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Abstract Background The cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) is comparable to that of patients with diabetes mellitus (DM). Although several studies have indicated high prevalence's of DM in RA patients, little is known about how this affects their CVD risk. Objectives To examine indications for, and use of antihypertensive treatment (a-HT) and lipid-lowering therapy (LLT) in RA patients with DM (RA-DM) and RA patients without DM (RAwoDM). Further, to compare the prevalence of various types of CVD across RA-DM and RAwoDM. Methods The cohort was derived from the SUrvey of cardiovascular disease Risk Factor in patients with Rheumatoid Arthritis (SURF-RA), which was performed in 53 centres/17 countries in 5 world regions (West and East Europe; North and Latin America; and Asia) from 2014 - 2019. Indication for a-HT was defined as: 1) systolic/diastolic blood pressure (BP) ≥140/90 mm Hg, 2) self-reported hypertension, and/or 3) current use of a-HT. Indication for LLT was defined according to ESC guidelines. CVD risk estimates (by SCORE) were multiplied by 1.5 according to EULAR recommendations. Target treatment targets for BP and lipids were defined according to ESC guidelines applicable at the time data were recorded. Results Presence of comorbid DM was available in 10 602 (73.1%) of the 14 503 RA patients included in SURF-RA, of whom 75 and 1262 patients reported DM type 1 and type 2, respectively (total 1337 patients, 12.6%). Although less often current smokers, RA-DM patients were more often previous smokers, male sex and had higher body mass index compared to RAwoDM (p<0.0001 for all). a-HT (84.7% vs 62.3%) and LLT (100% vs 47.2%) were more frequently indicated in RA-DM than in RAwoDM patients (p<0.0001 for both). RA-DM were more likely than RAwoDM to receive a-HT on indication (60.4% vs 57.6%, p<0.0001), while the difference in LLT use on indication was not significantly different (45.7% vs 42.5%, p=0.06). Moreover, RA-DM compared to RAwoDM patients had more often reached treatment goals when on a-HT (60.7% vs 54.1%, p<0.0001) and LLT (62.8% vs 48.9%, p<0.0001). Finally, the risk of all recorded established CVD (coronary heart disease, stroke, peripheral artery disease and atrial fibrillation) was increased by a factor of 2 to 3 in RA-DM compared to RAwoDM (Figure). Conclusion The effect of RA and comorbid DM on CVD risk appears to be additive. While CVD preventive medications are more often indicated in RA-DM than in RAwoDM patients, they are also more likely to receive such therapy and to reach CVD preventive treatment goals. The latter finding may be due to more developed CVD preventive care in DM compared to RA patients. Improved CVD preventive systems for patients with RA are warranted. CVD in RA patients with and without DM Funding Acknowledgement Type of funding source: Other. Main funding source(s): Lilly

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

Objective The link and interplay between different airway exposures and rheumatoid arthritis (RA) risk are unclear. This study was undertaken to determine whether respiratory disease is associated with development of RA, and specifically to examine this relationship by RA serostatus and smoking exposure. Methods Using data from the Epidemiological Investigation of Rheumatoid Arthritis study, this analysis included 1,631 incident RA cases and 3,283 matched controls recruited from 2006 to 2016. Linking these individuals to the National Patient Register provided information on past acute or chronic, upper or lower respiratory disease diagnoses. For each disease group, we estimated adjusted odds ratios (OR adj ) with 95% confidence intervals (95% CI) for RA, using logistic regression models adjusted for age, sex, residential area, body mass index, and education both overall and stratified by anti–citrullinated protein antibody (ACPA)/rheumatoid factor (RF) status and by smoking status. Results Respiratory disease diagnoses were associated with risk of RA, with an OR adj of 1.2 for acute upper respiratory disease (95% CI 0.8–1.7), 1.4 for chronic upper respiratory disease (95% CI 1.1–1.9), 2.4 for acute lower respiratory disease (95% CI 1.5–3.6), and 1.6 for chronic lower respiratory disease (95% CI 1.5–3.6). These associations were present irrespective of RF or ACPA status, though the association was somewhat stronger for ACPA/RF–positive than ACPA/RF–negative RA. The association between any respiratory disease and RA was stronger for nonsmokers (OR adj 2.1 [95% CI 1.5–2.9]) than for smokers (OR adj 1.2 [95% CI 0.9–1.5]). Conclusion Respiratory diseases increase the risk for both seropositive and seronegative RA, but only among nonsmokers. These findings raise the hypothesis that smoking and airway disease are associated with RA development through partly different mechanisms.

ObjectiveGiant cell arteritis (GCA) is a large‐vessel vasculitis that primarily affects the aorta and its branches. Extracranial branches of the carotid artery are frequently affected; however, intracranial involvement in GCA is rare.MethodsA retrospective medical record review was performed to identify all patients with intracranial GCA (IC‐GCA) from January 1996 through May 2018.ResultsNine patients with IC‐GCA were included (78% male; mean age, 72.1 years [SD: 7.9]). All patients met ACR criteria for GCA. The median time from onset of GCA to intracranial involvement was 0.6 months (interquartile range: 0.1‐5.1). All patients had neurologic symptoms, 89% had an ischemic cerebrovascular event. Transient or permanent vision loss was frequent (56% of patients). IC‐GCA was diagnosed by cranial imaging in all nine patients. Intracranial vasculitis most commonly affected the internal carotid artery (100%), followed by the vertebral artery (67%), posterior cerebral artery (67%), middle cerebral artery (44%), anterior cerebral artery (33%), and posterior inferior cerebral artery (11%). Intracranial vessel stenosis was present in 89%, occlusion in 33%, wall thickening in 33%, and dilation in 11%.All patients received glucocorticoids. Additional therapeutic agents included cyclophosphamide (67%) and tocilizumab (22%). Despite treatment, five patients had rapid deterioration and mortality. Comparing IC‐GCA patient survival to the expected rates from the US population, the standardized mortality ratio (95% CI) for IC‐GCA was 58.1 (18.9‐135.6).ConclusionAlthough rare, IC‐GCA is associated with significant morbidity and mortality. It occurs predominantly in men and presents with ischemic cerebrovascular events. Current treatment strategies appear to be of limited efficacy for IC‐GCA.

ObjectivePublished predictive models of disease outcomes in idiopathic inflammatory myopathies (IIMs) are sparse and of limited accuracy due to disease heterogeneity. Computational methods may address this heterogeneity by partitioning patients based on clinical and biological phenotype.MethodsTo identify new patient groups, we applied similarity network fusion (SNF) to clinical and biological data from 168 patients with myositis (64 adult polymyositis [PM], 65 adult dermatomyositis [DM], and 39 juvenile DM [JDM]) in the Rituximab in Myositis trial. We generated a sparse proof‐of‐concept bedside classifier using multinomial regression and identified characteristics that distinguished these groups. We conducted χ2 tests to link new patient groups with the myositis subtypes.ResultsSNF identified five patient groups in the discovery cohort that subdivided the myositis subtypes. The sparse multinomial regressor to predict patient group assignments (areas under the receiver operating characteristic curve = [0.78, 0.97]; areas under the precision‐recall curve = [0.55, 0.96]) found that autoantibody enrichment defined four of these groups: anti–Mi‐2, anti–signal recognition peptide (SRP), anti–nuclear matrix protein 2 (NXP2), and anti‐synthetase (Syn). Depletion of immunoglobulin M (IgM) defined the fifth group. Each group was associated with one subtype, with adult DM being associated with anti–Mi‐2 and anti‐Syn autoantibodies, JDM being associated with anti‐NXP2 autoantibodies, and adult PM being associated with IgM depletion and anti‐SRP autoantibodies. These associations enabled us to further resolve the current myositis subtypes.ConclusionUsing unsupervised machine learning, we identified clinically and biologically homogeneous groups of patients with IIMs, forming the basis of an integrated disease classification based on both clinical and biological phenotype, thus validating other approaches and what has been previously described.

Abstract Objective The study sought to determine the dependence of the Electronic Medical Records and Genomics (eMERGE) rheumatoid arthritis (RA) algorithm on both RA and electronic health record (EHR) duration. Materials and Methods Using a population-based cohort from the Mayo Clinic Biobank, we identified 497 patients with at least 1 RA diagnosis code. RA case status was manually determined using validated criteria for RA. RA duration was defined as time from first RA code to the index date of biobank enrollment. To simulate EHR duration, various years of EHR lookback were applied, starting at the index date and going backward. Model performance was determined by sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC). Results The eMERGE algorithm performed well in this cohort, with overall sensitivity 53%, specificity 99%, positive predictive value 97%, negative predictive value 74%, and AUC 76%. Among patients with RA duration <2 years, sensitivity and AUC were only 9% and 54%, respectively, but increased to 71% and 85% among patients with RA duration >10 years. Longer EHR lookback also improved model performance up to a threshold of 10 years, in which sensitivity reached 52% and AUC 75%. However, optimal EHR lookback varied by RA duration; an EHR lookback of 3 years was best able to identify recently diagnosed RA cases. Conclusions eMERGE algorithm performance improves with longer RA duration as well as EHR duration up to 10 years, though shorter EHR lookback can improve identification of recently diagnosed RA cases.