NVAF血栓发病患者外周血IL-33及其受体sST2 mRNA表达特征分析

    Expression characteristics of IL-33 and its receptor sST2 mRNA in the peripheral blood of patients with NVAF thrombosis

    • 摘要:
      目的 探究白细胞介素-33(IL-33) mRNA及其受体可溶性基质裂解素2(sST2) mRNA在非瓣膜性心房颤动(NVAF)患者抗凝治疗后发生血栓的预测价值。
      方法 选取2023年2月到2024年3月于九四〇医院接受诊治的340例NVAF患者为研究组,同期体检健康者100例作为对照组,按照随访期内发生终点事件情况(是否发生动脉血栓)将NVAF组分为血栓事件组(n=33例)以及无事件组(n=307例)两个亚组。采用RT-PCR测定受试者外周血中IL-33 mRNA、sST2 mRNA表达水平,并比较3组IL-33 mRNA、sST2 mRNA表达的差异,同时采用ROC曲线评价IL-33 mRNA、sST2 mRNA预测血栓事件的性能,采用Logistic多元回归分析得出优势比(OR),采用COX比例风险回归模型得出风险比(HR)。
      结果 与对照组比较,NVAF组及其两个亚组(血栓事件组和无事件组)IL-33 mRNA、sST2 mRNA表达明显升高(均P<0.01);血栓事件组IL-33 mRNA、sST2 mRNAT表达较无事件组、NVAF组均明显升高(均P<0.01)。外周血IL-33 mRNA、sST2 mRNA预测NVAF患者3个月内血栓事件的AUC分别为0.823、0.802,而联合诊断的AUC为0.923,且灵敏度为88.16%,特异度为85.58%,均高于单个指标;单因素分析结果显示,NVAF患者外周血IL-33 mRNA、sST2 mRNA与年龄、缺血事件、血管疾病、高血压、2型糖尿病和慢性心力衰竭等显著相关(均P<0.01),而与性别、抗凝药物类型和服药依从性等则无显著相关,多元Logistic回归分析显示IL-33 mRNA、sST2 mRNA与缺血事件、血管疾病、高血压、2型糖尿病和慢性心力衰竭等显著相关(均P<0.01),而与年龄则无显著相关。COX回归模型结果显示,外周血IL-33 mRNA、sST2 mRNA表达未高于临界值者与高于临界值者在3个月内的血栓事件相对HR分别为0.773和0.801,而两者联合预测时,其血栓事件相对HR为0.734,可有效识别血栓事件。
      结论 NVAF抗凝患者外周血中IL-33 mRNA、sST2 mRNA表达变化与多种临床病理因素相关,并与3个月内的血栓风险关系紧密,对此类患者发生血栓的预测有指导作用。

       

      Abstract:
      AIM To explore the predictive value of interleukin-33 (IL-33) mRNA and its receptor soluble matrix lysin 2 (sST2) mRNA in the occurrence of thrombosis in patients with non-valvular atrial fibrillation (NVAF) after anticoagulation therapy.
      METHODS A total of 340 patients with NVAF anticoagulation who were admitted to the 940th Hospital of Joint Logistics Support Force of PLA from February 2023 to March 2024 were selected as the research subjects. According to the end-point events during the follow-up period, the subjects were divided into thrombotic event groups (n=33 cases) and the event-free group (n=307 cases). In addition, 100 healthy people who had physical examinations during the same period were selected as the control group. Real-time fluorescent quantitative polymerase chain reaction (RT-PCR) was used to determine the expression of IL-33 mRNA and sST2 mRNA in the peripheral blood of the subjects. The differences in the expression of IL-33 mRNA and sST2 mRNA in the three groups were also compared. Meanwhile, the receiver operating characteristic (ROC) curve was used to evaluate the performance of IL-33 mRNA and sST2 mRNA in predicting thrombotic events. Logistic regression was used to obtain odds ratio (OR), and COX proportional hazard regression model was used to obtain the hazard ratio (HR).
      RESULTS  Compared with the control group, the expression of IL-33 mRNA and sST2 mRNA was significantly increased in the NVAF group and its two subgroups (thrombotic event group and no event group) (both P<0.01); The expression of IL-33 mRNA and sST2 mRNA in the thrombotic event group was significantly higher than that in the non event group and the NVAF group (both P<0.01). The AUC of predicting thrombotic events in NVAF patients within 3 months using peripheral blood IL-33 mRNA and sST2 mRNA were 0.823 and 0.802, respectively, while the AUC for combined diagnosis was 0.923, with a sensitivity of 88.16% and specificity of 85.58%, both higher than individual indicators; The results of univariate analysis showed that IL-33 mRNA and sST2 mRNA in the peripheral blood of NVAF patients were significantly correlated with age, ischemic events, vascular diseases, hypertension, type 2 diabetes and chronic heart failure (all P<0.01), while there was no significant correlation with gender, anticoagulant drug type and drug compliance. Multiple logistic regression analysis showed that IL-33 mRNA and sST2 mRNA were significantly correlated with ischemic events, vascular diseases, hypertension, type 2 diabetes and chronic heart failure (all P<0.01), but there was no significant correlation with age. The COX regression model results showed that the relative HR of thrombotic events within 3 months were 0.773 and 0.801 for those whose peripheral blood IL-33 mRNA and sST2 mRNA expression did not exceed the critical value and those who exceeded the critical value, respectively. When the two were combined for prediction, the relative HR of thrombotic events was 0.734, which can effectively identify thrombotic events.
      CONCLUSION The changes in the expression of IL-33 mRNA and sST2 mRNA in the peripheral blood of NVAF anticoagulation patients are related to a variety of clinicopathological factors, and are closely related to the risk of thrombosis, which provide references for the prediction of thrombosis in such patients.

       

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