{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:34:22Z","timestamp":1790663662528,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":620,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Union Commission's Seventh Framework programme"},{"name":"Netherlands Cardiovascular Research Initiative"},{"name":"Dutch Heart Foundation, Dutch Cardiovascular AllianceCVON2016-Early HFPEF","award":["2015-10"],"award-info":[{"award-number":["2015-10"]}]},{"name":"CVON She-PREDICTS","award":["2017-21"],"award-info":[{"award-number":["2017-21"]}]},{"DOI":"10.13039\/501100003130","name":"FWO","doi-asserted-by":"publisher","award":["G091018N"],"award-info":[{"award-number":["G091018N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"FWO","doi-asserted-by":"publisher","award":["G0B5930N"],"award-info":[{"award-number":["G0B5930N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G091018N"],"award-info":[{"award-number":["G091018N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0B5930N"],"award-info":[{"award-number":["G0B5930N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73\u2009\u00b1\u20096\u2009years; women 26%; LAVi 32\u2009\u00b1\u20099\u2009ml\/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population-based cohort (STANISLAS; n\u2009=\u20091640; mean age 49\u2009\u00b1\u200914\u2009years; women 51%; LAVi 23\u2009\u00b1\u20097\u2009ml\/m2). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase-2 (MMP-2), insulin-like growth factor binding protein-2 (IGFBP-2) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (false discovery rates [FDR] &amp;lt;0.05). These associations were externally replicated in STANISLAS (all FDR\u2009&amp;lt;0.05). Among these biomarkers, spironolactone decreased concentrations of MMP-2 and NT-proBNP, regardless of baseline LAVi (pinteraction\u2009&amp;gt;\u20090.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E\/e', blood pressure and serum procollagen type I C-terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi (pinteraction\u2009&amp;gt;\u20090.10).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In individuals without heart failure, LAVi was associated with MMP-2, IGFBP-2 and NT-proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3202","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T05:53:54Z","timestamp":1711432434000},"page":"1231-1241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic Profiles of Left Atrial Volume and Its Influence on Response to Spironolactone: Findings from the HOMAGE Trial and STANISLAS Cohort"],"prefix":"10.1093","volume":"26","author":[{"given":"Masatake","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]},{"name":"Department of Cardiology, Tokyo Medical University Hospital , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]},{"name":"Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto , Porto ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Duarte","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Bresso","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Huttin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Bozec","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Brunner La Rocca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Delles","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Hull, Castle Hill Hospital , Yorkshire ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology Campus Virchow Klinikum, Charit\u00e9 University Medicine Berlin and German Centre for Cardiovascular Research (DZHK), Partner Site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"CIMA Universidad de Navarra, Department of Pathology, Anatomy and Physiology Universidad de Navarra and IdiSNA , Pamplona ,","place":["Spain"]},{"name":"CIBERCV, Carlos III Institute of Health , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Pellicori","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Petutschnigg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and\/Cardiology, Campus Virchow Klinikum, Charit\u00e9 University Medicine Berlin, and German Heart Center Berlin, and Berlin Institute of Health (BIH), and German Centre for Cardiovascular research (DZHK) , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Job A.J.","family":"Verdonschot","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]},{"name":"Medical Specialties and Nephrology Dialysis Departments, Monaco Princess Grace Hospital and Monaco Private Hemodialysis Centre , Monaco ,","place":["Monaco"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, Inserm U1116, CHRU de 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