Association of Per- and Polyfluoroalkyl Substance Exposure with Coronary Stenosis and Prognosis in Acute Coronary Syndrome

Per- and polyfluoroalkyl substances (PFAS) have been associated with an increased risk of acute coronary syndromes (ACS), but the influence on the degree of coronary stenosis and prognosis is unclear. This study enrolled 571 newly diagnosed ACS cases and investigated the association of 12 PFAS with coronary stenosis severity and prognosis. Coronary stenosis was assessed via Gensini score (GS) and number of lesioned vessels (LVN). Prognosis was estimated by tracking major adverse cardiovascular events (MACE). Statistical analyses included ordered logistic regression, Cox regression, threshold effect models, Bayesian kernel machine regression, and quantile g-computation models. The adverse outcome pathway (AOP) framework was applied to reveal the underlying mechanism. The results showed positive association between perfluorooctanesulfonic acid (PFOS) and coronary stenosis, with an odds ratio (95% confidence interval, CI) of 1.33 (1.06, 1.67) for GS and 1.36 (1.08, 1.71) for LVN. PFOS significantly increased the incidence of poor prognosis, with hazard ratios (95% CI) of 1.96 (1.34, 2.89) for MACE. Threshold effects were observed for PFAS on coronary stenosis and prognosis, with PFOS thresholds of 4.65 ng/mL for GS, 4.54 ng/mL for LVN, and 5.14 ng/mL for MACE, and 5.03 ng/mL for nonfatal myocardial infarction. PFAS mixture exposure increased the occurrence of MACE and nonfatal myocardial infarction. The AOP framework shows that PFAS may impact protein binding, the cytoskeleton, multicellular biological processes, and heart function. In summary, our study revealed the adverse effects of PFAS on the degree of coronary stenosis and prognosis in ACS and identified potentially relevant molecular loci.