Possible Biological Pathways Affected by PFAS Associated with Increased Risk of CVD in Postmenopausal Women

by | Jul 23, 2024 | 2024, Cardiovascular Health, Environmental Health, Recent Articles, Women's Health

Written by Chrystal Moulton, Science Writer. Researchers also found 31 proteins that were significantly altered by tPFOS, PFOA, and PFBS.

cardiovascular healthPer and polyfluoroalkyl substances or PFAS are chemicals used in household products1,2. Per and polyfluoroalkyl substances (PFAS) once released remain in the environment for years and has been detected in the blood of more than 90% of the US population3,4. High concentrations of per and polyfluoroalkyl substances (PFAS) has been reported in postmenopausal women due to the cessation of menstruation5. For this reason, postmenopausal women, who are already particularly at risk for developing CVD, have a heightened risk of developing CVD after exposure to PFASs6,7. However, the mechanism through which PFAS affects the cardiovascular system in postmenopausal women is still not fully understood. In the current study, researchers explored the association between PFAS in postmenopausal women and the risk of CVD as well as the possible pathways for CVD development specific to coronary artery disease (CAD) and coronary microvascular disease (CMD8).

Researchers focused on three specific compounds of PFAS. These were perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorobutanesulphonic acid (PFBS). The study was designed as a prospective observational trial including seventy patients aged 45 to 78 years old. Among these patients, 21 were diagnosed with coronary artery disease (CAD), 23 were diagnosed with coronary microvascular disease (CMD), and 26 patients comprised the control group. Patients were included If they had an effective coronary angiography intervention, CAD- related chest pain, and positive non-invasive imaging results. Researchers collected a 5ml blood sample from patients with CAD or CMD for additional analysis. Researchers used the sample to assess the presence of PFOA, PFOS, and PFBS in each patient. The limit of quantification method and gas chromatography- mass spectrometry was used to detect the level of the targeted PFAS [i.e. PFOS, PFOA, PFBS] in the blood. Researchers also used various machine learning tools to quantify the association between the three PFAS and CMD/ CAD. They also determined possible pathways that these targeted PFAS alter which could increase the risk of CVD in postmenopausal women.

Demographic characteristics between the control, CMD patients, and CAD patients were similar9. Researchers detected 5 pM of PFOA, 20 pM of PFOS and 5 pM of PFBS among the study population. When comparing the overall serum concentration of the three PFAS to results found in the NHANES study, researchers found that PFBS levels were much higher within their current sample of patients compared to concentrations detected in the 2013- 2014 NHANES study. However, for PFOA and PFOS serum concentrations was higher for participants in the NHANES study compared to the current trial sample population. Utilizing machine learning, researchers tried to identify the best method to find a predictor of CAD versus CMD. For both CAD and CMD, random forest classification method demonstrated that PFOS was a strong predictor of CAD while PFOA and PFOS were moderate predictors of CMD. Researchers also found 31 proteins that were significantly altered by the three PFAS. All of them were linked to inflammation. Digging deeper, researchers used reactome pathway analysis to elucidate biochemical pathways these PFAS alter. Researchers found that amino acid biosynthesis, metabolism, and degradation pathways were affected in correlations with CMD/ PFOA and CAD/ PFOS. Researchers also found that metabolites correlated between PFOS and CAD were also involved in glycolysis and gluconeogenesis, as well as peroxisome proliferator activated receptor signaling pathways. In other words, glycolysis and gluconeogenesis, as well as peroxisome proliferator activated receptor signaling pathways were also specifically affected by PFOS in patients with CAD.

Overall, results from this study demonstrated that PFOS was a significant predictor of coronary artery disease (CAD) while PFOA was a moderate predictor of coronary microvascular disease (CMD). Both indicators were identified using the machine learning method known as random forest classification. Researchers also identified biochemical pathways through which PFOA, PFOS, and PFBS affect development CAD and CMD. Additional studies will be needed to verify these findings.

Source: Arredondo Eve, Alicia, Elif Tunc, Dhruv Mehta, Jin Young Yoo, Huriye Erbak Yilmaz, Sadık Volkan Emren, Filiz Akyıldız Akçay, and Zeynep Madak Erdogan. “PFAS and their association with the increased risk of cardiovascular disease in postmenopausal women.” Toxicological Sciences (2024): kfae065.

© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. 

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Posted July 23, 2024.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

References:

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