Mediation of the effect of serum uric acid on the risk of developing hypertension: A population-based cohort study

Abstract

Background: Serum uric acid (SUA) had been associated with incident hypertension, but it is uncertain whether and to what extent the effect of SUA is mediated by other metabolic factors. Methods: Data from the China Health and Retirement Longitudinal Study (CHARLS) during 2011 to 2015 was employed for this study. A total of 7639 participants aged between 35 and 96 years without hypertension was included. Cox proportional hazards model was used to investigate the association between elevated SUA and hypertension. A mediation model was used to separately explore mediating effects (MEs) of metabolic factors on the association between SUA and incident hypertension. Results: During a median 4.0 years of follow-up, 2348 individuals were diagnosed with hypertension. After adjustment for metabolic confounders, participants with the highest SUA quartile had a hazard ratio of 1.16 (1.02-1.33) compared with the lowest category for incident hypertension. The association between SUA and incident hypertension were partially mediated by waist circumference (WC; ME = 0.034), body mass index (BMI; ME = 0.016), triglycerides (TG; ME = 0.024), total cholesterol (TC; ME = 0.009), high density lipoprotein cholesterol (HDL-C; ME = 0.009), fasting plasma glucose (FPG; ME = 0.005), and glycated hemoglobin (HbA1c; ME = - 0.002). Additionally, proportional mediation was 32.7% by WC and 15.4% by BMI for obesity indicators; 23.1% by TG, 8.7% by TC, and 8.7% by HDL-C for blood lipid; and 4.8% by FPG and - 1.9% by HbA1c for blood glucose. Conclusions: The positive association between elevated SUA concentration and hypertension was reconfirmed in a Chinese population. Obesity indicators, blood lipids, and blood glucose may play important mediating roles in the pathways.