Abstract
BACKGROUND: Increasing evidence suggests a positive correlation between serum uric acid (SUA) levels and incident hypertension (IHT). However, few studies have focused on the sex-differential impact of SUA levels on IHT in populations with a normal body mass index (BMI). METHODS: This study included participants without hypertension who had a BMI in the normal range (18.5-23.9 kg/m(2)). Sex-specific quartiles of SUA levels (Q1-Q4) were defined as: ≤180, 181-213, 214-249, and >249 μmol/L for females; ≤282, 283-324, 325-373, and >373 μmol/L for males. IHT was considered present when systolic blood pressure (SBP) was ≥140 mmHg or diastolic blood pressure (DBP) was ≥90 mmHg, or antihypertensive drugs were used. Cox proportional hazards models and mediation analysis were performed to estimate hazard ratios (HRs) and potential mediators in the relationship between sex-differential SUA levels and IHT. RESULTS: This study included 24,538 participants, comprising 13,063 females and 11,475 males, with an IHT of 4.9% in females and 11.4% in males during 24 (12, 36) months. In the sex-stratified analysis, females exhibited higher unadjusted HRs for Q4 versus Q1 (HR = 3.487, 95% CI: 2.701-4.500; p < 0.001) compared to males (HR = 2.016, 95% CI: 1.719-2.365; p < 0.001). After adjustment for multiple variables, the HRs for females remained higher than those for males (2.237 [1.670-2.998] vs. 1.904 [1.601-2.265]); however, the magnitude of the difference was notably reduced. Mediation analysis indicated that the association between SUA levels and IHT was primarily driven by age (19.42%), low-density lipoprotein (LDL) cholesterol (10.90%), and triglycerides (10.46%) in females, and by BMI (9.94%), triglycerides (TG) (8.73%), serum creatinine (7.26%), and age (7.23%) in males. CONCLUSION: SUA levels among Chinese adults with a normal BMI range were positively associated with IHT, with an apparent stronger association in females than in males.