Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort
Open accessAbstract
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.
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Some cardiovascular biomarkers are increased in autonomic dysfunction underlying syncope, such as elevated copeptin (vasopressin), endothelin-1, and N-terminal pro-B-type natriuretic peptide in OH.
“Some cardiovascular biomarkers are increased in autonomic dysfunction underlying syncope, such as elevated copeptin (vasopressin), endothelin-1, and N-terminal pro-B-type natriuretic peptide in OH, 113,230,231”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [231]
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Developed in collaboration with, European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), and Heart Rhythm Society (HRS), societies, E. B. T. F., European Society of Emergency Medicine (EuSEM), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), American Geriatrics Society (AGS), European Neurological Society (ENS), et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp298 · Cited by 2,040 · see citing works
Daniels, L. B., & Maisel, A. S. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.09.021 · Cited by 994 · see citing works
Derivation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes
Quinn, J. V., Stiell, I. G., McDermott, D. A., Sellers, K. L., Kohn, M. A., & Wells, G. A. (2004) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(03)00823-0 · Cited by 432 · see citing works
Mechanism of Syncope in Patients With Isolated Syncope and in Patients With Tilt-Positive Syncope
Moya, A., Brignole, M., Menozzi, C., Garcia-Civera, R., Tognarini, S., Mont, L., Botto, G., Giada, F., Cornacchia, D., & on behalf of the International Study on Syncope of Uncertain Etiology (ISSUE) Investigators (2001) · Circulation · doi:10.1161/hc3601.095708 · Cited by 378 · see citing works
Brignole, M., Menozzi, C., Bartoletti, A., Giada, F., Lagi, A., Ungar, A., Ponassi, I., Mussi, C., Maggi, R., Re, G., et al. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehi647 · Cited by 332 · see citing works
Bartoletti, A. (2000) · Europace · doi:10.1053/eupc.2000.0125 · Cited by 315 · see citing works
Prospective evaluation and outcome of patients admitted for syncope over a 1 year period
Blanc, J. (2002) · European Heart Journal · doi:10.1053/euhj.2001.2975 · Cited by 303 · see citing works
The endocrine function of the heart
McGrath, M. F., de Bold, M. L. K., & de Bold, A. J. (2005) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2005.10.007 · Cited by 260 · see citing works
Nexfin Noninvasive Continuous Blood Pressure Validated Against Riva-Rocci/Korotkoff
Schattenkerk, D. W. E., LIESHOUT, J. J. V., van den Meiracker, A. H., Wesseling, K. H., Blanc, S., Wieling, W., van Montfrans, G. A., Settels, J. J., Wesseling, K. H., & Westerhof, B. E. (2009) · American Journal of Hypertension · doi:10.1038/ajh.2008.368 · Cited by 222 · see citing works
Copeptin in the Differential Diagnosis of Hyponatremia
Fenske, W., Störk, S., Blechschmidt, A., Maier, S. G. K., Morgenthaler, N. G., & Allolio, B. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1426 · Cited by 212 · see citing works
Sun, B. C., Emond, J. A., & Camargo, C. A. (2004) · Academic Emergency Medicine · doi:10.1197/j.aem.2004.05.032 · Cited by 193 · see citing works
Mechanisms of atrial natriuretic peptide secretion from the atrium
Dietz, J. R. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.06.008 · Cited by 180 · see citing works
Kirkby, N. S., Hadoke, P. W. F., Bagnall, A. J., & Webb, D. J. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707516 · Cited by 176 · see citing works
Syncope prevalence in the ED compared to general practice and population: a strong selection process
Olde Nordkamp, L. R. A., van Dijk, N., Ganzeboom, K. S., Reitsma, J. B., Luitse, J. S. K., Dekker, L. R. C., Shen, W.-K., & Wieling, W. (2009) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2008.02.022 · Cited by 158 · see citing works
Brignole, M. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl164 · Cited by 145 · see citing works
Plasma endothelin during upright tilt: relevance for orthostatic hypotension?
