Non-rheumatic Diseases Research Articles

Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study

Study objectivesObservational and cohort studies have associated Sjögren's syndrome (SS) with various types of cardiovascular disease (CVD), yet causal relationships have not been established. We employed Mendelian randomization (MR) to investigate potential causal links between SS and CVD in the general population. MethodsWe conducted a two-sample MR analysis using data from four distinct sources for 11 genome-wide significant single nucleotide polymorphisms (SNPs) associated with SS and data for 13 types of CVD sourced from FinnGen, IEU OpenGWAS, and GWAS catalog. The inverse variance weighted method was selected as the primary analytical approach, complemented by various sensitivity analyses. ResultsMR analyses provide evidence of a significantly increased risk of ischemic stroke associated with genetically predicted SS (odds ratio [OR], 1.0237; 95 % CI, 1.0096 to 1.0379; p = 0.0009), as well as suggestive evidence of a potential causal relationship between SS and an increased risk of chronic heart failure (OR, 1.0302; 95 % CI, 1.0020 to 1.0592; p = 0.0355). Sensitivity analyses reinforced these associations, demonstrating robustness and consistency across multiple statistical methods. The secondary analysis, conducted after outlier correction using MR-PRESSO and RadialMR methods, reaffirmed these associations and also indicated a suggestive causal link between SS and non-rheumatic valvular heart disease (OR, 1.0251; 95 % CI, 1.0021 to 1.0486; p = 0.0323). ConclusionsThis study demonstrates that genetically predicted SS is a potential causative risk factor for ischemic stroke, chronic heart failure, and non-rheumatic valvular heart disease on a large-scale population. However, further research incorporating ancestral diversity is required to confirm a causal relationship between SS and CVD.

Increased risk of stroke in non-rheumatic valvular disease associated with antiphospholipid syndrome (APS): a US nationwide study 2017-2019

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune syndrome characterized by the presence of antiphospholipid autoantibodies, arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopenia. Cardiac manifestations are also common which include coronary artery disease (CAD), non rheumatic valvular heart disorders (NRVHD), myocardial dysfunction, intracardiac thrombi and pulmonary hypertension. Valvular lesions occur likely due to immune complex deposition on the valves, causing fibrosis, calcification and subsequently valvular deformities. Literature review suggests prevalence of NRVHD in APS population is 30% and left sided valves are more involved than right. An increased risk of stroke has also been seen in APS patients with valvular disorders. Purpose Studies report variations in incidence of NRVHD in association with APS. To estimate the prevalence of NRVHD and their correlation with APS, we conducted a retrospective database analysis of hospitalizations across the United States. Additionally we investigated whether this association indicates a increased risk of ischemic stroke in this specific subpopulation. Methods The national inpatient sample (NIS) from 2017-2019 was queried for adult patients (age>18 yrs) admitted with a primary or secondary diagnosis of APS. These patients were stratified for different NRVHD including tricuspid stenosis, tricuspid insufficiency, pulmonary stenosis, pulmonary regurgitation, mitral stenosis, mitral insufficiency (MI), aortic stenosis (AS), and aortic regurgitation. Baseline risk factors and cardiac complications were compared. Multiple regression analysis was performed to study the association of NRVHD with stroke as the primary outcome in the subpopulation of APS hospitalizations. Results A total of 567600 adult patients hospitalized with diagnosis of APS were identified from the NIS 2017-2019 database. Among those, 33,095 had NRVHD with a mean age of 69 years. Of these, prevalence of males was 52.41% compared to females of 47.59%. In the cohort of APS, patients with NRVHD had a higher prevalence of coronary artery disease (43.78% vs 20.41%), diabetes mellitus (30.65% vs 27.56%), prior stroke (10.42% vs 7.78%) than those without valvular disorders. Among the APS population the most prevalent NRVHD were mitral insufficiency (MI), 2.45% and aortic stenosis (AS), 2.13%. In the cohort of NRVHD in APS hospitalizations, the odds of stroke was found to be 1.3 times higher with statistical significance (confidence interval (CI): 1.13-1.48, p <0.001) adjusted for relevant clinical and demographic risk factors such as tobacco abuse, CAD, diabetes mellitus, prior stroke. Conclusion This study shows 6.2% prevalence of NRVHD in APS population, of which MI and AS were common. NRVHD is also associated with higher odds of stroke in APS. Further studies are warranted in identifying the risk of stroke with NRVHD in APS population and emphasizing the need for early detection.

