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Heart rate variability and cardiovascular risk factors in patients with rheumatoid arthritis: a longitudinal study
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.ORCID iD: 0000-0002-7436-7900
Umeå University, Faculty of Medicine, Department of Radiation Sciences.ORCID iD: 0000-0002-1313-0934
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.ORCID iD: 0000-0002-3486-5251
2023 (English)In: Autonomic Neuroscience: Basic & Clinical, ISSN 1566-0702, E-ISSN 1872-7484, Vol. 249, article id 103119Article in journal (Refereed) Published
Abstract [en]

Background: It is established that the risk of cardiovascular disease (CVD) is increased in patients with Rheumatoid Arthritis (RA). Heart rate variability (HRV) is a method for evaluating the activity in the cardiac autonomic nervous system. Our aim was to assess the longitudinal development of HRV in patients with RA and compare with healthy controls. Furthermore, we wanted to investigate associations between HRV, inflammatory disease activity and cardiovascular complications in patients with RA over time.

Method: HRV was assessed with frequency-domain analysis at baseline and after five years in 50 patients with early RA, all being younger than 60 years. HRV indices were age-adjusted based on the estimated age-dependency in 100 age and sex matched healthy controls. Additionally, clinical data including serological markers, disease activity, and blood pressure were collected from the patients. Eleven years after inclusion CVD was assessed.

Results: At baseline, patients with RA presented with lower HRV compared to controls during deep breathing (6 breaths/min), paced normal breathing (12 breaths/min) and after passive tilt to the upright position. No significant change in HRV was observed at the five-year follow-up. A significant negative correlation was found between HRV parameters and systolic blood pressure (SBP) at baseline. A significant positive correlation was found between heart rate and inflammatory markers at baseline but not after five years. Nine patients had developed CVD after 11 years, but no significant association was found with baseline HRV data.

Conclusion: This study showed that patients with RA have autonomic imbalance both at an early stage of the disease and after five years, despite anti-rheumatic medication, but no correlation between HRV and inflammation markers were observed. Reduced HRV was also significantly negatively correlated with increased SBP. Hypertension is a common finding in patients with RA. Thus, significant decline of HRV could be a useful early marker for development of hypertension in patients with RA.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 249, article id 103119
Keywords [en]
Autonomic nervous system, Clinical physiology, Heart rate variability, Rheumatoid arthritis
National Category
Cardiac and Cardiovascular Systems Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-214502DOI: 10.1016/j.autneu.2023.103119PubMedID: 37703773Scopus ID: 2-s2.0-85170415207OAI: oai:DiVA.org:umu-214502DiVA, id: diva2:1799250
Funder
Region VästerbottenSwedish Research CouncilKnut and Alice Wallenberg FoundationSwedish Rheumatism AssociationVisare NorrSwedish Heart Lung FoundationStiftelsen Konung Gustaf V:s 80-årsfondSwedish Society of MedicineAvailable from: 2023-09-21 Created: 2023-09-21 Last updated: 2023-11-02Bibliographically approved
In thesis
1. Heart and lung function - in health and disease: methodological studies in clinical physiology
Open this publication in new window or tab >>Heart and lung function - in health and disease: methodological studies in clinical physiology
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Hjärt-och lungfunktion vid hälsa och sjukdom
Abstract [en]

The human heart and lungs constitute an intricate and dynamic system. Various clinical physiological examinations can be used to evaluate cardio-pulmonary function and identify abnormalities. Thus, it is important to understand how normal physiology presents, to be able to identify pathological findings. To distinguish normal from abnormal findings in a patient population compared to healthy controls, adequate, accurate and up-to-date reference materials are required. 

There is currently a lack of well-established sex and age specific reference materials that clearly state boundaries of normality for electrocardiography (ECG) variables. For lung function examinations there are several different reference materials available, being discordant between ethnicities. In addition, the relation between lung function, age, sex, and height has generally been difficult to model in an optimal way. This highlights the need for more adequate sex-specific models regarding age- and height-dependency of spirometry variables. 

Heart rate variability (HRV) is a method for evaluating the autonomic nervous system (ANS) and its influence on heart rate and blood pressure. Autonomic disturbances are characterized by an imbalance between the sympathetic and the parasympathetic nervous systems. It is well known that decreased HRV is associated with increased mortality. Autonomic imbalances are also associated with various pathological conditions, of which rheumatoid arthritis (RA) and ischemic heart disease (IHD) are studied in this thesis.

The purpose of this thesis was to describe the properties of different clinical physiological examinations and to investigate reference values relating to cardiovascular and pulmonary function in healthy individuals regarding age and sex. In addition, the aim was to assess the relationship between HRV, RA and CVD both cross sectionally and longitudinally. 

In a subjectively healthy population (n=219) of varying age, there were age and sex-dependent differences in ECG examinations. This emphasizes former findings and supports the need to establish age- and sex-specific reference values in the future. 

Lung function examinations in subjectively healthy persons (n=285) support and emphasize that the reference values presented by the Global Lung function Initiative (GLI) underestimate the pulmonary function in the adult Swedish population. The study showed that the model used in GLI can be updated with new values that are specific for the Caucasian population in Sweden. 

Patients with RA (n=50) presented with lower HRV than healthy controls (n=100) during autonomic provocation tests, both at baseline examinations and after five years. This indicates a cardiac autonomic imbalance. Furthermore, increased systolic blood pressure was associated with reduced HRV, thus a decrease in HRV could be a risk marker for developing arterial hypertension in this patient group.

Females with IHD (n=197) presented with lower HRV compared to controls (n=141) at baseline, and a higher mortality rate after 15 years. The higher mortality rate was only present in females < 60 years of age. For measurements obtained in the upright position, HRV was higher in females that died during follow-up compared to those who were alive. 

This thesis emphasizes the importance of validated and updated sex- and age- specific reference materials, and models that are well suited for different clinical physiological examinations. Additionally, HRV examinations exposed changes in the ANS related to RA as well as IHD, where findings were shown to be persistent over time and particularly pronounced during provocations. In the future, HRV assessment could be a useful tool to identify the increased risk of developing hypertension in patients with RA, or to customize treatment based on ANS response as the field of personalized medicine continues to evolve.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2023. p. 95
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2263
Keywords
clinical physiology, reference materials, ECG, dynamic spirometry, HRV, rheumatoid arthritis, cardiovascular disease, ischemic heart disease
National Category
Cardiac and Cardiovascular Systems Respiratory Medicine and Allergy Rheumatology and Autoimmunity Physiology
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:umu:diva-216108 (URN)9789180701907 (ISBN)9789180701914 (ISBN)
Public defence
2023-12-01, Bergasalen, Norrlands universitetssjukhus, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2023-11-10 Created: 2023-11-02 Last updated: 2023-11-02Bibliographically approved

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Erelund, SofiaSödergren, AnnaWiklund, UrbanSundström, Nina

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