Risk Of Rheumatic Disease Research Articles

Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Association of Cytokine IL-17, IL-4, IL-6, and IL-12 Gene Polymorphisms in Rheumatoid Arthritis Patients in a Tertiary Care Hospital in Bangladesh.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves cytokines in its pathogenesis. This study is aimed at investigating if gene polymorphisms in cytokines like IL-17, IL-4, IL-6, and IL-12 affect RA susceptibility and severity in the Bangladeshi population. This was a cross-sectional comparative study that included 40 diagnosed RA patients according to the American College of Rheumatology (ACR) criteria 2010, who were free from other rheumatological diseases, and 40 healthy subjects for comparison. The study used PCR-RFLP to determine the IL-17, IL-4, IL-6, and IL-12 cytokine gene polymorphisms. Patients had a mean age of 37.22 ± 6.70 years. Among the patients, 31 were female and 9 were male. The mean disease duration was 18.11 ± 7.39 months. The study found that rheumatoid arthritis patients with the IL-17F (7488 A/G) polymorphism with GG genotype (P = 0.006, OR = 8.56, 95% CI = 1.77 - 41.33) and IL-12B (1188 A/C) polymorphism with AC (P = 0.012, OR = 3.69, 95% CI = 1.43 - 9.53) and CC (P = 0.013, OR = 7.58, 95% CI = 1.56 - 36.88) genotypes were significantly associated with disease risk. Furthermore, patients with the IL-17F (7488) GG genotype and IL-12B (1188) AC and CC genotypes had higher rheumatoid arthritis disease severity and activity parameters. The study found no significant association between polymorphisms involving IL-4 (590 C/T) and IL-6 (174 G/C) genes and rheumatoid arthritis disease risk in the Bangladeshi population. Gene polymorphisms in cytokines IL-17F (7488 A/G) and IL-12B (1188 A/C) can predict disease susceptibility and severity in Bangladeshi rheumatoid arthritis patients.

Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses.

Although the association between obesity and risk of rheumatic disease is well established, the precise causal relation has not been conclusively proven. Here, we estimate the causal effect of body mass index (BMI) on the risk of developing 5 different rheumatic diseases. Linear and nonlinear mendelian randomization (MR) were used to estimate the effect of BMI on risk of rheumatic disease, and sex-specific effects were identified. Analyses were performed in 361,952 participants from the UK Biobank cohort for 5 rheumatic diseases: rheumatoid arthritis (n=8,381 cases), osteoarthritis (n=87,430), psoriatic arthropathy (n=933), gout (n=13,638), and inflammatory spondylitis (n=4,328). Using linear MR, we found that 1 SD increase in BMI increases the incidence rate for rheumatoid arthritis (incidence rate ratio [IRR] 1.52 [95% confidence interval (95% CI) 1.36-1.69]), osteoarthritis (IRR 1.49 [95% CI 1.43-1.55]), psoriatic arthropathy (IRR 1.80 [95% CI 1.31-2.48]), gout (IRR 1.73 [95% CI 1.56-1.92]), and inflammatory spondylitis (IRR 1.34 [95% CI 1.14-1.57]) in all individuals. BMI was found to be a stronger risk factor in women compared to men for psoriatic arthropathy (P for sex interaction=3.3 × 10-4 ) and gout (P for sex interaction=4.3 × 10-3 ), and the effect on osteoarthritis was stronger in premenopausal compared to postmenopausal women (P = 1.8 × 10-3 ). Nonlinear effects of BMI were identified for osteoarthritis and gout in men, and for gout in women. The nonlinearity for gout was also more extreme in men compared to women (P = 0.03). Higher BMI causes an increased risk for rheumatic disease, an effect that is more pronounced in women for both gout and psoriatic arthropathy. The novel sex- and BMI-specific causal effects identified here provide further insight into rheumatic disease etiology and mark an important step toward personalized medicine.

