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.