Rheumatoid Arthritis Disease Characteristics Research Articles

Hepatitis B virus infection status and clinical characteristics in patients with rheumatoid arthritis

Objective: To investigate the epidemiology of hepatitis B virus (HBV) infection in patients with rheumatoid arthritis (RA) in China and its association with RA disease characteristics. Methods: A cross-sectional study. A retrospective study was conducted on RA patients recruited from January 2001 to February 2023 in the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital. Demographic and clinical data were collected including age, gender, disease duration, active smoking, RA disease activity, physical function, radiographic assessment, serological markers of HBV infection and liver function indicators. According to the status of HBV infection, RA patients were grouped as chronic HBV infection, resolved HBV infection and no HBV infection groups. The distribution of each group and the clinical characteristics of RA patients were analyzed. Results: Among 1 941 RA patients, 1 461 (75.3%) completed HBV screening, including 335 males (22.9%) and 1 126 females (77.1%), with a mean age of (55.4±13.1) years. The prevalence of chronic HBV infection was 10.1%(148/1 461), which was significantly higher in male patients than in females [14.6%(49/335) vs 8.8%(99/1 126), P<0.001], especially among those males born from 1970 to 1979[20.0%(7/35) vs 8.5%(17/201), P=0.037] and 1980-1989 [31.8%(7/22) vs 10.5%(14/133), P=0.007]. Among 148 RA patients with chronic HBV infection, there were 5 cases (3.4%) of chronic hepatitis B, 2 cases (1.4%) of HBV-associated cirrhosis and 1 case (0.7%) of hepatocellular carcinoma. The prevalence of resolved HBV infection was 57.6%(841/1 461). There were 472(32.3%) patients with no HBV infection and 267(56.6%) of them showed negative anti-HBs. Among all RA patients, 15 (1.0%) patients had abnormal liver function, of which 7 cases were drug-induced liver injury, 5 cases were chronic hepatitis B, 2 cases were non-alcoholic fatty liver disease, and 1 case was primary biliary cholangitis. Conclusion: Chronic HBV infection remains a common complication in RA patients in China, the infection rate is 10.1%, and the screening and management of HBV infection should be strengthened in clinical practice.

Decline in Incidence of Extra-Articular Manifestations of Rheumatoid Arthritis: A Population-Based Cohort Study.

The focus of this study was to assess changes in the cumulative incidence of extra-articular manifestations of rheumatoid arthritis (ExRAs) and associated mortality risk. This study evaluated trends in occurrence of ExRAs using a population-based inception cohort that included all adult patients with incident rheumatoid arthritis (RA) from 1985 through 2014 meeting the 1987 American College of Rheumatology criteria. Patients were divided into two cohorts based on the incidence date of RA, 1985 to 1999 and 2000 to 2014. The occurrence of ExRAs was determined by manual chart review, and the 10-year cumulative incidence was estimated for each ExRA in both cohorts. Cox proportional hazard models were used to determine associations between specific demographic and RA disease characteristics and ExRAs and between ExRAs and mortality. There were 907 patients included, 296 in the 1985 to 1999 cohort and 611 in the 2000 to 2014 cohort. The 10-year cumulative incidence of any ExRA decreased significantly between the earlier and later cohorts (45.1% vs 31.6%, P < 0.001). This was largely driven by significant declines in subcutaneous rheumatoid nodules (30.9% vs 15.8%, P < 0.001) and nonsevere ExRAs (41.4% vs 28.8%, P = 0.001). Identified risk factors for the development of any ExRAs include rheumatoid factor positivity (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.43-2.86) and current smoking (HR 1.61, 95% CI 1.10-2.34). Mortality was increased in patients with either nonsevere (HR 1.83, 95% CI 1.18-2.85) or severe ExRAs (HR 3.05, 95% CI 1.44-6.49). The incidence of ExRAs has decreased over time. Mortality remains increased in patients with ExRAs.

