Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia

Background: Fasting and post-prandial hypertriglyceridernia have been associated with endothelial dysfunction. Objective: To investigate the effects of a 3-month treatment with fenofibrate (200 mg daily) on endothelial reactivity and inflammatory state in hypertriglyceridemic patients at fast and after an oral fat load. Methods: Brachial flow-mediated vasodilation (FMV) and the circulating levels of intercellular adhesion molecule (ICAM) and vascular cellular adhesion molecule (VCAM) were determined in 10 hypertriglyceridemic patients. Results: Before treatment, post-prandial phase was characterized by an increase in triglycerides (3.7+/-1 mmol/L at baseline vs. 4.2+/-1, 6.5+/-1, 6.6+/-2, and 5.3+/-2 mmol/L after 2, 4, 6, and 8 h), a decrease in FMV (4.3+/-2% at baseline vs. 2.8+/-1, 2.2+/-1, and 1.3+/-1% after 2, 4, and 6 h), and an increase in ICAM and VCAM. After fenofibrate there was a significant reduction in fasting triglycerides (3.7+/-1.3 vs. 2.1+/-0.8 mmol/L), ICAM (480+/-113 vs. 269+/-65 ng/mL) and VCAM (1821+/-570 vs. 1104+/-376 ng/mL), and an increase in FMV (4.3+/-2 vs. 7.1+/-2%). Post-prandially triglycerides increased (2.1+/-1 at baseline vs. 2.4+/-2 and 3.6+/-1 mmol/L after 4 and 6 h), FMV decreased (7.1+/-2 at baseline vs. 5.8+/-2, 5.5+/-2, 5.9+/-2, 6.4+/-2% after 2, 4, 6, and 8 h), and there was an increase of ICAM and VCAM. Before therapy post-prandial changes in FMV had an inverse correlation with the changes in triglycerides (r=-0.34; P<0.05) and ICAM (r=-0.66; P<0.001). Conclusions: The transient endothelial dysfunction observed in hypertriglyceridemic subjects during post-prandial lipemia is mediated by post-prandial triglyceride increase and by the activation of inflammatory response. The anti-inflammatory activity of fenofibrate may represent an additional mechanism of its favorable action on the endothelial function during fasting and the post-prandial phase.