Global, Regional, and National Burden of Nonrheumatic Valvular Heart Disease and Its Attributable Risk Factors in 204 Countries and Territories, 1990 to 2019: Results From the Global Burden of Disease Study 2019.

Nonrheumatic valvular heart disease (NRVD) is increasingly becoming a significant public health concern, particularly among older people. In the context of population aging, a detailed report on the epidemiological trends of NRVD is crucial for policymakers to effectively allocate health care resources. This study aimed to explore these trends using data from the GBD (Global Burden of Disease) 2019 study. We assessed the changing trends of the incidence, mortality, and disability-adjusted life years rates for NRVD by calculating the estimated annual percentage change for each. Additionally, we examined the impact of a region's level of social development on NRVD epidemiological trends and identified key risk factors contributing to NRVD-related deaths. Between 1990 and 2019, the global incidence of NRVD showed a gradual increase, with an estimated annual percentage change of 0.39 (95% CI, 0.30-0.48). The data revealed that women and older people are more likely to develop NRVD. High-sociodemographic index countries exhibited higher age-standardized incidence and mortality rates compared with low- and middle-sociodemographic index countries. The most significant risk factor for NRVD-related mortality was identified as high systolic blood pressure. Over the past 3 decades, the burden of NRVD has intensified, indicating a need for more health care resources to address this issue, which is closely associated with an aging population. Currently, high-sociodemographic index countries report the highest incidences and deaths due to NRVD. However, low- and middle-sociodemographic index countries should also implement measures to manage the rapidly increasing burden of NRVD.

Paediatric rheumatology in Nigeria: history, challenges and the future.

Pediatric rheumatology is a relatively new subspecialty in Nigeria. For many years, rheumatic disease had not been well-recognized or studied in Nigeria, so there has been a low suspicion index. The clinical presentation of most pediatric rheumatic diseases (PRDs) mimics non-rheumatic diseases making it a diagnostic challenge most of the time. The story has changed in Lagos since the creation of a pediatric rheumatology unit at the Lagos State University Teaching Hospital. There is now a high index of suspicion for these diseases in the hospital but no one knows about what is happening in the other 35 states of the country who do not have a pediatric rheumatologist. Major challenges being faced presently are poor awareness among healthcare workers and the community, high cost of investigations and medications, lack of pediatric rheumatologists in most hospitals in the country, lack of pediatric rheumatology training centers for both undergraduate and postgraduate training, and lack of research data. The healthcare community in Nigeria is looking forward to a future where pediatric rheumatology will be highly recognized and established.

TCT-644 Burden of Non-Rheumatic Calcific Aortic Valve Disease and Non-Rheumatic Degenerative Mitral Valve Disease in High-Income North America and West Europe From 1990 to 2021

TCT-644 Burden of Non-Rheumatic Calcific Aortic Valve Disease and Non-Rheumatic Degenerative Mitral Valve Disease in High-Income North America and West Europe From 1990 to 2021

Breakthrough SARS-CoV-2 infection in fully vaccinated patients with systemic lupus erythematosus: results from the COVID-19 Vaccination in Autoimmune Disease (COVAD) study

ObjectiveTo determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs).MethodsThe study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models.ResultsA total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89–6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04–5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively.ConclusionCOVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals.

Thirty-year Trend of Non-rheumatic Valvular Heart Disease: A Comparison of Pakistan with South Asia and Global Scenario

Thirty-year Trend of Non-rheumatic Valvular Heart Disease: A Comparison of Pakistan with South Asia and Global Scenario

Causal association between triglycerides and cholesterol-lowering medication with non-rheumatic valve disease: A 2-sample Mendelian randomization study.

