{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:45:07Z","timestamp":1790091907497,"version":"4.0.1"},"reference-count":36,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000349","name":"National Institute for Academic Anaesthesia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR300097"],"award-info":[{"award-number":["NIHR300097"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012373","name":"National Institute of Academic Anaesthesia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjanaesthesia.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["British Journal of Anaesthesia"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.bja.2024.10.040","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T07:28:28Z","timestamp":1734679708000},"page":"1300-1307","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["Preoperative activation of the renin\u2013angiotensin system and myocardial injury in noncardiac surgery: exploratory mechanistic analysis of the SPACE randomised controlled trial"],"prefix":"10.1016","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1240-4654","authenticated-orcid":false,"given":"Ana","family":"Gutierrez del Arroyo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8664-3001","authenticated-orcid":false,"given":"Tom E.F.","family":"Abbott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshaykumar","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Begum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-6165","authenticated-orcid":false,"given":"Priyanthi","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1982-3379","authenticated-orcid":false,"given":"David","family":"Brealey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert M.","family":"Pearse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5778-6188","authenticated-orcid":false,"given":"Vikas","family":"Kapil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-5164","authenticated-orcid":false,"given":"Gareth L.","family":"Ackland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bja.2024.10.040_bib1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/01.sla.0000179621.33268.83","article-title":"Determinants of long-term survival after major surgery and the adverse effect of postoperative complications","volume":"242","author":"Khuri","year":"2005","journal-title":"Ann Surg"},{"key":"10.1016\/j.bja.2024.10.040_bib2","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.bja.2022.06.019","article-title":"Long-term mortality following complications after elective surgery: a secondary analysis of pooled data from two prospective cohort studies","volume":"129","author":"Fowler","year":"2022","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.bja.2024.10.040_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2024.102510","article-title":"Exploring the need for reconsideration of trial design in perioperative outcomes research: a narrative review","volume":"70","author":"Kehlet","year":"2024","journal-title":"EClinicalMedicine"},{"key":"10.1016\/j.bja.2024.10.040_bib4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.bja.2020.02.003","article-title":"Early elevation in plasma high-sensitivity troponin T and morbidity after elective noncardiac surgery: prospective multicentre observational cohort study","volume":"124","author":"Ackland","year":"2020","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.bja.2024.10.040_bib5","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1001\/jama.2017.4360","article-title":"Association of postoperative high-sensitivity troponin levels with myocardial injury and 30-day mortality among patients undergoing noncardiac surgery","volume":"317","author":"Devereaux","year":"2017","journal-title":"JAMA"},{"key":"10.1016\/j.bja.2024.10.040_bib6","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1093\/eurheartj\/ehac798","article-title":"Long-term outcomes of perioperative myocardial infarction\/injury after non-cardiac surgery","volume":"44","author":"Puelacher","year":"2023","journal-title":"Eur Heart J"},{"key":"10.1016\/j.bja.2024.10.040_bib7","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1001\/jamacardio.2023.3241","article-title":"Prevalence and overlap of cardiac, renal, and metabolic conditions in US adults, 1999-2020","volume":"8","author":"Ostrominski","year":"2023","journal-title":"JAMA Cardiol"},{"key":"10.1016\/j.bja.2024.10.040_bib8","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1001\/jamacardio.2023.0720","article-title":"Efficacy and safety of low-dose triple and quadruple combination pills vs monotherapy, usual care, or placebo for the initial management of hypertension: a systematic review and meta-analysis","volume":"8","author":"Wang","year":"2023","journal-title":"JAMA