{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:32:46Z","timestamp":1791873166476,"version":"4.3.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Irene Patricia Hunt Memorial Hypertension Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Many medications (including most antihypertensives) and physiological factors affect the aldosterone\/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone\/angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST). Peripheral levels of eqAngII, plasma renin activity (PRA) and direct renin concentration (DRC) were measured.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>EqAngII showed good consistency with DRC and PRA independent of PA diagnosis, posture, and fludrocortisone administration. EqAngII showed close (P\u2009&amp;lt;\u20090.01) correlations with DRC (r\u2009=\u20090.691) and PRA (r\u2009=\u20090.754) during FST. DRC and PRA were below their assays\u2019 functional sensitivity in 43.9% and 15.1%, respectively, of the total 312 samples compared with only 7.4% for eqAngII (P\u2009&amp;lt;\u20090.01). Bland-Altman analysis revealed an overestimation of PRA and DRC compared with eqAngII in a subset of samples with low renin levels. The AA2R showed not only consistent changes with the ARR but also close (P\u2009&amp;lt;\u20090.01) correlations with the ARR, whether renin was measured by DRC (r\u2009=\u20090.878) or PRA (r\u2009=\u20090.880).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Dynamic changes of eqAngII and the AA2R show good consistency and close correlations with renin and the ARR. The eqAngII assay shows better sensitivity than DRC and PRA assays, especially at low concentrations. Whether the AA2R can reduce the impact of some factors that influence the diagnostic power of the ARR warrants further study.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaa001","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T07:08:02Z","timestamp":1578035282000},"page":"483-492","source":"Crossref","is-referenced-by-count":71,"title":["Measurement of Equilibrium Angiotensin II in the Diagnosis of Primary Aldosteronism"],"prefix":"10.1093","volume":"66","author":[{"given":"Zeng","family":"Guo","sequence":"first","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Poglitsch","sequence":"first","affiliation":[{"name":"Attoquant Diagnostics GmbH, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett C","family":"McWhinney","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus P J","family":"Ungerer","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health, Brisbane, Queensland, Australia"},{"name":"Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf H","family":"Ahmed","sequence":"first","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D","family":"Gordon","sequence":"first","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wolley","sequence":"first","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4317-8584","authenticated-orcid":false,"given":"Michael","family":"Stowasser","sequence":"first","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"2020030207595176400_hvaa001-B1","first-page":"1863","article-title":"Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology","volume":"85","author":"Fardella","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020030207595176400_hvaa001-B2","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1016\/j.jacc.2006.07.059","article-title":"A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients","volume":"48","author":"Rossi","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2020030207595176400_hvaa001-B3","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-0031-1295438","article-title":"Prevalence of primary aldosteronism in patient's cohorts and in population-based studies\u2014a review of the current literature","volume":"44","author":"Hannemann","year":"2012","journal-title":"Horm Metab Res"},{"key":"2020030207595176400_hvaa001-B4","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1161\/HYPERTENSIONAHA.113.01060","article-title":"Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study","volume":"62","author":"Savard","year":"2013","journal-title":"Hypertension"},{"key":"2020030207595176400_hvaa001-B5","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1161\/01.HYP.0000230444.01215.6a","article-title":"Renal damage in primary aldosteronism: results of the PAPY study","volume":"48","author":"Rossi","year":"2006","journal-title":"Hypertension"},{"key":"2020030207595176400_hvaa001-B6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1055\/s-0029-1243257","article-title":"Comorbidities in primary aldosteronism","volume":"42","author":"Quinkler","year":"2010","journal-title":"Horm Metab Res"},{"key":"2020030207595176400_hvaa001-B7","doi-asserted-by":"crossref","first-page":"917","DOI":"10.5604\/17322693.1218180","article-title":"The renin-angiotensin-aldosterone system (RAAS)\u2014physiology and molecular mechanisms of functioning","volume":"70","author":"Chaszczewska-Markowska","year":"2016","journal-title":"Postepy Hig Med Dosw (Online)"},{"key":"2020030207595176400_hvaa001-B8","volume-title":"The renin-angiotensin