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Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local setting.

Background In 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. Methods RA 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. Results A 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. Conclusions The 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.

Microvascular disease, or small-vessel disease, is a multisystem disorder with a common pathophysiological basis that differentially affects various organs in some patients. The prevalence of small-vessel disease in the heart has been found to be higher in women compared with men. Additionally, other diseases prominently affecting women, including heart failure with preserved ejection fraction, Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension (PAH), endothelial dysfunction in diabetes, diabetic cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, may have a common etiologic linkage related to microvascular disease. To the best of our knowledge this is the first article to investigate this potential linkage. We sought to identify various diseases with a shared pathophysiology involving microvascular/endothelial dysfunction that primarily affect women, and their potential implications for disease management. Advanced imaging technologies, such as magnetic resonance imaging and positron-emission tomography, enable the detection and increased understanding of microvascular dysfunction in various diseases. Therapies that improve endothelial function, such as those used in PAH, may also be associated with benefits across the full spectrum of microvascular dysfunction. A shared pathology across multiple organ systems highlights the need for a collaborative, multidisciplinary approach among medical subspecialty practitioners who care for women with small-vessel disease. Such an approach may lead to accelerated research in diseases that affect women and their quality of life.

Objectives Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. Methods Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. Results Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5–6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P Conclusion Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.

Objective.To assess trends in cardiovascular (CV) mortality in patients with incident rheumatoid arthritis (RA) in 2000–07 versus the previous decades, compared with non-RA subjects.Methods.The study population consisted of Olmsted County, Minnesota, USA residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria was met in 1980–2007) and non-RA subjects from the same underlying population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2014. Followup was truncated for comparability. Aalen-Johansen methods were used to estimate CV mortality rates, adjusting for competing risk of other causes. Cox proportional hazards models were used to compare CV mortality by decade.Results.The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 yrs; 68% women for both groups). Patients with incident RA in 2000–07 had markedly lower 10-year overall CV mortality (2.7%, 95% CI 0.6–4.9%) and coronary heart disease (CHD) mortality (1.1%, 95% CI 0.0–2.7%) than patients diagnosed in 1990–99 (7.1%, 95% CI 3.9–10.1% and 4.5%, 95% CI 1.9–7.1%, respectively; HR for overall CV death: 0.43, 95% CI 0.19–0.94; CHD death: HR 0.21, 95% CI 0.05–0.95). This improvement in CV mortality persisted after accounting for CV risk factors. Ten-year overall CV mortality and CHD mortality in 2000–07 RA incidence cohort was similar to non-RA subjects (p = 0.95 and p = 0.79, respectively).Conclusion.Our findings suggest significantly improved overall CV mortality, particularly CHD mortality, in patients with RA in recent years. Further studies are needed to examine the reasons for this improvement.

Objective.Women and men with rheumatoid arthritis (RA) have an increased risk for fragility fractures and cardiovascular disease (CVD), each of which has been reported to contribute to excess morbidity and mortality in these patients. Fragility fractures share similar risk factors for CVD but may occur at relatively younger ages in patients with RA. We aimed to determine whether a fragility fracture predicts the development of CVD in women and men with RA.Methods.We studied a population-based cohort with incident RA from 1955 to 2007 and compared it with age- and sex-matched non-RA subjects. We identified fragility fractures and CVD events following the RA incidence/index date, along with relevant risk factors. We used Cox models to examine the association between fractures and the development of CVD, in which fractures and CVD risk factors were modeled as time-dependent covariates.Results.There were 1171 subjects (822 women; 349 men) in each of the RA and non-RA cohorts. Over followup, there were 406 and 346 fragility fractures and 286 and 225 CVD events, respectively. The overall CVD risk was increased significantly for RA subjects following a fragility fracture (HR 1.81, 95% CI 1.38–2.37) but not for non-RA subjects (HR 1.18, 95% CI 0.85–1.63). Results were similar for women and men with RA.Conclusion.Fragility fractures in both women and men with RA are associated with an increased risk for CVD events and should raise an alert to clinicians to target these individuals for further screening and preventive strategies for CVD.

Smoking cessation in patients with RA is associated with reduced CVD event rates and improved lipid profiles and predicts lower RA disease activity

Objective To compare the frequency of and trends in hospitalizations after heart failure (HF) diagnosis in patients with and without rheumatoid arthritis (RA) during 1987–2015. Methods The study included a retrospectively identified population-based cohort of patients with incident HF and prior RA (age≥18 years, 1987 ACR criteria) and a cohort of incident HF patients without RA matched 3:1 on age, sex, and year of HF diagnosis. Hospitalizations at the time of HF diagnosis were excluded. All subjects were followed until death, migration, or 12/31/2015. Results The study included 212 patients with RA (mean age at HF diagnosis 78.3 years; 68% female) and 636 non-RA patients (mean age at HF diagnosis 78.6 years; 68% female). The hospitalization rate after HF diagnosis was higher in RA vs non-RA (rate ratio [RR] 1.17; 95%CI 1.08-1.26). Hospitalization rates in both groups have been declining since 2005 and the difference between patients with and without RA may be decreasing after 2010. The magnitude of the increase was similar in both sexes and across all ages. Patients with RA were more likely to be hospitalized for non-cardiovascular causes (RR 1.26; 95%CI 1.14-1.39), but not for HF or other cardiovascular causes compared to non-RA patients. Conclusions The hospitalization rate following HF diagnosis was higher in RA versus non-RA patients regardless of sex and age. Increased hospitalization risk in patients with RA was driven by increased rates of non-cardiovascular hospitalization.

