Autonomic nervous system (ANS) dysfunction has been suggested in patients with chronic fatigue syndrome (CFS). In this study, we sought to determine whether increased heart rate (HR) and reduced heart rate variability (HRV) parameters observed in CFS patients during wakefulness persist during sleep. To this end, we compared heart rate (HR) and HRV as indicators of ANS function in CFS subjects and non-fatigued (NF) controls in a population-based, case-control study. Thirty subjects with CFS and 38 NF controls, matched for age-, sex- and body mass index, were eligible for analysis. Main outcome measures included mean RR interval (RRI), HR, and HRV parameters derived from overnight ECG. Plasma aldosterone and norepinephrine levels, medicines with cardiovascular effect, and reported physical activity were examined as covariates. General Linear Models were used to assess significance of associations and adjust for potential confounders. Compared to controls, CFS cases had significantly higher mean HR (71.4 vs 64.8 bpm), with a shorter mean RRI [840.4 (85.3) vs 925.4(97.8) ms] (p<0.0004, each), and reduced low frequency (LF), very low frequency (VLF), and total power (TP) of HRV (p<0.02, all). CFS cases had significantly lower plasma aldosterone (p<0.05), and tended to have higher plasma norepinephrine levels. HR correlated weakly with plasma norepinephrine (r=0.23, p=0.05) and moderately with vitality and fatigue scores (r=-0.49 and 0.46, respectively, p<0.0001). Limitation in moderate physical activity was strongly associated with increased HR and decreased HRV. Nevertheless, among 42 subjects with similar physical activity limitations, CFS cases still had higher HR (71.8 bpm) than respective controls (64.9 bpm), p=0.023, suggesting that reduced physical activity could not fully explain CFS-associated differences in HR and HRV. After adjusting for potential confounders case-control differences in HR and TP remained significant (p<0.05).
Conclusion: the presence of increased HR and reduced HRV in CFS during sleep coupled with higher norepinephrine levels and lower plasma aldosterone suggest a state of sympathetic ANS predominance and neuroendocrine alterations. Future research on the underlying pathophysiologic mechanisms of the association is needed.