Abstract
Introduction
Evidence of the adverse metabolic health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) is increasing. However, the impact of PFAS on cardiovascular diseases remains controversial. This meta-analysis aimed to analyze the impact of PFAS on the stroke risk.
Content
Databases were searched for studies published up to November 1, 2022, which report the association between stroke and exposure to at least one of four main PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], perfluorononanoic acid [PFNA], and perfluorohexane sulfonic acid [PFHxS]). Data extraction and quality assessment were performed according to the Newcastle-Ottawa scale.
Summary and outlook
Four studies were included in this systematic review. Multivariate adjusted odds ratios (ORs) for incident stroke per 1-log unit increment in each serum PFAS were combined in the meta-analysis. The risk of development of stroke was not significantly associated with PFOA, PFOS, or PFNA exposure (PFOA: pooled odds ratio [OR]=1.001, 95 % confidence interval [CI]=0.975–1.028, p=0.934; PFOS: pooled OR=0.994, 95 % CI=0.972–1.017, p=0.601; PFNA: pooled OR=1.016, 95 % CI=0.920–1.123, p=0.752), whereas a moderately lower risk was associated with PFHxS exposure without statistical significance (pooled OR=0.953, 95 % CI=0.908–1.001, p=0.054). PFOA, PFOS, and PFNA exposure showed a neutral association, while PFHxS showed a possible inverse association with the risk of stroke. Therefore, this finding should be interpreted with caution. Further prospective observational studies with PFAS mixture analyses are warranted.
Funding source: National Research Foundation of Korea
Award Identifier / Grant number: RS-2023-00241801
-
Ethical approval: Not applicable.
-
Informed consent: Not applicable.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Research funding: This study was supported by National Research Foundation (NRF), funded by the Korean government (RS-2023-00241801). Funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
References
1. Lau, C, Anitole, K, Hodes, C, Lai, D, Pfahles-Hutchens, A, Seed, J. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 2007;99:366–94. https://doi.org/10.1093/toxsci/kfm128.Search in Google Scholar PubMed
2. Winquist, A, Steenland, K. Perfluorooctanoic acid exposure and thyroid disease in community and worker cohorts. Epidemiology 2014;25:255–64. https://doi.org/10.1097/ede.0000000000000040.Search in Google Scholar
3. Fenton, SE, Ducatman, A, Boobis, A, DeWitt, JC, Lau, C, Ng, C, et al.. Per-and polyfluoroalkyl substance toxicity and human health review: current state of knowledge and strategies for informing future research. Environ Toxicol Chem 2021;40:606–30. https://doi.org/10.1002/etc.4890.Search in Google Scholar PubMed PubMed Central
4. Grandjean, P, Heilmann, C, Weihe, P, Nielsen, F, Mogensen, UB, Budtz-Jorgensen, E. Serum vaccine antibody concentrations in adolescents exposed to perfluorinated compounds. Environ Health Perspect 2017;125:077018. https://doi.org/10.1289/ehp275.Search in Google Scholar PubMed PubMed Central
5. Girardi, P, Merler, E. A mortality study on male subjects exposed to polyfluoroalkyl acids with high internal dose of perfluorooctanoic acid. Environ Res 2019;179:108743. https://doi.org/10.1016/j.envres.2019.108743.Search in Google Scholar PubMed
6. Barry, V, Winquist, A, Steenland, K. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect 2013;121:1313–8. https://doi.org/10.1289/ehp.1306615.Search in Google Scholar PubMed PubMed Central
7. Velez, MP, Arbuckle, TE, Fraser, WD. Maternal exposure to perfluorinated chemicals and reduced fecundity: the MIREC study. Hum Reprod 2015;30:701–9. https://doi.org/10.1093/humrep/deu350.Search in Google Scholar PubMed PubMed Central
