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

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

Cardiorespiratory fitness levels and their association with cardiovascular profile in patients with rheumatoid arthritis: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the association of different physical fitness levels [assessed by the maximal oxygen uptake (VO2max) test] with cardiovascular disease (CVD) risk factors in patients with RA. METHODS: A total of 150 RA patients were assessed for cardiorespiratory fitness with a VO2max test and, based on this, were split in three groups using the 33rd (18.1 ml/kg/min) and 66th (22.4 ml/kg/min) centiles. Classical and novel CVD risk factors [blood pressure, body fat, insulin resistance, cholesterol, triglycerides, high-density lipoprotein (HDL), physical activity, CRP, fibrinogen and white cell count], 10-year CVD risk, disease activity (DAS28) and severity (HAQ) were assessed in all cases. RESULTS: Mean VO2max for all RA patients was 20.9 (s.d. 5.7) ml/kg/min. The 10-year CVD risk (P = 0.003), systolic blood pressure (P = 0.039), HDL (P = 0.017), insulin resistance and body fat (both at P < 0.001), CRP (P = 0.005), white blood cell count (P = 0.015) and fibrinogen (P < 0.001) were significantly different between the VO2max tertiles favouring the group with the higher VO2max levels. In multivariate analyses of variance, VO2max was significantly associated with body fat (P < 0.001), HDL (P = 0.007), insulin resistance (P < 0.003) and 10-year CVD risk (P < 0.001), even after adjustment for DAS28, HAQ and physical activity. CONCLUSION: VO2max levels are alarmingly low in RA patients. Higher levels of VO2max are associated with a better cardiovascular profile in this population. Future studies need to focus on developing effective behavioural interventions to improve cardiorespiratory fitness in RA

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

Exercise and inflammation

This is an accepted manuscript of an article published by Elsevier in Best Practice and Research: Clinical Rheumatology on 02/04/2020, available online: https://doi.org/10.1016/j.berh.2020.101504 The accepted version of the publication may differ from the final published version.�� 2020 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.Published versio

Sedentary behaviour is associated with increased long-term cardiovascular risk in patients with rheumatoid arthritis independently of moderate-to-vigorous physical activity

Background Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD). The physical dysfunction symptomatic of RA means people living with this disease spend large periods of the day sedentary, which may further elevate their risk of CVD. The primary aim of this study was to investigate relationships between objectively assessed sedentary behaviour patterns and light physical activity (LPA) with 10-year risk of CVD. Secondary aims were to explore the role of sedentary behaviour patterns and LPA for individual CVD risk factors and functional disability in RA. The extent to which associations were independent of moderate-to-vigorous physical activity (MVPA) engagement was also examined. Methods Baseline data from a subsample of participants recruited to the Physical Activity in Rheumatoid Arthritis (PARA) study were used to answer current research questions. Sixty-one patients with RA (mean age (± SD) = 54.92 ± 12.39 years) provided a fasted blood sample and underwent physical assessments to evaluate factors associated with their cardiovascular health. Sedentary behaviour patterns (sedentary time, sedentary bouts, sedentary breaks), LPA and MVPA were measured via 7-days of accelerometry. Ten-year CVD risk was computed (Q-risk-score2), and functional disability determined via questionnaire. Results Regressions revealed significant positive associations between sedentary time and the number of sedentary bouts per day ≥20 min with 10-year CVD risk, with the reverse true for LPA participation. Associations were independent of MVPA engagement. Conclusions Promoting LPA participation and restricting sedentary bouts to <20 min may attenuate long-term CVD risk in RA, independent of MVPA engagement

Measurement of sedentary time and physical activity in rheumatoid arthritis: an ActiGraph and activPAL™ validation study

