Association of PFAS and Metals with Cardiovascular Disease Risk: Exploring the Mediating Effect of Diet

Background: Cardiovascular disease (CVD) is a major global health burden influenced by genetic, behavioral, and environmental factors. Among these, exposure to per- and poly-fluoroalkyl substances (PFASs) and toxic metals has been increasingly implicated in adverse cardiovascular outcomes. However, the mediating role of dietary inflammation in these associations remains unclear. Objective: This study investigates the relationship between PFAS and metal exposures and CVD risk, focusing on the potential mediating role of diet, operationalized through the Dietary Inflammatory Index (DII). Additionally, this study examines age as an effect modifier in these associations. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle (n = 660), we assessed environmental exposures (lead, cadmium, mercury, perfluorooctanoic acid-PFOA, perfluorooctane sulfonate-PFOS), dietary inflammatory potential (DII), and cardiovascular markers (blood pressure, lipid profile, C-reactive protein). Statistical analyses included linear regression and Bayesian Kernel Machine Regression-Causal Mediation Analysis (BKMR-CMA) to estimate the direct, indirect (through DII), and total effects of exposure on CVD risk biomarkers. Results: Linear regression revealed significant associations between mercury and reduced systolic blood pressure (SBP) (p = 0.017) and cadmium with increased C-reactive protein (CRP) (p = 0.006). Mediation analysis suggested dietary inflammation may play a role, though estimates were imprecise. Conclusions: PFAS and metals may influence CVD risk through inflammatory pathways, with potential age-related differences. Future longitudinal studies are needed to clarify these complex interactions, reduce measurement error, and guide age-specific exposure regulations.