Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Cardiovascular Disease Incidence in Adults With Prediabetes: Findings From the Diabetes Prevention Program

Authors

Pi-I Debby Lin, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston MA USA.
Andres Cardenas, Department of Epidemiology and Population Health Stanford University Stanford CA USA.
Marinella Temprosa, Department of Biostatistics and Bioinformatics and Biostatistics Center Milken Institute School of Public Health, the George Washington University Washington DC USA.
Julianne Cook Botelho, Division of Laboratory Sciences National Center for Environmental Health, Centers for Disease Control and Prevention Atlanta GA USA.
Antonia M. Calafat, Division of Laboratory Sciences National Center for Environmental Health, Centers for Disease Control and Prevention Atlanta GA USA.
Diane R. Gold, Department of Environmental Health Harvard T.H. Chan School of Public Health Boston MA USA.
Emily Oken, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute Boston MA USA.
Abby F. Fleisch, Center for Interdisciplinary Population & Health Research MaineHealth Institute for Research Westbrook ME USA.

Document Type

Article

Publication Date

12-18-2025

Institution/Department

Center for Interdisciplinary Population & Health Research; Pediatrics

Journal Title

Journal of the American Heart Association

Abstract

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent, widespread environmental contaminants linked to cardiometabolic outcomes including obesity, hyperlipidemia, and diabetes. We examined whether baseline plasma PFAS concentrations are associated with incident cardiovascular disease (CVD) in adults with prediabetes, leveraging data from DPPOS (Diabetes Prevention Program Outcomes Study). METHODS: Among 1382 participants, we quantified baseline plasma concentrations of 6 PFAS. We used Cox proportional hazards models to estimate the risks of developing CVD outcomes during a median of 21 years of follow-up for each PFAS and used quantile g-computation to evaluate the joint effect of all 6 PFAS. Effect modification by age, sex, menopausal status, diet, and physical activity was explored. RESULTS: The incidence of major adverse cardiovascular events was 9.6%; 3.9% had CVD-related death. Each increase in interquartile range (1.1 ng/mL) in 2-(N-methyl-perfluorooctane sulfonamido) acetate was associated with a 16% higher risk of major adverse cardiovascular events (95% CI, 1-33%) and a 24% higher risk of CVD death (95% CI, 2-52%). Higher concentrations of perfluorohexane sulfonate, perfluorooctane sulfonate, 2-(N-ethyl-perfluorooctane sulfonamido) acetate, and perfluorooctanoate were associated with greater risk of CVD outcomes, including nonfatal myocardial infarction, hospitalized congestive heart failure, and cardiovascular death. However, PFAS mixture was not associated with CVD. Age, sex, treatment arm, physical activity, and diet did not modify the associations of individual PFAS. CONCLUSION: In adults with prediabetes, higher plasma concentrations of select PFAS, but not their mixture, were prospectively associated with increased CVD risk. These findings underscore PFAS as a potential environmental risk factor for CVD in high-risk populations. URL: https://clinicaltrials.gov/; Unique identifiers: NCT00004992 and NCT00038727.

First Page

e046298

Recommended Citation

Lin, Pi-I Debby; Cardenas, Andres; Temprosa, Marinella; Botelho, Julianne Cook; Calafat, Antonia M.; Gold, Diane R.; Oken, Emily; and Fleisch, Abby F., "Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Cardiovascular Disease Incidence in Adults With Prediabetes: Findings From the Diabetes Prevention Program" (2025). MaineHealth Maine Medical Center. 4237.
https://knowledgeconnection.mainehealth.org/mmc/4237