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Christopher Heeschen, MD; Stefanie Dimmeler, PhD; Stephan Fichtlscherer, MD; Christian W. Hamm, MD; Juergen Berger, PhD; Maarten L. Simoons, MD; Andreas M. Zeiher, MD; for the CAPTURE Investigators

JAMA. 2004;291:435-441.

Context  Experimental data suggest that placental growth factor (PlGF), a member of the vascular endothelial growth factor family, acts as a primary inflammatory instigator of atherosclerotic plaque instability and thus may be useful as a risk-predicting biomarker in patients with acute coronary syndromes (ACS).

Objective  To determine whether blood levels of PlGF predict risk for death or nonfatal myocardial infarction in patients with acute chest pain.

Design, Setting, and Patients  Measurement of PlGF levels as well as levels of markers of myocardial necrosis (troponin T [TnT]), platelet activation (soluble CD40 ligand [sCD40L]), and inflammation (high-sensitivity C-reactive protein [hsCRP]) in an inception cohort of 547 patients with angiographically validated ACS participating in the CAPTURE (c7E3 Fab Anti-Platelet Therapy in Unstable Refractory Angina) trial and in a heterogeneous cohort of 626 patients presenting with acute chest pain to an emergency department in Germany between December 1996 and March 1999.

Main Outcome Measure  Risk for death or nonfatal myocardial infarction after 30 days.

Results  In patients with ACS, elevated PlGF levels (>27.0 ng/L; 40.8% of patients) indicated a markedly increased risk of events at 30 days (14.8% vs 4.9%; unadjusted hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.79-6.24; P<.001). In a multivariable model, elevated levels of TnT (HR, 1.83; 95% CI, 1.05-3.86; P = .03), sCD40L (HR, 2.65; 95% CI, 1.41-4.99; P = .002), and PlGF (HR, 3.03; 95% CI, 1.54-5.95; P<.001) were independent predictors, while elevated hsCRP level was not (HR, 0.98; 95% CI, 0.53-1.98; P = .94). In patients with acute chest pain, elevated levels of PlGF predicted risk (21.2% vs 5.3%) (unadjusted: HR, 4.80; 95% CI, 2.81-8.21; P<.001; adjusted: HR, 3.00; 95% CI, 1.68-5.38; P<.001). Patients negative for all 3 markers (TnT, sCD40L, and PlGF) were at very low cardiac risk (7 days: no event; 30 days: 2.1% event rate).

Conclusions  Plasma PlGF levels may be an independent biomarker of adverse outcome in patients with suspected ACS. A single initial measurement of plasma PlGF appears to extend the predictive and prognostic information gained from traditional inflammatory markers.

Author Affiliations: Department of Cardiology, Johann Wolfgang Goethe University, Frankfurt, Germany (Drs Heeschen, Dimmeler, Fichtlscherer, and Zeiher); Kerckhoff Heart Center, Bad Nauheim, Germany (Dr Hamm); Institute of Mathematics and Computer Science in Medicine, University of Hamburg, Hamburg, Germany (Dr Berger); and Erasmus University, Thoraxcentre, Rotterdam, the Netherlands (Dr Simoons).

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