Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort

Fedorowski A, Burri P, Struck J, Juul-Moller S, Melander O (Lund University, Clinical Research Center, Malmo; Skane University Hospital, Malmo; Skane University Hospital, Malmo, Sweden; BRAHMS GmbH, Hennigsdorf, Germany). Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort (Symposium). J Intern Med 2013; 273: 359-367 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 60years, range 1593; 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) 1.8616.74; P<0.001] and CT-proET-1 (OR 7.17, 95% CI 2.4321.13; 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 2.4930.17; P<0.001). Furthermore, CSH was most frequently observed in the first quartile of MR-proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.6226.62; P=0.008) among those over 60years of age, whereas the cardioinhibitory reflex was strongly associated with low CT-proET-1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97696.6; 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 1.155.02; P=0.02), whereas low CT-proET-1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.250.70; 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.