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

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 = 0.085) and urinary Cd (P = 0.070) levels, whereas UA levels (P = 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.