Associations of Serum Per- and Polyfluoroalkyl Substance Concentrations with Dyslipidemia and Its Subtypes in an Adult Population from Shandong, East China

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent environmental pollutants associated with significant health risks. While PFAS exposure has been linked to endocrine diseases, epidemiological evidence regarding its association with dyslipidemia and its subtypes remains limited. This study comprehensively evaluated the associations between serum PFAS levels and dyslipidemia (including its subtypes) in adults, while also investigating the effects on the Triglyceride-Glucose (TyG) index. We recruited a group of adult participants from Shandong Province, East China, which consisted of individuals with dyslipidemia and healthy controls. Multiple statistical approaches were applied, including multivariable logistic regression for single-PFAS associations, quantile-based g-computation (qg-comp) model for mixture effects, and restricted cubic spline (RCS) models for dose–response analyses. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonate (PFOS), and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) were significantly associated with elevated TyG index levels. Exposure to PFOA and PFNA were associated with hypertriglyceridemia (odds ratio (OR) = 1.05, 95% confidence interval (CI): 1.01–1.09; OR = 2.01, 95% CI: 1.15–3.50, respectively) and low levels of high-density lipoprotein cholesterol (OR = 1.04, 95% CI: 1.00–1.07; OR = 1.63, 95% CI: 1.01–2.94, respectively). PFOS and 6:2 Cl-PFESA were associated with an increased risk of hypercholesterolemia (OR = 1.12, 95% CI: 1.02–1.23; OR = 1.27, 95% CI: 1.05–1.54, respectively). Furthermore, significant joint effects of PFAS mixture exposure were observed on the risk of dyslipidemia, hypertriglyceridemia, and hypercholesterolemia, respectively. Dose–response analyses revealed predominantly linear relationships between most PFAS concentrations and dyslipidemia and its subtypes. Exceptions included significant nonlinear relationships for PFOA, PFNA, and PFOS with dyslipidemia; for 6:2 Cl-PFESA with hypercholesterolemia; and for PFOA and PFNA with hypertriglyceridemia. Taken together, these findings suggest that exposure to specific PFAS may contribute to endocrine disruption and increase the risk of dyslipidemia in a compound and subtype-specific manner. This study provides novel epidemiological evidence by simultaneously delineating the distinct and joint effects of multiple PFAS on dyslipidemia phenotypes and the TyG index. Our findings underscore the utility of the TyG index as a potential predictive indicator and highlight the importance of considering complex exposure patterns and nonlinear relationships in assessing the cardiometabolic risks of PFAS.