Endoplasmic reticulum aminopeptidase-1 polymorphism increases the risk of rheumatoid arthritis

Abstract Objectives Endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphic changes cause autoimmunity. To understand the contribution of ERAP1 to the occurrence of rheumatoid arthritis (RA) disease, we investigated the relationship between ERAP1 and RA. Methods This study was conducted with 201 patients and 171 healthy controls. The rs26653, rs27044, rs27582, rs28096, and rs30187 polymorphic regions of ERAP1 were investigated. The comparison was done with Arlequin software and logistic regression. Haplotypes were analyzed with Phylogenetic Network software. ERAP1 was modeled using Promod3. Topological changes in ERAP1 were analyzed with TM-Score. Results The results showed that rs26653G&gt;C (p=0.002, OR=2.001, 95%CI=1.276–3.137), rs27044C&gt;G (p=0.037, OR=1.583, 95%CI=1.028–2.440), rs27582G&gt;A (p&lt;0.05, OR=0.348, 95%CI=0.194–0.622) and rs30187C&gt;T (p=0.006, OR=1.849, 95%CI=1.191–2.870) polymorphisms are associated with RA disease risk. The relationship between rs28096 polymorphism and RA disease risk could not be determined (p=0.509). The risk haplotype for rheumatoid arthritis was determined as [CGAAT]. It was determined that polymorphisms of ERAP1 cause changes in the entry pocket of substrate and ligand. Conclusions We report a haplotype [CGAAT] that is associated with RA risk from Turkey that has not been described before. These data will make important contributions to elucidating the molecular mechanism of RA.

Cardiovascular disease risk in rheumatoid arthritis.

Cardiovascular disease risk in rheumatoid arthritis.

The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis.

To evaluate whether statins lower cardiovascular disease (CVD) risk in RA and if tentative benefits are related to changes in coronary plaque burden or composition. In an observational cohort study, 150 patients without CVD underwent coronary atherosclerosis evaluation (total, noncalcified, partially and fully calcified plaque) with CT angiography. Prespecified cardiovascular events including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication and heart failure were prospectively recorded. Change in plaque burden and composition was re-assessed in 102 patients within 6.9 (0.3) years. Time-varying statin therapy, modeled using inverse probability treatment and censoring weights, did not significantly attenuate CVD risk in RA overall [adjusted odds ratio (OR) = 0.39 (95% CI: 0.15, 1.07), P =0.067]. However, statins associated with lower CVD risk in patients with baseline CRP > 0.5 mg/dl [adjusted OR = 0.09 (95%CI: 0.03, 0.30), P <0.001] but not in those with CRP < 0.5 mg/dl (P-interaction = 0.023), after controlling for Framingham-CVD score and time-varying bDMARD use. In patients treated with statin >50% of follow-up time, CRP did not associate with new plaque formation [adjusted OR = 0.42 (95% CI: 0.09, 1.94)], in contrast to statin-naïve [adjusted OR = 1.89 (95% CI:1.41, 2.54)] and statin-treated <50% time [adjusted-OR = 1.41 (95% CI: 1.03, 1.95), P-interaction = 0.029]. Statin therapy >50% follow-up time predicted dissipation [adjusted-OR = 5.84 (95% CI: 1.29, 26.55)] and calcification of prevalent noncalcified lesions [adjusted-OR = 4.16 (95% CI: 1.11, 15.54)], as well as new calcified plaque formation in segments without baseline plaque [adjusted-OR = 2.84 (95% CI:1.09, 7.41)]. Statin therapy associated with lower long-term cardiovascular risk in RA patients with higher inflammation. Moreover, statin therapy modified the impact of inflammation on new coronary plaque formation and predicted both regression and calcification of prevalent noncalcified lesions.

Risk of rheumatic disease in breast implant users: a qualitative systematic review.