Objective The long-term outcome of patients with nonradiographic axial spondyloarthritis (SpA) is unclear, particularly whether few or most progress to ankylosing spondylitis (AS). Our objective was to examine the progression to AS in a population-based inception cohort of patients with nonradiographic axial SpA. Methods The Rochester Epidemiology Project (REP) is a longstanding population-based study of health in the residents of Olmsted County, Minnesota. We searched the REP from 1985 to 2010 using diagnostic and procedural codes for back pain, HLA–B27, and magnetic resonance imaging of the pelvis, and we performed detailed chart reviews to identify subjects who fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axial SpA but did not have AS. We followed these subjects from disease onset to March 15, 2015, and used survival analysis to measure the time to progression to AS. Results After screening 2,151 patients, we identified 83 subjects with new-onset nonradiographic axial SpA. Over a mean follow-up of 10.6 years, progression to AS occurred in 16 patients. The probability that the condition would remain as nonradiographic axial SpA at 5, 10, and 15 years was 93.6%, 82.7%, and 73.6%, respectively. There was more frequent and more rapid progression among subjects in the imaging arm (n = 18) than among those in the clinical arm (n = 65) (28% versus 17%; hazard ratio 3.50 [95% confidence interval 1.15–10.6], P = 0.02). Conclusion Progression to AS occurred in a minority (26%) of patients with nonradiographic axial SpA over as long as 15 years of follow-up. This suggests that the classification criteria for nonradiographic axial SpA identifies many patients in whom the condition is unlikely to progress to AS or that nonradiographic axial SpA represents a prolonged prodromal state that takes longer to evolve to AS and thus requires longer follow-up.

To identify associations between immunostimulated cytokine production and disease characteristics, peripheral blood lymphocytes were collected from 155 adult patients with rheumatoid arthritis (RA) before and after a 5-year interval. The lymphocytes were activated in vitro with T-cell stimulants, cytosine-phosphate-guanine (CpG) oligonucleotide, and medium alone (negative control). Expression of 17 cytokines was evaluated with immunoassays, and factor analysis was used to reduce data complexity and identify cytokine combinations indicative of cell types preferentially activated by each immunostimulant. The findings showed that the highest numbers of correlations were between cytokine levels and rheumatoid factor (RF) positivity and between cytokine levels and disease duration. Scores for cytokines driven by CpG and medium alone were negatively associated with RF positivity and disease duration at baseline but positively associated with both at 5 years. Our findings suggest that RF expression sustained over time increases activation of B cells and monocytes without requirements for T-cell functions.

The study objective was to estimate secular trends in the overall incidence rate (IR) and prevalence rate (PR) of rheumatoid arthritis (RA); and subgroup-specific IR and PR by race, ethnicity, and sex in a multi-ethnic population of a large integrated health care delivery system. An ecological study was conducted within the adult population of Kaiser Permanente Southern California health plan. From January 1995 up to and including December 2014, annual IR and PR were calculated separately by race, ethnicity, sex and pooled overall. Depending on the stationarity of each ecological series, annual percentage change in IR and PR was evaluated using auto-regressive integrated moving average models. Average overall IR was 53 [95% confidence interval (CI) 46, 61] per 100,000 person-years. The overall as well as subgroup-specific annual IR of RA were unchanged from 1995 to 2014. In 1995, the overall PR of RA was 59 (44, 74) per 100,000 person-years which increased by 14% (7%, 21%) annually thereafter. The increase in PR in Caucasians was lower as compared to African American, Asian and other race (13% vs 15%, 15%, and 18%, respectively). Compared to non-Hispanic ethnicity, the increase in PR among Hispanic was higher (17% vs 14%). Over the past 2 decades, while the incidence of RA was unchanged, the prevalence had increased significantly overall as well as within every subgroup of race, ethnicity, and sex.

