Systematic review on internal exposure to per- and polyfluoroalkyl substances (PFAS) and risk of ischemic heart...

Per- and polyfluoroalkyl substances (PFAS) may elevate blood lipids, suggesting that PFAS may also target the cardiovascular system. This systematic review aimed to investigate the relationship between internal human exposure to main PFAS, i.e., perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) and ischemic heart diseases (IHD). Two systematic literature searches were performed in MEDLINE and EMBASE - most recently on January 8, 2025. Eligible studies analyzed associations between individual blood PFAS exposure and IHD among humans. Risk of bias was assessed using the OHAT Risk of Bias Rating Tool and evidence was synthesized using structured tables and vote counting based on direction of effect, as meta-analyses and dose-response analyses did not provide meaningfully interpretable results. The 16 studies included comprised 79,313 participants. Seven studies estimated rate ratios (RR) and nine estimated odds ratios (OR). Associations between PFOA exposure and IHD (RR) were small and exposure levels were heterogeneous. In the vote counting analysis of the association between PFOA exposure and IHD, 82.4% (95%-CI: 56.6%-96.2%) of effect estimates (RR) pointed in the harmful direction (low certainty). A harmful tendency was less pronounced for PFOS and IHD, with 60.0% (95%-CI: 14.7%-94.7%) of RR and 46.4% (95%-CI 27.5%-66.1%) of OR indicating a harmful relationship. For PFHxS, PFNA, and the sum of PFAS, the overall direction of the vote counting results differed between RR and OR (very low or low certainty). The relationship between PFAS and IHD remains unclear, so further longitudinal studies investigating dose-dependent effects are required.