Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis

J Am Coll Cardiol. 2005 Jan 18;45(2):229-37. doi: 10.1016/j.jacc.2004.09.060.


Objectives: The goal of this study was to determine the predictive value of pregnancy-associated plasma protein-A (PAPP-A) in patients with acute coronary syndromes (ACS).

Background: Pregnancy-associated plasma protein-A is a zinc-binding matrix metalloproteinase abundantly expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization.

Methods: In 547 patients with angiographically validated ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain, respectively, PAPP-A as well as markers of myocardial necrosis (troponin T [TnT]), ischemia (vascular endothelial growth factor [VEGF]), inflammation (high-sensitivity C-reactive protein [hsCRP]), anti-inflammatory activity (interleukin [IL]-10), and platelet activation (soluble CD40 ligand [sCD40L]) were determined. Patients were followed for the occurrence of death or myocardial infarction.

Results: In patients with ACS, elevated PAPP-A levels (>12.6 mIU/l) indicated an increased risk (odds ratio 2.44 [95% confidence interval (CI) 1.43 to 4.15]; p = 0.001). When the analysis was restricted to TnT-negative patients, PAPP-A still identified a subgroup of high-risk patients (odds ratio [OR] 2.72 [95% confidence interval (CI) 1.25 to 5.89]; p = 0.009). In a multivariable model, PAPP-A (OR 2.01; p = 0.015), sCD40L (OR 2.37; p = 0.003), IL-10 (OR 0.43; p = 0.003), and VEGF (OR 2.19; p = 0.018) were independent predictors. Prospective validation in patients with chest pain confirmed that PAPP-A levels reliably identify high-risk patients (adjusted OR 2.32 [95% CI 1.32 to 4.26]; p = 0.008). Patients negative for all three markers (TnT, sCD40L, and PAPP-A) were at very low cardiac risk (30 days: 3.0% event rate; no death).

Conclusions: The PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS. Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angina, Unstable / blood*
  • Angina, Unstable / complications
  • Angina, Unstable / mortality*
  • C-Reactive Protein / metabolism
  • CD40 Ligand / blood
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / mortality*
  • Female
  • Humans
  • Interleukin-10 / blood
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology*
  • Predictive Value of Tests
  • Pregnancy-Associated Plasma Protein-A / metabolism*
  • Prognosis
  • Syndrome
  • Troponin T / blood
  • Vascular Endothelial Growth Factor A / blood


  • Troponin T
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • CD40 Ligand
  • C-Reactive Protein
  • Pregnancy-Associated Plasma Protein-A