Exposure to cadmium, lead, and mercury and long-term mortality after stroke: a cohort study

BACKGROUND AND OBJECTIVE: While the neurotoxic effects of cadmium, lead, and mercury are well-documented, their associations with mortality outcomes in stroke survivors remain unclear. This study aimed to investigate the relationships between blood concentrations of these metals and mortality risk in individuals with a history of stroke. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) and National Death Index (NDI) spanning 1999-2018 were analyzed, including 765 stroke survivors. Metal levels were measured via Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and categorized into quartiles. Cox proportional hazards models evaluated associations with all-cause and cause-specific mortalities, adjusting for demographic, clinical, and lifestyle covariates in three hierarchical models. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Higher cadmium levels were significantly associated with increased all-cause mortality (fully adjusted HR, 2.02, 95%CI 1.30 to 3.16, p = 0.002). Lead demonstrated a significant association only in the highest quartile for all-cause mortality (HR 1.63, 95%CI 1.04 to 2.57, p = 0.035). Mercury exhibited protective effects against all-cause (HR 0.54, 95%CI 0.34 to 0.87, p = 0.011) and malignant neoplasm mortality (HR 0.08, 95%CI 0.02 to 0.39, p = 0.002). No significant associations were observed for cadmium or lead with cardio-cerebrovascular mortality, nor for lead with malignant neoplasm mortality. CONCLUSION: Elevated blood cadmium levels are independently associated with increased all-cause mortality in stroke survivors. Lead shows a modest association with all-cause mortality, while mercury may exert protective effects against specific mortality outcomes. Further studies are needed to confirm these findings and explore underlying mechanisms.