{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:41:30Z","timestamp":1787226090377,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T00:00:00Z","timestamp":1634947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7-242209-BIOSTAT-CHF"],"award-info":[{"award-number":["FP7-242209-BIOSTAT-CHF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Atrial fibrillation (AF) and heart failure (HF) are two growing epidemics that frequently co-exist. We aimed to gain insights into the underlying pathophysiological pathways in HF patients with AF by comparing circulating biomarkers using pathway overrepresentation analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>From a panel of 92 biomarkers from different pathophysiological domains available in 1620 patients with HF, we first tested which biomarkers were dysregulated in patients with HF and AF (n = 648) compared with patients in sinus rhythm (n = 972). Secondly, pathway overrepresentation analyses were performed to identify biological pathways linked to higher plasma concentrations of biomarkers in patients who had HF and AF. Findings were validated in an independent HF cohort (n = 1219, 38% with AF). Patient with AF and HF were older, less often women, and less often had a history of coronary artery disease compared with those in sinus rhythm. In the index cohort, 24 biomarkers were up-regulated in patients with AF and HF. In the validation cohort, eight biomarkers were up-regulated, which all overlapped with the 24 biomarkers found in the index cohort. The strongest up-regulated biomarkers in patients with AF were spondin-1 (fold change 1.18, P = 1.33 \u00d7 10\u221212), insulin-like growth factor-binding protein-1 (fold change 1.32, P = 1.08 \u00d7 10\u22128), and insulin-like growth factor-binding protein-7 (fold change 1.33, P = 1.35 \u00d7 10\u221218). Pathway overrepresentation analyses revealed that the presence of AF was associated with activation amyloid-beta metabolic processes, amyloid-beta formation, and amyloid precursor protein catabolic processes with a remarkable consistency observed in the validation cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In two independent cohorts of patients with HF, the presence of AF was associated with activation of three pathways related to amyloid-beta. These hypothesis-generating results warrant confirmation in future studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvab331","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T22:50:49Z","timestamp":1634770249000},"page":"2478-2487","source":"Crossref","is-referenced-by-count":13,"title":["Pathophysiological pathways in patients with heart failure and atrial fibrillation"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4663-7213","authenticated-orcid":false,"given":"Bernadet T","family":"Santema","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-1675","authenticated-orcid":false,"given":"Vicente Artola","family":"Arita","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9056-7152","authenticated-orcid":false,"given":"Iziah E","family":"Sama","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00eblle","family":"Kloosterman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-2998","authenticated-orcid":false,"given":"Maarten P","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans L A","family":"Nienhuis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle C","family":"Van Gelder","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Department of Cardiology, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9 matique 1433, INSERM U1116, Universit\u00e9 de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT , Nancy , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6691-8568","authenticated-orcid":false,"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 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozine M","family":"Ter Maaten","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1471-7016","authenticated-orcid":false,"given":"John G","family":"Cleland","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College , London , UK"},{"name":"Department of Cardiology, Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6553-5749","authenticated-orcid":false,"given":"Leong L","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester , UK"},{"name":"Department of Cardiology, NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D","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 , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4530-3078","authenticated-orcid":false,"given":"Chim C","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, School of Medicine Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee , Dundee , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Leicester , 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