Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort Study

F A Koopman, M W Tang, J Vermeij, M J de Hair, I Y Choi, M J Vervoordeldonk, D M Gerlag, J M Karemaker, P P Tak, F A Koopman, M W Tang, J Vermeij, M J de Hair, I Y Choi, M J Vervoordeldonk, D M Gerlag, J M Karemaker, P P Tak

Abstract

Background: Heart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) is accompanied by ANS imbalance. We hypothesized that ANS dysfunction may precede the development of RA, which would suggest that it plays a role in its etiopathogenesis.

Methods: First, we assessed HRV parameters in supine (resting) and upright (active) position in healthy subjects (HS, n=20), individuals at risk of developing arthritis (AR subjects, n=50) and RA patients (RA, n=20). Next, we measured resting heart rate (RHR), a parasympathetic HRV parameter, in an independent prospective cohort of AR subjects (n=45). We also evaluated expression levels of the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on circulating monocytes.

Findings: Both AR subjects (68 beats per minute (bpm), interquartile range (IQR) 68-73) and RA patients (68bpm, IQR 62-76) had a significantly higher RHR compared to HS (60bpm, IQR 56-63). RHR was significantly higher at baseline in individuals who subsequently developed arthritis. Expression levels of α7nAChR were lower in AR subjects with RHR ≥70bpm compared to those with RHR <70bpm, consistent with reduced activity of the parasympathetic cholinergic anti-inflammatory pathway.

Interpretation: These data support the notion that autonomic dysfunction precedes the development of RA.

Keywords: Autonomic nervous system; Heart rate; Heart rate variability; Norepinephrine; Preclinical; RA.

Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Resting heart rate in healthy subjects, AR subjects and RA patients (A) and resting heart rate in AR subjects that developed arthritis after follow-up (B). Abbreviations: AR: at risk, HS: healthy subjects; RA: rheumatoid arthritis; bpm: beats per minute, *p 

Fig. 2

Expression levels of the parasympathetic…

Fig. 2

Expression levels of the parasympathetic receptor, nicotinic acetylcholine receptor type 7 (α7nAChR) on…

Fig. 2
Expression levels of the parasympathetic receptor, nicotinic acetylcholine receptor type 7 (α7nAChR) on peripheral blood CD14 + monocytes AR subjects with resting heart rate
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Fig. 2
Fig. 2
Expression levels of the parasympathetic receptor, nicotinic acetylcholine receptor type 7 (α7nAChR) on peripheral blood CD14 + monocytes AR subjects with resting heart rate

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