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...

Full description

Bibliographic Details
Main Authors: Teemu Zetterman, Ritva Markkula, Teemu Miettinen, Eija Kalso
Format: Article
Language:English
Published: Nature Portfolio 2023-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-27581-9
_version_ 1797952555845681152
author Teemu Zetterman
Ritva Markkula
Teemu Miettinen
Eija Kalso
author_facet Teemu Zetterman
Ritva Markkula
Teemu Miettinen
Eija Kalso
author_sort Teemu Zetterman
collection DOAJ
description 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 (RRmean), 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 RRmean (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 RRmean (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 .
first_indexed 2024-04-10T22:49:26Z
format Article
id doaj.art-79fbd70a66f744edb837b38998212849
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-04-10T22:49:26Z
publishDate 2023-01-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-79fbd70a66f744edb837b389982128492023-01-15T12:09:10ZengNature PortfolioScientific Reports2045-23222023-01-0113111010.1038/s41598-023-27581-9Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trialTeemu Zetterman0Ritva Markkula1Teemu Miettinen2Eija Kalso3Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University and Helsinki University HospitalDepartment of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University and Helsinki University HospitalDepartment of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University and Helsinki University HospitalDepartment of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University and Helsinki University HospitalAbstract 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 (RRmean), 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 RRmean (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 RRmean (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 .https://doi.org/10.1038/s41598-023-27581-9
spellingShingle Teemu Zetterman
Ritva Markkula
Teemu Miettinen
Eija Kalso
Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial
Scientific Reports
title Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial
title_full Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial
title_fullStr Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial
title_full_unstemmed Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial
title_short Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial
title_sort heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses a clinical trial
url https://doi.org/10.1038/s41598-023-27581-9
work_keys_str_mv AT teemuzetterman heartratevariabilityresponsestocognitivestressinfibromyalgiaarecharacterisedbyinadequateautonomoussystemstressresponsesaclinicaltrial
AT ritvamarkkula heartratevariabilityresponsestocognitivestressinfibromyalgiaarecharacterisedbyinadequateautonomoussystemstressresponsesaclinicaltrial
AT teemumiettinen heartratevariabilityresponsestocognitivestressinfibromyalgiaarecharacterisedbyinadequateautonomoussystemstressresponsesaclinicaltrial
AT eijakalso heartratevariabilityresponsestocognitivestressinfibromyalgiaarecharacterisedbyinadequateautonomoussystemstressresponsesaclinicaltrial