Recent studies on the risk of rheumatic disease among breast implant users have reported conflicting results. The primary objective of this study was to provide a systematic and critical review of the literature on the association between breast implants and the risk of rheumatic disease. A qualitative systematic review was conducted in PubMed, MEDLINE, EMBASE, EBM-Reviews and CINAHL Complete from database inception to June 23rd, 2021. Eligible papers were full-length articles in English or French reporting original data on the incident risk of rheumatic disease among individuals with and without breast implants. Data were extracted from published reports and appraised using the Newcastle-Ottawa scale. The main outcome was incident risk of systemic sclerosis (SSc), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), fibromyalgia and other rheumatic disorders and symptoms. Out of 3,425 identified citations, 86 met inclusion criteria. Two cohort studies suggested a two-fold increase in risk of SSc, whereas three case-control studies showed no increase in risk. Three cohort studies did not find an increased risk of incident and confirmed SS among breast implant users, however symptoms of sicca, myalgia and fatigue were reported more frequently. A meta-analysis of heterogenous studies reported a less than two-fold increase in risk of RA. Studies did not support an association with SLE. Insufficient evidence was available for autoimmune myositis and other rheumatic diseases. Implant rupture detected on imaging was not clearly associated with incident rheumatic disease, although no studies specifically examined the risk associated with acute/traumatic rupture. Little data was available on the safety of saline breast implants. Explantation often led to temporary improvement. Based on a small number of high-quality and methodologically robust studies, an association between breast implants and a small increase in risk of SSc and RA could not be excluded. Symptoms of sicca, myalgia and fatigue were reported more frequently among breast implant users. Overall, there remains much uncertainty in regard to the association between breast implants and the risk of incident rheumatic diseases. Individuals considering the placement of breast implants should be informed of this uncertainty. This study was registered in the PROSPERO database (#CRD42019133616).

Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.

The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.

Interleukin 6 as a pathogenic factor mediating clinical manifestations and a therapeutic target for rheumatic diseases and depressive disorders

The review summarizes current idea on the key role of interleukin 6 (IL-6) in the pathogenesis of rheumatic diseases (RDs) and depressive disorders. It considers in detail the mechanisms by which IL6 induces the clinical and laboratory manifestations of RDs and depression; the influence of precipitating and predisposing stress factors, including childhood mental traumas, which increase the risk of RDs and depression, on IL-6 production. Particular attention is paid to the consideration of prospects for using IL-6 inhibitors in the therapy of depression.

044 Temporal patterns in physical activity and sedentary behaviour: implications for cardiovascular disease risk in rheumatoid arthritis

044 Temporal patterns in physical activity and sedentary behaviour: implications for cardiovascular disease risk in rheumatoid arthritis

Sitting time is negatively related to microvascular endothelium-dependent function in rheumatoid arthritis

BackgroundSedentary behaviour is linked to increased cardiovascular disease risk in Rheumatoid Arthritis (RA), but the biological processes underlying this relationship are not understood. ObjectivesTo investigate the cross-sectional associations of habitual sedentary behaviour, with endothelial function in RA. MethodsSixty-eight RA patients (Mage = 55 ± 12 years) underwent Laser Doppler Imaging with iontophoresis, to assess microvascular endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) function. Large-vessel endothelium-dependent and endothelium-independent functions were measured via flow-mediated dilation (FMD) and glyceryl trinitrate dilation (GTN), respectively. Habitual sedentary behaviour (hours/week sitting) was self-reported (International Physical Activity Questionnaire). ResultsRegressions revealed sitting time significantly negatively predicted microvascular endothelium-dependent function (ACh, unstandardizedβ = −3.25, p = .02, 95% CI [−6.07, −.42], R2 = 0.06), but did not associate with other endothelial function outcomes (SNP, FMD, GTN). ConclusionHabitual sedentary behaviour (sitting time) appears to be adversely linked to microvascular endothelium-dependent function among people living with RA.

