Plasma per- and polyfluoroalkyl substances (PFAS) and cardiometabolic risk factors in an elderly Spanish population at high cardiovascular risk

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals increasingly linked to cardiometabolic dysfunction. However, their joint effects as mixtures remain understudied, particularly in older adults. Objective: To evaluate associations between plasma concentrations of individual PFAS and PFAS mixtures and cardiometabolic risk factors in older adults with overweight/obesity and metabolic syndrome. Methods: We conducted a 1-year prospective study including 196 participants (men aged 55–75 and women 60–75) from the Reus center of the PREDIMED-Plus trial. Baseline plasma levels of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) were measured using validated UHPLC-MS/MS methods. Associations with cardiometabolic markers -adiposity, blood pressure, lipids, and glucose metabolism- were assessed using multivariable linear regression and quantile g-computation models. Results: At baseline, participants in the highest tertile of log-transformed PFHxS had higher BMI [β = 1.42 kg/m2; 95 % CI: 0.29 to 2.55]. Those in the highest tertiles of PFOA and PFNA had greater waist circumference [PFOA: β = 2.75 cm; 95 % CI: 0.60 to 4.89; PFNA: β = 4.29 cm; 95 % CI: 2.41 to 6.17]. Diastolic blood pressure was inversely associated with PFOA, both categorically and continuously [β = −3.41 mm Hg; 95 % CI: −6.24 to −0.59; β = −3.36 mm Hg; 95 % CI: −5.96 to −0.75]. Longitudinally, higher PFNA was linked to increases in fasting glucose [β = 11.9; 95 % CI: 0.16 to 23.9], waist circumference [β = 2.23 cm; 95 % CI: 0.96 to 5.42] and inverse association with HDL-cholesterol concentrations [β = −3.11 mg/dL; 95 % CI: −5.69 to −0.53]. PFAS mixture analysis also showed positive associations with fasting glucose (β = 10.4 mg/dL; 95 % CI: 1.82 to 19.2) and HbA1c (β = 0.30 %; 95 % CI: 0.00 to 0.60), mainly driven by PFNA, PFOA, and PFOS. Conclusions: PFNA, PFOA, and their mixtures were associated with adverse changes in glucose metabolism, HDL-cholesterol, and adiposity in older adults at high cardiometabolic risk. These findings highlight the need to evaluate PFAS mixtures and conduct long-term studies to clarify underlying mechanisms.