Dyslipidemia contributes to endothelial dysfunction and cardiovascular disease (CVD) in type 2 diabetes mellitus. While statin therapy reduces CVD in these patients, residual risk remains high. Fenofibrate corrects atherogenic dyslipidemia, but it is unclear whether adding fenofibrate to statin therapy lowers CVD risk. We investigated whether fenofibrate improves endothelial dysfunction in statin-treated type 2 diabetic patients. In a crossover study, 15 statin-treated type 2 diabetic patients, with LDL-cholesterol <2.6mmol/L and endothelial dysfunction (brachial artery flow-mediated dilatation (FMD) <6.0%), were randomized, double-blind, to fenofibrate 145mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment periods. Brachial artery FMD and endothelium-independent nitrate-mediated dilatation (NMD) were measured by ultrasonography at the start and end of each treatment period. Post-ischaemic forearm blood flow (PIFBF), a measure of microcirculatory endothelial function, and serum lipids, lipoproteins and apolipoprotein concentrations were also measured. Compared with placebo, fenofibrate increased FMD (mean absolute 2.1±0.6 vs -0.3±0.6%, p=0.04), but did not alter NMD (p=0.75). Fenofibrate also increased maximal PIFBF (median 3.5 (IQR 5.8) vs 0.3 (2.1) ml/100ml/min, p=0.001) and flow debt repayment (median 1.0 (IQR 3.5) vs -1.5 (3.0) ml/100ml, p=0.01). Fenofibrate lowered serum cholesterol, triglycerides, LDL-cholesterol, apolipoprotein (apo) B-100 and apoC-III (p≤0.03), but did not alter HDL-cholesterol or apoA-I. Improvement in FMD was inversely associated with on-treatment LDL-cholesterol (r=-0.61, p=0.02) and apoB-100 (r=-0.54, p=0.04) concentrations. Fenofibrate improves endothelial dysfunction in statin-treated type 2 diabetic patients. This may relate partly to enhanced reduction in LDL-cholesterol and apoB-100 concentrations.
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Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated type 2 diabetic patients
Argent
Tags: and-endothelial, brachial-artery, crossover-study, were-randomized
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