Association of perfluoroalkyl substances (PFAS) with lipid trajectories in midlife women: the Study of Women's Health Across the Nation

Abstract

BACKGROUND AND AIM: Despite lipid-lowering effects of perfluoroalkyl substances (PFAS) observed in rodent models, PFAS have been associated with unfavorable blood lipid profiles in human populations. However, evidence from longitudinal studies in the general population is limited. We examined the association of serum concentrations of PFAS with longitudinal trajectories of blood lipids in the Study of Women's Health Across the Nation. METHODS: We included 1143 women aged 45-56 years in 1999-2000. Concentrations of PFAS including linear and branched perfluorooctane sulfonic acid (n-PFOS and Sm-PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) were measured in serum collected at baseline. Total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides were measured in blood annually or biannually during follow-up through 2016. Using latent class growth models (LCGMs), trajectories of each lipid were estimated based on the population data. The associations between PFAS and lipid trajectory classes were evaluated by multinomial log-linear models with latent class membership as outcomes and log-transformed PFAS as exposure. RESULTS: Three distinct lipid trajectories (low, medium, and high trajectories) were identified. After adjustment for covariates, n-PFOS and Sm-PFOS were positively associated with higher LDL cholesterol [ORs (95% CI) for high vs. low trajectory per doubling of each PFAS: 1.28 (1.04, 1.56) and 1.24 (1.04, 1.48), respectively]. N-PFOS, n-PFOA, PFNA, and PFHxS were inversely associated with higher triglycerides [ORs (95% CIs) for high vs. low trajectory per doubling of each PFAS: 0.72 (0.55, 0.94), 0.65 (0.50, 0.84), 0.78 (0.62, 1.00), and 0.76 (0.62, 0.93), respectively]. The associations of PFAS with total or HDL cholesterol were insignificant. CONCLUSIONS: Higher serum concentrations of selected PFAS were associated with a higher trajectory of LDL cholesterol and a lower trajectory of triglycerides. Further studies on the underlying mechanisms of the findings are warranted. KEYWORDS: PFAS, dyslipidemia, midlife women