Chronic kidney disease, inflammation, and cardiovascular disease risk in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA), a prototypic systemic autoimmune inflammatory condition, confers an increased risk of cardiovascular disease (CVD). Recently, chronic kidney disease (CKD) was suggested to increase the risk of CVD in RA patients, and inflammation was identified as a critical, nontraditional CKD-associated risk factor for CVD. This study aimed to examine the combined effects of CKD and CVD in RA patients. MethodsIn this retrospective evaluation of 428 RA patients, the outcome of interest was the incidence of CVD. CKD was defined as an estimated glomerular filtration rate of <60mL/min/1.73m2 and/or positive dipstick tests for proteinuria of ≥3 months duration. C-reactive protein (CRP) was used as an inflammation marker, and a high CRP level was defined as a mean CRP value of ≥0.57mg/dL during the first 6 months of follow-up. Patients were categorized as follows: non-CKD with low CRP, non-CKD with high CRP, CKD with low CRP, and CKD with high CRP. ResultsDuring a median follow-up of 89 months, 67 patients (16%) had CKD, and 38 (9%) developed CVD. Using patients with non-CKD and low CRP as a reference group, the adjusted hazard ratios (HR, 95% confidence interval) for CVD were 1.88 (0.25–9.44) for patients with CKD/low CRP and 9.71 (3.27–31.97) for those with CKD/high CRP. ConclusionsThe coexistence of CKD and inflammation was associated with a higher risk of CVD than either condition alone in RA patients. Inflammation might increase the risk of CVD especially in patients with CKD.

Managing Cardiovascular Disease Risk in Rheumatoid Arthritis: Clinical Updates and Three Strategic Approaches.

By critically reviewing literature published within the past 5years, we aim to clarify current knowledge and gaps regarding CVD risk management in RA. We examine recent guidelines, recommendations, and evidence and discuss three approaches: (1) RA-specific management including treat-to-target and medication management, (2) assessment of comprehensive individual risk, and (3) targeting traditional CVD risk factors (hypertension, smoking, hyperlipidemia, diabetes, obesity, and physical inactivity) at a population level. Considering that 75% of US RA visits occur in specialty clinics, further research is needed regarding evidence-based strategies to manage and reduce CVD risk in RA. This review highlights clinical updates including US cardiology and international professional society guidelines, successful evidence-based population approaches from primary care, and novel opportunities in rheumatology care to reduce CVD risk in RA.

Rheumatologist and Primary Care Management of Cardiovascular Disease Risk in Rheumatoid Arthritis: Patient and Provider Perspectives.

Despite increased cardiovascular disease (CVD) risk, rheumatoid arthritis (RA) patients often lack CVD preventive care. We examined CVD preventive care processes from RA patient and provider perspectives to develop a process map for identifying targets for future interventions to improve CVD preventive care. Thirty-one participants (15 patients, 7 rheumatologists, and 9 primary care physicians [PCPs]) participated in interviews that were coded using NVivo software and analyzed using grounded theory techniques. Patients and providers reported that receipt of preventive care depends upon identifying and acting on risk factors, although most noted that both processes rarely occurred. Engagement in these processes was influenced by various provider-, system-, visit-, and patient-related conditions, such as patient activation or patients' knowledge about their risk. While nearly half of patients and PCPs were unaware of RA-CVD risk, all rheumatologists were aware of risk. Rheumatologists reported not systematically identifying risk factors, or, if identified, they described communicating about CVD risk factors via clinic notes to PCPs instead of acting directly due to perceived role boundaries. PCPs suggested that scheduling PCP visits could improve CVD risk management, and all participants viewed comanagement positively. Findings from this study illustrate important gaps and opportunities to support identifying and acting on CVD risk factors in RA patients from the provider, system, visit, and patient levels. Future work should investigate professional role support through improved guidelines, patient activation, and system-based RA-CVD preventive care strategies.

