High levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA2 has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM-1). Although treatment with fenofibrate reduces Lp-PLA2 mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA2 and sVCAM-1. Concentrations of Lp-PLA2 mass and sVCAM-1 levels were measured in plasma at baseline and after 3 weeks of fenofibrate treatment (160 mg/d) in 96 hypertriglyceridemic participants of the Genetics of Lipid-lowering Drugs and Diet Network study. Lp-PLA2 and sVCAM-1 were stratified by tertiles as determined by baseline levels of the respective target. Fenofibrate treatment resulted in a 30.1% mean increase in Lp-PLA2 mass (P = 0.0003) and a 14.7% mean increase in sVCAM-1 levels (P = 0.0096) but only in tertile1 of either target. In contrast, Lp-PLA 2 mass was reduced by 35.3% (P < 0.0001) in tertile 3. Soluble VCAM-1 levels were significantly reduced by 7.74% (P = 0.0109) and 17.2% (P < 0.0001) in tertiles 2 and 3, respectively. No associations were observed between Lp-PLA2 and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA2 mass and sVCAM-1, but only in those with elevated baseline levels of these biomarkers. The greatest reductions in Lp-PLA 2 levels were observed in individuals with Lp-PLA2 concentrations indicative of increased cardiovascular disease risk (>200 ng/mL).
Bibliographical noteFunding Information:
Supported by National Heart, Lung, and Blood Institute Grant U01HL072524-04 .