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ID PMID Title PublicationDate abstract
21515993 Regulation of B cell activating factor (BAFF) receptor expression by NF-ΚB signaling in r 2011 Jun 30 B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-ΚB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-ΚB p65, NF-ΚB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was analyzed by flow cytometry, realtime PCR and confocal staining after treatment with NF-ΚB inhibitors. NF-ΚB p65, NF-ΚB p50, BAFF, and BAFF-R were highly expressed in severe RA synovium relative to mild RA synovium or OA synovium. BAFF-R expression was reduced by NF-ΚB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-ΚB pathway in PBMCs of RA patients. BAFF/BAFF-R signaling is an important mechanism of pathogenesis in RA and that BAFF-R reduction by NF-ΚB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA.
21255563 Diagnostic utility of an anti-CCP point-of-care immunotest in Chinese patients with rheuma 2011 Apr 11 BACKGROUND: Early and accurate diagnosis of rheumatoid arthritis (RA) has become increasingly important. The clinical significance of anti-cyclic citrullinated peptide (CCP) antibody in Chinese RA adults was studied using an anti-CCP2 rapid test. METHODS: Anti-CCP antibody and rheumatoid factor (RF) were determined in 95 RA patients and 140 patients with rheumatic diseases other than RA. RESULTS: Two hundred and thirty five subjects were enrolled in this study. Both sensitivity and specificity of anti-CCP2 ELISA (78.9% & 95.7%) were higher than those of RF (67.4% & 84.3%). The area under the receiver operating characteristic curve for anti-CCP2 ELISA was 0.852 (95% CI: 0.792-0.913) which was larger than that for RF 0.775 (95% CI: 0.710-0.840). Both sensitivity and specificity (75.8% and 92.9%) of the anti-CCP2 rapid test were comparable to the ELISA. However, the sensitivity (62.1%) of a combined strategy by measuring anti-CCP antibody and RF was even lower than either marker alone although the specificity (98.6%) was slightly improved. CONCLUSIONS: Anti-CCP antibody is a valuable tool for diagnosis of RA in Chinese patients. With the use of the reliable and user-friendly anti-CCP rapid test, it may have an important role in the design of therapeutic strategies in RA patients.
20952476 Prognostic factors of radiological damage in rheumatoid arthritis: a 10-year retrospective 2011 Jan OBJECTIVE: to describe the longterm clinical and radiological outcomes in rheumatoid arthritis (RA) in a cohort in northwestern Greece; and to investigate predictive factors of radiological damage at the 10-year followup in patients with RA. METHODS: we studied the disease course and outcome of 144 patients with RA and radiographs of the hands and wrists available at baseline and at 10 years. Baseline measurements and time-averaged measures of swollen joint count (SJC) and inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were tested in univariate analysis, and then those presenting a statistically significant association with either Larsen score at 10 years or annual progression rate were included in 2 logistic regression models in order to determine relevant independent prognostic factors. RESULTS: a significant clinical improvement was noted, associated with a decrease of inflammatory markers along the timepoints. Larsen score and the number of erosive joints were increased. In the univariate analysis, both final Larsen score at 10 years and accelerated annual radiological progression rate were significantly associated with baseline radiographic measurements (Larsen score and number of erosive joints), the presence of autoantibodies [anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor of IgA and IgM isotype], disease duration, and time-averaged measures of ESR, CRP, and SJC. In the logistic regression analysis, the baseline Larsen score, anti-CCP antibodies, and time-averaged CRP presented significant and independent associations with Larsen score at 10 years. An accelerated annual radiological progression rate was also predicted by baseline Larsen score and time-averaged measures of SJC and CRP. CONCLUSION: despite clinical improvement, the radiologic progression of RA continues over time, because of the underlying inflammatory process. Baseline radiographic damage, anti-CCP antibodies, and time-averaged CRP constitute the main predictive factors of poor radiologic outcome in the long term.
