Heart rate variability and inflammatory bowel disease in humans: A systematic review and meta-analysis

Abstract

The autonomic nervous system (ANS) maintains homeostasis in the gastrointestinal tract, including immunity, inflammation and motility, through the brain-gut axis. To date, the associations between ANS function and inflammatory bowel disease (IBD) have been controversial and inconclusive in human studies. PubMed, Cochrane Library, and Embase were searched through February 2020 for articles reporting these association between heart rate variability (HRV), an indirect measure of ANS activity, and IBD. The standardized mean differences and 95% confidence intervals (CIs) were calculated. Ten eligible studies involving 273 ulcerative colitis patients, 167 Crohn's disease patients and 208 healthy controls were included. The values of the total power (SMD = -0.83, 95% CI = -1.44, -0.21), high frequency (SMD = -0.79, 95% CI = -1.20, -0.38), RR interval (SMD = -0.66, 95% CI = -1.04, -0.27), standard deviation of the RR intervals (SMD = -1.00, 95% CI = -1.73, -0.27), percentage of RR intervals with a greater than 50-millisecond variation (SMD = -0.82, 95% CI = -1.33, -0.30) and the square root of the mean squared differences in successive RR intervals (SMD = -0.71, 95% CI = -1.15, -0.26) of the IBD patients were lower than those of the healthy controls, and moderate to large effect sizes were observed in all HRV indices, except for low frequency (SMD = -0.41, 95% CI = 0.95, 0.13). IBD was strongly associated with an overall decrease in HRV, indicating substantially decreased ANS activity. Furthermore, the parasympathetic nerve displayed a stronger inverse association with ANS activity than the sympathetic nerve, indicating ANS dysfunction in patients with IBD.

Figure 1

Flow diagram of the search strategy and study selection process.

Figure 2

Forest plots of studies investigating the frequency-domain indices of HRV in healthy controls and patients with IBD. The combined SMDs and 95% CIs were separately calculated using random-effects models of TP (A), LF (B), HF (C) and the LF/HF ratio (D). CI = confidence interval, HF = high frequency, HRV = heart rate variability, LF = low frequency, SMD = standardized mean differences.

Figure 3

Forest plots of studies investigating the time-domain indices of HRV in healthy controls and patients with IBD. The combined SMDs and 95% CIs were separately calculated using random-effects models of the RR interval (A), SDNN (B), pNN50 (C) and RMSSD (D). pNN50 = percentage of RR intervals with greater than 50 milliseconds of variation, RMSSD = square root of the mean squared differences of successive RR intervals, SMD = standardized mean difference, SDNN = standard deviation of the RR intervals.

Figure 4

Begg's Funnel plots with Begg test of the meta-analysis of the HRV indices and IBD. Plots of the frequency-domain HRV indices (A) and time-domain HRV indices (B) are shown. LF = low frequency, HF = high frequency, LF/HF = low frequency to high frequency ratio, HRV = heart rate variability, pNN50 = percentage of RR intervals with greater than 50 milliseconds of variation, RMSSD = square root of the mean squared differences of successive RR intervals, SDNN = standard deviation of the RR intervals, se = standard error, SMD = standardized mean difference.