Differential effect of hypolipidemic drugs on lipoprotein-associated phospholipase A2

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass.

In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily). Fifty patients with Type IV dyslipidemia were given micronised fenofibrate (200 mg daily). Low- and high-density lipoprotein (LDL and HDL, respectively) subclass analysis was performed electrophoretically, whereas lipoprotein subfractions were isolated by ultracentrifugation. Ezetimibe reduced plasma Lp-PLA2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions. Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA2 on dense LDL subfraction (LDL-5). Fenofibrate preferentially reduced the Lp-PLA2 activity and mass associated with the VLDL+IDL and LDL-5 subfractions. Among studied drugs only fenofibrate increased HDL-associated Lp-PLA2 (HDL-Lp-PLA2) activity and mass attributable to a preferential increase in Lp-PLA2 associated with the HDL-3c subfraction.

Ezetimibe, rosuvastatin, and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins. Furthermore, fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2. The clinical implications of these effects remain to be established.