Adrenergic hyperactivity: a missing link between multiple sclerosis and cardiovascular comorbidities?
The aim of the study is to investigate differences in non-standard adrenergic baroreflex sensitivity (BRS) indices in patients with different phenotypes of multiple sclerosis (pwMS) and healthy controls (HC). Retrospective analysis of types of systolic blood pressure (BP) curves during Valsalva maneuver (VM) [balanced (BAR), augmented (AAR) and suppressed (SAR) autonomic responses] and adrenergic baroreflex sensitivity (BRSa) measured with BRSa1, α-BRSa and β-BRSa in patients with clinically isolated syndrome (CIS), relapsing remitting multiple sclerosis (RRMS), progressive multiple sclerosis (PMS) and HC. We also investigated correlations between BRSa1, α-BRSa, β-BRSa and resting catecholamine levels. pwMS had higher α-BRSa compared to HC (p = 0.02). There was no difference in BRSa1, s and β-BRSa between patients with CIS, RRMS and PMS. There was no association between pwMS and HC, and the type of sBP curve [χ2 = 4.332, p = 0.114]. pwMS and BAR or AAR had higher supine systolic and diastolic BP compared to pwMS and SAR. There was a significant correlation between α-BRSa and upright systolic BP (rp =0.194, p = 0.017), α-BRSa and norepinephrine (rs =0.228, p = 0.021), and BRSa1 and epinephrine (rs = 0.226, p = 0.040). pwMS and HC exhibit different alpha-adrenergic response to Valsalva maneuver. These results may explain the connection between MS and increased cardiovascular risk.
KeywordsMultiple sclerosis Valsalva maneuver Cardiovascular autonomic dysfunction Adrenergic baroreflex sensitivity
Study concept and design: MH. Acquisition of data: TM, BN, DP, MKS, LC, MH. Analysis and interpretation of data: TM, BN, DP, MKS, LC, MH. Drafting of the manuscript: MH. Critical revision of the manuscript for important intellectual content: TM, BN, DP, MKS, LC, MH. Administrative, technical, and material support: TM, BN, DP, MKS, LC, MH.
This study was funded by the Installation Research project 2622 of the Croatian Science Foundation and University of Zagreb research support for the academic years 2015/2016 and 2016/2017.
Compliance with ethical standards
Conflict of interest
None of the authors have relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
We retrospectively analyzed data of all patients with the diagnosis of clinically isolated syndrome (CIS), relapsing remitting multiple sclerosis (RRMS), progressive forms of multiple sclerosis (PMS) and healthy controls (HC), who were examined in the Referral Center for Autonomic Nervous System Disorders, University Hospital Center Zagreb. Ethical committees of the University Hospital Center Zagreb approved the study.
All patients signed informed consent at the examination.
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