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We evaluated the prognostic value of IGFBP7 in patients with heart failure and examined associations to uncover potential new pathophysiological pathways related to increased plasma IGFBP7 concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We have measured plasma IGFBP7 concentrations in 2250 subjects with new-onset or worsening heart failure (BIOSTAT-CHF cohort). Higher IGFBP7 plasma concentrations were found in older subjects, those with worse kidney function, history of atrial fibrillation, and diabetes mellitus type 2, and in subjects with higher number of HF hospitalizations. Higher IGFBP7 levels also correlate with the levels of several circulating biomarkers, including higher NT-proBNP, hsTnT, and urea levels. Cox regression analyses showed that higher plasma IGFBP7 concentrations were strongly associated with increased risk of all three main endpoints (hospitalization, all-cause mortality, and combined hospitalization and mortality) (HR 1.75, 95% CI 1.25\u20132.46; HR 1.71, 95% CI 1.39\u20132.11; and HR 1.44, 95% CI 1.23\u20131.70, respectively). IGFBP7 remained a significant predictor of these endpoints in patients with both reduced and preserved ejection fraction. Likelihood ratio test showed significant improvement of all three risk prediction models, after adding IGFBP7 (P &amp;lt; 0.001). A biomarker network analysis showed that IGFBP7 levels activate different pathways involved in the regulation of the immune system. Results were externally validated in BIOSTAT-CHF validation cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IGFPB7 presents as an independent and robust prognostic biomarker in patients with HF, with both reduced and preserved ejection fraction. We validate the previously published data showing IGFBP7 has correlations with a number of echocardiographic markers. Lastly, IGFBP7 pathways are involved in different stages of immune system regulation, linking heart failure to senescence pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14120","type":"journal-article","created":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T10:20:00Z","timestamp":1662891600000},"page":"4167-4176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), a Link Between Heart Failure and Senescence"],"prefix":"10.1093","volume":"9","author":[{"given":"Valentina","family":"Bracun","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"van Essen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"Stavanger University Hospital, University of Bergen , Bergen ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universite de Lorraine | Inserm, Centre d'Investigations Cliniques , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties | Radiological Sciences and Public Health | Institute of Cardiology, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies (BCRT) | German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences | University of Leicester | Glenfield Hospital | and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Department of Heart Diseases, Wroclaw Medical University , Wroc\u0142aw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens | School of Medicine, Attikon University Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics | Institute of Health and Wellbeing, University of Glasgow | Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine | Medical Research Institute | Ninewells Hospital & Medical School, University of Dundee , Dundee ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences | University of Leicester | Glenfield Hospital | and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canxia","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"de Wit","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The 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