Serial measurement of monocyte chemoattractant protein-1 after acute coronary syndromes: results from the A to Z trial.
OBJECTIVE
This study sought to determine whether the novel biomarker monocyte chemoattractant protein (MCP)-1 adds prognostic value to standard risk assessment tools and biomarkers after acute coronary syndromes (ACS).


BACKGROUND
Monocyte chemoattractant protein-1 is a chemokine recruiting signal for monocytes that may function as both a mediator and biomarker of ACS.


METHODS
Monocyte chemoattractant protein-1 was measured at baseline (n = 4,244), 4 months (n = 3,603), and 12 months (n = 2,950), and correlated with clinical events in the Z phase of the A to Z (Aggrastat to Zocor) trial, which compared early intensive versus delayed and less intensive statin therapy after ACS.


RESULTS
Rates of death and the composite end points of death or myocardial infarction (MI); death, MI, or heart failure; and cardiovascular death, MI, readmission for ACS, or stroke increased across baseline quartiles of MCP-1 and among patients with MCP-1 greater than versus less than or equal to the pre-specified threshold of 238 pg/ml (p < 0.01 for each). After adjustment for standard risk predictors and levels of C-reactive protein and B-type natriuretic peptide, MCP-1 >238 pg/ml remained independently associated with mortality (hazard ratio 2.16; 95% confidence interval 1.54 to 3.02) and with each composite end point, and increased the C-statistic of the fully adjusted mortality model from 0.76 to 0.78 (p < 0.0001). A value of MCP-1 >238 pg/ml at the 4-month follow-up visit was also independently associated with mortality after 4 months (hazard ratio 1.76; 95% confidence interval 1.12 to 2.76). Elevated MCP-1 levels did not identify patients who derived incremental benefit from intensive statin therapy.


CONCLUSIONS
Monocyte chemoattractant protein-1 provides independent prognostic value in the acute and chronic phases after ACS and merits further evaluation as a prognostic marker and potential therapeutic target.
Donald W. Reynolds Cardiovascular Clinical Research Center, UT Southwestern Medical Center, Dallas, Texas 75390-9047, USA. james.delemos@utsouthwestern.edu
James A
JA
de Lemos
David A
DA
Morrow
Michael A
MA
Blazing
Petr
P
Jarolim
Stephen D
SD
Wiviott
Marc S
MS
Sabatine
Robert M
RM
Califf
Eugene
E
Braunwald
D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis*; D000368:Aged; D015415:Biomarkers; D018932:Chemokine CCL2 / Q000097:blood*; D003324:Coronary Artery Disease / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors