Correlation Between Serum GDF-15 Level and Pulmonary Vascular Morphological Changes and Prognosis in Patients with Pulmonary Arterial Hypertension

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2023 Jun 8

PMID 37288264

Authors

Yasenjiang Maimaiti

Hui Cheng

Zitong Guo

Xiaolin Yu

Adilijiang Tuohuti

Guoqing Li

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate how serum GDF-15 concentration affects pulmonary artery hemodynamics and pulmonary vascular morphological changes in patients with pulmonary arterial hypertension.

Methods: A total of 45 patients admitted to our hospital from December 2017 to December 2019, were selected for the study. Pulmonary vascular hemodynamics and pulmonary vascular morphology were detected by RHC and IVUS. Serum GDF-15 levels were detected by enzyme-linked immunosorbent assay (ELISA). Based on the concentration of GDF-15, the patients were divided into two groups-the normal GDF-15 group (GDF-15 <1,200 pg/ml, 12 cases) and the elevated GDF-15 group (GDF-15 ≥1,200 pg/ml, 33 cases). A statistical analysis was performed to compare the effects of normal blood GDF-15 levels and high serum GDF-15 levels on hemodynamics and pulmonary vascular morphology in each group of patients.

Results: The average levels of RVP, sPAP, dPAP, mPAP, and PVR in patients with elevated GDF-15 levels were higher than those in patients with normal GDF-15 levels. The difference between the two groups was statistically significant ( < 0.05). The average levels of Vd, elastic modulus, stiffness index β, lesion length, and PAV in the normal GDF-15 group were lower than those in the elevated GDF-15 group. The average levels of compliance, distensibility, and minimum l umen area were higher than those in the elevated GDF-15 group. The difference between the two groups was statistically significant ( < 0.05). The survival analysis results showed that the 1-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 100% and 87.9%, respectively, and that the 3-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 91.7% and 78.8%, respectively. The survival rates of the two groups were compared by the Kaplan Meier method, and the difference was not statistically significant ( > 0.05).

Conclusion: Patients with pulmonary arterial hypertension with elevated GDF-15 levels have higher pulmonary arterial pressure, higher pulmonary vascular resistance, and more serious pulmonary vascular lesions, which are potentially more harmful. There was no statistically significant difference in survival rates among patients with different serum GDF-15 levels.

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References

Tuder R . Pulmonary vascular remodeling in pulmonary hypertension. Cell Tissue Res. 2016; 367(3):643-649. PMC: 5408737. DOI: 10.1007/s00441-016-2539-y. View

Wischhusen J, Melero I, Fridman W . Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front Immunol. 2020; 11:951. PMC: 7248355. DOI: 10.3389/fimmu.2020.00951. View

Wang Y, Chen J, Sang T, Chen C, Peng H, Lin X . NAG-1/GDF15 protects against streptozotocin-induced type 1 diabetes by inhibiting apoptosis, preserving beta-cell function, and suppressing inflammation in pancreatic islets. Mol Cell Endocrinol. 2022; 549:111643. DOI: 10.1016/j.mce.2022.111643. View

Ackermann K, Bonaterra G, Kinscherf R, Schwarz A . Growth differentiation factor-15 regulates oxLDL-induced lipid homeostasis and autophagy in human macrophages. Atherosclerosis. 2019; 281:128-136. DOI: 10.1016/j.atherosclerosis.2018.12.009. View

Fayed H, Coghlan J . Pulmonary Hypertension Associated with Connective Tissue Disease. Semin Respir Crit Care Med. 2019; 40(2):173-183. DOI: 10.1055/s-0039-1685214. View

Rosenzweig E, Abman S, Adatia I, Beghetti M, Bonnet D, Haworth S . Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management. Eur Respir J. 2018; 53(1). PMC: 6351335. DOI: 10.1183/13993003.01916-2018. View

Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J . GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med. 2011; 17(5):581-8. DOI: 10.1038/nm.2354. View

Mathai S, Suber T, Khair R, Kolb T, Damico R, Hassoun P . Health-related Quality of Life and Survival in Pulmonary Arterial Hypertension. Ann Am Thorac Soc. 2015; 13(1):31-9. PMC: 4722843. DOI: 10.1513/AnnalsATS.201412-572OC. View

Qi P, Ma M, Kuai J . Identification of growth differentiation factor 15 as a pro-fibrotic factor in mouse liver fibrosis progression. Int J Exp Pathol. 2021; 102(3):148-156. PMC: 8139377. DOI: 10.1111/iep.12398. View

10.

