Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.
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 mlU 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.
Bayes-Genis
A
A
Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minn 55905, USA.
Conover
C A
CA
Overgaard
M T
MT
Bailey
K R
KR
Christiansen
M
M
Holmes
D R
DR
Virmani
R
R
Oxvig
C
C
Schwartz
R S
RS
D000368:Aged; D000787:Angina Pectoris / Q000097:blood; D000789:Angina, Unstable / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D016757:Death, Sudden, Cardiac; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis; D009206:Myocardium / Q000473:pathology; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011379:Prognosis; D012044:Regression Analysis
D015415:Biomarkers; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein; D011266:Pregnancy-Associated Plasma Protein-A