Serum uric acid and the risk of hypertension in a Middle Eastern cohort: A 10-year prospective study discovering BMI-mediated associations and gender-specific vulnerabilities

Hypertension (HTN), a modifiable cardiovascular risk factor, remains a global public health challenge. Serum uric acid (SUA) has been implicated in HTN pathogenesis, but the evidence is conflicting. This study investigated the association between SUA and 10-year HTN incidence, stratified by sex and body mass index (BMI), in a Middle Eastern cohort. A 10-year prospective cohort analysis using data from 828 adults (53.5% male) aged 20 to 74 years in Yazd, Iran, sourced from the Yazd Healthy Heart Project. Participants free of baseline HTN (defined as systolic blood pressure/diastolic blood pressure < 130/80 mm Hg, no antihypertensive use, and no prior diagnosis) were categorized into hyperuricemic (SUA > 5.5 mg/dL [males], >4.6 mg/dL [females]) and normouricemic groups. Incident HTN was defined as systolic/diastolic blood pressure ≥ 130/80 mm Hg, antihypertensive use, or medical diagnosis. Hyperuricemia was associated with a 59% higher HTN risk (odds ratio [OR] = 1.59, 95% confidence interval [CI]: 1.14-2.20), but this attenuated after BMI adjustment (OR = 1.16, 95% CI: 0.73-1.85). Stratified analyses revealed borderline associations in men (adjusted OR = 1.79, 95% CI: 1.01-3.19, P = .05) and normal-weight individuals (BMI < 25 kg/m²: OR = 2.32, 95% CI: 1.04-5.22), persisting across adjustment models. No associations were observed in the women or overweight/obese subgroups. Hyperuricemic individuals exhibited higher baseline BMI and dyslipidemia (P < .01). Elevated SUA independently predicts HTN risk in men and normal-weight individuals, suggesting context-dependent mechanisms. Adiposity mediates the population-level association, while SUA's direct vascular effects may dominate in leaner subgroups.