血清可溶性生长刺激表达基因2蛋白水平在结缔组织病相关肺动脉高压患者预后评估中的价值

The prognostic value of sST2 in connective tissue disease-related pulmonary arterial hypertension

目的探讨血清可溶性生长刺激表达基因2蛋白(sST2)在CTD相关肺动脉高压(PAH)患者预后评估中的价值。方法回顾性分析2017年1月至2022年7月期间在南京医科大学第一附属医院风湿免疫科由右心导管诊断的60例CTD-PAH患者临床资料。采用Excel表格收集患者基线及随访资料:血清sST2水平、人口统计学资料、原发病和PAH临床特征资料、治疗方案、生存状态和临床恶化事件的发生时间。主要研究终点是3年首次发生临床恶化事件。通过t检验或Wilcoxon秩和检验比较不同组间的连续变量,χ^(2)检验比较分类变量;通过Kaplan-Meier方法计算患者3年无临床恶化事件生存率,对数秩和检验比较组间差异;通过单因素和多因素COX比例风险模型分析CTD-PAH患者发生临床恶化事件的独立危险因素。结果与sST2<35 ng/ml患者相比,sST2≥35 ng/ml的CTD-PAH患者WHO心功能分级Ⅲ~Ⅳ级、平均右心房压力N末端脑钠肽前体(NT-proBNP)和CRP水平更高[13/34与19/26,χ^(2)=7.19,P=0.007;4.00(3.00,6.00)mmHg与8.00(4.00,12.00)mmHg,Z=-2.98,P=0.003;474.30(135.70,1947.50)ng/L与2650.50(485.33,5906.50)ng/L,Z=-2.72,P=0.007;3.24(2.56,7.01)mg/L与9.66(3.20,19.33)mg/L,Z=-2.50,P=0.012];Kaplan-Meier分析显示sST2≥35 ng/ml患者3年无临床恶化事件生存率显著降低(24.1%与84.0%,P=0.001);多因素COX回归分析显示sST2是CTD-PAH患者3年临床恶化事件发生风险增加的独立危险因素[HR值(95%CI)=1.020(1.001,1.039),P=0.035]。结论血清sST2是CTD-PAH患者发生临床恶化事件的独立危险因素。

Objective To explore the value of serum soluble growth stimulation expressed gene 2(sST2)in predicting prognosis of patients with connective tissue disease-related pulmonary arterial hypertension(CTD-PAH).Methods This retrospective cohort study enrolled 60 CTD-PAH patients diagnosed by right heart catheterization(RHC)during Jan 2017 and Jul 2022.Baseline and follow-up data collected including the levels of sST2,demographic data,clinical data of CTD and PAH,treatment regimen of CTD and PAH,survival status and the onset time of clinical deterioration events.The primary endpoint was the first occurring of clinical deterioration in 3-years.The t-test or Wilcoxon rank-sum test was used for continuous variables com-parison between different groups,and the chi-square test was used to compare categorical variables.Event-free survival rates were evaluated using Kaplan-Meier analysis and groups comparison were performed by the log-rank test.COX univariate and multivariate proportional hazard models were used to identify independent risk factors for poor prognosis.Results Compared with the patients with sST2<35 ng/ml,CTD-PAH patients with sST2≥35 ng/ml showed higher WHO cardiac funcation class(Ⅲ-Ⅳ),mean right atrial pressure,N-terminal probrain na-triuretic peptide(NT-proBNP)and CRP levels[13/34 vs 19/26,χ^(2)=7.19,P=0.007;4.00(3.00,6.00)mmHg vs 8.00(4.00,12.00)mmHg,Z=-2.98,P=0.003;474.30(135.70,1947.50)ng/L vs 2650.50(485.33,5906.50)ng/L,Z=-2.72,P=0.007;3.24(2.56,7.01)mg/L vs 9.66(3.20,19.33)mg/L,Z=-2.50,P=0.012];Kaplan-Meier analysis showed that event-free survival rate in 3 years was significantly lower in patients with sST2≥35 ng/ml(24.1%vs 84.0%,P=0.001).Multivariate COX regression analysis showed that sST2 was an independent predictor of clinical worsening in patients with CTD-PAH[HR(95%CI)=1.020(1.001,1.039),P=0.035].Conclusion Serum sST2 is an independent risk factor for clinical deterioration in CTD-PAH patients.