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Women are disproportionately affected by chronic autoimmune diseases (AD) like systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis (RA), and Sjögren's syndrome. Traditional evaluations often underestimate the associated cardiovascular disease (CVD) and stroke risk in women having AD. Vitamin D deficiency increases susceptibility to these conditions. CVD risk prediction in AD can benefit from surrogate biomarker for coronary artery disease (CAD), such as carotid ultrasound. Due to non-linearity in the CVD risk stratification, we use artificial intelligence-based system using AD biomarkers and carotid ultrasound. Investigate the relationship between AD and CVD/stroke markers including autoantibody-influenced plaque load. Second, to study the surrogate biomarkers for the CAD and gather radiomics-based features such as carotid intima-media thickness (cIMT), and plaque area (PA). Third and final, explore the automated CVD/stroke risk identification using advanced machine learning (ML) and deep learning (DL) paradigms. Analysed biomarker data from women with AD, including carotid ultrasonography imaging, clinical parameters, autoantibody profiles, and vitamin D levels. Proposed artificial intelligence (AI) models to predict CVD/stroke risk accurately in AD for women. There is a strong association between AD duration and elevated cIMT/PA, with increased CVD risk linked to higher rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs) levels. AI models outperformed conventional methods by integrating imaging data and disorder-specific factors. Interdisciplinary collaboration is crucial for managing CVD/stroke in women with chronic autoimmune diseases. AI-based assisted risk stratification methods may improve treatment decision-making and cardiovascular outcomes., Competing Interests: Declarations. Conflict of interest: All authors are full-time employees at their indicated affiliation institutions, which are public universities and hospitals. None of the authors received fees, bonuses or other benefits for the work described in the manuscript. Ethical approval: Ethical clearance was obtained from the ethical committee of the University of Tours. All participants provided written informed consent for data collection and publication prior to data collection. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. We acknowledge that the manuscript was written and edited by authors only., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA., Methods: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease., Results: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk., Conclusions: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The field of precision medicine endeavors to transform the healthcare industry by advancing individualised strategies for diagnosis, treatment modalities, and predictive assessments. This is achieved by utilizing extensive multidimensional biological datasets encompassing diverse components, such as an individual's genetic makeup, functional attributes, and environmental influences. Artificial intelligence (AI) systems, namely machine learning (ML) and deep learning (DL), have exhibited remarkable efficacy in predicting the potential occurrence of specific cancers and cardiovascular diseases (CVD)., Methods: We conducted a comprehensive scoping review guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Our search strategy involved combining key terms related to CVD and AI using the Boolean operator AND. In August 2023, we conducted an extensive search across reputable scholarly databases including Google Scholar, PubMed, IEEE Xplore, ScienceDirect, Web of Science, and arXiv to gather relevant academic literature on personalised medicine for CVD. Subsequently, in January 2024, we extended our search to include internet search engines such as Google and various CVD websites. These searches were further updated in March 2024. Additionally, we reviewed the reference lists of the final selected research articles to identify any additional relevant literature., Findings: A total of 2307 records were identified during the process of conducting the study, consisting of 564 entries from external sites like arXiv and 1743 records found through database searching. After 430 duplicate articles were eliminated, 1877 items that remained were screened for relevancy. In this stage, 1241 articles remained for additional review after 158 irrelevant articles and 478 articles with insufficient data were removed. 355 articles were eliminated for being inaccessible, 726 for being written in a language other than English, and 281 for not having undergone peer review. Consequently, 121 studies were deemed suitable for inclusion in the qualitative synthesis. At the intersection of CVD, AI, and precision medicine, we found important scientific findings in our scoping review. Intricate pattern extraction from large, complicated genetic datasets is a skill that AI algorithms excel at, allowing for accurate disease diagnosis and CVD risk prediction. Furthermore, these investigations have uncovered unique genetic biomarkers linked to CVD, providing insight into the workings of the disease and possible treatment avenues. The construction of more precise predictive models and personalised treatment plans based on the genetic profiles of individual patients has been made possible by the revolutionary advancement of CVD risk assessment through the integration of AI and genomics., Interpretation: The systematic methodology employed ensured the thorough examination of available literature and the inclusion of relevant studies, contributing to the robustness and reliability of the study's findings. Our analysis stresses a crucial point in terms of the adaptability and versatility of AI solutions. AI algorithms designed in non-CVD domains such as in oncology, often include ideas and tactics that might be modified to address cardiovascular problems., Funding: No funding received., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s).)