23245655 The usefulness of computer-aided joint space analysis in the assessment of rheumatoid arth 2013 Jul OBJECTIVE: Computer-aided joint space analysis (CAJSA) is a newly developed technique for the measurement of radiogeometrically detectable joint space widths of the metacarpal-phalangeal (JSD-MCP) and proximal-interphalangeal articulations (JSD-PIP). The aim of this study was to verify the sensitivity and specificity of these CAJSA measurements in the assessment of established RA. METHODS: Four hundred and fifty-eight participants (248 healthy subjects, 210 RA patients) underwent computerized semi-automated measurements of the JSD-MCP and JSD-PIP articulations (CAJSA, Radiogrammetry Kit, Version 1.3.6) based on digitally performed radiographs. The Sharp joint space narrowing score was also performed to determine RA-related joint space narrowing. RESULTS: The significant severity-dependent reduction for JSD-MCP was -44.0% and for JSD-PIP, -25.94% between Sharp scores 0 and 3. The sensitivity and specificity of JSD-MCP (total) was 88.1% versus 77.8%, respectively (AUC = 0.920; P < 0.001). Furthermore, JSD-PIP (total) revealed a lower sensitivity and specificity with 61.4% and 88.7% (AUC = 0.878; P < 0.001). CONCLUSION: The CAJSA method presented a reliable assessment of disease-related joint space narrowing in patients suffering from RA with excellent sensitivity and specificity. By providing quantitative data, other scoring methods could be significantly improved, and thereby the accuracy of the diagnosis and a better therapeutic evaluation could be achieved.
21519352 Interleukin-33 biology with potential insights into human diseases. 2011 Jun Interleukin (IL)-33 is a member of the IL-1 family of cytokines. IL-33 is a nuclear protein that is also released into the extracellular space, and thus acts as a dual-function molecule, as does IL-1α. Extracellular IL-33 binds to the cell-surface receptor ST2, leading to the activation of intracellular signaling pathways similar to those used by IL-1. Unlike conventional cytokines, IL-33 might be secreted via unconventional pathways, and can be released upon cell injury as an alarmin. IL-33 is expressed in cells that are in contact with the environment, and acts as an early inducer of inflammation. Its production is then upregulated in inflamed tissues, thus contributing to the further amplification of inflammatory responses. Studies of IL-33-deficient mice will provide more information on intracellular functions of this cytokine. A large body of evidence supports the pathogenic role of IL-33 in asthma and possibly other inflammatory airway conditions. Furthermore, IL-33 has been shown to be involved in experimental models of arthritis and potentially has a pathogenic role in ulcerative colitis and fibrotic conditions, suggesting that IL-33 antagonists might be of interest for the treatment of asthma, rheumatoid arthritis and ulcerative colitis. However, IL-33 also appears to exert important functions in host defense against pathogens and to display cardioprotective properties, which might have implications for the clinical use of IL-33 blockade.
22971036 Economic outcomes for celecoxib: a systematic review of pharmacoeconomic studies. 2012 Aug Osteoarthritis and rheumatoid arthritis are conditions that are associated with significant clinical burden, and impact on patients' functional status and quality of life. Medical costs related to treating these common and disabling conditions place an economic strain on healthcare systems. This systematic review was conducted to investigate the impact of celecoxib on healthcare costs for patients with rheumatoid arthritis and osteoarthritis. In total, 24 studies examined economic outcomes associated with celecoxib in patients with these conditions. Six of these studies evaluated economic outcomes in developing regions, including Mexico, Asia and Turkey. Across all geographies, most studies were cost-effectiveness analyses comparing celecoxib with nonselective NSAIDs alone or in combination with gastroprotective agents. Overall, based on local standards, economic models indicated favorable cost-effectiveness profiles for celecoxib compared with nonselective NSAIDs and other active-treatment options. Cost analyses indicated that the use of celecoxib resulted in lower direct medical costs.
