title: 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.
  
  
  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.affiliation: 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
authors.forename: Robert S
authors.initials: RS
authors.lastname: Rosenson
authors.forename: David A
authors.initials: DA
authors.lastname: Wolff
authors.forename: Anna L
authors.initials: AL
authors.lastname: Huskin
authors.forename: Irene B
authors.initials: IB
authors.lastname: Helenowski
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Rademaker
mesh_terms: 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
chemical_list: 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