Search

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.

Objective To examine trends in glucocorticoid (GC) use and dosing among patients diagnosed with rheumatoid arthritis (RA) over time. Methods A population-based inception cohort of RA patients diagnosed during 1980–2007 was followed longitudinally through their medical records until death, migration, or December 31, 2008. GC start and stop dates were collected, along with doses in prednisone equivalents. Results The study population comprised 349 patients (68% women) diagnosed in 1980–1994 and 464 (69% women) diagnosed in 1995–2007, with a median followup of 15.3 and 5.7 years, respectively. A higher proportion of patients started GCs in their first year of disease in 1995–2007 (68% versus 36%; P < 0.001), but the starting dose (mean 8.7 versus 10.3 mg; P = 0.08) and cumulative dose in the first year of use (mean 1.8g [mean daily dose 4.9 mg] versus 2.1 gm [mean daily dose 5.8 mg]; P = 0.48) were not different. A higher proportion also discontinued GCs in their first year of disease in the 1995–2007 cohort (P < 0.001). These differences in GC initiation and discontinuation persisted throughout followup. Prevalence of GC use was higher in the 1995–2007 cohort for the first 3 years of disease. Conclusion More patients are starting GCs early in their disease course now compared to previously, which is consistent with established treatment guidelines. A higher proportion are also discontinuing GCs, but the proportion of patients taking GCs at any given point of disease during the first 4 years is higher now than previously. Despite early addition of a disease-modifying antirheumatic drug, some patients may not be able to discontinue GCs over the long term.

Rheumatic diseases are associated with an increased risk of cardiovascular (CV) mortality attributed to a higher incidence of heart failure (HF) and ischemic heart disease. Although traditional CV risk factors contribute to the increased incidence seen in this population, by themselves they do not account for the increased risk; in fact, obesity and hyperlipidemia may play a paradoxic role. Immune-mediated mechanisms and chronic inflammation likely play a role in the pathogenesis of CV disease in patients with rheumatic diseases. The usual clinical features of ischemic heart disease and HF are less likely to be seen in this patient population.

Rheumatoid arthritis (RA) is associated with a variety of kidney disorders. However, it is unclear whether the development of reduced kidney function is higher in patients with RA compared to the general population.Retrospective review.Incident adult-onset RA cases (813) and a comparison cohort of non-RA individuals (813) in Olmsted County, MN, in 1980-2007.Baseline demographic and clinical variables.Reduced kidney function: (1) estimated glomerular filtration rate (eGFR)60mL/min/1.73m(2) and (2) eGFR45mL/min/1.73m(2) on 2 consecutive occasions at least 90 days apart; cardiovascular disease (CVD); and death.The cumulative incidence of reduced kidney function was estimated adjusting for the competing risk of death.Of 813 patients with RA and 813 non-RA individuals, mean age was 56±16 (SD) years, 68% were women, and 9% had reduced kidney function at baseline. The 20-year cumulative incidence of reduced kidney function was higher in patients with RA compared with non-RA participants for eGFR 60mL/min/1.73m(2) (25% vs 20%; P=0.03), but not eGFR45mL/min/1.73m(2) (9% vs 10%; P=0.8). The presence of CVD at baseline (HR, 1.77; 95% CI, 1.14-2.73; P=0.01) and elevated erythrocyte sedimentation rate in patients with RA (HR per 10-mm/h increase, 1.08; 95% CI, 1.00-1.16; P=0.04) was associated with increased risk of eGFR60mL/min/1.73m(2). eGFR60mL/min/1.73m(2) was not associated with increased risk of CVD development in patients with RA (HR, 0.99; 95% CI, 0.63-1.57; P=0.9), however, a greater reduction in GFR (eGFR45mL/min/1.73m(2)) was associated with increased risk of CVD (HR, 1.93; CI, 1.04-3.58; P=0.04).Reduced kidney function was defined by estimating equations for kidney function. We are limited to deriving associations from our findings.Patients with RA were more likely to develop reduced kidney function over time. CVD and associated factors appear to play a role. The presence of RA in individuals with reduced kidney function may lead to an increase in morbidity from CVD development, for which awareness may provide a means for optimizing care.

