Dr Antonis Stavropoulos-Kalinoglou

There is convincing evidence to suggest that exercise interventions can significantly improve disease-related outcomes as well as comorbidities in rheumatic and musculoskeletal diseases (RMDs). All exercise interventions should be appropriately defined by their dose, which comprises of two components: a) the FITT (frequency, intensity, time and type) and b) the training (ie, specificity, overload, progression, initial values, reversibility, and diminishing returns) principles. In the published RMD literature, exercise dosage is often misreported, which in "pharmaceutical treatment terms", this would be the equivalent of receiving the wrong medication dosage. Lack of appropriately reporting exercise dosage in RMDs, therefore, results in limited clarity on the effects of exercise interventions on different outcomes while it also hinders reproducibility, generalisability and accuracy of research findings. Based on the collective but limited current knowledge, the main purpose of the present Position Statement is to provide specific guidance for RMD researchers to help improve the reporting of exercise dosage and help advance research into this important field of investigation. We also propose the use of the IMPACT-RMD toolkit, a tool that can be used in the design and reporting phase of every trial.

People with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Both pharmacological treatment and exercise are suggested in the management of CVD risk in RA. This study explored the effects of exercise and anti-TNF treatment on CVD risk in RA. Twenty RA patients (70% female, 50 (10) years) completed a 3-month exercise intervention and 23 RA patients (65% female, 54 (15) years) started anti-TNF treatment. Markers of disease activity, CVD risk, and vascular function were assessed before and after 3-months of intervention/treatment. Both exercise and anti-TNF treatment improved functional ability and fatigue, anti-TNF treatment was more successful in improving inflammation, disease activity, functional ability and pain. Exercise induced a reduction in overall CVD risk and improvement in vascular function, which was significantly different from anti-TNF treatment where no such changes were found. These findings showed that exercise and anti-TNF had differential effects on CVD risk in RA, and should be combined for optimal CVD risk reduction. Whereas anti-TNF treatment is likely to impact on CVD risk through reducing the systemic inflammatory load, exercise should be recommended to people with RA as an effective self-management strategy to reduce CVD risk further. Once RA patients have responded successfully to anti-TNF treatment, increasing exercise should be encouraged to reduce the risk for CVD. Thus, supporting exercise programmes when the disease is controlled, is likely to enhance the uptake and the maintenance of exercise, which will result in additional benefits to cardiovascular health and wellbeing in people with RA.

Metabolism is one of the most important physiological functions. Resting energy expenditure, physical activity and diet are the main factors of total metabolism but the contribution of these components to total energy expenditure may be significantly changed with chronic inflammatory diseases such as rheumatoid arthritis (RA). RA is a disease that alters normal metabolism due to the overproduction of pro-inflammatory cytokines and may lead to rheumatoid cachexia. This review focuses on the individual components of total energy expenditure and discusses how physical activity and diet may influence resting metabolism both in the healthy population as well as patients with RA. Moreover, information is provided regarding the available patents (i.e. equipment and prediction equations) that may be used in order to predict metabolism in the normal population and RA patients. © 2008 Bentham Science Publishers Ltd.

The introduction of statins and drugs blocking the renin angiotensin aldosterone system in the treatment of cardiovascular diseases (CVD) in the general population has led to substantial reductions in morbitity and mortality. Recent evidence suggests multiple actions of these agents, including modulation of the immune response and attenuation of inflammation. Even though several studies have addressed the anti-inflammatory properties of these drugs in the general population, only few studies have focused on their potential benefit when administered to patients with rheumatoid arthritis (RA), a chronic systemic disease characterised by both inflammatory joint damage and excess cardiovascular mortality. The present review focuses on the potential role of these agents in reducing the excess CVD (by controlling cardiovascular risk factors, improving endothelial dysfunction, reducing size and increasing stability of atheromatous plaques, activating the fibrinolytic system and reducing systemic inflammation) and in controlling the disease itself (both systemic and localised joint inflammation), in RA patients. Overall, the review has strong evidence to support the effects of statins on reducing cardiovascular risk, however by comparison the evidence supporting their efficacy in RA is relatively weak. © 2008 Bentham Science Publishers Ltd.