Cardiovascular risk age and vascular age estimations in predicting cardiovascular events in rheumatoid arthritis patients

Background There is a 2-fold increased risk of heart failure (HF) in rheumatoid arthritis (RA) compared to the general population. Little is known about hospitalisation rates in patients with RA and HF. Objectives We aimed to compare the frequency of and trends in hospitalizations after HF diagnosis in patients with and without RA during 1987–2015 and to assess risk factors for hospitalizations following HF in RA. Methods The study included a retrospectively identified population-based cohort of patients with incident HF and prior RA (age ≥18 years, 1987 ACR criteria) and a cohort of incident HF patients without RA matched 3:1 on age, sex, and year of HF diagnosis. Hospitalizations at the time of HF diagnosis were excluded. All subjects were followed until death, migration, or 12/31/2015. Person-years methods and rate ratios (RR) from Poisson regression models were used to compare hospitalisation rates (number of hospitalizations divided by person-years of follow-up) between the groups. Conditional frailty models were used to examine risk factors for hospitalisation. Results The study included 212 patients with RA (mean age at HF diagnosis 78.3 years; 68% female) and 636 non-RA patients (mean age at HF diagnosis 78.6 years; 68% female). The hospitalisation rate after HF diagnosis was higher in RA vs non-RA (RR 1.16; 95% CI 1.08–1.25). This difference may be decreasing after 2010 (figure 1). The magnitude of the increase was similar in both sexes and across all ages. In a subset with available echocardiography (n=68 RA and 449 non-RA), HF with preserved ejection fraction (HFpEF) was similarly prevalent in RA (57%) vs non-RA (51%; p=0.3). Among those with HF with reduced ejection fraction (HFrEF) RA patients had more hospitalizations than non-RA subjects (RR 1.65; 95% CI 1.29–2.09); this was not observed in HFpEF (RR 0.80; 95% CI 0.63–1.01). Following HF diagnosis, RA patients were more likely to be hospitalised for non-cardiovascular causes (RR 1.26; 95% CI 1.14–1.39), but not for HF (RR 0.96; 95% CI 0.76–1.21) or other cardiovascular causes (RR 0.99; 95% CI 0.81–1.20) compared to the non-RA patients. Readmission rates within 30 days of prior discharge were similar in RA and non-RA (p=0.14). Smoking (current or former), prior myocardial infarction (MI) and higher score on Charlson comorbidity index were associated with increased risk for hospitalisation: hazard ratio (HR) 1.33, 95% CI 1.06–1.68; HR 1.37, 95% CI 1.03–1.82; and HR 1.10, 95% CI 1.06–1.14, respectively. Conclusions Hospitalisation rate following HF diagnosis was 16% higher in RA than in non-RA patients regardless of sex and age. This difference was particularly apparent between 1990 and 2010. Increased hospitalisation risk was mostly among patients with RA who had HFrEF rather than HFpEF, and was predominantly due to non-cardiovascular causes. Smoking, prior MI and Charlson comorbidity index were associated with increased risk of hospitalisation suggesting that increased complexity of management of patients with comorbid RA may play a role in more frequent hospitalizations in the RA cohort. Disclosure of Interest None declared

ObjectivesPatients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA.MethodsIn 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions.Results5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all pConclusionsIn a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

Objective.Immunoglobulin free light chains (FLC) represent biomarkers of B cell activity in rheumatoid arthritis (RA) and are associated with all-cause mortality in the general population. Our objective was to evaluate the relationships of serum FLC to preclinical disease, RA characteristics, and mortality in RA compared to non-RA subjects.Methods.A population-based study in Olmsted County, Minnesota, USA, was performed by crosslinking a large cohort in the general population having available serum FLC measurements with established RA incidence and prevalence cohorts. Serum κ, λ, and total FLC and their trends relative to RA incidence were compared between RA and non-RA subjects. Regression models were used to determine the associations between FLC, disease characteristics, and mortality, testing for differential effects of FLC on mortality in RA.Results.Among 16,609 subjects, 270 fulfilled the criteria for RA at the time of FLC measurement. Mean total FLC were significantly higher in RA compared to non-RA subjects (4.2 vs 3.3 mg/dl, p < 0.001). FLC became elevated 3–5 years before the clinical onset of RA and remained elevated during followup. Polyclonal FLC were found to predict higher mortality in persons with RA, though elevation to the highest decile had a relatively lower effect on mortality in RA compared to non-RA subjects.Conclusion.Elevation of serum FLC precedes the development of RA and may be useful in monitoring B cell activity and disease progression. FLC are associated with mortality among patients with RA as well as the general population.

Objective Cardiovascular 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. Methods Thirteen 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. Results A 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. Conclusion Efforts 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.

Patients with rheumatoid arthritis (RA) have increased risk of heart failure with preserved ejection fraction. The development and progression of left ventricular dysfunction before onset of clinical heart failure are unknown. The objective of this study was to evaluate longitudinal changes in cardiac structure and function of patients with RA compared with persons in the general population.A prospective longitudinal study of a population-based cohort of 160 patients with RA and a population-based cohort of 1391 persons without RA (non-RA cohort) was performed. Each participant underwent 2-dimensional, pulsed-wave tissue Doppler echocardiography at baseline and after 4 to 5years of follow-up. Age- and sex-adjusted linear regression models were used to test for differences between the RA and non-RA cohorts in annualized rates of change for echocardiographic parameters.Mitral A velocity increased more rapidly among the patients with RA than the non-RA cohort (age- and sex-adjusted parameter estimate, 0.030; P0.001). Correspondingly, the mean mitral inflow E/A ratio decreased faster in the RA cohort than the non-RA cohort (adjusted parameter estimate, -0.096; P0.001). The left atrial volume index increased at a higher rate in the RA cohort than the non-RA cohort (adjusted parameter estimate, 0.150; P0.001).This pattern of echocardiographic findings confirms previous cross-sectional studies and indicates that subclinical changes in diastolic function occur more rapidly over 5years in RA patients than in the general population. Further research into the mechanisms of myocardial disease in these patients and the relationship with disease activity and treatment is warranted.

