Study On The Relationship Between Per-and Polyfluoroalkyl Substances In Serum And Cardiovascular Disease Biomarkers

Per-and polyfluoroalkyl substances(PFASs)are typical environmental endocrine disrupting compounds.Epidemiological studies have shown that human exposure to PFASs may result in adverse effects on their cardiovascular system.Cardiovascular disease(CVD)is a serious threat to human health.At present,the cardiovascular mortality rate ranks first among the total causes of death among urban and rural residents in China.However,most studies only evaluated the individual impact of a single PFAS on specific CVD biomarkers,which may lead to underestimating or overestimating the actual risk of PFASs mixtures to human health.Therefore,it is of great significance for subsequent health risk research to comprehensively evaluate the relationship between PFASs mixtures and blood CVD biomarkers through human biomonitoring and the application of mixture models.In this study,575 participants in Jinan city were recruited to investigate the internal exposure levels and distribution characteristics of legacy and novel PFASs of a general population in China.Nineteen legacy and novel PFASs in the serum samples donated by these participants were detected by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS).Most PFASs could be detected,among which perfluorooctanoic acid(PFOA),perfluorooctane sulfonic acid(PFOS),and perfluorohexane sulfonic acid(PFHxS)were the main contributors to total PFASs burden with the median concentration of 11.337 ng/mL,7.639 ng/mL and 2.602 ng/mL,respectively,followed by 6:2 chlorinated polyfluoroalkyl ether sulfonate(6:2 CI-PFESA),a typical novel PFAS,with a median concentration reaching 1.829 ng/mL.Our results suggest that it is necessary to assess human health risks induced by 6:2 Cl-PFESA exposure.The serum concentrations of most PFASs were positively correlated with each other,indicating their similar exposure source,exposure route and/or metabolic process.To some extent,serum PFASs concentrations varied by gender,age and body mass index(BMI)and they were identified as confounding factors by directed acyclic graph,which were included in subsequent multiple linear regression models and BKMR(Bayesian kernel machine regression)models for correction.The study explored the associations between serum PFASs and four CVD biomarkers including triglycerides(TG),total cholesterol(CHO),high-density lipoprotein(HDL)and lowdensity lipoprotein(LDL)by using multiple linear regression models and BKMR models.After controlling potential confounding factors such as gender,age,and BMI,the results from multiple linear regression model showed that perfluoroundecanoic acid(PFUnDA)(β=-0.42,p=0.003)was significant negatively associated with TG;PFOS(β=0.19,p=0.029)and perfluorotridecanoic acid(PFTrDA)(β=0.26,p=0.064)were positively associated with CHO;perfluorononanoic acid(PFNA)(β=-0.46,p=0.001)was negatively associated with HDL,while opposite associations were found between perfluorodecanoic acid(PFDA)(β=0.25,p=0.060)and PFTrDA(β=0.59,p=0.000)between HDL;PFOS(β=0.22,p=0.008)and perfluorobutanoic acid(PFBA)(β=0.07,p=0.083)also showed(marginal)significant positive associations with LDL.Results from BKMR modelling indicated that PFASs mixture had a positive dose-effect on CHO and LDL,and no obvious effect of PFASs mixture on TG and HDL could be detected.The main contributor of the mixture effect on TG,CHO,HDL,and LDL were PFOA,PFNA,PFUnDA,and PFTrDA,PFTrDA,PFOA,PFNA,and PFTrDA,PFOS respectively.The dose-effect curve of some PFASs on CVD biomarkers was nonlinear,and the interaction effect between PFNA and PFUnDA on TG might exist.The associations between individual PFASs and CVD biomarkers assessed by BKMR and multiple linear regression models were generally consistent,but BKMR model could solve the problem of potential multicollinearity between PFASs,could detect the nonlinear effect of PFASs,and evaluate the mixture effects of PFASs.This study is a pilot study for the follow-up study on human epidemiological study to evaluate the health risks induced by PFASs,providing data support for the environmental pollution and human exposure risk assessment of PFASs to a certain extent.Of note,CHO and LDL level increased with PFASs mixtures,and elevated CHO and LDL are well-established CVD risk factors.Thus,our results suggest that PFASs mixtures may pose adverse health effects on the human body.In addition,the adverse effect of PFAS mixtures support the viewpoint that PFASs need to be regulated as an umbrella of pollutants.