Objectives: To assess whether body mass index (BMI) and body fat (BF) differ between rheumatoid arthritis (RA) patients, patients with non-inflammatory arthritis (osteoarthritis, OA) and healthy individuals, and whether disease specific measures of adiposity are required to accurately reflect BF in these groups. Methods: 641 individuals were assessed for BMI (kg/m

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Objective: Basal metabolic rate (BMR) is the most important indicator of human metabolism and its abnormalities have been linked to undesirable health outcomes. Cigarette smoking associates with increased BMR in healthy individuals; it is also related with worse disease outcomes in patients with rheumatoid arthritis (RA), in whom BMR is high due to hypercatabolism caused by systemic inflammation. We aimed to investigate whether smokers with RA demonstrated higher BMR levels than their non-smoking counterparts. Methods: A total of 53 patients with RA (36 female, 17 male, 20 current smokers) were assessed for: BMR (indirect calorimetry), anthropometrical data, fat-free mass (bioelectrical impedance), physical function (health assessment questionnaire; HAQ) and disease activity (disease activity score DAS28 and C reactive protein). Results: RA smokers and non-smokers were not significantly different for age, height, weight, body mass index and fat-free mass. Compared to non-smokers, smokers with RA demonstrated significantly higher BMR (mean (SD) 1513.9 (263.3) vs 1718.1 (209.2) kcal/day; p<0.001) and worse HAQ (1.0 (0.8) vs 1.7 (0.8); p = 0.01). The BMR difference was significantly predicted by the interaction smoking/gender (p = 0.04). BMR was incrementally higher in light, moderate and heavy smokers (p = 0.018), and correlated with the daily number of cigarettes smoked (r = 0.68, p = 0.04). Conclusion: Current cigarette smoking further increases BMR in patients with RA and has a negative impact on patients' self-reported functional status. Education regarding smoking cessation is needed for the RA population.

Hypertension (HT) is highly prevalent in rheumatoid arthritis (RA). Serum uric acid (SUA) has been associated with HT in the general population. The mutual exclusion of gout and RA, and the systemic inflammatory component of RA may alter this association in this patient population. We explored a potential association between SUA levels and HT in RA and evaluated whether this association is independent of HT risk factors, RA characteristics and relevant drugs. A total of 400 consecutive RA patients were assessed. SUA and complete biochemical profile were measured. Demographic, HT-related factors, RA characteristics and drugs were assessed as potential covariates. Results were analysed using binary logistic models to test the independence of the association between SUA and HT. SUA levels were higher in hypertensive compared to normotensive RA patients (5.44±1.6mgdl

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Objectives: Rheumatoid arthritis (RA) is accompanied by increased resting energy expenditure (REE) and decreased fat-free mass (FFM). This is referred to as rheumatoid cachexia and is attributed to high levels of tumour necrosis factor-α (TNF-α). This study aimed to investigate the effects of anti-TNF-α therapy on REE, body composition, physical activity and protein intake in RA patients. Methods: Twenty RA patients [50% female; age: (mean ± s.d.) 61.1 ± 6.8 yrs; body mass index (BMI): 28.3 ± 3.7 kg/m

