A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis. Damage to the endothelium may predispose the vessel to atherosclerosis and increase the risk for cardiovascular disease. Assessments of peripheral endothelial function are good indicators of early abnormalities in the vascular wall and correlate well with assessments of coronary endothelial function. The present manuscript details the important methodological steps necessary for the assessment of microvascular endothelial function using laser Doppler imaging with iontophoresis, large vessel endothelial function using flow-mediated dilatation, and carotid atherosclerosis using carotid artery ultrasound. A discussion on the methodological considerations for each of the techniques is also presented, and recommendations are made for future research

Symmetric Dimethylarginine Is Not Associated with Cumulative Inflammatory Load or Classical Cardiovascular Risk Factors in Rheumatoid Arthritis: A 6-Year Follow-Up Study

Symmetric dimethylarginine (SDMA) indirectly inhibits nitric oxide (NO) synthesis and predicts cardiovascular and all-cause mortality in high-risk patients. The aim of our study was to investigate the associations of cumulative inflammatory burden (assessed by serial measurements of inflammatory markers) and classical cardiovascular (CV) disease risk factors with SDMA in RA patients. 201 RA patients (155 females, median age 67 (59�73)) were assessed at baseline (2006). Classical CV disease risk factors were recorded and systemic inflammation was determined by themeasurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) SDMA levels were measured by enzyme-linked immunosorbent assay.Mean SDMA levels in RA population were 0.40 (0.40�0.53) ����mol/L. No significant association between SDMA and cumulative inflammatory load was established in the analysis. SDMA levels were not found to be significantly related to CV disease risk factors.We explored the potential relationship between SDMA and cumulative inflammatory burden in patients with RA and obtained negative results. SDMA did not relate to CV disease risk factors in our population and its clinical significance as a surrogate marker of endothelial dysfunction in patients with RA remains to be determined

Artificial intelligence-based preventive, personalized and precision medicine for cardiovascular disease/stroke risk assessment in rheumatoid arthritis patients: a narrative review

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP3) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™–aiP3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature

The effects of exercise on cardiovascular disease risk factors and cardiovascular physiology in rheumatoid arthritis

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA.Published versio

Physical activity but not sedentary activity is reduced in primary Sjögren’s syndrome

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren’s syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594–3158) versus 3708 (1732–8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135–375) versus 343 (223–433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0–480) versus 1560 (570–3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0–480) versus 480 (0–1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS

Should patients with rheumatic diseases take pain medication in order to engage in exercise?

[No abstract available

Physical activity, exercise and rheumatoid arthritis: Effectiveness, mechanisms and implementation

Rheumatoid arthritis (RA) is characterised by functional disability, pain, fatigue and body composition alterations that can further impact on the physical dysfunction seen in RA. RA is also associated with systemic manifestations, most notably an increased risk for cardiovascular disease. There is strong evidence to suggest that increasing physical activity and/or exercise can simultaneously improve symptoms and reduce the impact of systemic manifestations in RA. However, implementation of interventions to facilitate increased physical activity and/or exercise within routine clinical practice is slow because of not only patient-specific and healthcare professional-related barriers but also lack of relevant infrastructure and provision. We review the evidence supporting the physiological adaptations and beneficial effects occurring as a result of increased physical activity and/or exercise in RA and propose an implementation model for facilitating the long-term engagement of patients with RA. We propose that implementation should be led, in a pragmatic manner, by rheumatology healthcare practitioners and supported by social innovation. © 2019 Elsevier Lt

A different perspective: Inflammatory rheumatic diseases and other organs

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Exercise and inflammation

Based on current knowledge deriving from studies in animals and humans (the general population and patients with non-communicable diseases), there is biological plausibility that exercise may have anti-inflammatory effects. This may be particularly important for patients with chronic inflammatory rheumatic and musculoskeletal diseases (RMDs). The present review discusses the current state-of-the-art on exercise and inflammation, explores how exercise can moderate inflammation-dependent RMD outcomes and the most prevalent systemic manifestations and addresses the relationship between the dosage (particularly the intensity) of exercise and inflammation. We conclude that present data support potential beneficial effects of exercise on inflammation, however, the evidence specifically in RMDs is limited and inconclusive. More targeted research is required to elucidate the effects of exercise on inflammation in the context of RMDs. © 202

Endothelial dysfunction as a determinant of trastuzumab-mediated cardiotoxicity in patients with breast cancer

BACKGROUND: Breast cancer is the most common cancer in females in the UK and has greater severity in patients who overexpress human epidermal growth receptor 2 (HER2) proteins in the breast tissue. Trastuzumab is a humanised monoclonal antibody and is targeted towards blocking the HER2 pathway and effectively reduces the recurrence of breast cancer and associated mortality. However, trastuzumab is also associated with an increased risk of cardiotoxicity which likely results from inhibition of the HER2 pathway. Under normal conditions HER2 pathways help maintain the integrity of the myocardial contractile elements, as well as the coronary vasculature, but trastuzumab inhibits these survival pathways and increases the risk for congestive heart failure (CHF). In the present review, we summarise the pathways that are implicated in the development of CHF in patients receiving trastuzumab. We also highlight the role of trastuzumab-mediated endothelial dysfunction and CHF