Journal of the American Heart Association · 2025
Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Cardiovascular Disease Incidence in Adults With Prediabetes: Findings From the Diabetes Prevention Program.
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Lin Pi-I Debby, Cardenas Andres, Temprosa Marinella, Botelho Julianne Cook, Calafat Antonia M, Gold Diane R, Oken Emily, Fleisch Abby F
Аннотация
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. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifiers: NCT00004992 and NCT00038727.
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. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifiers: NCT00004992 and NCT00038727.