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

Ruiqi Yang; Yiling Chen; Xu Hui; Xin Fan; Xiaonan Li; Weize Kong; Qian Liu; Yizhuo Chen; Kaiwen Wang; Xinyi Li; Peijing Yan; Jinhui Tian; Yongbin Lu

doi:10.1111/jebm.70049

Journal of Evidence-Based Medicine ›› 2025, Vol. 18 ›› Issue (2) : e70049 DOI: 10.1111/jebm.70049

ARTICLE

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

Ruiqi Yang ¹^,²^,³
, Yiling Chen ⁴
, Xu Hui ¹^,²^,³
, Xin Fan ⁴
, Xiaonan Li ⁴
, Weize Kong ¹^,²^,³
, Qian Liu ¹^,²^,³
, Yizhuo Chen ⁵
, Kaiwen Wang ¹^,⁴
, Xinyi Li ¹^,⁴
, Peijing Yan ⁶
, Jinhui Tian ¹^,²^,³
, Yongbin Lu ¹^,²^,³

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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.

Keywords

cadmium / dose–response relationship / hypertension / synergistic effect / uric acid

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Ruiqi Yang, Yiling Chen, Xu Hui, Xin Fan, Xiaonan Li, Weize Kong, Qian Liu, Yizhuo Chen, Kaiwen Wang, Xinyi Li, Peijing Yan, Jinhui Tian, Yongbin Lu. Sex Differences in the Effects of Cadmium and Uric Acid Levels on Hypertension Risk: A Dose–Response Relationship and Synergistic Effect Study. Journal of Evidence-Based Medicine, 2025, 18(2): e70049 DOI:10.1111/jebm.70049