Evidence of reduced parasympathetic autonomic regulation in inflammatory joint disease: A meta-analyses study

Semin Arthritis Rheum. 2018 Aug;48(1):134-140. doi: 10.1016/j.semarthrit.2017.11.010. Epub 2017 Dec 5.


Background: Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are inflammatory joint disorders (IJD) with increased risk of cardiovascular disease (CVD). Autonomic dysfunction (AD) is a risk factor for CVD, and parasympathetic AD is linked to key features of IJD such as inflammation, physical inactivity and pain. Heart-rate variability (HRV) is a marker of cardiac AD. The study objective was to compare parasympathetic cardiac AD, measured by HRV, between patients with IJD and healthy controls, using meta-analysis methodology, and to examine the impact of inflammation, physical inactivity and pain on HRV in IJD.

Methods: Medline, Embase and Amed were searched. Inclusion criteria were adult case-control studies published in English or a Scandinavian language, presenting HRV data in IJD. Two measures of HRV and 3 from the Ewing protocol were selected: square root of mean squared difference of successive R-R intervals (RMSSD), high frequency (HF), Ewing protocol; standing (E-S), breathing (E-B) and Valsalva (E-V). Patients with RA, SpA and healthy controls were compared separately using random-effects meta-analyses of standardized mean differences (SMD).

Results: In all, 35 papers were eligible for inclusion. For RMSSD the pooled SMD (95% CI) RA vs. controls was -0.90 (-1.35 to -0.44), for SpA vs. controls; -0.34 (-0.73 to 0.06). For HF pooled SMD RA vs. controls was -0.78 (-0.99 to -0.57), for SpA vs. controls; -0.04 (-0.22 to 0.13). All Ewing parameters were significantly lower in cases, except for E-V which was comparable between cases and controls in patients with RA.

Conclusion: Patients with IJD have cardiac parasympathetic AD which is related to inflammation.

Keywords: Autonomic dysfunction; Heart-rate variability; INFLAMMATORY joint disease; Rheumatoid arthritis; Spondyloarthritis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arthritis, Rheumatoid / physiopathology*
  • Autonomic Nervous System Diseases / physiopathology*
  • Heart Rate / physiology
  • Humans
  • Inflammation / physiopathology
  • Parasympathetic Nervous System / physiopathology*
  • Spondylarthritis / physiopathology*