Objective: The aim of this study was to compare the risk of major cardiovascular events (MACE) and venous thromboembolic events (VTE) between tumour necrosis factor (TNF) and Janus kinase (JAK) inhibitors in patients with rheumatoid arthritis (RA)., Methods: We researched PubMed, Scopus, Cochrane Library, and clinicaltrials.gov until December of 2023 for randomised controlled trials (RCTs) and observational studies. The outcomes studied were MACE (stroke, heart attack, myocardial infarction, sudden cardiac death) and VTE (deep vein thrombosis, pulmonary embolism). We pooled data using random effects model. Risk for the reported outcomes was expressed as odds ratio (OR) with a 95% confidential interval (CI). We performed a subgroup analysis based on study design., Results: We identified 23 studies, 20 of which compared the odds for MACE and 14 the odds for VTE between JAK and TNF inhibitors in RA patients. Ten studies were RCTs and the rest were observational. Regarding MACE risk we pooled data from a total of 215,278 patients (52,243 were treated with JAK inhibitors, while the rest 163,035 were under TNF inhibitors). Compared with TNF inhibitors, the OR for JAK inhibitors in regards with MACE risk was 0.87 (0.64-1.17, p<0.01). Regarding VTE, a total of 176,951 patients were analysed (41,375 JAK inhibitors users and 135,576 TNF inhibitors users). The OR for VTE for JAK inhibitors compared with TNF inhibitors was 1.28 (0.89-1.84, p<0.01)., Conclusion: According to our results, there is no statistically significant difference for MACE or VTE in RA patients who receive either JAK or TNF inhibitors., Competing Interests: The authors declare no conflict of interest., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Introduction/objectives: Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) - a biomarker of atherosclerosis - and assessments of macrovascular endothelial function in patients with SSc., Methods: This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT)., Results: Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (≤ 4 years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25 mm/h and C-reactive protein [CRP] > 5 mg/L) showed no associations, except from a significant positive correlation between ADMA levels and cΙΜΤ mean (r = 0.370, p = 0.044) in individuals with early SSc., Conclusions: The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease. Key Points • ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc. •ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study. •The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: To describe the prevalence of atrial fibrillation (AF) in patients with rheumatoid arthritis (RA), and to evaluate the proportion of patients with AF receiving guideline-recommended anticoagulation for prevention of stroke, based on data from a large international audit., Methods: The cohort was derived from the international audit SU rvey of cardiovascular disease R isk F actors in patients with R heumatoid A rthritis (SURF-RA) which collected data from 17 countries during 2014-2019. We evaluated the prevalence of AF across world regions and explored factors associated with the presence of AF with multivariable logistic regression models. The proportion of AF patients at high risk of stroke (CHA 2 DS 2 -VASc ≥ 2 in males and ≥ 3 in females) receiving anticoagulation was examined., Results: Of the total SURF-RA cohort (n = 14,503), we included RA cases with data on whether the diagnosis of AF was present or not (n = 7,665, 75.1% women, mean (SD) age 58.7 (14.1) years). A total of 288 (3.8%) patients had a history of AF (4.4% in North America, 3.4% in Western Europe, 2.8% in Central and Eastern Europe and 1.5% in Asia). Factors associated with the presence of AF were older age, male sex, atherosclerotic cardiovascular disease, heart failure and hypertension. Two-hundred and fifty-five (88.5%) RA patients had a CHA 2 DS 2 -VASc score indicating recommendation for oral anticoagulant treatment, and of them, 164 (64.3%) were anticoagulated., Conclusion: Guideline-recommended anticoagulant therapy for prevention of stroke due to AF may not be optimally implemented among RA patients, and requires special attention., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background and Aims: Rheumatoid arthritis (RA) patients are at a high risk of atherosclerotic cardiovascular disease (ASCVD). This implies a need for meticulous CVD risk factor recording and control., Objectives: The aim was to evaluate the international prevalence of ASCVD in RA patients and to audit the prevalence and control of CVD risk factors., Methods: A SU rvey of cardiovascular disease R isk F actors in patients with R heumatoid A rthritis (SURF-RA) was performed at 53 centres in 19 countries in three continents between 2014 and 2019. CVD risk factors, medication, and physical and laboratory measurements were recorded. CVD risk was estimated using the ESC's SCORE system., Results: Among 14503 RA patients in Western (n=8493) and Central and Eastern (n=923) Europe, Mexico (n=407), North America (n=4030) and Asia (n=650) (mean age 59.9 years, 74.5% female), ASCVD was present in 15%, varying from 2.5% in Mexico to 21% in Central and Eastern Europe. Sixty-two percent reported hypertension and 63% had a LDL-c of > 2.5 mmol/L. Mean BMI was 27.4 kg/m 2 in the total cohort, highest in North America (29.7 kg/m 2 ), and lowest in Asia (23.8 kg/m 2 ). A sixth of patients were current smokers, and 13% had diabetes mellitus. Approximately 45% had an estimated high or very high risk of fatal CVD according to SCORE algorithm, and ¾ of patients had only ≤4/6 CVD risk factors at recommended target., Conclusion: Among RA patients across three continents, established CVD and CVD risk factors are common, although geographical variation exists. Furthermore, CVD risk factors often remain inadequately controlled., (© 2022 The Mediterranean Journal of Rheumatology (MJR).)

