Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome.

Abstract

OBJECTIVE:

The aim of this study was to determine the effects of fenofibrate (160 mg/day) 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 (> or = 1.7 and < 6.9 mmol/l) and two or more of the Adult Treatment Panel III criteria for the metabolic syndrome were randomly assigned to fenofibrate (160 mg/day) 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) VLDL particles. The number of fasting total LDL particles was reduced in fenofibrate-treated subjects (-19.0%, P = 0.0033) primarily due to reductions in small LDL particles (-40.3%, P < 0.0001); these treatment differences persisted postprandially. Fasting and postprandial oxidized fatty acids were reduced in fenofibrate-treated subjects compared with placebo-administered subjects (-15.3%, P = 0.0013, and 31.0%, P < 0.0001, respectively), and fenofibrate therapy lowered fasting and postprandial soluble vascular cell adhesion molecule-1 (VCAM-1) (-10.9%, P = 0.0005, and -12.0%, P = 0.0001, respectively) as well as fasting and postprandial soluble intercellular adhesion molecule-1 (ICAM-1) (-14.8%, P < 0.0001, and -15.3%, P < 0.0001, respectively). Reductions in VCAM-1 and ICAM-1 were 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 antiatherosclerotic effects were most highly correlated with reductions in large VLDL particles.

• Authors: Robert S Rosenson, David A Wolff, Anna L Huskin, Irene B Helenowski, Alfred W Rademaker
• Journal: Diabetes care (Diabetes Care) Vol. 30 Issue 8 Pg. 1945-51 (Aug 2007) ISSN: 1935-5548 [Electronic] United States
• PMID: 17483155 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins B
• Blood Glucose
• Fatty Acids, Nonesterified
• Hypolipidemic Agents
• Insulin
• Lipids
• Lipoproteins
• Placebos
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Fenofibrate

Topics

• Adult
• Apolipoproteins B (blood)
• Blood Glucose (metabolism)
• Blood Pressure
• Double-Blind Method
• Fatty Acids, Nonesterified (blood)
• Female
• Fenofibrate (therapeutic use)
• Humans
• Hypertriglyceridemia (blood, complications, drug therapy)
• Hypolipidemic Agents (therapeutic use)
• Insulin (blood)
• Intercellular Adhesion Molecule-1 (blood)
• Lipids (blood)
• Lipoproteins (blood)
• Male
• Metabolic Syndrome (blood, complications, drug therapy)
• Middle Aged
• Oxidative Stress
• Patient Selection
• Placebos
• Postmenopause
• Vascular Cell Adhesion Molecule-1 (blood)