title: Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort.
abstract: OBJECTIVE
  The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.
  
  
  METHODS
  An observational study was conducted including 255 patients (mean age 60 years, range 15-93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head-up 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-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), midregional fragments of pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM).
  
  
  RESULTS
  A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty-five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR-proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86-16.74; P < 0.001] and CT-proET-1 (OR 7.17, 95% CI 2.43-21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT-proET-1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49-30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR-proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62-26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT-proET-1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97-696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT-proET-1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15-5.02; P = 0.02), whereas low CT-proET-1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25-0.70; P = 0.001).
  
  
  CONCLUSIONS
  The levels of MR-proANP and CT-proET-1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.
authors.affiliation: Department of Clinical Sciences, Lund University, Clinical Research Center, Malmö, Sweden. artur.fedorowski@med.lu.se
authors.forename: A
authors.initials: A
authors.lastname: Fedorowski
authors.forename: P
authors.initials: P
authors.lastname: Burri
authors.forename: J
authors.initials: J
authors.lastname: Struck
authors.forename: S
authors.initials: S
authors.lastname: Juul-Möller
authors.forename: O
authors.initials: O
authors.lastname: Melander
mesh_terms: D000293:Adolescent; D053607:Adrenomedullin / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D004562:Electrocardiography; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D012189:Retrospective Studies; D013575:Syncope / Q000097:blood* / Q000503:physiopathology; D014667:Vasopressins / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D010446:Peptide Fragments; D014667:Vasopressins; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor