Association between Perfluoroalkyl and polyfluoroalkyl substances exposure and hypercholesterolemia among U.S. adults: A cross-sectional study

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent organic pollutants. Evidence supporting the association between PFAS concentrations and lipid levels has been reported; however, a comprehensive study of the intricate association between PFAS exposure and hypercholesterolemia is still lacking. We analyzed the data of 2292 adults from the 2015-2018 National Health and Nutrition Examination Survey. Multivariate logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) models were used to assess the association of single and multiple exposures to PFAS with the prevalence of hypercholesterolemia among U.S. adults. For the single PFAS exposure analysis, multivariate logistic regression analysis results showed that exposure to ln-transformed perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS) were significantly and positively associated with the prevalence of hypercholesterolemia in the overall population (odds ratio (OR)_LnPFHxS: 1.20, 95 % confidence interval [CI]: 1.05-1.36; OR_LnPFOA: 1.21, 95 % CI: 1.03-1.41; OR_LnPFOS: 1.18, 95 % CI: 1.03-1.34). For the PFAS mixture exposure analysis, the WQS (OR: 1.16, 95 % CI: 1.00-1.35) and Qgcomp (OR: 1.17, 95 % CI: 1.03-1.32) models consistently confirmed the positive effect of combined exposure to multiple PFAS on the prevalence of hypercholesterolemia, with LnPFHxS being the main contributor. In the BKMR model, a positive association trend was observed between mixture PFAS and hypercholesterolemia, along with interactions among PFAS. In conclusion, our study suggests that higher PFAS concentrations may increase the risk of hypercholesterolemia in U.S. adults; however, further prospective studies are required to demonstrate this.