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

Circulation. 2003 Feb 11;107(5):690-5. doi: 10.1161/01.cir.0000049742.68848.99.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Alanine / therapeutic use
  • Biomarkers / blood
  • Chemokine CCL2 / blood*
  • Cohort Studies
  • Confounding Factors, Epidemiologic
  • Coronary Disease / blood*
  • Coronary Disease / drug therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Predictive Value of Tests
  • Pyrrolidines / therapeutic use
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Reference Values
  • Risk Assessment
  • Risk Factors
  • Survival Analysis
  • Time
  • Treatment Outcome

Substances

  • Biomarkers
  • Chemokine CCL2
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Pyrrolidines
  • orbofiban
  • Alanine