Supplementary Material for: Association of Persistent Organic Pollutants Polychlorinated Biphenyls and Dioxins with Cardiovascular-Kidney-Metabolic Syndrome and Its Prognosis: A Nationally Representative Study

Background: Persistent organic pollutants (POPs) may be risk factors for the development and progression of cardiovascular-kidney-metabolic (CKM) syndrome. This study aimed to evaluate the effects of polychlorinated biphenyls (PCBs) and dioxins on CKM syndrome, as well as the mediating role of inflammatory cells in these associations.
Methods: Data on PCB and dioxin-like compound exposure and CKM syndrome were obtained from the National Health and Nutrition Examination Survey 2005-2012. We applied multivariable logistic regression, weighted quantile sum regression, quantile g-computation, and subgroup analyses to assess the individual and combined health effects of PCBs and dioxin-like compounds on CKM syndrome. Mediation analyses evaluated the role of inflammatory cells in the relationship between these pollutants and CKM syndrome. Cox proportional hazards regression was performed to explore the impact of PCB and dioxin exposure on mortality risk among patients at different CKM syndrome stages.
Results: Exposure to PCB138, PCB153, PCB180, 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (hexa-CDDs), and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDDs) was associated with increased risk of advanced CKM syndrome by approximately 4%, 3%, 3%, ,3% and 2%, respectively. In the mixture effect analysis, a combination of PCBs and dioxins was found to synergistically increase the risk of advanced CKM syndrome. Weighted quantile sum regression identified 1,2,3,4,6,7,8-heptachlorodibenzofuran (HXCDF) as the most significant contributor to this increased risk. Furthermore, white blood cells, lymphocytes and neutrophils mediated the associations between PCBs, dioxin-like compounds, and advanced CKM syndrome, with mediation proportions ranging from 1.77% to 3.95%. Exposure to PCBs (except HXCDF) and dioxins was associated with increased mortality risk in CKM stage 0-2 patients, while exposure to hexa-CDDs was associated with increased all-cause mortality risk in CKM stage 3-4 patients.
Conclusion: Exposure to PCBs and dioxin-like compounds increases the risk of advanced CKM syndrome and mortality across different CKM syndrome stages. Inflammatory cells play a mediating role in the relationship between these pollutants and advanced CKM syndrome.