Sex Differences in the Effects of Cadmium and Uric Acid Levels on Hypertension Risk: A Dose–Response Relationship and Synergistic Effect Study

ABSTRACT Objective This study explored the independent and synergistic effects of cadmium (Cd) and uric acid (UA) levels on hypertension risk, with a focus on sex differences. Methods Data from 8043 National Health and Nutrition Examination Survey participants were analyzed using logistic regression, restricted cubic spline (RCS), and interaction effect models. A meta‐analysis of eight studies was also conducted. Results Blood, urinary Cd, and UA levels were more strongly associated with hypertension in females than in males ( p < 0.05). Among females, blood Cd (odds ratio [OR] = 1.84, 95% confidence interval [CI]: 1.20–2.83), urinary Cd (OR = 3.38, 95% CI: 2.15–5.30), and UA levels (OR = 3.67, 95% CI: 2.47–5.45) were significantly associated with increased hypertension risk. RCS analysis showed linear dose–response relationships for blood ( P non‐linear = 0.085) and urinary Cd ( P non‐linear = 0.070) levels, whereas UA levels ( P non‐linear = 0.031) exhibited a non‐linear association with hypertension risk. Multiplicative interaction showed 176% (OR = 2.76, 95% CI: 2.00–3.80) and 370% (OR = 4.70, 95% CI: 3.49–6.33) increased hypertension risks for high blood Cd–UA and urinary Cd–UA levels, respectively. Additive interaction confirmed synergy (relative excess risk due to interaction [RERI] = 1.74, 95% CI: 0.37–3.10). The meta‐analysis using a random‐effects model confirmed that blood Cd (OR = 1.93, 95% CI: 1.28–2.93) and urinary Cd levels (OR = 1.81, 95% CI: 0.93–3.50) were significantly increased hypertension risk. Conclusions Elevated Cd and UA levels independently and synergistically increased hypertension risk, especially in females, highlighting the need for targeted prevention strategies.