{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:04:04Z","timestamp":1789736644230,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,20]],"date-time":"2013-03-20T00:00:00Z","timestamp":1363737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Research Council","award":["282225"],"award-info":[{"award-number":["282225"]}]},{"name":"Region Skane"},{"name":"Hulda and Conrad Mossfelt Foundation"},{"name":"King Gustaf V and Queen Victoria Foundation"},{"name":"Wallenberg Foundation"},{"name":"Lennart Hanssons Memorial Fund"},{"DOI":"10.13039\/501100006310","name":"Swedish Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006310","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Heart and Lung Foundation"},{"DOI":"10.13039\/501100004817","name":"Medical Faculty of Lund University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004817","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Malm\u00f6 University Hospital"},{"name":"Care North Consortium"},{"name":"Albert P\u00e5hlsson Research Foundation"},{"DOI":"10.13039\/501100003173","name":"Crafoord Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003173","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ernhold Lundstr\u00f6ms Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2013,4]]},"abstract":"Objectives<\/jats:title>The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.<\/jats:p><\/jats:sec>Design and setting<\/jats:title>An observational study was conducted including 255 patients (mean age 60\u00a0years, range 15\u201393; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head\u2010up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C\u2010terminal pro\u2010arginine vasopressin (CT<\/jats:styled-content>\u2010proAVP<\/jats:styled-content>), C\u2010terminal endothelin\u20101 precursor fragment (CT<\/jats:styled-content>\u2010proET<\/jats:styled-content>\u20101), midregional fragments of pro\u2010atrial natriuretic peptide (MR<\/jats:styled-content>\u2010proANP<\/jats:styled-content>) and pro\u2010adrenomedullin (MR<\/jats:styled-content>\u2010proADM<\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS<\/jats:styled-content>), 85 (33%) with orthostatic hypotension (OH<\/jats:styled-content>) and 47 (18%) with carotid sinus hypersensitivity (CSH<\/jats:styled-content>); in addition, 74 (29%) patients had more than one diagnosis. Thirty\u2010five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS<\/jats:styled-content> was highest in the first quartile of MR<\/jats:styled-content>\u2010proANP<\/jats:styled-content> [Q1 vs. Q4: odds ratio (OR<\/jats:styled-content>) 5.57, 95% confidence interval (CI<\/jats:styled-content>) 1.86\u201316.74; P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.001] and CT<\/jats:styled-content>\u2010proET<\/jats:styled-content>\u20101 (OR<\/jats:styled-content> 7.17, 95% CI<\/jats:styled-content> 2.43\u201321.13; P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.001). By contrast, the probability of OH<\/jats:styled-content> was highest in the fourth quartile of CT<\/jats:styled-content>\u2010proET<\/jats:styled-content>\u20101 (Q4 vs. Q1: OR<\/jats:styled-content> 8.66, 95% CI<\/jats:styled-content> 2.49\u201330.17; P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.001). Furthermore, CSH<\/jats:styled-content> was most frequently observed in the first quartile of MR<\/jats:styled-content>\u2010proANP<\/jats:styled-content> (Q1 vs. Q4: OR<\/jats:styled-content> 6.57, 95% CI<\/jats:styled-content> 1.62\u201326.62; P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.008) among those over 60\u00a0years of age, whereas the cardioinhibitory reflex was strongly associated with low CT<\/jats:styled-content>\u2010proET<\/jats:styled-content>\u20101 levels (Q1 vs. Q4: OR<\/jats:styled-content> 69.7, 95% CI<\/jats:styled-content> 6.97\u2013696.6; P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.001). Moreover, in patients with VVS<\/jats:styled-content>, a high concentration of CT<\/jats:styled-content>\u2010proET<\/jats:styled-content>\u20101 was predictive of OH<\/jats:styled-content> (OR<\/jats:styled-content> per 1 SD<\/jats:styled-content> 2.4, 95% CI<\/jats:styled-content> 1.15\u20135.02; P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.02), whereas low CT<\/jats:styled-content>\u2010proET<\/jats:styled-content>\u20101 suggested involvement of the cardioinhibitory reflex (OR<\/jats:styled-content> per 1SD<\/jats:styled-content> 0.42, 95% CI<\/jats:styled-content> 0.25\u20130.70; P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.001).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The levels of MR<\/jats:styled-content>\u2010proANP<\/jats:styled-content> and CT<\/jats:styled-content>\u2010proET<\/jats:styled-content>\u20101 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12043","type":"journal-article","created":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T13:35:19Z","timestamp":1365773719000},"page":"359-367","source":"Crossref","is-referenced-by-count":59,"title":["Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA<\/scp> cohort"],"prefix":"10.1111","volume":"273","author":[{"given":"A.","family":"Fedorowski","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund University Clinical Research Center Malm\u00f6 Sweden"},{"name":"Arrhythmia Department Sk\u00e5ne University Hospital Malm\u00f6 Sweden"},{"name":"Unit of Clinical Physiology and Nuclear Medicine Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Burri","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Clinical Research Center Malm\u00f6 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