TY - JOUR
T1 - Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes
AU - de Lemos, James A
AU - Morrow, David A.
AU - Sabatine, Marc S.
AU - Murphy, Sabina A.
AU - Gibson, C. Michael
AU - Antman, Elliott M.
AU - McCabe, Carolyn H.
AU - Cannon, Christopher P.
AU - Braunwald, Eugene
PY - 2003/2/11
Y1 - 2003/2/11
N2 - 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.
AB - 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.
KW - Infarction
KW - Inflammation
KW - Ischemia
KW - Leukocytes
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U2 - 10.1161/01.CIR.0000049742.68848.99
DO - 10.1161/01.CIR.0000049742.68848.99
M3 - Article
C2 - 12578870
AN - SCOPUS:0037432168
SN - 0009-7322
VL - 107
SP - 690
EP - 695
JO - Circulation
JF - Circulation
IS - 5
ER -