{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:59:41Z","timestamp":1789419581290,"version":"build-2803163510"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P\u2009&amp;lt;\u20090.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r2\u2009=\u20090.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors\/angiotensin receptor blockers after 3\u2009months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06\u20131.27, P\u2009=\u20090.002, per log increase). Analyses in the validation cohort yielded comparable findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1437","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T23:57:57Z","timestamp":1551916677000},"page":"732-743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Bio-Adrenomedullin as a Marker of Congestion in Patients with New-Onset and Worsening Heart Failure"],"prefix":"10.1093","volume":"21","author":[{"given":"Jozine M.","family":"ter Maaten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan","family":"Kremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biniyam G.","family":"Demissei","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Struck","sequence":"additional","affiliation":[{"name":"Sphingotec GmbH , Hennigsdorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Sphingotec GmbH , Hennigsdorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK), and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin ,","place":["Germany"]},{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen (UMG) , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester ,","place":["UK"]},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"University of Bergen , Bergen ,","place":["Norway"]},{"name":"Stavanger University Hospital , Stavanger ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Institute of Cardiology, Radiological Sciences and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester ,","place":["UK"]},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.R.","family":"Romaine","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester ,","place":["UK"]},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Cleland","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Inserm CIC1433, Universit\u00e9 de Lorrain, CHU de Nancy , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital & Medical School , Dundee ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The 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