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Coronary Artery Calcification Is Related to Inflammation in Rheumatoid Arthritis: A Long-Term Follow-Up Study
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
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2016 (English)In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 1261582Article in journal (Refereed) Published
Abstract [en]

Objective. A long-term follow-up of patients with rheumatoid arthritis (RA) to evaluate factors related to coronary artery calcification (CAC). Methods. All 22 eligible patients (4 males/18 females, mean age 65 years, and RA-duration 30-36 years) from the original (baseline; n = 39) study of atherosclerosis were included. Inflammation, cardiovascular risk factors, and biomarkers were measured at baseline. At follow-up 13 years later, CAC was assessed by computed tomography (CT) and the grade of inflammation was measured. Multivariate analysis of differences between patients with low (0-10) and high CAC (>10) was done by orthogonal projection to latent structures (OPLS). Results. Ten patients had CAC 0-10 and 12 had >10 (range 18-1700). Patients with high CAC had significantly higher ESR (24.3 versus 9.9 mm/h) and swollen joint count (2 versus 0). The OPLS models discriminated between patients having high or low CAC. With only baseline variables, the sensitivity was 73% and the specificity 82%. The model that also included inflammatory variables from follow-up had a sensitivity of 89% and a specificity of 85%. Exclusion of baseline intima media thickness and plaque from the latter model modestly reduced the accuracy (sensitivity 80% and specificity 83%). Conclusions. CAC is related to inflammation in patients with RA.

Place, publisher, year, edition, pages
2016. article id 1261582
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-126539DOI: 10.1155/2016/1261582ISI: 000383093900001PubMedID: 27648442OAI: oai:DiVA.org:umu-126539DiVA, id: diva2:1038431
Available from: 2016-10-18 Created: 2016-10-10 Last updated: 2019-04-12Bibliographically approved
In thesis
1. Atherosclerotic cardiovascular disease in rheumatoid arthritis: aspects of pathogenesis and risk
Open this publication in new window or tab >>Atherosclerotic cardiovascular disease in rheumatoid arthritis: aspects of pathogenesis and risk
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with rheumatoid arthritis (RA) have an increased prevalence and severity of atherosclerosis, and a corresponding increased risk of cardiovascular disease. The mechanisms causing this are not well elucidated, but both traditional cardiovascular risk factors and RA-associated factors have been associated with atherosclerosis and increased risk of cardiovascular events in patients with RA. Cardiovascular risk estimation based on traditional cardiovascular risk factors, often underestimates the risk in patients with RA. The aims of this thesis were to examine factors and biomarkers associated with atherosclerosis in patients with RA, and to evaluate an algorithm for cardiovascular risk estimation in patients with RA.

Methods Patients with early RA in the four northernmost counties of Sweden have since 1995 been included in a prospective study of both the progress of RA and comorbidities. Besides clinical data, radiographs, genetic markers and autoantibodies are registered. Paper I includes 665 patients aged 40-80 years from that cohort, in whom the 10-year risk of a first cardiovascular event was estimated with both Expanded Cardiovascular Risk Prediction Score in Rheumatoid Arthritis (ERS-RA), and the general population based ACC/AHA algorithm. The estimations were then compared to the actual outcomes. Paper II examines factors associated with coronary artery calcification (CAC) in 22 patients with long-standing RA. Papers III and IV use data from a cohort of patients <60 years of age at diagnosis of RA (n=79), in whom development of atherosclerosis has been prospectively followed since diagnosis of RA. This is a subset of patients from the larger cohort in paper I. Controls matched for age and sex (n=44) are examined as well. In paper III, phenotypes of T-cells and IgG-antibodies against cytomegalovirus (CMV) are analysed in relation to carotid intima-media thickness (IMT). In paper IV, bone mineral density and markers and regulators of bone metabolism are analysed in relation to IMT.

Results Cardiovascular risk estimation with the RA-specific algorithm ERS-RA is not superior to estimation with the ACC/AHA algorithm. Both algorithms underestimate the risk in patients with a high grade of inflammation and in patients with an estimated moderate risk. In patients with long-standing RA, presence of CAC is associated with inflammatory activity, both at time of examination and in earlier stages of RA. Presence of anti-CMV IgG antibodies and altered T-cells (both CD4+ and CD8+) lacking the co-stimulatory molecule CD28 (CD28null) are associated with a higher IMT, and patients IgG-positive for CMV have a rapid increase in IMT after onset of RA. Regulators of bone metabolism (sclerostin, osteoprotegerin and osteocalcin) are associated with a higher IMT in patients with RA.

Conclusion Cardiovascular risk estimation in patients with RA still needs to be improved. The fact that CMV-positivity, altered populations of T-cells and IMT all are associated, and that also regulators of bone metabolism reflect IMT, suggests that the pathogenesis of atherosclerosis in patients with RA is multifactorial.  This thesis provides knowledge of the accelerated development of atherosclerosis in RA and could possibly be relevant also in other chronic inflammatory diseases, where markers of accelerated atherosclerosis and increased cardiovascular risk are lacking.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2019. p. 56
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2029
Keywords
Rheumatoid arthritis, inflammation, atherosclerosis, cardiovascular disease, risk estimation, cytomegalovirus, T-cells, bone turnover, osteoprotegerin, osteocalcin
National Category
Rheumatology and Autoimmunity
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-158137 (URN)978-91-7855-047-0 (ISBN)
Public defence
2019-05-10, Sal 933, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
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Available from: 2019-04-17 Created: 2019-04-12 Last updated: 2019-04-16Bibliographically approved

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Wahlin, BengtMeedt, ThomasJonsson, FredrikHenein, Michael Y.Wållberg-Jonsson, Solveig

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