Rodriguez Alvarez Adriana A, Cieri Isabella F, Boya Mounika Naidu, Patel Shiv, Agrawal Aniket, Ferreira Sasha P Suarez, Alli Christianah, Sharma Shruti, Dua Anahita
Division of Vascular and Endovascular Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Department of Immunology, Tufts University School of Medicine, Boston, MA, United States.
Front Med (Lausanne). 2025 Jul 24;12:1615816. doi: 10.3389/fmed.2025.1615816. eCollection 2025.
Inflammation occurs in the initial stage of arterial atherosclerosis and serves as the first step in thrombus generation, with elevated inflammatory markers predicting myocardial infarction in coronary artery disease patients. Inflammation is known to alter the course of multiple diseases and can thus, also impact recovery post-treatment and surgical outcomes. Yet, there is a paucity of data regarding the relationship between inflammatory biomarkers and arterial thrombotic potential in peripheral artery disease (PAD) patients post-revascularization. Our pilot study attempts to fill this gap by evaluating if the expression of inflammatory biomarkers in PAD patients correlates with the incidence of thrombotic events post-revascularization.
Plasma samples were prospectively collected from PAD patients who underwent revascularization from 2021 to 2023 at monthly time points for 6 months from the procedure. Patients were followed for a total of 6 months post-procedure and those who experienced thrombotic events were identified. Nine patients with thrombotic events and 16 with non-thrombotic events along with 5 healthy volunteers were analyzed. Plasma samples were analyzed for the following pro-inflammatory markers: IL-1β (Interleukin-1 beta), IL-6, and TNF- (Tumor Necrosis Factor - alpha), GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor), IFNγ (Interferon-gamma), IL-8, MCP-1 (Monocyte Chemoattractant Protein-1). The Kruskal-Wallis test was performed to compare bio-inflammatory marker levels between groups.
A total of 303 patients were enrolled, of which 59 had thrombotic events. There were no differences between medications or disease burden between groups. Levels of circulating IL-6 and TNF- were significantly higher in the thrombosis cohort compared to the non-thrombosis cohort (55 vs. 38, < 0.02) and (159 vs. 110, < 0.02) respectively. Although there was a trend toward significance for IL-1β between the thrombotic cohort and non-thrombotic cohort, it did not reach statistical significance (18 vs. 11.5, = NS). There was no difference observed in aspirin's ability to dampen the inflammatory response between the two groups as all patients were on aspirin between the groups evaluated.
Pro-inflammatory markers IL-6 and TNF- are significantly increased in patients, 1 month prior to an arterial thrombotic event, as compared to patients without thrombotic events. These biomarkers could predict impending thrombosis in patients with PAD post-revascularization.
炎症发生在动脉粥样硬化的初始阶段，是血栓形成的第一步，炎症标志物升高可预测冠心病患者发生心肌梗死。已知炎症会改变多种疾病的进程，因此也会影响治疗后的恢复和手术结果。然而，关于外周动脉疾病（PAD）患者血管重建后炎症生物标志物与动脉血栓形成潜力之间的关系，数据较少。我们的初步研究试图通过评估PAD患者炎症生物标志物的表达是否与血管重建后血栓形成事件的发生率相关来填补这一空白。
前瞻性收集2021年至2023年接受血管重建的PAD患者的血浆样本，在术后6个月内每月采集一次。术后对患者进行总共6个月的随访，确定发生血栓形成事件的患者。分析了9例发生血栓形成事件的患者、16例未发生血栓形成事件的患者以及5名健康志愿者。对血浆样本进行以下促炎标志物分析：白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、干扰素-γ（IFNγ）、白细胞介素-8（IL-8）、单核细胞趋化蛋白-1（MCP-1）。采用Kruskal-Wallis检验比较各组间生物炎症标志物水平。
共纳入303例患者，其中59例发生血栓形成事件。两组之间的药物治疗或疾病负担无差异。与非血栓形成队列相比，血栓形成队列中循环IL-6和TNF-α水平显著更高（分别为55对38，P<0.02）和（159对110，P<0.02）。虽然血栓形成队列和非血栓形成队列之间IL-1β有显著趋势，但未达到统计学意义（18对11.5，P=无显著性差异）。两组之间阿司匹林抑制炎症反应的能力没有差异，因为在评估的组中所有患者都服用了阿司匹林。
与未发生血栓形成事件的患者相比，在动脉血栓形成事件前1个月，患者体内促炎标志物IL-6和TNF-α显著升高。这些生物标志物可以预测PAD患者血管重建后即将发生的血栓形成。
