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Original research article
Syndromes of orthostatic intolerance and syncope in young adults
  1. Viktor Hamrefors1,2,3,
  2. Jasmina Medic Spahic1,3,
  3. David Nilsson1,
  4. Martin Senneby1,2,
  5. Richard Sutton4,
  6. Olle Melander1,3 and
  7. Artur Fedorowski1,5
  1. 1 Department of Clinical Sciences, Lund University, Malmö, Sweden
  2. 2 Department of Medical Imaging and Physiology, Skåne University Hospital, Malmö, Sweden
  3. 3 Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
  4. 4 National Heart and Lung Institute, Imperial College, Hammersmith Hospital Campus, London, UK
  5. 5 Department of Cardiology, Skåne University Hospital, Malmö, Sweden
  1. Correspondence to Dr Viktor Hamrefors; viktor.hamrefors{at}


Objective To explore the clinical and neuroendocrine characteristics of syndromes of orthostatic intolerance and syncope in young adults.

Methods Two hundred and thirty-six patients aged 18–40 years with orthostatic intolerance and/or syncope were examined by head-up tilt test (HUT). Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1 and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were analysed. Patients’ history, haemodynamic parameters and plasma biomarkers were related to main diagnoses such as vasovagal syncope (VVS), postural tachycardia syndrome (POTS), orthostatic hypotension (OH) and negative HUT.

Results No self-reported symptom of orthostatic intolerance was highly specific for any diagnosis. Patients with VVS (n=103) were more likely to be men (p=0.011) and had lower resting heart rate (HR; 66±11) compared with POTS (73±11; n=72; p=0.001) and negative HUT (74±11; n=39; p=0.001). Patients with POTS demonstrated greater rise in norepinephrine (p=0.008) and CT-proAVP (p=0.033) on standing compared with negative HUT, and lower resting MR-proANP compared with VVS (p=0.04) and OH (p=0.03). Patients with OH had lower resting renin (p=0.03). Subjects with a resting HR <70 and MR-proANP >45 pm/L had an OR of 3.99 (95 % CI 1.68 to 9.52; p=0.002) for VVS compared with subjects without any of these criteria; if male sex was added the OR was 21.8 (95% CI 3.99 to 119; p<0.001).

Conclusions Syndromes of orthostatic intolerance and syncope share many characteristics in younger persons. However, patients with VVS are more likely to be men, have lower HR and higher MR-proANP at rest compared with POTS, which might be taken into account at an early stage of evaluation.


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  • Contributors All authors (VH, JMS, DN, MS, RS, OM, AF) participated in 1) conception and design or analysis and interpretation of data; 2) drafting of the manuscript or revising it critically and 3) final approval of the manuscript submitted.

  • Competing interests AF and OM are listed as co-inventors on a patent application 'Biomarkers for the diagnosis, prognosis, assessment and therapy stratification of syncope' (PCT/EP2013/001081) for the use of BRAHMS CT-proAVP, CT-proET-1, MR-proADM and MR-proANP for diagnosis of syncope. RS is a consultant to Medtronic.

  • Patient consent All patients signed an informed consent, however not a specific BMJ form. All data were unidentified and results are presented on group level only.

  • Ethics approval The Regional Ethical Review Board in Lund, Sweden accepted the study protocol (ref no 82/2008).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Any requests for data sharing should be made to the corresponding author.