[show abstract][hide abstract] ABSTRACT: Fenofibrate significantly reduces circulating triglyceride (TG) concentrations, particularly in individuals with elevated levels. The purpose of the current study was to determine whether fenofibrate treatment reduces markers of oxidative stress, oxidized low density lipoprotein (ox-LDL) and 8-isoprostane (8-isoP), in a manner similar to TG where those with the highest levels show the greatest reductions.
The concentrations of TG, 8-isoP, and ox-LDL were measured in plasma before and after 3 weeks of fenofibrate treatment (160 mg/d) in a sub-cohort (n=187) of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study.
Data were divided into tertiles as determined by pre-treatment values of the respective target. Fenofibrate treatment resulted in significant reductions in TG concentrations by 24.2% (p<0.0001), 41.9% (p < 0.0001), and 46.6% (p < 0.0001) in tertiles 1, 2, and 3, respectively. Significant reductions were also observed in ox-LDL of 7.2% (p=0.0096), 8.5% (p = 0.0019) and 12.1% (p < 0.0001) in tertiles 1, 2, and 3, respectively. Finally, fenofibrate treatment resulted in a 32.7% increase (p=0.0201) in 8-isoP levels in tertile 1, but a significant decrease of 34.4% (p < 0.0001) in tertile 3.
This study is the largest to date to demonstrate that fenofibrate reduces oxidative stress and the first to show a suppressive effect on 8-isoP levels in individuals with a high oxidative burden following short term (3 wk) drug therapy. Those with the highest baseline levels of ox-LDL and 8-isoP showed the greatest reductions following fenofibrate treatment. Given the role of oxidative stress in atherosclerosis and coronary heart disease, our observations may partially explain the efficacy of fenofibrate in reducing cardiovascular events in select patients.
[show abstract][hide abstract] ABSTRACT: High levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA(2) has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM-1). Although treatment with fenofibrate reduces Lp-PLA(2) mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA(2) and sVCAM-1. Concentrations of Lp-PLA(2) 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-PLA(2) 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-PLA(2) 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-PLA(2) and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA(2) 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-PLA(2) concentrations indicative of increased cardiovascular disease risk (>200 ng/mL).
Translational Research - TRANSL RES. 01/2011; 158(2):99-105.