Cardiovascular autonomic regulation, inflammation and pain in rheumatoid arthritis

Ahmed M Adlan,James P Fisher,Gregory Y.H Lip,Jet J.C.S Veldhuijzen Van Zanten,George D Kitas,Julian F.R Paton

doi:10.1016/j.autneu.2017.09.003

Abstract

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory condition characterised by reduced heart rate variability (HRV) of unknown cause. We tested the hypothesis that low HRV, indicative of cardiac autonomic cardiovascular dysfunction, was associated with systemic inflammation and pain. Given the high prevalence of hypertension (HTN) in RA, a condition itself associated with low HRV, we also assessed whether the presence of hypertension further reduced HRV in RA.MethodsIn RA-normotensive (n = 13), RA-HTN (n = 17), normotensive controls (NC; n = 17) and HTN (n = 16) controls, blood pressure and heart rate were recorded. Time and frequency domain measures of HRV along with serological markers of inflammation (high sensitivity C-reactive protein [hs-CRP], tumour necrosis factor-α [TNF-α] and interleukins [IL]) were determined. Reported pain was assessed using a visual analogue scale.ResultsTime (rMSSD, pNN50%) and frequency (high frequency power, low frequency power, total power) domain measures of HRV were lower in the RA, RA-HTN and HTN groups, compared to NC (p = 0.001). However, no significant differences in HRV were noted between the RA, RA-HTN and HTN groups. Inverse associations were found between time and frequency measures of HRV and inflammatory cytokines (IL-6 and IL-10), but were not independent after multivariable analysis. hs-CRP and pain were independently and inversely associated with time domain (rMMSD, pNN50%) parameters of HRV.ConclusionsThese findings suggest that lower HRV is associated with increased inflammation and independently associated with increased reported pain, but not compounded by the presence of HTN in patients with RA.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with substantially increased cardiovascular mortality and risk (Solomon et al, 2003; Pujades-Rodriguez et al, 2016)
Resting heart rate (HR) was similar in RA and RA-HTN groups but higher compared to normotensive controls (NC) and HTN controls (p = 0.008, Table 1)
Time domain, frequency domain (HF, low frequency (LF)) and non-linear (SD1, SD2) parameters of heart rate variability (HRV) were similar in RA, RA-HTN and HTN groups and lower compared to NC (Table 1) (HTN vs. NC, p = 0.092)

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with substantially increased cardiovascular mortality and risk (Solomon et al, 2003; Pujades-Rodriguez et al, 2016). Low heart rate variability (HRV) indicative of reduced cardiac parasympathetic function predicts mortality risk following myocardial infarction (Bigger et al, 1992; La Rovere et al, 1998) and may contribute to the increased cardiovascular risk seen in RA. Studies of RA patients that have examined the associations between inflammation and cardiac parasympathetic activity have been limited (e.g., cytokine concentrations not assessed) and reported equivocal results (Adlan et al, 2014). Another possible explanation for the observed reduction in HRV in RA patients is increased patient-reported pain. Conclusions: These findings suggest that lower HRV is associated with increased inflammation and independently associated with increased reported pain, but not compounded by the presence of HTN in patients with RA

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Results

Conclusion