Abstract

Objective: We previously reported that serum uric acid (UA) levels might predict future BP elevation and renal complications. Obese and hypertensive individuals have frequently higher UA than lean or normotensive individuals. Furthermore, epidemiological studies demonstrated that hyperuricemia (hyperUA) is a cardiovascular risk ( i.e. coronary artery disease, myocardial infarction). The present study evaluated the effect of weight loss (WL) on serum UA levels and its mechanisms, and further compared the benefits of WL protocol on UA levels between calorie restricted diet and exercise. Methods: The 3 groups each comprised 30 obese, hypertensive men. BMI, fat-mass, waist-to-hip ratio (W/H), BP, plasma norepinephrine (NE), HOMA-IR and UA were measured every 2 weeks over 24 weeks with WL regimen. WL protocol was achieved with i) mild calorie restricted diet (1800 kcal & 8-10g NaCl/day; D) alone, ii) mild exercise (>1-hour walking, approximately 20,000 steps/day; EX), or iii) mild calorie restricted diet (1800 kcal &8-10g NaCl/day) + mild exercise (D+EX). Results: All basal parameters and prevalence of hyperUA were similar among the 3 groups (prevalence of hyperUA at entry, D 66.7%, EX 66.7%, D+EX 70.0%). At 24 weeks, the D+EX group showed a significantly higher prevalence of normotensive subjects and subjects with normal UA levels compared to the D or EX alone group (prevalence of normal UA: D+EX 80.0%, D 63.3%, EX 53.3%, D+EX vs. D, χ 2 =8.71, P<0.05, D+EX vs. EX, χ 2 =13.92, P<0.05, D vs EX, χ2=4.32, P=0.057). In the D alone group, plasma NE decreased significantly at 2 weeks, and UA decreased at 4 weeks. Significant reductions in BMI, fat-mass and BP were observed at 8 weeks, and HOMA-IR decreased at 12 weeks. In the EX alone group, significant reductions of fat-mass and HOMA-IR were observed at 4 weeks. UA and NE were significantly reduced at 8 weeks whilst decreases in BP were detected at 12 weeks. BMI and W/H were similar at 8 weeks between D alone and EX alone groups. In the D+EX group, significant reductions in UA and NE were observed at 2 weeks followed by significant decreases in BMI, fat-mass, W/H, BP and HOMA-IR at 4 weeks. The magnitudes of reductions of all parameters were greatest in the D+EX group than D or EX alone groups. Reductions in UA over 24 weeks correlated positively with decreases in total fat-mass (r=0.391, P<0.05) and plasma NE (r=0.301, P<0.05) in all subjects. Conclusions: Serum UA levels decreased significantly in all WL regimens (D, EX, D+EX), however a mild calorie restricted diet was more beneficial treatment on serum UA reduction associated with suppression on plasma NE than exercise. Serum UA reduction with WL regimen were observed prior to significant WL or BP reduction, but synchronized with suppression on sympathetic nervous activity. In conclusion, WL is a beneficial treatment for UA reduction in obese hypertensive patients.

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