{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:48:08Z","timestamp":1785768488089,"version":"3.56.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RE\/18\/6\/34217"],"award-info":[{"award-number":["RE\/18\/6\/34217"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["HOMAGE project (305507)"],"award-info":[{"award-number":["HOMAGE project (305507)"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01469"],"award-info":[{"award-number":["PI18\/01469"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CB16\/11\/00483"],"award-info":[{"award-number":["CB16\/11\/00483"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,2]]},"abstract":"\n Aims<\/jats:title>\n The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C\u2010terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C\u2010terminal telopeptide to matrix metalloproteinase\u20101 ratio (CITP:MMP\u20101), associated with high collagen cross\u2010linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP\u20101 and spironolactone on cardiac function in the HOMAGE trial.<\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n \n Patients at risk of HF were randomized to spironolactone (\n n<\/jats:italic>\n \u00a0=\u00a0260) or not (\n n<\/jats:italic>\n \u00a0=\u00a0255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP\u20101 was used as an indirect measure of collagen cross\u2010linking. Higher baseline CITP:MMP\u20101 (i.e. lower collagen cross\u2010linking) was associated with greater reductions in LAVI with spironolactone at both one (\n p<\/jats:italic>\n \u00a0=\u00a00.003) and nine (\n p<\/jats:italic>\n \u00a0=\u00a00.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP\u20101 (estimated lowest collagen cross\u2010linking) [mean differences\n spiro\/control<\/jats:sub>\n : \u22121.77 (95% confidence interval, CI \u22122.94 to \u22120.59) and \u22122.52 (95% CI \u22124.46 to \u22120.58) mL\/m\n 2<\/jats:sup>\n ; interaction\n p<\/jats:italic>\n across\u2010tertiles<\/jats:sub>\n \u00a0=\u00a00.005; interaction\n p<\/jats:italic>\n third tertile<\/jats:sub>\n \u00a0=\u00a00.008] with a similar trend for N\u2010terminal pro\u2010B\u2010type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross\u2010linking tertile [mean differences\n spiro\/control<\/jats:sub>\n : \u22120.47 (95% CI \u22120.66 to \u22120.28) and \u22120.31 (95% CI \u22120.59 to \u22120.04) ng\/L; interaction\n p<\/jats:italic>\n across\u2010tertiles<\/jats:sub>\n \u00a0=\u00a00.09; interaction\n p<\/jats:italic>\n third tertile<\/jats:sub>\n \u2009<\u20090.001].\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross\u2010linking (indirectly assessed by serum CITP:MMP\u20101).<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ejhf.2394","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T01:39:06Z","timestamp":1638149946000},"page":"321-331","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Biomarker\u2010based assessment of collagen cross\u2010linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the\n HOMAGE<\/scp>\n clinical trial"],"prefix":"10.1093","volume":"24","author":[{"given":"Susana","family":"Ravassa","sequence":"first","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA Pamplona Spain"},{"name":"CIBERCV, Carlos III Institute of Health Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA Pamplona Spain"},{"name":"CIBERCV, Carlos III Institute of Health Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, U1116, CHRU de Nancy, F\u2010CRIN INI\u2010CRCT Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, U1116, CHRU de Nancy, F\u2010CRIN INI\u2010CRCT Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Bozec","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, U1116, CHRU de Nancy, F\u2010CRIN INI\u2010CRCT Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Pellicori","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing University of Glasgow, Glasgow Royal Infirmary Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Mariottoni","sequence":"additional","affiliation":[{"name":"Department of Cardiology Cortona Hospital Arezzo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Cosmi","sequence":"additional","affiliation":[{"name":"Department of Cardiology Cortona Hospital Arezzo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hazebroek","sequence":"additional","affiliation":[{"name":"Department of Cardiology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Job A.J.","family":"Verdonschot","sequence":"additional","affiliation":[{"name":"Department of Cardiology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Cuthbert","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Hull, Castle Hill Hospital Cottingham 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 Centre for Cardiovascular Research (DZHK), Partner Site Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda U.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA Pamplona Spain"},{"name":"CIBERCV, Carlos III Institute of Health Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Cardiology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A.","family":"Staessen","sequence":"additional","affiliation":[{"name":"Non\u2010Profit Research Institute Alliance for the Promotion of Preventive Medicine, Mechelen (APPREMED) Mechelen Belgium"},{"name":"Biomedical Sciences Group, Faculty of Medicine University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","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 Germany"},{"name":"Berlin Institute of Health Berlin Germany"}],"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 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Hull, Castle Hill Hospital Cottingham UK"}],"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, Glasgow Royal Infirmary Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, U1116, CHRU de Nancy, F\u2010CRIN INI\u2010CRCT Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"D\u00edez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA Pamplona Spain"},{"name":"CIBERCV, Carlos III Institute of Health Madrid Spain"},{"name":"Departments of Nephrology and Cardiology Cl\u00ednica Universidad de Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA Pamplona Spain"},{"name":"CIBERCV, Carlos III Institute of Health Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the HOMAGE Trial Committees and 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