Previous studies have found a possible causal relationship between triglycerides and lipid-lowering drugs and valvular disease. The aim of this study was to explore the potential causal relationship between triglycerides and lipid-lowering drugs and valvular disease using Mendelian randomization (MR) analysis. Data sets associated with triglycerides (441,016 participants and 12,321,875 single nucleotide polymorphisms [SNPs]) and cholesterol-lowering drugs (209,638 participants and 9851,867 SNPs) were retrieved from the Genome-Wide Association Study (GWAS) database. A total of 297 and 49 SNPs significantly associated with triglycerides and cholesterol-lowering drugs, respectively (P < 5 × 10-8), were identified. Similarly, data sets for non-rheumatic valve diseases (NVDs) (361,194 participants and 10,080,950 SNPs) were obtained from the GWAS database. Inverse variance weighting was used as the primary method for calculating the odds ratio (OR) and 95% confidence intervals (CI). The MR-Egger, weighted median, and weighted mode analyses were also used to test the robustness of the main results. The MR-Egger intercept test and the MR-PRESSO test were used to evaluate horizontal pleiotropy. Inverse variance weighted (IVW) results showed that both triglyceride and cholesterol-lowering medication were positively associated with NVDs (OR = 1.001, 95% CI 1.000-1.0012, P = 0.006; OR = 1.007, 95% CI 1.003-1.010; P = 0.002). This study suggests that both triglyceride and cholesterol-lowering medications are positively associated with NVDs, suggesting that lowering triglyceride levels or the use of cholesterol-lowering medications may reduce the incidence of NVDs. However, larger samples are required for further validation.

COVID-19 severity, breakthrough infections and vaccine safety in young individuals with autoimmune diseases: insights from the COVAD study

Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18–35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy.

Global Epidemiologic Trends and Projections to 2030 in Non-Rheumatic Degenerative Mitral Valve Disease from 1990 to 2019: An Analysis of the Global Burden of Disease Study 2019.

No studies have updated the epidemiologic changes in non-rheumatic degenerative mitral valve disease (DMVD) since 2019, thus this study utilized data from the Global Study of Diseases, Injuries, and Risk Factors 2019 (GBD2019) to assess the burden of DMVD in 204 countries and territories over the period 1990-2019, as well as changes in the prevalence, incidence, deaths and changes in disability-adjusted life years (DALYs). Using the results from the GBD2019, analyzing the incidence, prevalence, deaths, and DALYs rates, as well as their age-standardized rates (ASR). Based on the human development index (HDI), the socio-demographic index (SDI), age, and sex. In 2019, there were 24.229 million (95% uncertainty interval (UI) 23.081-25.419 million) existing cases of DMVD worldwide, with 1.064 million (95% UI 1.010-1.122 million) new cases and 0.034 million (95% UI 0.028-0.043 million) deaths, and 0.883 million (95% UI 0.754-1.092 million) disability-adjusted life years. The incidence, prevalence, deaths, and DALYs of DMVD and their ASR showed significant differences across sex, age groups, regions, and countries from 1990 to 2019. It is projected that by 2030, the incidence of DMVD in females will be 0.72 million with an ASR of 15.59 per 100,000 population, 0.51 million in males with an ASR of 11.75 per 100,000 population, and a total incidence of 1.23 million with an ASR of 14.03 per 100,000 population. DMVD remains a significant public health problem that cannot be ignored, despite a decreasing trend in the ASR of global incidence, prevalence, deaths and DALYs from 1990 to 2019. However, we note an adverse development trend in countries with low socio-demographic indexes and seriously aging societies, and sex inequality is particularly prominent. This indicates the need to reposition current prevention and treatment strategies, with some national health administrations developing corresponding strategies for preventing an increase in DMVD based on local health, education, economic conditions, sex differences, and age differences.

Nailfold Capillaroscopy: A Comprehensive Review on Its Usefulness in Both Clinical Diagnosis and Improving Unhealthy Dietary Lifestyles.

Since the 1970s, the utility of nailfold capillaroscopy (NFC) in diagnosing rheumatological disorders such as systemic sclerosis has been well established. Further studies have also shown that NFC can detect non-rheumatic diseases such as diabetes, glaucoma, dermatitis, and Alzheimer disease. In the past decade, nailfold capillary morphological changes have also been reported as symptoms of unhealthy lifestyle habits such as poor diet, smoking, sleep deprivation, and even psychological stress, all of which contribute to slow blood flow. Therefore, studying the relationships between the morphology of nailfold capillaries and lifestyle habits has a high potential to indicate unhealthy states or even pre-disease conditions. Simple, inexpensive, and non-invasive methods such as NFC are important and useful for routine medical examinations. The present study began with a systematic literature search of the PubMed database followed by a summary of studies reporting the assessment of morphological changes detected by NFC, and a comprehensive review of NFC's utility in clinical diagnosis and improving unhealthy dietary lifestyles. It culminates in a summary of dietary and lifestyle health promotion strategy, assessed based on NFC and other related measurements that indicate healthy microvascular blood flow and endothelial function.

The Prevalence and Predictors of Atherosclerotic Coronary Artery Disease in Rheumatic and Non-rheumatic Valvular Heart Disease Patients.