system","author":"Nicholls","year":"1993"},{"key":"2020030207595176400_hvaa001-B9","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1210\/jc.2015-4061","article-title":"The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline","volume":"101","author":"Funder","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2020030207595176400_hvaa001-B10","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1161\/01.HYP.0000038478.59760.41","article-title":"Drug effects on aldosterone\/plasma renin activity ratio in primary aldosteronism","volume":"40","author":"Mulatero","year":"2002","journal-title":"Hypertension"},{"key":"2020030207595176400_hvaa001-B11","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1055\/s-0031-1295460","article-title":"Factors affecting the aldosterone\/renin ratio","volume":"44","author":"Stowasser","year":"2012","journal-title":"Horm Metab Res"},{"key":"2020030207595176400_hvaa001-B12","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1210\/jc.2010-2918","article-title":"Effect of contraceptives on aldosterone\/renin ratio may vary according to the components of contraceptive, renin assay method, and possibly route of administration","volume":"96","author":"Ahmed","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2020030207595176400_hvaa001-B13","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1210\/jc.2016-3851","article-title":"Effect of combined hormonal replacement therapy on the aldosterone\/renin ratio in postmenopausal women","volume":"102","author":"Ahmed","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"2020030207595176400_hvaa001-B14","doi-asserted-by":"crossref","first-page":"E340","DOI":"10.1210\/jc.2010-1355","article-title":"Are women more at risk of false-positive primary aldosteronism screening and unnecessary suppression testing than men?","volume":"96","author":"Ahmed","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2020030207595176400_hvaa001-B15","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/cen.12705","article-title":"Should aldosterone suppression tests be conducted during a particular phase of the menstrual cycle, and, if so, which phase? Results of a preliminary study","volume":"83","author":"Ahmed","year":"2015","journal-title":"Clin Endocrinol"},{"key":"2020030207595176400_hvaa001-B16","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3317\/jraas.2001.022","article-title":"Diagnosis and management of primary aldosteronism","volume":"3","author":"Stowasser","year":"2001","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2020030207595176400_hvaa001-B17","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1097\/00004872-200311000-00025","article-title":"High rate of detection of primary aldosteronism, including surgically treatable forms, after \u201cnon-selective\u201d screening of hypertensive patients","volume":"21","author":"Stowasser","year":"2003","journal-title":"J Hypertens"},{"key":"2020030207595176400_hvaa001-B18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.mce.2003.10.006","article-title":"Primary aldosteronism\u2014careful investigation is essential and rewarding","volume":"217","author":"Stowasser","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"2020030207595176400_hvaa001-B19","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1055\/s-0043-121468","article-title":"Can screening and confirmatory testing in the management of patients with primary aldosteronism be improved?","volume":"49","author":"Stowasser","year":"2017","journal-title":"Horm Metab Res"},{"key":"2020030207595176400_hvaa001-B20","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s40262-013-0072-7","article-title":"Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects","volume":"52","author":"Haschke","year":"2013","journal-title":"Clin Pharmacokinet"},{"key":"2020030207595176400_hvaa001-B21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1470320316669880","article-title":"Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-fingerprint","volume":"17","author":"van Rooyen","year":"2016","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2020030207595176400_hvaa001-B22","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.healun.2016.08.022","article-title":"Effects of angiotensin-converting-enzyme inhibitor therapy on the regulation of the plasma and cardiac tissue renin-angiotensin system in heart transplant patients","volume":"36","author":"Kovarik","year":"2017","journal-title":"J Heart Lung Transplant"},{"key":"2020030207595176400_hvaa001-B23","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1373\/clinchem.2017.278705","article-title":"Low- and high-renin heart failure phenotypes with clinical implications","volume":"64","author":"Pavo","year":"2018","journal-title":"Clin Chem"},{"key":"2020030207595176400_hvaa001-B24","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jacc.2016.11.064","article-title":"Roles of angiotensin peptides and recombinant human ACE2 in heart failure","volume":"69","author":"Basu","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2020030207595176400_hvaa001-B25","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1161\/HYPERTENSIONAHA.119.12786","article-title":"Angs (angiotensins) of the alternative renin-angiotensin system predict outcome in patients with heart failure and preserved