血清可溶性致癌抑制因子-2与肺动脉高压血流动力学参数及预后的相关性分析

doi:10.3877/cma.j.issn.1674-6902.2025.04.020

目的

分析血清可溶性致癌抑制因子-2(soluble suppression of tumorigenicity-2, sST-2)与肺动脉高压(pulmonary arterial hypertension, PAH)血流动力学的相关性，及sST-2对PAH预后的预测。

方法

选择2020年1月至2024年12月我院收治的71例PAH患者为对象。患者接受右心导管插入术后采集血液样本，通过Presage™ST2测定血清sST-2。Spearman相关性和多变量线性回归分析血清sST-2与平均肺动脉压(mean pulmonary arterial pressure, mPAP)、肺动脉楔压(pulmonary artery wedge pressure, PAWP)、肺血管阻力(pulmonary vascular resistance, PVR)、右心房压(right atrial pressure, RAP)、肺动脉血氧分压(PaO₂)、肺动脉血二氧化碳分压(pulmonary artery carbon dioxide saturation, PaCO₂)的关系。

结果

PAH患者血清sST-2中位值为41.12 ng/ml。随访结束，临床恶化21例(29.57%)，包括WHO-FC恶化5例，PAH-特异性治疗升级4例，因心力衰竭或肺动脉高压进展再次住院8例，PAH相关死亡4例。PAH患者血清sST-2与mPAP(rho＝0.328，P<0.001)、PVR(rho＝0.331，P<0.001)、世界卫生组织功能分类(rho＝0.305，P<0.001)、NYHA心功能分级(rho＝0.196，P＝0.031)呈正相关，与PaO₂(rho＝－0.313，P<0.001)和6分钟步行距离(6MWD)(rho＝0.269，P＝0.003)呈负相关。多变量线性回归分析显示，sST-2与WHO-FC、mPAP和PAR呈正相关，与6MWD、PaO₂呈负相关(P<0.05)。多因素分析显示，sST-2(HR＝1.007，P＝0.003)和PaO₂(HR＝0.930，P＝0.016)是影响PAH患者临床恶化的预测性变量。sST-2联合PaO₂预测PAH患者临床恶化风险的灵敏性和特异性分别为88.89%和61.18%。

结论

PAH患者血清sST-2水平高，高sST-2与患者功能状态差和异常血流动力学有关。sST-2是PAH患者临床恶化预测因素，与PaO₂结合具有预测意义。

关键词: 可溶性致癌抑制因子-2, 肺动脉高压, 血流动力学, 相关性, 预后

Objective

To analyze the correlation between serum soluble suppression of tumorigenicity-2 (sST-2) levels and pulmonary arterial hypertension (PAH) hemodynamics, and to evaluate the predictive value of sST-2 for PAH prognosis.

Methods

Seventy-one PAH patients admitted to our hospital from January 2020 to December 2024 were enrolled. Blood samples were collected after right heart catheterization, and serum sST-2 levels were measured using the Presage ST2 assay. Spearman correlation and multivariate linear regression analyses were performed to assess the relationships between serum sST-2 and mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), right atrial pressure (RAP), partial pressure of oxygen in pulmonary artery blood (PaO₂), and partial pressure of carbon dioxide in pulmonary artery blood (PaCO₂).

Results

The median serum sST-2 level in PAH patients was 41.12 ng/ml. By the end of follow-up, clinical worsening occurred in 21 patients (29.57%), including 5 cases of WHO functional class (WHO-FC) deterioration, 4 cases requiring escalation of PAH-specific therapy, 8 cases rehospitalized due to heart failure or PAH progression and 4 deaths related to PAH. Serum sST-2 showed positive correlations with mPAP (rho=0.328, P<0.001), PVR (rho=0.331, P<0.001), WHO-FC (rho=0.305, P<0.001), and NYHA functional class (rho=0.196, P=0.031), and negative correlations with PaO₂(rho=-0.313, P<0.001) and 6-minute walking distance (6MWD) (rho=-0.269, P=0.003). Multivariate linear regression analysis revealed that sST-2 was positively associated with WHO-FC, mPAP, and PVR, and negatively associated with 6MWD and PaO₂(P<0.05). Multivariate analysis identified sST-2 (HR=1.007, P=0.003) and PaO₂(HR=0.930, P=0.016) as predictive variables for clinical worsening in PAH patients. The combination of sST-2 and PaO₂ achieved a sensitivity of 88.89% and specificity of 61.18% for predicting the risk of clinical worsening in PAH patients.

Conclusions

PAH patients exhibit elevated serum sST-2 levels. Higher sST-2 is associated with poor functional status and abnormal hemodynamics. sST-2 serves as a predictor of clinical worsening in PAH patients and demonstrates predictive value when combined with PaO₂.