The paradox of concurrent coronary artery disease (CAD) among patients with rheumatic and non-rheumatic valvular heart disease (RVHD; non-RVHD) is unclear. We aimed to evaluate the impact of the RVHD and non-RVHD on the prevalence of CAD and various risk factors, assess the number of diseased coronaries, clinical profile and the possible predictors of CAD in these patients, which may clarify the paradox and provide an insight for the prevention of CAD. The records of 106 valvular heart disease patients who had undergone valve replacement surgery at the King Faisal Cardiac Centrefrom January 2014 to October 2019 were evaluated. The clinical data and established risk factors were compared andlogistic regression analyses were performed to identify plausible predictors of CAD. Transthoracic echocardiographic diagnosis of 106 patients confirmed, 43 had RVHD (56.4 ± 8 years), of whom six (13.9%) had CAD with the highest mitral valve regurgitation (p < 0.01), and 63 had non-RVHD (60.0 ± 12 years). Of these, 31 patients showed the highest CAD (49.2%). Single- and triple-vessel disease was most common in RVHD and non-RVHD patients with concurrent CAD (33.3%; 41.9%, respectively), while non-RVHD patients also had quadruple vessel disease. The mean age of the RVHD and non-RVHD patients with coexisting CAD was significantly higher (66.7 ± 5; 66.7 ± 8 years) than those without CAD (46.1± 12.0; 54.7± 20, respectively). RVHD patients showed a significantly lower prevalence of diabetes, dyslipidaemia, hypertension, inflammatory cells, hepatorenal function markers, ejection fraction, and regional wall motion abnormality compared to RVHD patients with coexisting CAD (p < 0.01). Bivariate analysis indicated white blood cells, monocytes, neutrophils, gamma-glutamyl-transferase (GGT), bilirubin and blood urea nitrogen (BUN) to be significantly lower in RVHD patients. Predictors of high risk of CAD were BUN and hyperlipidaemia for RVHD and BUN, creatinine and GGT for non-RVHD patients. The prevalence of CAD in Saudi RVHD patients was significantly lower than in the Western countries, whereas non-RVHD was higher. The low prevalence may partly be attributed to age, reduced mitral regurgitation, and low frequency of risk and inflammatory factors.

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey.

To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10-15] IIMs vs 13 [11-15] non-IIM AIRDs vs 15 [13-17] nrAIDs vs 17 [15-18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10-15) IIMs vs 15 (13-17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

Polyautoimmunity in Patients With Anticyclic Citrullinated Peptide Antibody-Positive and -Negative Rheumatoid Arthritis: a Nationwide Cohort Study From Denmark.

This study aimed to compare the prevalence and incidence of polyautoimmunity between anticyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative patients with rheumatoid arthritis (RA). In a nationwide register-based cohort study, patients with RA (disease duration ≤ 2 yrs) in the DANBIO rheumatology register with an available anti-CCP test in the Register of Laboratory Results for Research were identified. The polyautoimmunity outcome included 21 nonrheumatic autoimmune diseases identified by linkage between the Danish Patient Registry and Prescription Registry. The age- and sex-adjusted prevalence ratio (PR) was calculated by modified Poisson regression to estimate the prevalence at diagnosis in anti-CCP-positive vs anti-CCP-negative patients. The hazard ratio (HR) of polyautoimmunity within 5 years of entry into DANBIO was estimated in cause-specific Cox regression models. The study included 5839 anti-CCP-positive and 3799 anti-CCP-negative patients with RA. At first visit, the prevalence of prespecified polyautoimmune diseases in the Danish registers was 11.1% and 11.9% in anti-CCP-positive and anti-CCP-negative patients, respectively (PR 0.93, 95% CI 0.84-1.05). The most frequent autoimmune diseases were autoimmune thyroid disease, inflammatory bowel disease, and type 1 diabetes mellitus. During a mean follow-up of 3.5 years, only a few (n = 210) patients developed polyautoimmunity (HR 0.6, 95% CI 0.46-0.79). Polyautoimmunity as captured through the Danish National Patient Registry occurred in approximately 1 in 10 patients with RA at time of diagnosis regardless of anti-CCP status. In the years subsequent to the RA diagnosis, only a few and mainly anti-CCP-negative patients developed autoimmune disease.

Global prevalence of cardiovascular diseases by gender and age during 2010-2019.