Rheumatoid arthritis (RA) is a multiorgan inflammatory disorder affecting approximately 1% of the population that leads to progressive joint destruction and disability. Patients with RA exhibit a high risk of cardiovascular disease, which results in premature morbidity and mortality and reduced life expectancy, when compared with the general population. Among various guises of myocardial involvement, heart failure (HF) has been recently recognized as an important contributory factor to the excess cardiovascular mortality associated with RA. HF in RA typically presents with occult clinical symptomatology and is mainly associated with structural and functional left ventricular abnormalities leading to diastolic dysfunction, while systolic myocardial performance remains well preserved. As isolated diastolic dysfunction is a predictor of high mortality, the evaluation of patients in early asymptomatic stages, when treatment targeting the heart is more likely to be effective, is of great importance. Although patient history and physical examination remain the cornerstones of HF evaluation, noninvasive imaging of cardiac chambers, coronary arteries, and great vessels may be necessary. Echocardiography, nuclear techniques, and invasive coronary angiography are already established in the routine assessment of HF; however, many aspects of HF pathophysiology in RA remain obscure, due to the limitations of currently used techniques. The capability of cardiovascular magnetic resonance (CMR) to capture early tissue changes allows timely detection of pathophysiologic phenomena of HF in RA, such as myocardial inflammation and myocardial perfusion defects, due to either macrovascular (coronary artery disease) or microvascular (vasculitis) disease. Therefore, CMR may be a useful tool for early, accurate diagnosis and research in patients with RA.

Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease with significant, often debilitating joint involvement, associated extraarticular manifestations, excess comorbidity and increased mortality.

Item does not contain fulltext Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field.

Physicians must possess knowledge and skills to address the gaps facing the US health care system. Educators advocate for reform in undergraduate medical education (UME) to align competencies with the Triple Aim. In 2014, five medical schools and one state university began collaborating on these curricular gaps. The authors report a framework for the Science of Health Care Delivery (SHCD) using six domains and highlight curricular examples from each school. They describe three challenges and strategies for success in implementing SHCD curricula. This collaboration highlights the importance of multi-institutional partnerships to accelerate innovation and adaptation of curricula.

Factors associated with dissection from inflammatory aortic aneurysms may be different from those in the general population.The aim of this study was to evaluate the risk factors for aortic dissection/rupture in patients with giant cell arteritis (GCA) and aortic aneurysms.A population-based incident cohort of patients with a diagnosis of GCA from 1950 to 2004 was used. All patients with aortic aneurysms diagnosed 1 year prior to GCA diagnosis or any time thereafter were included. Cox proportional hazard models were used to evaluate risk factors for aortic dissection/rupture.The study included 33 patients (91% women) with GCA and aortic aneurysms. Mean age at diagnosis of aortic aneurysm was 83.6 years. There were 27 thoracic aneurysms and 19 abdominal aneurysms. Eight patients developed aortic dissection/rupture (both thoracic and abdominal aorta in 5 cases, thoracic aorta only in 2 cases, and isolated abdominal aorta in 1 case).Older age (hazard ratio [HR], 0.27 per 10 years; 95% confidence interval [CI], 0.09-0.86) and later calendar year at diagnosis of aortic aneurysm (HR, 0.29 per 10 years; 95% CI, 0.13-0.69) were associated with decreased risk of dissection/rupture. Size of the thoracic aneurysm (HR, 1.17; 95% CI, 0.69-1.99) was not associated with dissection/rupture. Histopathology showed active aortitis in 4 of 7 patients with aortic dissection/rupture compared with 0 of 7 patients with aortic aneurysm without dissection/rupture.Aneurysm size was not a predictor of aortic dissection/rupture in this cohort of patients with GCA. The higher frequency of active aortitis in patients with dissection suggests that active inflammation may play a role.

Longitudinal care of a community-based cohort of patients with rheumatoid arthritis (RA) was evaluated retrospectively. Candidate determinants of disability included visual analog scales (VAS) for patient global assessment and pain, comorbidities, and medications. The outcome was the ‘patient-acceptable symptom state’ for disability as defined by the Health Assessment Questionnaire (HAQ) disability index, using a cutoff of

Objective To examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods We used data from patients with GCA (1950–2004) and RA (1955–2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results The correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0–1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5–7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4–5 years. However, the RA incidence power spectrum main peak is broader (8–11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4–5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. The link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.

