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

https://doi.org/10.1016/j.semarthrit.2017.11.010Get rights and content

Abstract

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.

Section snippets

Background

Cardiac autonomic dysfunction (AD) is linked to arrhythmias, all-cause mortality and death following myocardial infarction [1], [2]. There is a complex interplay between the immune and parasympathetic autonomic systems, with evidence of mutual regulation [3]. Parasympathetic AD is also linked to physical inactivity and is more prevalent in patients who suffer from chronic pain [4].

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are inflammatory joint disorders (IJD) with an excess risk of

Methods

These meta-analyses were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA statement).

Theory and calculations

For the comparison of the disease groups with the healthy controls, we conducted random-effects meta-analyses using standardized mean differences. The analyses were run separately for patients with RA and SpA. Within each diagnostic category we ran separate meta-analyses for each of the variables RMSSD, HF, E-S, E-B and E-V. Sensitivity analyses were performed. Forest plots were examined for heterogeneity and when significant heterogeneity was displayed outliers were removed in descending order

Results

The final literature search was performed in August 2016. Supplementary Table 3 presents the complete search strategy. Supplementary Figure 1 presents a summary of the findings of literature search, screening and selection process. The database search identified 1015 records. In addition 120 records were found through searching grey literature (conference abstracts and internet searches) and bibliographies. After duplicates had been removed, 847 records remained, and these titles and abstracts

Discussion

This study reports significantly lower markers of cardiac parasympathetic modulation, measured as both RMSSD and HF, in patients with RA compared to healthy controls. RMSSD and HF values for SpA patients were comparable between patients and controls. For the Ewing battery the heart-rate variation was also significantly lower for patients vs. controls, except for the heart-rate variation under the Valsalva test in patients with RA which although numerically lower in RA patients did not reach

Conclusion

Patients with IJD have lower cardiac parasympathetic modulation compared to healthy controls. There is a cross-sectional inverse relationship between level of inflammation and parasympathetic AD.

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    Disclosures: The authors S.A.P., E.E.S., G.S. and H.D. declare no conflict of interest. D.S.O. is currently employed by Polar Electro, Finland.

    Funding statement: This work was sponsored by the Research Fund at Diakonhjemmet Hospital and by Extra-Stiftelsen, Norway. The sponsors have not been involved in the data-analyses, writing or submission of this paper.

    1

    This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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