21691744 Methotrexate attenuates the Th17/IL-17 levels in peripheral blood mononuclear cells from h 2012 Aug To investigate whether the inhibition of Th17/interleukin (IL)-17 contributes to the beneficial effects of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected. The cells were stimulated with monoclonal antibodies to CD3 and CD28 in the absence or presence of MTX. After coincubation, IL-17 production was detected at both the mRNA and protein levels, and the percentage of cells positive for both CD4 and IL-17 in PBMCs was analyzed by flow cytometry. PBMCs of healthy donors and RA patients were stimulated with CD3 and CD28 monoclonal antibodies to produce high levels of IL-17. The augmentation of IL-17 at the mRNA and protein levels was significantly inhibited when PBMC cultures were preincubated with MTX. Compared with PBMCs of healthy donors, PBMCs of RA patients produced higher levels of IL-17, and this increase in IL-17 levels was more inhibited by MTX pretreatment. MTX inhibited IL-17 at the mRNA level in a dose-dependent manner, but not at the protein level, in both PBMCs of healthy donors and RA patients. MTX did not affect the percentage of CD4- and IL-17-positive cells in PBMCs. MTX dose dependently suppressed the production of IL-17 at the mRNA level by PBMCs from healthy donors and RA patients. Suppression of IL-17 by MTX may contribute to its potent anti-inflammatory role in RA therapy.
21549221 Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationshi 2011 Aug The complement system is an essential component of innate immunity and also plays an important role in modulating adaptive immunity. It comprises more than 30 plasma and membrane-bound proteins and can be activated through three pathways: the classical, the alternative and the lectin pathways. Its activation contributes to the pathogenesis of several autoimmune and inflammatory conditions. The evidence of complement activation in synovial fluid of Rheumatoid Arthritis (RA) patients is abundant, while few data exist in Psoriatic Arthritis (PsA) patients. Levels of complement proteins are generally depressed in the synovial fluid of patients with RA, reflecting consumption of complement. On the other hand, elevated levels of several complement cleavage products have been observed in synovial fluid. Involvement of complement in the pathogenesis of RA was also confirmed in animal models of arthritis: mice deficient for complement proteins are protected against the development of collagen-induced arthritis and administration of the anti-C5 monoclonal antibody prevents the onset of this arthritis. In the last decade anti-tumor necrosis factor agents have shown to be effective for the treatment of both RA and PsA and some studies suggest that the interaction between TNFα and complement system may contribute to the pathogenesis of these diseases. Reduction of the complement activation could be one of the mechanism by which TNFα-inhibitors exert their effectiveness in inflammatory arthritides. Because of these findings, complement could be an attractive therapeutic target both in RA and in PsA.
21211616 Genetic basis of autoantibody positive and negative rheumatoid arthritis risk in a multi-e 2011 Jan 7 Discovering and following up on genetic associations with complex phenotypes require large patient cohorts. This is particularly true for patient cohorts of diverse ancestry and clinically relevant subsets of disease. The ability to mine the electronic health records (EHRs) of patients followed as part of routine clinical care provides a potential opportunity to efficiently identify affected cases and unaffected controls for appropriate-sized genetic studies. Here, we demonstrate proof-of-concept that it is possible to use EHR data linked with biospecimens to establish a multi-ethnic case-control cohort for genetic research of a complex disease, rheumatoid arthritis (RA). In 1,515 EHR-derived RA cases and 1,480 controls matched for both genetic ancestry and disease-specific autoantibodies (anti-citrullinated protein antibodies [ACPA]), we demonstrate that the odds ratios and aggregate genetic risk score (GRS) of known RA risk alleles measured in individuals of European ancestry within our EHR cohort are nearly identical to those derived from a genome-wide association study (GWAS) of 5,539 autoantibody-positive RA cases and 20,169 controls. We extend this approach to other ethnic groups and identify a large overlap in the GRS among individuals of European, African, East Asian, and Hispanic ancestry. We also demonstrate that the distribution of a GRS based on 28 non-HLA risk alleles in ACPA+ cases partially overlaps with ACPA- subgroup of RA cases. Our study demonstrates that the genetic basis of rheumatoid arthritis risk is similar among cases of diverse ancestry divided into subsets based on ACPA status and emphasizes the utility of linking EHR clinical data with biospecimens for genetic studies.