8. Dunder, L, Lind, PM, Salihovic, S, Stubleski, J, Karrman, A, Lind, L. Changes in plasma levels of per-and polyfluoroalkyl substances (PFAS) are associated with changes in plasma lipids – a longitudinal study over 10 years. Environ Res 2022;211:112903. https://doi.org/10.1016/j.envres.2022.112903.Search in Google Scholar PubMed
9. Salihovic, S, Stubleski, J, Karrman, A, Larsson, A, Fall, T, Lind, L, et al.. Changes in markers of liver function in relation to changes in perfluoroalkyl substances – a longitudinal study. Environ Int 2018;117:196–203. https://doi.org/10.1016/j.envint.2018.04.052.Search in Google Scholar PubMed
10. Chung, SM, Heo, DG, Kim, JH, Yoon, JS, Lee, HW, Kim, JY, et al.. Perfluorinated compounds in adults and their association with fasting glucose and incident diabetes: a prospective cohort study. Environ Health 2022;21:101. https://doi.org/10.1186/s12940-022-00915-2.Search in Google Scholar PubMed PubMed Central
11. Ding, N, Karvonen-Gutierrez, CA, Mukherjee, B, Calafat, AM, Harlow, SD, Park, SK. Per-and polyfluoroalkyl substances and incident hypertension in multi-racial/ethnic women: the study of women’s health across the nation. Hypertension 2022;79:1876–86. https://doi.org/10.1161/hypertensionaha.121.18809.Search in Google Scholar
12. Hur, KY, Moon, MK, Park, JS, Kim, SK, Lee, SH, Yun, JS, et al.. 2021 Clinical practice guidelines for diabetes mellitus of the Korean diabetes association. Diabetes Metab J. 2021;45:461–81. https://doi.org/10.4093/dmj.2021.0156.Search in Google Scholar PubMed PubMed Central
13. Lee, SH, Han, K, Kwon, HS, Kim, MK. Frequency of exposure to impaired fasting glucose and risk of mortality and cardiovascular outcomes. Endocrinol Metab 2021;36:1007–15. https://doi.org/10.3803/enm.2021.1218.Search in Google Scholar
14. Boehme, AK, Esenwa, C, Elkind, MS. Stroke risk factors, genetics, and prevention. Circ Res 2017;120:472–95. https://doi.org/10.1161/circresaha.116.308398.Search in Google Scholar
15. Osorio-Yanez, C, Sanchez-Guerra, M, Cardenas, A, Lin, PD, Hauser, R, Gold, DR, et al.. Per-and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: results from the diabetes prevention program outcomes study. Environ Int 2021;151:106446. https://doi.org/10.1016/j.envint.2021.106446.Search in Google Scholar PubMed PubMed Central
16. Soheimi, SSA, Rahman, AA, Latip, AN, Ibrahim, E, Kadir, SASH. Understanding the impact of perfluorinated compounds on cardiovascular diseases and their risk factors: a meta-analysis study. Int J Environ Res Publ Health 2021;18:8345. https://doi.org/10.3390/ijerph18168345.Search in Google Scholar PubMed PubMed Central
17. Wen, ZJ, Wei, YJ, Zhang, YF, Zhang, YF. A review of cardiovascular effects and underlying mechanisms of legacy and emerging per-and polyfluoroalkyl substances (PFAS). Arch Toxicol 2023;97:1195–245.10.1007/s00204-023-03477-5Search in Google Scholar PubMed
18. Feng, X, Long, G, Zeng, G, Zhang, Q, Song, B, Wu, KH. Association of increased risk of cardiovascular diseases with higher levels of perfluoroalkylated substances in the serum of adults. Environ Sci Pollut Res Int 2022;29:89081–92. https://doi.org/10.1007/s11356-022-22021-z.Search in Google Scholar PubMed
19. Hutcheson, R, Innes, K, Conway, B. Perfluoroalkyl substances and likelihood of stroke in persons with and without diabetes. Diabetes Vasc Dis Res 2020;17:1479164119892223. https://doi.org/10.1177/1479164119892223.Search in Google Scholar PubMed PubMed Central
20. Schillemans, T, Donat-Vargas, C, Lindh, CH, de Faire, U, Wolk, A, Leander, K, et al.. Per-and polyfluoroalkyl substances and risk of myocardial infarction and stroke: a nested case-control study in Sweden. Environ Health Perspect 2022;130:37007. https://doi.org/10.1289/ehp9791.Search in Google Scholar