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This systematic review investigates the effectiveness of exercise interventions in improving disease-related characteristics in patients with rheumatoid arthritis (RA). It also provides suggestions for exercise programmes suitable for improving the cardiovascular profile of RA patients and proposes areas for future research in the field. Six databases (Medline, Cochrane Library, CINAHL, Google Scholar, EMBASE and PEDro) were searched to identify publications from 1974 to December 2006 regarding RA and exercise interventions. The quality of the studies included was determined by using the Jadad scale. Initial searches identified 1342 articles from which 40 met the inclusion criteria. No studies were found investigating exercise interventions in relation to cardiovascular disease in RA. There is strong evidence suggesting that exercise from low to high intensity of various modes is effective in improving disease-related characteristics and functional ability in RA patients. Future studies are required to investigate the effects of exercise in improving the cardiovascular status of this patient population. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Objectives: To assess the association of body mass index (BMI) with modifiable cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (HA). Methods: BMI, disease activity, selected CVD risk factors and CVD medication were assessed in 378 (276 women) patients with RA. Patients exceeding accepted thresholds in ≥3 CVD risk factors were classified as having the metabolic syndrome (MetS). Results: BMI independently associated with hypertension (OR = 1.28 (95% CI = 1.22 to 1.34); p = 0.001), high- density lipoprotein (OR = 1.10 (95% CI = 1.06 to 1.15); p = 0.025), insulin resistance (OR = 1.13 (95% CI = 1.08 to 1.18); p = 0.000) and MetS (OR = 1.15 (95% CI = 1.08 to 1.21); p = 0.000). In multivariate analyses, BMI had the strongest associations with CVD risk factors (F1-354 = 8.663, p = 0.000), and this was followed by lipid-lowering treatment (F1-354 = 7.651, p = 0.000), age (F1-354 = 7.541, p = 0.000), antihypertensive treatment (F1-354 = 4.99 7, p = 0.000) and gender (F1-354 = 4.70 7, p = 0.000). Prevalence of hypertension (p = 0.004), insulin resistance (p = 0.005) and MetS (p = 0.000) was significantly different between patients with RA who were normal, overweight and obese, and BMI differed significantly according to the number of risk factors present (p = 0.000). Conclusions: Increasing BMI associates with increased CVD risk independently of many confounders. RA-specific BMI cut-off points better identify patients with RA at increased CVD risk. Weight-loss regimens should be developed and applied in order to reduce CVD in patients with RA.

Objectives The aim of this study was to assess the relationship between specific erythrocyte fatty acid levels and vascular health in type 1 diabetes (T1D) with and without insulin resistance (IR). Methods We analyzed baseline pretreatment data in a subset of 23 patients with T1D from a previously published randomized controlled trial consisting of comprehensive erythrocyte-derived fatty acid profiles and a panel of inflammation-associated endothelial markers. Estimated glucose disposal rate was used to identify and categorize patients with IR. We utilized principal component analysis (PCA) to cluster vascular biomarkers to compute a single “vascular signal” and utilized univariate linear regression models to investigate the association with IR and fatty acid profiles. Results Subjects with IR displayed significantly higher levels of linoleic acid (p=0.001), lower levels of eicosapentaenoic acid (EPA) (p<0.001), lower levels of omega-3 polyunsaturated fatty acid (n-3PUFA) (p<0.006) and an increased omega-6 (n-6)PUFA:n-3PUFA ratio (p=0.001). IR was associated with significantly higher linoleic acid levels, total n-6PUFA and an increased ratio of n-6PUFA:n-3PUFA, and negatively associated with arachidonic acid and EPA levels, total saturated fatty acid and total n-3PUFA. The PCA-derived vascular biomarker cluster was positively associated with linoleic acid and n-6PUFA:n-3PUFA ratio, and inversely associated with EPA. Conclusions Specific erythrocyte membrane fatty acid compositions are associated with impaired vascular health and IR in adults with T1D. These findings suggest that IR and risk of associated complications may be influenced by specific fatty acid profiles, and thus potentially modified by the selective targeting of dietary fatty acids.

