D. M. Colquhoun, A. M. Tonkin, and for the Long-Term Intervention With Pravastatin in White Blood Cell Count Predicts Reduction in Coronary Heart Disease Mortality With Pravastatin Circulation, April 12, 2005; 111(14): 1756 - 1762. [Abstract] [Full Text] [PDF] |
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E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF] |
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A. Yonemura, Y. Momiyama, Z. A. Fayad, M. Ayaori, R. Ohmori, K. Higashi, T. Kihara, S. Sawada, N. Iwamoto, M. Ogura, et al. Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging J. Am. Coll. Cardiol., March 1, 2005; 45(5): 733 - 742. [Abstract] [Full Text] [PDF] |
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M. Gola, S. Bonadonna, M. Doga, and A. Giustina Growth Hormone and Cardiovascular Risk Factors J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1864 - 1870. [Abstract] [Full Text] [PDF] |
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L. Sironi, E. Gianazza, P. Gelosa, U. Guerrini, E. Nobili, A. Gianella, B. Cremonesi, R. Paoletti, and E. Tremoli Rosuvastatin, but not Simvastatin, Provides End-Organ Protection in Stroke-Prone Rats by Antiinflammatory Effects Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 598 - 603. [Abstract] [Full Text] [PDF] |
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V. M. Campese, M. K. Nadim, and M. Epstein Are 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors Renoprotective? J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S11 - S17. [Abstract] [Full Text] [PDF] |
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R. Schnabel, H. J. Rupprecht, K. J. Lackner, E. Lubos, C. Bickel, J. Meyer, T. Munzel, F. Cambien, L. Tiret, S. Blankenberg, et al. Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: results from the AtheroGene study Eur. Heart J., February 1, 2005; 26(3): 241 - 249. [Abstract] [Full Text] [PDF] |
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P. Bogaty, J. M. Brophy, L. Boyer, S. Simard, L. Joseph, F. Bertrand, and G. R. Dagenais Fluctuating Inflammatory Markers in Patients With Stable Ischemic Heart Disease Arch Intern Med, January 24, 2005; 165(2): 221 - 226. [Abstract] [Full Text] [PDF] |
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P. M Ridker, C. P. Cannon, D. Morrow, N. Rifai, L. M. Rose, C. H. McCabe, M. A. Pfeffer, E. Braunwald, and the Pravastatin or Atorvastatin Evaluation and Inf C-Reactive Protein Levels and Outcomes after Statin Therapy N. Engl. J. Med., January 6, 2005; 352(1): 20 - 28. [Abstract] [Full Text] [PDF] |
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K. M. Choi, K. W. Lee, S. G. Kim, N. H. Kim, C. G. Park, H. S. Seo, D. J. Oh, D. S. Choi, and S. H. Baik Inflammation, Insulin Resistance, and Glucose Intolerance in Acute Myocardial Infarction Patients without a Previous Diagnosis of Diabetes Mellitus J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 175 - 180. [Abstract] [Full Text] [PDF] |
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S. C. Smith Jr, J. L. Anderson, R. O. Cannon III, Y. Y. Fadl, W. Koenig, P. Libby, S. E. Lipshultz, G. A. Mensah, P. M Ridker, and R. Rosenson CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Report From the Clinical Practice Discussion Group Circulation, December 21, 2004; 110(25): e550 - e553. [Full Text] [PDF] |
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S Van Doornum, G McColl, and I P Wicks Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis Ann Rheum Dis, December 1, 2004; 63(12): 1571 - 1575. [Abstract] [Full Text] [PDF] |
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J. Pleiner, G. Schaller, F. Mittermayer, S. Zorn, C. Marsik, S. Polterauer, S. Kapiotis, and M. Wolzt Simvastatin Prevents Vascular Hyporeactivity During Inflammation Circulation, November 23, 2004; 110(21): 3349 - 3354. [Abstract] [Full Text] [PDF] |
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