Abstract 3699: Type II Secretory Phospolipase A2 Plasma Concentrations Predict Cardiovascular Events in Patients with Coronary Heart Disease
Purpose: Type II secretory phospholipase A2 (sPLA2) is widely expressed in hepatocytes, macrophages, endothelial cells, platelets, and vascular SMCs, and is up-regulated in response to various pro-inflammatory compounds. Possible atherogenic mechanisms of sPLA2 include triggering of local inflammatory cellular responses. Since there are only few studies that have investigated the predictive value of sPLA2, we sought to evaluate whether sPLA2 is associated with prognosis in a large cohort of patients with clinically overt coronary heart disease (CHD).
Methods: Plasma concentrations of sPLA2 (ng/mL) were determined by ELISA (Cayman Chemical Co., Ann Arbor, MI, USA) at baseline in a cohort of 1,047 patients aged 30 –70 years with CHD participating in an in-patient rehabilitation program after an acute coronary syndrome. The Cox proportional hazards model was used to determine the prognostic value of sPLA2 on a combined endpoint (fatal and non-fatal myocardial infarction (MI) and stroke) after adjustment for covariates.
Results: During follow-up (mean 4.1 years) 95 patients (9.0%) experienced a secondary CVD event. Baseline levels of sPLA2 were higher in subjects who experienced an event compared to event free-subjects (5.21±6.33 vs. 3.95±5.38 ng/mL, p<0.0001). sPLA2 was positively correlated with age (r=0.24, p=0.0001), C-reactive protein (CRP) (r=0.52, p<0.0001), LDL cholesterol (r=0.08, p<0.008), cystatin C (r=0.29, p<0.0001), and NT-proBNP (r=0.27, p<0.0001), but only marginally with body mass index (BMI) (r=0.07, p=0.04). In a multivariate model, sPLA2 was associated with an increased hazard ratio (HR) of future cardiovascular events. After controlling for age, gender, BMI, smoking, history of MI and diabetes mellitus, severity of CHD, HDL-C, LDL-C, statin use, cystatin C, NT-proBNP, Lp-PLA2, and CRP, the HR was 1.42 (95% confidence interval (CI) 0.78 –2.59), and 1.92 (95% CI, 1.05–3.51) when the second and the top tertile were compared to the bottom tertile.
Conclusions: Concentrations of sPLA2-II appear to be predictive of secondary CVD events in patients with manifest CHD independent of a variety of potential risk factors including markers of inflammation, renal function, and hemodynamic stress.