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

Inflammation, carotid intima-media thickness and atherosclerosis in rheumatoid arthritis

Carotid intima-media thickness (cIMT) reflects early atherosclerosis and predicts cardiovascular events in the general population. An increased cIMT is present in patients with rheumatoid arthritis, compared with control individuals, from the early stages of the disease and is thought to indicate accelerated atherosclerosis, but direct evidence is not available. Whether cIMT is susceptible to rapid and potentially reversible change depending on the intensity of inflammation in states of high-grade systemic inflammation, such as rheumatoid arthritis, remains unknown. If this is the case, an increased cIMT in such disease states may not reflect structural vessel wall damage, and may not be a good predictor of future cardiovascular events in these particular populations. Prospective, long-term, longitudinal studies are needed to address these questions

Body-size phenotypes and cardiometabolic risk in Rheumatoid Arthritis

Objectives: Obesity is a significant contributor to metabolic complications. However, such complications are not uniform in people with similar body-size. The existence of normal-weight individuals with and obese individuals without metabolic complications has been described in the general population and is important in the context of cardiovascular disease (CVD). This has not been investigated in rheumatoid arthritis (RA), a condition associated with increased cardiometabolic risk. This study aims to identify the prevalence and predictors of body-size phenotypes in RA and investigate their associations with CVD risk. Methods: Body mass index (BMI: kg/m2), body fat (BF) and fat free mass (FFM), RA characteristics and CVD risk factors were assessed in 363 (262 females) volunteers with RA. Abnormal cardiometabolic status was defined as the presence of >1 of the following: hypertension, increased triglycerides or increased Low or reduced High Density Lipoprotein, high glucose, insulin resistance. Results: Among normal-weight, overweight, and obese participants 25%, 45.8%, 57.1% respectively were metabolically abnormal. Old age (B= 1.032, err=0.011; p= 0.005), waist circumference (B= 1.057, err= 0.011; p= 0.000), and smoking cessation (B= 1.425, err= 0.169; p=0.036) were significant predictors for metabolic abnormality. Conclusions: A significant number of RA patients present with different body-size and metabolic phenotypes. BMI alone is not a sufficient indicator of cardiometabolic risk in RA; this may have significant implications in their CVD risk evaluation. Body fat distribution seems to be a significant contributor to such abnormalities. Further research is needed, focusing on the metabolic properties of specific adipose depots of RA patient

Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain

BACKGROUND: Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery. METHODS: We have investigated spinal drug administration systems for patients with failed back syndrome and chronic mechanical low back pain by patient questionnaire study of the efficacy of this therapy and a case notes review. RESULTS: 36 patients (97% of 37 approached) completed questionnaires, 24 with failed back syndrome and 12 with chronic mechanical low back pain. Recalled pre-treatment levels with current post-treatment levels of pain and a range of quality of life measures (recorded on 11-point numerical rating scales) were compared. Pain improved significantly in both groups (Wilcoxan signed ranks test, p < 0.005). The majority of quality of life measures improved significantly in the failed back syndrome group (Wilcoxan signed ranks test, p < 0.005) although work interruption and the effect of pain on sex life did not change. There was a trend towards improvement in the majority of quality of life measures in the mechanical back pain group but this did not reach statistical significance due to the smaller numbers in this cohort (p > 0.005, Wilcoxan signed ranks test with Bonferroni correction). Diamorphine was used in all 37 patients, bupivacaine in 32, clonidine in 27 and baclofen in 3. The mean dose of diamorphine increased for the first 2 years but did not change 2–6 years post implant, averaging 4.5 mg/day. Revision surgery was required in 24% of cases, but reduced to 12% in the later years of our experience. CONCLUSIONS: We conclude that spinal drug administration systems appear to be of benefit in alleviating pain in the failed back syndrome and chronic mechanical low back pain but need to be examined prospectively

Endothelial injury in rheumatoid arthritis: a crosstalk between dimethylarginines and systemic inflammation

BACKGROUND: Symmetric (SDMA) and asymmetric (ADMA) dimethylarginines have emerged as novel biomarkers of cardiovascular disease (CVD) in several disease settings associated with atherosclerosis. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by high CVD mortality and morbidity. ADMA and SDMA levels are abnormal in RA patients, but their correlation with assessments of endothelial function and structure remains unknown. We aimed to investigate whether SDMA and ADMA are associated with carotid intima media thickness (cIMT) and arterial stiffness as well as non-invasive assessments of in vivo micro- and macrovascular endothelial function in RA patients with high systemic inflammatory load. METHOD: ADMA and SDMA levels were measured using immunoassays in 197 RA individuals. Twenty-six of these [23 (86.4%) females, median age 70, quartiles (60, 73)] were identified as having high inflammatory markers [erythrocyte sedimentation rate (ESR) >25 mm/hr and C-reactive protein (CRP) > 5 mg/L], and were compared to the remainder of the cohort. Patients underwent assessments of microvascular endothelium-dependent and endothelium-independent function [laser Doppler imaging with iontophoresis of acetylcholine (Ach) and sodium-nitroprusside (SNP) respectively], macrovascular endothelium-dependent and endothelium-independent function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilation respectively), and vascular morphology [pulse wave analysis, and carotid intima media thickness (cIMT)]. RESULTS: Significant interactions with inflammation were detected in the associations between ACh and both SDMA (p = 0.014) and ADMA:SDMA ratio (p = 0.027), as well as between SNP and SDMA (p = 0.042) and between arterial stiffness and ADMA:SDMA (p = 0.036), with the associations being stronger in the patients with high inflammatory markers in each case. CONCLUSIONS: Besides their emerging role as markers of endothelial dysfunction SDMA and ADMA may promote endothelial injury in RA as mediators of the adverse effects of systemic inflammation on micro- and macrovasculature respectively in patients with active disease

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

This is an accepted manuscript of an article published by Taylor & Francis in Expert Review of Clinical Immunology on 28/01/2020, available online: https://doi.org/10.1080/1744666X.2020.1714438 The accepted version of the publication may differ from the final published version.Pain is the main symptom in most rheumatic and musculoskeletal diseases (RMDs). It has debilitating effects in terms of mobility, physical function, sleep, mood, fatigue, and overall quality of life. This is why pain and its associates are some of the predominant outcomes evaluated regularly in response to pharmaceutical or any other interventions involved in the management of RMDs.Published versio

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

This is an accepted manuscript of an article published by Elsevier in Best Practice and Research: Clinical Rheumatology in October 2018, available online: https://doi.org/10.1016/j.berh.2019.03.013 The accepted version of the publication may differ from the final published version.© 2019 Elsevier Ltd 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.Published versio