BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification.

METHODS AND RESULTS: This study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13-14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11-400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes.

CONCLUSIONS: Prediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.

[Untagged]
━ Included
━ ━ Human
━ ━ ━ Pregnant women
━ ━ ━ ━ Case-control
━ ━ ━ ━ Cohort
━ ━ ━ ━ Cross-sectional
━ ━ ━ Infants
━ ━ ━ ━ Case-control
━ ━ ━ ━ Cohort
━ ━ ━ ━ Cross-sectional
━ ━ ━ Children
━ ━ ━ ━ Case-control
━ ━ ━ ━ Cohort
━ ━ ━ ━ Cross-sectional
━ ━ ━ General population
━ ━ ━ ━ Case-control
━ ━ ━ ━ Cohort
━ ━ ━ ━ Cross-sectional
━ ━ ━ Occupational
━ ━ ━ ━ Case-control
━ ━ ━ ━ Cohort
━ ━ ━ ━ Cross-sectional
━ ━ Animal
━ ━ ━ Acute
━ ━ ━ Short-term
━ ━ ━ Subchronic
━ ━ ━ Chronic
━ ━ ━ Developmental
━ ━ ━ Multigenerational
━ Excluded
━ ━ Manually excluded in SWIFT-Review
━ ━ Automatically excluded via ML in SWIFT-Active Screener
━ ━ Manually excluded in Distiller (TIAB)
━ ━ Manually excluded in Distiller (full-text)
━ ━ ━ No data provided
━ ━ ━ No relevant exposure
━ ━ ━ Unable to obtain full-text
━ ━ ━ Wildlife study
━ Supplemental
━ ━ Mechanistic (in vitro/ex vivo/in silico)
━ ━ ADME
━ ━ PK/PBPK
━ ━ Non-mammalian model
━ ━ Transgenic mammalian model
━ ━ Non-oral or non-inhalation route
━ ━ ━ Exposure duration
━ ━ ━ ━ Acute
━ ━ ━ ━ Short-term
━ ━ ━ ━ Subchronic
━ ━ ━ ━ Chronic
━ ━ ━ ━ Developmental
━ ━ ━ ━ Other/unclear
━ ━ ━ Route of exposure
━ ━ ━ ━ Oral (gavage)
━ ━ ━ ━ Dermal
━ ━ ━ ━ Injection
━ ━ ━ ━ Intravenous
━ ━ ━ ━ Other/unclear
━ ━ Exposure only
━ ━ Mixture
━ ━ Case reports/series (n≤3)
━ ━ No original data
━ ━ Conference abstract
━ ━ ECHA read-across
━ ━ Presumed duplicate
━ ━ Other supplemental
━ Chemicals
━ ━ Not specified
━ ━ 1-Butanesulfonic acid, 1,1,2,2,3,3,4,4,4-nonafluoro-, salt with sulfonium, dimethylphenyl- (1:1)
━ ━ 1-Hexene, 3,3,4,4,5,5,6,6,6-nonafluoro-, polymer with ethene and 1,1,2,2-tetrafluoroethene
━ ━ 1H,1H,2H-Perfluorocyclopentane
━ ━ 1H,1H,5H-Perfluoropentanol
━ ━ 2-Chloro-1,1,1,2-tetrafluoroethane
━ ━ 2H,2H,3H,3H-Perfluorooctanoic acid
━ ━ 3-Methoxyperfluoro(2-methylpentane)
━ ━ 3-Perfluoroheptylpropanoic acid
━ ━ 3,3,4,4,5,5,6,6,6-Nonafluorohexene
━ ━ 4:2 Fluorotelomer alcohol
━ ━ 6:2 Fluorotelomer alcohol
━ ━ 6:2 Fluorotelomer methacrylate
━ ━ 6:2 Fluorotelomer sulfonic acid
━ ━ 8:2 Fluorotelomer alcohol
━ ━ 8:2 Fluorotelomer sulfonic acid
━ ━ Bis(2-hydroxyethyl)ammonium perfluorobutanesulfonate
