on March 31, 2003
Circulation. 2003
Published online before print March 31, 2003, doi: 10.1161/01.CIR.0000065232.57371.25
Published online before print March 31, 2003, doi: 10.1161/01.CIR.0000065232.57371.25
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Submitted on December 17, 2002
From the Division of Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany (C.H., S.D., S.F., A.M.Z.); Kerckhoff Heart Center, Bad Nauheim, Germany (C.W.H.); and Erasmus University, Thoraxcentre, Rotterdam, the Netherlands (E.B., M.L.S.). * To whom correspondence should be addressed. E-mail: c.heeschen{at}em.uni-frankfurt.de.
Background--Convincing evidence suggests that atherosclerosis is an inflammatory disease. The inflammatory response is an important determinant of atherosclerotic plaque instability. Therefore, we investigated the prognostic impact of key inflammatory players, namely the inflammatory marker C-reactive protein (CRP) and the antiinflammatory cytokine interleukin-10 (IL-10), in patients with acute coronary syndromes. Methods and Results--IL-10, CRP, and troponin T were measured at baseline and before discharge in 547 patients enrolled in the placebo group of the c7E3 Anti Platelet Therapy in Unstable Refractory angina (CAPTURE) trial. Death and nonfatal myocardial infarction were recorded during 6-month follow-up. IL-10 levels did not correlate with troponin T concentrations but were inversely correlated with CRP levels (P<0.001). Patients with elevated IL-10 levels (>3.5 pg/mL; n=276) were at significantly lower risk compared with patients with elevated IL-10 levels (hazard ratio, 0.33; 95% confidence interval [CI], 0.25 to 0.76; P=0.002). The predictive value of IL-10 was independent of myocardial necrosis but significantly interacted with CRP levels. CRP-positive patients with IL-10 serum levels above the calculated threshold value of 3.5 pg/mL were protected from the increased cardiac risk of CRP-positive patients with low IL-10 levels (adjusted hazard ratio, 0.25; 95% CI, 0.10 to 0.63; P=0.003). Moreover, discharge IL-10 levels >2.5 pg/mL were associated with lower cardiac risk during 6-month follow-up (hazard ratio, 0.38; 95% CI, 0.19 to 0.83; P=0.005). Conclusions--Elevated IL-10 serum levels are associated with a more favorable prognosis in patients with acute coronary syndromes and elevated CRP levels. These data demonstrate the importance of the balance between proinflammatory and antiinflammatory markers as a major determinant of patients' outcome in acute coronary syndromes.
Revised on February 7, 2003
Accepted on February 7, 2003
Serum Level of the Antiinflammatory Cytokine Interleukin-10 Is an Important Prognostic Determinant in Patients With Acute Coronary Syndromes
Christopher Heeschen MD*,
Key words: angina • prognosis • inflammation • C-reactive protein • troponin
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