Circulating Pregnancy-Associated Plasma Protein A Predicts Outcome in Patients With Acute Coronary Syndrome but No Troponin I Elevation

BACKGROUND: Risk stratification in troponin (cTn)-negative acute coronary syndrome (ACS) remains a clinical challenge. We investigated the predictive value of circulating pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque activity, in these patients. METHODS AND RESULTS: Two hundred consecutive hospitalized ACS patients were included, of whom 136 (69 men and 67 women; mean+/-SD age, 66+/-16 years) remained cTnI-negative for up to 24 hours. PAPP-A was measured at admission, 6 to 12 hours, and 24 hours. During 6-month follow-up, 26 (19.1%) of the cTnI-negative patients reached a primary end point (cardiovascular death, myocardial infarction, or revascularization). At a cutoff level of 2.9 mIU/L, elevated PAPP-A was an independent predictor of adverse outcome (adjusted risk ratio RR, 4.6; 95% confidence interval, 1.8 to 11.8; P=0.002). Another independent predictor was admission CRP >2.0 mg/L (RR, 2.6; P=0.03). CONCLUSIONS: Measurement of plasma PAPP-A, a zinc-binding matrix metalloproteinase, is a strong independent predictor of ischemic cardiac events and need of revascularization in patients who present with suspected myocardial infarction but remain troponin negative.