Objectives To assess whether HOUSES (HOUsing-based index of socioeconomic status (SES)) is associated with risk of and mortality after rheumatoid arthritis (RA). Design We conducted a population-based case–control study which enrolled population-based RA cases and their controls without RA. Setting The study was performed in Olmsted County, Minnesota. Participants Study participants were all residents of Olmsted County, Minnesota, with RA identified using the 1987 American College of Rheumatology criteria for RA from 1 January 1988, to 31 December 2007, using the auspices of the Rochester Epidemiology Project. For each patient with RA, one control was randomly selected from Olmsted County residents of similar age and gender without RA. Primary and secondary outcome measure The disease status was RA cases and their matched controls in relation to HOUSES as an exposure. As a secondary aim, post-RA mortality among only RA cases was an outcome event. The associations of SES measured by HOUSES with the study outcomes were assessed using logistic regression and Cox models. HOUSES, as a composite index, was formulated based on a summed z-score for housing value, square footage and number of bedrooms and bathrooms. Results Of the eligible 604 participants, 418 (69%) were female; the mean age was 56±15.6 years. Lower SES, as measured by HOUSES, was associated with the risk of developing RA (0.5±3.8 for controls vs −0.2±3.1 for RA cases, p=0.003), adjusting for age, gender, calendar year of RA index date, smoking status and BMI. The lowest quartile of HOUSES was significantly associated with increased post-RA mortality compared to higher quartiles of HOUSES (HR 1.74; 95% CI 1.10 to 2.74; p=0.017) in multivariate analysis. Conclusions Lower SES, as measured by HOUSES, is associated with increased risk of RA and mortality after RA. HOUSES may be a useful tool for health disparities research concerning rheumatological outcomes when conventional SES measures are unavailable.

The challenges faced in improving the prevention and management of rheumatic and musculoskeletal diseases (RMDs) across the globe are addressed in the inaugural White Paper from the World Forum on Rheumatic amd Musculoskeletal Diseases (WFRMD) published in this issue [1]. The WFRMD, convened by Dr Mustafa Al Maini, brings together leaders from the international rheumatological community who are committed to promoting collaborative strategies to deal with this burden and work with major organisations such as ILAR, ACR, EULAR, PANLAR and AFLAR and policy makers such as theWorld Health Organisation (WHO). It is an important and timely initiaitive to increase awareness of the major burden that rheumatic and musculoskeletal diseases have on individuals and society and to explore opportunities to address these challenges on a local and global scale. This is the mission of WFRMD (www.wfrmd.org). It fits within the context of the Global Alliance for Musculoskeletal Health which the Bone and Joint Decade has brought together to call for action by policy makers to deal with the burden of RMDs (http://bjdonline.org). Musculoskeletal health is essential to independent living and self-sustainability as well as enabling people to keep physically active and reduce the risk of non-communicable diseases. It is threatened by a wide range of RMDs at all stages of life. Other risks such as obesity, injuries related to occupation and sports and more serious trauma such as falls and road injuries can often result in musculoskeletal disability. These RMDs are often long term and are an important comorbidity amongst the chronic diseases we accumulate as we age. An RMD as a comorbidity magnifies the physical disability that people suffer [2]. All these factors affecting musculoskeletal health along with the ageing of populations result in the great and growing prevalence and disability across the globe [3]. Further, exacerbating these trends is the growing need for people, as they age, to be able to continue to contribute economically to society with delayed retirement ages becoming commonplace inmany countries around the world. Health and social care systems are struggling to cope with ageing populations and their multimorbidity. For these reasons, there is an urgency to deal with the challenges of rheumatic and musculoskeletal diseases, challenges which are not currently being addressed by policies and priorities of health systems around the globe [4]. Indeed, RMDs are not considered a major noncommunicable disease by the WHO [5] or UN [6]. As a consequence, there is great and growing avoidable disability. The Bone and Joint Decade has responded by bringing together all stakeholders—professional, scientific and patient organisations as a Global Alliance for Musculoskeletal Health calling for action by decision makers to implement policies to deal with this burden (http://bjdonline.org/call-for-action/). The specific challenges and opportunities for the rheumatology community have been considered by the inaugural meeting of the World Forum on Rheumatic and Musculoskeletal Diseases on the 26th of September in Abu Dhabi and are reported in this issue [1]. Subsequent papers are planned to address issues raised in the White Paper. This is much needed as the expert community must propose solutions for the decision makers to deal with these challenges. The burden of RMDs on individuals and societies is now well documented [3, 7–15], and there are many evidenceA. D. Woolf (*) Global Alliance for Musculoskeletal Health of the Bone and Joint Decade, University of Plymouth Peninsula College of Medicine and Dentistry, Plymouth, England, UK e-mail: anthony.woolf@btopenworld.com

