Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial

Abstract

Fibromyalgia (FM) is associated with sympathetically dominant dysautonomia, but the connection between dysautonomia and FM symptoms is unclear. Dysautonomia can be analysed with heart rate variability (HRV) and it has been proposed that FM patients comprise subgroups with differing profiles of symptom severity. In our study, 51 female FM patients aged 18 to 65 years and 31 age-matched healthy female controls followed a 20-min protocol of alternating relaxation and cognitive stress (mental arithmetic). Heart rates and electrocardiograms were registered. The HRV measures of heart rate (HR), mean interval between heart beats (RR_mean), root mean squared interval differences of successive beats (RMSSD), and the standard deviation of intervals between normal heart beats (SDNN) were analysed with generalized linear modelling. Features in HRV reactivity which differed between FM patients and controls were used to cluster the FM patients and cluster characteristics were analysed. FM patients had higher baseline HR (72.3 [SD 12.7] vs 64.5 [7.80], p < 0.001) and lower RR_mean (0.844 [0.134] vs 0.934 [0.118], p = 0.002), compared with controls. They also reacted to repeated cognitive stress with an attenuated rise in HR (- 4.41 [95% CI - 7.88 to - 0.93], p = 0.013) and attenuated decrease of RR_mean (0.06 [95 CI 0.03 to 0.09], p < 0.001), compared with controls. Clustering of FM patients by HRV reactivity resulted in three clusters characterised by (1) normal levels of HRV and HRV reactivity with low levels of depressive mood and anxiety, (2) reduced levels of HRV and impaired HRV reactivity with increased levels of depressive mood and high levels of anxiety, and (3) lowest HRV and most impaired HRV reactivity with the highest scores for depressive mood and anxiety. Our results show that FM patients have lower HRV than healthy controls and their autonomous reactions to cognitive stress are attenuated. Dysautonomia in FM associates with mood disturbance. Trial registration ClinicalTrials.gov (NCT03300635). Registered October 3 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03300635 .

Figure 1

Mean scores of individual items in the Fibromyalgia Impact Questionnaire in the three clusters of the fibromyalgia patients. Item 1 (Impairment): Were you able to (subitems A–J: do shopping, prepare meals, etc.)?; Item 2 (Days unwell): Of the 7 days in the past week, how many days did you feel good? (higher score = more days unwell); Item 5 (Pain): How bad has your pain been? (visual analogue scale [VAS]); Item 6 (Fatigue): How tired have you been? (VAS); Item 7 (Unrefreshed): How have you felt when you get up in the morning? (VAS); Item 8 (Stiffness): How bad has your stiffness been? (VAS); Item 9 (Anxiety): How nervous, or anxious have you felt? (VAS); Item 10 (Depression): How depressed or blue have you felt? (VAS). Significant differences in Anxiety between clusters 2 and 3 compared with cluster 1, and Depression between cluster 3 compared with cluster 1 at p < 0.05 (Tukey’s HSD).

Figure 2

Box plots of the fibromyalgia impact questionnaire (FIQ), pain catastrophizing scale (PCS), perceived stress scale (PSS), and state-trait anxiety inventory A (state anxiety, STAI-A) and B (trait anxiety, STAI-B), scores in the three clusters of fibromyalgia patients.

Figure 3

Mean heart rate (HR, beats per minute), RMSSD (ms), subjective pain (numeric rating scale [NRS] from 0 to 10), and subjective stress (NRS from 0 to 10) levels during the measurement in the three fibromyalgia patient clusters (FM1, 2, 3) and healthy controls (Con). BL baseline, R1 first relaxation phase, S1 first cognitive stress phase, R2 second relaxation phase, S2 second cognitive stress phase, R3 third and final relaxation phase.