20676797 The psychological impact of arthritis: the effects of illness perception and coping. 2011 Mar BACKGROUND: Coping and illness perception are considered to be important contributors in the relationship between physical and psychological factors in rheumatoid arthritis (RA). AIMS: The aim of this study was to examine the complex relationship of coping and illness perception on physical and psychological factors in RA using a structural model. METHODS: We assessed coping, illness perception, depression, anxiety, pain, arthritis-related disability and perceived social support in 68 adults with RA. RESULTS: Greater pain was detected in patients with increased scores on passive coping scale, greater severity of physical disability and increased depression and anxiety. Illness perception was found to be a mediator in the relationship between physical disability and passive coping on one hand and depression, anxiety and pain on the other. CONCLUSIONS: The hypothesised structural model has proven to be a useful paradigm for understanding the associations between multiple factors in RA presentation: clinical, emotional, personal and cognitive.
23179259 Immunoglobulin subtypes predict therapy response to the biologics in patients with rheumat 2013 Jun To analyze the effectiveness of rituximab (RTX) versus alternative TNF antagonists (aTNFs) on rheumatoid arthritis (RA) disease activity in different subgroups of patients and relation with extraarticular manifestations of RA and to assess that RF-subsets have potential as predictors of clinical response to RTX. Patients with RA (n = 40, M/F: 3/37) who received aTNFs at least 6 months with good response (group I; n = 20) or discontinued at least one aTNFs because of the ineffectiveness and subsequently received RTX at least one course (group II; n = 20) were retrospectively evaluated. IgM-, IgA-, IgG-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) levels were measured by ELISA technique. Extraarticular manifestations and radiological scores were also recorded. The mean (SD) age was 51.7 ± 6.5 years in group I and 52.1 ± 6.1 years in group II patients (p > 0.05). The median disease durations were higher in group II than group I [8.0 (2-30) vs. 13 (3-35) years, respectively, p = 0.04]. Presence of RF [13(61.9 %) vs. 20(100 %) p = 0.001] and extraarticular involvement [5(25 %) vs. 13(65 %) p = 0.01] were higher in group II patients. When Ig-RF subgroups analyzed, all subgroup (IgA, IgM, IgG) levels were higher in group II (p = 0.001, p = 0.05, p = 0.001). IgA-RF levels were significantly high in patients with extraarticular involvement (p = 0.04). Association between high RF levels and having extraarticular manifestations in RA patients may largely be attributed to the IgA isotype.
22275179 Association of industry funding with the outcome and quality of randomized controlled tria 2012 Jul OBJECTIVE: To assess the association of industry funding with the characteristics, outcome, and reported quality of randomized controlled trials (RCTs) of drug therapy for rheumatoid arthritis (RA). METHODS: The Medline and Cochrane Central Register of Controlled Trials databases were searched to identify original RA drug therapy RCTs published in 2002-2003 and 2006-2007. Two reviewers independently assessed each RCT for the funding source, characteristics, outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or not positive), and reporting of methodologic measures whose inadequate performance may have biased the assessment of treatment effect. RCTs that were registered at ClinicalTrials.gov and completed during the study years were assessed for publication bias. RESULTS: Of the 103 eligible RCTs identified, 58 (56.3%) were funded by industry, 19 (18.4%) were funded by nonprofit sources, 6 (5.8%) had mixed funding, and funding for 20 (19.4%) was not specified. Industry-funded RCTs had significantly more study centers and subjects, while nonprofit agency-funded RCTs had longer duration and were more likely to study different treatment strategies. Outcome could be assessed for 86 (83.5%) of the 103 RCTs studied. The funding source was not associated with a higher likelihood of positive outcomes favoring the sponsored experimental drug (75.5% of industry-funded RCTs had a positive outcome, compared with 68.8% of non-industry-funded RCTs, 40% of RCTs with mixed funding, and 81.2% of RCTs for which funding was not specified). Industry-funded RCTs showed a trend toward a higher likelihood of nonpublication (P=0.093). Industry-funded RCTs were more frequently associated with double-blinding, an adequate description of participant flow, and performance of an intent-to-treat analysis. CONCLUSION: Industry funding was not associated with a higher likelihood of positive outcomes of published RCTs of drug therapy for RA, and industry-funded RCTs performed significantly better than non-industry-funded RCTs in terms of reporting the use of some key methodologic quality measures.
