Effect of febuxostat on vascular endothelial function and elasticity in patients with asymptomatic hyperuricemia

Meijuan DONG; Li MAO; Huixin ZHANG; Kun AN

ABSTRACT

Objective:

To evaluate the effect of febutostat on vascular endothelial function, intima-media thickness(C-IMT) and elasticity of the carotid artery in patients with asymptomatic hyperuricemia.

Methods:

This study was a randomized controlled clinical trial that enrolled asymptomatic hyperuricemia patients from the outpatient and inpatient departments of Huai′an First People′s Hospital from October 2018 to October 2020. The participants were randomly divided into two groups the Febuxostat group and the control group. Serum triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), nitric oxide(NO), endothelin-1(ET-1), malondialdehyde(MDA), and superoxide dismutase(SOD) were measured at baseline and 1, 3, and 6 months after treatment, and brachial artery flow-mediated dilation(FMD) was quantified by color Doppler ultrasound. The following parameters of the common carotid artery were detected at baseline and 12 months after treatment C-IMT, arterial compliance(AC), one-point pulse wave velocity(PWV), stiffness index(β), and pressure-strain elasticity modulus(Ep). The differences before and after treatment and between the two groups were compared. Pearson correlation was used to analyze the correlation between ΔUA and ΔNO, ΔET-1, ΔC-IMT, ΔAC, Δβ, ΔEp, and ΔPWVβ after treatment with febuxostat.

Results:

Compared with baseline, TG, HOMA-IR, ET-1 and MDA were significantly lower, while FMD, NO and SOD were significantly higher after 3-months treatment with febuxostat. After 12-months treatment, there was no significant difference in C-IMT or Ep, but there was an increase in AC and a decrease in PWVβ or β compared with baseline. There was a negative correlation between ΔFMD and ΔUA( r=-0.403, P=0.004), but there were no correlations between ΔNO and ΔUA( r=-0.187, P=0.194), ΔET-1 and ΔUA( r=0.038, P=0.791) after 6-months treatment. And ΔUA was an independent factor for ΔFMD( F=2.94, P=0.003, adjusted R2=0.139). After 12-months treatment, there was a negative correlation between ΔAC and ΔUA, and a positive correlation between ΔPWVβ and ΔUA, but there were no correlations between the following indicators ΔC-IMT and ΔUA( r=0.169, P=0.240), Δβ and ΔUA( r=-0.214, P=0.136), ΔEp and ΔUA( r=-0.077, P=0.597). In the control group, there were no differences among the above indicators between each follow-up time and baseline.

Conclusion:

Febuxostat improves vascular endothelial function and elasticity in patients with asymptomatic hyperuricemia, which may be related to the decreased oxidative stress response.