The aim of this study was to evaluate the global, gender, and age-related cardiovascular disease (CVD) burden during 2010-2019. Not only the global trend in the prevalence of CVDs was studied but also whether there was a statistically significant difference between genders and ages during 2010-2019. Detailed information from 2010 to 2019, including global rates of prevalence of 11 categories of CVD, was collected from the Global Burden of Disease Study 2019. The statistical methods used to analyze the results of this study are the independent samples t-test and one-way analysis of variance (ANOVA) test. The global prevalence rate of CVDs increased from 0.061% in 2010 to 0.070% in 2019. There was a statistically significant difference in prevalence rates between genders in all cardiovascular diseases except atrial fibrillation and flutter. Females have higher prevalence rates of CVDs worldwide. Moreover, females have statistically significantly higher prevalence rates of stroke, hypertensive heart disease, rheumatic heart disease, non-rheumatic valvular heart disease, endocarditis, peripheral artery disease and other cardiovascular and circulatory diseases globally. On the other hand, males have statistically significantly higher prevalence rates of cardiomyopathy and myocarditis, and ischemic heart disease globally. Rheumatic heart disease has a statistically significantly higher prevalence rate in the age group of 25-49 years than the other age groups. The significance of this study is not only that it has succeeded in evaluating the global, gender, and age-related cardiovascular disease (CVD) burden, finding statistically significant associations, but it is also the only study to achieve this goal in the last decade.

Insights into the immunological description of cryoglobulins with regard to detection and characterization in Slovenian rheumatological patients

The detection of cryoglobulins (CG) used to diagnose cryoglobulinemic vasculitis requires strict adherence to protocol, with emphasis on the preanalytical part. Our main objectives were to introduce a more sensitive and specific protocol for the detection of CG and to characterize CG in Slovenian patients diagnosed with cryoglobulinemic vasculitis, other vasculitides, connective tissue diseases or non-rheumatic diseases examined at the Department of Rheumatology (University Medical Centre Ljubljana). Samples were routinely analyzed for the presence of CG with the protocol using the Folin-Ciocalteu reagent. In the newly introduced protocol, the type of CG was determined by immunofixation on visually observed positive samples and the concentration of CG in the cryoprecipitate and rheumatoid factor (RF) activity were measured by nephelometry. RF, C3c and C4 were measured in patients` serum and a decision tree analysis was performed using all results. The agreement between negative and positive results between the two protocols was 86%. Of the 258 patient samples tested, we found 56 patients (21.7%) with positive CG (37.5% - type II, 62.5% - type III). The RF activity was observed in 21.4% of CG positive subjects. The median concentration of type II CG was significantly higher than that of type III CG (67.4 mg/L vs. 45.0 mg/L, p = 0.037). Patients with type II had lower C4 concentrations and higher RF compared to patients with type III CG. In the decision tree, C4 was the strongest predictor of cryoglobulinemia in patients. With the newly implemented protocol, we were able to improve the detection and quantification of CG in the samples of our rheumatology patients and report the results to adequately support clinicians.

Anti-SSA Ro52 and anti-Ro60 autoantibodies: association with clinical phenotypes.

Anti-SSA autoantibodies can be differentiated according to their antigenic target proteins as anti-Ro60 (60 kDa) or anti-Ro52 (52 kDa). Anti-SSA(Ro60) antibodies are clearly associated with connective tissue diseases (CTD), but the clinical significance of anti-SSA(Ro52) antibodies remains unclear. The aim of the present study was to analyse the disease phenotype of patients with anti-Ro52 and/or anti-Ro60 antibodies. A multicentre, cross-sectional study was carried out of positive anti-Ro52 and/or Ro60 antibodies patients followed at 10 Rheumatology centres from January 2018 until December 2021. Patients were categorised into 3 groups: group 1 (Ro52+/Ro60-); group 2 (Ro52-/Ro60+); group 3 (Ro52+/Ro60+). Antinuclear antibodies were evaluated by indirect immunofluorescence assay and further screened for anti-extractable nuclear antigen (ENA) antibodies. Demographicsand clinical data were compared between the 3 groups, by patients' medical chart review. Univariate analysis was performed and subsequently logistic regression was used to identify intergroup differences and calculate the odds ratio with a 95% confidence interval (95% CI). We included 776 patients [female: 83.1%; median age: 59 (46-71) years]. Groups 1, 2, and 3 comprised 31.1%, 32.6%, and 36.3% of the patients, respectively. Anti-Ro52 antibody alone was more frequently associated with non-rheumatic diseases, older age, and men (p<0.05). Among patients with CTD, the diagnosis of systemic lupus erythematosus is 3 and 2 times more prevalent in groups 2 and 3, respectively, than in group 1 [OR 2.8 (95% CI 1.60, 4.97), p<0.001; OR 2.2 (95% CI 1.28, 3.86), p<0.01]. In group 2, the diagnosis of undifferentiated CTD is more frequent than in the other groups. Group 1 was more frequently associated with inflammatory myositis than group 2 [OR 0.09 (95% CI 0.01, 0.33), p<0.001] or group 3 [OR 0.08 (95% CI 0.01, 0.29), p<0.001]. Group 1 was also more frequently associated with arthritis (p<0.01), interstitial lung disease (p<0.01), and myositis (p<0.01). Anti-Ro52+ antibody alone is frequently found in patients with non-rheumatic diseases. In addition, anti-Ro52+ antibody is also prevalent in patients with CTD and associated with clinical phenotypes that are different from anti-Ro60+ antibody.

