Pregancy-associated plasma protein-a levels in patients with acute coronary syndromes - Comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis

OBJECTIVES The goal of this stud), was to determine the predictive value of pregnancy-associated plasma protein-A (PAPP-A) in patients with acute coronary syndromes (ACS). BACKGROUND Pregnancy-associated plasma protein-A is a zinc-binding matrix meralloproteinase abundandy expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization. METHODS In 547 patients with angiographically validated ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain, respectively, PAPP-A as well as markers of myocardial necrosis (troponin T [TnT]), ischermia (vascular endothelial growth factor [VEGF]), inflammation (high-sensitivity C-reactive protein [hsCRP]), anti-inflammatory, activity (interleukin [IL]-10), and platelet activation (soluble CD40 ligand [sCD40L]) were determined. Patients were followed for the occurrence of death or myocardial infarction. RESULTS In patients with ACS, elevated PAPP-A levels (>12.6 mIU/l) indicated an increased risk (odds ratio 2.44 [95% confidence interval (CI) 1.43 to 4.15]; p = 0.001). When the analysis was restricted to TnT-negative patients, PAPP-A still identified a subgroup of high-risk-patients (odds ratio [OR] 2.72 [95% confidence interval (CI) 1.25 to 5.89]: p = 0.009). In a multivariable model, PAPP-A (OR 2.01) p = 0.015), sCD40L (OR 2.37, p = 0.003). IL-10, (OR 0.43; p = 0.003), and VEGF (OR 2.19: p = 0.018) were independent predictors. Prospective validation in patients with chest pain confirmed that PAPP-A levels reliably, identify, high-risk patients (adjusted OR 2.32 [95% CI 1.32 to 4.26]; p = 0.008). Patients negative for A three markers (TnT, sCD40L, and PAPP-A,) were at very low cardiac risk (30 days: 3.0% event rate; no death). CONCLUSIONS The PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS. Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS. (C)2005 by the American College of Cardiology Foundation.