Impact of disease activity on patient-reported subjective cognitive decline in patients with rheumatoid arthritis

Aim: To evaluate the association of disease activity with patient-reported subjective cognitive decline (SCD) in patients with rheumatoid arthritis (RA) stratified by age. Methods: A cross-sectional analysis using data from the CorEvitas RA registry was utilized. The clinical disease activity index (CDAI) was used along with patient-reported problems thinking, age, and gender. The association of CDAI with patient-reported SCD was estimated using logistic regression models adjusted for sociodemographic characteristics, comorbidities, RA disease characteristics, and medication use. Additional models estimated and tested the moderating effect of patient age (&lt; 55 years vs. ≥ 55 years). Results: A total of 3,041 out of 33,537 patients (9.1%), reported SCD with a mean CDAI of 16.2 [standard deviation (SD): 12.5] vs. 10.1 (SD: 10.8) in those who did not. The adjusted odds ratio (OR) for low, moderate, and severe disease activity vs. remission was 2.17 [95% confidence intervals (CI): 1.88–2.50], 3.25 (95% CI: 2.82–3.75), and 3.84 (95% CI: 3.29–4.48) respectively. Age had a moderating effect with the association of disease activity and self-reported SCD more prevalent in those aged &lt; 55 years. The ORs for low, moderate, and severe disease activity were 3.37, 5.59, and 5.76 respectively for age &lt; 55 vs. 1.90, 2.67, and 3.37 respectively for age ≥ 55 (P = 0.0001). The patient global component of CDAI displayed the highest OR of risk for SCD broken out by quartiles (1, 1.62, 2.80, and 4.55). Conclusions: Increasing disease activity is associated with a higher likelihood of patient-reported SCD. The effect was more pronounced in younger RA patients and patients with a higher patient global score.

Mean Platelet Volume in a Series of 315 Patients with Rheumatoid Arthritis: Relationship with Disease Characteristics, including Subclinical Atherosclerosis and Cardiovascular Comorbidity.

Mean platelet volume (MPV) refers to the average platelet size in femtoliters. Increased or decreased MPV has been associated with several disorders, including inflammatory and cardiovascular diseases. In the present study, our objective was to analyze the relationship of MPV with disease activity in a large and well-characterized series of patients with rheumatoid arthritis (RA). This is a cross-sectional study that included 315 patients with RA and 208 controls matched by sex and age. Complete blood count, including MPV, was assessed. Multivariable analysis was performed to examine the relationship of MPV with RA disease characteristics, carotid atherosclerosis, and traditional cardiovascular factors, including a comprehensive profile of lipid molecules and insulin resistance or beta cell function indices. The multivariable analysis, which includes other hematological modifications produced by the disease and platelet values, showed that MPV levels were significantly lower in RA patients than in controls. Erythrocyte sedimentation rate and interleukin-6, but not C-reactive protein, were negatively correlated with MPV after adjustment for covariates. Similarly, disease activity and MPV had a significant and independent negative correlation. No relationships were found between MPV and cardiovascular risk factors, lipid profile or insulin resistance indices or subclinical atherosclerosis. In conclusion, patients with RA have lower levels of MPV than controls. MPV is negatively related to acute phase reactants and disease activity in RA.

Red Cell Distribution Width Association with Subclinical Cardiovascular Disease in Patients with Rheumatoid Arthritis.

Red cell distribution width (RDW) is a measure of the variation in mean corpuscular volume that reflects the degree of anisocytosis on the peripheral blood smear. RDW value variation has been implicated in several disorders including chronic inflammatory processes and cardiovascular (CV) diseases. In the present work, our objective was to study the relationship that RDW has with the characteristics of the disease in patients with rheumatoid arthritis (RA), focusing on CV risk factors and subclinical atherosclerosis. A cross-sectional study was conducted that included 430 patients with RA and 208 controls matched by sex and age. Complete blood count, including RDW, was assessed. Multivariable analysis was performed to analyze the relationship of RDW with RA disease characteristics, subclinical carotid atherosclerosis, and traditional CV factors, including a comprehensive profile of lipid molecules and insulin resistance and beta cell function indices. After multivariable adjustment, the RDW was significantly higher in RA patients compared with controls (beta coefficient 1.0 [95% confidence interval 0.2 to 1.8] %, p = 0.020). Furthermore, although the erythrocyte sedimentation rate showed a positive and significant relationship with RDW, this association was not found with C-reactive protein and interleukin-6. A positive and independent relationship was observed between DAS28-ESR disease activity score and RDW. However, no association was found between the RDW and other disease activity scores that do not include erythrocyte sedimentation rate in their formula. The SCORE2 CV risk algorithm was positively and significantly associated with higher RDW values. Likewise, a negative relationship was found between RDW with total cholesterol and low-density lipoprotein cholesterol, and a positive relationship was found between RDW and insulin resistance indices. In conclusion, RDW values are higher in RA patients compared to matched controls. Although the relationship of RDW with disease activity was not consistent, RDW shows associations with subclinical CV disease risk factors, including dyslipidemia and insulin resistance, and with the SCORE2 CV disease-risk prediction algorithm.

