Clinical research
Coronary artery disease
Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: Comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis

https://doi.org/10.1016/j.jacc.2004.09.060Get rights and content
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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.

Abbreviations and acronyms

ACS
acute coronary syndromes
CAPTURE c7E3
Anti Platelet Therapy in Unstable Refractory Angina trial
CI
confidence interval
hsCRP
high-sensitivity C-reactive protein
IL
interleukin
PAPP-A
pregnancy-associated plasma protein A
ROC
receiver operating characteristic
sCD40L
soluble CD40 ligand
TnT
troponin T
VEGF
vascular endothelial growth factor

Cited by (0)

Trial participants have been published previously (see reference 17).