Associations of Serum PFAS with Electrocardiographic Abnormalities in Older Adults and Electrophysiological Characterization

Per- and polyfluoroalkyl substances (PFAS) are highly
persistent
pollutants increasingly implicated in cardiovascular toxicity, yet
their impacts on cardiac electrophysiology remain poorly defined.
In this cross-sectional, community-based study of 3450 adults aged
≥ 60 years, we assessed associations between individual and
combined PFAS exposures and electrocardiographic (ECG) abnormalities.
Based on Minnesota Code classification, higher serum concentrations
of multiple PFAS were associated with greater odds of both minor and
major ECG abnormalities, with near-linear exposure–response
trends. Weighted quantile sum regression assigned the highest mixture
weights to 6:2 Cl-PFESA and several long-chain PFAS. Higher PFAS burden
was linked to prolonged QRS duration and QTc and shortened T-wave
duration, consistent with altered ventricular depolarization and repolarization.
Domain-stratified and leave-one-domain-out analyses supported domain-dependent
associations with repolarization metrics most consistently linked
to 6:2 Cl-PFESA in minor abnormalities. Integrating in vitro electrophysiology
with in silico molecular dynamics provided biological plausibility
for the population findings. Overall, the study outlines a domain-resolved
framework for subclinical cardiac electrical alterations associated
with environmental chemical exposure and provides multilevel evidence
of domain-specific associations between PFAS exposure and cardiac
electrophysiological patterns.