Associations between Per- and Polyfluoroalkyl Chemicals and Abdominal Aortic Calcification in Middle-Aged and Older Adults
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INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) have infiltrated countless everyday products, raising concerns about potential effects on human health, specifically on the cardiovascular system and the development of abdominal aortic calcification (AAC). However, our understanding of this relationship is still limited. OBJECTIVES: This study aims to investigate the effects of PFAS on AAC using machine learning algorithms. METHODS: Leveraging the power of machine learning technique, extreme gradient boosting (XGBoost), we assessed the relationship between PFAS exposure and AAC risk. We focused on three PFAS compounds, perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) through multiple logistic regression, restricted cubic spline (RCS), and quantile g-computation (QGC) models. To get more insight into the underlying mechanisms, mediation analyses are used to investigate the potential mediating role of fatty acids and blood cell fractions in AAC. RESULTS: Our findings indicate that elevated serum levels of PFHxS and PFDeA are associated with the increased risk of AAC. The QGC analyses underscore the overall positive association between the PFAS mixture and AAC risk, with PFHxS carrying the greatest weight, followed by PFDeA. The RCS analyses reveal a dose-dependent increase between serum PFHxS concentration and AAC risk in an inverted V-shape way. Moreover, age and PFHxS exposure are identified as the primary factors contributing to abdominal aortic calcification risk in SHapley Additive exPlanation (SHAP) summary plot combined with XGBoost technique. Although PFAS significantly change the profile of fatty acids, we do not find any mediating roles of them in AAC. Despite strong associations between PFAS exposure and hematological indicators, our analysis does not find evidence that these indicators mediate the development of AAC. CONCLUSIONS: In summary, our study highlights the detrimental impact of PFAS on abdominal aortic health and emphasizes the need for further research to understand the underlying mechanisms involved.
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Higher serum PFHxS and PFDeA concentrations are linked to increased abdominal aortic calcification (AAC) risk, with a dose-dependent relationship for PFHxS.
“Notably, higher serum PFHxS and PFDeA concentrations have been linked to increased abdominal aortic calcification (AAC) risk, with a dose-dependent relationship observed for PFHxS; furthermore, age and PFHxS levels were the strongest predictors in SHAP-XGBoost models [76].”
From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [76]
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“Notably, higher serum PFHxS and PFDeA concentrations have been linked to increased abdominal aortic calcification (AAC) risk, with a dose-dependent relationship observed for PFHxS; furthermore, age and PFHxS levels were the strongest predictors in SHAP-XGBoost models [76].”
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Yang, J., Wu, J., & Wa̅ng, Y. (2025) · Environmental Science & Technology Letters · doi:10.1021/acs.estlett.5c01048 · Cited by 4 · see citing works
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F–53B exacerbates doxorubicin-induced cardiotoxicity by impairing NRF2-dependent ferroptosis defense
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Persistent Organic Pollutants and Cardiotoxicity
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“Elevated PFAS levels have been associated with an increased risk of hypertension, atherosclerosis, and other cardiovascular disorders, all of which are closely linked to kidney disease (Meneguzzi, Fava, Castelli, & Minuz, 2021; Yang, Wang, Li, & Wāng, 2024) .”
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An Exploration of Machine Learning Methods in Human Biomonitoring
Singh, K., Bi, J., Musende, M., Collins, S. P., Borghese, M. M., Hu, J. M. Y., Pollock, T., St-Amand, A., Hennessy, D. A., & Buckeridge, D. L. (2026) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph23050680
Imaging and Molecular Biomarkers of PFAS-Related Vascular Aging: A Narrative Review
Borghini, A., Faita, F., Simonini, L., Palazzo, M., Sagheddu, C., Cavigli, C., Donzelli, G., Bustaffa, E., Masi, S., Gorini, F., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27136064 · Cited by 1 · see citing works
“The other two studies [29,30], based on cohorts extracted from NHANES 2013–2014, exclusively assess aortic calcifications through dual-energy X-ray absorptiometry.”
- Authors
- Yang, J., Wang, T., Li, K., & Wāng, Y.
- Affiliations
- Anhui Medical University (CN)
- Shanxi Medical University (CN)
- Corresponding author
- Wāng, Yán
- Venue
- Journal of Advanced Research
- Publisher
- Elsevier BV
- Published
- 2025-04
- Volume
- 70
- Pages
- 203-222
- ISSN
- 2090-1224 (ISSN-L)
- 2090-1232
- PMC
- PMC11976567
- OpenAlex
- W4396640539
- Cited by
- 15
- References
- 77
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 3
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Advanced Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82103883)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
- Keywords
- per- and polyfluoroalkyl substances, PFAS, abdominal aortic calcification, perfluorohexane sulfonic acid, perfluorodecanoic acid, perfluorononanoic acid, cardiovascular risk, fatty acids, dose-response relationship, mediation analysis, middle-aged and older adults
- MeSH terms
- Machine Learning, Aged, Aorta, Abdominal, Decanoic Acids, Environmental Exposure, Female, Fluorocarbons, Humans, Male, Middle Aged, Risk Factors, Vascular Calcification
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