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| 6. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 8. |
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| 9. |
- Crowson, Cynthia S., et al.
(författare)
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Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 77:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. Methods: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. Results: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). Conclusions: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.
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| 10. |
- Ehlers, L, et al.
(författare)
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2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:9, s. 1160-1166
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Tidskriftsartikel (refereegranskat)abstract
- Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care.
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| 13. |
- Turesson, Carl, et al.
(författare)
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Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis
- 2007
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 66:1, s. 70-75
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rheumatoid arthritis is associated with increased cardiovascular mortality and morbidity. Objective: To assess the effect of severe extra-articular rheumatoid arthritis (ExRA) manifestations on the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis. Methods: Patients with ExRA (n = 81) according to predefined criteria and controls (n = 184) without evidence of extra-articular disease were identified from a large research database of patients with rheumatoid arthritis. In a structured review of the medical records, the occurrence and the date of onset of clinically diagnosed CVD events were noted. Cox proportional hazards models were used to estimate the effect of ExRA on the risk of first ever CVD events after the diagnosis of rheumatoid arthritis. ExRA manifestations were modelled as time-dependent covariates, with adjustment for age, sex and smoking at the diagnosis of rheumatoid arthritis. Onset of erosive disease and rheumatoid factor seropositivity were entered as time-dependent variables. Patients were followed until onset of CVD, death or loss to follow-up. Results: ExRA was associated with a significantly increased risk of first ever CVD events (p < 0.001), and also with an increased risk of new-onset coronary artery disease, adjusted for age, sex and smoking (hazard ratio (HR): 3.16; 95% confidence interval (95% CI: 1.58 to 6.33). The association between ExRA and any first ever CVD event remained significant when controlling for age, sex, smoking, rheumatoid factor and erosive disease (HR: 3.25; 95% CI: 1.59 to 6.64). Conclusion: Severe ExRA manifestations are associated with an increased risk of CVD events in patients with rheumatoid arthritis. This association is not due to differences in age, sex, smoking, rheumatoid factor or erosive joint damage. It is suggested that systemic extra-articular disease is a major determinant of cardiovascular morbidity in rheumatoid arthritis.
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| 14. |
- Weiss, A, et al.
(författare)
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Personality Polygenes, Positive Affect, and Life Satisfaction
- 2016
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 19:5, s. 407-417
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Tidskriftsartikel (refereegranskat)abstract
- Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximalN= 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
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| 15. |
- Elfishawi, Mohanad, et al.
(författare)
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Lower Frequency of Comorbidities Prior to Onset of Giant Cell Arteritis : A Population-Based Study
- 2023
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 50:4, s. 526-531
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the frequency of comorbidities and metabolic risk factors at and prior to giant cell arteritis (GCA) diagnosis. METHODS: This is a retrospective case control study of patients with incident GCA between January 1, 2000, and December 31, 2019, in Olmsted County, Minnesota. Two age- and sex-matched controls were identified, and each assigned an index date corresponding to an incidence date of GCA. Medical records were manually abstracted for comorbidities and laboratory data at incidence date, 5 years, and 10 years prior to incidence date. Twenty-five chronic conditions using International Classification of Diseases, 9th revision, diagnosis codes were also studied at incidence date and 5 years prior to incidence date. RESULTS: One hundred and twenty-nine patients with GCA (74% female) and 253 controls were identified. At incidence date, the prevalence of diabetes mellitus (DM) was lower among patients with GCA (5% vs 17%; P = 0.001). At 5 years prior to incidence date, patients were less likely to have DM (2% vs 13%; P < 0.001) and hypertension (27% vs 45%; P = 0.002) and had a lower mean number (SD) of comorbidities (0.7 [1.0] vs 1.3 [1.4]; P < 0.001) compared to controls. Moreover, patients had significantly lower median fasting blood glucose (FBG; 96 mg/dL vs 104 mg/dL; P < 0.001) and BMI (25.8 vs 27.7; P = 0.02) compared to controls. Multivariable logistic regression analysis revealed negative associations for FBG with GCA at 5 and 10 years prior to diagnosis/index date. CONCLUSION: DM prevalence and median FBG and BMI were lower in patients with GCA up to 5 years prior to diagnosis, suggesting that metabolic factors influence the risk of GCA.
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| 17. |
- Jakobsson, Karin, et al.
