Associations between environmental endocrine-disrupting chemicals exposure and cardiometabolic markers: integrated epidemiological and in silico analyses

Environmental endocrine-disrupting chemicals (EDCs) are increasingly implicated in cardiometabolic disorders. Conventional studies have focused on specific types of pollutants or individual cardiometabolic outcomes, failing to address the comprehensive impact of real-world exposure to a mixed EDC on cardiometabolic alterations. In this cross-sectional study of 324 Chinese adults, 91 urinary EDCs across nine classes were measured, with 75 compounds (detection frequency ≥ 50%) retained for analysis. Associations between EDC exposure and eight cardiometabolic markers, including blood pressure, glycemic, and lipid profiles, were evaluated using multivariable linear regression, weighted quantile sum regression, and advanced Bayesian kernel machine regression. Individual EDCs were associated with cardiometabolic markers, while EDC mixtures showed nominal associations with several outcomes. Stratified analyses further suggested age-related heterogeneity in the mixture associations with DBP and TG, particularly between middle-aged and young participants. To elucidate potential mechanisms, network toxicology, molecular docking, and molecular dynamics simulations were integrated. The results suggested that EDC-related cardiometabolic alterations may involve shared oxidative and inflammatory pathways, as well as chemical-specific vascular, apoptotic, and lipid metabolic processes. These findings provide human observational evidence for associations between complex EDC exposure and cardiometabolic markers and generate hypotheses for future mechanistic studies.