Associations between Mixture of Perfluoroalkyl Substances and Lipid Profile in a Highly Exposed Adult Community in the Veneto Region

Abstract

Background: Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters. Methods: Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20–64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals. Results: We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 4.09, 95% CI: 3.47–4.71), HDL-C (β: 1.13, 95% CI: 0.92–1.33) and LDL-C (β: 3.14, 95% CI: 2.65–3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (ψ: 4.04, 95% CI 3.5–4.58), HDL-C (ψ: 1.07, 95% CI 20.87–1.27) and LDL-C (ψ: 2.71, 95% CI 2.23–3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender. Conclusions: The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS.

Assessing the performance of a targeted absolute quantification isotope dilution liquid chromatograhy tandem mass spectrometry assay versus a commercial nontargeted relative quantification assay for detection of three major perfluoroalkyls in human blood

“…An additional method for assessing two measurement techniques involves examining their relationship to a common third variable. In our study, we opted to use cholesterol levels, as prior research has established connections between at least PFOS and PFOA levels and cholesterol levels 17–20 . The evaluation of both abundances from nontargeted analysis and concentrations from conventional assays in relation to cholesterol yielded strikingly similar Speakmans' rho values.…”

“…Thus, the main aim of the current study is to compare absolute plasma concentrations of PFAS obtained by protein precipitation and matrix matched calibration isotope dilution UHPLC–MS/MS with semiquantitative relative concentration measurements performed on the same plasma samples using a widely used commercial nontargeted platform. Further, numerous prior studies have reported an association between perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) concentrations and cholesterol levels 17–21 . Therefore, we aimed to compare the relationship of PFOA and PFOS obtained from these two assays with total cholesterol levels.…”

“…Further, numerous prior studies have reported an association between perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) concentrations and cholesterol levels. [17][18][19][20][21] Therefore, we aimed to compare the relationship of PFOA and PFOS obtained from these two assays with total cholesterol levels.…”

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk

“…Chen et al, 2020 53 (Continued ) 81,[100][101][102] In the large studies, total serum PFAS and individual PFAS (PFOA, PFHxS, and PFOS) also were found to be associated with higher HDL-C, but in the small studies, PFOA was reported to be associated with lower HDL-C concentrations in exposed versus control participants or not associated with HDL-C. 81,[100][101][102] Total serum PFASs were not found to be associated with serum triglycerides, but PFOA and PFHxS (not PFNA or PFOS) were reported to be linked with increased serum triglycerides. 81,[100][101][102] Analysis of participants from a contaminated community in Sweden (3760 participants) also reported associations between PFOA, PFHxS, and PFOS and higher total cholesterol, LDL-C, and HDL-C. 103 Null associations were reported for PFAS and triglycerides. 103 Cross-sectional studies in North America have analyzed associations between PFAS and serum lipids in the general population and contaminated communities.…”

“…Cross-sectional studies in multiple countries have investigated associations between PFAS and serum lipids with strong associations in contaminated communities in Europe, North America, Asia, and Australia. Cross-sectional analyses (from small [97 participants] to large [34 633 participants]) in the contaminated area of the Veneto Region (Italy) consistently demonstrated that total serum PFAS and individual PFAS (PFOA, PFNA, PFHxS, and PFOS) are associated with higher total serum cholesterol and LDL-C. 81,100–102 In the large studies, total serum PFAS and individual PFAS (PFOA, PFHxS, and PFOS) also were found to be associated with higher HDL-C, but in the small studies, PFOA was reported to be associated with lower HDL-C concentrations in exposed versus control participants or not associated with HDL-C. 81,100–102 Total serum PFASs were not found to be associated with serum triglycerides, but PFOA and PFHxS (not PFNA or PFOS) were reported to be linked with increased serum triglycerides. 81,100–102 Analysis of participants from a contaminated community in Sweden (3760 participants) also reported associations between PFOA, PFHxS, and PFOS and higher total cholesterol, LDL-C, and HDL-C. 103 Null associations were reported for PFAS and triglycerides.…”