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Subclinical cardiovascular disease and health related quality of life in patients with radiographic axial spondyloarthritis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.ORCID iD: 0000-0002-8129-8771
2024 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Hälsorelaterad livskvalitet och subkliniska tecken på kardiovaskulär sjukdom vid radiografisk axial spondylartrit (Swedish)
Abstract [en]

Background: Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. The global prevalence of r-axSpA is between 0.1-1.4%. The disease is associated with extra-musculoskeletal manifestations (EMMs) such as anterior uveitis (AU), as well as increased risk of cardiovascular disease (CVD)-related comorbidities such as atherosclerosis that significantly contribute to mortality and the burden of disease in patients with r-axSpA. The increased CVD risk is not fully explained by traditional CVD risk factors, and little is known about the difference in CVD risk profiles between the sexes. Moreover, the association of disease related variables and subclinical signs of CVD by ultrasound remain to be comprehensively investigated in a well-characterized and sex stratified patient cohort. Additionally, studies investigating factors related to health-related quality of life (HRQoL) in patients with r-axSpA acknowledge that r-axSpA patients have a lower HRQoL than the general population. However, constancy in study methods and comparison to general population controls, especially stratified by sex, are limited. 

Objectives: The global aim of this thesis was to explore novel methods relating to the evaluation, detection, and monitoring of factors contributing to the burden of CVD in patients with r-axSpA, and to increase knowledge about HRQoL. More specifically, to study the impact of r-axSpA on HRQoL (Paper 1) and identify novel ultrasound markers of subclinical CVD (Papers 2-4) in patients with r-axSpA, overall, stratified by sex, and compared to controls. 

Materials and methods: Paper 1: The Short Form-36 (SF-36) questionnaire was used to assess HRQoL in patients with r-axSpA from Western Sweden (n=210, females 42.4%). Each patient was compared to 5 age- and sex-matched persons from the SF-36 Swedish normative population database (n=1055). Papers 2-4: Ultrasound was used to (i) assess bilateral common carotid arterial (CCA) stiffness by calculation of b-stiffness index and circumferential 2D strain (Paper 2); (ii) measure mean bilateral carotid intima media thickness (cIMT) and investigate its relationship with biomarkers of inflammation (Paper 3); and (iii) assess the mean thickness of the epicardial adipose tissue (EAT) deposit and its associations with traditional CVD related risk factors (Paper 4). Papers 2-4 used a well characterized patient group from Northern Sweden (‘Backbone cohort’, n=155, female 31.0%). The control group for paper 2 included 46 age- and sex- matched persons from the local population, with no traditional CVD risk factors. The control group for papers 3 and 4, was derived from the Umeå region Swedish CArdioPulmonary bioImaging Study (SCAPIS) recall study (n= 400, females 51.0%). All results were presented stratified by sex. Uni- and multi-variate regression analysis methods were used to evaluate associations with disease and demographic variables. All studies were of cross-sectional design.

Results: Paper 1: Patients exhibited significantly lower HRQoL compared to controls (P<0.001). Upon stratification by sex, both sexes scored significantly lower physical compared to the mental HRQoL scores. Multivariable logistic regression analysis found that patients with a longer disease duration, worse physical function (assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI), high disease activity (measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS)), or who lived alone had significantly lower physical HRQoL. Lower mental HRQoL was associated with fatigue, high ASDAS and living alone. Some differences in sex were also found. Paper 2: Patients had higher mean bilateral CCA b-stiffness index, and lower 2D CCA circumferential strain, compared to controls. Multivariate linear regression analysis found that several disease related parameters, in addition to age, were related to 2D circumferential strain (R2 0.33), whereas only age was related to b-stiffness index (R2 0.19). Paper 3: Linear regression analysis, with various adjustment models, showed that patients had increased cIMT compared to controls. White blood cell (WBC)- and monocyte- count were the only inflammatory biomarkers associated with cIMT. This association was only seen in male patients and remained after adjustments. Paper 4: Mean EAT was thicker in r-axSpA patients overall and stratified by sex compared to controls. No difference in mean EAT was found between the sexes. There were borderline significant associations between EAT thickness and cholesterol levels in male patients.

Conclusion: Patients with r-axSpA have decreased HRQoL and increased subclinical indicators of CVD compared to controls. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may be improved in patients with r-axSpA. Additionally, ultrasound methods are non-invasive, and easily obtainable, offering additional insights into the factors that influence the risk of CVD in r-axSpA patients. Although further studies are required to validate novel ultrasound methods, these techniques represent a powerful approach to non-invasively to detect, monitor, and help manage CVD related comorbidities. 