Risk factors for the rapid increase in risk of acute coronary events in patients with new-onset rheumatoid arthritis: a nested case-control study.

To investigate risk factors for acute coronary syndrome (ACS) in patients with new-onset rheumatoid arthritis (RA). We performed a nested case-control study of patients with incident RA included in the Epidemiological Investigation of RA study. Cases with ACS were identified using Swedish national health registers and matched with up to 5 controls without ACS, based on incidence density-based sampling. Information on potential exposures (clinical disease activity, serologic features, genetic markers, comorbidities, pharmacotherapies, and sick leave) was collected from medical charts and register-based sources. We identified 138 cases and 624 controls. Smoking, history of myocardial infarction, and >50 days of sick leave the year following RA onset were associated with an increased risk of ACS. Area under the curve measurements of C-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score in 28 joints (DAS28), and global health in the upper tertile during the first year and the complete followup period were both strongly associated with an increased risk of ACS. Treatment with disease-modifying antirheumatic drugs did not alter the ACS risk, nor did the presence of rheumatoid factor (RF) or shared epitope alleles, whereas high anti-citrullinated protein antibody (ACPA) levels were borderline significantly associated with ACS risk. In this study of risk factors for ACS in incident RA, clinical markers of inflammatory activity, disease activity, and total number of days of sick leave and disability pension during the first year following RA onset were identified as ACS risk factors. We found no association with RF, which was previously linked to cardiovascular disease risk in RA, but there was a borderline significant association with high ACPA levels.

Prevalence of musculoskeletal symptoms in the five urban regions of Brazil-the Brazilian COPCORD study (BRAZCO).

The objective of this study is to describe the prevalence of musculoskeletal symptoms (MSK-S) in the five urban geographical regions of Brazil using the Portuguese version of the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) core questionnaire (CQ)-BRAZCO study. From April to May 2013, a population-based survey was conducted by applying the CQ for 5000 individuals aged over 15years in 16 capitals of the Brazilian regions. Trained teams assessed the MSK-S and socioeconomic status. The sample consisted of representative quotas of the Brazilian population, proportional to the capitals' population density. It respected the groups' quotas of gender and age and included all socioeconomic classes, educational levels, and occupations. There were 1342 (26.9%) participants who presented MSK-S unrelated to trauma in 7days preceding the interview. A higher prevalence of these complaints were in females (65.2%), elderly people, in the north region of the country (30.7%), and a lower prevalence was found in single individuals (41.7%) and in the south (23.3%). The most frequent pain sites were the spine (76.7%) and knees (49.6%), and the mean pain intensity was 6.8 (VAS). The BRAZCO study shows that Brazilian population presents a higher rate of MSK-S unrelated to trauma than many Asian countries. These results can be applied to guide the assessment of prevalence of rheumatic diseases. Additionally, it can help in the design of policies for health care workforce organization and its accessibility, as well as to reduce the risk of rheumatic diseases at the community level.

Circulating concentrations of the novel adipokine chemerin are associated with cardiovascular disease risk in rheumatoid arthritis.