Kovacs G, Dumitrescu D, Barner A, Greiner S, Grunig E, Hager A . Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol. 2018; 272S:11-19. DOI: 10.1016/j.ijcard.2018.08.083. View

11.

Geenen L, Baggen V, Kauling R, Koudstaal T, Boomars K, Boersma E . Growth differentiation factor-15 as candidate predictor for mortality in adults with pulmonary hypertension. Heart. 2019; 106(6):467-473. DOI: 10.1136/heartjnl-2019-315111. View

12.

Ploegstra M, Brokelman J, Roos-Hesselink J, Douwes J, van Osch-Gevers L, Hoendermis E . Pulmonary arterial stiffness indices assessed by intravascular ultrasound in children with early pulmonary vascular disease: prediction of advanced disease and mortality during 20-year follow-up. Eur Heart J Cardiovasc Imaging. 2017; 19(2):216-224. DOI: 10.1093/ehjci/jex015. View

13.

Li P, Lv H, Zhang B, Duan R, Zhang X, Lin P . Growth Differentiation Factor 15 Protects SH-SY5Y Cells From Rotenone-Induced Toxicity by Suppressing Mitochondrial Apoptosis. Front Aging Neurosci. 2022; 14:869558. PMC: 9201950. DOI: 10.3389/fnagi.2022.869558. View

14.

Lambrecht S, Smith V, De Wilde K, Coudenys J, Decuman S, Deforce D . Growth differentiation factor 15, a marker of lung involvement in systemic sclerosis, is involved in fibrosis development but is not indispensable for fibrosis development. Arthritis Rheumatol. 2014; 66(2):418-27. DOI: 10.1002/art.38241. View

15.

Li G, Li Y, Tan X, Jia P, Zhao J, Liu D . Plasma Growth Differentiation Factor-15 is a Potential Biomarker for Pediatric Pulmonary Arterial Hypertension Associated with Congenital Heart Disease. Pediatr Cardiol. 2017; 38(8):1620-1626. DOI: 10.1007/s00246-017-1705-7. View

16.

Xu G, Chen J, Jo S, Grayson T, Ramanadham S, Koizumi A . Deletion of Gdf15 Reduces ER Stress-induced Beta-cell Apoptosis and Diabetes. Endocrinology. 2022; 163(5). PMC: 9272264. DOI: 10.1210/endocr/bqac030. View

17.

Chung L, Liu J, Parsons L, Hassoun P, McGoon M, Badesch D . Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010; 138(6):1383-94. PMC: 3621419. DOI: 10.1378/chest.10-0260. View

18.

Lau E, Iyer N, Ilsar R, Bailey B, Adams M, Celermajer D . Abnormal pulmonary artery stiffness in pulmonary arterial hypertension: in vivo study with intravascular ultrasound. PLoS One. 2012; 7(3):e33331. PMC: 3316557. DOI: 10.1371/journal.pone.0033331. View

19.

Duran L, Kayhan S, Guzel A, Ince M, Kati C, Akdemir H . The prognostic values of GDF-15 in comparison with NT-proBNP in patients with normotensive acute pulmonary embolism. Clin Lab. 2014; 60(8):1365-71. DOI: 10.7754/clin.lab.2013.130827. View

20.

Galie N, Humbert M, Vachiery J, Gibbs S, Lang I, Torbicki A . 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS):.... Eur Heart J. 2015; 37(1):67-119. DOI: 10.1093/eurheartj/ehv317. View