Objective.To assess the occurrence, risk factors, morbidity, and mortality associated with lower extremity (LE) ulcers in patients with rheumatoid arthritis (RA).Methods.Retrospective review of Olmsted County, Minnesota, USA, residents who first fulfilled the 1987 American College of Rheumatology criteria for RA in 1980–2007 with followup to death, migration, or April 2012. Only LE ulcers that developed after the diagnosis of RA were included.Results.The study included 813 patients with 9771 total person-years of followup. Of them, 125 developed LE ulcers (total of 171 episodes), corresponding to a rate of occurrence of 1.8 episodes per 100 person-years (95% CI: 1.5, 2.0 per 100 person-yrs). The cumulative incidence of first LE ulcers was 4.8% at 5 years after diagnosis of RA and increased to 26.2% by 25 years. Median time for the LE ulcer to heal was 30 days. Ten of 171 episodes (6%) led to amputation. LE ulcers in RA were associated with increased mortality (HR 2.42; 95% CI 1.71, 3.42), adjusted for age, sex, and calendar year. Risk factors for LE ulcers included age (HR 1.73 per 10-yr increase; 95% CI 1.47, 2.04), rheumatoid factor positivity (HR 1.63; 95% CI 1.05, 2.53), presence of rheumatoid nodules (HR 2.14; 95% CI 1.39, 3.31), and venous thromboembolism (HR 2.16; 95% CI 1.07, 4.36).Conclusion.LE ulcers are common among patients with RA. The cumulative incidence increased by 1% per year. A significant number require amputation. Patients with RA who have LE ulcers are at a 2-fold risk for premature mortality.

Objective.Older women and men with rheumatoid arthritis (RA) are at increased risk for fractures, but limited information is available on fracture risk in younger individuals with RA and whether such risk occurs early in the disease onset or only when older. We determined the risk for fractures in both young and older women and men following RA diagnosis.Methods.We studied a population-based inception cohort with RA from Olmsted County, Minnesota, USA. We identified 822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110 men diagnosed before age 50) and an equal number of paired non-RA subjects, matched by sex and birth year. Incident fractures were collected through review of complete (inpatient and outpatient) medical records available through the linkage system of the Rochester Epidemiology Project.Results.The hazard ratio (HR; 95% CI) for a non-pathologic fracture occurring from no more than moderate trauma was 1.63 (1.36–1.96) for women and 1.40 (1.02–1.93) for men with RA. Findings were consistent for women and men diagnosed with RA at age ≥ 50 years [HR, 1.43 (1.16–1.77) and 1.34 (0.92–1.94), respectively], or at age < 50 years [HR, 2.34 (1.61–3.42) and 1.74 (0.91–3.30), respectively]. However, young women, but not young men, with RA were at increased fracture risk even before age 50 years (HR, 1.95 [1.08–3.51] and 0.82 [0.28–2.45], respectively).Conclusion.Young men with RA are at increased risk for fractures only when older, whereas young women with RA have an elevated fracture risk even while still young.

Objective Pulmonary disease represents an important extraarticular manifestation of rheumatoid arthritis (RA). While the association of RA and interstitial lung disease is widely acknowledged, obstructive lung disease (OLD) in RA is less well understood. We therefore aimed to assess the incidence, risk factors, and mortality of OLD in patients with RA. Methods We examined a population-based incident cohort of patients with RA and a comparison cohort of individuals without RA. OLD was defined using a strict composite criterion. Cox proportional hazards models were used to compare OLD incidence between the RA and comparator cohorts to investigate risk factors and to explore the impact of OLD on patient survival. Results A total of 594 patients with RA and 596 subjects without RA were followed for a mean of 16.3 and 19.4 years, respectively. The lifetime risk of developing OLD was 9.6% for RA patients and 6.2% for subjects without RA (hazard ratio [HR] 1.54, 95% confidence interval [95% CI] 1.01–2.34). The risk of developing OLD was higher among male patients, among current or former smokers, and for individuals with more severe RA. Survival of RA patients diagnosed with OLD was worse compared to those without OLD (HR 2.09, 95% CI 1.47–2.97). Conclusion Patients with RA are at higher risk of developing OLD, which is significantly associated with premature mortality. Effective diagnostic and therapeutic strategies to detect and manage OLD in patients with RA may help to improve survival in these patients.

Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD), although strategies to detect subclinical CVD are poorly characterised. The purpose of this study was to assess myocardial function by speckle-tracking echocardiography strain imaging in patients with RA without known CVD.Eighty-seven patients with RA selected from a population-based sample underwent echocardiography. Left ventricular (LV) and right ventricular (RV) longitudinal peak systolic strain were measured. A subset of 59 patients with RA was compared with 59 age-, gender- and race-matched subjects with normal echocardiography and no CVD or risk factors.The mean ± SD age of the patients with RA and the normal patients was 55.7±12.1 and 54.5±12.2 years (p=0.42), respectively, with 45 (76%) women in each group. Global LV strain (-15.7±3.2% vs -18.1±2.4%, p0.001) and RV strain (-17.9±4.7% vs -20.7±2.4%, p0.001) was reduced in patients with RA compared with normal patients. Among all 87 patients with RA the mean disease duration and C-reactive protein at echocardiography were 10.0±6.1 years and 3.5±3.7 mg/L, and 74% were seropositive. Adjusted univariate regression analysis demonstrated a significant correlation between global LV strain and RA Health Assessment Questionnaire disability index (p=0.032), and borderline associations with prior use of oral corticosteroids (p=0.062) and methotrexate (p=0.054) after adjustment for age, gender, blood pressure, body mass index, heart rate and LV mass index.Global longitudinal LV and RV strain is reduced in patients with RA compared with healthy patients. Strain abnormalities correlate with RA disease severity. Strain imaging by echocardiography may detect early myocardial dysfunction in RA.

Objective To study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) and no history of heart failure compared with that in subjects with neither RA nor a history of heart failure, and to determine the impact of RA on LV remodeling. Methods A cross-sectional, community-based study was conducted among adult (age ≥50 years) patients with RA and age- and sex-matched subjects with neither RA nor a history of heart failure. All participants underwent standard 2-dimensional Doppler echocardiography. LV geometry was classified into the following 4 categories based on relative wall thickness and sex-specific cutoffs for the LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry. Results Among 200 patients with RA and 600 age- and sex-matched subjects without RA, the mean age was 65 years, and 74% of the individuals in both cohorts were female. Compared with subjects without RA, patients with RA were significantly more likely to have abnormal LV geometry (odds ratio [OR] 1.44, 95% confidence interval [95% CI] 1.03–2.00), even after adjusting for cardiovascular risk factors and comorbidities. Among subjects with abnormal LV geometry, the odds of concentric LV remodeling were significantly increased in patients with RA (OR 4.73, 95% CI 2.85–7.83). In linear regression analyses, the LV mass index appeared to be lower in patients with RA who were currently receiving corticosteroids (β ± SE −0.082 ± 0.027, P = 0.002), even after adjusting for cardiovascular risk factors and comorbidities. Conclusion RA was strongly associated with abnormal LV remodeling (particularly concentric LV remodeling) among RA patients without heart failure. This association remained significant after adjustment for cardiovascular risk factors and comorbidities. RA disease–related factors may promote changes in LV geometry. The biologic mechanisms underlying LV remodeling warrant further investigation.

