PFAS exposure, particularly PFOS-dominated mixtures, may represent an environmental correlate of stroke risk, with lipid dysregulation potentially contributing to this association.
Individual PFAS compounds (PFOA, PFOS, PFHxS, and PFNA) each showed positive associations with self-reported stroke in U.S. adults.
Near-linear dose-response relationships with no apparent thresholds were observed for PFOA, PFHxS, and PFNA, while PFOS exhibited a threshold effect.
PFAS mixtures were positively associated with stroke risk, with PFOS contributing the largest weight in the mixture.
Serum lipids, specifically total cholesterol (TC) and LDL-cholesterol, partially mediated the associations between PFAS and stroke.
The study identified critical knowledge gaps in the literature regarding dose-response relationships, mixture effects, and biological pathways linking PFAS to cerebrovascular disease prior to this analysis.
This research suggests that exposure to a class of synthetic chemicals called PFAS (per- and polyfluoroalkyl substances), sometimes called 'forever chemicals' because they do not break down easily in the environment or the human body, is associated with a higher likelihood of stroke. Using health data from nearly 51,000 U.S. adults collected between 2003 and 2012, the researchers found that higher blood levels of four specific PFAS compounds—PFOA, PFOS, PFHxS, and PFNA—were each individually linked to greater stroke risk. When these chemicals were considered together as a mixture, people with higher combined PFAS exposure had roughly 52% higher odds of stroke compared to those with lower exposure, with a compound called PFOS contributing most strongly to this mixture effect. The study also explored how PFAS might affect stroke risk biologically. One clue came from looking at blood cholesterol levels: the researchers found that elevated total cholesterol and LDL ('bad') cholesterol explained a small but statistically meaningful portion (about 2–11%) of the link between PFAS and stroke. This suggests that PFAS may partly raise stroke risk by disrupting the body's lipid (fat) regulation, though most of the association appears to work through other mechanisms not yet identified. Notably, three of the four PFAS compounds showed a continuous, near-linear relationship with stroke risk, meaning there was no clear 'safe' threshold below which risk disappeared, while PFOS appeared to have a threshold effect around 3.73 ng/mL. This research matters because PFAS are found in drinking water, food packaging, non-stick cookware, and many other everyday products, meaning human exposure is widespread. Stroke is a leading cause of disability and death worldwide, so identifying modifiable environmental contributors is important for public health. This study suggests that reducing exposure to PFAS—particularly PFOS—could potentially help lower the population burden of stroke, though further research is needed to confirm the causal nature of these associations and to fully understand the biological mechanisms involved.
Li S, Yang Z, Tian X, Wu Y, Song J, Wang W, et al.. (2026). Revealing the Link Between Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Stroke: A Comprehensive Epidemiological and Network Toxicology Perspective.. Cardiovascular toxicology. https://doi.org/10.1007/s12012-026-10157-0