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

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

Abstract

Abstract:

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

Yang Ren, Fang Lin, Wenjuan Jiang, Ni Wang, Feifei Du, Yaxin Qiao. Correlation analysis of serum soluble suppression of tumorigenicity-2 with hemodynamic parameters and prognosis of pulmonary arterial hypertension[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(04): 609-614.

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Figures/Tables 4

References 30

1	任成山，卞士柱，胡明冬. 肺动脉高压的成因及治疗新理念[J/CD]. 中华肺部疾病杂志(电子版), 2023, 16(1): 1-5.
2	Ruopp NF, Cockrill BA. Diagnosis and treatment of pulmonary arterial hypertension: a review[J]. Jama, 2022, 327(14): 1379-1391.
3	Gelzinis TA. Pulmonary hypertension in 2021: part I-definition, classification, pathophysiology, and presentation[J]. J Cardiothorac Vasc Anesth, 2022, 36(6): 1552-1564.
4	Akdogan A, Sarı A, Sade LE. Primary systemic Vasculitides as a cause of group Ⅳ pulmonary hypertension[J]. Anatol J Cardiol, 2023, 27(12): 677.
5	Wissmüller M, Tichelbäcker T, Finke K, et al. Pulmonale hypertonie im zusammenhang mit linksherzerkrankungen (Gruppe 2)[Pulmonary hypertension associated with left heart disease (group 2)][J]. Dtsch Med Wochenschr, 2023, 148(23): 1498-1506.
6	Gonzalez-Hermosillo LM, Cueto-Robledo G, Roldan-Valadez E, et al. Right heart catheterization (RHC): a comprehensive review of provocation tests and hepatic hemodynamics in patients with Pulmonary Hypertension (PH)[J]. Curr Probl Cardiol, 2022, 47(12): 101351.
7	Guglielmi G, Krishnathasan K, Constantine A, et al. Cardiac catheterisation in pulmonary arterial hypertension: Tips and tricks to enhance diagnosis and guide therapy[J]. Int J Cardiol Congenit Heart Dis, 2024, 17: 100527.
8	Banaszkiewicz M, Gᶏsecka A, Darocha S, et al. Circulating blood-based biomarkers in pulmonary hypertension[J]. J Clin Med, 2022, 11(2): 383.
9	Khan S, Rasool ST. Current use of cardiac biomarkers in various heart conditions[J]. Endocr Metab Immune Disord Drug Targets, 2021, 21(6): 980-993.
10	Cao S, Qin X, Li C, et al. The IL-33/ST2 axis affects adipogenesis through regulating the TRAF6/RelA pathway[J]. Int J Mol Sci, 2024, 25(22): 12005.
11	Park S, Kim IC, Kim H, et al. Ability of soluble ST2 to predict left ventricular remodeling in patients with acute coronary syndrome[J]. Heart Vessels, 2022, 37(2): 173-183.
12	Ahmadzadeh K, Dizaji SR, Balabandian M, et al. Soluble suppression of tumorigenicity-2 as a candidate prognostic marker for stroke: A systematic review[J]. Ann Lab Med, 2023, 43(6): 585-595.
13	中华医学会呼吸病学分会肺栓塞与肺血管病学组，中国医师协会呼吸医师分会肺栓塞与肺血管病工作委员会，全国肺栓塞与肺血管病防治协作组，等. 中国肺动脉高压诊断与治疗指南(2021版)[J]. 中华医学杂志，2021, 101(1): 11-51.
14	Pratama RS, Hartopo AB, Anggrahini DW, et al. Serum soluble suppression of tumorigenicity-2 level associates with severity of pulmonary hypertension associated with uncorrected atrial septal defect[J]. Pulm Circ, 2020, 10(2): 2045894020915832.
15	Kerkütlüoglu M, Gunes H, Atilla N, et al. Relationship between soluble ST2 level and chronic thromboembolic pulmonary hypertension (CTEPH) in acute pulmonary embolism (PE) patients[J]. Cureus, 2023, 15(7): e42449.
16	张艺萱，罗金丹，葛小丽，等. 先天性心脏病伴PH血清H-FABP、NT-proBNP与肺动脉内径、血流速度及PASP的关系[J/CD]. 中华肺部疾病杂志(电子版), 2024, 17(2): 252-255.
17	Huang F, Chen WY, Ma J, et al. Paradoxical role of interleukin-33/suppressor of tumorigenicity 2 in colorectal carcinogenesis: Progress and therapeutic potential[J]. World J Clin Cases, 2022, 10(1): 23.
18	鱼帆，苏小慧，卞士柱，等. 肺动脉高压无创诊断和病情评估技术研究进展[J/CD]. 中华肺部疾病杂志(电子版), 2024, 17(6): 1031-1036.
19	Cheng TY, Chen YC, Li SJ, et al. Interleukin-33/ST2 axis involvement in atrial remodeling and arrhythmogenesis[J]. Transl Res, 2024, 268: 1-12.
20	Borghi SM, Carvalho TT, Bertozzi MM, et al. Role of the interleukin-33 (IL-33)/suppressor of tumorigenicity 2(ST2) signaling in superoxide anion-triggered inflammation and pain behavior in mice[J]. Chem Biol Interact, 2025, 413: 111476.
21	Miftode RS, Petris AO, Onofrei Aursulesei V, et al. The novel perspectives opened by ST2 in the pandemic: a review of its role in the diagnosis and prognosis of patients with heart failure and COVID-19[J]. Diagnostics, 2021, 11(2): 175.
22	Günther F, Straub RH, Hartung W, et al. Increased serum levels of soluble ST2 as a predictor of disease progression in systemic sclerosis[J]. Scand J Rheumatol, 2022, 51(4): 315-322.
23	Chen J, Xiao P, Song D, et al. Growth stimulation expressed gene 2 (ST2): Clinical research and application in the cardiovascular related diseases[J]. Front Cardiovasc Med, 2022, 9: 1007450.
24	Hojda SE, Chis IC, Clichici S. Biomarkers in pulmonary arterial hypertension[J]. Diagnostics, 2022, 12(12): 3033.
25	Iannazzo F, Pellicano C, Colalillo A, et al. Interleukin-33 and soluble suppression of tumorigenicity 2 in scleroderma cardiac involvement[J]. Clin Exp Med, 2023, 23(3): 897-903.
26	Boxhammer E, Köller C, Paar V, et al. Systolic pulmonary artery pressure and cardiovascular biomarkers-new non-invasive ways to detect pulmonary hypertension in patients with severe aortic valve stenosis undergoing TAVR？[J]. Rev Cardiovasc Med, 2022, 23(7): 224.
27	Vu LD, Saravia J, Jaligama S, et al. Deficiency in ST2 signaling ameliorates RSV-associated pulmonary hypertension[J]. Am J Physiol Heart Circ Physiol, 2021, 321(2): H309-H317.
28	Ghali R, Altara R, Louch WE, et al. IL-33 (interleukin 33)/sST-2 axis in hypertension and heart failure[J]. Hypertension, 2018, 72(4): 818-828.
29	Miura-Takahashi E, Tsudome R, Suematsu Y, et al. An elevated level of soluble suppression of tumorigenicity 2, but not galectin-3, is associated with the presence of coronary artery disease in hypertensive patients[J]. Hypertens Res, 2025, 48(2): 650-661.
30	Du X, Kumar P, Liu C, et al. Soluble suppression of tumorigenicity 2 associated with left ventricular thrombosis in patients with ST-segment elevation myocardial infarction[J]. BMC Cardiovasc Disord, 2025, 25(1): 204.

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

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

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

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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