Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: Relations with baseline lipid profiles
Journal
Atherosclerosis
Journal Volume
170
Journal Issue
2
Pages
315-323
Date Issued
2003
Author(s)
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-1β (IL-1β), 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 500mg/dl and total cholesterol levels of >200mg/dl were randomly assigned to receive either simvastatin (20mg/day) (n=35) or micronized fenofibrate (200mg/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-1β, 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 ?40mg/dl, only fenofibrate significantly improved the endothelium-dependent FMD. On the other hand, in the subgroup with HDL-C >40mg/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. ? 2003 Elsevier Ireland Ltd. All rights reserved.
SDGs
Other Subjects
C reactive protein; CD40 antigen; CD40 ligand; cholesterol; fenofibrate; high density lipoprotein cholesterol; interleukin 1beta; low density lipoprotein cholesterol; simvastatin; triacylglycerol; adult; aged; artery blood flow; artery dilatation; article; brachial artery; cholesterol blood level; clinical trial; controlled clinical trial; controlled study; correlation analysis; disease marker; double blind procedure; drug effect; drug efficacy; drug screening; endothelium; female; functional assessment; human; hyperlipidemia; inflammation; ischemic heart disease; lipid analysis; major clinical study; male; patient; priority journal; protein blood level; randomized controlled trial; triacylglycerol blood level
Type
journal article