Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 60, Issue 4, Pages 332-338Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2012.04.023
Keywords
acute coronary syndrome(s); atherothrombosis; ischemia; metalloproteinase; PAPP-A
Categories
Funding
- Accumetrics
- AstraZeneca
- Bayer Healthcare
- Beckman Coulter
- Biosite
- Bristol-Myers Squibb
- CV Therapeutics
- Daiichi Sankyo
- Eli Lilly Co.
- GlaxoSmithKline
- Merck Co.
- Nanosphere
- Novartis Pharmaceuticals
- Ortho-Clinical Diagnostics
- Pfizer
- Roche Diagnostics
- Sanofi-Aventis
- Schering-Plough
- Siemens
- Singulex
- Gilead
- Johnson Johnson
- National Health, Lung, and Blood Institute [R01 HL096738, R01 HL098280, HHSN268201000033C]
- Beckman-Coulter
- Amgen
- BRAHMS
- Abbott
- Roche
- Menarini International
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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 mu IU/ml was chosen from pilot work in this cohort. Results PAPP-A >6.0 mu IU/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 mu g/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. (J Am Coll Cardiol 2012;60:332-8) (C) 2012 by the American College of Cardiology Foundation
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