Abstract 16267: Burden of Cardiovascular Disease in Sub-Saharan Africa

Introduction: This study aims to explore the burden of cardiovascular disease (CVD) and associated risk factors in Sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD). Hypothesis: That the burden of CVD has increased in SSA over time, and there are associated risk factors contributing to this burden. Methods: We analyzed CVD prevalence, mortality, and incidence in 46 SSA countries using Bayesian regression, demographic methodologies, and mortality-to-incidence ratios. Disability-adjusted life years (DALYs) were calculated, and risk factors were assessed through the comparative risk assessment framework of the GBD. Results: Between 1990 and 2019, CVD prevalence in SSA increased by 131.7%, with a modest rise of 2.1% in age-standardized prevalence rates. Ischemic heart disease, stroke (CVA), and rheumatic heart disease were the most prevalent conditions. CVD deaths increased from 564,140 to 1,003,893, with a 14.4% decrease in death rates. Non-rheumatic valvular disease showed a significant increase. DALYs increased by 68.4%, but some CVDs saw decreases in DALY rates. Conclusions: Despite rising CVD prevalence in SSA, age-standardized rates only modestly increased. However, the persistently high burden, increasing non-rheumatic valvular disease, and rising DALYs highlight challenges in prevention and management. These findings highlight the persistent challenge of CVD in SSA and emphasize the need for continued efforts in prevention and management strategies to address the growing burden of CVD in this region.

Abstract 14558: Causes and Predictors of Short-Term Readmissions Following Percutaneous Left Atrial Appendage Closure Procedure in Patients With and Without Rheumatic Mitral Valve Disease

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, characterized by erratic heart beats. AF increases the risk of thromboembolic events particularly stroke. Percutaneous left atrial appendage closure (LAAC) is an alternative option to prevent embolic stroke in patients with AF who have contraindication to anticoagulants. Up to our knowledge, this is the first National Readmission Database (NRD) study to elucidate the difference in readmission rates between rheumatic vs non-rheumatic AF patients who underwent LAAC. Methods: We utilized the Nationwide Readmissions Database (NRD) between the years 2016-2020. The study involved hospitalizations with rheumatic mitral valve disease (R-MVD) and non-rheumatic mitral valve disease (NR-MVD) who underwent LAAC using ICD-10 diagnostic codes. We deemed this as the index admission. We excluded patients less than 18 years old and October-December hospitalizations from 90-day readmission analysis, due to lack of adjoining period to assess readmission. Results: Among 9,150 patients with mitral valve disease who underwent LAAC in their index hospitalizations, 9,122 were discharged alive. 4,200 patients (45.8%) were readmitted in 90-days. R-MVD 90-day readmission rate compared to NR-MVD (52.3% vs 40.7% respectively, p&lt;0.001). The most common cause of readmission in both groups was atrial fibrillation, 96% of total readmissions in R-MVD and 97% of total readmissions in NR-MVD group. This was followed by “accidental puncture and laceration of a digestive system organ or structure” in 0.3% of R-MVD group vs “mitral valve insufficiency” in 0.7% of NR-MVD readmission causes. Figure 1 shows the Forest plot of multivariate analysis of independent factors associated with readmissions. Conclusion: Among AF patients who underwent LAAC with or without history of mitral valve rheumatic heart disease, those with history of R-MVD had significantly higher 90-day readmission rate.