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  • 401. Zhang, Yuan
    et al.
    Johansson, Linda
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Rudin, Anna
    Carlsson, Lena
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Maglio, Cristina
    In overweight subjects, serum adiponectin predicts the development of rheumatoid arthritis independently of other adipokines2019In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, p. 298-298Article in journal (Other academic)
    Abstract [en]

    Background: Adipokines, such as adiponectin, leptin, resistin and visfatin, are cytokines produced by the adipose tissue and involved in metabolism and inflammation1 . Adiponectin is elevated in both serum and synovial fluid of subjects with rheumatoid arthritis (RA), suggesting a possible role of this adipokine in the pathogenesis of RA 2,3. Circulating levels of leptin, resistin, and visfatin are also higher in subjects with RA compared to controls 2,4.

    Objectives: Aim of this study was to determine if adiponectin, leptin, resistin, and visfatin predict the development of RA.

    Methods: Two nested-case control studies were performed including presymptomatic participants of two cohorts from Sweden: the Swedish Obese Subjects (SOS) study and a cohort of individuals identified within the Medical Biobank of northern Sweden. The SOS is a clinical trial including 4047 subjects with obesity6 . During a follow-up for up to 29 years, 92 subjects developed RA. Among those 92 subjects, 82 subjects with available serum at baseline were matched 1:5 with 410 subjects who did not develop RA during follow-up. Matching was based on baseline age, sex, body-mass index (BMI), bariatric surgery yes/no, year of inclusion, and smoking. A nested case-control study of 88 sex- and age-matched pairs was performed within the Medical Biobank of Northern Sweden using blood samples donated before the onset of the first RA symptoms. The pre-dating time before onset of symptoms of RA was 8.5±5.0 years7 . Baseline serum levels of adiponectin, leptin, resistin, and visfatin were measured using the Quantikine ELISA kit from R&D Systems (Wiesbaden, Germany). Visfatin could not be measured in the Biobank cohort, due to lack of serum. Both binary logistic as well as conditional logistic regression analyses were used to determine if adipokines were elevated years before the onset of RA.

    Results: In a multivariable analysis including adiponectin, leptin, resistin, visfatin performed in the SOS cohort, serum adiponectin was associated with a higher risk for RA independently of other adipokines (Odds ratio, OR, 1.1, 95% confidence interval, CI, 1.0-1.1, p value=0.01). Leptin, resistin and visfatin levels were not associated with the risk of RA. In the Biobank cohort, no association between adipokines and risk for RA was detected. However, when stratifying the population according to BMI, in the subgroup having BMI>25 (n=109), adiponectin levels were associated with higher risk for RA (OR 1.2, 95% CI 1.0-1.36, p=0.03), independently of leptin and resistin levels. Virtually the same results were obtained in both the SOS and the Biobank cohorts when conditional logistic regression analysis was used.

    Conclusion: Our results suggest that higher serum adiponectin levels predict the development of RA in subjects with overweight/obesity.

  • 402. Ziegelasch, Michael
    et al.
    Forslind, Kristina
    Skogh, Thomas
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kastbom, Alf
    Berglin, Ewa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Decrease in bone mineral density during three months after diagnosis of early rheumatoid arthritis measured by digital X-ray radiogrammetry predicts radiographic joint damage after one year2017In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, no 1, article id 195Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Periarticular osteopenia is an early sign of incipient joint injury in rheumatoid arthritis (RA), but cannot be accurately quantified using conventional radiography. Digital X-ray radiogrammetry (DXR) is a computerized technique to estimate bone mineral density (BMD) from hand radiographs. The aim of this study was to evaluate whether decrease in BMD of the hands (BMD loss), as determined by DXR 3 months after diagnosis, predicts radiographic joint damage after 1 and 2 years in patients with early RA.

    METHODS: Patients (n = 176) with early RA (<12 months after onset of symptoms) from three different Swedish rheumatology centers were consecutively included in the study, and 167 of these patients were included in the analysis. Medication was given in accordance with Swedish guidelines, and the patients were followed for 2 years. Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) were measured at baseline, and 28-joint Disease Activity Score (DAS28) was assessed at each visit. Radiographs of the hands and feet were obtained at baseline, 3 months (hands only) and 1 and 2 years. Baseline and 1-year and 2-year radiographs were evaluated by the Larsen score. Radiographic progression was defined as a difference in Larsen score above the smallest detectable change. DXR-BMD was measured at baseline and after 3 months. BMD loss was defined as moderate when the decrease in BMD was between 0.25 and 2.5 mg/cm2/month and as severe when the decrease was greater than 2.5 mg/cm2/month. Multivariate regression was applied to test the association between DXR-BMD loss and radiographic damage, including adjustments for possible confounders.

