Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes

James A de Lemos, David A. Morrow, Marc S. Sabatine, Sabina A. Murphy, C. Michael Gibson, Elliott M. Antman, Carolyn H. McCabe, Christopher P. Cannon, Eugene Braunwald

Research output: Contribution to journalArticlepeer-review

362 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)690-695
Number of pages6
JournalCirculation
Volume107
Issue number5
DOIs
StatePublished - Feb 11 2003

Keywords

  • Infarction
  • Inflammation
  • Ischemia
  • Leukocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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