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  • 1. Agca, R.
    et al.
    Heslinga, S. C.
    Rollefstad, S.
    Heslinga, M.
    McInnes, B.
    Peters, M. J. L.
    Kvien, T. K.
    Dougados, M.
    Radner, H.
    Atzeni, F.
    Primdahl, J.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    van Rompay, J.
    Zabalan, C.
    Pedersen, T. R.
    Jacobsson, L.
    de Vlam, K.
    Gonzalez-Gay, M. A.
    Semb, A. G.
    Kitas, G. D.
    Smulders, Y. M.
    Szekanecz, Z.
    Sattar, N.
    Symmons, D. P. M.
    Nurmohamed, M. T.
    EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, nr 1, s. 17-28Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

  • 2. Berglund, S
    et al.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine: a six-year follow-up study2009Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 27, nr 5, s. 822-825Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate whether homocysteine is linked to atherothrombotic (AT) events in patients with rheumatoid arthritis (RA). METHODS: Analysis of homocysteine (Hcy) levels was carried out in 235 consecutive RA patients. They were followed-up for 6.5 years or until death, with analysis of AT risk factors and the type and length of DMARD and corticosteroid treatment. The disease history before inclusion was collected. Six categories of AT events were defined. In addition, the diagnosis of the patients at follow-up was co-analyzed with the nationwide population-based Swedish Inpatient Register and Death Register to certify all events. RESULTS: The Hcy level was found to be higher in males (p<0.05) and increased with age (p<0.001). Patients with folic acid supplementation had significantly lower levels, while those on corticosteroids had higher levels. High Hcy levels predicted AT events (n=48) during a 6.5-year follow-up adjusted for age and male sex in a logistic regression analysis. CONCLUSION: In this study, RA patients on folic acid had lower Hcy levels. High Hcy levels (in addition to age, sex and diabetes) predicted AT event prospectively.

  • 3.
    Bjorsenius, I.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Increased progression of atherosclerosis in patients with rheumatoid arthritis is partially reflected by disease severity at the time of diagnosis: 11-year prospective follow-up2018Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, s. 20-21Artikel i tidskrift (Övrigt vetenskapligt)
  • 4.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Berglin, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Möller, Bozena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Smedby, Torgny
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Magnusson, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study2014Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 16, nr 2, s. R94-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Disease activity, severity and co-morbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in early disease.

    METHODS: In this study, 950 RA patients were followed regularly from inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender/swollen joints, visual analogue scale (VAS) pain/global, disease activity score (DAS28)) and function (health assessment questionnaire (HAQ)). Disease severity, measured by radiographs of hands/feet (erosions, Larsen score), extra-articular disease, nodules and co-morbidities and treatment (disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, biologics, nonsteroidal anti-inflammatory drugs (NSAIDs)) were recorded at inclusion and after 5 years. Autoantibodies (rheumatoid factor (RF), anti-nuclear antibodies (ANA), antibodies against cyclic citrullinated peptides (ACPA)) and genetic markers (human leukocyte antibody (HLA)-shared epitope, protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analyzed at inclusion. Data were stratified as young (YORA) and late (LORA) onset RA, defined as being below/above median age (58 years) at onset.

    RESULTS: LORA was associated with lower frequency of ACPA (P <0.05) and carriage of PTPN22-T variant (P <0.01), but with greater disease activity at inclusion measured as ESR (P < 0.001), CRP (P <0.01) and accumulated disease activity (area under the curve for DAS28) at 6 (P <0.01), 12 (P <0.01) and 24 months (P <0.05), and a higher HAQ score (P <0.01) compared with YORA. At baseline and 24 months, LORA was more often associated with erosions (P <0.01 for both) and a higher Larsen score (P <0.001 for both). LORA was more often treated with corticosteroids (P <0.01), less often with methotrexate (P <0.001) and biologics (P <0.001). YORA was more often associated with early DMARD treatment (P <0.001). Multiple regression analyses supported our findings regarding impact of age on chosen treatment.

    CONCLUSION: YORA patients were more frequently ACPA-positive. LORA was more often associated with erosions, higher Larsen scores, disease activity and HAQ at baseline. Nevertheless, YORA was treated earlier with DMARDs, whilst LORA was more often treated with corticosteroids and with less DMARDs in early disease. This could have implications for development of co-morbidities.