    RESULTS: DXR-BMD loss during the initial 3 months occurred in 59% of the patients (44% moderate, 15% severe): 32 patients (19%) had radiographic progression at 1 year and 45 (35%) at 2 years. In multiple regression analyses, the magnitude of DXR-BMD loss was significantly associated with increase in Larsen score between baseline and 1 year (p = 0.033, adjusted R-squared = 0.069).

    CONCLUSION: DXR-BMD loss during the initial 3 months independently predicted radiographic joint damage at 1 year in patients with early RA. Thus, DXR-BMD may be a useful tool to detect ongoing joint damage and thereby to improve individualization of therapy in early RA.

  • 403.
    Ärlestig, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Genetic studies in rheumatoid arthritis: familial studies and analysis of relationships to atherothrombotic comorbidity2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background. Rheumatoid arthritis (RA) is an autoimmune disease mainly affecting the joints but has also extra articular manifestations and an increased cardiovascular (CV) co-morbidity. Rheumatoid factor (RF) and antibodies against citrullinated proteins/peptides (ACPA) are diagnostically important and are related to a more severe disease. The aetiology is unknown but RA is considered a complex disease caused by both genetic and environmental factors. The heritability is estimated to be 60% with the main contribution from the HLA region. The relative homogeneity of the population in northern Sweden due to low immigration and founder effects has shown to be suitable for genetic studies.

    Objectives. The aim of this thesis has been to identify genes contributing to the susceptibility of RA and the CV co-morbidity in particular. To achieve this, multi-case families from the four northern most counties of Sweden were collected for linkage studies to identify susceptibility genes. Association studies with genetic polymorphisms in genes, involved in inflammation or being of importance for atherothrombotic manifestations (ATM) in the general population, were performed in RA-patients concerning ATM e.g. myocardial infarction, angina pectoris with intervention, stroke/TIA, deep vein thrombosis/pulmonary embolism (DVT/PE) at follow-up.

    Methods & Results. 47 families with 134 affected and 216 unaffected relatives were included in a genome-wide linkage study (GWL) performed with microsatellite markers at an average of 10cM resolution analysed using ABI PRISM 3730 DNA sequencer and non-parametric multipoint linkage in the Merlin program. Eight linked loci were identified with HLA as the most significant and a novel region on chromosome 14. In a follow-up analysis on a custom Illumina chip, with 13 additional families, yielding a total of 198 affected and 197 unaffected relatives. The majority of the 1536 single nucleotide polymorphisms (SNPs) used in the Illumina follow-up analyses was focused on chromosome 14. Statistical analyses with linkage and transmission disequilibrium test narrowed the region to 4 cM, a region containing multiple plausible RA candidate genes (Paper I). In Paper II  serum samples from 163 affected and 157 first degree relatives were analysed with EliA ACPA assay on ImmunoCAP250 for ACPA (IgA, IgG, IgM) and RF (IgA, IgM) isotypes. Both concentrations and frequencies were increased among the relatives compared with controls but lower compared with RA-patients and with a different relative distribution of the isotypes.

    The genetic contribution to ATM was studied in Paper III and IV using selected SNPs analysed using ABI PRISM 7900HT sequence detector system. In Paper III, RA-patients (n=467) were compared with age and sex matched controls (n=696) with respect to SNPs in tumor necrosis factor receptor II (TNFRII)(M196R), ß-fibrinogen -455 (G-455A), plasminogen activator inhibitor type-1 (PAI-1) (4G/5G) and Factor XIIIA (Val34Leu). Hypertension was predicted by TNFRII R allele and to a higher extent in combination with the A-allele in ß-fibrinogen. The 4G allele in PAI-1 was more frequent in patients with ischemic heart disease (IHD) and the FXIIIA Leu34 variant in patients with DVT/PE. In Paper IV, the minor allele of the polymorphism in growth differentiation factor 15 (GDF15) was found to be associated with RA (n=696) per se but also to ATM, a SNP in the 9p21.3 locus was also associated with ATM. A significant association to stroke was found in female patients homozygote for the minor allele of GDF15. Stoke among male patients was significantly associated with carrying the major allele of two SNPs in the CD40 gene. DVT/PE was associated with the minor allele of GDF15.

