Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects with Hypertriglyceridemia and the Metabolic Syndrome

Abstract

Objectives The aim of this study was to determine the effects of fenofibrate (160 mg/d) on fasting and postprandial lipoproteins, oxidized fatty acids, and inflammatory mediators in subjects with hypertriglyceridemia and the metabolic syndrome.

Research Design and Methods Fifty-nine subjects with fasting hypertriglyceridemia (≥1.7 mmol/L and <6.9 mmol/L) and two or more of the Adult Treatment Panel III criteria of the metabolic syndrome were randomized to fenofibrate (160 mg/d) or placebo in a double-blind controlled clinical trial.

Results Fenofibrate treatment lowered fasting triglycerides (-46.1%, p<0.0001) and postprandial (area under the curve) triglycerides (-45.4%, p<0.0001) due to significant reductions in postprandial levels of large (-40.8%, p<0.0001) and medium (-49.5%, p<0.0001) very low-density lipoprotein (VLDL) particles. Fasting total low-density lipoprotein (LDL) particle number was reduced in fenofibrate treated subjects (-19.0%, p = 0.0033) due primarily to reductions in small LDL particles (-40.3%, p<0.0001); these treatment differences persisted postprandial. Fasting and postprandial oxidized fatty acids were reduced in fenofibrate-treated subjects compared to placebo (-15.3%, p = 0.0013 and 31.0%, p<0.0001, respectively), and fenofibrate therapy lowered fasting and postprandial soluble VCAM-1 (-10.9%, p = 0.0005 and -12.0%, p = 0.0001, respectively) as well as fasting and postprandial soluble ICAM-1 (-14.8%, p<0.0001 and -15.3%, p<0.0001, respectively). Reduction in VCAM-1 and ICAM-1 was correlated with reductions in fasting and postprandial large VLDL particles (p<0.0001) as well as postprandial oxidized fatty acids (p<0.0005).

Conclusions Triglyceride-lowering therapy with fenofibrate reduced fasting and postprandial free fatty acid oxidation and inflammatory responses, and these anti-atherosclerotic effects were most highly correlated with reductions in large VLDL particles.