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Pro-inflammatory Blood Markers and Heart Rate Variability in Apnoea as a Reflection of Basal Vagal Tone
KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. Karolinska Institutet, Sweden.ORCID iD: 0000-0001-7807-8682
KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems. University of Borås, Sweden.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Pro-inflammatory cytokines play a crucial role in inflammatory response, which istightly regulated by the nervous system to avoid the damage caused by inflammation. There isevidence for a cholinergic anti-inflammatory pathway that includes afferent and efferent vagalnerves that sense the inflammation and stimulate the anti-inflammatory response. Non-functionalanti-inflammatory response might lead to excessive and chronic inflammation e.g., rheumatoidarthritis (RA), inflammatory bowel disease (IBD), and poor outcome. Heart rate variability(HRV) has been proposed as a potential tool to monitor the level of anti-inflammatory activitythrough the monitoring of vagal activity. In this paper, the association of pro-inflammatorymarkers with HRV indices is evaluated. We used a database called “Heart Biomarker Evaluationin Apnea Treatment (HeartBEAT)” that consists of 6±2 hours of Electrocardiogram (ECG)recordings during nocturnal sleep from 318 patients at baseline and 301of them at 3 monthsfollow-up. HRV indices are calculated from ECG recordings of 5-360 minutes. The results showa statistically significant correlation between heart rate (HR) and pro-inflammatory cytokines,independent of duration of ECG analysis. HRV indices e.g., standard deviation of all RRintervals (SDNN) show an inverse relation to the pro-inflammatory cytokines. Longer ECGrecordings show a higher potential to reflect the level of anti-inflammatory response. In light oftheories for the cholinergic anti-inflammatory pathway, a combination of HR and HRV as areflection of basal vagal activity might be a potential prognostic tool for interventional guidance.

Keyword [en]
Heart Rate Variability, HRV, cholinergic anti-inflammatory pathway, basal vagal tone, sampling of time-invariant system, CRP, pro-inflammatory blood markers, inflammation
National Category
Other Medical Engineering
Research subject
Medical Technology
Identifiers
URN: urn:nbn:se:kth:diva-191361OAI: oai:DiVA.org:kth-191361DiVA: diva2:956324
Note

QC 20160901

Available from: 2016-08-30 Created: 2016-08-30 Last updated: 2016-09-02Bibliographically approved
In thesis
1. Towards Heart Rate Variability Tools in P-Health: Pervasive, Preventive, Predictive and Personalized
Open this publication in new window or tab >>Towards Heart Rate Variability Tools in P-Health: Pervasive, Preventive, Predictive and Personalized
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heart rate variability (HRV) has received much attention lately. It has been shown that HRV can be used to monitor the autonomic nervous system and to detect autonomic dysfunction, especially vagal dysfunction. Reduced HRV is associated with several diseases and has also been suggested as a predictor of poor outcomes and sudden cardiac death. HRV is, however, not yet widely accepted as a clinical tool and is mostly used for research. Advances in neuroimmunity with an improved understanding of the link between the nervous and immune systems have opened a new potential arena for HRV applications. An example is when systemic inflammation and autoimmune disease are primarily caused by low vagal activity; it can be detected and prognosticated by reduced HRV. This thesis is the result of several technical development steps and exploratory research where HRV is applied as a prognostic diagnostic tool with preventive potential. The main objectives were 1) to develop an affordable tool for the effective analysis of HRV, 2) to study the correlation between HRV and pro-inflammatory markers and the potential degree of activity in the cholinergic anti-inflammatory pathway, and 3) to develop a biofeedback application intended for support of personal capability to increase the vagal activity as reflected in increased HRV. Written as a compilation thesis, the methodology and the results of each study are presented in each appended paper. In the thesis frame/summary chapter, a summary of each of the included papers is presented, grouped by topic and with their connections. The summary of the results shows that the developed tools may accurately register and properly analyse and potentially influence HRV through the designed biofeedback game. HRV can be used as a prognostic tool, not just in traditional healthcare with a focus on illness but also in wellness. By using these tools for the early detection of decreased HRV, prompt intervention may be possible, enabling the prevention of disease. Gamification and serious gaming is a potential platform to motivate people to follow a routine of exercise that might, through biofeedback, improve HRV and thereby health.

Abstract [sv]

Hjärtfrekvensvariabilitet (HRV) har senaste tiden rönt en hel del uppmärksamhet och flera teknikerför analys av HRV i tids- resp. frekvensområdet samt medels icke-linjära metoder har utvecklats.Det har visats att HRV kan användas för att övervaka det autonoma nervsystemet (ANS) blandannat för att upptäcka särskilt vagala störningar inom ANS. Minskad HRV förknippas med flerasjukdomar såsom diabetes, reumatoid artrit, depression, kronisk hjärtsjukdom och har ävenföreslagits som prediktor för dålig prognos och plötslig hjärtdöd. HRV är dock ännu inte allmäntaccepterat som ett kliniskt verktyg utan används främst inom forskning. Framsteg inomneuroimmunitetsområdet med ökad förståelse för sambandet mellan nerv- och immunsystem, haröppnat en nytt potentiell område för HRV-applikationer. Ett exempel är när systemiskinflammationoch autoimmun sjukdom primärt orsakas av låg vagal aktivitet, vilket kan upptäckas ochprognostiseras via minskad HRV. Denna avhandling är resultatet av flera tekniska utvecklingsstegoch explorativ forskning där HRV tillämpas i syfte att utveckla ett prognostiskt diagnostiskt verktygmed förebyggande potential. Huvudsyften har varit: 1) att utveckla ett prisvärt verktyg för eneffektiv och enkel analys av HRV 2) att studera sambandet mellan HRV och pro-inflammatoriskamarkörer och därigenom potentiellt återspegla graden av aktivitet i den kolinergaantiinflammatoriska effektorvägen 3) att utveckla datorprogramvara för ett biologisktåterkopplingssystem där individen med egen träning ökar sin vagala aktivitet vilket sedanåterspeglas i en ökad HRV. I denna sammanläggningsavhandling finns utförlig beskrivning av varjeingående studies metod och resultat artikar I-VI. I ramberättelsen presenteras en kortsammanfattning av metoder och resultat, grupperade efter ämne och sammanhang.Sammanfattningsvis visar resultaten att de utvecklade verktygen adekvat registrerar och analyserarHRV korrekt enkelt , samt att HRV kan påverkas av spel-träning. HRV i framtaget koncept harpotential att användas som ett skarpt prognostiskt verktyg, inte bara för traditionell vård med fokuspå sjukdom, utan också inom friskvård. Framtagna verktyg möjliggör tidig upptäckt av minskadHRV, snabb intervention och prevention. Spelifiering med seriöst spelande utgör en potentiellplattform som motiverar en träningsrutin och som genom återkoppling kan öka HRV och därmedvälmåendet.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2016. 50 p.
Series
TRITA-STH : report, ISSN 1653-3836 ; 2016:5
Keyword
Heart Rate Variability, Cholinergic Anti-inflammatory Pathway, Autonomic Nervous System, Vagal activity, Biofeedback, Gamification, Serious Gaming, Inflammatory Markers, Raspberry PI
National Category
Other Medical Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-190182 (URN)978-91-7729-069-8 (ISBN)
External cooperation:
Public defence
2016-09-26, T2, Blickagången 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
VINNOVA
Note

QC 20160902

Available from: 2016-09-02 Created: 2016-08-11 Last updated: 2016-09-04Bibliographically approved

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