    Conclusion. A novel locus on chromosome 14 of importance for RA susceptibility in northern Sweden was found. The minor allele of TNFRII separately and together with the minor allele of ß-fibrinogen -455 was associated with hypertension and the 4G allele in PAI-1 was associated with IHD and  the Leu34 variant was associated with DVT/PE in RA patients. The GDF15 minor allele was associated with RA per se, ATM and DVT/PE in RA patients and a genotype in the SNP on 9p21.3 was associated with ATM. Stroke among females was associated with GDF15 and stroke among males with two SNPs in CD40.

  • 404.
    Ärlestig, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Brink, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Hansson, Monika
    Jakobsson, Per Johan
    Holmdahl, Rikard
    Mathsson, Linda
    Ronnelid, Johan
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Single Nucleotide Polymorphisms within the HLA-DRB1 Gene in Relation to Antibodies Against Citrullinated Peptides in Individuals Prior to the Development of Rheumatoid Arthritis2012In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, no 10, p. S180-S180Article in journal (Other academic)
  • 405.
    Ärlestig, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Einarsdottir, Elisabet
    Research Program Unit, Molecular Medicine, University of Helsinki, Finland.
    Holmberg, Dan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Novel risk locus on chromosome 14 in multi-case families with rheumatoid arthritis from northern SwedenManuscript (preprint) (Other academic)
  • 406.
    Ärlestig, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Mullazehi, Mohammed
    Department of Immunology, Genetics and Pathology, Uppsala University.
    Kokkonen, Heidi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rönnelid, Johan
    Department of Immunology, Genetics and Pathology, Uppsala University.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Antibodies against cyclic citrullinated peptides of IgG, IgA and IgM isotype and rheumatoid factor of IgM and IgA isotype are increased in unaffected members of multicase rheumatoid arthritis families from northern Sweden2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no 6, p. 825-829Article in journal (Refereed)
    Abstract [en]

    Background Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years.

    Objective To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk factors.

    Methods 51 multicase families consisting of 163 individuals with rheumatoid arthritis (RA) (mean±SD age, 60±14 years; disease duration 21 years; 71.8% female) and with 157 first-degree relatives unaffected by RA (54±17 years; 59.9% female) were recruited. Isotypes of antibodies against CCPs (IgG, IgA and IgM) and RFs (IgM and IgA) were determined using automated enzyme immunoassays. Cut-off levels were established using receiver operating characteristic curves based on values for 100 unrelated healthy controls.

    Results The concentrations and frequencies of all anti-CCP and RF isotypes were significantly increased in first-degree relatives and patients with RA compared with unrelated healthy controls. The relative distribution of IgA and IgM isotypes was higher than IgG in the relatives, whereas the IgG isotype dominated in patients with RA. The patients carried human leucocyte antigen-shared epitope (HLA-SE) significantly more often than the relatives (71.4% vs 53.9%, p=0.01), while the frequency of the PTPN22 T variant was similar. HLA-SE, combined with smoking, was significantly related to all combinations of anti-CCP and RF isotypes in patients with RA. No such relationships were found for the first-degree relatives.

    Conclusions All anti-CCP and RF isotypes analysed occurred more commonly in unaffected first-degree relatives from multicase families than in controls, but with different isotype distribution from patients with RA.

  • 407.
    Ärlestig, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rantapää Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9p21.3 region in patients with rheumatoid arthritis and cardiovascular diseaseManuscript (preprint) (Other academic)
  • 408.
    Ärlestig, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Polymorphisms of the Genes Encoding CD40 and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease2012In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 39, no 5, p. 939-945Article in journal (Refereed)
    Abstract [en]

    Objective. Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM). Methods. A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 +/- 13.2 years, and mean disease duration of 15.5 +/- 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587), CD40 (rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex). Results. The distribution of genotypes of GDF15/MIC-1 differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of the GDF15/MIC-1 G allele (OR 2.21, 95% CI 1.17-4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15-3.19). Stroke/TIA in women was associated with GDF15/MIC-1 GG genotype (OR 3.75, 95% CI 1.06-13.33), while stroke/TIA in men was associated with CD40 homozygous major alleles (OR 6.48, 95% CI 1.31-32.0 and OR 2.78,95% CI 0.78-9.91, respectively). DVT/PE was associated with polymorphism in the GDF15/MIC-1 gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30-9.58). Conclusion. The gene polymorphisms analyzed were associated with different ATM in RA. The GDF15/MIC-1 gene polymorphism was also associated with RA per se, suggesting a common etiology for RA and ATM. (First Release April 15 2012; J Rheumatol 2012;39:939-45; doi:10.3899/jrheuin.111336)

  • 409.
    Ärlestig, Lisbeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Polymorphism of genes related to cardiovascular disease in patients with rheumatoid arthritis2007In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 25, no 6, p. 866-871Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyze candidate genes, related to cardiovascular disease (CVD) in general, and potentially involved in the inflammatory process, in RA patients from northern Sweden.

