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

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Abstract
Objectives— We sought to evaluate whether lipoprotein-associated phospholipase A2 (Lp-PLA2), 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-PLA2 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-PLA2 after adjustment for various covariates, including markers of inflammation, renal function, and hemodynamic stress. In multivariable analyses, Lp-PLA2 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-PLA2 mass compared with the bottom tertile and 2.40 (95% CI, 1.35 to 4.29) for Lp-PLA2 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-PLA2 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. We found that lipoprotein-associated phospholipase A2 (Lp-PLA2) strongly predicts secondary cardiovascular events in patients with manifest coronary heart disease (CHD). In multivariable analysis, even including markers of inflammation, renal function, and hemodynamic stress, patients in the top tertile of the Lp-PLA2 mass and activity distribution showed &2-fold increased risk compared with those in the bottom tertile.