Literature DB >> 17483155

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

Robert S Rosenson1, David A Wolff, Anna L Huskin, Irene B Helenowski, Alfred W Rademaker.   

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.

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Year:  2007        PMID: 17483155     DOI: 10.2337/dc07-0015

Source DB:  PubMed          Journal:  Diabetes Care        ISSN: 0149-5992            Impact factor:   19.112


  38 in total

1.  Triglycerides and cardiovascular events in ACS: the need for combined lipid-altering therapies.

Authors:  Robert S Rosenson; Bertram Pitt
Journal:  Nat Clin Pract Cardiovasc Med       Date:  2008-12-17

2.  A treasure of pharmacogenomic insights into postprandial lipoproteinemia and therapeutic responses to fibrate therapy: lessons from GOLDN.

Authors:  Robert S Rosenson
Journal:  Curr Atheroscler Rep       Date:  2009-05       Impact factor: 5.113

3.  Dyslipidaemia: Small triumph for fenofibrate therapy in dyslipidaemia.

Authors:  Robert S Rosenson
Journal:  Nat Rev Cardiol       Date:  2017-02-02       Impact factor: 32.419

Review 4.  Fenofibrate: a review of its use in dyslipidaemia.

Authors:  Kate McKeage; Gillian M Keating
Journal:  Drugs       Date:  2011-10-01       Impact factor: 9.546

5.  AVE8134, a novel potent PPARα agonist, improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats.

Authors:  Hans Ludwig Schäfer; Wolfgang Linz; Eugen Falk; Maike Glien; Heiner Glombik; Marcus Korn; Wolfgang Wendler; Andreas W Herling; Hartmut Rütten
Journal:  Acta Pharmacol Sin       Date:  2012-01       Impact factor: 6.150

Review 6.  PPARalpha: an emerging therapeutic target in diabetic microvascular damage.

Authors:  Anne Hiukka; Marianna Maranghi; Niina Matikainen; Marja-Riitta Taskinen
Journal:  Nat Rev Endocrinol       Date:  2010-06-22       Impact factor: 43.330

7.  Fenofibrate attenuates impaired ischemic preconditioning-mediated cardioprotection in the fructose-fed hypertriglyceridemic rat heart.

Authors:  Lalita Babbar; Nanjaian Mahadevan; Pitchai Balakumar
Journal:  Naunyn Schmiedebergs Arch Pharmacol       Date:  2013-01-17       Impact factor: 3.000

8.  Association of common C-reactive protein (CRP) gene polymorphisms with baseline plasma CRP levels and fenofibrate response: the GOLDN study.

Authors:  Jian Shen; Donna K Arnett; Laurence D Parnell; James M Peacock; Chao-Qiang Lai; James E Hixson; Michael Y Tsai; Michael A Province; Robert J Straka; Jose M Ordovas
Journal:  Diabetes Care       Date:  2008-02-19       Impact factor: 19.112

Review 9.  Does the addition of fibrates to statin therapy have a favorable risk to benefit ratio?

Authors:  Eliot A Brinton
Journal:  Curr Atheroscler Rep       Date:  2008-02       Impact factor: 5.113

10.  Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

Authors:  Russell Scott; Richard O'Brien; Greg Fulcher; Chris Pardy; Michael D'Emden; Dana Tse; Marja-Riitta Taskinen; Christian Ehnholm; Anthony Keech
Journal:  Diabetes Care       Date:  2008-11-04       Impact factor: 19.112

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