Background Patients with rheumatoid arthritis (RA) undergo radiologic investigations for disease and comorbidity evaluation. The actual use of radiologic imaging in RA is unknown. Methods Using the Rochester Epidemiology Project medical record linkage system, adult patients from previously assembled population-based cohorts of Olmsted County, Minnesota, residents who fulfilled the 1987 American College of Rheumatology criteria for RA in 1988 to 2007 and comparator subjects without RA of similar age and gender were studied. Data on all radiologic procedures performed were collected. Results The study included 650 patients with RA and 650 patients without RA. Patients with RA had significantly more radiographs of the chest (rate ratio [RR], 1.33; 95% confidence interval [CI], 1.28-31.38), upper extremity (RR, 2.97; 95% CI, 2.80-83.17), lower extremity (RR, 2.05; 95% CI, 1.94-102.16), spine (RR, 1.46; 95% CI, 1.35-41.59), and hip, pelvis, or sacroiliac joints (RR, 1.14; 95% CI, 1.03-11.26), as well as bone radionuclide (RR, 1.90; 95% CI, 1.50-52.44) and dual-energy x-ray absorptiometry imaging (RR, 1.77; 95% CI, 1.59-61.98) compared with patients without RA. Among patients with RA, having a positive rheumatoid factor was associated with an increased likelihood of undergoing radiologic procedures (RR, 1.05; 95% CI, 1.02-11.07). Women with RA underwent more imaging procedures than men (RR, 1.20; 95% CI, 1.16-21.23). Conclusions Patients with RA undergo more radiologic procedures than patients without RA. Among patients with RA, women and patients with a positive rheumatoid factor have more radiologic procedures. The utilization of radiography is likely a reflection of overall disease burden. Despite some guidelines, routine hand wrist radiographs were not obtained with regularity; "overuse" is unlikely.

Objective. To investigate the incidence of atrial fibrillation (AF) among patients with rheumatoid arthritis (RA) compared to the general population.Methods. A population-based inception cohort of Olmsted County, Minnesota, residents with incident RA in 1980–2007 and a cohort of non-RA subjects from the same population base were assembled and followed until 12/31/2008. The occurrence of AF was ascertained by medical record review.Results. The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 (SD:15.7) years, 68% women in both cohorts). The prevalence of AF was similar in the RA and non-RA cohorts at RA incidence/index date (4% versus 3%;P=0.51). The cumulative incidence of AF during follow-up was higher among patients with RA compared to non-RA subjects (18.3% versus 16.3% at 20 years;P=0.048). This difference persisted after adjustment for age, sex, calendar year, smoking, and hypertension (hazard ratio: 1.46; 95% CI: 1.07, 2.00). There was no evidence of a differential impact of AF on mortality in patients with RA compared to non-RA subjects (hazard ratio 2.5 versus 2.8; interactionP=0.31).Conclusion. The incidence of AF is increased in patients with RA, even after adjustment for AF risk factors. AF related mortality risk did not differ between patients with and without RA.

Autoimmune rheumatic diseases can affect the cardiac vasculature, valves, myocardium, pericardium, and conduction system, leading to a plethora of cardiovascular manifestations that can remain clinically silent or lead to substantial cardiovascular morbidity and mortality. Although the high risk of cardiovascular pathology in patients with autoimmune inflammatory rheumatological diseases is not owing to atherosclerosis alone, this particular condition contributes substantially to cardiovascular morbidity and mortality-the degree of coronary atherosclerosis observed in patients with rheumatic diseases can be as accelerated, diffuse, and extensive as in patients with diabetes mellitus. The high risk of atherosclerosis is not solely attributable to traditional cardiovascular risk factors: dysfunctional immune responses, a hallmark of patients with rheumatic disorders, are thought to cause chronic tissue-destructive inflammation. Prompt recognition of cardiovascular abnormalities is needed for timely and appropriate management, and aggressive control of traditional risk factors remains imperative in patients with rheumatic diseases. Moreover, therapies directed towards inflammatory process are crucial to reduce cardiovascular disease morbidity and mortality. In this Review, we examine the multiple cardiovascular manifestations in patients with rheumatological disorders, their underlying pathophysiology, and available management strategies, with particular emphasis on the vascular aspects of the emerging field of 'cardiorheumatology'.