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 ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nailfold videocapillaroscopy (NVC) changes in systemic sclerosis (SSc) are correlated with vascular complications, such as pulmonary arterial hypertension (PAH), supporting a potential link between peripheral and internal organ vasculopathy. The current stage of knowledge regarding NVC and PAH is discussed, focusing on the assessment of peripheral microangiopathy and a potential relationship with functional, echocardiographic, and haemodynamic markers of cardiac dysfunction. A comprehensive literature search was carried out to identify all studies focusing on NVC findings in patients with PAH, diagnosed with right heart catheterization. The majority of the studies examined NVC findings in patients with SSc-PAH, while three studies reported NVC abnormalities in patients with idiopathic PAH. Besides the pulmonary vasculature, a systemic component of microangiopathy seems to be involved in PAH. Well-designed prospective trials are warranted to validate NVC as a biomarker, with clinical implications in the diagnostic evaluation, risk stratification, and overall management of PAH in the daily clinical setting.

Systemic autoimmune inflammatory disorders confer a higher risk of cardiovascular (CV) disease leading to increased morbidity and mortality and reduced life expectancy compared to the general population. CV risk in systemic sclerosis (SSc) has not been studied extensively but surrogate markers of atherosclerosis namely carotid intima media thickness (cIMT) and pulse wave velocity (PWV) are impaired in some but not all studies in SSc patients. The aim of this study was to investigate the prevalence of subclinical atherosclerosis assessed by cIMT and PWV between two well-characterized SSc and Rheumatoid Arthritis (RA) cohorts. Consecutive SSc patients attending the Scleroderma Clinic were compared with RA patients recruited in the Dudley Rheumatoid Arthritis Co-morbidity Cohort (DRACCO), a prospective study examining CV burden in RA. Augmentation Index (Aix75) and cIMT were measured in all participants. Propensity score matching was utilised to select patients from the two cohorts with similar demographic characteristics, CV risk factors and inflammatory load. Unpaired analysis was performed using unpaired t test for continuous variables and χ 2 test for dichotomous variables. Statistical analysis was repeated using paired t test for continuous normal variables and McNemar's test for dichotomous variables. Fifty five age- and sex-matched SSc and RA patients were included in the analysis. No difference was demonstrated between SSc and RA subjects regarding cIMT (0.66 mm vs 0.63 mm, respectively) and Aix75% measurements (33.4 vs 31.7, respectively) neither in paired (p = 0.623 for cIMT and p = 0.204 for Aix%) nor in unpaired t test analysis (p = 0.137 for cIMT and p = 0.397 for AIx%). The results of this comparative study show that subclinical atherosclerosis is comparable between SSc and RA, a systemic disease with well-defined high atherosclerotic burden. Such findings underscore the importance of CV risk management in SSc in parallel with other disease-related manifestations.

