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.