21. Simpson, C, Winquist, A, Lally, C, Steenland, K. Relation between perfluorooctanoic acid exposure and strokes in a large cohort living near a chemical plant. Environ Res 2013;127:22–8. https://doi.org/10.1016/j.envres.2013.10.002.Search in Google Scholar PubMed
22. Greenland, S, Robins, JM. Estimation of a common effect parameter from sparse follow-up data. Biometrics 1985;41:55–68. https://doi.org/10.2307/2530643.Search in Google Scholar
23. Donat-Vargas, C, Bergdahl, IA, Tornevi, A, Wennberg, M, Sommar, J, Koponen, J, et al.. Associations between repeated measure of plasma perfluoroalkyl substances and cardiometabolic risk factors. Environ Int 2019;124:58–65. https://doi.org/10.1016/j.envint.2019.01.007.Search in Google Scholar PubMed
24. Jeddi, MZ, Zuanna, TD, Barbieri, G, Fabricio, ASC, Dapra, F, Fletcher, T, et al.. Associations of perfluoroalkyl substances with prevalence of metabolic syndrome in highly exposed young adult community residents-A cross-sectional study in veneto region, Italy. Int J Environ Res Publ Health 2021;18:1194. https://doi.org/10.3390/ijerph18031194.Search in Google Scholar PubMed PubMed Central
25. Donat-Vargas, C, Bergdahl, IA, Tornevi, A, Wennberg, M, Sommar, J, Kiviranta, H, et al.. Perfluoroalkyl substances and risk of type II diabetes: a prospective nested case-control study. Environ Int 2019;123:390–8. https://doi.org/10.1016/j.envint.2018.12.026.Search in Google Scholar PubMed
26. Su, TC, Kuo, CC, Hwang, JJ, Lien, GW, Chen, MF, Chen, PC. Serum perfluorinated chemicals, glucose homeostasis and the risk of diabetes in working-aged Taiwanese adults. Environ Int 2016;88:15–22. https://doi.org/10.1016/j.envint.2015.11.016.Search in Google Scholar PubMed
27. Andersen, ME, Hagenbuch, B, Apte, U, Corton, JC, Fletcher, T, Lau, C, et al.. Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms. Toxicology 2021;459:152845. https://doi.org/10.1016/j.tox.2021.152845.Search in Google Scholar PubMed PubMed Central
28. Liu, G, Zhang, B, Hu, Y, Rood, J, Liang, L, Qi, L, et al.. Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study. Environ Health 2020;19:5. https://doi.org/10.1186/s12940-020-0561-8.Search in Google Scholar PubMed PubMed Central
29. Papadopoulou, E, Nicolescu, A, Haug, LS, Husoy, T, Deleanu, C, Dirven, H, et al.. Lipoprotein profiles associated with exposure to poly-and perfluoroalkyl substances (PFASs) in the EuroMix human biomonitoring study. Environ Pollut 2022;308:119664. https://doi.org/10.1016/j.envpol.2022.119664.Search in Google Scholar PubMed
30. Salihovic, S, Fall, T, Ganna, A, Broeckling, CD, Prenni, JE, Hyotylainen, T, et al.. Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances. J Expo Sci Environ Epidemiol 2019;29:196–205. https://doi.org/10.1038/s41370-018-0060-y.Search in Google Scholar PubMed
31. Lind, PM, Salihovic, S, Stubleski, J, Karrman, A, Lind, L. Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years – a longitudinal study. Environ Health 2018;17:59. https://doi.org/10.1186/s12940-018-0403-0.Search in Google Scholar PubMed PubMed Central
32. Wielsoe, M, Long, M, Ghisari, M, Bonefeld-Jorgensen, EC. Perfluoroalkylated substances (PFAS) affect oxidative stress biomarkers in vitro. Chemosphere 2015;129:239–45. https://doi.org/10.1016/j.chemosphere.2014.10.014.Search in Google Scholar PubMed
33. Omoike, OE, Pack, RP, Mamudu, HM, Liu, Y, Strasser, S, Zheng, S, et al.. Association between per and polyfluoroalkyl substances and markers of inflammation and oxidative stress. Environ Res 2021;196:110361. https://doi.org/10.1016/j.envres.2020.110361.Search in Google Scholar PubMed
