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

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.