Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome
- Robert S. Rosenson, MD1,
- David A. Wolff, MS2,
- Anna L. Huskin, RN, BSN2,
- Irene B. Helenowski, MS3 and
- Alfred W. Rademaker, PHD3
- 1Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan
- 2Lipoprotein and Hemorheology Research Facility, Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- 3Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Address correspondence and reprint requests to Robert S. Rosenson, MD, Division of Cardiovascular Medicine, University of Michigan, Domino's Farms, 24 Frank Lloyd Wright Dr., Lobby A, Ann Arbor, MI 48106-0736. E-mail: rrosenso{at}umich.edu
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 (≥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.
- apoB, apolipoprotein B
- AUC, area under the curve
- CHD, coronary heart disease
- ICAM-1, intercellular adhesion molecule-1
- IDL, intermediate-density lipoprotein
- NF-κB, nuclear factor- κB
- NMR, nuclear magnetic resonance
- OH-FA, monohydroxy fatty acid
- oxLDL, oxidized LDL
- VA-HIT, Veterans Administration HDL Intervention Trial
- VCAM-1, vascular cell adhesion molecule-1
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 4 May 2007. DOI: 10.2337/dc07-0015.
R.S.R. has received honoraria from and has served on a speaker's bureau for Abbott Laboratories, Inc., and has received honoraria from and served on a consultant/advisory board for LipoScience, Inc.
The authors had full access to the data and take responsibility for its integrity. All authors have read and agree to the manuscript as written. Statisticians (I.B.H. and A.W.R.) employed by Northwestern University performed the statistical analysis based on specific requests of the investigators. Final data were made available to the authors who, independent of the sponsor, assessed the data analysis as well as the interpretation and writing of the results.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0015.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted April 26, 2007.
- Received January 17, 2007.
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