Abstract 1724: Elevated Levels of the Atherosclerotic Lesion Metalloproteinase PAPPA Are an Independent Predictor of Cardiovascular Death or CHF in STEMI: Results from the CLARITY-TIMI 28 Biomarker Study
Background: Pregnancy associated plasma proteinase A (PAPPA) is a metalloproteinase found in unstable atherosclerotic lesions. The prognostic value of PAPPA in ST-elevation myocardial infarction (STEMI) is unknown.
Methods: We measured circulating PAPPA levels using an ELISA (Diagnostic Systems) in a case-cohort of 731 STEMI pts undergoing lysis in CLARITY-TIMI 28 and followed for 30 d. Multivariable Cox proportional hazards regression was used to adjust for demographics, comorbidities, infarct location, Killip class, and type of lytic.
Results: The median level of PAPPA was 1.67 mIU/ml (IQR 0.18–9.89 mIU/ml). Patients with higher levels of PAPPA were more likely to be male, but tended to be less likely to have hypertension or diabetes, have an anterior MI, or present in Killip class II–IV. After multivariable adjustment, patients in the top 3 quartiles were at significantly higher risk for cardiovascular death or heart failure (Figure⇓, left, P=0.03). PAPPA levels were not correlated with other biomarkers of death or CHF, including NT-proBNP and ST2 (r<0.10 for both). In a multivariable model that adjusted for clinical covariates, all 3 biomarkers were independent predictors of CV death or CHF (Figure⇓, right, P<0.02 for each) and their addition to clinical risk factors significantly raised the c-statistic from 0.74 to 0.80 (P=0.003).
Conclusion: Circulating levels of PAPPA at presentation are a significant predictor of a threefold increased risk of CV death or CHF in patients with STEMI. In a multimarker model, PAPPA, NT-proBNP, and ST2 were significant and complementary predictors of risk, and their addition to clinical risk factors significantly improved the c-statistic.