Herpes zoster or shingles is a common cutaneous disorder caused by the reactivation of latent varicella-zoster virus dormant in the cranial nerve or dorsal root ganglia. It usually manifests as a dermatomal distribution of a vesicular eruption that can cause significant morbidity (1). Herpes zoster is known to be more frequent in patients with conditions that depress cell-mediated immunity, including malignancy, HIV, transplantation, immunosuppressive disorders and treatment with immunosuppressants (2). The overall rate of herpes zoster in patients with rheumatoid arthritis (RA) is increased compared to the general population, with a greater risk in individuals using traditional disease modifying antirheumatic drugs (DMARDs) or biologic therapies (3). Use of prednisone in RA is an important predisposing factor for herpes zoster, and its use in conjunction with DMARDs increases the risk beyond that seen with the DMARDs alone (4). Many unanswered questions remain regarding the relationship between RA and reactivation of herpes zoster, and how RA related disease features, treatment and herpes zoster prevention measures might be addressed to avoid recurrent and complicated herpes zoster in these patients. We performed a population-based study to assess the incidence, time trends, risk factors and severity of herpes zoster in a well defined population of patients with RA. This information should serve the eventual goal of identifying possible strategies that could be employed to minimize the risk of development of herpes zoster 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.

Objective Obesity is an underrecognized risk factor for rheumatoid arthritis (RA). In recent years, both the prevalence of obesity and the incidence of RA have been rising. Our objective was to determine whether the “obesity epidemic” could explain the recent rise in the incidence of RA. Methods An inception cohort of Olmsted County, Minnesota residents who fulfilled the 1987 American College of Rheumatology criteria for RA in 1980–2007 was compared to population-based controls (matched on age, sex, and calendar year). Heights, weights, and smoking statuses were collected from medical records. Obesity was defined as a body mass index ≥30 kg/m2. Conditional logistic regression was used to assess the influence of obesity on developing RA. Population attributable risk was used to estimate the incidence of RA in the absence of obesity. Results The study included 813 patients with RA and 813 controls. Both groups had extensive medical history available prior to the incidence/index date (mean 32.2 years), and ∼30% of each group was obese at the incidence/index date. The history of obesity was significantly associated with developing RA (odds ratio 1.24, 95% confidence interval 1.01–1.53; adjusted for smoking status). In 1985–2007, the incidence of RA rose by an increment of 9.2 per 100,000 among women. Obesity accounted for 4.8 per 100,000 (52%) of this increase. Conclusion Obesity is associated with a modest risk for developing RA. Given the rapidly increasing prevalence of obesity, this has had a significant impact on RA incidence and may account for much of the recent increase in the incidence of RA.

International audience; BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52*8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24*9% of deaths worldwide in 2010, down from 15*9 million (34*1%) of 46*5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2*5 to 1*4 million), lower respiratory infections (from 3*4 to 2*8 million), neonatal disorders (from 3*1 to 2*2 million), measles (from 0*63 to 0*13 million), and tetanus (from 0*27 to 0*06 million). Deaths from HIV/AIDS increased from 0*30 million in 1990 to 1*5 million in 2010, reaching a peak of 1*7 million in 2006. Malaria mortality also rose by an estimated 19*9% since 1990 to 1*17 million deaths in 2010. Tuberculosis killed 1*2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34*5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1*5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12*9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1*3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5*1 million deaths) was marginally higher in 2010 (9*6%) compared with two decades earlier (8*8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1*3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

The Methodology Committee of the Patient Centered Outcomes Research Institute (PCORI) has released for public comment the draft of its first report recommending standards for the conduct of research leading to evidence-based, patient-centered health interventions.

