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


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.
Rosenson
Robert S
RS
Division of Cardiovascular Medicine, University of Michigan, Domino's Farms, 24 Frank Lloyd Wright Dr., Lobby A, Ann Arbor, MI 48106-0736, USA. rrosenso@umich.edu
Wolff
David A
DA
Huskin
Anna L
AL
Helenowski
Irene B
IB
Rademaker
Alfred W
AW
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D018384:Oxidative Stress; D018579:Patient Selection; D010919:Placebos; D017698:Postmenopause; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D001055:Apolipoproteins B; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D010919:Placebos; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011345:Fenofibrate