Motivation: The early screening of cardiovascular diseases (CVD) can lead to effective treatment. Thus, accurate and reliable atherosclerotic carotid wall detection and plaque measurements are crucial. Current measurement methods are time-consuming and do not utilize the power of knowledge-based paradigms such as artificial intelligence (AI). We present an AI-based methodology for the joint automated detection and measurement of wall thickness and carotid plaque (CP) in the form of carotid intima-media thickness (cIMT) and total plaque area (TPA), a class of AtheroEdge™ system (AtheroPoint™, CA, USA)., Method: The novel system consists of two stages, and each stage comprises an independent deep learning (DL) model. In Stage I, the first DL model segregates the common carotid artery (CCA) patches from ultrasound (US) images into the rectangular wall and non-wall patches. The characterized wall patches are integrated to form the region of interest (ROI), which is then fed into Stage II. In Stage II, the second DL model segments the far wall region. Lumen-intima (LI) and media-adventitial (MA) boundaries are then extracted from the wall region, which is then used for cIMT and PA measurement., Results: Using the database of 250 carotid scans, the cIMT error using the AI model is 0.0935±0.0637 mm, which is lower than those of all previous methods. The PA error is found to be 2.7939±2.3702 mm 2 . The system's correlation coefficient (CC) between AI and ground truth (GT) values for cIMT is 0.99 (p < 0.0001), which is higher compared with the CC of 0.96 (p < 0.0001) shown by the earlier DL method. The CC for PA between AI and GT values is 0.89 (p < 0.0001)., Conclusion: A novel AI-based strategy was applied to carotid US images for the joint detection of carotid wall thickness (cWT) and plaque area (PA), followed by cIMT and PA measurement. This AI-based strategy shows improved performance using the patch technique compared with previous methods using full carotid scans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: People living with HIV (PLWH) are at high cardiovascular disease (CVD) risk. Traditional CVD risk scores do not accurately reflect their CVD risk. Noninvasive subclinical vascular damage (SVD) biomarkers are valid surrogates of CVD and able to stratify CVD risk., Setting: We tested whether 4 widely applied CVD risk scores [Framingham (FRS), Atherosclerotic CVD, Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D), and Greek-specific European Society of Cardiology (ESC) risk scores] are associated with or detect the presence, incidence, and progression of arteriosclerosis, atheromatosis, and arterial hypertrophy in PLWH and uninfected individuals., Methods: We prospectively examined (at baseline and 3-year follow-up) 10 different arterial sites applying 5 different noninvasive vascular biomarkers and measured all 4 CVD risk scores at baseline., Results: In both PLWH (n = 138) and uninfected (n = 664) individuals, the CVD risk scores (except the ESC) performed differently but reasonably well in identifying the presence of SVD, but all scores failed to predict the incidence/progression of overall SVD. The most clinically useful biomarkers (carotid plaque/atheromatosis) revealed that in PLWH, only the FRS was able to stratify the progression (11% of the low-risk, 33.3% of the medium-risk, and 0% of the high-risk group)., Conclusions: This extensive vascular phenotyping study demonstrated the clear need to incorporate vascular imaging in CVD risk stratification, in addition to designing more accurate HIV-specific CVD risk models. The use of FRS would further enable treatment optimization and CVD prevention strategies in PLWH at medium CVD risk because one-third of carotid atheromatosis progresses within 3 years.