━ ━ Dodecafluoroheptanol
━ ━ (Heptafluorobutanoyl)pivaloylmethane
━ ━ Heptafluorobutanol
━ ━ Methyl perfluoro(3-(1-ethenyloxypropan-2-yloxy)propanoate)
━ ━ Nafion
━ ━ ━ Included
━ ━ ━ ━ Animal
━ ━ ━ ━ ━ Short-term
━ ━ ━ ━ Human
━ ━ ━ ━ ━ Occupational
━ ━ ━ ━ ━ ━ Cross-sectional
━ ━ ━ Excluded
━ ━ ━ ━ Manually excluded in Distiller (TIAB)
━ ━ ━ ━ Manually excluded in Distiller (full-text)
━ ━ ━ Supplemental
━ ━ ━ ━ ADME
━ ━ ━ ━ Exposure only
━ ━ ━ ━ Mechanistic (in vitro/ex vivo/in silico)
━ ━ ━ ━ Non-mammalian model
━ ━ ━ ━ Non-oral or non-inhalation route
━ ━ ━ ━ ━ Exposure duration
━ ━ ━ ━ ━ ━ Chronic
━ ━ ━ ━ ━ ━ Short-term
━ ━ ━ ━ ━ ━ Subchronic
━ ━ ━ ━ ━ Route of exposure
━ ━ ━ ━ ━ ━ Injection
━ ━ ━ ━ ━ ━ Intravenous
━ ━ ━ ━ ━ ━ Other/unclear
━ ━ ━ ━ Other supplemental
━ ━ ━ Chemicals
━ ━ ━ ━ Nafion
━ ━ N-Ethyl-N-(2-hydroxyethyl)perfluorooctanesulfonamide
━ ━ N-Ethylperfluorooctanesulfonamide
━ ━ N-Methyl-N-(2-hydroxyethyl)perfluorooctanesulfonamide
━ ━ N-Methylperfluorooctanesulfonamide
━ ━ Pentafluoropropanoic anhydride
━ ━ Perfluamine
━ ━ Perfluoro-1,3-dimethylcyclohexane
━ ━ Perfluoro-1-iodohexane
━ ━ Perfluoro-2,5-dimethyl-3,6-dioxanonanoic acid
━ ━ Perfluoro-2-methyl-3-oxahexanoic acid
━ ━ Perfluoro-3-(1H-perfluoroethoxy)propane
━ ━ Perfluoro-3,6-dioxaheptanoic acid
━ ━ Perfluoro(N-methylmorpholine)
━ ━ Perfluoro(propyl vinyl ether)
━ ━ Perfluorobutanesulfonyl fluoride
━ ━ Perfluorocyclohexanecarbonyl fluoride
━ ━ Perfluoroheptanesulfonate
━ ━ Perfluoroheptanesulfonic acid
━ ━ Perfluoroheptanoic acid
━ ━ Perfluoroisobutyl methyl ether
━ ━ Perfluoromethylcyclopentane
━ ━ Perfluorooctanesulfonamide
━ ━ Perfluorooctanesulfonyl fluoride
━ ━ Perfluoropentanoic acid
━ ━ Perfluoropropanoic acid
━ ━ Perfluorotetradecanoic acid
━ ━ Perfluorotridecanoic acid
━ ━ Perfluoroundecanoic acid
━ ━ Propanoic acid, 3-[1-[difluoro[(trifluoroethenyl)oxy]methyl]-1,2,2,2-tetrafluoroethoxy]...
━ ━ Sodium perfluorodecanesulfonate
━ ━ Tetrabutylphosphonium perfluorobutanesulfonate
━ ━ Tetraethylammonium perfluorooctanesulfonate
━ ━ Trichloro((perfluorohexyl)ethyl)silane
━ ━ Triethoxy((perfluorohexyl)ethyl)silane
━ ━ Trifluoroacetic acid
━ ━ Trifluoromethanesulfonic acid
━ ━ 3:3 Fluorotelomer carboxylic acid
━ ━ 4:2 Fluorotelomer sulfonic acid
━ ━ Perfluoro(2-methyl-3-oxahexanoyl) fluoride
━ ━ Propane, 1,1,1,2,2,3,3-heptafluoro-3-[(trifluoroethenyl)oxy]-, polymer with tetrafluoroethene
━ ━ Perfluoro-3-methoxypropanoic acid
━ ━ Perfluoro(4-methoxybutanoic) acid

References (17373 found)