22748510 Risk of mortality, fatal infection, and fatal malignancy related to use of anti-tumor necr 2012 Dec OBJECTIVE: To estimate rates of all-cause mortality, fatal infection, and fatal malignancy in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor-α (anti-TNF) biologics. METHODS: A retrospective cohort study of RA patients initiating therapy with adalimumab, etanercept, or infliximab from January 2000 to December 2008 was conducted using an administrative database of a large health care insurer. Patients were followed for the occurrence of fatal events, which were identified using the National Death Index database. Overall and anti-TNF biologic-stratified incidence rates per 1000 person-years were calculated. Primary analyses were time-on-drug based on current anti-TNF biologic exposure on the outcome date for fatal infection and intent-to-treat based on the anti-TNF biologic initiated at cohort entry for fatal malignancy. RESULTS: Seven thousand seven hundred thirty-four patients initiated an anti-TNF biologic with 13,296 person-years of observation. Seventy-one deaths were identified, including 12 fatal infections and 21 fatal malignancies. The all-cause mortality rate was 5.34 per 1000 person-years. Incidence rates for fatal infection were similar among anti-TNF biologic current exposure groups (0.78 to 0.88 per 1000 person-years). Incidence rates for fatal malignancy were similar among anti-TNF biologic initiator groups (1.24 to 1.84 per 1000 person-years). CONCLUSIONS: The all-cause mortality rate in RA patients treated with anti-TNF biologics was lower than in previous studies in similar non-US populations, but comparable to mortality rates in the US general population. Fatal infection and fatal malignancy rates were similar across anti-TNF biologic groups. Further studies, designed to detect risk differences associated with anti-TNF biologic use and baseline risk factors, would provide additional information.
21765104 Evaluation of 19 autoimmune disease-associated loci with rheumatoid arthritis in a Colombi 2011 Sep OBJECTIVE: Recent studies have identified several common genes associated with multiple autoimmune diseases that support the hypothesis of the presence of shared or general autoimmunity genes. However, most of this work has been performed in populations of white origin. The main objectives of this study are to replicate the genotype-phenotype correlation between 19 such variants and rheumatoid arthritis (RA), and to evaluate gene-gene interactions between these genes in individuals from an ethnically homogenous nonwhite Colombian population. METHODS: Nineteen single-nucleotide polymorphisms (SNP) from 16 genes/loci were genotyped in 353 RA cases and 368 controls. For each SNP, allelic and genotype-based association tests were applied to evaluate genotype-phenotype correlation. Permutation-based tests were used to validate the statistical significance. Gene-gene interactions were assessed by logistic regression. RESULTS: We replicated the genetic association with rs13277113 (p = 0.0009, OR 1.46) and rs2736340 (p = 0.0001, OR 1.63) from C8orf13-BLK (8p23.1, associated with RA and systemic lupus erythematosus), and rs763361 (p = 0.03) from CD226 (18q22.3, associated with multiple sclerosis and type 1 diabetes) in the Colombian population. The population-attributable risks were estimated as 27%, 34%, and 16% for rs13277113, rs2736340, and rs763361, respectively. We also detected evidence for gene-gene interaction between SNP in MMEL1 (rs3890745) and C80rf13-BLK (rs13277113; p = 0.0002). CONCLUSION: Our results demonstrate that the IL2/IL21 region, C8orf13-BLK, and CD226 influence RA in Colombians, and RA shares some of the pathogenic mechanisms associated with other autoimmune diseases.
