title: Advances in physical activity prescription for rheumatoid arthritis and the influence on cardiovascular risk
Creators: name: Bannell, D
Publisher: name: Liverpool John Moores University
Year: 2025

description: There is a plethora of evidence that people living with rheumatoid arthritis (RA) demonstrate reduced engagement in physical activity (PA) and exercise in comparison to their non-RA counterparts (Lee et al., 2012b, Summers et al., 2019). This has been demonstrated in multiple ways, such as device-based accelerometery measurements (Prioreschi et al., 2013) and self-reported questionnaires (Sokka et al., 2008). Physical inactivity is a known traditional cardiovascular disease (CVD) risk factor, that has been observed to increase CVD risk in people living with RA (Metsios et al., 2009). Indeed, CVD represents the primary cause of mortality in people living with RA (Kitas and Gabriel, 2011). The ~50% increased CVD risk in people living with RA compared to the general population (Agca et al., 2017) is explained by both traditional (e.g., physical inactivity, hypertension) and specific novel RA (e.g. systemic inflammation) risk factors (Skeoch and Bruce, 2015). It has been suggested that these risk factors should be considered collectively to have the best possible impact on reducing CVD risk (Liao and Solomon, 2013, Skeoch and Bruce, 2015). PA represents a modifiable CVD risk factor in RA that may benefit both disease symptoms as well as CVD risk. As such, it is important to assess the latest novel advances in PA prescription for people living with RA, due to their known inactivity, in order to positively impact these patients holistically in terms of their disease specific issues and overall health. It is equally important to examine vascular function in people living with RA as changes in vascular structure and function across the vascular tree may be involved in the development of CVD and are also modifiable. Previous research has observed mixed findings in various vascular, though the cerebrovasculature in particular is an under researched area in the RA population, despite emerging evidence of links between RA and cerebrovascular disease (Wiseman et al., 2016). The overarching aim of the body of work described in this thesis was to explore advances in PA prescription for people living with RA, as well as assessing the influence this may have on CVD risk. In addition, previous literature employing exercise interventions in people living with RA was examined in order to assess its quality and try to understand potential reasons why people with RA remain inactive despite the known benefits. Chapter 3 examined the feasibility and acceptability of a home-based exercise and PA intervention supported by mHealth technology, and a home-based exercise intervention supported by the provision of virtual exercise resources in sedentary individuals, as well as remote data collection techniques. Anthropometric and PA data were collected remotely prior to and following a home-based exercise intervention incorporating i) mobile health (mHealth) technology and exercise counselling, or ii) online resources only. Semi-structured interviews to explore participant experiences were conducted pre- and post-intervention. Data provided novel evidence that both interventions had a positive impact on exercise behaviour, though preliminary outcome data demonstrated greater improvements in PA and adherence to exercise prescription were evident in the mHealth technology supported intervention. This included a greater increase in moderate-to-vigorous PA (MVPA) completed in 10-minute bouts (MVPA+10) in the mHealth group (58 min/wk; CI= -0.06, 0.98, d= 0.47) compared to the online resources group (14 min/wk, CI= -0.32, 0.54, d= 0.12). Moreover, data also revealed that remote data collection techniques were a feasible approach to obtain data. Positive participant perceptions of both the mHealth supported exercise intervention and remote data collection techniques reinforced the feasibility of both remote interventions and data collection. Chapter 4 utilised both the mHealth supported intervention style and remote data collection piloted in Chapter 3 by examining the effectiveness of an mHealth technology supported intervention to increase PA levels in people living with RA. Secondary to this, the study assessed adherence and compliance to the intervention, and the effect on basic clinical outcomes, quality of life and disease activity. Fifty people with RA were randomised to either MOTIVATE RA (mHealth supported walking intervention) or conventional care (CC) groups. Both groups underwent the remote assessment of general health and disease outcomes, anthropometrics and PA prior (T1) to and after (T2) a 12-week intervention period, followed by a three-month optional follow-up assessment (T3). The MOTIVATE RA group demonstrated greater levels of PA at the end of the intervention compared to the CC group, though it is important to note that no outcomes reached statistical significance. The MOTIVATE RA group were performing 103 minutes (95% CI = -17, 224; P = 0.09) more MVPA than the CC group at T2. Additionally, the MOTIVATE RA group’s average accelerations