Rheumatoid Arthritis and Cognitive Impairment or Dementia: An Updated Review of Epidemiological Data.

Rheumatoid arthritis (RA) is hypothesized to be associated with cognitive impairment and dementia, including Alzheimer's disease, through shared biological processes related to inflammation. It is important to elucidate this potential relationship as both conditions confer increased morbidity and even mortality among older adults. This narrative review provides a survey of recent epidemiologic studies, examining the association between rheumatoid arthritis and either dementia or cognitive impairment. Sixteen studies were included after searching in PubMed and EMBASE. All were published between 2012 and 2022 and were characterized as epidemiologic studies (either cohort, cross-sectional, or case-control). Studies varied in location, design, measures of exposure and outcome, and covariates considered. Of the 16 studies included, only five found statistically significant positive associations between RA and dementia or cognitive impairment. One study found an inverse relationship, while five studies found no associations at all. The remaining five studies found variable statistically significant associations between demographic or RA disease characteristics and cognitive measures. Given these mixed findings, further studies at both the mechanistic and population level are needed to clarify the possible shared biological underpinnings of these two conditions.

Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme

ObjectiveLongitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts,...

Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis.

Muscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA. This cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index > 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching). In total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P < 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P > 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P < 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P < 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138-2.132)], and myopenia [AOR 2.983, 95% CI (1.192-7.465)] was independently associated with physical dysfunction in the patients with early RA. Our data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.

Associations of periodontal status in periodontitis and rheumatoid arthritis patients.

PurposeThe aim of this study was to assess the association between the clinical status of rheumatoid arthritis (RA) and periodontitis (PD) in patients diagnosed with PD and to evaluate the impact of RA treatment on the severity of PD.MethodsThe study included 148 participants with PD, of whom 64 were also diagnosed with RA (PD+RA group), while 84 age-matched participants were rheumatologically healthy (PD-only group). PD severity was assessed by the following periodontal parameters: clinical attachment loss, probing pocket depth (PPD), bleeding on probing (BOP), alveolar bone loss, and number of missing teeth. RA disease characteristics and impact of disease were evaluated by the Disease Activity Score 28 using C-reactive protein, disease duration, RA treatment, the RA Impact of Disease tool, and the Health Assessment Questionnaire. Outcome variables were compared using parametric and non-parametric tests and associations were evaluated using regression analysis with the calculation of odds ratios (ORs).ResultsParticipants in the PD+RA group had higher mean PPD values (2.81 ± 0.59 mm vs. 2.58 ± 0.49 mm, P=0.009) and number of missing teeth (6.27±4.79 vs. 3.93±4.08, P=0.001) than those in the PD-only group. A significant association was found between mean PPD and RA (OR, 2.22; 95% CI, 1.16–4.31; P=0.016). Within the PD+RA group, moderate to severe periodontal disease was significantly more prevalent among participants with higher RA disease activity (P=0.042). The use of biologic disease-modifying antirheumatic drugs (bDMARDs) was associated with a lower BOP percentage (P=0.016).ConclusionsIn patients with PD, RA was associated with a higher mean PPD and number of missing teeth. The severity of PD was affected by the RA disease clinical activity and by treatment with bDMARDs, which were associated with a significantly lower mean BOP percentage.

Survey of cardiovascular disease and risk factor management in patients with rheumatoid arthritis across 5 world regions: results from the SURF-RA

