From the Departments of Medicine, Brigham and Women's Hospital and
Harvard Medical School, Boston, Mass (P.M.R., M.A.P., F.M.S., E.B.); the
Children's Hospital Medical Center, Boston (N.R.); the University of
Texas School of Public Health, Houston (L.A.M.); the Veterans Administration
Medical Center, Tucson, Ariz (S.G.); and the University of Missouri, Columbia
(G.C.F.).
Correspondence to Dr Paul M. Ridker, Division of Cardiovascular Diseases, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail pmridker{at}bics.bwh.harvard.edu
Background—We studied whether
inflammation after myocardial infarction (MI) is a risk factor for
recurrent coronary events and whether randomized treatment with
pravastatin reduces that risk.
Methods and Results—A nested case-control design was used
to compare C-reactive protein (CRP) and serum amyloid A (SAA) levels in
prerandomization blood samples from 391 participants in the
Cholesterol and Recurrent Events (CARE) trial who
subsequently developed recurrent nonfatal MI or a fatal
coronary event (cases) and from an equal number of age- and
sex-matched participants who remained free of these events during
follow-up (control subjects). Overall, CRP and SAA were higher among
cases than control subjects (for CRP P=0.05; for SAA
P=0.006) such that those with levels in the highest
quintile had a relative risk (RR) of recurrent events 75% higher than
those with levels in the lowest quintile (for CRP RR=1.77,
P=0.02; for SAA RR=1.74, P=0.02). The
study group with the highest risk was that with consistent
evidence of inflammation (elevation of both CRP and SAA) who were
randomly assigned to placebo (RR=2.81, P=0.007); this
risk estimate was greater than the product of the individual risks
associated with inflammation or placebo assignment alone. In stratified
analyses, the association between inflammation and risk was
significant among those randomized to placebo (RR=2.11,
P=0.048) but was attenuated and nonsignificant among
those randomized to pravastatin (RR=1.29,
P=0.5).
Conclusions—Evidence of inflammation after MI is associated with
increased risk of recurrent coronary events. Therapy with
pravastatin may decrease this risk, an observation
consistent with a nonlipid effect of this agent.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Inflammation, Pravastatin, and the Risk of Coronary Events After Myocardial Infarction in Patients With Average Cholesterol Levels
Key Words: C-reactive protein • serum amyloid A • myocardial infarction • atherosclerosis • cholesterol
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L. M. Biasucci CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Clinical Use of Inflammatory Markers in Patients With Cardiovascular Diseases: A Background Paper Circulation, December 21, 2004; 110(25): e560 - e567. [Abstract] [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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P. Amarenco, J. Labreuche, P. Lavallee, and P.-J. Touboul Statins in Stroke Prevention and Carotid Atherosclerosis: Systematic Review and Up-to-Date Meta-Analysis Stroke, December 1, 2004; 35(12): 2902 - 2909. [Abstract] [Full Text] [PDF]
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A. Zanchetti, G. Crepaldi, M. G. Bond, G. Gallus, F. Veglia, G. Mancia, A. Ventura, G. Baggio, L. Sampieri, P. Rubba, et al. Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of PHYLLIS--A Randomized Double-Blind Trial Stroke, December 1, 2004; 35(12): 2807 - 2812. [Abstract] [Full Text] [PDF]
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M. Madjid, I. Awan, J. T. Willerson, and S. W. Casscells Leukocyte count and coronary heart disease: Implications for risk assessment J. Am. Coll. Cardiol., November 16, 2004; 44(10): 1945 - 1956. [Abstract] [Full Text] [PDF]
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K. Becker and M. Chopp Role of Statins in the Treatment and Prevention of Stroke: Introduction Stroke, November 1, 2004; 35(11_suppl_1): 2706 - 2707. [Full Text] [PDF]
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K. Esposito, D. Giugliano, F. Nappo, R. Marfella, and for the Campanian Postprandial Hyperglycemia Study Regression of Carotid Atherosclerosis by Control of Postprandial Hyperglycemia in Type 2 Diabetes Mellitus Circulation, July 13, 2004; 110(2): 214 - 219. [Abstract] [Full Text] [PDF]
