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Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes

Comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis

Christopher Heeschen, MD^*,*, Stefanie Dimmeler, PhD^*, Christian W. Hamm, MD, FACC, Stephan Fichtlscherer, MD^*, Maarten L. Simoons, MD, FACC, Andreas M. Zeiher, MD, FACC^* CAPTURE Study Investigators

^* Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Frankfurt, Germany
Kerckhoff Heart Center, Bad Nauheim, Germany
Erasmus University, Thoraxcentre, Rotterdam, the Netherlands

View larger version (18K): [in a new window]   Figure 1 Pregnancy-associated plasma protein A (PAPP-A) and high-sensitivity C-reactive protein (hsCRP) plasma levels, respectively, according to the baseline troponin T status. Only for illustrative purposes, outliers are marked as circles. Importantly, all data points were included in the statistical analysis.

View larger version (19K): [in a new window]   Figure 2 Soluble CD40 ligand and high-sensitivity C-reactive protein (hsCRP) plasma levels, respectively, according to the baseline pregnancy-associated plasma protein A (PAPP-A) status. Only for illustrative purposes, outliers are marked as circles. Importantly, all data points were included in the statistical analysis.

View larger version (36K): [in a new window]   Figure 3 Association between the pregnancy-associated plasma protein A (PAPP-A) plasma levels and the cardiac event rate at 24 h, 72 h, 30 days, and 6 months according to the PAPP-A quintile in the placebo group of the Anti Platelet Therapy in Unstable Refractory Angina (CAPTURE) study (n = 547). Differences in event rates between the quintiles were significant at 72 h (p = 0.019), 30 days (p = 0.008), and 6 months (p = 0.004) of follow-up. MI = myocardial infarction.

View larger version (19K): [in a new window]   Figure 4 Receiver operating characteristic curve analysis for the predictive value of pregnancy-associated plasma protein A (PAPP-A) plasma levels for the occurrence of death or nonfatal myocardial infarction at six months of follow-up (n = 547). Solid line = sensitivity (%); dotted line = specificity (%).

View larger version (18K): [in a new window]   Figure 5 Kaplan-Meier event rate curves showing the cumulative incidence of death or nonfatal myocardial infarction (MI) at 72 h (a) and 6 months of follow-up (b) according to the baseline pregnancy-associated plasma protein A (PAPP-A) plasma level (diagnostic threshold 12.6 mIU/l; n = 547).

View larger version (16K): [in a new window]   Figure 6 Predictive value of pregnancy-associated plasma protein A (PAPP-A) for the incidence of death and nonfatal myocardial infarction (MI) at six months of follow-up was also apparent in patients without troponin T (TnT) elevation (a) and was restricted to patients with low levels of the anti-inflammatory cytokine interleukin (IL)-10 (b). Diagnostic thresholds were 12.6 mIU/l for PAPP-A, 10 mg/l for high-sensitivity C-reactive protein, and 3.5 ng/l for IL-10 (n = 547). *p < 0.01 versus PAPP-A low; **p < 0.01 versus PAPP-A low.

View larger version (16K): [in a new window]   Figure 7 Predictive value of pregnancy-associated plasma protein A (PAPP-A) in patients with acute chest pain for the incidence of death and nonfatal myocardial infarction (MI) during 30 days of follow-up (a). In patients that were negative both for troponin T (TnT) and soluble CD40 ligand (sCD40L), PAPP identified a subgroup suffering from increased cardiovascular risk during 30 days of follow-up (b). Diagnostic thresholds were 12.6 mIU/l for PAPP-A, 0.1 µg/l for TnT, and 5.0 µg/l for sCD40L (n = 644). Solid lines = TnT high; dotted lines = TnT low; open bars = PAPP-A low; solid bars = PAPP-A high.