{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:43:14Z","timestamp":1740166994998,"version":"3.37.3"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Copenhagen University Hospital, Rigshospitalet"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Women continue to have a worse prognosis following ST-elevation myocardial infarction (STEMI) compared to men, despite advancements in treatment. This study investigates whether neurohormonal biomarker differences contribute to sex-related disparities in mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>A total of 1892 consecutive STEMI patients from two tertiary heart centres were included. Admission neurohormonal activation defined as pro-atrial natriuretic peptide (proANP) and mid-regional pro-adrenomedullin (MR-proADM) was measured in blood drawn prior to acute coronary angiography (CAG). The primary endpoint was 1-year mortality stratified according to sex and biomarker level. Of 1782 (94%) with biomarkers available, 476 (27%) of patients were women. They were older (68 vs. 62 years), had longer symptom-to-angiography delay (211 vs. 181\u2005min), and displayed a higher one-year mortality rate (12% vs. 7.4%, P &amp;lt; 0.001) compared to men. The neurohormonal response was higher in women compared to men [median (interquartile range) proANP 1050 (671\u20131591) vs. 772 (492\u20131294) pmol\/L, P &amp;lt; 0.001); MR-proADM 0.80 (0.63\u20131.03) vs. 0.70 (0.58\u20130.89) nmol\/L, P &amp;lt; 0.001]. In women, a level at or above the median was independently associated with a significantly higher mortality risk when adjusting for age, left ventricular ejection fraction, diabetes, heart failure, symptom onset to CAG, left-sided culprit lesion, obesity, renal dysfunction, primary percutaneous intervention, admission systolic blood pressure, and multivessel disease (HR proANP 6.05, 95% CI 1.81\u201320.3, P = 0.004; HR MR-proADM 3.49, 95% CI 1.42\u20138.62, P = 0.007). In men, there was an independent prognostic association for proANP but not for MR-proADM (HR proANP 2.38, 95% CI 1.18\u20134.81, P = 0.015; HR MR-proADM 1.74, 95% CI 0.89\u20133.40, P = 0.11).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Increased neurohormonal activation (MR-proADM and proANP) is associated with higher mortality in women compared to men. Neurohormonal activation may contribute to the observed sex-related differences in mortality.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjacc\/zuae141","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T23:43:40Z","timestamp":1733874220000},"page":"31-39","source":"Crossref","is-referenced-by-count":0,"title":["Neurohormonal response is associated with mortality in women with ST-elevation myocardial infarction"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0793-4557","authenticated-orcid":false,"given":"Joakim Bo","family":"Kunkel","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet , Inge Lehmanns Vej 7, 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-0898","authenticated-orcid":false,"given":"Helle","family":"S\u00f8holm","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet , Inge Lehmanns Vej 7, 2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Cardiology, Zealand University Hospital , Roskilde ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8426-617X","authenticated-orcid":false,"given":"Sarah L D","family":"Holle","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet , Inge Lehmanns Vej 7, 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-3829","authenticated-orcid":false,"given":"Jens P","family":"Goetze","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet , Copenhagen ,","place":["Denmark"]},{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-378X","authenticated-orcid":false,"given":"Lene","family":"Holmvang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet , Inge Lehmanns Vej 7, 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4838-2429","authenticated-orcid":false,"given":"Lisette O","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Odense University Hospital , Odense ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5133-5820","authenticated-orcid":false,"given":"Annam P","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Emergency Medical Services, Capital Region of Denmark , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-5845","authenticated-orcid":false,"given":"Jacob E","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet , Inge Lehmanns Vej 7, 2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Cardiology, Odense University Hospital , Odense ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1199-0981","authenticated-orcid":false,"given":"Christian","family":"Hassager","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet , Inge Lehmanns Vej 7, 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1543-8948","authenticated-orcid":false,"given":"Martin","family":"Frydland","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet , Inge Lehmanns Vej 7, 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,12,9]]},"reference":[{"key":"2025013112540044000_zuae141-B1","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/eurheartj\/ehz898","article-title":"Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome","volume":"41","author":"Haider","year":"2020","journal-title":"Eur Heart J"},{"key":"2025013112540044000_zuae141-B2","doi-asserted-by":"crossref","DOI":"10.1093\/ehjopen\/oeac042","article-title":"Sex-related differences in the management and outcomes of patients hospitalized with ST-elevation myocardial infarction: a comparison within four European myocardial infarction registries","volume":"2","author":"Hellgren","year":"2022","journal-title":"Eur Heart J Open"},{"key":"2025013112540044000_zuae141-B3","doi-asserted-by":"crossref","first-page":"e002423","DOI":"10.1161\/JAHA.115.002423","article-title":"Natriuretic peptides in the regulation of cardiovascular physiology and metabolic