{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T21:13:16Z","timestamp":1770844396322,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T00:00:00Z","timestamp":1646438400000},"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":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Left ventricular ejection fraction (LVEF) can provide haemodynamic information and may influence the response to spironolactone and other heart failure (HF) therapies. We aimed to study patient characteristics and circulating protein associations with LVEF, and whether LVEF influenced the response to spironolactone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      HOMAGE enrolled patients aged &gt;60\u2009years at high risk of developing HF with a LVEF \u226545%. Overall, 527 patients were randomized to either spironolactone or standard of care for \u22489\u00a0months, and 276 circulating proteins were measured using Olink\u00ae technology. A total of 364 patients had available LVEF determined by the Simpson's biplane method. The respective LVEF tertiles were: tertile 1: &lt;60% (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0122), tertile 2: 60%\u201365% (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0121), and tertile 3: &gt;65% (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0121). Patients with a LVEF &gt;65% had smaller left ventricular chamber size and volumes, and lower natriuretic peptide levels. Compared to patients with a LVEF &lt;60%, those with LVEF &gt;65% had higher levels of circulating c\u2010c motif chemokine ligand\u201023 and interleukin\u20108, and lower levels of tissue plasminogen activator, brain natriuretic peptide (BNP), S100 calcium binding protein A12, and collagen type I alpha 1 chain (COL1A1). Spironolactone significantly reduced the circulating levels of BNP and COL1A1 without significant treatment\u2010by\u2010LVEF heterogeneity: BNP change\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a0\u22120.36 log\n                      <jats:sub>2<\/jats:sub>\n                      and COL1A1 change\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a0\u22120.16 log\n                      <jats:sub>2<\/jats:sub>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001 for both; interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.1 for both). Spironolactone increased LVEF from baseline to month 9 by 1.1% (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.007).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with higher LVEF had higher circulating levels of chemokines and inflammatory markers and lower levels of stretch, injury, and fibrosis markers. Spironolactone reduced the circulating levels of natriuretic peptides and type 1 collagen, and increased LVEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2455","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T23:29:50Z","timestamp":1645658990000},"page":"771-778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Influence of ejection fraction on biomarker expression and response to spironolactone in people at risk of heart failure: findings from the\n                    <scp>HOMAGE<\/scp>\n                    trial"],"prefix":"10.1093","volume":"24","author":[{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Cardiovascular Research and Development Center, Department of Surgery and Physiology Faculty of Medicine of the University of Porto  Porto Portugal"},{"name":"Universit\u00e9 de Lorraine Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433, U1116, CHRU de Nancy, F\u2010CRIN INI\u2010CRCT  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Job A.J.","family":"Verdonschot","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Collier","sequence":"additional","affiliation":[{"name":"London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Mariottoni","sequence":"additional","affiliation":[{"name":"Department of Cardiology Cortona Hospital  Arezzo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Cosmi","sequence":"additional","affiliation":[{"name":"Department of Cardiology Cortona Hospital  Arezzo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Hazebroek","sequence":"additional","affiliation":[{"name":"Department of Cardiology Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe","family":"Cuthbert","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Hull, Castle Hill Hospital  Cottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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)  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephane","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Cardiology Maastricht University Medical Center  Maastricht 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Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew L.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Hull, Castle Hill Hospital  Cottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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 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