Environmental Exposure to Emerging Per- and Polyfluoroalkyl Substances and Cardiovascular Diseases: A Mixture Analysis.

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with potential cardiovascular effects. However, evidence on their combined (mixture) impact remains limited. Objectives: To assess associations between individual and mixed PFAS exposures and cardiovascular disease (CVD) outcomes among US adults. Methods: We conducted a cross-sectional study of 5,719 participants from the National Health and Nutrition Examination Survey (NHANES) 2015-2020. Serum concentrations of seven PFAS were used as exposure biomarkers. Cardiovascular outcomes were based on self-reported physician diagnoses. Associations between individual PFAS and CVD were evaluated using Firth logistic regression, while mixture effects were examined using weighted quantile sum (WQS) regression, adjusting for demographic and behavioral covariates. Results: Several PFAS were positively associated with CVD outcomes. ME-PFOSA-AcOH, PFNA, and PFOA showed consistent associations with higher odds of heart attack, congestive heart failure, and coronary heart disease. In mixture analyses, higher combined PFAS exposure was associated with increased odds of all evaluated cardiovascular outcomes. PFOA contributed the largest relative weight in multiple models, while lower weights for other compounds reflect reduced statistical contribution rather than lack of potential toxicity. Conclusion: PFAS exposures, both individually and as mixtures, were associated with higher odds of cardiovascular conditions. These findings underscore the importance of mixture-based approaches in environmental health research. Due to the cross-sectional design, causal relationships cannot be established, and longitudinal studies are needed.