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S. Fichtlscherer, S. Breuer, C. Heeschen, S. Dimmeler, and A. M. Zeiher Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease J. Am. Coll. Cardiol., July 7, 2004; 44(1): 44 - 49. [Abstract] [Full Text] [PDF]
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D.D. Waters and K.K. Khush Management of the acute coronary syndrome patient Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C49 - C57. [Abstract] [Full Text] [PDF]
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P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
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R. Paoletti, A. M. Gotto Jr, and D. P. Hajjar Inflammation in Atherosclerosis and Implications for Therapy Circulation, June 15, 2004; 109(23_suppl_1): III-20 - III-26. [Abstract] [Full Text]
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J. Davignon Beneficial Cardiovascular Pleiotropic Effects of Statins Circulation, June 15, 2004; 109(23_suppl_1): III-39 - III-43. [Abstract] [Full Text]
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P. Amarenco and A. M. Tonkin Statins for Stroke Prevention: Disappointment and Hope Circulation, June 15, 2004; 109(23_suppl_1): III-44 - III-49. [Abstract] [Full Text] [PDF]
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J. A. Schaar, E. Regar, F. Mastik, E. P. McFadden, F. Saia, C. Disco, C. L. de Korte, P. J. de Feyter, A. F.W. van der Steen, and P. W. Serruys Incidence of High-Strain Patterns in Human Coronary Arteries: Assessment With Three-Dimensional Intravascular Palpography and Correlation With Clinical Presentation Circulation, June 8, 2004; 109(22): 2716 - 2719. [Abstract] [Full Text] [PDF]
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A. Segev, S. Kassam, C. E Buller, H. K Lau, J. D Sparkes, P. W Connelly, P. H Seidelin, M. K Natarajan, E. A Cohen, and B. H Strauss Pre-procedural plasma levels of C-reactive protein and interleukin-6 do not predict late coronary angiographic restenosis after elective stenting Eur. Heart J., June 2, 2004; 25(12): 1029 - 1035. [Abstract] [Full Text] [PDF]
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 R. Kleemann, L. Verschuren, B.-J. de Rooij, J. Lindeman, M. M. de Maat, A. J. Szalai, H. M. G. Princen, and T. Kooistra Evidence for anti-inflammatory activity of statins and PPAR{alpha} activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro Blood, June 1, 2004; 103(11): 4188 - 4194. [Abstract] [Full Text] [PDF]
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J. T. Willerson and P. M. Ridker Inflammation as a Cardiovascular Risk Factor Circulation, June 1, 2004; 109(21_suppl_1): II-2 - II-10. [Abstract] [Full Text] [PDF]
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J. P.J. Halcox and J. E. Deanfield Beyond the Laboratory: Clinical Implications for Statin Pleiotropy Circulation, June 1, 2004; 109(21_suppl_1): II-42 - II-48. [Abstract] [Full Text] [PDF]
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D. G. Hackam and S. L. Shumak C-reactive protein for the prediction of cardiovascular risk: Ready for prime-time? Can. Med. Assoc. J., May 11, 2004; 170(10): 1563 - 1565. [Full Text] [PDF]
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B Boland and G Goderis Statins in patients at high risk of cardiovascular disease presenting with peripheral artery disease Eur. Heart J., May 1, 2004; 25(9): 712 - 713. [Full Text] [PDF]
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 F. R. DANESH and Y. S. KANWAR Modulatory effects of HMG-CoA reductase inhibitors in diabetic microangiopathy FASEB J, May 1, 2004; 18(7): 805 - 815. [Abstract] [Full Text] [PDF]
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Yasmin, C. M. McEniery, S. Wallace, I. S. Mackenzie, J. R. Cockcroft, and I. B. Wilkinson C-Reactive Protein Is Associated With Arterial Stiffness in Apparently Healthy Individuals Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 969 - 974. [Abstract] [Full Text]
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 P. Gervois, R. Kleemann, A. Pilon, F. Percevault, W. Koenig, B. Staels, and T. Kooistra Global Suppression of IL-6-induced Acute Phase Response Gene Expression after Chronic in Vivo Treatment with the Peroxisome Proliferator-activated Receptor-{alpha} Activator Fenofibrate J. Biol. Chem., April 16, 2004; 279(16): 16154 - 16160. [Abstract] [Full Text] [PDF]
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