Prognostic Utility of Lipoprotein-Associated Phospholipase A 2 for Cardiovascular Outcomes in Patients With Stable Coronary Artery Disease

OBJECTIVE: To determine the prognostic utility of lipoprotein-associated phospholipase A2 (Lp-PLA2) for specific adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD), independent of traditional risk factors and high-sensitivity C-reactive protein (hs-CRP). METHODS AND RESULTS: We measured Lp-PLA2 in 3766 patients with stable CAD from the PEACE trial. Patients were followed for a median of 4.8 years for adverse cardiovascular events including death, myocardial infarction (MI), coronary revascularization, hospitalization for unstable angina (UA), and stroke. Multivariable Cox regression was used to adjust for traditional cardiovascular risk factors and to conduct multimarker analyses that included hs-CRP. After adjustment for baseline characteristics, patients in higher quartiles of Lp-PLA2 remained at significantly greater risk for the composite of cardiovascular death, MI, coronary revascularization, UA, or stroke (P<0.001 for trend, adj HR 1.41, 95% CI 1.17 to 1.70, for patients in 4th versus 1st quartile). The association was consistent regardless of a patient's sex, cholesterol levels, or use of lipid-lowering therapy. When analyzed together, both hs-CRP and Lp-PLA2 were highly significant predictors of acute coronary syndromes (cardiovascular death, MI, or UA) (P for trend <0.001 for hs-CRP and 0.005 for Lp-PLA2), whereas only Lp-PLA2 was a significant predictor of coronary revascularization (P=0.01 for trend). CONCLUSIONS: In stable CAD, an elevated level of Lp-PLA2 was a significant predictor of nonfatal adverse cardiovascular outcomes independent of traditional clinical risk factors and hs-CRP. Further investigation will be needed to establish whether therapies that lower Lp-PLA2 reduce cardiovascular risk.