Per- and polyfluoroalkyl substances: A novel risk factor for cardiovascular disease

Cardiovascular diseases (CVDs) are the major contributor to global mortality. Exposure to per- and polyfluoroalkyl substances (PFAS), synthetic chemicals that are persistent in the environment and the human body, has emerged as a novel risk factor for CVDs. In this review, we conducted a structured literature search in PubMed and Web of Science to identify original research articles published up to February 14, 2025. We summarized the epidemiological findings for the impact of PFAS exposure on CVDs and the pathologic precursors of CVDs including hypertension, atherosclerosis, and arterial stiffness. Although inconclusive, current evidence suggests a potential association between PFAS exposure, primarily legacy congeners such as perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS), with increased incidence, prevalence, and mortality of various CVDs, including ischemic heart disease and stroke, as well as elevated blood pressure, aggravated atherosclerosis, and arterial stiffening. Sex, age, socioeconomic status, and underlying health conditions may influence susceptibility to the cardiovascular effects of PFAS exposure; however, current evidence remains inconclusive. Future work is needed to assess the safety of a broader range of PFAS compounds, particularly the emerging ones. The majority of the existing studies evaluating the association between PFAS exposure and CVDs are cross-sectional. Experimental and longitudinal studies are warranted to establish the causal relationship between PFAS exposure and CVDs, as well as to elucidate the underlying biological mechanisms.