Patients with rheumatoid arthritis (RA) have an excess burden of cardiovascular (CV) disease (CVD). CV risk scores for the general population may not accurately predict CV risk for patients with RA. A population-based inception cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA from 1988 to 2007 was followed until death, migration, or December 31, 2008. CV risk factors and CVD (myocardial infarction, CV death, angina, stroke, intermittent claudication, and heart failure) were ascertained by medical record review. Ten-year predicted CVD risk was calculated using the general Framingham and the Reynolds risk scores. Standardized incidence ratios were calculated to compare observed and predicted CVD risks. The study included 525 patients with RA aged ≥30 years without previous CVD. The mean follow-up period was 8.4 years, during which 84 patients developed CVD. The observed CVD risk was 2-fold higher than the Framingham risk score predicted in women and 65% higher in men, and the Reynolds risk score revealed similar deficits. Patients aged ≥75 years had observed CVD risk >3 times the Framingham-predicted risk. Patients with positive rheumatoid factor or persistently elevated erythrocyte sedimentation rates also experienced more CVD events than predicted. In conclusion, the Framingham and Reynolds risk scores substantially underestimated CVD risk in patients with RA of both genders, especially in older ages and in patients with positive rheumatoid factor. These data underscore the need for more accurate tools to predict CVD risk in patients with RA.

To highlight recent evidence regarding the contribution of traditional and nontraditional [e.g. inflammatory markers, rheumatoid arthritis (RA) features] risk factors toward the excess cardiovascular risk in RA.The impact of traditional risk factors on the development of cardiovascular disease in persons with RA is an area of active research. Some are more prevalent among people with RA (e.g. smoking); others appear to have paradoxical relationships (e.g. body mass index), and findings remain inconsistent with others (e.g. dyslipidemia). Collectively the data suggest that cardiovascular risk factors behave differently in RA. Thus, risk scores developed for the general population based on traditional cardiovascular risk factors alone are unlikely to accurately estimate cardiovascular risk in RA, highlighting the need for RA-specific risk prediction tools.Nontraditional risk factors, in particular RA disease activity/severity measures, including inflammatory markers, disease activity scores, seropositivity, physical disability, destructive changes on joint radiographs, extra-articular manifestations, and corticosteroid use, have repeatedly shown significant associations with increased cardiovascular risk. Medications used to treat RA may also affect cardiovascular risk. A recent meta-analysis suggests that all nonsteroidal anti-inflammatory drugs confer some cardiovascular risk. The cardiovascular risks/benefits associated with use of disease-modifying antirheumatic drugs and/or biologics remain controversial, as does the role of statins in RA.Cardiovascular disease remains a major problem for people with RA. Future work should focus on further delineating the underlying biological mechanisms involved, developing and evaluating risk assessment tools and biomarkers, as well as prevention/treatment strategies specific to the RA population.

Objective.To determine the frequency of hypothyroidism in patients with rheumatoid arthritis (RA), and to elucidate the association of hypothyroidism and development of cardiovascular disease (CVD) in these patients.Methods.A retrospective medical record review was performed using all incident cases of adult-onset RA from Olmsted County, MN, USA, that fulfilled criteria for RA in the years 1988–2007. Patients with and without thyroid disease were followed longitudinally for the development of CVD.Results.A cohort of 650 patients with RA and an age and sex-matched comparison cohort of 650 patients without RA was assembled (both cohorts mean age 55.8 yrs; 69% were women). There was no significant difference between cohorts in the presence of hypothyroid disease or subclinical hypothyroidism at time of RA diagnosis. No significant difference was found in the cumulative incidence of hypothyroid disease between the 2 cohorts. Hypothyroid disease was found to be significantly associated with CVD in patients with RA (hazard ratio 2.0; 95% CI 1.1, 3.6). This difference remained significant and unchanged after adjustment for traditional CV risk factors (HR 2.0; 95% CI 1.1, 3.6).Conclusion.No significant difference was found in either incidence or prevalence of hypothyroidism between patients with and those without RA. Hypothyroid disease was significantly associated with CVD in patients with RA, even after adjustment for other traditional CV risk factors.