Place, publisher, year, edition, pages
Umeå: Umeå University, 2024. , p. 126
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2270
Keywords [en]
Radiographic axial spondyloarthritis, health related quality of life, cardiovascular disease, ultrasound, common carotid artery, intima media thickness, epicardial adipose tissue
National Category
Rheumatology and Autoimmunity Cardiac and Cardiovascular Systems Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medicine; cardiovascular disease; rheumatology
Identifiers
URN: urn:nbn:se:umu:diva-223462ISBN: 9789180702102 (print)ISBN: 9789180702119 (electronic)OAI: oai:DiVA.org:umu-223462DiVA, id: diva2:1852166
Public defence
2024-05-16, Hörsal B, Byggnad 1D, T9, Norrlands universitetssjukhus, Daniel Naezéns väg, 907 37 Umeå, Umeå, 09:00 (English)
Opponent
Supervisors
Note

Disputation also via Zoom.

Available from: 2024-04-25 Created: 2024-04-17 Last updated: 2024-04-19Bibliographically approved
List of papers
1. Factors related to health-related quality of life in ankylosing spondylitis, overall and stratified by sex
Open this publication in new window or tab >>Factors related to health-related quality of life in ankylosing spondylitis, overall and stratified by sex
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2018 (English)In: Arthritis Research & Therapy , E-ISSN 1478-6362, Vol. 20, no 1, article id 284Article in journal (Refereed) Published
Abstract [en]

Background: Ankylosing spondylitis (AS) begins early in life and often leads to reduced physical function, but less is known about the impacts it has on health-related quality of life (HRQoL). The aims of this study were to assess HRQoL using the Short Form-36 (SF-36) in a cohort of patients with AS compared with controls and to examine associations between SF-36 scores and spinal radiographic changes, physical function, disease activity and demographic data overall and stratified by sex.

Methods: A cohort of patients with AS from Western Sweden were assessed using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with spinal radiographs, clinical examination and questionnaires, including the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Patient Global (BASG) and SF-36. Each patient's SF-36 results were compared with those of five age-matched and sex-matched persons (n=1055) from the SF-36 Swedish normative population database. Associations between SF-36 physical component summary (PCS) and mental component summary (MCS) scores and disease-related and demographic factors were investigated using univariate and multivariable ogistic regression analyses with PCS and MCS below/above their respective median values as dependent variables.

Results: A total of 210 patients, age (median, IQR) 49.0 (21.2) years, symptom duration 24.0 (21.0) years, men 57.6% and HLAB27 87.1% were included. Patients with AS scored significantly lower (p<0.001) compared to controls in all SF-36 domains and component summaries; PCS 42.4 (14.5) in AS versus 52.4 (11.8) in controls and MCS 47.9 (20.0) in AS versus 54.1 (10.1) in controls. Both men and women scored significantly lower in PCS compared with MCS. Multivariable logistic regression analyses revealed that living without a partner (OR 2.38, 95% CI 1.00-5.67), long symptom duration (year in decade OR 1.66, 95% CI 1.16-2.37), higher BASFI (OR 1.98, 95% CI 1.46-2.70) and ASDAS 2.1 (OR 3.32, 95% CI 1.45-7.62) were associated with worse PCS, while living without a partner (OR 3.04, 95% CI 1.34-6.91), fatigue (visual analogue scale for global fatigue greater than the median (OR 6.36, 95% CI 3.06-13.19) and ASDAS 2.1 (OR 2.97, 95% CI 1.41-6.25) with worse MCS. Some differences between sexes were observed in the results.

Conclusions: The patients with AS had significantly lower HRQoL compared with controls. PCS was more affected compared to MCS in both sexes. Both disease-related and demographic factors were associated with HRQoL, partly overlapping for PCS and MCS. Factors associated with HRQoL showed some differences between sexes. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may potentially be improved.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2018
Keywords
Ankylosing spondylitis, Health-related quality of life, Medical outcome survey short form-36, Disease tivity, Fatigue, Cross-sectional study, Observational study
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-155216 (URN)10.1186/s13075-018-1784-8 (DOI)000454395300001 ()30587228 (PubMedID)2-s2.0-85059232454 (Scopus ID)
Funder
Swedish Rheumatism AssociationRegion VästerbottenSwedish Society of MedicineSwedish Research Council
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2024-04-18Bibliographically approved
2. Biomechanical properties of common carotid arteries assessed by circumferential two-dimensional strain and β stiffness index in patients with ankylosing spondylitis
Open this publication in new window or tab >>Biomechanical properties of common carotid arteries assessed by circumferential two-dimensional strain and β stiffness index in patients with ankylosing spondylitis
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2021 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 48, no 3, p. 352-360Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, two-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to 1) compare with age- and sex-matched controls and to 2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in AS patients.