Cardiol"},{"key":"10.1016\/j.bja.2024.10.040_bib9","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1001\/jamacardio.2022.3345","article-title":"Longer-term all-cause and cardiovascular mortality with intensive blood pressure control: a secondary analysis of a randomized clinical trial","volume":"7","author":"Jaeger","year":"2022","journal-title":"JAMA Cardiol"},{"key":"10.1016\/j.bja.2024.10.040_bib10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/emmm.201000080","article-title":"Angiotensin II revisited: new roles in inflammation, immunology and aging","volume":"2","author":"Benigni","year":"2010","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.bja.2024.10.040_bib11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41569-019-0244-8","article-title":"Counter-regulatory renin-angiotensin system in cardiovascular disease","volume":"17","author":"Paz Ocaranza","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"10.1016\/j.bja.2024.10.040_bib12","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1093\/eurheartj\/ehad716","article-title":"Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial","volume":"45","author":"Ackland","year":"2024","journal-title":"Eur Heart J"},{"key":"10.1016\/j.bja.2024.10.040_bib13","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1093\/eurheartj\/ehac270","article-title":"2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery","volume":"43","author":"Halvorsen","year":"2022","journal-title":"Eur Heart J"},{"key":"10.1016\/j.bja.2024.10.040_bib14","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00134-015-4157-7","article-title":"Incidence and associations of acute kidney injury after major abdominal surgery","volume":"42","author":"O'Connor","year":"2016","journal-title":"Intensive Care Med"},{"key":"10.1016\/j.bja.2024.10.040_bib15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bja.2020.09.023","article-title":"Systematic review and consensus definitions for the Standardized Endpoints in Perioperative Medicine (StEP) initiative: cardiovascular outcomes","volume":"126","author":"Beattie","year":"2021","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.bja.2024.10.040_bib16","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1093\/eurheartj\/ehy712","article-title":"Novel endotypes in heart failure: effects on guideline-directed medical therapy","volume":"39","author":"Tromp","year":"2018","journal-title":"Eur Heart J"},{"key":"10.1016\/j.bja.2024.10.040_bib17","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1093\/ehjci\/jead218","article-title":"Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification","volume":"24","author":"Rauseo","year":"2023","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"10.1016\/j.bja.2024.10.040_bib18","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1093\/ehjdh\/ztab042","article-title":"Echocardiographic phenogrouping by machine learning for risk stratification in the general population","volume":"2","author":"Sabovcik","year":"2021","journal-title":"Eur Heart J Digit Health"},{"key":"10.1016\/j.bja.2024.10.040_bib19","first-page":"1","article-title":"NbClust: an R package for determining the relevant number of clusters in a data set","volume":"61","author":"Charrad","year":"2014","journal-title":"J\u00a0Stat Software"},{"key":"10.1016\/j.bja.2024.10.040_bib20","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1210\/jc.2010-0225","article-title":"Effect of atenolol on aldosterone\/renin ratio calculated by both plasma renin activity and direct renin concentration in healthy male volunteers","volume":"95","author":"Ahmed","year":"2010","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.bja.2024.10.040_bib21","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1001\/jama.2023.17087","article-title":"A\u00a0new dawn for aldosterone as a therapeutic target in hypertension","volume":"330","author":"Williams","year":"2023","journal-title":"JAMA"},{"key":"10.1016\/j.bja.2024.10.040_bib22","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1161\/HYPERTENSIONAHA.122.17964","article-title":"Aldosterone as a mediator of cardiovascular damage","volume":"79","author":"Buffolo","year":"2022","journal-title":"Hypertension"},{"key":"10.1016\/j.bja.2024.10.040_bib23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1161\/01.HYP.0000226054.53527.bb","article-title":"Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity","volume":"48","author":"Nagata","year":"2006","journal-title":"Hypertension"},{"key":"10.1016\/j.bja.2024.10.040_bib24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nm1545","article-title":"Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity","volume":"13","author":"Leopold","year":"2007","journal-title":"Nat