Inflammatory biomarker profiling in classical orthostatic hypotension: Insights from the SYSTEMA cohort
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Objective: To investigate the inflammatory biomarker signature associated with classical orthostatic hypotension (OH). Methods: A cross-sectional study including 778 patients with unexplained syncope and/or orthostatic intolerance undergoing head-up tilt test (HUT) and supine blood sampling. Of these, 98 met diagnostic criteria of classical OH and 181 demonstrated normal haemodynamic response during HUT. Blood plasma samples were analysed by antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory and cancer-related human protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by multivariate principal component analysis (PCA), and verification by univariate ANOVA with Bonferroni correction. Results: Patients with classical OH were older (68 vs. 60 years; p < 0.001) and more likely to be men (58 vs. 41%; p < 0.001). PCA and Bonferroni-adjusted ANOVA identified midkine (MK), immunoglobulin-like transcript 3 (ILT-3), regenerating islet-derived protein 4 (REG-4), and tartrate-resistant acid phosphatase type 5 (TR-AP) as the most robust targeted biomarker signature for OH. In multivariate regression analysis adjusting for age, sex, cardiovascular disease and risk factors, the results remained significant for ILT-3 (p = 0.036), MK (p = 0.008) and REG-4 (p = 0.024), but not for TR-AP. Conclusions: Targeted protein profiling in classical orthostatic hypotension reveals a biomarker signature associated with immunoregulatory functions and vascular inflammation. Circulating levels of midkine, immunoglobulin-like transcript-3, regenerating islet-derived protein-4 are elevated in orthostatic hypotension, suggesting a complex interplay among inflammation, autonomic dysfunction and atherothrombosis.
Date Issued
2018-03-22
Date Acceptance
2017-12-06
Citation
International Journal of Cardiology, 2018, 259, pp.192-197
ISSN
0167-5273
Publisher
Elsevier
Start Page
192
End Page
197
Journal / Book Title
International Journal of Cardiology
Volume
259
Copyright Statement
© 2017 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License http://creativecommons.org/licenses/by-nc-nd/4.0/
Subjects
1102 Cardiovascular Medicine And Haematology
Cardiovascular System & Hematology
Publication Status
Published