Lipoprotein-Associated Phospholipase A 2 Predicts Future Cardiovascular Events in Patients With Coronary Heart Disease Independently of Traditional Risk Factors, Markers of Inflammation, Renal Function, and Hemodynamic Stress

Abstract

Objectives— We sought to evaluate whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), an emerging marker of cardiovascular risk, is associated with prognosis in patients with coronary heart disease (CHD). Methods and Results— Plasma concentrations and activity of Lp-PLA 2 were determined in 1051 patients aged 30 to 70 years with CHD who were followed for &4 years. A Cox proportional hazards model was used to determine the prognostic value of Lp-PLA 2 after adjustment for various covariates, including markers of inflammation, renal function, and hemodynamic stress. In multivariable analyses, Lp-PLA 2 mass and activity were strongly associated with cardiovascular events after controlling for traditional risk factors, severity of CHD, statin treatment, cystatin C, and N-terminal proBNP. The hazard ratio (HR) for recurrent events was 2.65 (95% confidence interval [CI], 1.47 to 4.76) for the top tertile of Lp-PLA 2 mass compared with the bottom tertile and 2.40 (95% CI, 1.35 to 4.29) for Lp-PLA 2 activity. After additional adjustment for low-density lipoprotein (LDL), the HRs were only moderately attenuated (mass: 2.09; 95% CI, 1.10 to 3.96; activity: 1.81; 95% CI, 0.94 to 3.49, respectively), but the latter was no longer statistically significant. Conclusions— Increased concentrations of Lp-PLA 2 predict future cardiovascular events in patients with manifest CHD independent of a variety of potential risk factors including markers of inflammation, renal function, and hemodynamic stress.