Abstract 19878: Metalloproteinase PAPP-A and Outcomes in Patients with ACS: Observations from the MERLIN-TIMI 36 Trial
Background: Pregnancy associated plasma protein-A (PAPP-A) is a high molecular weight, zinc-binding metalloproteinase. Initial studies have suggested that PAPP-A is associated with vulnerable coronary plaque and may be used as a predictor of cardiovascular disease and mortality. We investigated whether PAPP-A would be useful for risk assessment in patients presenting with NSTE-ACS.
Methods: We measured cardiac PAPP-A (Beckman Coulter DSL ELISA) at baseline in all pts with available samples (n=3782) presenting with NSTE-ACS and randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Pts were followed for an average of one yr. Endpoints were adjudicated by a blinded Clinical Endpoints Committee. The primary endpoint for this analysis was CV death (CVD) or MI. A cutpoint of 6.0 uIU/mL was chosen based on pilot work.
Results: PAPP-A > 6.0 uIU/mL at presentation was associated with higher rates of CVD or MI at 30 days (7.4% vs 3.7%, HR 2.01, 95% CI 1.43 – 2.82, p<0.001) and at one year (HR 1.63; 95% CI 1.29 – 2.05, p<0.001). At 30 days (Figure A), PAPP-A was associated with higher rates of CVD (HR 1.94; 95% CI 1.07 – 3.52, p=0.027) and MI (HR 1.82; 95% CI 1.22 – 2.71, p=0.003) individually. When stratified by baseline cTnI (Accu-TnI, cutpoint 0.03 ug/L), PAPP-A remained associated with CVD/MI at 1 year (Figure B). After adjustment for cTnI, ST deviation, age, gender, diabetes, smoking, HTN, and history of CAD, PAPP-A was independently associated with the risk of CVD/MI at 30 days (adj HR 1.61; 95% CI 1.14 – 2.27, p=0.007) and 1 year (adj HR 1.34; 95% CI 1.06 – 1.69, p=0.015). SPAN> SPAN>
Conclusions: PAPP-A was independently associated with short and long-term risk of recurrent cardiovascular events in patients with NSTE-ACS, along with clinical predictors and cTnI. This finding adds to emerging evidence supporting PAPP-A as a candidate prognostic marker in patients with ACS, and supports investigation of its therapeutic implications.
- © 2010 by American Heart Association, Inc.