Background In the general population it is well documented that females have their CVD diagnosed at a later stage compared to males. Wether this is true also for rheumatoid arthritis (RA) patients is not known. Objectives To evaluate if cardiovascular disease (CVD) risk prediction and event rates differed between the sexes, and if adjustments for traditional and RA specific risk factors were of importance. Methods RA cohorts from 13 rheumatology centers were compared. Data on CVD risk factors and RA characteristics were collected at baseline; CVD outcomes were collected using standardized definitions. Standardized incidence ratios (SIR) were calculated with respect to sex using the following risk calculators FRS, SCORE, ACC/AHA and QRISK II. Results 5638 patients with RA and no prior CVD were included (mean age: 55.3 [SD: 14.0] years, 76% female). During a mean follow-up of 5.8 (SD: 4.4) years, 437 patients developed CVD events. SIRs (95% CI) using the various CVD risk calculators were for females and males: FRS: 1.02 (0.80, 1.31) and 0.86 (0.67, 1.12) (p=0.19), SCORE: 0.34 (0.17, 0.67) and 0.25 (0.11, 0.58) (p=0.98), ACC/AHA: 0.72 (0.50, 1.04) and 0.56 (0.36, 0.88) (p=0.74) and QRISKII 0.61 (0.47, 0.79) and 0.52 (0.35, 0.79) (p=0.42). The 10 year CVD-free survival differed significantly between the sexes, when adjusting for a) age, b) age and CVD risk factors and c) age, CVD risk factors and RA disease characteristics (Females [mean %±SD] 88.3±0.3, males 79.4±0.4), p Conclusions In a large international cohort of patients with RA, there was no sex difference in the ability of the various risk calculators to predict CVD. CVD-free survival was significantly higher in females, even after adjustments for both traditional and RA specific risk factors. Acknowledgement ATACC-RA collaborators: T.K. Kvien (Diakonhjemmet hospital, Oslo, Norway), E.L. Matteson (Mayo Clinic, Rochester, United States), K. Douglas and A. Sandoo (Dudley Group NHS Foundation Trust, West Midlands, United Kingdom), E. Arts and J. Fransen (Radboud University Medical Centre, Nijmegen, Netherlands), P.P. Sfikakis and E. Zampeli (University of Athens, Athens, Greece), S. Rantapaa-Dahlqvist and S. Wallberg-Jonsson and L. Innala (University of Umea, Umea, Sweden), G. Karpouzas (Harbor UCLA Medical Center RHU, Torrance, United States), D. Solomon and K. Liao (Harvard Medical School Brigham and Women9s Hospital, Boston, United States), M.A. Gonzalez-Gay and A. Corrales (Hospital Universitario Marques de Valdecilla, Santander (Cantabria), Spain), P.H. Dessein and L. Tsang (University of Witwatersrand, Johannesburg, South Africa), H. El-Gabalawy and C. Hitchon (University of Manitoba, Winnipeg, Manitoba, Canada), V.P. Ramos and I.C. Yanez (Instituto Nacional de Ciencias Medicas y Nutriciόn Salvador Zubiran, Mexico City, Mexico), M. van de Laar and H. Vonkeman and I. Meek (Hospital Medisch Spectrum Twente, Enschede, Netherlands), E. Husni and R. Overman (Cleveland Clinic, Cleveland, United States), I. Colunga and D. Galarza (Hospital Universitario “Dr. Jose E. Gonzalez”, Monterrey, Mexico) Disclosure of Interest None declared

Background Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with rheumatoid arthritis (RA). Objectives To externally validate risk calculators recommended for use in patients with RA including the European League Against Rheumatism (EULAR) 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA) and QRISK2. Methods Seven RA cohorts from United Kingdom, Norway, Netherlands, United States, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared to other risk calculators (ACC/AHA, Framingham Adult Treatment Panel III [FRS-ATP] and Reynolds Risk Score) using c-statistics and net reclassification index (NRI). Results Among 1796 RA patients without prior CVD (mean age: 54.0 [SD: 14.0] years, 74% female), 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA (mean: 8.8%, SD: 9.8%) was comparable to FRS-ATP (mean: 9.1%, SD:8.3%) and Reynolds (mean: 9.2%, SD: 12.2%), but lower than ACC/AHA (mean: 9.8%, SD: 12.1%) and QRISK2 (mean: 15.5%, SD: 13.9%) estimates. Discrimination was not improved for ERS-RA (c-statistic=0.69), QRISK2 or EULAR multiplier applied to FRS-ATP and ACC/AHA (c-statistic=0.72 for all) compared to ACC/AHA and FRS-ATP (c-statistic=0.72 for both). The NRI for ERS-RA were low (-0.8% vs. ACC/AHA and 2.3% vs. FRS-ATP). The NRI for QRISK2 compared ACC/AHA was low (-2.4%). The NRI for QRISK2 compared to FRS-ATP was higher, but not significant (NRI: 25.0%, 95% CI: -9.4–34.7%). The EULAR multiplier only reclassified 6 patients above the 7.5% treatment threshold for the ACC/AHA calculator and 3 patients above the 20% treatment threshold for the FRS-ATP calculator, so the NRI was negligible. Conclusions The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population. Acknowledgement The ATACC-RA consortium: S Gabriel, C Crowson, E Matteson, G Kitas, K Douglas, A Sandoo, AG Semb, S Rollefstad, E Ikdahl, T Kvien, P Van Riel, E Arts, J Fransen, S Rantapaa-Dahlqvist, S Wallberg-Jonsson, L Innala, G Karpouzas, P Sfikakis, E Zampeli, P Dessein, L Tsang, MA Gonzalez-Gay, A Corrales, H El-Gabalawy, C Hitchon, V Pascual Ramos, I Contreras Yanez, M van de Laar, H Vonkeman, I Meek, E Husni, R Overman, I Colunga, D Galarza Disclosure of Interest None declared

