Association of\nPer- and Polyfluoroalkyl Substance\nExposure with Coronary Stenosis and Prognosis in Acute Coronary Syndrome

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