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

Antoni Bayes-Genis, Cheryl A. Conover, Michael T. Overgaard, Kent R. Bailey, Michael Christiansen, David R. Holmes, Renu Virmani, Claus Oxvig, Robert S. Schwartz

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Abstract

Background: Circulating markers indicating the instability of atherosclerotic plaques could have diagnostic value in unstable angina or acute myocardial infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloproteinase, as a marker of acute coronary syndromes. Methods: We examined the level of expression of PAPP-A in eight culprit unstable coronary plaques and four stable plaques from eight patients who had died suddenly of cardiac causes. We also measured circulating levels of PAPP-A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 patients with acute myocardial infarction, 20 with unstable angina, 19 with stable 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 unstable angina or acute myocardial infarction than in patients with stable angina and controls (P<0.001). A PAPP-A threshold value of 10 mIU per liter identified 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 levels of C-reactive protein and free IGF-I, but not with markers of myocardial 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 reflect the instability of atherosclerotic plaques. PAPP-A is a new candidate marker of unstable angina and acute myocardial infarction.

Original languageEnglish (US)
Pages (from-to)1022-1029
Number of pages8
JournalNew England Journal of Medicine
Volume345
Issue number14
DOIs
StatePublished - Oct 4 2001

ASJC Scopus subject areas

  • Medicine(all)

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    Bayes-Genis, A., Conover, C. A., Overgaard, M. T., Bailey, K. R., Christiansen, M., Holmes, D. R., Virmani, R., Oxvig, C., & Schwartz, R. S. (2001). Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. New England Journal of Medicine, 345(14), 1022-1029. https://doi.org/10.1056/NEJMoa003147