  • 5.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Möller, Bozena
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Magnusson, Staffan
    Smedby, Torgny
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Öhman, Marie-Louise
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Cardiovascular events in early rheumatoid arthritis (RA) are a result of inflammatory burden and traditional risk factors: a five year prospective study2011Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, nr 4, s. R131-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Co-morbidity and mortality due to cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Most published studies in this field are retrospective or cross sectional. We investigated the presence of traditional and disease related risk factors for CVD at the onset of RA and during the first 5 years following diagnosis. We also evaluated their potential for predicting a new cardiovascular event (CVE) during the 5 year follow-up period and the modulatory effect of pharmacological treatment.

    Methods All patients from the four northern-most counties of Sweden with early RA are since December 1995 consecutively recruited at diagnsosis (T0) into a large survey on the progress of the disease. Information regarding cardiovascular co-morbidity and related predictors was collected from clinical records and supplemented with questionnaires. By April 2008, 700 patients had been included of whom 442 patients had reached the 5-year follow-up (T5).

    Result Among the 442 patients who reached T5 during the follow-up period, treatment for hypertension increased from 24.5 to 37.4% ( p<0.001)), diagnosis of diabetes mellitus (DM) from 7.1 to 9.5%(p<0.01) whilst smoking decreased from 29.8 to 22.4 % ( p<0.001) and the BMI from 26.3 to 25.8( p<0.05) , respectively. By T5, 48 patients had suffered a new CVE of which 12 were fatal. A total of 23 patients died during the follow-up period. Age at disease onset, male sex, a previous CVE, DM, treatment for hypertension, triglyceride level, cumulative disease activity (AUC DAS28), extra-articular disease, corticosteroid use, shorter duration of treatment with DMARDs and use of COX-2 inhibitors increased the hazard rate for a new CVE. A raised ESR at inclusion and AUC DAS28 at 6 months increased the hazard rate of CVE independently whilst DMARD treatment was protective in multiple Cox extended models adjusted for sex and CV risk factors. The risk of a CVE due to inflammation was potentiated by traditional CV risk factors.

    Conclusion The occurrence of new CV events in very early RA was explained by traditional CV risk factors and was potentiated by high disease activity. Treatment with DMARDs decreased the risk. The results may have implications for cardio-protective strategies in RA.

  • 6.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Möller, Bozena
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Smedby, Torgny
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Magnusson, Staffan
    Berglin, Ewa H
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Age at onset determines severity and choice of treatment in early rheumatoid arthritis2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr 10, s. S908-S908Artikel i tidskrift (Refereegranskat)
  • 7.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sjöberg, C.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Berglin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Magnusson, S.
    Moller, B.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Smedby, T.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Comorbidity in early rheumatoid arthritis - which is the role of inflammation?2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, s. 406-406Artikel i tidskrift (Övrigt vetenskapligt)
  • 8.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sjöberg, C
    Möller, B
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Smedby, T
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Magnusson, S
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Comorbidity in patients with early rheumatoid arthritis: does inflammation matter?Manuskript (preprint) (Övrigt vetenskapligt)
  • 9.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sjöberg, Clara
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Berglin, Ewa H
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Möller, Bozena
    Rantapää-Dahlqvist, Solbritt M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Comorbidity in early rheumatoid arthritis: does inflammation matter?2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S176-S176, Meeting Abstract: 408Artikel i tidskrift (Refereegranskat)
  • 10.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sjöberg, Clara
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Möller, Bozena
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Smedby, Torgny
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Magnusson, Staffan
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Co-morbidity in patients with early rheumatoid arthritis - inflammation matters2016Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, artikel-id 33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Patients with rheumatoid arthritis (RA) suffer from co-morbidities that contribute to a shortened lifespan. Inflammation is important for the development of cardiovascular disease, but little is known on its relationship with other co-morbidities. We investigated the role of inflammation for the development of new comorbidities in early RA. Methods: Since 1995, all patients with early RA in Northern Sweden are included in a prospective study on comorbidities, with a total of 950 patients being included. At the time for this study, 726 had been ill for >= 5 years. Data on co-morbidities, clinical and laboratory disease activity and pharmacological therapy were collected from patient records and further validated using a questionnaire at RA onset (T0) and after 5 years (T5). Results: Of the patients, 53.2 % of the patients had one or more co-morbidity at onset, the commonest being: hypertension (27.3 %), obstructive pulmonary disease (13.9 %), diabetes (8.0 %), hypothyroidism (6.3 %) and malignancy (5.0 %). After 5 years, 41.0 % had developed at least one new co-morbidity, the most common being: hypertension (15.1 %), malignancy (7.6 %), stroke/transient ischemic accident (5.1 %), myocardial infarction (4.3 %) and osteoporosis (3.7 %). Age at disease onset, a raised erythrocyte sedimentation rate (ESR) at inclusion, previous treatment with glucocorticoids (GC; p < 0.001 for all), extra-articular RA (Ex-RA; p < 0.01), DAS28 (area under the curve) at 24 months (p < 0.05), previous smoking at inclusion (p = 0.058) and male gender (p < 0.01) were associated with a new co-morbidity overall at T5. Treatment with biologics (p < 0.05) reduced the risk. In multiple logistic regression modelling, ESR (p = 0.036) at inclusion was associated with a new co-morbidity after 5 years, adjusted for age, sex, smoking and GC treatment. In a similar model, Ex-RA (p < 0.05) was associated with a new co-morbidity at T5. In a third model, adjusted for age and sex, a new pulmonary co-morbidity was associated with a smoking history at inclusion (p < 0.01), but not with ESR. Conclusion: There was substantial co-morbidity among early RA patients already at disease onset, with considerable new co-morbidity being added during the first five years. Measures of disease activity were associated with the occurrence of a new co-morbidity indicating that the inflammation is of importance in this context.