Patients with rheumatoid arthritis (RA) have an increased incidence of cardiovascular disease (CVD) compared to the general population (1, 2). Patients with RA also have increased premature mortality, some of which is due to this increased risk of CVD (3). Like CVD, noncardiac vascular disease may be a manifestation of systemic involvement in RA, and may have important impact on the health of patients with RA. While there is a considerable body of literature regarding the risk of heart disease as a component of the overall CVD risk burden in patients with RA, there is very little known about the incidence, risk, and outcome of noncardiac vascular disease among these patients. The primary focus of interest in vascular disease in the study of patients with RA has been on coronary artery disease, but it is likely that the entire vasculature is affected. Less well studied is noncardiac vascular disease in RA, including venous thromboembolism (VTE) (4–7), transient ischemic attack (8, 9), stroke (10–13), aortic aneurysm (14), arterial thromboembolism (6), and peripheral artery disease (15–17). Little is known regarding the potential risk factors for noncardiac vascular disease and what influence the traditional cardiovascular risk factors of previous myocardial infarction, obesity, diabetes, hypertension, and smoking have on development of these events in patients with RA. The contribution of these risk factors has been examined in relation to ischemic stroke (11), but as yet no study has addressed these risk factors in relation to other noncardiac vascular diseases. There are some data regarding the effect of RA therapies on ischemic stroke in patients with RA (11, 18), but there is little information about how medications used to treat RA might influence the incidence of other noncardiac vascular diseases (6). The purpose of this study was to investigate the incidence of noncardiac vascular disease events in a community-based incidence cohort of patients with RA and to compare this incidence to that in the general population in the same community. Among patients with RA, the incidence of noncardiac vascular disease events was also compared to that found in an earlier decade in a previous study by our group (10). In addition, we examined risk factors that may be associated with development of these events in patients with RA.

OBJECTIVE To investigate the association between 347 single-nucleotide polymorphisms within candidate genes of the tumor necrosis factor, interleukin 1 and interleukin 6 families with neutrophil count. PATIENTS AND METHODS Four hundred cases with heart failure after myocardial infarction (MI) were matched by age, sex, and date of incident MI to 694 controls (MI without post-MI heart failure). Both genotypes and neutrophil count at admission for incident MI were available in 314 cases and 515 controls. RESULTS We found significant associations between the TNFSF8 polymorphisms rs927374 ( P =5.1 × 10 5 ) and rs2295800 ( P =1.3 × 10 −4 ) and neutrophil count; these single-nucleotide polymorphisms are in high linkage disequilibrium ( r 2 =0.97). Associations persisted after controlling for clinical characteristics and were unchanged after adjusting for case-control status. For rs927374, the neutrophil count of GG homozygotes (7.6±5.1) was 16% lower than that of CC homozygotes (9.0±5.2). CONCLUSION The TNFSF8 polymorphisms rs927374 and rs2295800 were associated with neutrophil count. This finding suggests that post-MI inflammatory response is genetically modulated.

Objective Understanding of the personal risks for rheumatoid arthritis (RA) and other rheumatic diseases remains poor, despite advances in knowledge with regard to their pathogenesis, therapeutics, and clinical impact, in part because the personal lifetime risk of developing these diseases is unknown. This study was undertaken to estimate the lifetime risk of RA, as well as other inflammatory autoimmune rheumatic diseases, including systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica (PMR), giant cell arteritis, ankylosing spondylitis, and Sjogren's syndrome, and to provide an overall estimate of the risk of developing inflammatory autoimmune rheumatic disease over a lifetime. Methods Using the incidence rates obtained from our population-based studies of rheumatic diseases among residents of Olmsted County, Minnesota, and mortality rates from life tables for the general population, we estimated the sex-specific lifetime risk of rheumatic disease. Results The lifetime risk of RA developing in US adults was 3.6% for women and 1.7% for men, and the lifetime risk of rheumatoid factor-positive RA was 2.4% for women and 1.1% for men. The second most common inflammatory autoimmune rheumatic disease was PMR, with a lifetime risk of 2.4% for women and 1.7% for men. The overall lifetime risk of inflammatory autoimmune rheumatic disease was 8.4% for women and 5.1% for men. Conclusion One in 12 women and 1 in 20 men will develop an inflammatory autoimmune rheumatic disease during their lifetime. These results can serve as useful guides in counseling patients regarding their lifetime risk of these conditions and have important implications regarding disease awareness campaigns.

