Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: A systematic review

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Abstract

Objective

The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia (FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects.

Methods

To obtain relevant articles, PubMed and Web of Knowledge were searched for case–control studies. Selection of the literature was based on selection criteria ascertaining studies with adult human patient groups comparing HRV. Risk of bias and levels of evidence were determined.

Results

Sixteen case–control studies were included, 10 comparing FM patients to controls and 6 comparing CFS patients to controls. Methodological quality was moderate to good. Both time domain and frequency domain measurements were used. The majority of the researchers observed lower HRV in FM patients compared to healthy control persons, as well as increased sympathetic activity and a blunted autonomic response to stressors. Resistance training improved HRV in FM patients. In CFS patients HRV was only reduced during sleep.

Conclusion

FM patients show more HRV aberrances and indices of increased sympathetic activity. Increased sympathetic activity is only present in CFS patients at night. Since direct comparisons are lacking and some confounders have to be taken into account, further research is warranted. The role of pain and causality can be subject of further research, as well as therapy studies directed to reduced HRV.

Introduction

The autonomous nervous system is part of the peripheral nervous system and is responsible for maintaining important functions, such as involuntary vital parameters (blood pressure, heart rate, respiration, and temperature). The two branches, the sympathetic and parasympathetic branch, have antagonistic influences on most bodily functions, which contributes to the homeostasis in the body. Disruptions in homeostasis (ie, stress) place demands on the body that are met by the activation of, among others, the sympathetic nervous system [1]. In case of chronic stress, the tolerance of the stress response may be exceeded, giving rise to chronic diseases [2]. A large number of these chronic diseases are accompanied by chronic pain and fatigue. This has led to the assumption that abnormal sympathetic activation could be involved in the pathogenesis of chronic pain and fatigue syndromes. This hypothesis is further based on the observations that pain and fatigue are often correlated to symptoms of autonomic dysfunction [3], [4].

In consequence, much interest has recently been expressed in the possible role of the autonomic nervous system in the pathogenesis of chronic pain and fatigue syndromes, like fibromyalgia (FM) and the chronic fatigue syndrome (CFS) [5]. Both are considered as related syndromes, supported by the high percentages of overlap between the two syndromes (35–70%) [6], but in the meantime substantial differences have been reported [7], [8].

Much of the common symptoms could be attributed to a dysfunction of the autonomic nervous system [9]. Due to sympathetic hyperactivation and/or parasympathetic dysfunction, the body is no longer able to respond to different stressors, which can explain the fatigue, stiffness, sensitive tender points [10], [11], exercise intolerance [12], sleeping problems [13], etc.

There are different ways for evaluating autonomic function. The most commonly used, fastest, and least invasive method is measuring heart rate variability (HRV), analyzing the variability of time between successive R waves (R–R interval analysis). There are two ways to analyze these R–R intervals. Time domain analysis of heart rate variability uses statistical methods to quantify the variation of the standard deviation or the differences between successive R–R intervals. Frequency domain analysis of heart rate variability enables us to calculate the respiratory-dependent high-frequency and the low-frequency power. High-frequency power is mediated by vagal activity, while low-frequency power has been suggested to represent predominantly sympathetic modulation [14].

This reliable biomarker [15] is based on the fact that heart rate is not constant, but oscillates around an average value. The antagonistic effects of the sympathetic branch and parasympathetic branch of the autonomic nervous system on the sinus node are responsible for this constant variability.

HRV analyses have been used in different populations and the literature provides strong evidence for HRV changes to have an important prognostic value in health and disease. Decreased HRV would indicate poor health [16], [17]. Besides HRV as relevant outcome measure for cardiovascular morbidity and mortality, there is growing knowledge regarding HRV in the pathogenesis of chronic pain and fatigue syndromes. Since both FM and CFS are typical chronic pain syndromes with specific similarities and differences and with symptoms that could be attributed to autonomic dysfunction, it seemed interesting to list the present knowledge on the differences and similarities in HRV in patients with FM and patients with CFS compared to healthy individuals. When reduced HRV would seem to play a major role in FM or CFS, this information could be used to steer and assess the effects of the rehabilitation of these patients. In that case, therapy could address autonomic dysfunctions (eg, exercise therapy, relaxation, and breathing exercises) and HRV could be used as an outcome to assess progression and to provide biofeedback.