events","volume":"4","author":"Kerkel\u00e4","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"2025013112540044000_zuae141-B4","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.jacc.2006.12.038","article-title":"Prognostic value of midregional pro-adrenomedullin in patients with acute myocardial infarction","volume":"49","author":"Khan","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2025013112540044000_zuae141-B5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jemt.10052","article-title":"Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions","volume":"57","author":"Kitamura","year":"2002","journal-title":"Microsc Res Tech"},{"key":"2025013112540044000_zuae141-B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00021.2015","article-title":"Mechanistic pathways of sex differences in cardiovascular disease","volume":"97","author":"Regitz-Zagrosek","year":"2017","journal-title":"Physiol Rev"},{"key":"2025013112540044000_zuae141-B7","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/ejhf.1771","article-title":"Sex-related differences in contemporary biomarkers for heart failure: a review","volume":"22","author":"Suthahar","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"2025013112540044000_zuae141-B8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.21037\/jlpm.2019.01.03","article-title":"Pathophysiological mechanisms determining sex differences in circulating levels of cardiac natriuretic peptides and cardiac troponins","volume":"4","author":"Clerico","year":"2019","journal-title":"J Lab Precis Med"},{"key":"2025013112540044000_zuae141-B9","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.atherosclerosis.2013.03.006","article-title":"Association of MR-proadrenomedullin with cardiovascular risk factors and subclinical cardiovascular disease","volume":"228","author":"Neumann","year":"2013","journal-title":"Atherosclerosis"},{"key":"2025013112540044000_zuae141-B10","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.amjcard.2016.06.043","article-title":"Gender, high-sensitivity troponin I, and the risk of cardiovascular events (from the Nord-Tr\u00f8ndelag Health Study)","volume":"118","author":"Lyngbakken","year":"2016","journal-title":"Am J Cardiol"},{"key":"2025013112540044000_zuae141-B11","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1177\/2048872619896063","article-title":"Biomarkers predictive of late cardiogenic shock development in patients with suspected ST-elevation myocardial infarction","volume":"9","author":"Frydland","year":"2020","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"key":"2025013112540044000_zuae141-B12","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/2048872617706503","article-title":"Risk factors of late cardiogenic shock and mortality in ST-segment elevation myocardial infarction patients","volume":"7","author":"Obling","year":"2018","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"key":"2025013112540044000_zuae141-B13","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1056\/NEJMoa2102953","article-title":"New Creatinine- And Cystatin C-Based Equations To Estimate GFR without race","volume":"385","author":"Inker","year":"2021","journal-title":"N Engl J Med"},{"key":"2025013112540044000_zuae141-B14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1373\/clinchem.2003.021204","article-title":"Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma","volume":"50","author":"Morgenthaler","year":"2004","journal-title":"Clin Chem"},{"key":"2025013112540044000_zuae141-B15","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1373\/clinchem.2005.051110","article-title":"Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay","volume":"51","author":"Morgenthaler","year":"2005","journal-title":"Clin Chem"},{"key":"2025013112540044000_zuae141-B16","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/ehf2.13734","article-title":"Baseline characteristics, management, and predictors of early mortality in cardiogenic shock: insights from the FRENSHOCK registry","volume":"9","author":"Delmas","year":"2022","journal-title":"ESC Heart Fail"},{"key":"2025013112540044000_zuae141-B17","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1177\/2047487314538856","article-title":"MR-proANP improves prediction of mortality and cardiovascular events in patients with STEMI","volume":"22","author":"Lindberg","year":"2015","journal-title":"Eur J Prev Cardiol"},{"key":"2025013112540044000_zuae141-B18","doi-asserted-by":"crossref","first-page":"S158","DOI":"10.1016\/j.cardfail.2008.07.127","article-title":"Gender difference in B-type natriuretic peptide levels in patients with acute myocardial infarction","volume":"14","author":"Yoshida","year":"2008","journal-title":"J Card Fail"},{"key":"2025013112540044000_zuae141-B19","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1177\/2048872615568964","article-title":"B-type natriuretic peptide as a predictor of ischemia\/reperfusion injury immediately after myocardial reperfusion in patients with ST-segment elevation acute myocardial infarction","volume":"5","author":"Arakawa","year":"2016","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"key":"2025013112540044000_zuae141-B20","doi-asserted-by":"crossref","first-page":"617705","DOI":"10.3389\/fcvm.2020.617705","article-title":"Gender-related differences in heart failure biomarkers","volume":"7","author":"Cediel","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"2025013112540044000_zuae141-B21","doi-asserted-by":"crossref","first-page":"e008123","DOI":"10.1161\/JAHA.117.008123","article-title":"MR-proADM as a prognostic marker in patients with ST-segment-elevation myocardial infarction\u2014dANAMI-3 (a Danish study of optimal acute treatment of patients with STEMI) substudy","volume":"7","author":"Falkentoft","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"2025013112540044000_zuae141-B22","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1161\/CIR.0000000000001052","article-title":"Heart disease and stroke statistics\u20142022 update: a report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"2025013112540044000_zuae141-B23","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1093\/eurheartj\/ehw334","article-title":"Cardiovascular