{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:46:43Z","timestamp":1785840403919,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe aortic valve stenosis (AS) and pulmonary hypertension (PH) are life-threatening cardiovascular conditions, necessitating early detection and intervention. Recent studies have explored the role of Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) in cardiovascular pathophysiology. Understanding its involvement may offer novel insights into disease mechanisms and therapeutic targets for these conditions. A total of 102 patients (46 female, 56 male) with severe AS undergoing a transcatheter aortic valve replacement (TAVR) in a single-center study were classified using echocardiography tests to determine systolic pulmonary artery pressure (sPAP) and the presence (sPAP \u2265 40 mmHg) or absence (sPAP &lt; 40 mmHg) of PH. Additionally, serial laboratory determinations of IGF-BP2 before, and at 24 h, 96 h, and 3 months after intervention were conducted in all study participants. Considering the entire cohort, patients with PH had significant and continuously higher serum IGF-BP2 concentrations over time than patients without PH. After subdivision by sex, it could be demonstrated that the above-mentioned results were only verifiable in males, but not in females. In the male patients, baseline IGF-BP2 levels before the TAVR was an isolated risk factor for premature death after intervention and at 1, 3, and 5 years post-intervention. The same was valid for the combination of male and echocardiographically established PH patients. The predictive role of IGF-BP2 in severe AS and concurrent PH remains unknown. A more profound comprehension of IGF-BP2 mechanisms, particularly in males, could facilitate the earlier consideration of the TAVR as a more effective and successful treatment strategy.<\/jats:p>","DOI":"10.3390\/ijms25158220","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T09:37:25Z","timestamp":1722332245000},"page":"8220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Insulin-like Growth Factor-Binding Protein 2 in Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Gender-Based Perspective"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-3853","authenticated-orcid":false,"given":"Elke","family":"Boxhammer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4743-3220","authenticated-orcid":false,"given":"Vera","family":"Paar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7265-8560","authenticated-orcid":false,"given":"Kristen","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah X.","family":"Gharibeh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Bovenkamp-Aberger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7118-501X","authenticated-orcid":false,"given":"Richard","family":"Rezar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lichtenauer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta C.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5679-4872","authenticated-orcid":false,"given":"Moritz","family":"Mirna","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.amjmed.2016.10.005","article-title":"Aortic Stenosis: Pathophysiology, Diagnosis, and Therapy","volume":"130","author":"Joseph","year":"2017","journal-title":"Am. J. Med."},{"key":"ref_2","first-page":"371","article-title":"Aortic Stenosis: Diagnosis and Treatment","volume":"93","author":"Grimard","year":"2016","journal-title":"Am. Fam. Physician"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.mayocp.2018.01.020","article-title":"Management of Patients with Aortic Valve Stenosis","volume":"93","author":"Kanwar","year":"2018","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e054222","DOI":"10.1136\/bmjopen-2021-054222","article-title":"Transcatheter aortic valve implantation versus surgical aortic valve replacement in patients with severe aortic stenosis: A systematic review and meta-analysis","volume":"11","author":"Swift","year":"2021","journal-title":"BMJ Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1093\/eurheartj\/ehab375","article-title":"Eight-year outcomes for patients with aortic valve stenosis at low surgical risk randomized to transcatheter vs. surgical aortic valve replacement","volume":"42","author":"Thyregod","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1093\/eurheartj\/ehac803","article-title":"ESC\/EACTS vs. ACC\/AHA guidelines for the management of severe aortic stenosis","volume":"44","author":"Lee","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3928\/00989134-20150414-02","article-title":"Severe Symptomatic Aortic Stenosis in Older Adults: Pathophysiology, Clinical Manifestations, Treatment Guidelines, and Transcatheter Aortic Valve Replacement (TAVR)","volume":"41","author":"Yurek","year":"2015","journal-title":"J. Gerontol. Nurs."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.tcm.2020.12.005","article-title":"Pulmonary hypertension in aortic valve stenosis","volume":"32","author":"Maeder","year":"2022","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1111\/echo.14633","article-title":"Right ventricle assessment in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation","volume":"37","author":"Santoro","year":"2020","journal-title":"Echocardiography"},{"key":"ref_10","first-page":"1319","article-title":"Prevalence of pulmonary hypertension in aortic stenosis and its influence on outcomes","volume":"109","author":"Ratwatte","year":"2023","journal-title":"Heart (Br. Card. Soc.)"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.jacc.2022.08.757","article-title":"Impact of Periprocedural Pulmonary Hypertension on Outcomes after Transcatheter Aortic Valve Replacement","volume":"80","author":"Miyamoto","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.jcmg.2018.02.015","article-title":"Pulmonary Hypertension in Patients with Severe Aortic Stenosis: Prognostic Impact after Transcatheter Aortic Valve Replacement: Pulmonary Hypertension in Patients Undergoing TAVR","volume":"12","author":"Alushi","year":"2019","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, W., Yu, K., Zhao, S.Y., Mo, D.G., Liu, J.H., Han, L.J., Li, T., and Yao, H.C. (2023). The impact of circulating IGF-1 and IGFBP-2 on cardiovascular prognosis in patients with acute coronary syndrome. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1126093"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hoeflich, A., David, R., and Hjortebjerg, R. (2018). Current IGFBP-Related Biomarker Research in Cardiovascular Disease-We Need More Structural and Functional Information in Clinical Studies. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00388"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ijcard.2018.09.091","article-title":"Insulin like growth factor binding protein 2 (IGFBP-2) for risk prediction in patients with severe aortic stenosis undergoing Transcatheter Aortic Valve Implantation (TAVI)","volume":"277","author":"Muessig","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1093\/eurheartj\/ehx381","article-title":"Staging classification of aortic stenosis based on the extent of cardiac damage","volume":"38","author":"Pibarot","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1007\/s10554-014-0498-5","article-title":"Determinants of pulmonary hypertension development in moderate or severe aortic stenosis","volume":"30","author":"Ahn","year":"2014","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/eurheartj\/ehab395","article-title":"2021 ESC\/EACTS Guidelines for the management of valvular heart disease","volume":"43","author":"Vahanian","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_19","first-page":"114","article-title":"Incidence, predictors, and impact on prognosis of systolic pulmonary artery pressure and its improvement after transcatheter aortic valve implantation: A multicenter registry","volume":"27","author":"Conrotto","year":"2015","journal-title":"J. Invasive Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/echo.14611","article-title":"Correlation between Doppler echocardiography and right heart catheterization assessment of systolic pulmonary artery pressure in patients with severe aortic stenosis","volume":"37","author":"Schewel","year":"2020","journal-title":"Echocardiography"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1164\/rccm.201701-0218PP","article-title":"Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary","volume":"195","author":"Vogelmeier","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yang, J., Griffiths, M., Nies, M.K., Brandal, S., Damico, R., Vaidya, D., Tao, X., Simpson, C.E., Kolb, T.M., and Mathai, S.C. (2020). Insulin-like growth factor binding protein-2: A new circulating indicator of pulmonary arterial hypertension severity and survival. BMC Med., 18.","DOI":"10.1186\/s12916-020-01734-3"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/s41390-020-01113-x","article-title":"Pediatric pulmonary hypertension: Insulin-like growth factor-binding protein 2 is a novel marker associated with disease severity and survival","volume":"88","author":"Griffiths","year":"2020","journal-title":"Pediatr. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Guiot, J., Bondue, B., Henket, M., Corhay, J.L., and Louis, R. (2016). Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis. BMC Pulm. Med., 16.","DOI":"10.1186\/s12890-016-0249-6"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cytogfr.2019.03.005","article-title":"Insulin-like growth factor binding proteins and angiogenesis: From cancer to cardiovascular disease","volume":"46","author":"Slater","year":"2019","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2002591","DOI":"10.1183\/13993003.02591-2020","article-title":"Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: Machine learning on proteomics from the DETECT cohort","volume":"57","author":"Bauer","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10679","DOI":"10.1038\/s41598-021-87701-1","article-title":"Inflammatory profile of induced sputum composition in systemic sclerosis and comparison with healthy volunteers","volume":"11","author":"Jacquerie","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1530\/eje.1.02064","article-title":"Inflammation is a modulator of the insulin-like growth factor (IGF)\/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis","volume":"154","author":"Street","year":"2006","journal-title":"Eur. J. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10882","DOI":"10.1038\/s41598-021-90333-0","article-title":"Serum IGFBP-2 in systemic sclerosis as a prognostic factor of lung dysfunction","volume":"11","author":"Guiot","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s43168-020-00050-x","article-title":"Non-invasive IGFBP1, IGFBP2 biomarkers as predictors and outcomes of usual interstitial pneumonia (UIP) therapeutic response","volume":"15","author":"Habeb","year":"2021","journal-title":"Egypt. J. Bronchol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kletzer, J., Hecht, S., Ramsauer, S., Scharinger, B., Kaufmann, R., Kammler, J., Kellermair, J., Akbari, K., Blessberger, H., and Steinwender, C. (2023). A Story of PA\/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-The Rise of IGF-BP2 and GDF-15. J. Cardiovasc. Dev. Dis., 10.","DOI":"10.3390\/jcdd10010022"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Rodriguez-Arias, J.J., and Garc\u00eda-\u00c1lvarez, A. (2021). Sex Differences in Pulmonary Hypertension. Front. Aging, 2.","DOI":"10.3389\/fragi.2021.727558"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/bph.12281","article-title":"Pulmonary arterial hypertension: Basis of sex differences in incidence and treatment response","volume":"171","author":"Mair","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/(SICI)1097-4695(20000605)43:3<269::AID-NEU5>3.0.CO;2-D","article-title":"Estradiol and progesterone regulate the expression of insulin-like growth factor-I receptor and insulin-like growth factor binding protein-2 in the hypothalamus of adult female rats","volume":"43","author":"Chowen","year":"2000","journal-title":"J. Neurobiol."},{"key":"ref_35","first-page":"E99","article-title":"Associations of insulin-like growth factor binding protein-2 with metabolic profile and hepatic fat deposition in asymptomatic men and women. American journal of physiology","volume":"325","author":"Rauzier","year":"2023","journal-title":"Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1530\/EJE-18-0422","article-title":"IGFBP-2 and aging: A 20-year longitudinal study on IGFBP-2, IGF-I, BMI, insulin sensitivity and mortality in an aging population","volume":"180","author":"Carlson","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s12031-015-0589-3","article-title":"Insulin-like Growth Factor Binding Protein-2 Promotes Adhesion of Endothelial Progenitor Cells to Endothelial Cells via Integrin \u03b15\u03b21","volume":"57","author":"Feng","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JME-14-0215","article-title":"Endothelial cells and the IGF system","volume":"54","author":"Bach","year":"2015","journal-title":"J. Mol. Endocrinol."},{"key":"ref_39","first-page":"138","article-title":"Elevated systolic pulmonary artery pressure is a substantial predictor of increased mortality after transcatheter aortic valve replacement in males, not in females","volume":"113","author":"Boxhammer","year":"2024","journal-title":"Clin. Res. Cardiol. Off. J. Ger. Card. Soc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8220\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:25:08Z","timestamp":1760109908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,27]]},"references-count":39,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158220"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158220","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,27]]}}}