Cited by 125Lipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular DiseasesCholesterol and Lipid Metabolism

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Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles

Wang, Tzung-Dau, Chen, Wen-Jone, Lin, Jong-Wei, Cheng, Ching-Chih, Chen, Ming-Fong, Lee, Yuan-Teh·2003·Atherosclerosis

DOI 10.1016/s0021-9150(03)00296-x

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Abstract

Given that combination therapy with statin plus fibrate confers a risk of myopathy, it is worthwhile to determine whether statin or fibrate monotherapy is associated with greater clinical benefit in individuals with combined hyperlipidemia. In this randomized double-blind study, we compared the efficacy of simvastatin and fenofibrate on indexes of endothelial function (flow-mediated dilation (FMD) of the brachial artery) and inflammatory markers (plasma high-sensitivity C-reactive protein (CRP), interleukin-1 beta (IL-1 beta), soluble CD40, and soluble CD40 ligand (sCD40L) levels), as surrogate indicators of future coronary heart disease (CHD), in patients with combined hyperlipidemia. A total of 70 patients with plasma triglyceride levels between 200 and 500 mg/dl and total cholesterol levels of >200 mg/dl were randomly assigned to receive either simvastatin (20 mg/day) (n=35) or micronized fenofibrate (200 mg/day) (n=35) for 8 weeks. Treatment with simvastatin was associated with significantly greater reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), while the decrease in triglycerides was significantly greater in patients receiving fenofibrate. Both fenofibrate and simvastatin markedly reduced plasma levels of high-sensitivity CRP, IL-1 beta, and sCD40L, and improved endothelium-dependent FMD without mutual differences. The changes in plasma inflammatory markers did not correlate with baseline clinical characteristics in both groups. However, the improvement in FMD with fenofibrate treatment correlated inversely with baseline high-density lipoprotein cholesterol (HDL-C) levels, whereas the improvement in FMD with simvastatin treatment was positively related to HDL-C levels. Accordingly, in the subgroup with a baseline HDL-C of < or =40 mg/dl, only fenofibrate significantly improved the endothelium-dependent FMD. On the other hand, in the subgroup with HDL-C >40 mg/dl, only treatment with simvastatin achieved significant improvement in FMD. The data here indicate that in patients with combined hyperlipidemia, both fenofibrate and simvastatin have comparative beneficial effects on various inflammatory markers and differential beneficial effects on endothelial function according to baseline HDL-C levels. These findings should be validated by additional prospective studies, in which patients are stratified by baseline HDL-C prior to randomization.

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Authors: Wang, T.-D., Chen, W.-J., Lin, J.-W., Cheng, C.-C., Chen, M.-F., & Lee, Y.-T.
Affiliations: National Taiwan University (TW)
National Taiwan University Hospital (TW)
Corresponding author: Lee, Yuan-Teh
ORCID: Wang, Tzung-Dau
Chen, Wen-Jone
Venue: Atherosclerosis
Publisher: Elsevier BV
Published: 2003-10
Volume: 170
Issue: 2
Pages: 315-323
ISSN: 0021-9150 (ISSN-L)
DOI: 10.1016/s0021-9150(03)00296-x
OpenAlex: W2083042102
Cited by: 125
References: 39
Citations by year: 2026: 1 · 2024: 1 · 2023: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 3
FWCI: 16.20
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Atherosclerosis (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords: mixed dyslipidemia, fenofibrate, simvastatin, statin-fibrate combination therapy, endothelial function, flow-mediated dilation, inflammatory markers, high-sensitivity C-reactive protein, IL-1β, soluble CD40 ligand, HDL cholesterol, triglycerides, LDL cholesterol, coronary heart disease risk, statin-induced myopathy
MeSH terms: Hypolipidemic Agents, C-Reactive Protein, Double-Blind Method, Drug Therapy, Combination, Endothelium, Vascular, Female, Humans, Hyperemia, Hyperlipidemia, Familial Combined, Interleukin-1, Lipids, Male, Middle Aged, Fenofibrate, Vasodilation, Inflammation Mediators, CD40 Antigens, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, CD40 Ligand

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Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles

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