Mediating Role of Glucose-Lipid Metabolism in the Association between the Increased Risk of Coronary Heart Disease and Exposure to Organophosphate Esters, Phthalates, and Polycyclic Aromatic Hydrocarbons.

There is a lack of human evidence concerning the cardiovascular effects of combined exposure to endocrine disruptors. This case-control study sought to investigate coronary heart disease (CHD) associations with exposure to organophosphate flame retardants (OFRs), phthalates (PAEs), and polycyclic aromatic hydrocarbons (PAHs) among 148 adults with coronary-angiography-diagnosed CHD and 320 healthy adults from southern China. The mediating role of glucose-lipid metabolism was also explored. Bayesian kernel machine regression suggested that when exposure status was fixed to the 75th percentile with the median value as the reference, exposure to OFRs, PAEs, and PAHs was associated with an 84% (95% CI: 36%-134%), 132% (12%-252%), and 214% (89%-331%) increased risk of developing CHD, respectively. Weighted quantile sum regression indicated urinary bis(2-butoxyethyl) phosphate (BBOEP), dibutyl phosphate (DBP), monoisononyl phthalate (miNP), and metabolites of phenanthrene may be major contributors to the overall effect of mixtures. In further analyses on identified chemical risk factors, mediation analyses suggested exposure to phenanthrene may increase the risk of CHD via elevating total cholesterol and blood glucose, while exposure to DiNP mainly associates with serum lipids. Besides, we observed a slight mediation effect of oxidative DNA damage between urinary BBOEP and risk of CHD. These results provide potential direction for further experimental studies. Longitudinal evidence is needed to clarify the causation of the results.