Urine cadmium and the risk of cardiovascular morbidity and mortality: results from the Chang Gung Research Database

Aims To investigate the association between urine cadmium (U-Cd) and the risk of cardiovascular morbidity and mortality in an adult population from Taiwan. Methods and results A total of 10 713 adults with data on U-Cd assessments in the Chang Gung Research Database were enrolled and stratified into quartiles according to baseline U-Cd levels. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of acute myocardial infarction (AMI), coronary intervention, ischaemic stroke, and cardiovascular mortality. Secondary outcomes included major adverse coronary events (MACE, comprising AMI and coronary intervention), ischaemic stroke, cardiovascular mortality, and all-cause mortality. The median U-Cd concentration was 1.00 μg/g creatinine. In the fully adjusted Cox proportional hazard model, individuals in the highest (4th) U-Cd quartile were associated with significantly increased risks of MACCE (HR: 1.88; 95% CI:1.20–2.95), ischaemic stroke (HR: 2.22; 95% CI: 1.07–4.61), cardiovascular mortality (HR: 2.56; 95% CI: 1.17–5.60), and all-cause mortality (HR: 1.67; 95% CI: 1.22–2.29) compared with those in the lowest (1st) U-Cd quartile. Restricted cubic spline analysis revealed a positive, non-linear relationship between continuous U-Cd levels and these outcomes, which was approximately linear up to a U-Cd concentration of around 1.3 μg/g creatinine, after which the association plateaued. No significant association was observed for MACE (HR: 1.62; 95% CI: 0.75–3.50). The association between U-Cd and MACCE was consistent across all analysed subgroups, including never-smokers, ever-smokers, and both sexes. Conclusion Cd exposure was associated with an increased risk of cardiovascular morbidity and mortality in this representative Asian population. Lay summary This study demonstrated that Cd exposure, even at relatively low levels, was significantly associated with increased risks of cardiovascular morbidity, cardiovascular mortality, and all-cause mortality. The risk increase exhibited an approximately linear relationship with U-Cd concentration up to around 1.3 μg/g creatinine, beyond which it plateaued. The increased risk of major adverse cardiovascular and cerebrovascular events associated with Cd exposure was consistent across all evaluated subgroups, including never-smokers, ever-smokers, and both sexes.