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


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.
de Lemos
James A
JA
TIMI Study Group, Donald W. Reynolds Cardiovascular Clinical Research Center, the University of Texas, Southwestern Medical School, Dallas, TX 75390-9047, USA. james.delemos@utsouthwestern.edu
Morrow
David A
DA
Sabatine
Marc S
MS
Murphy
Sabina A
SA
Gibson
C Michael
CM
Antman
Elliott M
EM
McCabe
Carolyn H
CH
Cannon
Christopher P
CP
Braunwald
Eugene
E
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000409:Alanine / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood*; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011237:Predictive Value of Tests; D011759:Pyrrolidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012016:Reference Values; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013995:Time; D016896:Treatment Outcome
D015415:Biomarkers; D018932:Chemokine CCL2; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011759:Pyrrolidines; C120234:orbofiban; D000409:Alanine