  • 11.
    Isaksson, J.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Screening and simple counselling affect traditional cardiovascular risk factors in patients with early rheumatoid arthritis2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr Suppl. 127 Meeting Abstract PP234, s. 76-76Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) and increased mortality in CVD. The cause of this increase has not been completely established, but chronic inflammation is thought to play a role. Traditional cardiovascular risk factors also appear to be important and may be potentiated by this inflammation. The Swedish Society for Rheumatology (SRF) has developed a set of guidelines for screening and primary prevention of CVD in patients with RA. The aim of this study was to evaluate these guidelines in a clinical setting.

    Method: Forty-seven patients newly diagnosed with RA during 2012 at the Department of Rheumatology, University Hospital of Umeå were recruited. Three months after initial diagnosis of RA, patients were examined physically and blood samples were collected with regard to traditional cardiovascular risk factors according to the guidelines from the SRF. Tests of cardiorespiratory fitness were also performed. Additionally, patients received simple counselling regarding matters of diet, tobacco use and exercise from a nurse and a physiotherapist, respectively. The counselling session, based upon national guidelines from the National Food Agency and the Public Health Agency, was performed once per patient and lasted for approximately 45 minutes. A follow-up was performed 9 months after the first examination. This intervention was integrated into the clinic’s pre-existing early RA follow-up programme. The results were adjusted for disease activity and disability.

    Results: Among the 47 included patients, 45 reached the 9-month follow-up. Two were excluded because of delayed follow-up. Mean diastolic blood pressure decreased significantly from 80 to 77 mmHg (p < 0.05). Mean S-cholesterol decreased significantly from 5.5 to 5.2 mmol/L (p < 0.05). Mean ApoA1/ApoB decreased significantly from 0.73 to 0.65 (p < 0.05). In all the remaining variables (waist circumference, BMI, systolic blood pressure, LDL, HDL, triglycerides, FP-glucose), a clear decreasing trend could be observed (p > 0.05). Aerobic capacity according to Åstrand remained unchanged (p > 0.05).

    Conclusions: Several traditional risk factors for CVD were improved at the 9-month follow-up. This suggests that this model of screening according to the SRF guidelines and simple counselling according to national guidelines might be useful in primary prevention of CVD in patients with RA.