Depending on physiological context, the adipokine chemerin can reduce or enhance cardiovascular risk. We investigated whether chemerin concentrations represent cardiovascular disease risk in rheumatoid arthritis (RA). We assessed ELISA-determined chemerin concentrations and those of 4 early endothelial activation molecules as well as angiopoietin 2, which mediates angiogenesis and thereby contributes to advanced atherosclerosis, the common carotid artery intima-media thickness (cIMT), and carotid artery plaque by ultrasound in 236 patients (114 black and 122 white) with RA. Relationships were identified in potential confounder and mediator-adjusted mixed regression models. Mean (SD) chemerin and median (interquartile range) angiopoietin 2 concentrations were 114 (35) ng/ml and 2560 (2044-3341) pg/ml, respectively; the mean (SD) cIMT was 0.708 (0.110) mm, and 40.3% of patients had plaque. Chemerin concentrations were not related to those of early endothelial activation molecules, but associated with those of angiopoietin 2 [β SE = 0.002 (0.0004), p < 0.0001] and plaque [OR 1.006 (95% CI 1.00-1.013), p = 0.05] in all patients. The presence of major conventional cardiovascular risk factors, generalized and abdominal obesity, and RA severity markers modified the independent chemerin-cardiovascular risk relations (interaction p < 0.05). Consequently, chemerin concentrations were associated with cIMT in those with but not without overweight or generalized obesity and abdominal obesity [β SE = 0.001 (0.0003), p = 0.005 and 0.001 (0.0001), p = 0.001 vs -0.001 (0.0004), p = 0.2 and -0.0002 (0.0004), p = 0.6, respectively], and with plaque in those without but not with generalized obesity [OR 1.008 (95% CI) 1.000-1.016, p = 0.03 vs 1.003 (0.990-1.017), p = 0.6, respectively]. The β (SE) for the chemerin-intima-media thickness relations in patients with overweight or generalized obesity and abdominal obesity were larger than in those without these characteristics (p < 0.0001 and = 0.04, respectively). Chemerin is associated with endothelial activation and atherosclerosis in RA. Adiposity influences the chemerin-atherosclerotic phenotype relations in RA.

Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum levels in rheumatoid arthritis after interleukin-6 receptor blockade.

Inflammatory/metabolic factors and imbalance of haemostasis contribute to cardiovascular disease risk in rheumatoid arthritis (RA). Interleukin-6 (IL-6), a cytokine that plays an important role in immune responses, is implicated in its pathogenesis. In this study, the effects of the IL-6 receptor inhibitor, tocilizumab, on serum adipokines and coagulation/fibrinolysis factors in RA patients were examined. Nineteen consecutive patients (18 women, aged 48 ± 9 years) received six monthly infusions of 8 mg/kg tocilizumab for moderate or severe RA. Disease activity/severity, as well as serum levels of chemerin apelin, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), glucose, insulin and lipids were measured at baseline and at 1, 3 and 6 months thereafter. Chemerin and PAI-1 levels decreased significantly from baseline through 3 to 6 months (from 256 ± 79 to 174 ± 12 and 210 ± 85 ng/ml; from 73 ± 27 to 56 ± 22 and 51 ± 28 pg/ml, respectively). Other adipokines did not change, despite increases in adiposity. In multivariate models, significant independent associations were found between baseline chemerin with age, body mass index, remission of disease, HAQ-Di, CRP and PAI-1. Chemerin decrease at 6 months was significantly associated with PAI-1 and IL-6 changes at 6 months. Baseline PAI-1 associated negatively with remission of disease and total cholesterol, while PAI-1 change at 6 months associated with chemerin changes and smoking status. In conclusion, inhibition of IL-6 signaling in RA favorably alters chemerin and PAI-1 levels in an interrelated manner, despite increasing adiposity. This might represent a dual anti-inflammatory and anti-thrombotic/fibrinolytic mechanism of tocilizumab that may reduce cardiovascular event risk in RA patients.

OP0193 The Rheumatoid Arthritis -Risk Locus CCR6 and Its Snp-Dependent Response to Estrogen: A Possible Genomic Link between Sex Hormones and the IL-17 Inflammatory Pathway

BackgroundThe CCR6-CCL20–mediated migration of Th17 cells to inflamed tissues may represent an important mechanism in the etiology of rheumatoid arthritis (RA). The CCR6 polymorphism rs3093023 is associated with RA disease...

AB0351 The Novel Adipokine Chemerin is A Biomarker of Cardiovascular Risk in Patients with Rheumatoid Arthritis

BackgroundWhereas chemerin contributes to the pathophysiology of rheumatoid arthritis (RA) (1), its role in the enhanced cardiovascular disease risk in RA is unknown. In non-RA subjects, dependent on physiological context,...