METHODS: In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3±11.2 years, 102(68.5%) men, 146 (98%) HLA-B27 positive, were examined. Bilateral CCAs were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients were compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction or stroke.

RESULTS: Mean bilateral circumferential 2D strain was lower in AS patients compared with controls, 7.9±2.6% vs 10.3±1.9%, p<0.001 whereas mean bilateral β stiffness index was higher, 13.1±1.6mmHg/mm vs 12.3±1.3mmHg/mm, p=0.018. In multivariable linear regression analyses strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis and treatment with csDMARD and/or bDMARD (R2 0.33), while stiffness was associated with age (R2 0.19).

CONCLUSION: Both CCA circumferential 2D strain and β stiffness index differed between AS patients and controls. Strain was associated with AS-related factors and age while stiffness with age, suggesting that the obtained results reflect different pathogenic vascular processes.

Place, publisher, year, edition, pages
The Journal of Rheumatology, 2021
Keywords
ankylosing spondylitis, cardiovascular disease, common carotid artery, ultrasound
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-173519 (URN)10.3899/jrheum.200146 (DOI)000658238100009 ()32611672 (PubMedID)2-s2.0-85102932664 (Scopus ID)
Available from: 2020-07-13 Created: 2020-07-13 Last updated: 2024-04-17Bibliographically approved
3. Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation
Open this publication in new window or tab >>Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation
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2024 (English)In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 43, no 5, p. 1559-1570Article in journal (Refereed) Published
Abstract [en]

Objective: There is an increased risk for cardiovascular disease (CVD) in patients with radiographic axial spondyloarthritis (r-axSpA). In this cross-sectional study, we aimed to, overall and stratified by sex, (i) compare ultrasound derived carotid intima media thickness (cIMT), between patients and controls, and (ii) investigate associations between cIMT, clinical disease activity and inflammation-related laboratory markers in patients with r-axSpA.

Method: In total, 155 patients diagnosed with r-axSpA using the modified New York criteria and 400 controls were included. Bilateral carotid ultrasound, laboratory testing, and questionaries were acquired. Disease-specific assessments were carried out for patients. Linear regression analysis was used to assess associations.

Results: Linear regression analyses showed that patients with r-axSpA had increased mean cIMT compared to controls (mean ± SD, 0.8 ± 0.1 mm vs 0.7± 0.1 mm, respectively, unstandardized β (95% CI) -0.076 (-0.10, -0.052), P < 0.001) adjusted for smoking status and age. Linear regression analyses for patients with r-axSpA showed that only males presented significant associations between cIMT and inflammation-related laboratory markers, white blood cell (WBC) count (mean ± SD, 6.8 ± 1.6 109/L) and monocytes (0.6 ± 0.2 109/L); WBC count (unstandardized β (95% CI) 0.019 (0.0065, 0.031), P = 0.003, R2 = 0.57) and monocytes (0.13 (0.0047, 0.26), P = 0.041, R2 = 0.55), adjusted for age, smoking status, body mass index, hypertension, dyslipidemia, diabetes mellitus, ASDAS-CRP, and treatment with DMARDs and glucocorticoids. No significant association was found between cIMT and clinical disease activity assessed by ASDAS-CRP.

Conclusion: Patients with r-axSpA had significantly increased cIMT compared to controls. In male patients, higher WBC and monocyte count were associated with an increase in cIMT suggesting the role of inflammation in the development of atherosclerosis. 

Place, publisher, year, edition, pages
Springer Nature, 2024
Keywords
Cardiovascular disease (CVD), Carotid intima-media thickness (cIMT), Radiographic axial spondyloarthritis (r-axSpA), Ultrasound
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-221778 (URN)10.1007/s10067-024-06913-8 (DOI)001176391500001 ()38443604 (PubMedID)2-s2.0-85186622797 (Scopus ID)
Funder
Swedish Research CouncilRegion VästerbottenStiftelsen Konung Gustaf V:s 80-årsfond
Available from: 2024-03-06 Created: 2024-03-06 Last updated: 2024-04-18Bibliographically approved
4. Association of epicardial adipose tissue thickness in radiographic axial spondyloarthritis with traditional cardiovascular risk factors
Open this publication in new window or tab >>Association of epicardial adipose tissue thickness in radiographic axial spondyloarthritis with traditional cardiovascular risk factors
Show others...
(English)Manuscript (preprint) (Other academic)
Keywords
Epicardial adipose tissue, echocardiography, radiographic axial spondyloarthritis, sex, cardiovascular disease
National Category
Rheumatology and Autoimmunity
Research subject
rheumatology; cardiovascular disease
Identifiers
urn:nbn:se:umu:diva-223459 (URN)
Available from: 2024-04-17 Created: 2024-04-17 Last updated: 2024-04-18

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