Pregnancy-associated plasma protein a as a marker of acute coronary syndromes

Background: Circulating markers indicating the instability of atherosclerot ic plaques could have diagnostic value in unstable angina or acute myocardi al infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloproteinase, as a marker of acute c oronary syndromes. Methods: We examined the level of expression of PAPP-A in eight culprit uns table coronary plaques and four stable plaques from eight patients who had died suddenly of cardiac causes. We also measured circulating levels of PAP P-A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 pat ients with acute myocardial infarction, 20 with unstable angina, 19 with st able angina, and 13 controls without atherosclerosis. Results: PAPP-A was abundantly expressed in plaque cells and extracellular matrix of ruptured and eroded unstable plaques, but not in stable plaques. Circulating PAPP-A levels were significantly higher in patients with unstab le angina or acute myocardial infarction than in patients with stable angin a and controls (P<0.001). A PAPP-A threshold value of 10 mIU per liter iden tified patients who had acute coronary syndromes with a sensitivity of 89.2 percent and a specificity of 81.3 percent. PAPP-A levels correlated with l evels of C-reactive protein and free IGF-I, but not with markers of myocard ial injury (troponin I and the MB isoform of creatine kinase). Conclusions: PAPP-A is present in unstable plaques, and circulating levels are elevated in acute coronary syndromes; these increased levels may reflec t the instability of atherosclerotic plaques. PAPP-A is a new candidate mar ker of unstable angina and acute myocardial infarction. (N Engl J Med 2001; 345:1022-9.) Copyright (C) 2001 Massachusetts Medical Society.