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They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi\u2010omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.<\/jats:p>","DOI":"10.1111\/bcpt.13949","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:10:41Z","timestamp":1696990241000},"page":"141-152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Per\u2010 and polyfluoroalkyl substances and cardiometabolic diseases: A review"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-1630","authenticated-orcid":false,"given":"Tessa","family":"Schillemans","sequence":"first","affiliation":[{"name":"Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Donat\u2010Vargas","sequence":"additional","affiliation":[{"name":"Cardiovascular and Nutritional Epidemiology, Institute of 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