Abstract Background Patients with rheumatoid arthritis (RA) are at high risk for cardiovascular disease (CVD). Purpose The aim of this survey was to evaluate updated information on CVD risk factors, comorbidities, RA disease characteristics, RA and CVD preventive medication in patient with RA. Methods The audit is termed SUrvey of cardiovascular disease Risk Factors in patients with Rheumatoid Arthritis (SURF-RA) and was performed in 53 centres/19 countries/5 world regions in 2014–2019. SURF-RA have been performed in patients with coronary heart disease, in primary care, and now in patients with stroke, SLE and antiphophlipid syndrome. The survey was approved by the Data Protection Officer (2017/7243) and a GDPR evaluation has been performed (10/10–2018). Results Among 14 503 patients with RA in West (n=8 493) and East (n=923) Europe, Latin (n=407) and North (n=4 030) America and Asia (n=650) the mean (SD) age was 59.9 (13.6) years, and 2/3 or more were female (table). RA disease duration was comparable across the world regions, ranging from 9.9 to 12.6 years. The prevalence of atherosclerotic CVD (ASCVD) was lowest in Latin America (2.5%) and highest in East Europe (21.4%), and this pattern was similar regarding familial premature CVD. The mean prevalence (% of each entity) of blood pressure above 140/90 mmHg was 5.3%, of low density lipoprotein cholesterol &amp;gt;2.5 mmol/L: 63.3%. Overall, 29% used antihypertensive medication, lowest in West Europe (17.4%) and highest in East Europe (57.0%), and 26.4% used lipid lowering agent(s), lowest in Asia (7.2%) and highest in North America (31.1%). Body mass index &amp;gt;30 kg/m2 was present in 26.6%, with the smallest waist circumference in Asia [mean (SD): 84.1 (13.6) cm] and highest in East Europe [92.5 (15.5) cm]. The proportion of current smokers was on average: 16.2%, lowest in Asia (7.8%) and highest in East Europe (28.5%). Conclusion The high prevalence of CVD risk factors and ASCVD in patients with RA across five world regions shows that there is still an unmet need for vigilance and improved implementation of preventive measures in this high CVD risk patient population. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Lilly

Management of dyslipidaemia and hypertension in patients with rheumatoid arthritis in 19 countries

Abstract Background/Introduction The realisation that subjects with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD) has led to a growing interest in risk factor control in such people, but whether this has influenced the management of dyslipidaemia and hypertension (HT) is uncertain. Purpose To describe differences in lipid and blood pressure (BP) levels among patients with RA from five world regions. Furthermore, to evaluate attainment of guideline recommended targets for lipid lowering and antihypertensive treatment. Methods The SUrvey of CVD Risk Factors in patients with RA (SURF-RA) was conducted at 53 centres in 19 countries from 2014 to 2019. Data including demographics, RA disease characteristics, CVD comorbidity, risk factors and use of preventive treatment was collected. HT was defined as self-reported HT, and/or measured BP &amp;gt;140/90 mmHg, and/or use of anti HT medication (a-HT). The treatment goal of a-HT was BP &amp;lt;140/90 mmHg. The 10-year risk of a fatal CVD event was calculated by the European CVD risk calculator, the Systematic COronary Risk Evaluation (SCORE), and was thereafter multiplied with 1.5 as recommended by the European League Against Rheumatism. Patients were classified in a high or very high CVD risk group according to the 2012 European Society of Cardiology guidelines, with low density lipoprotein cholesterol (LDL-c) goal at &amp;lt;2.6 and &amp;lt;1.8 mmol/L, respectively. Results In total, 14503 RA patients were included. The mean age was 59.8±13.6 years, most of whom (74%) were female. Nearly 2/3 of the patients were hypertensive. Use of a-HT in the total population differed substantially between the cohorts with limited use in West Europe and Latin America (17.4% and 24.8%), in contrast to North America and East Europe (46.8% and 57.0%). On average, half of those with HT were at the recommended BP goal. The lowest BP goal attainment was seen in Asia, West and East Europe (40.8–43.1%), and the highest in North America (63.5%). Overall 51.5% had an indication for lipid lowering therapy (LLT), and of these only 43.5% were taking LLT. Only 34.0% of patients with an indication for LLT were at recommended LDL-c goals. The proportion of RA patients on target for LDL-c varied greatly between regions, from 23.1% in East Europe to 51.0% in North America. The LDL-c goal attainment was higher in RA patients at high risk (45.1%) compared to those at very high risk of CVD (18.0%). Conclusion(s) This large international survey on RA patients revealed considerable geographical differences in CVD preventive treatment. Only one half of subjects were at blood pressure goals, and achievement of lipid goals was even poorer at one third of those eligible for treatment, which is lower than what is reported for subjects with coronary heart disease. We conclude that there is a substantial need for improvement in CVD preventive measures in RA patients. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted research collaboration with Lilly

Prediction of cardiovascular events in rheumatoid arthritis using risk age calculations: evaluation of concordance across risk age models

BackgroundIn younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics.MethodsRA patients aged 30–70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up.ResultsA total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R2 values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15–32% of patients. C-statistics ranged 0.68–0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results.ConclusionsThe cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.