Med"},{"key":"10.1016\/j.bja.2024.10.040_bib25","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1161\/01.RES.0000159937.05502.d1","article-title":"Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells","volume":"96","author":"Jaffe","year":"2005","journal-title":"Circ Res"},{"key":"10.1016\/j.bja.2024.10.040_bib26","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1161\/CIRCRESAHA.108.174235","article-title":"Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and\u00a0promote leukocyte adhesion","volume":"102","author":"Caprio","year":"2008","journal-title":"Circ Res"},{"key":"10.1016\/j.bja.2024.10.040_bib27","doi-asserted-by":"crossref","first-page":"5070","DOI":"10.1210\/jc.2005-0681","article-title":"Evidence for abnormal left ventricular structure and function in normotensive individuals with familial hyperaldosteronism type I","volume":"90","author":"Stowasser","year":"2005","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.bja.2024.10.040_bib28","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1097\/SLA.0000000000004044","article-title":"Comparison of perioperative outcomes in heart failure patients with reduced versus preserved ejection fraction after noncardiac surgery","volume":"275","author":"Huang","year":"2022","journal-title":"Ann Surg"},{"key":"10.1016\/j.bja.2024.10.040_bib29","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/S0140-6736(20)31964-4","article-title":"Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis","volume":"396","author":"Narula","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.bja.2024.10.040_bib30","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1210\/clinem\/dgac539","article-title":"Circulating plasma concentrations of ACE2 in primary aldosteronism and cardiovascular outcomes","volume":"107","author":"Wu","year":"2022","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.bja.2024.10.040_bib31","doi-asserted-by":"crossref","first-page":"j3984","DOI":"10.1136\/bmj.j3984","article-title":"Trends for prevalence and incidence of resistant hypertension: population based cohort study in the UK 1995-2015","volume":"358","author":"Sinnott","year":"2017","journal-title":"BMJ"},{"key":"10.1016\/j.bja.2024.10.040_bib32","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/ajh.2009.138","article-title":"Dual blockade of the renin-angiotensin-aldosterone system: beyond the ACE inhibitor and angiotensin-II receptor blocker combination","volume":"22","author":"Bomback","year":"2009","journal-title":"Am J Hypertens"},{"key":"10.1016\/j.bja.2024.10.040_bib33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/01.hjh.0000202812.72341.99","article-title":"Renin inhibition with aliskiren: where are we now, and where are we going?","volume":"24","author":"Azizi","year":"2006","journal-title":"J\u00a0Hypertens"},{"key":"10.1016\/j.bja.2024.10.040_bib34","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1097\/00005344-199002000-00015","article-title":"Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition","volume":"15","author":"Mooser","year":"1990","journal-title":"J\u00a0Cardiovasc Pharmacol"},{"key":"10.1016\/j.bja.2024.10.040_bib35","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1681\/ASN.2009030307","article-title":"Stimulation of renin secretion by angiotensin II blockade is Gsalpha-dependent","volume":"21","author":"Chen","year":"2010","journal-title":"J\u00a0Am Soc Nephrol"},{"key":"10.1016\/j.bja.2024.10.040_bib36","doi-asserted-by":"crossref","first-page":"e287","DOI":"10.1161\/CIR.0000000000001024","article-title":"Diagnosis and management of patients with myocardial injury after noncardiac surgery: a scientific statement from the American Heart Association","volume":"144","author":"Ruetzler","year":"2021","journal-title":"Circulation"}],"container-title":["British Journal of Anaesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091224007037?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0007091224007037?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T17:07:28Z","timestamp":1767719248000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0007091224007037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["S0007091224007037"],"URL":"https:\/\/doi.org\/10.1016\/j.bja.2024.10.040","relation":{},"ISSN":["0007-0912"],"issn-type":[{"value":"0007-0912","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Preoperative activation of the renin\u2013angiotensin system and myocardial injury in noncardiac surgery: exploratory mechanistic analysis of the SPACE randomised controlled trial","name":"articletitle","label":"Article Title"},{"value":"British Journal of Anaesthesia","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bja.2024.10.040","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Ltd on behalf of British Journal of Anaesthesia.","name":"copyright","label":"Copyright"}]}}