Inflammatory biomarker profiling in classical orthostatic hypotension: Insights from the SYSTEMA cohort. (15th May 2018)

• Record Type: Journal Article
• Authors: Johansson, Madeleine; Ricci, Fabrizio; Aung, Nay; Sutton, Richard; Melander, Olle; Fedorowski, Artur
• Is Part Of: International journal of cardiology. Volume 259(2018)
• Page Start: 192
• Page End: 197
• Publication Date: 2018-05-15
• Subjects: Dysautonomia -- Inflammation -- Autonomic function -- Biomarker -- Cardiovascular system pathology; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2017.12.020
• Languages: English
• ISSNs: 0167-5273

Abstract

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. Highlights: Dysautonomia and inflammation have multifaceted and reciprocal interactions. OH revealed a proteomic signature of inflammation and immunoregulatory functions. Inflammation and autonomic dysfunction are likely intertwined in atherothrombosis.