Association between periodontitis and anti-citrullinated protein antibodies in rheumatoid arthritis patients: a cross-sectional study

AimThe aim of this study was to evaluate the association between periodontal parameters related with the periodontal disease severity and the presence and levels of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients.Materials and methodsThis cross-sectional study included 164 RA patients. Socio-demographics and RA disease characteristics, including ELISA-detected ACPA (anti-CCP-2), were recorded. Exposure was assessed by periodontal parameters: plaque index (PI), bleeding on probing (BoP), probing pocket depth, and clinical attachment levels (CAL). Presence and levels of ACPAs (outcome) and exposure variables were compared by both parametric and non-parametric tests and associations were evaluated by adjusted odds ratio (OR).ResultsA significant association was observed between the presence of anti-CCP antibodies and severity of periodontal outcomes such as the mean CAL (OR 1.483, p = 0.036), mean PI (OR 1.029, p = 0.012), and the number of pockets ≥ 5 mm (OR 1.021, p = 0.08). High anti-CCP antibodies levels were associated with mean CAL, mean PI, and number of pockets ≥ 5 mm with an OR of 1.593 (p = 0.043), 1.060 (p < 0.001), and 1.031 (p = 0.031), respectively. Furthermore, a significant increase of 4.45 U/mL in anti-CCP antibodies levels (p = 0.002) in RA patients was found for each pocket ≥ 5 mm after adjusting for age, gender, smoking, time of disease evolution, and RA activity.ConclusionsIn RA patients, the severity of periodontal conditions such as mean CAL, mean PI, and the number of pockets ≥ 5 mm were linearly associated with both the presence and levels of anti-CCP antibodies.

Gender Impact on Rheumatoid Arthritis Disease Characteristics in A Cohort of Egyptian Patients

AbstractBackground: Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by various extra-articular manifestations and progressive articular damage. It has been a common perception that RA is more severe in females, but the literature is not clear about gender difference regarding RA disease course and prognosis.Aim of Study: To compare between male and female patients with rheumatoid arthritis regarding demographic, clinical characteristics, laboratory features, treatment received as well as the functional disabilities.Patients and Methods: Two hundred and ten RA patients consecutively recruited from the Rheumatology Department outpatient Clinic, Cairo University Hospitals from December 2017 to May 2018. Patients were divided based on sex and were compared regarding clinical characteristics, laboratory features, medications received, disease activity score 28 (DAS28) and The Stanford Health Assessment Questionnaire (HAQ).Results: Out of our studied patients 176 (83.8%) were females and 34 (16.2%) males with male to female ratio 5:1. Female RA patients were statistically significant younger age (p=0.04) and statistically significant had lower hemoglobin level (p=0.00), also had higher number of Tender Joint Count (TJC) (p=0.4), higher DAS28 score (p=0.3), higher health assessment questionnaire score (p=0.5), and more frequently receiving methotrexate (p=0.3) than male RA patients although the differences did not reach statistical significance. On the other hand male RA patients were statistically significant more smoker (p=0.00), and statistically significant more frequently having subcutaneous nodule (p=0.004).Conclusion: Female RA patients demonstrated slightly worse levels of disease activity and functional disability, although the difference did not reach statistical significance.

HLA-DRB1 Haplotypes, Shared Epitope, and Disease Outcomes in US Veterans with Rheumatoid Arthritis.

To evaluate associations of HLA-DRB1 haplotypes and shared epitope (SE) with rheumatoid arthritis (RA) severity and all-cause mortality in RA. Patients with RA from the Veterans Affairs Rheumatoid Arthritis (VARA) registry were followed from enrollment until death or December 31, 2013. Clinical characteristics, DNA, and serum were collected at enrollment. Radiographic damage, the presence or absence of subcutaneous nodules, disease activity measures, and functional status were assessed at enrollment and updated during followup. Sixteen HLA-DRB1 haplotypes and SE status were determined from banked DNA. Associations between HLA-DRB1 haplotypes, RA disease characteristics, and mortality were assessed in multivariable regression models. Within VARA, 1443 participants had genotyping and accrued 6150 patient-years of followup. Haplotypes VKA, VRA, LRA, SRA, SRE, SKR, and SEA, and SE alleles were significantly associated with seropositivity for rheumatoid factor (RF) and/or anticyclic citrullinated peptide (anti-CCP). Haplotypes VKA and SKR were associated with higher RF concentrations, while VRA, DRE, and GRQ were associated with lower RF concentrations. Haplotypes VKA, VRA, and LRA were associated with higher concentrations of anti-CCP antibody, while haplotypes SRA, SRE, LEA, SKR, and SEA were significantly associated with lower anti-CCP concentrations. Haplotype VKA (OR 1.39, 95% CI 1.08-1.80) was associated with increased frequency of radiographic damage at enrollment but none of the haplotypes were associated with the presence of subcutaneous nodules. Haplotypes SKA (HR 1.52, 95% CI 1.26-1.83) was associated with higher mortality. HLA-DRB1 haplotypes are independently and variably associated with seropositivity, autoantibody concentrations, and outcomes in RA.

