Association Between Blood Cadmium Levels and Stroke Risk: A Cross-sectional Analysis of NHANES 1999-2018

Background Stroke is a leading cause of mortality and disability worldwide, with traditional risk factors explaining only 60-70% of stroke pathogenesis. The association between cadmium exposure, an emerging environmental toxin, and stroke risk remains unclear, particularly regarding the potential mediating role of inflammatory responses. This study aimed to systematically evaluate the association between blood cadmium concentrations and stroke prevalence using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Methods This cross-sectional study analyzed 10,434 participants aged ≥20 years from NHANES 1999-2018. Blood cadmium levels were measured using inductively coupled plasma mass spectrometry. Stroke prevalence was assessed through structured interviews. Multivariable logistic regression, restricted cubic splines, and mediation analysis were employed to evaluate associations and potential biological pathways. Results Among 10,434 participants, 404 (3.9%) had a history of stroke. Blood cadmium concentrations were significantly higher in stroke patients compared to non-stroke individuals (0.66±0.68 μg/L vs 0.52±0.61 μg/L, P<0.001). After adjusting for demographics, lifestyle factors, and comorbidities, each 1 μg/L increase in blood cadmium was associated with a 48.8% increased stroke risk (OR=1.488, 95% CI: 1.292-1.713, P<0.001). The highest cadmium quartile showed a 118.7% increased stroke risk compared to the lowest quartile (OR=2.187, 95% CI: 1.413-3.384, P<0.001). Mediation analysis revealed that white blood cell count mediated 11.0% of the association (95% CI: 2.1%, 19.9%), suggesting inflammatory pathways as potential mechanisms. Conclusions Blood cadmium exposure is significantly associated with increased stroke risk, with evidence of a clear dose-response relationship. Inflammatory mechanisms may partially mediate this association. These findings highlight the importance of environmental cadmium exposure as a modifiable risk factor for stroke prevention.