Lipoprotein-associated phospholipase A2 predicts future cardiovascular events in patients with coronary heart disease independently of traditional risk factors, markers of inflammation, renal function, and hemodynamic stress

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 approximate to 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.