Awareness and perceived risk of cardiovascular disease among individuals living with rheumatoid arthritis is low: results of a systematic literature review

BackgroundIndividuals with rheumatoid arthritis (RA) are at risk of developing cardiovascular disease (CVD), but patient perceptions of CVD are not routinely assessed. We performed a systematic literature review to evaluate awareness of the association between RA and CVD, and perceived risk of CVD among individuals with RA.MethodsThree electronic databases (MEDLINE, EMBASE, and PubMed) were searched for English language articles between the years of 1990–2018. Search terms pertained to RA, CVD, knowledge, awareness, or perceptions of CVD risk. s were screened for inclusion/exclusion by two independent reviewers.ResultsA total of 33 abstracts were screened and 6 underwent full review. The overall sample size was 478 subjects and included patients with established RA who were predominantly female with a mean age range of 53 to 64 years. RA disease characteristics relevant to CVD were not uniformly reported, including the use of DMARDs, corticosteroids, or NSAIDs. A high proportion of subjects (range 73 to 97%) were unaware of an increased risk of developing CVD in relation to their RA, and this frequently occurred in those with a greater number of traditional CVD risk factors. Misperceptions about CVD were common, and the majority of subjects misestimated their actual CVD risk.ConclusionIndividuals with RA at highest risk for CVD report low awareness and perceived risk of this comorbidity. This represents a knowledge gap in need of intervention but must be tailored to patients’ needs. An understanding of the system- and individual-level barriers preventing CVD awareness is needed. Only then will approaches to improve CVD screening and management in RA be successful.

Sex and Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease more common in women than men (3:1). Although sex-based differences may play a complex role in promoting an autoimmune dysfunction, to date the comprehensive knowledge of the link between sex and RA is still partially lacking. Furthermore, males and females have been demonstrated to differently deal with their chronic pathologies, modifying the perceived sex-based burden of disease. Gender medicine is a newly approach focusing on the impact of gender differences on human physiology, pathophysiology, and clinical features of diseases, analyzing the complex interrelation and integration of sex and psychological and cultural behavior. A better comprehension of possible factors influencing sexual dimorphism in RA susceptibility, pattern of presentation, disease activity, and outcome could contribute to a tailored approach, in order to limit the morbidity of the disease. RA disease activity seems to be higher in women, whereas the response rate to synthetic and biologic disease-modifying therapies appears to be better in males. Moreover, the common strategies for RA management may be affected by concomitant pregnancy or childbearing desire, with particular regard to treatments with potential teratogenic effects or impact on fertility. Finally, comorbidities, such as fibromyalgia, major depression, and osteoporosis, are more frequent in females, while the impact of sex on cardiovascular risk is still controversial. Moving from the role of sex in influencing RA pathogenesis, epidemiology, and disease characteristics, this review explores the evidence on how sex can have an impact on strategies for managing patients with RA.

Arterial Inflammation Detected With 18 F-Fluorodeoxyglucose-Positron Emission Tomography in Rheumatoid Arthritis.

In addition to traditional risk factors, excess cardiovascular disease (CVD) in rheumatoid arthritis (RA) is attributed to enhanced vascular and/or systemic inflammation. In several small studies using 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (18 F-FDG-PET/CT) to directly assess vascular inflammation, FDG uptake was higher in RA patients than in controls. Using a substantially larger sample of RA patients, we sought to identify RA disease characteristics independently associated with vascular FDG uptake. RA patients underwent cardiac FDG-PET/CT, with aortic inflammation assessed by quantification of FDG uptake in the ascending aorta, calculated as the mean and maximum (max) standardized uptake value (SUV) of the entire ascending aorta and of its most diseased segment (SUV MDS). Univariate and multivariable regression models were constructed to model the associations of patient characteristics with aortic FDG uptake. Ninety-one RA patients were scanned. In multivariable models, in addition to the independent associations of hypertension and body mass index with increased aortic FDG uptake, the prevalence of rheumatoid nodules correlated with the SUV mean and SUV MDS mean measures, while anti-cyclic citrullinated peptide (anti-CCP) antibodies correlated inversely with these measures and with the SUV max and SUV MDS max (P < 0.05). A significant association of RA disease activity with aortic FDG uptake was observed but was restricted to anti-CCP seropositivity. Traditional CV risk factors and RA disease characteristics (rheumatoid nodules and the Disease Activity Score in 28 joints using the C-reactive protein level in anti-CCP antibody-positive individuals) were independently associated with ascending aortic FDG uptake in RA patients without clinical CVD.