    METHODS: Four hundred and sixty-seven individuals (345 females; 122 males) with RA (ACR criteria), having a mean age of 61.8 +/- 13.0 years and mean disease duration of 16.2 +/- 12.1 years, were consecutively recruited and followed-up for 3 years. The prevalence of CVD, [(ischemic heart disease (IHD), deep vein thromboses/pulmonary embolism (DVT/PE) and/or stroke/TIA] and hypertension was registered. Candidate genes encoding for Beta-fibrinogen (G-455A), Factor XIIIA (Val34Leu), plasminogen activator inhibitor type-1 (PAI-1 4G/5G), and tumor necrosis factor receptor (TNFR)II (M196R) were analysed. Controls (n = 672) were randomly selected according to age and gender from the Medical Biobank of Northern Sweden. Polymorphisms were genotyped using a TaqMan 9700HT and the 5'nuclease allelic discrimination assay.

    RESULTS: The genotypes, carriers and alleles did not differ in distribution between patients and controls. Carriage of the TNFRII R variant was more frequent among patients with hypertension (p = 0.018). The genotype distribution of PAI-1 in patients with IHD differed significantly (p = 0.002) because carriage of 4G was more frequent (p = 0.024). Combined carriage of TNFRII 196R variant and Beta-fibrinogen-455A was a stronger predictor for hypertension than each genotype separately. The distribution of FXIIIA genotypes deviated significantly in RA patients with DVT/PE (p = 0.028) with an increased frequency of the Leu34 variant.

    CONCLUSION: The unusual alleles of TNFRII, PAI-1 and FXIIIA were associated with CVD in RA patients. The combination of several of the rare types further increased the predictive values for CVD.

  • 410.
    Åberg, Emmi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    The lever of urate in plasma is associated with first-time myocardial infarction - a nested case control study in Northern Sweden2019Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 411.
    Ångström, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Aerobic capacity in rheumatoid arthritis: aspects of associations with cardiovascular risk factors and disease activity2018Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rheumatoid arthritis (RA) is a systemic and inflammatory disease that has been associated with an increased morbidity and mortality in cardiovascular disease (CVD). Low aerobic capacity is one of the strongest independent risk factors for CVD and all-cause mortality in the general population. In patients with longstanding RA, low aerobic capacity has been related with a worse cardiovascular profile and an increased risk of CVD mortality. As a consequence of this, low aerobic capacity might provide an additional risk factor for CVD in patients with RA. The aim of this thesis was to describe the associations between aerobic capacity and risk factors for CVD as well as disease activity in patients with early RA, and also the effects of intensive exercise therapy on traditional risk factors for CVD and disease activity in patients with longstanding RA.

    Paper I, a cross-sectional study including 67 patients with early RA, mean (SD) age 53.1 (14.4), assessments of aerobic capacity, CVD risk factors, disease activity and functional ability were taken. Data were analysed for the associations between aerobic capacity and CVD risk factors and disease activity. In paper II, an intervention study, including 13 patients with RA, median age (Q1-Q3) 57 (44-64) years, aerobic capacity, pulse wave analysis (PWA), CVD risk factors, and disease activity were analysed for changes after 10 weeks of intensive exercise therapy. Additional follow-up was made after 25 weeks.

    In paper I, the mean (SD) aerobic capacity was 31.6 (8.7) ml O2/kg/min. CVD risk factors and disease activity were all in favour of patients with higher aerobic capacity. In a multiple regression model, adjusted for age and sex, aerobic capacity was significantly associated with percent body fat (β=-0.502, 95%CI=-0.671;-0.333) and triglycerides (β=-2.365, 95%CI=-4.252;-0.479). In paper II, intensive exercise over ten weeks was shown to be a feasible method to significantly improve aerobic capacity (p=≤0.05), systolic blood pressure (p=≤0.01) and the number of tender joints (p=≤0.05). No detrimental effect on disease activity was recorded.

