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Sex‐Specific Cross‐Sectional Associations and Exploratory Mediation Analysis of Cardiovascular Disease Risk by Neutrophil‐to‐Lymphocyte Ratio in Cadmium‐Exposed Populations

Year: 2026

Type: article

Abstract: Background Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with its burden continuing to rise. Environmental cadmium (Cd) exposure has emerged as a potential risk factor for CVD. This study aimed to investigate the associations between Cd exposure and CVD risk, and to explore cross‐sectional associations and a potential inflammatory pathway using exploratory mediation analysis. Methods This study utilized data from the National Health and Nutrition Examination Survey. Logistic regression models were used to identify factors influencing CVD risk. Dose–response relationships were evaluated using restricted cubic splines (RCS). Exploratory mediation analysis was conducted to assess the potential mediating role of NLR in the association between Cd exposure and CVD risk. Results Individuals with CVD had significantly higher levels of blood Cd, urinary Cd, and NLR than controls ( p < 0.05) in both sexes. In males, the highest quartile (Q4) of blood Cd (OR = 3.06, 95% CI: 1.45‐6.46, p = 0.004) and urinary Cd (OR = 3.02, 95% CI: 1.52–6.02, p = 0.002) were significantly associated with higher CVD prevalence. Conversely, no significant association was observed in females for blood Cd ( p = 0.505), and the association for urinary Cd ( p = 0.046) was notably weaker and less robust than that in males. Interaction analyses confirmed sex‐specific differences (p‐interaction < 0.05). NLR showed significant exploratory mediating effects (indirect effects), accounting for 9.4% (95% CI: 3.5%–15.2%) of the blood Cd–CVD link and 5.0% (95% CI: 1.9%–8.1%) of the urinary Cd–CVD link in males. Similar significant mediation was observed in the general population for blood Cd: 7.2% (95% CI: 2.2%–12.2%), and for urinary Cd: 6.4% (95% CI: 2.8%–10.0%). Conclusions This cross‐sectional study identified significant sex‐specific and dose‐dependent associations between Cd exposure and CVD risk. Inflammatory responses, particularly those reflected by elevated NLR, were cross‐sectionally associated with the observed Cd–CVD link, suggesting a potential pathway that warrants prospective validation, especially in males.

Source: Cardiology Research and Practice

DOI: 10.1155/crp/3957573