Challenges of developing a cardiovascular risk calculator for patients with rheumatoid arthritis.

ObjectiveCardiovascular disease (CVD) risk calculators designed for use in the general population do not accurately predict the risk of CVD among patients with rheumatoid arthritis (RA), who are at increased risk of CVD. The process of developing risk prediction models involves numerous issues. Our goal was to develop a CVD risk calculator for patients with RA.MethodsThirteen cohorts of patients with RA originating from 10 different countries (UK, Norway, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico) were combined. CVD risk factors and RA characteristics at baseline, in addition to information on CVD outcomes were collected. Cox models were used to develop a CVD risk calculator, considering traditional CVD risk factors and RA characteristics. Model performance was assessed using measures of discrimination and calibration with 10-fold cross-validation.ResultsA total of 5638 RA patients without prior CVD were included (mean age: 55 [SD: 14] years, 76% female). During a mean follow-up of 5.8 years (30139 person years), 389 patients developed a CVD event. Event rates varied between cohorts, necessitating inclusion of high and low risk strata in the models. The multivariable analyses revealed 2 risk prediction models including either a disease activity score including a 28 joint count and erythrocyte sedimentation rate (DAS28ESR) or a health assessment questionnaire (HAQ) along with age, sex, presence of hypertension, current smoking and ratio of total cholesterol to high-density lipoprotein cholesterol. Unfortunately, performance of these models was similar to general population CVD risk calculators.ConclusionEfforts to develop a specific CVD risk calculator for patients with RA yielded 2 potential models including RA disease characteristics, but neither demonstrated improved performance compared to risk calculators designed for use in the general population. Challenges encountered and lessons learned are discussed in detail.

Prevalence of Metabolic Syndrome in Treatment Naïve Rheumatoid Arthritis and Correlation With Disease Parameters.

This study aims to assess the prevalence of metabolic syndrome (MetS) in treatment naïve rheumatoid arthritis (RA) in an Indian population and correlate RA disease characteristics with presence of MetS. The study included 84 RA patients (18 males, 66 females; mean age 44.8±12.5 years; range 18 to 72 years) diagnosed according to 2010 American College of Rheumatology-European League Against Rheumatism classification criteria who were treatment naïve or did not receive disease modifying antirheumatic drugs for more than six weeks and 120 age and sex-matched apparently healthy controls (35 males, 85 females; mean age 44.1±12.7 years; range 18 to 75 years). The frequency of MetS was assessed using National Cholesterol Education Program- Adult Treatment Panel III 2004 revised criteria. Patients were also assessed in terms of disease activity, using disease activity score 28 erythrocyte sedimentation rate. Logistic regression was used to identify predictors of MetS in RA. Metabolic syndrome was found in 39.28% of RA group and 20% of control group according to National Cholesterol Education Program- Adult Treatment Panel III 2004 (p<0.005). MetS was most commonly detected in the 51 to 60 age group (65%). RA group was significantly more likely to have low high-density lipoprotein (63.09%), high triglyceride (53.57%), elevated blood pressure (41.66%) levels, and elevated waist circumference (38.09%). In RA group, disease activity score 28 (odds ratio: 6.51, confidence interval: 1.19-35.46 p=0.03), C-reactive protein (odds ratio: 1.13, confidence interval: 1.05-1.21 p<0.001), and duration of disease (odds ratio: 1.82, confidence interval: 1.04-3.18 p=0.03) remained independent predictors for presence of MetS in RA. The frequency of MetS was higher in RA group compared to control group. Higher systemic inflammatory marker, disease duration, and disease activity score 28 remained independent predictors associated with presence of MetS. These findings suggest that RA patients should be screened early for presence of MetS to check for and reduce risk of atherosclerotic vascular diseases.