We examined changes in selected muscle performance parameters after 8 weeks of interval training using two opposite running inclinations. We hypothesized that the uphill training will affect endurance muscle performance outcomes, whereas the downhill training will affect power muscle performance outcomes. Fourteen physically active volunteers were randomly assigned into either the Uphill group (UG; n = 7; uphill interval running at +10% incline) or the Downhill group (DG; n = 7; downhill interval running at -10% incline) and completed 16 training sessions. Each session consisted of ten 30 s treadmill runs at 90% of maximum aerobic speed (MAS) with a work to rest ratio of 1:2. Vertical jump performance, isometric (MVC) and isokinetic torque of knee extensors and flexors, and fatigue of knee extensors were evaluated pre and post-training. Moreover, body composition (via bioimpedance) and vastus lateralis muscle architecture (via ultrasonography) were assessed pre and post-training. Relative lean tissue mass, relative fat mass, and squat jump (cm) significantly (p < .05) changed from baseline values by +4.5 ± 4.0%, -11.5 ± 9.6%, and +9.5 ± 11.7%, respectively, only in the DG. Similarly, DG improved absolute values of knee extension rate of torque development and impulse (p < .05), whereas knee flexion peak torque angle significantly decreased in both groups (p < .05). On the other hand, the UG increased the number of repetitions achieved during the fatigue protocol and total work by 21.2 ± 32.6% and 13.8 ± 21.2%, respectively (p < .05). No differences were found between groups in muscle architecture. Introducing variations in slope during HIIT could be used to induce specific improvements toward muscle endurance or power performance characteristics.

© 2019, Springer Nature Limited. New research indicates that tocilizumab limits the beneficial effects of exercise on abdominal fat loss. What does this mean for patients with chronic disease who are being treated with tocilizumab or other inhibitors of IL-6 signalling?

Rheumatoid arthritis (RA) associates with excess cardiovascular (CV) morbidity and mortality. Hypertension, a highly prevalent entity in RA, has been associated with the endothelin-1 (ET-1) gene locus (EDN1) in some groups, such as Afro-Caribbean, the obese, and in low-renin states, but not in the general population as a whole. High levels of plasma ET-1 have been observed in RA. This study evaluated the potential association of EDN1 gene locus and serum ET-1 levels with hypertension in patients with RA. Genomic DNA and serum samples were collected from 397 well-characterized RA patients; DNA was also available from 401 local general population controls without RA. To explore the overall relevance of EDN1, two suitable single-nucleotide polymorphisms (SNPs), rs1800541 and rs5370, were selected and haplotype analysis was performed. Both SNPs were identified using real-time polymerase chain reaction (PCR) and melting curve analysis. Genetic analysis was related to hypertension as dichotomous trait and to blood pressure indices as continuous variables. Serum endothelin levels were also assessed in the RA patients. No genotype or haplotype differences were observed between RA and control subjects. Within RA, logistic regression analysis of each SNP separately revealed a threefold increase in the adjusted odds of being hypertensive of rs5370 TT homozygotes compared to GG homozygotes (OR = 2.89, 95%CI: 1.02 to 8.19). After adjustment for multiple potential confounders, haplotype analysis revealed an additive effect of the rs1800541-rs5370 T-T haplotype on hypertension (OR = 2.96, 95%CI: 1.28 to 6.86; p = .011), systolic blood pressure (SBP) (Β = 6.75 ± 2.57 mm Hg; p = .009), and pulse pressure (PP) (Β = 4.37 ± 2.12 mm Hg; p = .040). There was an increased prevalence of raised ET-1 levels amongst hypertensive RA patients, whereas a similar trend was observed for T-T haplotype carriers. RA patients who carry the rs1800541-rs5370 T-T EDN1 haplotype appear more likely to be hypertensive with an increased SBP and PP. These findings, if replicated in future studies, could be used as a screening tool for RA patients at increased hypertension, and thus cardiovascular, risk.

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 patients

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with significant functional impairment and increased risk for cardiovascular disease. Along with pharmacological therapy, exercise seems to be a very promising intervention to improve disease-related outcomes, including functional ability and systemic manifestations, such as the increased cardiovascular risk. In this review, we discuss the physiological mechanisms by which exercise improves inflammation, cardiovascular risk and psychological health in patients with rheumatoid arthritis (RA) and describe in detail how exercise can be incorporated in the management of this disease using real examples from our clinical practice.

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.