Cardiovascular Disease (CVD) in Systemic Lupus Erythematosus (SLE) and Neuropsychiatric SLE (NPSLE) has an estimated prevalence of 50% and 40%, respectively and both constitute major causes of death among SLE patients. In this review, a combined brain/heart Magnetic Resonance Imaging (MRI) for SLE risk stratification has been proposed. The pathophysiologic background of NPSLE includes microangiopathy, macroscopic infarcts and accelerated atherosclerosis. Classic brain MRI findings demonstrate lesions suggestive of NPSLE in 50% of the NPSLE cases, while advanced MRI indices can detect pre-clinical lesions in the majority of them, but their clinical impact still remains unknown. Cardiac involvement in SLE includes myo-pericarditis, valvular disease/endocarditis, Heart Failure (HF), coronary macro-microvascular disease, vasculitis and pulmonary hypertension. Classic and advanced Cardiovascular Magnetic Resonance (CMR) indices allow function and tissue characterization for early diagnosis and treatment follow-up of CVD in SLE. Although currently, there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SLE, it may have a place in cases with clinical suspicion of brain/heart involvement, especially in patients at high risk for CVD/stroke such as SLE with antiphospholipid syndrome (SLE/APS), in whom concurrent cardiac and brain lesions have been identified. Furthermore, it may be of value in SLE with multi-organ involvement, NPSLE with concurrent cardiac involvement, and recent onset of arrhythmia and/or heart failure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The vasculitides are a heterogeneous group of disorders, characterized by inflammatory cell infiltration and necrosis of blood vessels that cause vascular obstruction or aneurysm formation, affecting various organs such as lungs, kidneys, skin and joints. Cardiac involvement is commonly encountered in primary systemic vasculitis and it is associated with increased morbidity and mortality. Depending on the dominant pathophysiological mechanism, heart complications may manifest in different ways, including myocardial ischemia due to impaired micro- or macrovascular circulation, progressive heart failure following valvular heart disease and myocardial dysfunction, (sub) clinical myocarditis, pericarditis, pulmonary hypertension as well as arteritis of coronary vessels. Beyond cardioprotective regimens, aggressive immunosuppression reduces the inflammatory burden and modulates the progression of cardiovascular complications. Perioperative management of inflammation, when surgical treatment is indicated, improves surgical success rates and postoperative long-term prognosis. We aim to provide an overview of the pathogenetic, diagnostic and therapeutic principles of cardiovascular involvement disease in the various forms of systemic vasculitis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Biological therapies have represented a cornerstone in the treatment of immune-mediated inflammatory diseases. Their advent combined with implementation of a treat-to-target approach has meant that remission or low disease activity are now realistic targets for treatment achieved by a significant number of patients. However, biologicals are not risk free and their elevated costs continue to present an important economic burden to national healthcare services. "Can we wean patients with inflammatory arthritis from biological therapies?" Over the last decade this question has become increasingly important as to define the best management strategies in terms of efficacy, safety and economic outcomes. Not surprisingly this has generated an interesting debate as to whether reasons to taper biologics outweigh reasons not to taper and evidence in support of either of these schools of thought is persistently growing. AIM: In this article we reviewed the contents of the relevant session from the 2019 Controversies in Rheumatology and Autoimmunity meeting in Florence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Systemic sclerosis (SSc) is a chronic, systemic disease characterized by fibrosis of the skin and internal organs, vasculopathy, and auto-immune activation. On the top of severe organ involvement such as interstitial lung and myocardial fibrosis, pulmonary hypertension, and renal crisis, individuals diagnosed with SSc may suffer from a number of comorbidities. This is a narrative review according to published recommendations and we searched the online databases MEDLINE and EMBASE using as key words the following terms: systemic sclerosis, scleroderma, myocardial fibrosis in combination with micro- and macro-vascular disease, cardiac involvement, atherosclerosis, cardiovascular disease and coronary arteries, infections, cancer, depression, osteoporosis, and dyslipidemia. Although data are usually inconclusive it appears that comorbidities with significant impact on life expectancy, namely cardiovascular disease, infections, and cancer as well as phycological disorders affecting emotional and mental health are highly prevalent in SSc population. Thereafter, the aim of this review is to summarize the occurrence and the clinical significance of such comorbidities in SSc population and to discuss how rheumatologists can incorporate the management of these conditions in daily clinical practice.

Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals, respectively, at baseline. HIV infection was independently associated with carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was independently associated with age, years of smoking, and exposure to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5 cases/100 patients, respectively. Carotid atheromatosis progression was significantly associated with NNRTI exposure. People living with HIV infection exhibited high prevalence and incidence of subclinical arterial damage and site-specific predilection for the carotids. These investigations may help optimize HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis, emphasizing the need to consider the atherogenic potential of antiretroviral drugs in management strategies.

Objective: Knee osteoarthritis (OA) is a risk factor for a decline in gait speed. Daily walking reduces the risk of developing slow gait speed and future persistent functional limitation. However, the protective role of walking intensity is unclear. We investigated the association of substituting time spent not walking, with walking at light and moderate-to-vigorous intensities for incident slow gait over 2-years, among people with or at high risk of knee OA., Method: We used baseline and 2-year follow-up data from the Multicenter Osteoarthritis (MOST) study (n = 1731) and the Osteoarthritis Initiative (OAI, n = 1925). Daily walking intensity was objectively assessed using accelerometer-enabled devices, and classified as; not walking (<1 steps/min), very-light (1-49 steps/min), light (50-100 steps/min), and moderate-to-vigorous (>100 steps/min). We defined slow gait during a 20-m walk, as <1 m/s and <1.2 m/s. Isotemporal substitution evaluated time-substitution effects on incident slow gait outcomes at 2-years., Results: Replacing 20 min/day of not walking with walking at a moderate-to-vigorous intensity, demonstrated small to moderate reductions in the risk of developing a gait speed <1.0 m/s (Relative Risk [95% confidence interval (CI)]; MOST = 0.51 [0.27, 0.98], OAI = 0.21 [0.04, 0.98]), and <1.2 m/s (MOST = 0.73 [0.53, 1.00], OAI = 0.65 [0.36, 1.18]). However, only risk reductions for <1.0 m/s met statistical significance. Replacing not walking with very-light or light intensity walking was not associated with the risk of developing slow gait outcomes., Conclusion: When possible, walking at a moderate-to-vigorous intensity (>100 steps/min) may be best recommended in order to reduce the risk of developing critical slow gait speed among people with, or at high risk of knee OA., (Copyright © 2018 Osteoarthritis Research Society International. All rights reserved.)

