In order to investigate the effects of fenofibrate on lipoprotein-associated phospholipase A2 (Lp-PLA2) and changes in LDL subclasses, Robert S. Rosenson designed a randomized, double-blind, controlled trial over a 3-month period in 55 hypertriglyceridemic subjects with the metabolic syndrome. As the main outcome measure, Lp-PLA2 mass decreased by 13.2% in subjects treated with fenofibrate. In the entire study population, changes in Lp-PLA2 mass were positively associated with changes in LDL cholesterol and LDL particle number as well as with changes in large and small LDL particles. Although changes in oxidized fatty acids and oxidized LDL particles were not associated with Lp-PLA2, fenofibrate induced significant changes in both oxidized fatty acids and oxidized LDL particle concentrations. Changes in Lp-PLA2 were not associated with changes in inflammatory markers. Based on these results, Rosenson concluded that therapies reporting reductions in Lp-PLA2 mass should account for metabolic syndrome changes in the distribution of LDL subclasses.
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