Heavy metals and mortality in cardiovascular-kidney-metabolic syndrome: Insights from the NHANES cohort

Cardiovascular-kidney-metabolic (CKM) syndrome is a high-risk condition, but the effect of environmental heavy metal exposure on long-term mortality in this population remains unclear. Data from 14,967 U.S. adults with CKM syndrome from National Health and Nutrition Examination Survey 2005 to 2018 were analyzed. Blood concentrations of cadmium, lead, mercury, manganese, and selenium were measured. Mortality outcomes were obtained from the National Death Index through 2019. Cox proportional hazards models estimated hazard ratios for all-cause and cardiovascular mortality, adjusting for demographic, behavioral, and clinical covariates. Dose-response relationships were explored using smooth curve fitting and threshold effect analyses. Elevated cadmium and lead levels were significantly associated with increased all-cause mortality (HR for cadmium: 2.60 [95% CI: 2.04-3.31] for levels <0.93 µg/L) and cardiovascular mortality (HR for cadmium: 2.14 [95% CI: 1.42-3.23] for levels <1.00 µg/L). Nonlinear associations were observed for both, with plateau effects beyond specific thresholds. Manganese and selenium exhibited U-shaped or inverse associations with mortality risk, with manganese showing a decrease in mortality risk at low levels (HR: 0.88 [95% CI: 0.78-0.98] for levels <7.13 µg/L) and an increase at higher concentrations (HR: 1.03 [95% CI: 0.98-1.07] for levels >7.13 µg/L). Sensitivity analyses confirmed the findings, and Kaplan-Meier curves indicated significant differences in survival across metal exposure tertiles. In U.S. adults with CKM syndrome, elevated cadmium and lead levels were associated with higher mortality, while manganese and selenium showed nonlinear relationships with mortality risk. These findings underscore the importance of addressing heavy metal exposure in the CKM population.