on January 20, 2003
Circulation. 2003
Published online before print January 20, 2003, doi: 10.1161/01.CIR.0000049742.68848.99
Published online before print January 20, 2003, doi: 10.1161/01.CIR.0000049742.68848.99
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Submitted on August 28, 2002
From the TIMI Study Group (J.A.d.L., D.A.M., M.S.S., S.A.M., C.M.G., E.M.A., C.H.M., C.P.C., E.B.); Donald W. Reynolds Cardiovascular Clinical Research Center, the University of Texas, Southwestern Medical School, Dallas, Tex (J.A.d.L.); the Cardiovascular Division, Brigham and Women's Hospital, Boston, Mass (D.A.M., M.S.S., E.M.A., C.P.C., E.B.); and Harvard Clinical Research Institute, Boston Mass (S.A.M., C.M.G.). * To whom correspondence should be addressed. E-mail: james.delemos{at}utsouthwestern.edu.
Background--Monocyte chemoattractant protein-1 (MCP-1) is a chemokine responsible for the recruitment of monocytes to sites of inflammation. MCP-1 appears to play a critical role at multiple stages in atherosclerosis, including the initiation of the fatty streak, promotion of plaque instability, and remodeling after myocardial infarction. Methods and Results--MCP-1 was measured from frozen plasma specimens in 279 healthy volunteers and 2270 patients with acute coronary syndromes enrolled in the Oral Glycoprotein IIb/IIIa Inhibition with Orbofiban in Patients with Unstable Coronary Syndromes (OPUS-TIMI) 16 trial. Median [25th, 75th percentiles] MCP-1 levels were 157 [124, 196] pg/mL in healthy volunteers and 178 [128, 238] pg/mL in the OPUS-TIMI 16 population (P<0.001). In OPUS-TIMI 16, baseline MCP-1 levels were associated with older age, female sex, hypertension, diabetes, prior coronary disease, and renal insufficiency (P<0.01 for each) but not with smoking status, body mass index, ejection fraction, troponin I or C-reactive protein. After adjustment for differences in baseline characteristics, ECG changes, troponin I, and C-reactive protein, an MCP-1 level >75th percentile (corresponding to the 90th percentile in the healthy volunteers) was associated with an increased risk of death or myocardial infarction through 10 months of follow-up (adjusted hazard ratio, 1.53; 95% CI, 1.09 to 2.14; P=0.01). Conclusions--In a large cohort of patients with acute coronary syndromes, an elevated baseline level of MCP-1 was associated both with traditional risk factors for atherosclerosis as well as an increased risk for death or myocardial infarction, independent of baseline variables. Because it appears to play a crucial role at multiple stages of atherosclerosis, MCP-1 is attractive as a surrogate biomarker and merits further study as a potential therapeutic target.
Revised on October 24, 2002
Accepted on October 28, 2002
Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes
James A. de Lemos MD*,
Key words: infarction • ischemia • leukocytes • inflammation
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