Prognostic Utility of Secretory Phospholipase A2 in Patients with Stable Coronary Artery Disease

Open Access
Publisher Website
Google Scholar
Abstract
BACKGROUND: Secretory phospholipase A2 (sPLA2) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA2 for risk stratification in coronary artery disease (CAD). METHODS: We measured plasma sPLA2 activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications. RESULTS: After multivariable adjustment, sPLA2 was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.13–2.14) and cardiovascular death or heart failure (1.91, 1.20–3.03). In further multivariable assessment, increased activity levels of sPLA2 were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.06–2.04), independent of lipoprotein-associated phospholipase A2 mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.668–0.675, P = 0.01). sPLA2, N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively). CONCLUSIONS: sPLA2 activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA2 as a therapeutic target.
Funding Information
  • National Heart, Lung, and Blood Institute
  • Knoll Pharmaceuticals
  • Abbott Laboratories
  • AstraZeneca
  • GlaxoSmithKline
  • Eisai
  • Merck
  • Siemens
  • Buhlmann
  • Singulex
  • Brahms
  • diaDexus
  • OrthoClinical Diagnostics
  • NIH (R01 HL094390)

This publication has 19 references indexed in Scilit: