Heavy metal exposure and risk of all-cause and cardiovascular mortality in population with cardiovascular-kidney-metabolic syndrome stage 0–3: a cohort study

BACKGROUND: Evidence on the association between blood metal exposure and mortality among adults with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 remains limited. We examined the associations of blood lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), and manganese (Mn) with all-cause and cardiovascular mortality in this population. METHODS: We analyzed data from 4,394 adults with CKM stages 0-3 from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 linked to mortality records. Blood metal concentrations were measured using inductively coupled plasma mass spectrometry. Weighted Cox proportional hazards models, restricted cubic spline (RCS) analyses, and weighted quantile sum (WQS) regression were used to assess associations of individual and mixed metal exposures with mortality outcomes. RESULTS: In the fully adjusted model, elevated blood Cd levels were associated with a higher risk of all-cause mortality (HR = 1.71, 95% CI: 1.26-2.33). In contrast, blood Se showed an inverse association with all-cause mortality, with lower risks observed in Q2 (HR = 0.61, 95% CI: 0.41-0.90) and Q4 (HR = 0.59, 95% CI: 0.38-0.93). RCS analyses showed nonlinear associations of Cd and Se with all-cause mortality. Cd exhibited an inverted U-shaped pattern, whereas Se showed an L-shaped inverse association. WQS regression suggested a positive association between mixed metal exposure and all-cause mortality (HR = 1.16, 95% CI: 0.99-1.34; P = 0.046). Associations with cardiovascular mortality were weaker and less consistent. CONCLUSIONS: Among U.S. adults with stage 0-3 cardiovascular-kidney-metabolic syndrome, elevated blood cadmium levels and reduced blood selenium levels were potentially associated with a higher risk of all-cause mortality.