The associations between perfluoroalkyl substances and lipid profile in an exposed young adult population in the Veneto Region

Abstract

Background Residents of a large area of the Veneto Region (North-Eastern Italy) were exposed for decades to drinking water contaminated by perfluoroalkyl substances (PFASs). PFASs have been consistently associated with raised serum lipids, mainly in cross-sectional studies and in background exposure contexts, but the shape of the dose-response relationships has been poorly investigated. The objectives of our study were to evaluate the association between serum PFASs and serum lipids and its dose-response shape in a large exposed population.Methods A cross-sectional study was conducted in 16,224 individuals aged 20-39 years recruited in the Regional health surveillance program. 15,720 subjects were analysed after excluding pregnant women (n=327), participants reporting use of cholesterol lowering medications (n=67) or with missing information on the selected covariates (n=110). Twelve serum PFASs were measured by by HPLC-MS; three (PFOA, PFOS and PFHxS) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides were measured by enzymatic assays in automated analysers and low-density lipoprotein cholesterol (LDL-C), non-HDL cholesterol and total/HDL cholesterol ratio were calculated. The associations between ln-transformed PFASs and lipids were assessed through generalized additive models using smoothing thin plate splines. Potential confounders of the lipid/PFAS association were selected through directed acyclic graph.Results There were highly significant positive associations between the ln of PFOA, PFOS, and PFHxS and TC, HDL-C, and LDL-C. Significant but nonlinear association between ln PFOA and triglycerides was seen. Each ln-increase in PFOA was associated with an increase of 1.94 mg/dL (95% CI 1.48-2.41) in TC, with 4.99 mg/dL (CI 4.12-5.86) for PFOS and 2.02 mg/dL (CI 1.45-2.58) for PFHxS.Conclusions Investigations of the shape of exposure-response associations using smoothing splines show a positive non-linear association with the largest increases in cholesterol levels occurring at the lowest range of PFAS concentrations.