Inflammasomes are large intracellular complexes that induce inflammation in response to exogenous and endogenous damage signals. They regulate production and release of the proinflammatory cytokines IL-1β and IL-18, playing a defensive role against infections. Inflammasomes have also been involved in the pathogenesis of a wide range of autoinflammatory conditions that are caused by dysregulation of the IL-1 pathway, such as cryopyrinopathies and hereditary periodic fever syndromes. On top of that, research in recent years suggests that defects in inflammasome regulation and signaling associate with a number of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and others. In this review, we describe the inflammasome and mechanisms that trigger it, provide a brief review of autoinflammatory disorders and discuss the current understanding and emerging data from experimental and clinical studies for the role of the innate immune system and inflammasomes in the biology and pathogenesis of systemic autoimmune diseases.

Although large-scale population studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of myocardial infarction, this is not confirmed in patients with rheumatoid arthritis (RA). Herein, we review the litterature on the differential effects of NSAIDs on cardiovascular risk in osteoarthritis (OA) versus RA and discuss possible explanations for this discrepancy. To assess a potential additive effect of age in non-RA populations, we compared weighted mean age between RA patients and unselected NSAID users included in cohort and case-control studies that estimate the cardiovascular risk of NSAIDs, assuming that the main indication for NSAID usage in elderly populations is OA. Our hypothesis that advanced age in osteoarthtitis compared to RA patients confounds the effect of NSAIDs on cardiovasular risk was not confirmed. Several other hypotheses that can be proposed to explain this counterintuitive effect of NSAIDs on the cardiovascular risk of RA patients are discussed. We conclude that patients with RA have a lower cardiovascular disease risk associated with the use of NSAIDs, probably due to the nature of their disease per se, until further research indicates differently.

Rheumatoid arthritis (RA) is associated with high rates of cardiovascular events mainly due to coronary and cerebrovascular atherosclerotic disease. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines are endogenous inhibitors of nitric oxide synthase and have been repeatedly linked with adverse cardiovascular outcomes in the general population and various disease settings. Alanine-glyoxylate aminotransferase 2 (AGTX2) is considered an alternative metabolic pathway contributing to the clearance of dimethylarginines in humans. The aim of the current study was to investigate the effect of specific AGXT-2 gene polymorphisms on circulating levels of ADMA or SDMA in patients with RA. Serum ADMA and SDMA levels were measured in 201 individuals with RA [median age: 67 years (IQR: 59-73), 155 females]. Two single nucleotide polymorphisms (SNPs) in the AGXT-2 gene-rs37369 and rs28305-were genotyped. Distributions of SDMA and ADMA were skewed, hence comparisons across the gene polymorphisms were performed using Kruskal-Wallis tests, and summarized using medians and interquartile ranges. Univariable analysis did not demonstrate a significant difference in the levels of SDMA or ADMA amongst the different genotypic groups of either rs37369AGXT2 (p = 0.800, 0.977) or rs28305AGXT2 (p = 0.463, 0.634). In multivariable analyses, ADMA levels were found to be significantly associated with erythrocyte sedimentation rate and estimated glomerular filtration rate, whilst SDMA levels were significantly associated with estimated glomerular filtration rate and quantitative insulin sensitivity check index. After adjustments for these factors, the relationship between the AGXT2 gene variants and both ADMA and SDMA remained non-significant. Our study in a well-characterized RA population did not show an association between serum concentrations of dimethylarginines and genetic variants of the AGXT2 gene.