Background Fatigue is a common problem in patients with rheumatoid arthritis (RA) which is highly endorsed by the RA patients. Flare represents an important aspect of RA disease experience with a crucial impact on patients9 well-being. The impact of RA flares on fatigue in patients with RA is not fully understood. Objectives We aimed to assess the association of RA flares, functional status, pain and well-being with fatigue perception in patients with RA using self-assessment questionnaires. Methods Patients with RA (age≥18 yrs; 1987 ACR criteria) participating in an ongoing population-based cohort study completed flare-assessment in RA (FLARE) questionnaire and Bristol Rheumatoid Arthritis Fatigue (BRAF) questionnaire, as well as Health Assessment Questionnaire (HAQ) with visual analogue scale for pain (VAS pain) on 100mm scale during a study visit (2012-2014), and submitted a blood sample for C-reactive protein (CRP) and interleukin-6 (IL6) assessment. Retrospective medical records review was performed to collect physician clinical assessment (PCA) and patient global assessment (PGA) of RA disease activity on 100mm scale for the most recent clinical visit prior to the study visit. Pearson9s correlation was used to examine relationships between the variables. Results The study included 190 RA patients (mean age 63 years; 75% female; mean RA duration 13.6 yrs). The mean (standard deviation; SD) of the overall FLARE score was 2.52 (2.55) on 0-10 scale; 1.86 (2.45) for systemic subscale; 3.32 (3.09) for joint subscale. The mean (SD) of the overall BRAF score was 12.72 (13.55) on 0-70 scale; the subscale scores were as follows: physical fatigue 3.65 (4.43), living with fatigue 3.66 (4.45); cognitive fatigue 3.18 (3.21) and emotional fatigue 2.25 (2.64). Mean (SD) CRP was 4.15 (5.8) mg/L; IL6 3.48 (5.52) pg/ml; HAQ 0.66 (0.66); VAS pain 28.8 (24.8). BRAF score overall and all subscales were statistically significantly correlated with FLARE, HAQ, VAS pain, PGA and PCA (except for cognitive fatigue subscale which was only marginally associated with PCA, p=0.08; see Table). There were no statistically significant associations of BRAF with CRP, IL6 or patient9s gender. Younger age was statistically significantly associated with higher BRAF score overall, and in particularly with cognitive fatigue, but not with other BRAF subscales. Shorter RA duration was significantly associated with higher “living with fatigue” BRAF score. Conclusions Flares of RA disease activity, as well as worsening functional status, pain, and overall well-being, but not inflammatory marker levels, are highly correlated with increased perception of fatigue. Our findings underscore the important role of RA flares in shaping the quality of life in patients with RA, and suggest an intricate relationship between self-perception of fatigue and flare, not reflected by inflammatory marker measures in patients with RA. Further studies are warranted to better understand the concept of RA flare and its impact on patient-reported outcomes. Disclosure of Interest None declared

The objectives of this study were to assess medication adherence rate and attrition rate in first-time adalimumab (ADA) or etanercept (ETA) users in rheumatoid arthritis (RA) patients. This study also identified the risk factors associated with nonadherence and treatment abandonment.This was a retrospective study with a 2-year follow-up. A total 2151 adult RA patients (18 years of age and older) who initiated ADA or ETA treatment in the Kaiser Permanente Southern California health plan between 2002 and 2009 were identified. Among those on treatment in the first year, continuous treatment receipt was determined by having at least 1 medication refill in the second year; otherwise treatment was considered as abandoned. Medication adherence was measured through proportion of days covered (PDC) and compared between patients continuously on treatment and those abandoning treatment. Risk factors of nonadherence (PDC80%) and treatment abandonment were estimated by a multinomial logistic regression model.Patients who abandoned treatment had significantly lower PDC (37.3%) and lower average number of refills (5.1) than adherers (PDC = 88.8%; average number of refills = 12.4) and nonadherers (PDC = 53.3%; average refills = 8.2). Age, African Americans (odds ratio [OR], 1.49; 95% CI, 1.03-2.17), corticosteroids use (OR, 0.80; 95% CI, 0.63-0.98), and history of physical/occupational therapy (OR = 0.66; 95% CI, 0.46-0.93) were associated with nonadherence, whereas having a comorbidity (OR, 1.24; 95% CI, 1.01-1.57) was associated with treatment abandonment. The difference in PDC between ADA and ETA was no longer statistically significant after excluding the treatment abandonment group. A higher proportion of ADA users abandoned treatment than ETA users (42.9% vs 32.2%).Taking into account treatment abandonment when measuring medication adherence in ADA and ETA use in RA patients can provide a fair and clinically meaningful view of patients' medication-taking behavior.