Key words: Soluble suppression of tumorigenicity-2, Pulmonary hypertension, Hemodynamics, Correlation, Prognosis

表1 PAH患者临床恶化风险COX风险回归分析

影响因素	β	S.E.	HR(95%CI)	Walds	P值
6MWD	－0.002	0.001	0.998(0.996~1.001)	1.289	0.256
NYHA心功能分级	0.106	0.106	1.111(0.903~1.368)	0.990	0.320
WHO-FC	0.624	0.346	1.867(0.947~3.681)	3.250	0.071
吸烟史	－0.140	0.522	0.870(0.312~2.420)	0.072	0.789
高血压	0.080	0.387	1.083(0.507~2.314)	0.043	0.836
射血分数	0.002	0.023	1.002(0.957~1.048)	0.005	0.945
NT-proBNP	0.061	0.522	1.063(0.382~2.959)	0.014	0.907
CI	－0.028	0.144	0.973(0.733~1.291)	0.037	0.848
PaCO₂	0.033	0.409	1.033(0.463~2.303)	0.006	0.937
PaO₂	－0.090	0.027	0.914(0.867~0.965)	10.717	0.001
mPAP	－0.003	0.011	0.997(0.997~1.018)	0.061	0.805
PAWP	0.037	0.046	1.038(0.948~1.136)	0.642	0.423
PVR	0.001	0.027	1.001(0.950~1.055)	0.002	0.961
RAP	0.088	0.031	1.092(1.028~1.160)	8.179	0.004
sST-2≥41.12 ng/ml	0.009	0.002	1.009(1.004~1.013)	14.833	0.000

表1 PAH患者临床恶化风险COX风险回归分析

影响因素	β	S.E.	HR(95%CI)	Walds	P值
6MWD	－0.002	0.001	0.998(0.996~1.001)	1.289	0.256
NYHA心功能分级	0.106	0.106	1.111(0.903~1.368)	0.990	0.320
WHO-FC	0.624	0.346	1.867(0.947~3.681)	3.250	0.071
吸烟史	－0.140	0.522	0.870(0.312~2.420)	0.072	0.789
高血压	0.080	0.387	1.083(0.507~2.314)	0.043	0.836
射血分数	0.002	0.023	1.002(0.957~1.048)	0.005	0.945
NT-proBNP	0.061	0.522	1.063(0.382~2.959)	0.014	0.907
CI	－0.028	0.144	0.973(0.733~1.291)	0.037	0.848
PaCO₂	0.033	0.409	1.033(0.463~2.303)	0.006	0.937
PaO₂	－0.090	0.027	0.914(0.867~0.965)	10.717	0.001
mPAP	－0.003	0.011	0.997(0.997~1.018)	0.061	0.805
PAWP	0.037	0.046	1.038(0.948~1.136)	0.642	0.423
PVR	0.001	0.027	1.001(0.950~1.055)	0.002	0.961
RAP	0.088	0.031	1.092(1.028~1.160)	8.179	0.004
sST-2≥41.12 ng/ml	0.009	0.002	1.009(1.004~1.013)	14.833	0.000

图1 血清sST-2水平与PAH血流动力学参数相关性注：PaCO₂为动脉二氧化碳分压；PaO₂为动脉氧分压；mPAP为平均肺动脉压；PAWP为肺动脉楔压；PVR为肺血管阻力；RAP为毛右心房压；sST-2为可溶性致癌抑制因子-2

图2 PAH患者血清sST-2与临床参数的相关性注：6MWD为6分钟步行距离；NYHA为纽约心脏病学会；WHO-FC为世界卫生组织功能分类；NT-proBNP为N末端脑钠肽前体；sST-2为可溶性致癌抑制因子-2

表2 血清sST-2与PAH多变量线性回归分析

变量	未标准化系数B	S.E.	t值	P值	95%CI	偏相关系数
6MWD	－0.268	0.100	－2.684	0.008	－0.465~－0.070	－0.243
WHO-FC	42.114	17.069	2.467	0.015	8.304~75.924	0.224
NYHA心功能分级	20.385	14.382	1.417	0.159	－8.102~48.873	0.131
血流动力学参数
mPAP	3.173	0.837	3.790	0.000	1.515~4.832	0.333
PVR	0.119	0.031	3.857	0.000	0.058~0.181	0.338
PaO₂	－3.499	1.031	－3.392	0.000	－5.542~－1.456	－0.302

表2 血清sST-2与PAH多变量线性回归分析

变量	未标准化系数B	S.E.	t值	P值	95%CI	偏相关系数
6MWD	－0.268	0.100	－2.684	0.008	－0.465~－0.070	－0.243
WHO-FC	42.114	17.069	2.467	0.015	8.304~75.924	0.224
NYHA心功能分级	20.385	14.382	1.417	0.159	－8.102~48.873	0.131
血流动力学参数
mPAP	3.173	0.837	3.790	0.000	1.515~4.832	0.333
PVR	0.119	0.031	3.857	0.000	0.058~0.181	0.338
PaO₂	－3.499	1.031	－3.392	0.000	－5.542~－1.456	－0.302

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Correlation analysis of serum soluble suppression of tumorigenicity-2 with hemodynamic parameters and prognosis of pulmonary arterial hypertension

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Correlation analysis of serum soluble suppression of tumorigenicity-2 with hemodynamic parameters and prognosis of pulmonary arterial hypertension