© 2020 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1007/s00296-020-04608-2© 2020, The Author(s). Accurate measurement of sedentary time and physical activity (PA) is essential to establish their relationships with rheumatoid arthritis (RA) outcomes. Study objectives were to: (1) validate the GT3X+ and activPAL3μ™, and develop RA-specific accelerometer (count-based) cut-points for measuring sedentary time, light-intensity PA and moderate-intensity PA (laboratory-validation); (2) determine the accuracy of the RA-specific (vs. non-RA) cut-points, for estimating free-living sedentary time in RA (field-validation). Laboratory-validation: RA patients (n = 22) were fitted with a GT3X+, activPAL3μ™ and indirect calorimeter. Whilst being video-recorded, participants undertook 11 activities, comprising sedentary, light-intensity and moderate-intensity behaviours. Criterion standards for devices were indirect calorimetry (GT3X+) and direct observation (activPAL3μ™). Field-validation: RA patients (n = 100) wore a GT3X+ and activPAL3μ™ for 7 days. The criterion standard for sedentary time cut-points (RA-specific vs. non-RA) was the activPAL3μ™. Results of the laboratory-validation: GT3X—receiver operating characteristic curves generated RA-specific cut-points (counts/min) for: sedentary time = ≤ 244; light-intensity PA = 245–2501; moderate-intensity PA ≥ 2502 (all sensitivity ≥ 0.87 and 1-specificity ≤ 0.11). ActivPAL3μ™—Bland–Altman 95% limits of agreement (lower–upper [min]) were: sedentary = (− 0.1 to 0.2); standing = (− 0.7 to 1.1); stepping = (− 1.2 to 0.6). Results of the field-validation: compared to the activPAL3μ™, Bland–Altman 95% limits of agreement (lower–upper) for sedentary time (min/day) estimated by the RA-specific cut-point = (− 42.6 to 318.0) vs. the non-RA cut-point = (− 19.6 to 432.0). In conclusion, the activPAL3μ™ accurately quantifies sedentary, standing and stepping time in RA. The RA-specific cut-points offer a validated measure of sedentary time, light-intensity PA and moderate-intensity PA in these patients, and demonstrated superior accuracy for estimating free-living sedentary time, compared to non-RA cut-points.Published versio

Investigating the effectiveness and feasibility of exercise on microvascular reactivity and quality of life in systemic sclerosis patients: study protocol for a feasibility study

Background: Raynaud’s phenomenon is one of the first clinical manifestations observed in systemic sclerosis (SSc). This microvasculature disorder affects mostly the digits in over 95% of SSc patients, significantly affecting their healthrelated quality of life (HRQoL) and incurring higher hospital admissions and other healthcare costs. Exercise is known to improve both micro- and macrovascular function – aerobic exercise and resistance training, separately or combined, have been demonstrated to lead to significant vasculo-physiological improvements in conditions that present vasculopathy. However, the effects of a combined exercise programme on microcirculation in SSc patients has yet to be investigated. Therefore, the purpose of this study is to assess the effects of high-intensity interval training (HIIT) combined with circuit resistance training on the microvascular function in the digital area of SSc patients. Methods: This will be a randomised controlled, feasibility trial with two arms, wherein 30 patients with SSc in receipt of medical treatment will be randomly assigned to usual care (medical treatment) or to a 12-week supervised exercise programme. Patients in the exercise group will undertake two, 45-min sessions each week consisting of 30 min HIIT (30 s 100% peak power output/30 s passive recovery) on the arm crank ergometer and 15 min of upper body circuit resistance training. Patients will be assessed before as well as at 3 and 6 months following randomisation. Primary outcomes of the study will be recruitment and retention rate, intervention acceptability and adherence to the exercise programme. Secondary outcomes include the digital area cutaneous microvascular function (laser Doppler fluximetry combined with iontophoresis), physical fitness, functional ability, upper back transcutaneous oxygen tension, body composition and quality of life (EQ-5D-5L). Selected interviews with a subsample of patients will be undertaken to explore their experiences of having Raynaud’s phenomenon and the acceptability of the exercise intervention and study procedures. Discussion: Data from this study will be used to identify the feasibility of a combined exercise programme to be implemented in SSc patients, the acceptability of the intervention and the study design, and to determine the effects of exercise on the microvasculature. Overall, this study will provide sufficient data to inform and support a full multicentre clinical trial

Implementation of Physical Activity in the Curricula of Medical Schools and Healthcare Professions Across Europe: The VANGUARD Project Study Protocol

"Introduction: The 2018 published World Health Organisation (WHO) Europe physical activity factsheet reports, specify agreed targets for physical activity and articulate the need to improve the education of medical doctors and healthcare practitioners in order to increase physical activity and reduce sedentary time in people at risk and/or living with Noncommunicable Diseases (NCDs). Given the dearth of relevant initiatives and the continuous need to increase physical activity participation towards better health management of NCDs, the aim of this study is to embed physical activity in the undergraduate curricula of future frontline healthcare professionals (medical doctors and allied health professions) in European countries. Methods: The Virtual Advice, Nurturing, Guidance on Universal Action, Research and Development for physical activity and sport engagement (VANGUARD) project consists of a collaborative partnership Consortium between six European Universities, WHO Europe and Ministry representatives that has been developed to implement physical activity in the curricula of medical schools and healthcare professions. The methodology of the VANGUARD project is informed by the WHO implementation guidance and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. Discussion: Through a carefully planned implementation process and via using established appropriate implementation evaluation tools, the end result of the VANGUARD project will be the a) implementation of a physical activity module in six different European Universities (five medical schools and one physiotherapy department) and b) development of a toolkit/guide, in order to assist other healthcare systems and European Universities to develop relevant grass-root innovations for addressing the decline in physical activity levels.