21459948 Relationship of focal erosions, bone mineral density, and parathyroid hormone in rheumatoi 2011 Jun OBJECTIVE: To investigate the relationship among focal bone erosions and bone mineral density (BMD), 25(OH) vitamin D (25OHD), and parathyroid hormone (PTH) values in patients with rheumatoid arthritis (RA). METHODS: The study included 1191 RA patients (1014 women, 177 men, mean age 58.9 ± 11.1 yrs) participating in a multicenter, cross-sectional study. RESULTS: Radiographic evidence of typical bony erosions on hands or forefeet was found in 64.1% of patients. In those with bone erosions as compared to those without, mean BMD Z score values were significantly lower at both the spine (-0.74 ± 1.19 vs -0.46 ± 1.31; p = 0.05) and the hip (-0.72 ± 1.07 vs -0.15 ± 1.23; p < 0.001). In the subgroup of patients not taking vitamin D supplements, PTH levels were significantly higher in those with erosive arthritis (25.9 ± 14.0 vs 23.1 ± 11.6 pg/ml; p = 0.01); whereas the 25OHD concentrations were very similar in the 2 groups. The mean differences for BMD and PTH among the erosive and nonerosive RA remained statistically significant when values were simultaneously adjusted for all disease and mineral metabolism factors (i.e., age, sex, menopause, disease duration, Disease Activity Score 28-joint count, Health Assessment Questionnaire, activities of daily living, Steinbrocker functional state, glucocorticoid therapy, body weight, and bisphosphonate treatment). CONCLUSION: Our results suggest that the presence of bone erosions in RA correlates with low BMD levels and high PTH levels, and that these associations are independent of the degree of functional impairment and other common determinants of bone mass and mineral metabolism in adults with RA. These findings suggest that treatments to prevent bone loss or suppress PTH levels might positively affect the progression of bone erosions in RA.
22328738 Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic 2012 Aug OBJECTIVE: A number of rheumatoid arthritis (RA) susceptibility genes have been identified in recent years. Given the overlap in phenotypic expression of synovial joint inflammation between RA and psoriatic arthritis (PsA), the authors explored whether RA susceptibility genes are also associated with PsA. METHODS: 56 single nucleotide polymorphisms (SNPs) mapping to 41 genes previously reported as RA susceptibility loci were selected for investigation. PsA was defined as an inflammatory arthritis associated with psoriasis and subjects were recruited from the UK and Ireland. Genotyping was performed using the Sequenom MassArray platform and frequencies compared with data derived from large UK control collections. RESULTS: Significant evidence for association with susceptibility to PsA was found toa SNP mapping to the REL (rs13017599, p(trend)=5.2×10(4)) gene, while nominal evidence for association (p(trend)<0.05) was found to seven other loci including PLCL2 (rs4535211, p=1.7×10(-3)); STAT4 (rs10181656, p=3.0×10(-3)) and the AFF3, CD28, CCL21, IL2 and KIF5A loci. Interestingly, three SNPs demonstrated opposite effects to those reported for RA. CONCLUSIONS: The REL gene, a key modulator of the NFκB pathway, is associated with PsA but the allele conferring risk to RA is protective in PsA suggesting that there are fundamental differences in the aetiological mechanisms underlying these two types of inflammatory arthritis.
22467274 Impact of statin discontinuation on mortality in patients with rheumatoid arthritis: a pop 2012 Jun OBJECTIVE: To evaluate the impact of statin discontinuation on cardiovascular disease (CVD) mortality and all-cause mortality in a population-based cohort of patients with rheumatoid arthritis (RA). METHODS: We conducted a population-based longitudinal study of RA patients with incident statin use followed from 1996 to 2006 using administrative health data. Statin discontinuation was defined as persistent nonuse for ≥3 months during the therapy course. Primary outcomes were mortality from all CVDs (CVD mortality) and secondary outcomes were deaths from all causes (all-cause mortality). Cox proportional hazards models with statin discontinuation as a time-dependent variable were used and multivariable models were adjusted for age, sex, comorbidities, and risk factors for mortality, and proxy indicators of RA severity. RESULTS: Over 16,144 person-years of followup in the cohort of 4,102 incident statin users, we documented 198 deaths due to CVD and 467 deaths overall. Adjusted hazard ratios for the association of statin discontinuation with death were 1.60 (95% confidence interval [95% CI] 1.15-2.23) for CVD mortality and 1.79 (95% CI 1.46-2.20) for all-cause mortality. The association between statin discontinuation and mortality outcomes was not modified by timing of the first statin prescription, age, and sex (P values for interaction ≥0.29). CONCLUSION: These population-based data indicate that statin discontinuation in patients with RA is associated with an increased risk of death from CVD and all causes. Findings provide support for the importance of compliance with therapy in RA patients who are prescribed statins.
