Objective: Examine the effect of ABT-335 (fenofibric acid) on postprandial lipemia and susceptibility of plasma lipoproteins to Cu++-mediated oxidation in patients with metabolic syndrome. Methods and results: This is a randomized double-blind, placebo-controlled study with cross-over and includes a 4-week wash-out period between the two treatment periods. At the end of each 8-week treatment period, subjects were challenged with a standardized mixed meal followed by blood collection over the ensuing 6h. Plasma lipoproteins were isolated by a combination of ultracentrifugation and FPLC for the continuous monitoring of conjugated dienes formation as an assessment of oxidative susceptibility. Fasting plasma TG was reduced by 20% (p<0.0002) and there was a modest reduction in hsCRP (6.1%, p<0.06). There was no change in either HDLc or LDLc in these subjects. Postprandial lipemia was reduced with ABT-335 as demonstrated by a 28.5% reduction ( p<0.0005) in incremental area under the curve for TG during the 6-hperiod after the meal challenge. Lag times for both fasting LDL (+16%) and postprandial LDL (+28%) were increased with the ABT-335 therapy, suggestive of reduced oxidative susceptibility. Co-incubation with autologous HDL did not reduced LDL oxidative susceptibility in these patients. Conclusion: ABT-335 therapy reduced fasting and postprandial triglycerides in patients with metabolic syndrome. Autologous HDL may be dysfunctional in these patients as co-incubation with HDL failed to reduce oxidative susceptibility of LDL. During ABT-335 therapy, LDL was less susceptible to Cu++-mediated oxidative modification, in spite of the lack of changes in LDLc levels. © 2013.
Le, N. A., Farkas-Epperson, M., Sweeney, M. E., Wilson, P. W. F., & Virgil Brown, W. (2013). Effect of ABT-335 (fenofibric acid) on meal-induced oxidative stress in patients with metabolic syndrome. Atherosclerosis, 231(2), 268–273. https://doi.org/10.1016/j.atherosclerosis.2013.09.022