Changing cardiovascular disease risk, cardiorespiratory fitness and muscle strength by exercise in rheumatoid arthritis

People with rheumatoid arthritis (RA) often suffer from elevated cardiovascular disease (CVD) risks and muscle weakness, which affects their quality of life. An important means to improve these disease outcomes is via exercise. While exercise guidelines exist for individuals with arthritis, there remains insufficient evidence regarding the effects of different exercise dosages on disease outcomes. Therefore, in clinical practise, patients with RA may not always be provided with the optimal exercise intervention thereby, resulting in sub-optimal treatment outcomes. Treatment outcomes could be improved through the better understanding of exercise on disease symptoms. The main aims of this thesis were to first, quantitatively and qualitatively investigate the effectiveness of exercise as a disease modifier in a specific sub-group of RA patients with high CVD risks. Second, to investigate the metabolic activity of the muscles of patients with RA and use this as foundation to develop a protocol to investigate the effects of exercise on underlying mechanisms of muscle weakness in patients with RA. In this concluding chapter, the main findings are discussed, followed by considerations on methodological strengths and limitations, clinical implications, and directions for future research. Chapter 2 describes a cross-sectional study to determine CRF and PA levels and to investigate their association in patients with CVD-RA. Following up from this study, Chapter 3 is a longitudinal study which investigates the safety of moderate-to-high intensity exercise on patients with CVD-RA and; the effects of exercise on CRF, disease activity and CV risk factors in patients with CVD-RA. A qualitative study is performed on the same group of patients to assess the experience of the patients who underwent the exercise intervention. The results are presented in Chapter 4. Chapter 5 provides a scoping review of current evidence on the efficacy of simultaneous administration of exercise and DMARDs on disease activity. To gain insight into the muscle pathology of RMD patients, a methodological study is described in Chapter 6. In this study, F18-fluordeoxyglucose ([18F]-FDG) positron emission tomography and computed tomography (PET/CT) scans were used to assess and compare pathophysiological muscle glucose uptake between patients with rheumatic musculoskeletal diseases (RMDs) and non-RMDs controls. To further explore the association of muscle characteristics with exercise, Chapter 7 provides a study protocol to explore differential responses of exercise intervention on muscle strength in patients with RMDs.