Prospective Evaluation of Pregnancy-Associated Plasma Protein-A and Outcomes in Patients With Acute Coronary Syndromes

• Published in: Journal of the American College of Cardiology 2012-07, Vol.60 (4), p.332-338
• Main Authors: Bonaca, Marc P., MD, MPH, Scirica, Benjamin M., MD, Sabatine, Marc S., MD, MPH, Jarolim, Petr, MD, PhD, Murphy, Sabina A., MPH, Chamberlin, Janna S, Rhodes, Daniel W., MD, MPH, Southwick, Paula C., PhD, Braunwald, Eugene, MD, Morrow, David A., MD, MPH
• Format: Article
• Language: English
• Subjects: Acetanilides - adverse effects; Acetanilides - therapeutic use; Acute Coronary Syndrome - blood; Acute Coronary Syndrome - drug therapy; Acute Coronary Syndrome - mortality; acute coronary syndrome(s); Acute coronary syndromes; Aged; Aged, 80 and over; atherothrombosis; Biological and medical sciences; Biomarkers - blood; Cardiology; Cardiology. Vascular system; Cardiovascular; Cause of Death; Coronary heart disease; Coronary vessels; Electrocardiography; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Female; Heart; Heart attacks; Humans; Internal Medicine; ischemia; Kaplan-Meier Estimate; Male; Medical sciences; metalloproteinase; Middle Aged; Multivariate Analysis; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Myocardial Infarction - mortality; Myocarditis. Cardiomyopathies; PAPP-A; Piperazines - adverse effects; Piperazines - therapeutic use; Plasma; Predictive Value of Tests; Pregnancy; Pregnancy-Associated Plasma Protein-A - metabolism; Prognosis; Prospective Studies; Ranolazine; Recurrence; Risk Assessment; Signal Processing, Computer-Assisted; Survival Analysis; Troponin - blood
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2012.04.023

Objectives This study sought to investigate whether pregnancy-associated plasma protein-A (PAPP-A) is useful for risk assessment in non–ST-segment elevation acute coronary syndrome (NSTE-ACS). Background PAPP-A is a high molecular weight, zinc-binding metalloproteinase that is associated with vulnerable plaque and may be a predictor of cardiovascular disease and mortality. Methods We measured PAPP-A at baseline in 3,782 patients with non NSTE-ACS randomized to ranolazine or placebo in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) trial and followed for an average of 1 year. A cut point of 6.0 μIU/ml was chosen from pilot work in this cohort. Results PAPP-A >6.0 μIU/ml at presentation was associated with higher rates of cardiovascular death (CVD) or myocardial infarction (MI) at 30 days (7.4% vs. 3.7%, hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.43 to 2.82; p < 0.001) and at 1 year (14.9% vs. 9.7%, HR: 1.63; 95% CI: 1.29 to 2.05; p < 0.001). PAPP-A was also associated with higher rates of CVD (HR: 1.94; 95% CI: 1.07 to 3.52, p = 0.027) and myocardial infarction (HR: 1.82; 95% CI: 1.22 to 2.71, p = 0.003) individually at 30 days. There was no difference in the risk associated with PAPP-A stratified by baseline cardiac troponin I [Accu-TnI >0.04 μg/l], p interaction = 0.87). After adjustment for cardiac troponin I, ST-segment deviation, age, sex, diabetes, smoking, hypertension, and coronary artery disease, PAPP-A was independently associated with CVD/myocardial infarction at 30 days (adjusted HR: 1.62, 95% CI: 1.15 to 2.29; p = 0.006) and 1 year (adjusted HR: 1.35, 95% CI: 1.07 to 1.71; p = 0.012). PAPP-A also improved the net reclassification for CVD/MI (p = 0.003). There was no significant interaction with ranolazine. Conclusions PAPP-A was independently associated with recurrent cardiovascular events in patients with NSTE-ACS. This finding supports PAPP-A as a candidate prognostic marker in patients with ACS and supports investigation of its therapeutic implications.