  • 12.
    Makoveichuk, Elena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ruge, Toralph
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Nilsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    High concentrations of Angiopoietin-like Protein 4 detected in serum from patients with rheumatoid arthritis can be explained by non-specific antibody reactivity2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 1, artikel-id e0168922Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Angiopoietin-like protein 4 (ANGPTL4) is suggested to be a master regulator of plasma triglyceride metabolism. Our aim was to study whether the previously reported high levels of ANGPTL4 detected in serum from patients with rheumatoid arthritis (RA) by ELISA was due to any specific molecular form of this protein (oligomers, monomers or fragments). ANGPTL4 levels were first determined in serum from 68 RA patients and 43 age and sex matched control subjects and the mean values differed by a factor of 5.0. Then, ANGPTL4 was analyzed after size exclusion chromatography (SEC) of serum samples. With serum from one of the RA patients with high levels of ANGPTL4, the dominant reactivity was found in fractions corresponding to high-molecular weight proteins. In addition, a minor peak of reactivity eluting late from the column was found both in the patient and in controls. By the use of Hetero-Block r, and by careful selection of antibodies, we documented non-specific reactions for ANGPTL4 in 39% of samples from the RA patients, most likely due to cross-reactivity of the antibodies with rheumatoid factor (RF). The corresponding figure for control subjects was 6.3%. After corrections for non-specific reactions, the mean level of ANGPTL4 in serum from RA patients was still significantly higher than in control individuals (mean levels were 101 +/- 62 and 67 +/- 39 ng/ml respectively, P = 0.02). We re-analyzed samples from our previously published studies on ANGPL4 levels in patients on hemodialysis and patients with diabetes type 2. These samples did not show false positive reactions. The levels of ANGPTL4 were comparable to those detected previously.

  • 13.
    Ruge, Toralph
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wallberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Larsson, A.
    Arnlov, J.
    Circulating plasma levels of cathepsin S and L are not associated with disease severity in patients with rheumatoid arthritis2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr 5, s. 371-373Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rheumatoid arthritis (RA) is characterized by chronic synovitis and articular cartilage destruction. Increased activities of cathepsin S and cathepsin L, two potent cysteine proteases, are thought to play a role in the pathogenesis of the irreversible articular cartilage destruction. Nevertheless, data regarding the potential importance of the cathepsins as circulating biomarkers in RA patients are limited. Method: Subjects enrolled in this study are part of a larger study where patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study. In total, 71 patients were included, along with 44 age-and sex-matched control subjects. Plasma levels of cathepsin S and L were analysed. Disease severity was assessed using the 28-joint count Disease Activity Score (DAS28). Results: Plasma levels of cathepsin S and L were significantly increased in patients with RA compared to healthy controls (p < 0.05 for both). However, in the patients with RA, no association between the cathepsins and the severity of the disease, as characterized by DAS28, was observed (p > 0.51). Conclusions: Although circulating levels of cathepsin S and L were significantly increased in patients with recently diagnosed RA, our data do not support the notion that circulating levels of cathepsins are relevant biomarkers for disease severity.

  • 14.
    Södergren, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Askling, J.
    Bengtsson, K.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jernberg, T.
    Lindström, U.
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Clinical Epidemiology Section, Department of Medicine Solna, Karolinska Institutet, Stockholm.
    Mantel, A.
    Jacobsson, L. T.
    Case fatality over 365 days after first acute coronary syndrome in patients with ankylosing spondylitis2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 341-341Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Södergren, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Bengtsson, Christine
    Moller, Bozena
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    The Extent of Subclinical Atherosclerosis Is Partially Predicted by the Inflammatory Load: A Prospective Study over 5 Years in Patients with Rheumatoid Arthritis and Matched Controls2015Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, nr 6, s. 935-942Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. This prospective followup study investigated subclinical atherosclerosis in relation to traditional cardiovascular disease (CVD) risk factors and inflammation in patients with rheumatoid arthritis (RA) recruited at diagnosis compared with controls. Methods. Patients diagnosed with early RA were consecutively recruited into a prospective study. From these, a subgroup aged <= 60 years (n = 71) was consecutively included for ultrasound measurement of intima-media thickness (IMT) and flow-mediated dilation (FMD) at inclusion (T0) and after 5 years (T5). Age-and sex-matched controls (n = 40) were also included. Results. In the Wilcoxon signed-rank test, both IMT and FMD were significantly aggravated at T5 compared to baseline in patients with RA, whereas only IMT was significantly increased in controls. In univariate linear regression analyses among patients with RA, the IMT at T5 was significantly associated with age, systolic blood pressure (BP), cholesterol, triglycerides, Systematic Coronary Risk Evaluation (SCORE), and Reynolds Risk Score at baseline (p < 0.05). Similarly, FMD at T5 was significantly inversely associated with age, smoking, systolic BP, SCORE, and Reynolds Risk Score (p < 0.05). A model with standardized predictive value from multiple linear regression models including age, smoking, BP, and blood lipids at baseline significantly predicted the observed value of IMT after 5 years. When also including the area under the curve for the 28-joint Disease Activity Score over 5 years, the observed value of IMT was predicted to a large extent. Conclusion. This prospective study identified an increased subclinical atherosclerosis in patients with RA. In the patients with RA, several traditional CVD risk factors at baseline significantly predicted the extent of subclinical atherosclerosis 5 years later. The inflammatory load over time augmented this prediction.

