Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort

J Intern Med. 2013 Apr;273(4):359-67. doi: 10.1111/joim.12043.

Abstract

Objectives: The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.

Design and setting: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenomedullin / blood
  • Adult
  • Aged
  • Aged, 80 and over
  • Atrial Natriuretic Factor / blood
  • Biomarkers / blood*
  • Electrocardiography*
  • Endothelin-1 / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Retrospective Studies
  • Syncope / blood*
  • Syncope / physiopathology
  • Vasopressins / blood
  • Young Adult

Substances

  • Biomarkers
  • C-terminal proendothelin-1
  • Endothelin-1
  • Peptide Fragments
  • Vasopressins
  • Adrenomedullin
  • Atrial Natriuretic Factor