Citations

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.

Aim The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention. Methods The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014–2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM. Results The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM. Conclusion CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA .

Abstract Aims To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). Methods and results The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014–19. The treatment goal for BP was &lt;140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination. Conclusion We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

ObjectivePayments from the pharmaceutical industry to practicing physicians may influence prescribing behavior. This study was undertaken to investigate the nature, quantity, and geographic distribution of payments to US rheumatologists.MethodsGeneral payments from industry sponsors to US rheumatologists from 2014 to 2019 were extracted from the Centers for Medicare and Medicaid Services Open Payments database. Gender was identified by linking physicians to the National Plan and Provider Enumeration System registry. Data were reported in aggregate, trends over time were assessed using linear regression models, and differences by gender were analyzed using the Wilcoxon rank sum test.ResultsOver the 6‐year time period from 2014 to 2019, a total of 1,610,668 payments totaling $221,254,966 were made to 5,723 rheumatologists. The median payment was $15 (interquartile range [IQR] $10 to $22), and the median total amount received by individual rheumatologists over the 6‐year period was $2,818 (IQR $464 to $11,560). The majority of rheumatologists (3,416 of 5,723 [60%]) received less than $5,000, but 368 of 5,723 (6%) received more than $100,000 each and accounted for 78% of the total. The yearly value of payments increased over time ($3,703,264 per year; P < 0.001), and the median payment to male rheumatologists was significantly higher than the median payment to female rheumatologists ($3,723 [IQR $542 to $15,841] versus $2,084 [IQR $394 to $8,186]; P < 0.001).ConclusionThe value of industry payments has increased over time, and a large amount is concentrated among a small number of rheumatologists. Future studies should investigate the degree to which industry payments have influenced prescribing in the field of rheumatology.

Background/Purpose: To update the epidemiology of systemic sclerosis and evaluate the performance of the American College of Rheumatology/European League Against Rheumatism 2013 versus 1980 American Rheumatism Association classification criteria in a US population-based cohort. Methods: An inception cohort of patients with incident systemic sclerosis from 1 January 1980 through 31 December 2018, in Olmsted County, Minnesota, was identified based on comprehensive individual medical record review. Incidence and prevalence rates were age- and sex-adjusted to the 2010 US white population. Survival rates were compared with expected rates in the general population. Fulfillment of 1980 and 2013 classification criteria was ascertained. Results: A total of 85 incident cases of systemic sclerosis (91% female, mean age = 55.4 ± 16 years) and 49 prevalent cases on 1 January 2015 were identified. The overall age- and sex-adjusted annual incidence was 25 (95% confidence interval = 20–31) per million population, with no change in incidence over time. The age- and sex-adjusted prevalence was 436 (95% confidence interval = 313–558) per 1,000,000 population. 77 (91%) patients fulfilled the 2013 classification criteria, and 38 (45%) fulfilled the 1980 criteria. Mortality among patients with systemic sclerosis was significantly higher in comparison to the general population, with a standardized mortality ratio of 2.48 (95% confidence interval = 1.76–3.39) and no evidence of improvement over time. Conclusion: Systemic sclerosis developed in 25 persons/million/year with no change over the 39-year study period. The 2013 classification criteria perform significantly better than the 1980 criteria but failed to classify 9% of patients. Systemic sclerosis portends a 2.5-fold higher risk of mortality than the general population, with no evidence of improved survival over time.

Background/Purpose Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that regulates cholesterol homeostasis by inducing posttranslational modification and lysosomal degradation of low‐density lipoprotein receptor (LDLR). However, the role of PCSK9 in dyslipidemia associated with rheumatoid arthritis (RA) is not well studied. The aim of this study was to examine how PCSK9 levels correlate with age [30–45; 46–60; and 61–80 years], sex, and RA disease, and with CD36, a major scavenger receptor targeted for proteasomal degradation by PCSK9. Methods De‐identified human RA serum samples (n=66; 33 female and 33 male) were obtained from patients diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and healthy, age and gender‐matched serum samples were used for evaluation. Serum levels of human PCSK9 and CD36 were determined using commercially available ELISA kits. Results The mean (SD) age of healthy group [55.6 (11.2) years] and RA group [57.2 (10.4) years] was observed. Results of the ELISA showed that the serum levels of PCSK9 in RA group is reduced by ~10% (mean ± SEM; 231 ± 11.6 ng/ml vs. 205 ± 11.1 ng/ml; p<0.14). Interestingly, our gender‐based analysis showed that the basal serum PCSK9 levels were around 30% higher in the healthy female group compared to the healthy male group (260 ± 15.9 ng/ml vs. 202 ± 15.4 ng/ml; p=0.01). Furthermore, from a disease perspective, we observed approximately 15% lower serum PCSK9 levels in female RA group (260 ± 15.9 ng/ml vs. 219 ± 14.4 ng/ml; p=0.078) compared to only a modest 5% decline in male RA group (202 ± 15.4 ng/ml vs. 191 ± 16.8 ng/ml; p=0.62) when compared to their respective gender control groups. Analysis of PCSK9 data based on age showed that while PCSK9 levels gradually decreased in healthy female group [274.4 ± 38.9 ng/ml in 30–45y range vs. 241 ± 20.7 ng/ml in 61–80y], we observed an accelerated decrease in serum PCSK9 levels in RA female group [278.5 ± 62.4 ng/ml in 30–45y range vs. 220 ± 19.2 ng/ml in 46–60y; p=0.14]. This suggests that PCSK9 levels rapidly decline with RA progression in aging females. Interestingly, the serum PCSK9 levels in both healthy and RA male groups showed declines at a later stage of life [61–80y range; p<0.001], implicating that PCSK9 levels deplete in male groups, independent of RA disease pathogenesis. Serum CD36 levels in healthy female group were modestly low when compared to the serum levels in healthy male group [mean ± SEM; 1121 ± 164 pg/ml vs. 1280 ± 216 pg/ml; p<0.562]. Interestingly, while the CD36 levels were around 30% higher in RA males compared to the healthy male controls, we observed a modest decrease in serum CD36 by 15–20% in RA females when compared to the healthy female controls. Conclusion Our findings provide evidence of the gender differences in serum PCSK9 levels and its modulation with age. Furthermore, it is speculated that an early decline in serum PCSK9 in female RA patients may contribute towards the establishment of RA in females. Support or Funding Information Washington State University, Spokane, WA This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

ObjectiveThe objective of this study was to describe differences in the clinical course of patients with rheumatoid arthritis (RA) who are antinuclear antibody (ANA)–positive compared with those who are ANA‐negative.MethodsThis was a retrospective population‐based cohort study of residents in Olmsted County, Minnesota, who first fulfilled 1987 American College of Rheumatology criteria for RA in 2009‐2014. Data were collected on first documentation of joint swelling. Data on rheumatoid factor or anti‐cyclic citrullinated peptide antibody testing and the ANA level were also collected. Comparisons between groups were performed by using χ2 and rank sum tests.ResultsIn this cohort, 64% of patients were tested for ANA within ±90 days of RA criteria fulfillment. In the161 patients with ANA testing, 25% were ANA‐positive. Patients who were ANA‐positive were younger, female, and less likely to be current smokers. ANA positivity did not differ between patients with RA who were seropositive and seronegative. In seropositive patients who were ANA‐positive, there was an increased time to fulfillment of RA criteria, increased time to treatment with disease‐modifying antirheumatic drugs (DMARDs), and increased likelihood of being treated with hydroxychloroquine as opposed to methotrexate. Other outcomes, including disease activity and mortality, did not differ significantly between groups.ConclusionIn patients with RA, important differences exist between those who are ANA‐positive and ANA‐negative in terms of time to fulfillment of RA criteria and time to DMARD initiation as well as choice of initial pharmacotherapy. These findings could indicate a difference in clinical presentation or perception of patients with RA who are ANA‐positive. Further research is needed to study the long‐term outcomes of patients with RA who are ANA‐positive.

ObjectiveTo determine the incidence of psoriatic arthritis (PsA) in a US population and describe trends in incidence and mortality over 5 decades.MethodsThe previously identified population‐based cohort that included Olmsted County, Minnesota residents ≥18 years of age who fulfilled PsA criteria during 1970–1999 was extended to include patients with incident PsA during 2000–2017. Age‐ and sex‐specific incidence rates and point prevalence, adjusted to the 2010 US White population, were reported.ResultsThere were 164 incident cases of PsA in 2000–2017 (mean ± SD age 46.4 ± 12.0 years; 47% female). The overall age‐ and sex‐adjusted annual incidence of PsA per 100,000 population was 8.5 (95% confidence interval [95% CI] 7.2–9.8) and was higher in men (9.3 [95% CI 7.4–11.3]) than women (7.7 [95% CI 5.9–9.4]) in 2000–2017. Overall incidence was highest in the 40–59 years age group. The incidence rate was relatively stable during 2000–2017, with no evidence of an overall increase or an increase in men only (but a modest increase of 3% per year in women), compared to 1970–1999 when a 4%‐per‐year increase in incidence was observed. Point prevalence was 181.8 per 100,000 population (95% CI 156.5–207.1) in 2015. The percentage of women among those with PsA increased from 39% in 1970–1999 and 41% in 2000–2009 to 54% in 2010–2017 (P = 0.08). Overall survival in PsA did not differ from the general population (standardized mortality ratio 0.85 [95% CI 0.61–1.15]).ConclusionThe incidence of PsA in this predominantly White US population was stable in 2000–2017, in contrast to previous years. However, an increasing proportion of women with PsA was found in this study.

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