Purpose: Rheumatoid arthritis (RA) patients display high levels of oxidative stress. Transient exercise-induced increases in oxidative stress are thought to be adaptive in healthy populations. This study investigated the effect of exercise on markers of oxidative stress in RA, following acute exercise and a period of exercise training. Methods: Acute exercise study: RA patients (N = 12, age: 56 ± 11) undertook a bout of exercise (30-40 min, 70 % VO 2MAX ), and blood samples were taken before and after exercise to assess markers of oxidative stress. Training study: RA patients (N = 19, age: 56 ± 10) were randomised into either a control or exercise group, who undertook 3 exercise sessions per week (30-40 min @70 % VO 2MAX ) for 3 months. Plasma markers of oxidative stress (protein carbonyls (PC), lipid hydroperoxides (LOOH), 3-nitrotyrosine (3-NT), total antioxidant capacity (TAC) and catalase (CAT) activity), inflammation (interleukin-8 (IL-8) and C-reactive protein (CRP)) and nitric oxide metabolites (NOx) were assessed before and after training. Results: Acute exercise study: Protein carbonyls (PC) (+18 %) and NOx (+27 %) were significantly increased following exercise. Training study: 3-nitrotyrosine (3-NT) decreased (2.18 ± 1.78 to 1.10 ± 0.93 μM) in the exercise group only, alongside increases in aerobic fitness (24.45 ± 4.98 to 27.10 ± 4.51 ml/kg/min -1 ) and reductions in disease activity score (DAS: 3.47 ± 1.17 to 2.88 ± 0.76). PC, LOOH, TAC, IL-8, CRP and NOx concentrations, and CAT activity were unchanged in both groups. Conclusions: Aerobic exercise training did not increase markers of oxidative stress in RA patients. 3-Nitrotyrosine and disease activity were decreased following exercise training. © 2014 Springer-Verlag Berlin Heidelberg.

Background: We investigated the effects of individualised combined resistance and aerobic exercise on microvascular and macrovascular function in rheumatoid arthritis (RA) patients. Methods: Forty age-matched, gender-matched and body mass index (BMI)-matched patients were allocated to either an exercise group, receiving a 6 months tailored aerobic and resistance exercise intervention, or controls receiving only information about the benefits of exercise. Participants were assessed for microvascular (acetylcholine (Ach) and sodium nitroprusside (SNP)) and macrovascular (flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)) endothelial function, maximal oxygen uptake, disease activity and severity (C-reactive protein (CRP), disease activity score 28 and health assessment questionnaire). Data were collected at baseline, 3 months and at the end of the intervention (6 months). Results: At baseline, demographic, anthropometric, disease-related characteristics and endothelial function parameters were similar between the exercise and control groups (p > 0.05). Repeated measures analysis of variance revealed a significant improvement in endothelial function parameters at 3 (GTN: p < 0.001) or 6 months (Ach: p=0.016, SNP: p=0.045, FMD: p=0.016) in the exercise but not in the control group. Generalised estimated equations detected that maximal oxygen uptake was a strong predictor for the observed changes in Ach (p=0.009) and GTN (p < 0.001) whereas logCRP for SNP (p=0.017) and GTN (p=0.008). Conclusions: An exercise programme designed to meet individual needs and physical abilities significantly improves microvascular and macrovascular function in parallel with disease-related characteristics in RA patients. The potential long-term beneficial effects of such interventions at reducing cardiovascular risk in these patients merit further exploration. Clinical Trial Registration: ISRCTN50861407.

Obesity is characterised by low-grade inflammation and could potentially affect disease activity and severity in patients with rheumatoid arthritis (RA). Body mass index (BMI), body fat (BF), erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, physical function (health assessment questionnaire) and presence of erosions and joint surgery were assessed in 294 (female = 219) volunteers with established RA [age 63.3 (56.2-69.6); disease duration 13 (7-20) years]. Smoking status, rheumatoid factor and anti-cyclic citrullinated peptide positivity were also assessed. BMI and BF independently associated with disease characteristics. Compared to normal-weight patients, underweight and obese had higher C-reactive protein (p = 0.046) and physical dysfunction (p = 0.034). BMI or BF did not associate with presence of erosions or joint surgery. In patients with established RA, both very low and very high BMI and BF associate independently with increased disease activity and physical dysfunction; however, this does not seem to associate with presence of erosions or joint surgery. Further longitudinal studies are required to address this apparent dissociation. © Clinical Rheumatology 2008.