ObjectiveTo examine the impact of systemic inflammation and serum lipids on cardiovascular disease (CVD) in rheumatoid arthritis (RA).MethodsIn a population-based RA incident cohort (1987 American College of Rheumatology criteria first met between 1988 and 2007), details were collected of serum lipid measures, erythrocyte sedimentation rates (ESRs), C-reactive protein (CRP) measures and cardiovascular events, including ischaemic heart disease and heart failure. Cox models were used to examine the association of lipids and inflammation with the risk of CVD and mortality, adjusting for age, sex and year of RA incidence.ResultsThe study included 651 patients with RA (mean age 55.8 years, 69% female); 67% were rheumatoid factor positive. ESR was associated with the risk of CVD (HR=1.2 per 10 mm/h increase, 95% CI 1.1 to 1.3). Similar findings, although not statistically significant, were seen with CRP (p=0.07). A significant non-linear association for total cholesterol (TCh) with risk of CVD was found, with 3.3-fold increased risk for TCh ConclusionInflammatory measures (particularly, ESR) are significantly associated with the risk of CVD in RA. Lipids may have paradoxical associations with the risk of CVD in RA, whereby lower TCh and LDL levels are associated with increased cardiovascular risk.

Rheumatoid arthritis is associated with an excess risk of cardiovascular disease, but current cardiovascular risk models might not be adequate to fully predict individual risk in a patient with this disease. Does the solution lie in closer collaboration between rheumatologists and cardiologists?

Objective To conduct a systematic review to identify and describe the scope and nature of the research evidence on the effectiveness of interventions to improve health care quality or reduce disparities in the care of disadvantaged populations with osteoarthritis (OA) as an example of a common chronic disease. Methods We searched electronic databases from 1950 through February 2010 and grey literature for relevant articles using any study design. Studies with interventions designed explicitly to improve health care quality or reduce disparities in the care of disadvantaged adult populations with OA and including an evaluation were eligible. We used the PROGRESS-Plus framework to identify disadvantaged population subgroups. Results Of 4,701 citations identified, 10 met the inclusion criteria. Eight were community based and 6 targeted race/ethnicity/culture. All 10 studies evaluated interventions aimed at people with OA; 2 studies also targeted the health care system. No studies targeted health care providers. Nine of 10 studies evaluated arthritis self-management interventions; all showed some benefit. Only 1 study compared the difference in effect between the PROGRESS-Plus disadvantaged population and the relevant comparator group. Conclusion There are few studies evaluating the effectiveness of interventions to improve health care quality in disadvantaged populations with OA. Further research is needed to evaluate interventions aimed at health care providers and the health care system, as well as other patient-level interventions. Gap intervention research is also needed to evaluate whether interventions are effective in reducing documented health care inequities.

The systemic vasculitides are multisystem disorders characterised by the inflammation of blood vessels and tissue necrosis. Classified by the size of the vessels affected, the large vessel vasculitides include giant cell arteritis (GCA) and Takayasu's arteritis (TA). These are anatomically, epidemiologically and clinically distinct conditions. They are often associated with considerable morbidity and mortality. The classification of vasculitis has been an area of controversy for many years and current classification criteria remain suboptimal. Although intensive efforts are under way to improve them, a further understanding of the aetiology and pathogenesis of these diseases is required to develop more sensitive and specific diagnostic tests. These efforts, however, have been hampered by the low prevalence of these diseases. The establishment of national and international registries is encouraged to enhance valuable data collection. These are anatomically, epidemiologically and clinically distinct conditions. This article summarises the current classification systems for systemic vasculitis and their limitations. We also review the presently known epidemiology, risk factors and morbidity and mortality associated with GCA and TA.