Li Haoran, Yang Ming, Zhao Jiaxin, Tan Zhenzhen, Li Longfei, An Ziwen, Liu Yi, Liu Xuehui, Zhang Xiaoguang, Lu Jingchao, Li Ang, Guo Huicai
Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang 050017, China.
Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Environ Health (Wash). 2024 Dec 3;3(3):291-307. doi: 10.1021/envhealth.4c00166. eCollection 2025 Mar 21.
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.
全氟和多氟烷基物质（PFAS）与急性冠状动脉综合征（ACS）风险增加有关，但对冠状动脉狭窄程度和预后的影响尚不清楚。本研究纳入了571例新诊断的ACS病例，调查了12种PFAS与冠状动脉狭窄严重程度及预后的关联。通过Gensini评分（GS）和病变血管数量（LVN）评估冠状动脉狭窄情况。通过追踪主要不良心血管事件（MACE）评估预后。统计分析包括有序逻辑回归、Cox回归、阈值效应模型、贝叶斯核机器回归和分位数g计算模型。应用不良结局途径（AOP）框架揭示潜在机制。结果显示，全氟辛烷磺酸（PFOS）与冠状动脉狭窄呈正相关，GS的比值比（95%置信区间，CI）为1.33（1.06，1.67），LVN的比值比为1.36（1.08，1.71）。PFOS显著增加了不良预后的发生率，MACE的风险比（95%CI）为1.96（1.34，2.89）。观察到PFAS对冠状动脉狭窄和预后存在阈值效应，GS的PFOS阈值为4.65 ng/mL，LVN为4.54 ng/mL，MACE为5.14 ng/mL，非致命性心肌梗死为5.03 ng/mL。PFAS混合物暴露增加了MACE和非致命性心肌梗死的发生。AOP框架显示，PFAS可能影响蛋白质结合、细胞骨架、多细胞生物学过程和心脏功能。总之，我们的研究揭示了PFAS对ACS患者冠状动脉狭窄程度和预后的不良影响，并确定了潜在的相关分子位点。