  • 16.
    Södergren, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Bengtsson, Christine
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Möller, Bozena
    Department of Rheumatology, Sunderby Hospital, Luleå, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Is Lipoprotein-Associated Phospholipase A2a Link between Inflammation and Subclinical Atherosclerosis inRheumatoid Arthritis?2015Ingår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikel-id 673018Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation, is associated with cardiovascular disease. This prospective study of an inception cohort aimed to investigate whether the level of Lp-PLA2 is associated with subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Methods. Patients from northern Sweden diagnosed with early RA were consecutively recruited into an ongoing prospective study. From these, all patients <= 60 years (n = 71) were included for measurements of subclinical atherosclerosis at inclusion (T0) and five years later (T5). Forty age-and sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score, and Larsen score were calculated, and blood samples were drawn from all individuals at T0 and T5. Results. There was no significant difference in the level of Lp-PLA2 between patients with RA and controls (p > 0.05). In simple linear regression models among patients with RA, Lp-PLA2 at T0 was significantly associated with intima media thickness (IMT) at T0 and T5, flow mediated dilation (FMD) at T0 and T5, ever smoking, male sex, HDL-cholesterol (inversely), non-HDL-cholesterol, SCORE, Reynolds Risk Score, and Larsen score (p < 0.05). Conclusion. In this cohort of patients with early RA, the concentration of Lp-PLA2 was associated with both subclinical atherosclerosis and disease severity.

  • 17.
    Södergren, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Boman, Kurt
    Department of Medicine, Skellefteå Hospital, Lasarettsvägen, Skellefteå.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Lundström, Elisabet
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Smedby, Torgny
    Department of Rheumatology, Östersund Hospital, Kyrkgatan, 831 83 Östersund, Sweden.
    Söderlund, Lisbet
    Department of Rheumatology, Sunderby Hospital, 971 80 Luleå, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness2010Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 12, nr 4, s. R158-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION : In this study we aimed to investigate whether there are indications of premature atherosclerosis, as measured by endothelial dependent flow-mediated dilation (ED-FMD) and intima media thickness (IMT), in patients with very early RA, and to analyze its relation to biomarkers of endothelial dysfunction, taking inflammation and traditional cardiovascular disease (CVD) risk factors into account.

    METHODS : Patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study of CVD co-morbidity. Of these, all patients aged ≤60 years were consecutively included in this survey of CVD risk factors (n = 79). Forty-four age and sex matched controls were included. IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography. Blood was drawn for analysis of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA)-mass, VonWillebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), sE-selectin, sL-selectin and monocyte chemotactic protein-1 (MCP-1). In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months.

    RESULTS : There were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation. However after 18 months there was a significant increase in the IMT among the patients with RA (P < 0.05). Patients with RA had higher levels of VWF, sICAM-1 (P < 0.05) and of MCP-1 (P = 0.001) compared with controls. In RA, IMT was related to some of the traditional CVD risk factors, tPA-mass, VWF (P < 0.01) and MCP-1 and inversely to sL-selectin (P < 0.05). In RA, ED-FMD related to sL-selectin (P < 0.01). DAS28 at baseline was related to PAI-1, tPA-mass and inversely to sVCAM-1 (P < 0.05) and sL-selectin (P = 0.001).

    CONCLUSIONS : We found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls. However, in patients with early RA, IMT and ED-FMD were, to a greater extent than in controls, related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis. After 18 months, IMT had increased significantly in RA patients but not in controls.