ejection fraction","volume":"74","author":"Binder","year":"2019","journal-title":"Hypertension"},{"key":"2020030207595176400_hvaa001-B26","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1210\/jc.2018-01041","article-title":"Aldosterone LC-MS\/MS assay-specific threshold values in screening and confirmatory testing for primary aldosteronism","volume":"103","author":"Guo","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2020030207595176400_hvaa001-B27","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1001\/jama.1966.03110120079018","article-title":"Postural augmentation of plasma renin activity: importance in diagnosis of renovascular hypertension","volume":"197","author":"Cohen","year":"1966","journal-title":"JAMA"},{"key":"2020030207595176400_hvaa001-B28","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1172\/JCI105543","article-title":"Postural augmentation of plasma renin activity and aldosterone excretion in normal people","volume":"46","author":"Cohen","year":"1967","journal-title":"J Clin Invest"},{"key":"2020030207595176400_hvaa001-B29","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1152\/physrev.00026.2015","article-title":"Primary aldosteronism: changing definitions and new concepts of physiology and pathophysiology both inside and outside the kidney","volume":"96","author":"Stowasser","year":"2016","journal-title":"Physiol Rev"},{"key":"2020030207595176400_hvaa001-B30","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1373\/clinchem.2015.251009","article-title":"Plasma renin activity: the importance of correct sample type","volume":"62","author":"Haymond","year":"2016","journal-title":"Clin Chem"},{"key":"2020030207595176400_hvaa001-B31","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1373\/clinchem.2004.033654","article-title":"Direct renin assay and plasma renin activity assay compared","volume":"50","author":"Hartman","year":"2004","journal-title":"Clin Chem"},{"key":"2020030207595176400_hvaa001-B32","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1177\/1470320313494434","article-title":"The effect of blood collection procedure on plasma renin activity (PRA) and concentrations of direct renin (DRC) and aldosterone","volume":"16","author":"Glinicki","year":"2015","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2020030207595176400_hvaa001-B33","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1097\/00004872-199204000-00007","article-title":"Regulation of angiotensinogen gene expression by estrogen","volume":"10","author":"Gordon","year":"1992","journal-title":"J Hypertens"},{"key":"2020030207595176400_hvaa001-B34","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S0025-6196(11)62105-8","article-title":"Validity of the aldosterone-renin ratio used to screen for primary aldosteronism","volume":"76","author":"Montori","year":"2001","journal-title":"Mayo Clin Proc"},{"key":"2020030207595176400_hvaa001-B35","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1373\/clinchem.2008.118000","article-title":"Activity assays and immunoassays for plasma renin and prorenin: information provided and precautions necessary for accurate measurement","volume":"55","author":"Campbell","year":"2009","journal-title":"Clin Chem"},{"key":"2020030207595176400_hvaa001-B36","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1097\/HJH.0000000000000880","article-title":"Diagnostic accuracy of aldosterone and renin measurement by chemiluminescent immunoassay and radioimmunoassay in primary aldosteronism","volume":"34","author":"Burrello","year":"2016","journal-title":"J Hypertens"},{"key":"2020030207595176400_hvaa001-B37","first-page":"39","article-title":"Laboratory investigation of primary aldosteronism","volume":"31","author":"Stowasser","year":"2010","journal-title":"Clin Biochem Rev"},{"key":"2020030207595176400_hvaa001-B38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.mce.2011.07.034","article-title":"Acute and chronic regulation of aldosterone production","volume":"350","author":"Hattangady","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"2020030207595176400_hvaa001-B39","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/clinchem\/37.10.1811","article-title":"Plasma renin activity and plasma prorenin assays","volume":"37","author":"Sealey","year":"1991","journal-title":"Clin Chem"},{"key":"2020030207595176400_hvaa001-B40","first-page":"e400","article-title":"Measurement of angiotensin II at equilibrium in the diagnostic workup of primary aldosteronism\u2014impact of patient positioning and ACE inhibitor treatment","volume":"34","author":"Poglitsch","year":"2016","journal-title":"J Hypertens"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/66\/3\/483\/32741556\/hvaa001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/66\/3\/483\/32741556\/hvaa001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T08:00:30Z","timestamp":1583136030000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/66\/3\/483\/5739981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,18]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2,18]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvaa001","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3]]},"published":{"date-parts":[[2020,2,18]]}}}