    This thesis adds further knowledge of aerobic capacity and its associations with CVD risk factors and disease activity in patients with RA. Also, intensive exercise therapy was a feasible intervention to improve CVD risk factors. To include assessment of aerobic capacity in regular clinical practice may improve patient management as well as patient outcome in patients with RA.

  • 412.
    Ångström, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Hörnberg, Kristina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Sundström, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Wållberg Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Södergren, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Aerobic capacity is associated with disease activity and cardiovascular risk factors in early rheumatoid arthritis2020In: Physiotherapy Research International, ISSN 1358-2267, E-ISSN 1471-2865Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to investigate aerobic capacity and its associations with disease activity and risk factors for cardiovascular disease (CVD) in early rheumatoid arthritis (RA).

    Methods: This cross‐sectional study included 67 patients with early RA. Aerobic capacity was estimated with the Åstrand submaximal test adjusted according to the Nord‐Tröndelag Health Study formula. The following were also assessed: subclinical atherosclerosis by carotid intima‐media thickness and pulse wave analysis; body composition by dual X‐ray absorptiometry; estimated CVD mortality risk by the Systematic Coronary Risk Evaluation; disease activity by the Disease Activity Score 28, C‐reactive protein and erythrocyte sedimentation rate; blood lipids by total cholesterol, low‐density lipoproteins, high‐density lipoproteins, and triglycerides; and functional ability by the Stanford health assessment questionnaire. Univariate and multiple linear regression analyses were performed to explore the associations between variables.

    Results: The mean (SD) aerobic capacity was 31.6 (8.7) ml O2−1 kg min−1. Disease activity and risk factors for CVD were more favourable for patients with aerobic capacity above the median value. Aerobic capacity was associated with ESR and several CVD risk factors, independent of age and sex. In a multiple regression model that was adjusted for age and sex, aerobic capacity was significantly associated with per cent body fat (β = −0.502, 95% CI [−0.671, −0.333]) and triglycerides (β = −2.365, 95% CI [−4.252, −0.479]).

    Conclusions: Disease activity and risk factors for CVD were in favour for patients with a higher aerobic capacity. Aerobic capacity was associated with disease activity and several risk factors for CVD, independent of age and sex. In RA, these findings may provide insights into the benefits of using aerobic capacity as a marker to prevent CVD.

  • 413.
    Öhman, M.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Öhman, M-L
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    The apoB/apoA1 ratio predicts future cardiovascular events in patients with rheumatoid arthritis2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no 4, p. 259-264Article in journal (Refereed)
    Abstract [en]

    Objectives: Patients with rheumatoid arthritis (RA) have increased mortality and morbidity due to cardiovascular disease (CVD). A high apolipoprotein (apo)B/apoA1 ratio is known to predict cardiovascular events (CVEs) in the population. apoA1 has, besides anti-atherogenic effects, anti-inflammatory properties. The importance of apolipoproteins in the development of CVEs, in the context of lipids, haemostatic factors, and inflammation, was evaluated over 18 years in patients with RA. Method: Seventy-four patients with inflammatory active RA (61 females/13 males, mean age 63.6 years, disease duration 22.1 years) had been previously investigated in a study of haemostatic factors [tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI)-1, von Willebrand factor (vWF)], lipids (cholesterol and triglycerides), apolipoproteins (apoA1 and apoB), lipoprotein(a) [Lp(a)], and markers of inflammation [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and haptoglobin]. After 18 years, the first CVE during follow-up and the presence of traditional CV risk factors, extra-articular disease, and pharmacological treatment were registered. Cox proportional hazards regression was used to identify predictors of a new CVE. Results: A new CVE (n = 34) was predicted by the apoB/apoA1 ratio (p < 0.01), the triglyceride level (p < 0.01), PAI-1 (p < 0.01) and tPA (p < 0.01) activities, vWF (p < 0.001), ESR (< 0.001), CRP (< 0.05), and haptoglobin (p < 0.05). apoA1 (p = 0.056) and apoB (p < 0.05) correlated weakly and inversely with haptoglobin and CRP, respectively. In a multiple Cox regression model, adjusted for gender and previous CVD, the apoB/apoA1 ratio significantly predicted a new CVE, as did vWF, PAI-1, and ESR. Conclusions: The apoB/apoA1 ratio was a good predictor of CVE during 18 years of follow-up in patients with active RA. Apolipoproteins correlated negatively with inflammation.

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