(författare)
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Body mass index and the risk of giant cell arteritis-results from a prospective study
- 2015
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 54:3, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to examine potential risk factors for GCA in a nested case-control study based on two prospective health surveys. Methods. We used two population-based health surveys, the Malmo Preventive Medicine Program (MPMP) and the Malmo Diet Cancer Study (MDCS). Individuals who developed GCA after inclusion were identified by linking the MPMP and MDCS databases to several patient administrative registers. A structured review of the medical records of all identified cases was performed. Four controls for every confirmed case, matched for sex, year of birth and year of screening, were selected from the corresponding databases. Potential predictors of GCA were examined in conditional logistic regression models. Results. Eighty-three patients (70% women, 64% biopsy positive, mean age at diagnosis 71 years) had a confirmed diagnosis of GCA after inclusion in the MPMP or MDCS. A higher BMI was associated with a significantly reduced risk of subsequent development of GCA [odds ratio (OR) 0.91/kg/m(2) (95% CI 0.84, 0.98)]. Smoking was not a risk factor for GCA overall [OR 1.36 (95% CI 0.77, 2.57)], although there was a trend towards an increased risk in female smokers [OR 2.14 (95% CI 0.97, 4.68)]. In multivariate analysis, adjusted for smoking and level of formal education, the inverse association between BMI and GCA remained significant (P = 0.027). Conclusion. In this study, GCA was predicted by a lower BMI at baseline. Potential explanations include an effect of reduced adipose tissue on hormonal pathways regulating inflammation.
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| 18. |
- Jakobsson, Karin, et al.
(författare)
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The effect of clinical features and glucocorticoids on biopsy findings in giant cell arteritis
- 2016
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Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: To investigate the effect of baseline clinical characteristics and glucocorticoid treatment on temporal artery biopsy (TAB) findings in patients with giant cell arteritis (GCA). Methods: Individuals who developed GCA after inclusion in two population-based health surveys were identified through linkage to the local and the national patient registers. In addition, other patients diagnosed with GCA at the Departments of Internal Medicine and Rheumatology at an area hospital were included. A structured review of medical records and TAB pathology reports was performed. The presence or absence of giant cells, granuloma, fragmented internal elastic lamina, fibrosis and grade of inflammatory infiltrates were recorded. Results: In 183 cases with a confirmed clinical diagnosis of GCA, 139 were biopsied after start of glucocorticoids (median treatment duration 3 days; interquartile range 2-5). Patients with a positive TAB (77 %) had significantly higher C-reactive protein (CRP; p = 0.007) and erythrocyte sedimentation rate (ESR; p = 0.03) at the time of clinical diagnosis. A positive TAB tended to more common in women, but there was no difference in the proportion of patients with polymyalgia rheumatica or visual symptoms. Patients biopsied before or on the same day as initial treatment where more likely than those biopsied 1-3 days after treatment start to have positive biopsy [odds ratio (OR) 2.86; 95 % CI 1.06-7.70] as well as inflammatory infiltrates (OR 3.30; 95 % CI 1.15-9.49). There was no significant difference in the proportions of a fragmented internal lamina (p = 0.86), giant cells (p = 0. 10), granuloma (p = 0.19), minor inflammatory infiltrates (p = 0.47), major inflammatory infiltrates (p = 0.09), or overall positive biopsy (p = 0.17) report by treatment duration comparing: <= 0 days, 1-3 days, 4-6 days, 7-28 days. Among those biopsied 7-28 days after start of treatment, 80 % of TABs were positive, and histopathology features were not substantially different from those biopsied after shorter glucocorticoid treatment. Conclusion: Biopsies were more likely to be positive and have characteristic histopathologic features in patients with high CRP and ESR, and prior to start of corticosteroid treatment TABs taken 1-4 weeks after initiation of glucocorticoid treatment reveal changes consistent with GCA and therefore still yields clinically useful information for the diagnosis.
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| 19. |
- Myasoedova, Elena, et al.
(författare)
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Incidence of Extraarticular Rheumatoid Arthritis in Olmsted County, Minnesota, in 1995-2007 Versus 1985-1994: A Population-based Study.