were observed to be 1.2mg/day (95% CI = -3.5, 5.8; P = 0.61) higher than the CC group, crossing the threshold for a minimal clinically important different (MCID). Though there were limited differences in health and disease symptom related outcomes between groups (P &gt; 0.05). Adherence (73%) and compliance (91%) within the MOTIVATE RA group provided evidence that the intervention was feasible for people living with RA. Exploratory analysis of optional three-month follow up data in a subset of participants revealed no significant group*time interactions (P &gt; 0.05). The study demonstrated that mHealth technology supported interventions are feasible for people living with RA and data indicated that such interventions may elicit clinically meaningful change, via increases in MVPA. Chapter 5 explored the impact of RA on micro-, macro- and cerebrovascular function in comparison to matched controls via the concurrent assessment of vascular function across the vasculature tree. Seven females with a clinical diagnosis of RA and 8 female non-RA control participants were recruited to undergo a battery of vascular assessments including; endothelial function via brachial and femoral artery flow-mediated dilation assessment, cutaneous microvascular function assessment via response to post-occlusive reactive hyperaemia (PORH) and cerebrovascular function via measurements of cerebral reactivity to CO2 and cerebral autoregulation (CA). These preliminary data demonstrated microvascular dysfunction in people living with RA in both the upper and lower limbs. Peak cutaneous vascular conductance (CVC) in the RA group was lower than in the control group, though this did not reach statistical significance (-0.37 PU.mmHg-1, 95% CI = -0.82, 0.08, P = 0.10). The %base-peak in the RA group was lower than in the control group, though this did not reach statistical significance (-94%, 95% CI = -202, 15, P = 0.08). Vascular dysfunction was also present in people living with RA in the macrovasculature, though only in the lower limbs, with upper limb flow-mediated dilation (FMD) similar between RA and control groups. There was no difference in allometrically scaled FMD% in the RA group compared to their non-RA counterparts (-0.2%, 95% CI = -1.9, 1.5, P = 0.78). Allometrically scaled FMD% was lower in the RA group than the control group but was non-significant (-1.5%, 95% CI = -3.2, 0.3, P = 0.09). Finally, it was identified that there was no difference between the RA group and control group for cerebral reactivity to CO2. Absolute and relative gain of cardiovascular reactivity to CO2 (CVRCO2) and CVRCO2MAP (accounting for the effects of mean arterial pressure [MAP] changes on CVRCO2) during CO2 inhalation was not different between the RA and control groups (P &gt; 0.05, Table 5). Interestingly, dynamic cerebral autoregulation (dCA) appeared to demonstrate a more efficient response in the RA group compared with the control group. Normalised gain was lower in the RA group than in their non-RA counterparts, though this did not reach statistical significance (-0.29 %cm.s-1.%mmHg-1, 95% CI = -0.58, 0.00, P = 0.05). Though these preliminary data constituted a low sample size and lack of statistical power, as well as the absence of normative values making it hard to draw firm conclusions from these data. Overall, it was demonstrated that people living with RA may exhibit vascular dysfunction in both the micro- and macrovasculature, whilst the cerebrovascular appears unaltered. Chapter 6 employed a systematic scoping review to summarise existing exercise interventions utilised in randomised controlled trials (RCTs) involving individuals living with RA. This review assessed their level of reporting applying the Consensus on Exercise Reporting Template (CERT). Interventions involved a combination of supervised aerobic and resistance exercise completed over ~3 sessions per week, lasting a total of ˜147-162 minutes, most often at a moderate intensity. Exercise intervention reporting quality was poor, the median score was seven (range 1-13) out of 19. Thirteen exercise interventions had a CERT score of ≥10, while the remaining 37 interventions (74%) all scored &lt;10. This review demonstrates that the quality of reporting for exercise interventions designed for people living with RA is very poor. Significant improvements to reporting are needed in order to enable quality replication and improve translation into clinical settings. Collectively, the data contained within this thesis suggests that remote mHealth technology supported interventions are feasible for people living with RA and may elicit clinically meaningful changes in PA behaviour, with remote data collection techniques being feasible and successful in monitoring such interventions. Increasing PA is an important management strategy for RA as this thesis has also shown people living with RA may have vascular dysfunction across the vascular tree, which leads to increased CVD risk. Moreover, future research employing exercise interventions in people living with RA, in attempts to upregulate PA and lower CVD risk, need to significantly improve reporting standards in order for findings to translate to a clinical setting.