Synergistic effects of cadmium exposure and hypertension on all-cause and cardiovascular mortality in individuals with prediabetes

Environmental factors play a critical role in the pathogenesis of abnormal blood glucose and its complications. However, research on the relationship between environmental factors, blood glucose, and mortality is limited. Using NHANES (1999-2018) data, we analyzed the association between serum Cd concentrations and all-cause and cardiovascular disease (CVD) mortality in abnormal blood glucose individuals through multivariate weighted Cox proportional hazards models. Dose-response relationships were assessed using restricted cubic splines, and interaction effects between Cd exposure and other factors were also explored. Among 11,836 participants, 2379 deaths occurred. After full adjustment, high Cd concentrations significantly increased all-cause (HR=1.55, 95 % CI: 1.26-1.91) and CVD mortality (HR=1.58, 95 % CI: 1.12-2.21) in individuals with abnormal blood glucose. Cd exhibited a nonlinear positive association with all-cause mortality (P_nonlinear=0.011) and a linear association with CVD mortality (P_nonlinear=0.224). Stratified analysis showed a stronger association in prediabetes (pre-DM) than diabetes mellitus (DM) (P_{for interaction}<0.001 for all-cause mortality, P_{for interaction}=0.026 for CVD mortality). A threshold effect was observed at 0.62 µg/L in pre-DM population, above which the risk of all-cause mortality increased markedly. Moreover, high Cd and hypertension exhibited a significant synergistic effect on all-cause mortality (P_{for interaction}=0.047). Cd concentration is positively associated with mortality in individuals with abnormal blood glucose, particularly in the pre-DM population. These findings suggest that monitoring environmental pollutants such as Cd in the pre-DM population is crucial. Additionally, controlling blood glucose and blood pressure in populations with occupational exposure to heavy metals, such as Cd, is emphasized as an important public health measure.