Kaufmann, H., Oribe, E., & Oliver, J. A. (1991) · The Lancet · doi:10.1016/0140-6736(91)92370-h · Cited by 142 · see citing works
Parry, S. W., Reeve, P., Lawson, J. J., Shaw, F., Davison, J. M., Norton, M., Frearson, R., Kerr, S., & Newton, J. L. (2008) · Heart · doi:10.1136/hrt.2007.136457 · Cited by 110 · see citing works
Croci, F. (2002) · Europace · doi:10.1053/eupc.2002.0267 · Cited by 105 · see citing works
Bartoletti, A., Fabiani, P., Adriani, P., Baccetti, F., Bagnoli, L., Buffini, G., Cappelletti, C., Cecchini, P., Gianni, R., Lavacchi, A., et al. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi474 · Cited by 77 · see citing works
New Concepts in the Assessment of Syncope
Brignole, M., & Hamdan, M. H. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.11.056 · Cited by 75 · see citing works
Caruhel, P., Mazier, C., Kunde, J., et al. (2009) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2009.01.002 · Cited by 71 · see citing works
Neurohormonal Response to Head-Up Tilt and Its Role in Vasovagal Syncope
Jardine, D. L., Melton, I., Crozier, I., et al. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(9x)00084-9 · Cited by 69 · see citing works
Antunes‐Rodrigues, J., Machado, B. H., Andrade, H. A., Mauad, H., Ramalho, M. J., Reis, L. C., Silva-Netto, C. R., Favaretto, A. L., Gutkowska, J., & McCann, S. M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.15.6828 · Cited by 61 · see citing works
The venous system is the main determinant of hypotension in patients with vasovagal syncope
Fucă, G., Dinelli, M., Suzzani, P., Scarfo', S., Tassinari, F., & Alboni, P. (2006) · EP Europace · doi:10.1093/europace/eul095 · Cited by 57 · see citing works
Fedorowski, A., Burri, P., Juul‐Möller, S., & Melander, O. (2010) · EP Europace · doi:10.1093/europace/euq168 · Cited by 54 · see citing works
Self-citationFreitas, J. P., dos Santos, R. M., Azevedo, E. I., et al. (2006) · International Journal of Cardiology · doi:10.1016/j.ijcard.2006.03.052 · Cited by 21 · see citing works
Permanent increase in endothelin serum levels in vasovagal syncope
Magerkurth, C., Riedel, A., & Braune, S. (2005) · Clinical Autonomic Research · doi:10.1007/s10286-005-0291-6 · Cited by 19 · see citing works
Endothelin system polymorphisms in tilt test-induced vasovagal syncope
Sorrentino, S., Forleo, C., Iacoviello, M., et al. (2009) · Clinical Autonomic Research · doi:10.1007/s10286-009-0008-3 · Cited by 15 · see citing works
Neurohormonal Profile Before and After β‐Blockade in Patients with Neurocardiogenic Syncope
Roul, G., RIEHL‐ALEIL, V., Germain, P., & Bareiss, P. (1999) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.1999.tb00566.x · Cited by 14 · see citing works
Cardiovascular and Endocrine Responses to 90° Tilt During a 35-Day Saturation Dive to 46 and 37 ATA
Claybaugh, J. R., Lin, Y., Schafstall, H. G., et al. (2007) · Aviation Space and Environmental Medicine · doi:10.3357/asem.2014.2007 · Cited by 4 · see citing works
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2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya, A., de Lange, F. J., Deharo, J.-C., Elliott, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martín, A., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy037 · Cited by 1,951 · see citing works
Self-citationRicci, F., De Caterina, R., & Fedorowski, A. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.06.1084 · Cited by 472 · see citing works
Self-citationRicci, F., Fedorowski, A., Radico, F., Romanello, M., Tatasciore, A., Di Nicola, M., Zimarino, M., & De Caterina, R. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv093 · Cited by 310 · see citing works
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Nilsson, D., Sutton, R., Tas, W., Burri, P., Melander, O., & Fedorowski, A. (2015) · PLOS ONE · doi:10.1371/journal.pone.0128962 · Cited by 54 · see citing works
Self-citationSyndromes of orthostatic intolerance and syncope in young adults
Hamrefors, V., Spahic, J. M., Nilsson, D., Senneby, M., Sutton, R., Melander, O., & Fedorowski, A. (2017) · Open Heart · doi:10.1136/openhrt-2016-000585 · Cited by 23 · see citing works
Self-citationKrishnan, B., Patarroyo-Aponte, M., Duprez, D., Pritzker, M., Missov, E., & Benditt, D. G. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.02.015 · Cited by 13 · see citing works
- Authors
- Fedorowski, A., Burri, P., Struck, J., Juul‐Möller, S., & Melander, O.
- Affiliations
- Lund University (SE)
- Thermo Fisher Scientific (Germany) (DE)
- Skåne University Hospital (SE)
- Corresponding author
- Fedorowski, A.
- Venue
- Journal of Internal Medicine
- Publisher
- Wiley
- Published
- 2013-03-20
- Volume
- 273
- Issue
- 4
- Pages
- 359-367
- ISSN
- 0954-6820 (ISSN-L)
- 1365-2796
- OpenAlex
- W2042471252
- Cited by
- 62
- References
- 31
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 6 · 2016: 2 · 2015: 7 · 2014: 2 · 2013: 1
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- European Research Council (282225)
- Region Skane
- Hulda and Conrad Mossfelt Foundation
- King Gustaf V and Queen Victoria Foundation
- Wallenberg Foundation
- Lennart Hanssons Memorial Fund
- Swedish Medical Research Council
- Swedish Heart and Lung Foundation
- Medical Faculty of Lund University
- Malmö University Hospital
- Care North Consortium
- Albert Påhlsson Research Foundation
- Crafoord Foundation
- Ernhold Lundströms Research Foundation
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Keywords
- syncope, cardiovascular biomarkers, vasovagal syncope, orthostatic hypotension, carotid sinus hypersensitivity, MR-proANP, proadrenomedullin, head-up tilt, carotid sinus massage, nitroglycerin provocation, systemic blood pressure, heart rate variability, autonomic dysfunction
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Electrocardiography, Female, Humans, Male, Middle Aged, Atrial Natriuretic Factor, Peptide Fragments, Retrospective Studies, Syncope, Vasopressins, Biomarkers, Endothelin-1, Adrenomedullin, Young Adult
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