Abstract
BackgroundPostural 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.MethodsWe 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.ResultsPOTS 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.ConclusionsCardiovascular 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.
Highlights
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
POTS was defined as the reproduction of symptoms of orthostatic intolerance associated with heart rate increase > 30 bpm; or sinus tachycardia > 120 bpm during first 10 min of head-up tilt testing (HUT); or increase > 40 beats/min for those < 18 years of age, with history of orthostatic intolerance for at least 6 months [20]
We explored the change in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate Analysis of variance (ANOVA) with Bonferroni correction, as previously described [13, 14, 22]
Summary
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. Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by orthostatic intolerance and high prevalence among young women [1]. High-throughput multiplex protein arrays that rely on common methods such as polymerase chain reactions, require small sample volumes and are available at a fraction of the cost of large-scale platforms. Such a solution may provide an effective resource to discover disease pathways and identify novel therapeutic targets for individualised treatment based on biomarker profiling [8]. Multiprotein assays have been used to discover key mechanisms by which CV autonomic dysfunction is associated with increased CV morbidity and mortality [13, 14]
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