21985471 An observational study of endothelial function in early arthritis. 2012 May BACKGROUND: Endothelial dysfunction is present in established rheumatoid arthritis, but it is not clear at what stage of the disease this abnormality develops. We set out to determine whether endothelial damage/dysfunction is present in a group of patients with early arthritis (EA) (new onset inflammatory arthritis, EA). MATERIALS AND METHODS: Eighteen patients with EA, 48 healthy controls and 25 disease controls were recruited. Plasma was obtained for endothelial [von Willebrand factor (vWF) and soluble E-selectin] and angiogenesis markers (vascular endothelial growth factor and its receptor sFlt-1), adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1) and circulating endothelial cells (CECs, as a marker of endothelial damage). Microvascular endothelial function was assessed using laser Doppler perfusion imaging and macrovascular function using flow-mediated dilatation of the brachial artery. RESULTS: von Willebrand factor and CECs (both P < 0.05) were significantly elevated in EA suggesting endothelial dysfunction and damage but were unrelated to classical laboratory markers of inflammation C-reactive protein, erythrocyte sedimentation rate or IL6. No other biomarkers was elevated in EA. Microvascular and macrovascular abnormalities were confined to endothelium-independent (smooth muscle cell) responses. CONCLUSIONS: Endothelial damage/dysfunction is present early in the course of inflammatory arthritis but is not directly related to inflammation markers.
21791140 [Determining cardiovascular risk in patients with rheumatoid arthritis: prove the efficacy 2011 In the multidisciplinary Dutch guideline on Cardiovascular Risk Management (revision 2011) the recommendation for preventive treatment of elevated risks of cardiovascular disease in patients with arthritis lacks a trial-based justification. This section should therefore be removed. Introduction of clinical guidelines with recommendations justified by evidence of an unacceptably low grade is a growing international tendency that should be stopped.
21789720 [Serum and synovial adiponectin, resistin, and visfatin levels in rheumatoid arthritis pat 2011 Sep BACKGROUND: Recent data provided evidence on the implication of the adipocytokines adiponectin, visfatin, and resistin in inflammation, immune response, and tissue destruction and revealed several links between them and arthritis. AIM OF THE STUDY: The purpose of this study was to assess the levels of adiponectin, visfatin, and resistin in serum and synovial fluid of patients with rheumatoid arthritis (RA) and their relationship with disease activity. SUBJECTS AND METHODS: A total of 70 female patients with RA and 30 age- and sex-matched healthy controls were enrolled. The clinical activity of RA patients was assessed according to the 28 joint count Disease Activity Score and patients were classified into two groups: 39 patients with active disease (group A) and 31 patients in remission (group B). Synovial fluid was obtained by arthrocentesis of the affected knee joints from 39 patients with active disease. Serum adiponectin, visfatin, and resistin concentrations were measured in RA patients and controls, while a specific enzyme-linked immunosorbent assay was used to measure the synovial concentrations of adiponectin, visfatin, and resistin in the group of patients with active RA. RESULTS: Serum levels of adiponectin and visfatin were significantly higher in all RA patients and patients with active disease compared to the control group and patients in remission. No significant difference was observed in the resistin level between patients and controls. Serum and synovial adiponectin and visfatin were positively correlated with DAS28-ESR in RA patients with active disease. CONCLUSION: Our data demonstrated that adiponectin and visfatin are related to disease activity in RA patients and might be involved in the progression of RA. The English full-text version of this article is available at SpringerLink (under "Supplemental").