JACC Adv. 2026 Jul 28;5(8):103071. doi: 10.1016/j.jacadv.2026.103071. Online ahead of print.
ABSTRACT
BACKGROUND: Perfluoroalkyl/polyfluoroalkyl substances (PFAS) are emerging clinical and public health concerns, but their role in cardiovascular disease risk remains unclear. Inflammation and thrombosis may link PFAS and cardiovascular disease.
OBJECTIVE: We investigated the association between serum PFAS concentrations and inflammatory and hemostatic markers in midlife women, and whether these markers mediated the association between PFAS and incident hypertension.
METHODS: We analyzed 1,387 participants from the Study of Women's Health Across the Nation from 1999 to 2000 to 2015 to 2016. Linear mixed-effects models estimated the association of 7 PFAS with high-sensitivity C-reactive protein (hs-CRP), fibrinogen, factor VII activity, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator antigen. Quantile-g-computation evaluated mixture effects. Causal mediation analyses tested whether these markers mediated the PFAS-hypertension association.
RESULTS: Individual PFAS were positively associated with hs-CRP and PAI-1. For hs-CRP, per doubling of PFAS ranged from 3.59% (95% CI: 0.01%-7.30%) for branched perfluorooctane sulfonic acid isomers to 5.32% (95% CI: 1.67%-9.10%) for 2-(N-methyl-perfluorooctane sulfonamido) acetic acid. For PAI-1, per doubling of PFAS ranged from 2.41% (95% CI: -0.86% to 5.78%) for the linear perfluorooctane sulfonic acid isomer to 3.04% (95% CI: 0.24%-5.93%) for 2-(N-methyl-perfluorooctane sulfonamido) acetic acid. However, none of these associations remained statistically significant after false discovery rate correction. PFAS mixture effects were 6.15% (95% CI: -0.83% to 13.58%) for hs-CRP and 6.05% (95% CI: 0.29%-12.14%) for PAI-1. No associations were found with other markers, and biomarkers did not mediate the PFAS-hypertension association.
CONCLUSIONS: These findings suggest, but do not establish, that PFAS may be linked to inflammation and impaired fibrinolysis in midlife women.
PMID:42520653 | DOI:10.1016/j.jacadv.2026.103071