- 2011
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 38, s. 983-989
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess incidence and mortality effects of extraarticular rheumatoid arthritis (ExRA) in patients with incident RA in 1995-2007 compared to 1985-1994, in Olmsted County, Minnesota, USA. METHODS: Data on incident ExRA were abstracted from medical records of patients with RA - Olmsted County residents who first met the 1987 American College of Rheumatology criteria for RA between January 1, 1995, and December 31, 2007. Patients were followed until death, migration from Olmsted County, or December 31, 2008. ExRA were classified using the predefined criteria and compared to the corresponding 1985-1994 inception RA cohort (n = 147). RESULTS: The 1995-2007 cohort included 463 patients with RA followed for a mean of 6.3 years; mean age was 55.6 years, 69% were women, 67% were positive for rheumatoid factor (RF). The 10-year cumulative incidence of any ExRA (50.1%) and severe ExRA (6.7%) in the 1995-2007 cohort was similar to the 1985-1994 cohort (46.2% and 9.7%, respectively). The 10-year cumulative incidence of vasculitis, but not other features of ExRA, was significantly lower in the 1995-2007 cohort (0.6%) compared to the 1985-1994 cohort (3.6%). RF positivity, erosions/destructive changes, and use of methotrexate, other disease-modifying antirheumatic drugs and systemic corticosteroids were significantly associated with ExRA in the 1995-2007 cohort. ExRA was associated with mortality risk (HR 2.1, 95% CI 1.2, 3.7) in the 1995-2007 cohort. The decrease in mortality following ExRA in the 1995-2007 cohort versus the 1985-1994 cohort did not reach statistical significance (HR 0.6, 95% CI 0.3, 1.2, p = 0.16). CONCLUSION: ExRA remains a common complication associated with increased mortality in RA. The occurrence of vasculitis appears to be decreasing in recent years.
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| 20. |
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| 21. |
- Sekijima, Y., et al.
(författare)
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The biological and chemical basis for tissue-selective amyloid disease
- 2005
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 121:1, s. 73-85
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Tidskriftsartikel (refereegranskat)abstract
- Factors controlling the onset and progression of extracellular amyloid diseases remain largely unknown. Central to disease etiology is the efficiency of the endoplasmic reticulum (ER) machinery that targets destabilized mutant proteins for degradation and the enhanced tendency of these variants to aggregate if secreted. We demonstrate that mammalian cells secrete numerous transthyretin (TTR) disease-associated variants with wild-type efficiency in spite of compromised folding energetics. Only the most highly destabilized TTR variants are subjected to ER-associated degradation (ERAD) and then only in certain tissues, providing insight into tissue selective amyloidosis. Rather than a "quality control" standard based on wild-type stability, we find that ER-assisted folding (ERAF), based on global protein energetics, determines the extent of export. We propose that ERAF (influenced by the energetics of the protein fold, chaperone enzyme distributions, and metabolite chaperones) in competition with ERAD defines the unique secretory aptitude of each tissue. Copyright ©2005 by Elsevier Inc.
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| 22. |
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| 23. |
- Turesson, Carl, et al.
(författare)
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Cardiovascular co-morbidity in rheumatic diseases.
- 2008
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Ingår i: Vascular Health and Risk Management. - 1178-2048. ; 4:3, s. 605-614
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Forskningsöversikt (refereegranskat)abstract
- Patients with rheumatic disorders have an increased risk of cardiovascular disease (CVD). This excess co-morbidity is not fully explained by traditional risk factors. Disease severity is a major risk factor for CVD in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease mechanisms in atherosclerosis and rheumatic disorders include immune dysregulation and inflammatory pathways, which are potential targets for therapy. Lessons from RA and SLE may have implications for future research on the pathogenesis of atherosclerotic vascular disease in general. Recent data indicate that suppression of inflammation reduces the risk of CVD morbidity and mortality in patients with severe RA. The modest, but clinically relevant, efficacy of atorvastatin treatment in RA adds to the evidence for important anti-inflammatory properties for statins. There is increased recognition of the need for structured preventive strategies to reduce the risk of CVD in patients with rheumatic disease. Such strategies should be based on insights into the role of inflammation in CVD, as well as optimal management of life style related risk factors. In this review, the research agenda for understanding and preventing CVD co-morbidity in patients with rheumatic disorders is discussed.
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| 24. |
- Turesson, Carl, et al.
(författare)
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Cardiovascular risk factors, fitness and physical activity in rheumatic diseases.
- 2007
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Ingår i: Current Opinion in Rheumatology. - 1531-6963. ; 19:2, s. 190-196
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review There is increased recognition of an excess risk of cardiovascular disease in patients with rheumatic disorders. Physical inactivity is a frequent complication of arthritis, and also common in the general population. In this review, we highlight recent findings on risk factors for cardiovascular disease in patients with rheumatic diseases, and explore the role of physical activity for the prevention of cardiovascular disease. Recent findings Inflammatory mechanisms are clearly involved in cardiovascular disease in patients with systemic lupus erythematosus and rheumatoid arthritis. In rheumatoid arthritis, disability is also a major predictor of cardiovascular disease. A sedentary lifestyle increases the risk of cardiovascular disease in the general population, and high physical activity prevents cardiovascular disease mortality and morbidity. Successful treatment of rheumatic disease with control of inflammation and improved functional capacity may also reduce the risk of cardiovascular disease. Summary As part of the effort to prevent vascular comorbidity, regular exercise should be encouraged in patients with rheumatic diseases, and structured interventions to reduce adverse lifestyle factors scientifically evaluated.
