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Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome

Medic Spahic, Jasmina LU ; Ricci, Fabrizio LU ; Aung, Nay ; Hallengren, Erik LU ; Axelsson, Jonas LU ; Hamrefors, Viktor LU orcid ; Melander, Olle LU orcid ; Sutton, Richard and Fedorowski, Artur LU orcid (2020) In BMC Cardiovascular Disorders 20.
Abstract

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.

METHODS: We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage... (More)

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.

METHODS: We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction.

RESULTS: POTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS.

CONCLUSIONS: Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Cardiovascular Disorders
volume
20
article number
190
publisher
BioMed Central (BMC)
external identifiers
  • pmid:32321428
  • scopus:85083948938
ISSN
1471-2261
DOI
10.1186/s12872-020-01465-6
language
English
LU publication?
yes
id
41d686fd-3390-4225-a37a-3e54c778ec97
date added to LUP
2020-04-28 07:50:03
date last changed
2024-06-26 14:57:56
@article{41d686fd-3390-4225-a37a-3e54c778ec97,
  abstract     = {{<p>BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.</p><p>METHODS: We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction.</p><p>RESULTS: POTS patients were younger (26 vs. 31 years; p &lt; 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS.</p><p>CONCLUSIONS: Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.</p>}},
  author       = {{Medic Spahic, Jasmina and Ricci, Fabrizio and Aung, Nay and Hallengren, Erik and Axelsson, Jonas and Hamrefors, Viktor and Melander, Olle and Sutton, Richard and Fedorowski, Artur}},
  issn         = {{1471-2261}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Cardiovascular Disorders}},
  title        = {{Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome}},
  url          = {{http://dx.doi.org/10.1186/s12872-020-01465-6}},
  doi          = {{10.1186/s12872-020-01465-6}},
  volume       = {{20}},
  year         = {{2020}},
}