Longitudinal association of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) exposure with lipid traits, in a healthy unselected population.

Background: Perfluorooctanoic acid (PFOA) and Perfluorooctanesulfonic Acid (PFOS) are synthetic substances with long half-lives. Their presence is widespread and pervasive, and they are noted for their environmental persistence. Research has shown these chemicals to be associated with dyslipidaemia, although few studies have considered the long-term associations in the general population.

Objectives: The aim of this study was to consider the longitudinal and cross-sectional associations with lipid phenotypes.

Methods: We investigated the association of these chemicals with total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and the total cholesterol: high-density lipoprotein ratio (TC:HDL), in a healthy unselected British population of twins (n = 2069), measured at three timepoints between 1996 and 2014.

Results: Serum levels of PFOA and PFOS decreased over time during this period. We demonstrate longitudinal associations across serum levels of both PFOA and PFOS, finding positive associations with TC (PFOA:β = 0.51, p = 1.9e-07; PFOS:β = 0.24, p = 3.8e-05) and LDL (PFOA:β = 0.61, p = 1.7e-11; PFOS:β = 0.42, p = 1.6e-14), and consistent negative associations with HDL and PFOA (β = -0.12, p = 0.003) and PFOS (β = -0.25, p = <2e-16). We also observe cross-sectional associations of PFAS with lipids across all three timepoints.

Impact: PFAS remain persistent in the environment, despite regulations, due to their structural properties, leaving humans open to exposure. There is less understanding of how chronic low exposure to these chemicals, particularly within an unselected population, may impact health outcomes. This study reports the longitudinal associations of PFOA and PFOS over an 18-year window with 5 lipid phenotypes, highlighting that despite falling serum levels, PFAS exposure may lead to hyperlipidaemia. We further investigate the cross-sectional associations across three timepoints to understand time-dependent effects, demonstrating associations persist. This work aids our understanding on the long-term effect of chronic PFAS exposure.