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.

Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors

Cardiovascular diseases(CVDs)remain the leading cause of morbidity and mortality worldwide.Recently,accumulating evidence has revealed hepatic mediators,termed as liverderived secretory factors(LDSFs),play an important role in regulating CVDs such as atherosclerosis,coronary artery disease,thrombosis,myocardial infarction,heart failure,metabolic cardiomyopathy,arterial hypertension,and pulmonary hypertension.LDSFs presented here consisted of microbial metabolite,extracellular vesicles,proteins,and microRNA,they are primarily or exclusively synthesized and released by the liver,and have been shown to exert pleiotropic actions on cardiovascular system.LDSFs mainly target vascular endothelial cell,vascular smooth muscle cells,cardiomyocytes,fibroblasts,macrophages and platelets,and further modulate endothelial nitric oxide synthase/nitric oxide,endothelial function,energy metabolism,inflammation,oxidative stress,and dystrophic calcification.Although some LDSFs are known to be detrimental/beneficial,controversial findings were also reported for many.Therefore,more studies are required to further explore the causal relationships between LDSFs and CVDs and uncover the exact mechanisms,which is expected to extend our understanding of the crosstalk between the liver and cardiovascular system and identify potential therapeutic targets.Furthermore,in the case of patients with liver disease,awareness should be given to the implications of these abnormalities in the cardiovascular system.These studies also underline the importance of early recognition and intervention of liver abnormalities in the practice of cardiovascular care,and a multidisciplinary approach combining hepatologists and cardiologists would be more preferable for such patients.