Abstract 3356: Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Is an Independent Predictor of Adverse Cardiovascular Outcomes in Patients with Stable Coronary Artery Disease
Background: Lp-PLA2 cleaves oxidized LDL into pro-atherogenic fragments. The prognostic utility of Lp-PLA2 in patients with stable CAD remains largely unexplored, especially after adjusting for high sensitivity C-reactive protein (hs-CRP).
Methods: Lp-PLA2 mass (PLAC™ Test, diaDexus Inc.) and hs-CRP (Denka Seiken) were measured on baseline samples in 3766 pts enrolled in PEACE, a placebo-controlled trial of trandolapril in stable CAD. Pts were followed for a mean of 4.8 yrs for CV death (CVD), MI, and coronary revascularization (Revasc). Multivariable Cox regression was used to adjust for age, sex, CV risk factors, cholesterol, BMI, GFR, treatment group, other cardiac meds, and hs-CRP.
Results: Patients with higher levels of Lp-PLA2 were more likely to be male, Caucasian, smokers, have higher cholesterol and hs-CRP levels, and not be treated with lipid-lowering therapy. Higher levels of Lp-PLA2 were associated with a significantly greater risk of CVD/MI/Revasc (adj HR 1.09 for each SD increase, P=0.01). Dividing pts into quartiles based on Lp-PLA2 (Fig⇓), there was a significant stepwise increase in the cumulative incidence of CVD/MI/Revasc, which persisted after multivariable adjustment (P=0.008 for trend, adj HR 1.29, 95% CI 1.05–1.58, P=0.01 for pts in 4th vs. 1st quartile).
Conclusion: In the largest study to date of Lp-PLA2 in patients with stable CAD, an elevated level of Lp-PLA2 was a significant predictor of adverse CV outcomes, independent of traditional clinical risk factors and hs-CRP. Further investigation will need to determine the clinical utility of measuring Lp-PLA2 and whether therapies that lower Lp-PLA2 reduce cardiovascular risk.