Abstract 16063: Effect of Fenofibric Acid on Oxidative Susceptibility of Fasting and Postprandial Lipoproteins
Fenofibric acid (FENO 135 mg/day; Trilipix®) is safe and efficacious for reduction of triglycerides (TG) with minimal effect on LDL-C. We hypothesize changes in the metabolism of TG-rich lipoproteins may impact the oxidative susceptibility (oxSus) of LDL in the absence and presence of cupric ions (Cu++) as well as autologous HDL. Twenty seven patients with metabolic syndrome were randomized in a double-blind placebo-controlled crossover study with 8-week treatment and 4-week washout periods. At the end of each period, subjects consumed a standardized 450-kcal solid meal. Blood was collected for 6 hours after the meal. Lipoprotein-rich fraction (d<1.21 g/mL) was isolated by density ultracentrifugation. After both study periods LDL and HDL were isolated by FPLC for evaluation of oxSus in the presence and absence of Cu++. Mean fasting TG was reduced by 20% (p< 0.0002, 239 to 182 mg/dL) in subjects receiving FENO, associated with a 16.1% reduction in VLDL particle number (p<0.002). Percent changes in TC, HDL-C and LDL-C were not statistically significantly different between FENO and placebo (-0.8%, +3.6%, and +3.8%, respectively). Incremental area under the plasma TG curve was reduced by 28.5% (p< 0.0005) with FENO. Mean (± SD) lag time for LDL oxidation in the absence of Cu++ was 180 (± 84.1) min and was not affected by FENO therapy (157 ± 79.9). With Cu++, longer lag time was noted for both fasting (41.2 (23.2) versus 32.8 (18.0) min, p<0.01) and postprandial (32.0 (16.7) versus 25.5 (12.2) min, p<0.01) LDL during FENO. In co-incubations with autologous LDL and HDL, longer lag times were noted with fasting HDL during FENO (29.5 versus 19.3 min, p <0.03) but not with postprandial HDL (20.1 versus 16.4 min, p<0.09). Treatment with FENO resulted in reduction in fasting TG and improved postprandial lipemia. More importantly, susceptibility of plasma LDL to Cu++-induced oxidative modification was significantly reduced with treatment, both in the fasted and in the postprandial state, in spite of no change in LDL-C levels. Fasting HDL during the FENO period reduced LDL oxidation susceptibility but postprandial HDL did not.
- © 2012 by American Heart Association, Inc.