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| 26. |
- Turesson, Carl, et al.
(författare)
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Malignancy as a comorbidity in rheumatic diseases.
- 2013
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 52:1, s. 5-14
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Tidskriftsartikel (refereegranskat)abstract
- Patients with systemic autoimmune rheumatic diseases, particularly RA, SLE, SS and idiopathic inflammatory myopathies, are at increased risk of developing malignancies. Cancer occurrence adds to the disease burden in these patients, adversely affecting quality of life and life expectancy. This risk is related to the pathobiology of the underlying rheumatic disease including the inflammatory burden, immunological defects, and personal and environmental exposure such as smoking and some viral infections. Immunomodulatory therapies, especially chemotherapeutic agents, are also associated with an increased risk of cancer in these conditions. The decision to use immunomodulating therapies in patients with rheumatic disease must take into account the disease severity, expectations for disease control, comorbidities and host and environmental risk factors for cancer. Effective screening and monitoring strategies are important in reducing the risk of cancer in these patients.
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| 27. |
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| 28. |
- Turesson, Carl, et al.
(författare)
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Vasculitis in rheumatoid arthritis.
- 2009
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Ingår i: Current Opinion in Rheumatology. - 1531-6963. ; 21:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: To examine the occurrence and pathophysiology of vasculitis in rheumatoid arthritis (RA), describe the epidemiology and clinical features, and provide a therapeutic perspective. RECENT FINDINGS: With improved control of RA over the past two decades, the risk of severe outcomes such as vasculitis may be decreasing. Rheumatoid vasculitis continues to be associated with longstanding, erosive, seropositive disease, and it has recently been shown to be more frequent among patients with antibodies to cyclic citrullinated peptides. Apart from circulating immune complexes, expansion of cytotoxic CD28null T cells and circulating proinflammatory cytokines also play a role in the pathogenesis. The role of agents directed against the tumor necrosis factor (TNF) in the occurrence and management of rheumatoid vasculitis remains unclear, as rheumatoid vasculitis may be both associated with and treated with anti-TNF agents, once it has appeared. SUMMARY: Vasculitis in RA is generally associated with longstanding disease, has an important impact on a patient's well being, and markedly influences patient life expectancy. Advances in therapies for RA will likely continue to reduce the incidence of vasculitis, and improved management of cardiovascular comorbidity in patients with RA will be of particular benefit to those who suffer from vasculitis and other extraarticular manifestations.
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| 29. |
- Wadstrom, Karin, et al.
(författare)
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Associations between plasma metabolism-associated proteins and future development of giant cell arteritis: results from a prospective study
- 2024
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Ingår i: RHEUMATOLOGY. - : Oxford University Press. - 1462-0324 .- 1462-0332.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate the relationship between biomarkers associated with metabolism and subsequent development of GCA. Method Participants in the population-based Malmo Diet Cancer Study (MDCS; N = 30 447) who were subsequently diagnosed with GCA were identified in a structured process. Matched: GCA-free controls were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics metabolism panel (92 metabolic proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explained the variance in the proteome. Results: There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated [odds ratio (OR) per S.D. 1.67; 95% CI 1.08-2.57], and fructose-1,6-bisphosphatase 1 (FBP1) was negatively associated (OR per S.D. 0.59; 95% CI 0.35-0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled <8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those patients sampled closest to diagnosis, with a decreasing trend with longer time to GCA (P = 0.03). In the hypothesis-generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. Conclusion: Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.
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| 30. |
- Wadström, Karin, et al.
(författare)
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Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis: a prospective study
- 2023
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 62:6, s. 2304-2311
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the relation between biomarkers of inflammation and subsequent development of GCA. Method: Participants in the population-based Malmo Diet Cancer Study (MDCS; N=30 447), established 1991-96, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth and year of screening were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on eigenvalues, proteins with a factor loading of >0.50 were investigated. Results: Ninety-four cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-gamma was positively associated with GCA [odds ratio (OR) per S.D. 1.52; 95% CI 1.00, 2.30]. Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-gamma (OR 2.37; 95% CI 1.14, 4.92) and monocyte chemotactic protein 3 (MCP3) (OR 4.27; 95% CI 1.26, 14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25. Conclusion: Elevated IFN-gamma levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.