Objectives. Part of the deleterious effects of systemic inflammation on the cardiovascular system of patients with RA may be exerted via increased propensity to hypertension. IL-6 and TGF-β1 are important regulators of the inflammatory response. In some, but not all, studies, IL6 -174G/C (rs1800795) and TGFB1 869T/C (rs1982073) gene polymorphisms have been associated with hypertension in the general population. The present study addressed their potential association with hypertension in RA patients. Methods. TGFB1 869T/C and IL6 -174G/C were identified in 400 RA patients and 422 local, non-RA controls using real-time PCR and melting curve analysis. Binary logistic and linear regression models were used to identify the independence of the effects of the polymorphisms on hypertension. Results. Genotypic and allelic frequencies of the two polymorphisms were similar in RA and controls. Within the RA group, there was no significant association between IL6 -174G/C and hypertension, but TGF 869T-allele carriers had significantly increased prevalence of hypertension compared with CC homozygotes (70.2 vs 55.2%; P = 0.023). This association remained significant after adjustment for other hypertension risk factors and medication (odds ratio = 1.96; 95% CI 1.02, 3.77; P = 0.044), and was more pronounced in patients with increased systemic inflammation. Conclusions. This study suggests an association of TGFB1 869T/C, but not of IL6 -174G/C, with hypertension in RA patients. If this finding is confirmed in prospective studies, this polymorphism could be used as a screening tool for RA patients with higher risk of developing hypertension and lead to increased surveillance and earlier treatment. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Patients with rheumatoid arthritis (RA) are characterized by reduced physical activity and increased morbidity and mortality from cardiovascular disease (CVD). The aim of this study was to investigate associations between levels of physical activity and CVD risk profile in RA patients. Levels of physical activity were assessed in 65 RA patients (43 females). Using the International Physical Activity Questionnaire, patients were allocated into three groups: active, moderately active and inactive. Anthropometric characteristics, RA activity/severity, multiple classical and novel CVD risk factors and 10-year CVD event probability were assessed and compared among the three groups. Significant differences were detected among groups in systolic blood pressure (P = 0.006), cholesterol (P < 0.001), low-density lipoprotein (P = 0.01), homeostasis model assessment (P = 0.001), type-1 plasminogen activator inhibitor antigen (P < 0.001), tissue-type plasminogen activator antigen (P = 0.019), homocysteine (P = 0.027), fibrinogen (P = 0.001), apolipoprotein B (P = 0.002) and von Willebrand Factor (P = 0.001), with a consistent deterioration from the physically active to the physically inactive group. Multivariate analysis of variance revealed that levels of physical activity were significantly associated with the differences in all of the above variables (P < 0.05) after adjustment for age, weight, sex, smoking status, as well as RA disease activity and severity. This cross-sectional study suggests that physically inactive RA patients have significantly worse CVD risk profile compared with physically active patients. The possible beneficial impact of increased physical activity, including structured exercise, to the CVD risk of RA patients needs to be accurately assessed in prospective studies. © 2009, European Society of Cardiology. All rights reserved.