34. Behr, AC, Plinsch, C, Braeuning, A, Buhrke, T. Activation of human nuclear receptors by perfluoroalkylated substances (PFAS). Toxicol Vitro 2020;62:104700. https://doi.org/10.1016/j.tiv.2019.104700.Search in Google Scholar PubMed
35. Fragki, S, Dirven, H, Fletcher, T, Grasl-Kraupp, B, Gutzkow, KB, Hoogenboom, R, et al.. Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not? Crit Rev Toxicol 2021;51:141–64. https://doi.org/10.1080/10408444.2021.1888073.Search in Google Scholar PubMed
36. Li, CH, Ren, XM, Cao, LY, Qin, WP, Guo, LH. Investigation of binding and activity of perfluoroalkyl substances to the human peroxisome proliferator-activated receptor beta/delta. Environ Sci Process Impacts 2019;21:1908–14. https://doi.org/10.1039/c9em00218a.Search in Google Scholar PubMed
37. Kowalska, D, Sosnowska, A, Bulawska, N, Stepnik, M, Besselink, H, Behnisch, P, et al.. How the structure of per-and polyfluoroalkyl substances (PFAS) influences their binding potency to the peroxisome proliferator-activated and thyroid hormone receptors-an in silico screening study. Molecules 2023;28:479. https://doi.org/10.3390/molecules28020479.Search in Google Scholar PubMed PubMed Central
38. Meneguzzi, A, Fava, C, Castelli, M, Minuz, P. Exposure to perfluoroalkyl chemicals and cardiovascular disease: experimental and epidemiological evidence. Front Endocrinol 2021;12:706352. https://doi.org/10.3389/fendo.2021.706352.Search in Google Scholar PubMed PubMed Central
39. Lundin, JI, Alexander, BH, Olsen, GW, Church, TR. Ammonium perfluorooctanoate production and occupational mortality. Epidemiology 2009;20:921–8. https://doi.org/10.1097/ede.0b013e3181b5f395.Search in Google Scholar
40. Mastrantonio, M, Bai, E, Uccelli, R, Cordiano, V, Screpanti, A, Crosignani, P. Drinking water contamination from perfluoroalkyl substances (PFAS): an ecological mortality study in the Veneto Region, Italy. Eur J Publ Health 2018;28:180–5. https://doi.org/10.1093/eurpub/ckx066.Search in Google Scholar PubMed
41. Koshy, TT, Attina, TM, Ghassabian, A, Gilbert, J, Burdine, LK, Marmor, M, et al.. Serum perfluoroalkyl substances and cardiometabolic consequences in adolescents exposed to the World Trade Center disaster and a matched comparison group. Environ Int 2017;109:128–35. https://doi.org/10.1016/j.envint.2017.08.003.Search in Google Scholar PubMed PubMed Central
42. Averina, M, Brox, J, Huber, S, Furberg, AS. Exposure to perfluoroalkyl substances (PFAS) and dyslipidemia, hypertension and obesity in adolescents. The Fit Futures study. Environ Res 2021;195:110740. https://doi.org/10.1016/j.envres.2021.110740.Search in Google Scholar PubMed
43. Bijland, S, Rensen, PC, Pieterman, EJ, Maas, AC, van der Hoorn, JW, van Erk, MJ, et al.. Perfluoroalkyl sulfonates cause alkyl chain length-dependent hepatic steatosis and hypolipidemia mainly by impairing lipoprotein production in APOE*3-Leiden CETP mice. Toxicol Sci 2011;123:290–303. https://doi.org/10.1093/toxsci/kfr142.Search in Google Scholar PubMed
44. Buhrke, T, Kibellus, A, Lampen, A. In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths. Toxicol Lett 2013;218:97–104. https://doi.org/10.1016/j.toxlet.2013.01.025.Search in Google Scholar PubMed
45. Carlson, LM, Angrish, M, Shirke, AV, Radke, EG, Schulz, B, Kraft, A, et al.. Systematic evidence map for over one hundred and fifty per-and polyfluoroalkyl substances (PFAS). Environ Health Perspect 2022;130:56001. https://doi.org/10.1289/ehp10343.Search in Google Scholar PubMed PubMed Central
46. Lind, L, Salihovic, S, Lampa, E, Lind, PM. Mixture effects of 30 environmental contaminants on incident metabolic syndrome-A prospective study. Environ Int 2017;107:8–15. https://doi.org/10.1016/j.envint.2017.06.005.Search in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/reveh-2023-0021).
© 2023 Walter de Gruyter GmbH, Berlin/Boston