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| 31. |
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| 32. |
- Wadström, Karin, et al.
(författare)
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Apolipoproteins and the risk of giant cell arteritis-a nested case-control study
- 2024
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Ingår i: ARTHRITIS RESEARCH & THERAPY. - 1478-6354 .- 1478-6362. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe etiology of giant cell arteritis (GCA) and its predictors are incompletely understood. Previous studies have indicated reduced risk of future development of GCA in individuals with obesity and/or diabetes mellitus. There is limited information on blood lipids before the onset of GCA. The objective of the study was to investigate the relation between apolipoprotein levels and future diagnosis of GCA in a nested case-control analysis.MethodsIndividuals who developed GCA after inclusion in a population-based health survey (the Malmo Diet Cancer Study; N = 30,447) were identified by linking the health survey database to the local patient administrative register and the national patient register. A structured review of medical records was performed. Four controls for every validated case, matched for sex, year of birth, and year of screening, were selected from the database. Anthropometric measures, self-reported physical activity, based on a comprehensive, validated questionnaire, and non-fasting blood samples had been obtained at health survey screening. Concentrations of apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) in stored serum were measured using an immunonephelometric assay. Potential predictors of GCA were examined in conditional logistic regression models.ResultsThere were 100 cases with a confirmed clinical diagnosis of GCA (81% female; mean age at diagnosis 73.6 years). The median time from screening to diagnosis was 12 years (range 0.3-19.1). The cases had significantly higher ApoA-I at baseline screening compared to controls (mean 168.7 vs 160.9 mg/dL, odds ratio [OR] 1.57 per standard deviation (SD); 95% confidence interval [CI] 1.18-2.10) (SD 25.5 mg/dL). ApoB levels were similar between cases and controls (mean 109.3 vs 110.4 mg/dL, OR 0.99 per SD; 95% CI 0.74-1.32) (SD 27.1 mg/dL). The ApoB/ApoA1 ratio tended to be lower in cases than in controls, but the difference did not reach significance. The association between ApoA-I and GCA development remained significant in analysis adjusted for body mass index and physical activity (OR 1.48 per SD; 95% CI 1.09-1.99).ConclusionSubsequent development of GCA was associated with significantly higher levels of ApoA-I. These findings suggest that a metabolic profile associated with lower risk of cardiovascular disease may predispose to GCA.
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| 33. |
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| 34. |
- Wadström, Karin, et al.
(författare)
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Negative associations for fasting blood glucose, cholesterol and triglyceride levels with the development of giant cell arteritis
- 2020
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332 .- 1310-0505. ; 59:11, s. 3229-3236
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To investigate metabolic features that may predispose to GCA in a nested case-control study. Methods. Individuals who developed GCA after inclusion in a population-based health survey (the Malmo Preventive Medicine Project; N = 33 346) were identified and validated through a structured review of medical records. Four controls for every validated case were selected from the database. Results. A total of 76 cases with a confirmed incident diagnosis of GCA (61 % female, 65% biopsy positive, mean age at diagnosis 70 years) were identified. The median time from screening to diagnosis was 20.7 years (range 3.0-32.1). Cases had significantly lower fasting blood glucose (FBG) at baseline screening compared with controls [mean 4.7 vs 5.1 mmol/l (s.D. overall 1.5), odds ratio (OR) 0.35 per mmol/l (95% CI 0.17, 0.71)] and the association remained significant when adjusted for smoking [OR 0.33 per mmol/l (95% CI 0.16, 0.68)]. Current smokers had a reduced risk of GCA [OR 0.35 (95% CI 0.18, 0.70)]. Both cholesterol [mean 5.6 vs 6.0 mmol/l (s.D. overall 1.0)] and triglyceride levels [median 1.0 vs 1.2 mmol/l (s.D. overall 0.8)] were lower among the cases at baseline screening, with significant negative associations with subsequent GCA in crude and smoking-adjusted models [OR 0.62 per mmol/l (95% CI 0.43, 0.90) for cholesterol; 0.46 per mmol/l (95% CI 0.27, 0.81) for triglycerides]. Conclusion. Development of GCA was associated with lower FBG and lower cholesterol and triglyceride levels at baseline, all adjusted for current smoking, suggesting that metabolic features predispose to GCA.
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