Orthostatic Changes in Hemodynamics and Cardiovascular Biomarkers in Dysautonomic Patients
Open accessAbstract
BACKGROUND: Impaired autonomic control of postural homeostasis results in orthostatic intolerance. However, the role of neurohormones in orthostatic intolerance has not been explained. METHODS: Six-hundred-and-seventy-one patients (299 males; 55 ± 22 years) with unexplained syncope underwent head-up tilt (HUT) with serial blood sampling. Systolic blood pressure (SBP) and heart rate (HR) supine, after 3 min, and lowest BP/highest HR during HUT were recorded. Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal- endothelin-1 (CT-proET-1), and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were determined at supine and 3 min of HUT. Multivariate-adjusted logistic regression model was applied to compare 1st (reference) with 4th quartile of 3 min and maximal ΔSBP/ΔHR (i.e. pronounced hypotension or tachycardia) vs. changes in neuroendocrine biomarkers, respectively. RESULTS: Higher resting CT-proET-1 predicted BP fall at 3 min (Odds ratio (OR) per 1 SD: 1.62, 95%CI 1.18-2.22; p = 0.003), and max BP fall during HUT (1.82, 1.28-2.61; p = 0.001). Higher resting CT-proAVP predicted BP fall at 3 min (1.33, 1.03-1.73; p = 0.03), which was also associated with increase in CT-proAVP (1.86, 1.38-2.51; p = 0.00005) and epinephrine (1.47, 1.12-1.92; p = 0.05) during HUT. Lower resting MR-proANP predicted tachycardia at 3 min (0.37, 0.24-0.59; p = 0.00003), and max tachycardia during HUT (0.47, 0.29-0.77; p = 0.002). Further, tachycardia during HUT was associated with increase in epinephrine (1.60, 1.15-2.21; p = 0.005), and norepinephrine (1.87, 1.38-2.53; p = 0.005). CONCLUSIONS: Resting CT-proET-1 and CT-proAVP are increased in orthostatic hypotension, while resting MR-proANP is decreased in postural tachycardia. Moreover, early BP fall during orthostasis evokes increase in CT-proAVP and epinephrine, while postural tachycardia is associated with increase in norepinephrine and epinephrine.
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Atrial natriuretic peptide may be reduced in POTS.
“whereas atrial natriuretic peptide may be reduced in POTS. 113”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [113]
The Results section (page unavailable) reports lower supine MR-proANP, a marker of atrial natriuretic peptide production, in patients with a pronounced heart-rate increase on standing. It explicitly cautions that not all of those patients met POTS diagnostic criteria, so the finding supports the possibility but does not establish reduced ANP specifically in POTS. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSome 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 [113]
The Discussion (Main findings) reports elevated resting CT-proAVP, a vasopressin precursor fragment, and CT-proET-1, an endothelin-1 precursor fragment, in patients with orthostatic hypotension (OH). The Methods (Neuroendocrine biomarkers) lists the biomarkers measured, but not N-terminal pro-B-type natriuretic peptide; it measured MR-proANP instead. The claim’s NT-proBNP component is therefore not supported by this paper. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe group has recently demonstrated an exaggerated catecholamine response in postural tachycardia among patients with syncope and dysautonomic cardiovascular response to orthostasis.
“We have recently demonstrated an exaggerated catecholamine response in postural tachycardia among patients with syncope and dysautonomic cardiovascular response to orthostasis.19”
From Antiadrenergic autoimmunity in postural tachycardia syndrome (2017) · cites this paper as [19]
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“We have recently demonstrated an exaggerated catecholamine response in postural tachycardia among patients with syncope and dysautonomic cardiovascular response to orthostasis.(19) The catecholamine surge may be seen as a compensatory mechanism to override the a1AR malfunction associated with the proposed autoimmune b…”
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Self-citation
- Authors
- Nilsson, D., Sutton, R., Tas, W., Burri, P., Melander, O., & Fedorowski, A.
- Affiliations
- Lund University (SE)
- St Mary's Hospital (GB)
- Corresponding author
- Nilsson, David
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-06-08
- Volume
- 10
- Issue
- 6
- Pages
- e0128962
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4460014
- OpenAlex
- W1798205344
- Cited by
- 54
- References
- 31
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 3
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Crafoordska Stiftelsen
- Lunds Universitet
- Malmö Högskola
- Region Skåne
- Medical Research Council
- 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 › Cardiology and Cardiovascular Medicine › Takotsubo Cardiomyopathy and Associated Phenomena
- Keywords
- orthostatic intolerance, autonomic dysfunction, head-up tilt, neuroendocrine markers, endothelin-1, vasopressin, atrial natriuretic peptide, epinephrine, norepinephrine, renin, blood pressure, heart rate, syncope, neurohormones
- MeSH terms
- Blood Pressure, Female, Heart Rate, Hemodynamics, Humans, Hypotension, Orthostatic, Male, Middle Aged, Neurosecretory Systems, Reflex, Regression Analysis, Syncope, Systole, Tachycardia, Biomarkers, Odds Ratio, Tilt-Table Test, Primary Dysautonomias
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