Background: Intra-articular corticosteroid injections (IACI) are effective treatments for pain in knee osteoarthritis (KOA) but treatment response varies. There is uncertainty as to whether structural factors such as accurate placement of IACI affect outcome. We examined this question in a pragmatic observational study, using ultrasound (US) to verify accuracy of IACI., Methods: 105 subjects with KOA (mean age 63.1 years, 59% female) routinely referred for IACI underwent assessment of demographic factors, x-ray and US of the knee before aspiration and IACI (based on clinical landmarks) with 40 mg triamcinolone acetonide with lignocaine plus a small amount of atmospheric air by an independent physician. US demonstration of intra-articular mobile air, i.e. a positive air arthrosonogram, was used to determine accurate placement of injection. Both patients and injecting physicians were blind to the US findings. Pain at baseline, three and nine weeks post injection was assessed using the 500 mm WOMAC pain subscale and response defined as ≥ 40% reduction in pain from baseline. Inter-observer reliability of air-arthrosonogram assessment was good: κ 0.79 (three raters)., Results: Sixty-three subjects (60.6%) were responders at three weeks and 43 (45.7%) at nine weeks. Seventy-four subjects (70.5%) had a positive arthrosonogram. A positive air arthrosonogram did not associate with a higher rate of response to treatment (p 0.389 at three weeks, p 0.365 at nine weeks). There was no difference in US effusion depth, power Doppler signal or radiographic grade between responders and non-responders to the injection, but female gender associated with response at 3 weeks and previous injection with non-response at 9 weeks., Conclusions: Accurate intra-articular injection of corticosteroid results did not result in superior outcome in terms of pain compared to inaccurate injection in symptomatic knee OA.

Systemic Sclerosis (SSc) is an autoimmune disorder characterized by microvascular injury and diffuse fibrosis of the skin and internal organs. While macrovascular disease and higher risk for cardiovascular events are well documented in other systemic rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, the presence and extent of atherosclerosis among patients with SSc is yet to be established. Primary cardiac involvement, due to impairment of coronary microvascular circulation and myocardial fibrosis, considerably affects prognosis and life expectancy of individuals with SSc, representing one of the leading causes of death in this population. On the other hand the existence and prevalence of atherosclerotic coronary disease remains an issue of debate as studies comparing structural and morphological markers of atherosclerosis and cardiovascular events between SSc patients and the general population have yielded controversial results. The aim of this review is to summarize recent literature about the prevalence of cardiovascular disease in SSc, review the surrogate markers of CVD that have been evaluated and examine whether common pathogenic mechanisms exist between SSc and macrovascular disease.

Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality which cannot be fully explained by traditional CV risk factors; cumulative inflammatory burden and antirheumatic medication-related cardiotoxicity seem to be important contributors. Despite the acknowledgment and appreciation of CV disease burden in RA, optimal management of individuals with RA represents a challenging task which remains suboptimal. To address this need, the European League Against Rheumatism (EULAR) published recommendations suggesting the adaptation of traditional risk scores by using a multiplication factor of 1.5 if two of three specific criteria are fulfilled. Such guidance requires proper coordination of several medical specialties, including general practitioners, rheumatologists, cardiologists, exercise physiologists and psychologists to achieve a desirable result. Tight control of disease activity, management of traditional risk factors and lifestyle modification represent, amongst others, the most important steps in improving CV disease outcomes in RA patients. Rather than enumerating studies and guidelines, this review attempts to critically appraise current literature, highlighting future perspectives of CV risk management in RA.

Objective: Ciclosporin and MTX are used in idiopathic inflammatory myopathies (DM and PM) when patients incompletely respond to glucocorticoids. Their effectiveness is unproved in randomized controlled trials (RCTs). We evaluated their benefits in a placebo-controlled factorial RCT., Methods: A 56-week multicentre factorial-design double-blind placebo-controlled RCT compared steroids alone, MTX (15-25 mg weekly) plus steroids, ciclosporin (1-5 mg/kg/day) plus steroids and all three treatments. It enrolled adults with myositis (by Bohan and Peter criteria) with active disease receiving corticosteroids., Results: A total of 359 patients were screened and 58 randomized. Of the latter, 37 patients completed 12 months of treatment, 7 were lost to follow-up and 14 discontinued treatment. Patients completing 12 months of treatment showed significant improvement (P < 0.001 on paired t-tests) in manual muscle testing (14% change), walking time (22% change) and function (9% change). Intention to treat and completer analyses indicated that ciclosporin monotherapy, MTX monotherapy and ciclosporin/MTX combination therapy showed no significant treatment effects in comparison with placebo., Conclusion: Neither MTX nor ciclosporin (by themselves or in combination) improved clinical features in myositis patients who had incompletely responded to glucocorticoids., Trial Registration: International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/; ISRCTN40085050., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology.)