The present systematic literature review will try to summarize answers to the following research questions:

  • (1)

    Are there differences and/or similarities in HRV between adults with FM and adults with CFS?

  • (2)

    Are these differences and/or similarities different from healthy adult persons without pain?

  • (3)

    What is the clinical relevance of HRV in CFS and FM?

Section snippets

Methods

This systematic review is reported following the PRISMA-guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which is an updated statement addressing the conceptual and methodological issues of the original QUOROM Statement [18].

Study selection

As shown in Figure 1, a total of 248 studies were identified. After the two screening phases 16 case–control studies remained. None of the studies compared CFS patients to FM patients.

Risk of bias and level of evidence

The risk of bias and the level of evidence of the different studies are reported in Table 1.

In most cases (92% or 88 of the 96 items), the two researchers agreed. After a second review and a comparison of the eight differences, the reviewers reached a consensus for seven items. The remaining point of discussion

Discussion

The goal of the present systematic literature study was to compare HRV between CFS patients and FM patients in comparison to healthy controls and to describe the clinical relevance. As none of the studies directly compared CFS and FM patients, we reviewed the knowledge on HRV in patients with FM and in patients with CFS discuss them together in the discussion.

Although there are some inconsistencies and the level of evidence is moderate to low, mainly due to the included study designs

Conclusion

In general, the results of FM studies point towards significantly lower HRV with lower parasympathetic and increased sympathetic activity. When exposed to physical and mental stress, a blunted response is observed and there is a nocturnal increase in sympathetic activity compared to healthy subjects. Training improves HRV in FM. In CFS patients, differences with controls were only observed at night. Possibly, pain is the discriminating factor, although causality cannot be decided based on the

Acknowledgment

Mira Meeus is an awardee of the 2012 early research career grant of the International Association for the Study of Pain (IASP), funded by the Scan/Design Foundation by INGER and JENS BRUUN.

References (53)

  • S. Ozgocmen et al.

    R–R interval variation and sympathetic skin response in fibromyalgia

    Arch Med Res

    (2006)
  • H.R. Eriksen et al.

    Subjective health complaints, sensitization, and sustained cognitive activation (stress)

    J Psychosom Res

    (2004)
  • N. Julien et al.

    Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition

    Pain

    (2005)
  • R. Staud et al.

    Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients

    Pain

    (2003)
  • S. Bruehl et al.

    Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain

    Neurosci Biobehav Rev

    (2004)
  • M. Meeus et al.

    Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study

    Pain

    (2008)
  • V.K. Yeragani et al.

    Heart rate variability in patients with major depression

    Psychiatry Res

    (1991)
  • G.P. Chrousos et al.

    The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis

    J Am Med Assoc

    (1992)
  • M. Martinez-Lavin

    Biology and therapy of fibromyalgia—stress, the stress response system, and fibromyalgia

    Arthritis Res Ther

    (2007)
  • J.L. Newton et al.

    Autonomic dysfunction in primary biliary cirrhosis correlates with fatigue severity

    Eur J Gastroenterol Hepatol

    (2007)
  • H. Cohen et al.

    Autonomic nervous system derangement in fibromyalgia syndrome and related disorders

    Isr Med Assoc J

    (2001)
  • D.L. Goldenberg et al.

    High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice

    Arthritis Rheum

    (1990)
  • L.A. Bradley et al.

    Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome

    Curr Rev Pain

    (2000)
  • M. Meeus et al.

    Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome

    Clin Rheumatol

    (2007)
  • M. MartinezLavin et al.

    Orthostatic sympathetic derangement in subjects with fibromyalgia

    J Rheumatol

    (1997)
  • R. Furlan et al.

    Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia

    J Rheumatol

    (2005)
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