Lipoprotein-associated phospholipase A2 activity is associated with coronary artery disease and markers of oxidative stress: a case-control study

Abstract

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA 2) is a lipoprotein-bound enzyme that can release atherogenic isoprostanes from esterified phospholipids and that may be involved in inflammation and atherosclerosis. Objective: This study investigates the association between Lp-PLA2 activity and coronary artery disease (CAD) in relation to oxidative stress markers, in particular urinary 8-epi-prostaglandin F2α (8-epi-PGF2α). Design: We conducted a case-control study in which the cross-sectional relation between Lp-PLA2 activity, lipoproteins, and oxidative stress markers was determined in 799 patients with angiographically confirmed CAD and 925 healthy controls. Results: Lp-PLA2 activity was significantly (P < 0.001) higher in CAD cases than in controls (32.9 ± 0.46 and 29.7 ± 0.42 nmol · mL-1 · min-1, respectively). Both elevated Lp-PLA2 activity and urinary excretion concentrations of 8-epi-PGF2α were associated with greater CAD risk (P for trend < 0.001). Odds ratios for the upper quartiles of Lp-PLA2 activity and 8-epi-PGF2α.excretion were 2.47 (95% CI: 1.79, 3.40) and 2.19 (1.52, 3.15), respectively, after adjustment for sex, age, BMI, blood pressure, smoking and alcohol consumption status, and LDL and HDL cholesterol. When we examined the additive effect of both markers for CAD risk, the relation between 8-epi-PGF2α and CAD was weakened above the second quartile of Lp-PLA2 activity. Moreover, Lp-PLA2 activity was positively correlated with urinary excretion concentrations of 8-epi-PGF2α in controls (r=0.277, P<0.001) and cases (r=0.202, P<0.001) and with the tail moment of lymphocyte DNA (r=0.213, P < 0.001) in controls. Conclusion: This study shows an association of elevated Lp-PLA2 activity with CAD risk in relation to oxidant stress and thus supports a proatherogenic role of Lp-PLA2.