Mediating effects of insulin resistance on the development of hypertension associated with elevated serum uric acid: a prospective cohort study

Many studies have demonstrated that elevated serum uric acid independently increases the risk of developing hypertension. However, the role of insulin resistance in the relationship between serum uric acid and hypertension is still unelucidated. Based on a prospective cohort study, we aimed to examine the longitudinal link between serum uric acid and hypertension and whether this relationship was mediated by insulin resistance. Overall, 21,999 participants without hypertension or gout at baseline with a mean age of 46 ± 13 years in the Jinchang Cohort were included in our study. Adjusted Cox-regression analyses and mediation analyses were performed to assess the risk of hypertension by serum uric acid quartile distribution and whether insulin resistance mediated the association between serum uric acid and hypertension. During the first follow-up period, 3080 participants developed hypertension. After controlling for covariates, compared with the lowest quartile of serum uric acid, the risk of hypertension in the highest quartile was 1.21 (1.06, 1.38) in the overall population. The risks for males and females were 1.14 (1.00–1.29) and 1.30 (1.08–1.56), respectively. The correlation between serum uric acid and hypertension was especially observed in younger people (<30 years). The mediating effects of insulin resistance were 0.058 (0.051, 0.065), 0.030 (0.025, 0.036) and 0.056 (0.047, 0.065), and the proportions mediated were 39.73, 36.59 and 38.62% in the overall, male and female populations, respectively. Elevated serum uric acid levels are associated with an increased risk of incident hypertension, and insulin resistance may play a mediating role in the relationship between serum uric acid and hypertension.