  • 18.
    Södergren, Anna
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Reumatologi.
    Stegmayr, Birgitta
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Lundberg, Vivan
    Department of Medicine, Kalix Hospital, Kalix, Sweden .
    Öhman, Marie-Louise
    Umeå universitet, Samhällsvetenskaplig fakultet, Statistik.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Reumatologi.
    Increased incidence of and impaired prognosis after acute myocardial infarction among patients with seropositive rheumatoid arthritis.2007Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, ISSN Online ISSN 1468-2060, Vol. 66, nr 2, s. 263-266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To examine the incidence and outcome of acute myocardial infarction (AMI) in patients with rheumatoid arthritis compared with the general population, and to examine whether care and treatment of an AMI differs between patients and controls.

    Methods: The Multinational Monitoring of Trends and Determinants of Cardiovascular Disease register for northern Sweden was used to compare those incidences of AMI in a cohort of patients with rheumatoid arthritis with that in the general population. 35 patients with rheumatoid arthritis who had also experienced an AMI were identified. For each patient with rheumatoid arthritis, three controls with a history of AMI but without rheumatoid arthritis were randomly selected from the same register, and matched for age, sex and year of the AMI for evaluation of case fatality and potential differences in treatment of AMI.

    Results: The standardised incidence ratio for AMI was 2.9 in patients with rheumatoid arthritis compared with the general population (p<0.05). During the first 10 years after an AMI, patients with rheumatoid arthritis had a higher overall case fatality compared with controls (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.02 to 2.71). Survival time was decreased in the rheumatoid arthritis group compared with controls despite the same care and treatment.

    Conclusion: Both the incidence of and case fatality after an AMI were higher among patients with rheumatoid arthritis than among the general population. The results emphasise the necessity of optimising the preventive, diagnostic and caring strategies for AMI in rheumatoid arthritis.

  • 19.
    Södergren, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Öhman, Marie-Louise
    Umeå universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Increased incidence of stroke and impaired prognosis after stroke among patients with seropositive rheumatoid arthritis2009Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 27, nr 4, s. 641-644Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine the incidence of, and outcome after, a stroke in patients with rheumatoid arthritis (RA) compared with the general population. METHODS: The northern Sweden MONICA register was used to compare the incidence of stroke in a cohort of RA patients with the general population. Forty RA patients who had also suffered a stroke were identified. For each patient with RA, three controls with a history of stroke but without RA were randomly collected from the same register, and matched for age and sex. RESULTS: The standardised incidence ratio (SIR) for stroke was 2.7 in RA patients compared with the general population (p<0.05). During the follow-up, RA patients had a higher overall case fatality (CF) following stroke compared with controls (hazard ratio (HR) =1.70, p<0.05). CONCLUSIONS: Both the incidence of a stroke, and the subsequent CF, were higher among RA patients compared with the general population. The results emphasize the necessity of optimising the prevention of stroke and follow-up care after a stroke in RA.

  • 20.
    Wahlin, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Fasth, A. E.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Cd8+cd28- t-lymphocytes are associated with subclinical atherosclerosis in patients with rheumatoid arthritis2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 250-250Artikel i tidskrift (Övrigt vetenskapligt)
  • 21.
    Wahlin, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Fasth, Andreas
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Malmström, Vivianne
    Rahbar, Afsar
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Atherosclerosis in rheumatoid arthritis: associations between anti-cytomegalovirus IgG antibodies, CD4+CD28null T-cells, CD8+CD28null T-cells and intima-media thicknessManuskript (preprint) (Övrigt vetenskapligt)
  • 22.
    Wahlin, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ramnemark, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Osteoprotegerin and osteocalcin are associated with atherosclerosis in patients with rheumatoid arthritis: a prospective cohort studyManuskript (preprint) (Övrigt vetenskapligt)
  • 23.
    Wållberg-Jonsson, Solveig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Boman, Kurt
    Eriksson, Catharina
    Lundstrom, Elisabet
    Smedby, Torgny
    Moller, Bozena
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Progression of subclinical atherosclerosis over 5 years in patients with early rheumatoid arthritis2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, s. A92-A92Artikel i tidskrift (Övrigt vetenskapligt)
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