disease in Europe: epidemiological update 2016","volume":"37","author":"Townsend","year":"2016","journal-title":"Eur Heart J"},{"key":"2025013112540044000_zuae141-B24","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1161\/CIRCULATIONAHA.120.048015","article-title":"Is there a sex gap in surviving an acute coronary syndrome or subsequent development of heart failure?","volume":"142","author":"Ezekowitz","year":"2020","journal-title":"Circulation"},{"key":"2025013112540044000_zuae141-B25","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/jama.2012.199","article-title":"Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality","volume":"307","author":"Canto","year":"2012","journal-title":"JAMA"},{"key":"2025013112540044000_zuae141-B26","doi-asserted-by":"crossref","first-page":"e012161","DOI":"10.1161\/JAHA.119.012161","article-title":"Sex differences persist in time to presentation, revascularization, and mortality in myocardial infarction treated with percutaneous coronary intervention","volume":"8","author":"Stehli","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"2025013112540044000_zuae141-B27","doi-asserted-by":"crossref","first-page":"e020211","DOI":"10.1136\/bmjopen-2017-020211","article-title":"Gender disparities in first medical contact and delay in ST-elevation myocardial infarction: a prospective multicentre Swedish survey study","volume":"8","author":"Sederholm Lawesson","year":"2018","journal-title":"BMJ Open"},{"key":"2025013112540044000_zuae141-B28","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.2217\/bmm-2019-0158","article-title":"Proanp and Probnp in plasma as biomarkers of heart failure","volume":"13","author":"Davidovski","year":"2019","journal-title":"Biomark Med"},{"key":"2025013112540044000_zuae141-B29","doi-asserted-by":"crossref","first-page":"e001713","DOI":"10.1161\/CIRCGENETICS.117.001713","article-title":"Genome-wide association study implicates atrial natriuretic peptide rather than B-type natriuretic peptide in the regulation of blood pressure in the general population","volume":"10","author":"Salo","year":"2017","journal-title":"Circ Cardiovasc Genet"},{"key":"2025013112540044000_zuae141-B30","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1677\/joe.1.06815","article-title":"Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II","volume":"191","author":"Pearson","year":"2006","journal-title":"J Endocrinol"},{"key":"2025013112540044000_zuae141-B31","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1210\/en.2005-0664","article-title":"Female sex steroids increase adrenomedullin-induced vasodilation by increasing the expression of adrenomedullin2 receptor components in rat mesenteric artery","volume":"147","author":"Ross","year":"2006","journal-title":"Endocrinology"},{"key":"2025013112540044000_zuae141-B32","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1515\/cclm-2017-0309","article-title":"Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose","volume":"56","author":"Mark","year":"2017","journal-title":"Clin Chem Lab Med"},{"key":"2025013112540044000_zuae141-B33","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1016\/j.bbadis.2013.07.003","article-title":"Regulation of expression of atrial and brain natriuretic peptide, biomarkers for heart development and disease","volume":"1832","author":"Sergeeva","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"2025013112540044000_zuae141-B34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1373\/clinchem.2011.165696","article-title":"B-type natriuretic peptide: from posttranslational processing to clinical measurement","volume":"58","author":"Goetze","year":"2012","journal-title":"Clin Chem"},{"key":"2025013112540044000_zuae141-B35","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1515\/cclm-2017-1044","article-title":"Plasma midregional proadrenomedullin (MR-proADM) concentrations and their biological determinants in a reference population","volume":"56","author":"Krintus","year":"2018","journal-title":"Clin Chem Lab Med"},{"key":"2025013112540044000_zuae141-B36","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1093\/clinchem\/hvab109","article-title":"Sex differences in cardiac troponin I and T and the prediction of cardiovascular events in the general population","volume":"67","author":"Kimenai","year":"2021","journal-title":"Clin Chem"},{"key":"2025013112540044000_zuae141-B37","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1136\/bmj.38985.646481.55","article-title":"Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE)","volume":"333","author":"Fox","year":"2006","journal-title":"BMJ"},{"key":"2025013112540044000_zuae141-B38","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1053\/j.ajkd.2009.04.031","article-title":"Prognostic value of kidney function in patients with ST-elevation and non-ST-elevation acute myocardial infarction treated with percutaneous coronary intervention","volume":"54","author":"Seyfarth","year":"2009","journal-title":"Am J Kidney Dis"}],"container-title":["European Heart Journal: Acute Cardiovascular Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ehjacc\/advance-article-pdf\/doi\/10.1093\/ehjacc\/zuae141\/61000335\/zuae141.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjacc\/article-pdf\/14\/1\/31\/61000335\/zuae141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjacc\/article-pdf\/14\/1\/31\/61000335\/zuae141.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T12:54:30Z","timestamp":1738328070000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjacc\/article\/14\/1\/31\/7919382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,9]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12,9]]},"published-print":{"date-parts":[[2025,1,31]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjacc\/zuae141","relation":{},"ISSN":["2048-8726","2048-8734"],"issn-type":[{"type":"print","value":"2048-8726"},{"type":"electronic","value":"2048-8734"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,12,9]]}}}