Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis

Ahmed M. Adlan, Julian F R Paton, Gregory Y H Lip, George D. Kitas, James P. Fisher*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

18 Citations (Scopus)
236 Downloads (Pure)

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min–1) compared to NC (22 ± 9 bursts min–1; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients [5(3–8), 4 (2–7), 6 (4–9) ms mmHg–1] compared to NC [11 (8–15) ms mmHg–1; P = 0.002]. HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events.
Original languageEnglish
Pages (from-to)967-981
Number of pages15
JournalJournal of Physiology
Volume595
Issue number3
Early online date24 Oct 2016
DOIs
Publication statusPublished - 1 Feb 2017

Keywords

  • autonomic nervous system
  • cytokine
  • inflammation
  • pain

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    Adlan, A. M., Paton, J. F. R., Lip, G. Y. H., Kitas, G. D., & Fisher, J. P. (2017). Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis. Journal of Physiology, 595(3), 967-981. https://doi.org/10.1113/JP272944