The inflammatory pathogenesis of atherosclerosis is now well-established, owing to in vitro and in vivo studies and the application of high sensitivity assays for C-reactive protein (CRP) in the general population and specific groups at risk for cardiovascular disease (CVD). In view of the complexity of inflammation-induced atherosclerosis, the rationale for comparative studies of atherogenesis in rheumatic diseases with diverse inflammatory pathogenesis seems obvious; they are human in vivo models to study inflammatory mechanisms involved in atherosclerosis and the impact of treatment. Factors implicated in atherogenesis in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), familial Mediterranean fever (FMF) and Behçet's disease (BD) are discussed in this review. Evidence suggests that enhanced atherosclerosis causes premature cardiovascular events in the autoimmune disease, SLE, and the "high-grade" inflammatory rheumatic disease, RA. Preliminary data suggest that enhanced atherogenesis may accompany FMF in the absence of sufficient suppression of inflammation by colchicine. In the setting of BD, the role of atherosclerosis in the premature manifestation of coronary pathology has not been confirmed; coronary vasculitis and aneurysms appear to constitute the basis of myocardial infarction (MI) in BD. A variety of established and novel risk factors are believed to influence enhanced atherogenesis in rheumatic diseases. Antiphospholipid antibodies are thought to be intimately involved in atherogenesis in SLE and to a lesser extend in RA. CRP may play a more universal role in all rheumatic diseases. The application of high resolution ultrasound of peripheral arteries and other non-invasive techniques may allow targeted use of statins, ACE inhibitors, antiplatelet agents and other cardioprotective drugs in patients with rheumatic diseases, but this needs to be evaluated specifically in prospective studies. © 2010 Bentham Science Publishers Ltd.

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders associated with enhanced cardiovascular morbidity and mortality. Established high prevalence of classical cardiovascular risk factors may only partly explain cardiovascular phenomenon in this disease. Emerging risk factors, markers of inflammation and prothrombotic state such as platelet size are believed to reflect activity of RA. We aimed to study mean platelet volume (MPV) in a cohort of patients with RA and to clarify possible effects of classical cardiovascular and RA-associated risk factors on MPV. Demographic, clinical and a wide range of laboratory parameters, including MPV and platelet count, were obtained for 400 RA patients. Platelet size and count were also assessed in 360 non-RA controls from the local population. We found significantly increased MPV in RA patients compared with controls (P=0.001). The difference retained significant after adjustment for age and sex. High values of MPV (≥10.7 femtoliter [fL]) were more frequent in RA patients than in controls (21% vs 9.2%; P<0.0001). In RA patients, blood pressure greater than 140/90 mmHg was associated with high levels of MPV (Odds Ratio [OR] 2.2, 95% Confidence Interval [CI] 1.3-3.7; P=0.003). It is possible that MPV as a surrogate marker of platelet function reflects enhanced vascular risk. To further explore the role of MPV as a marker for cardiovascular risk in RA, prospective studies are warranted. © 2010 Bentham Science Publishers Ltd.

A number of mediators are involved in the inflammatory processes that affect joints and vascular wall of patients with rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFa) is one such mediator, and it is widely regarded as an important target for anti-rheumatic treatment. Most recent studies show that anti-TNFa medication suppresses inflammation and reduces overall activity of RA. The aim of the current study was to investigate changes of mean platelet volume (MPV) in response to the 3-month anti-TNFa therapy in RA. Twenty-one RA patients without established cardiovascular disease were recruited for anti-TNFa therapy and underwent thorough clinical and laboratory evaluation at baseline, 2 weeks, and 12 weeks. Anti-TNFa therapy resulted in a significant (p = 0.01) increase in MPV over the duration of the study (7.7 ± 0.9, 7.8 ± 1.1, and 8.4 ± 1.1 fL at baseline, 2 weeks, and 12 weeks, respectively). The results of the study expand perspectives of the use of MPV in conditions associated with high-grade inflammation, particularly RA, for monitoring anti-inflammatory treatment. More prospective studies with large numbers of patients are warranted to ascertain associations of high and low values of MPV with diverse markers of inflammation and vascular pathology. © 2010 Springer-Verlag.

Objective. It has been frequently stated that rheumatoid cachexia (RC) associates with increased cardiovascular risk; however, no studies to date have investigated this. The aim of this study was to investigate the association of RC with multiple novel and classical cardiovascular disease (CVD) risk factors and the presence of established CVD in rheumatoid arthritis (RA). Methods. A total of 34 RA patients with RC (RA+RC) were identified from a database of 400 RA patients using published RC criteria and compared to the remaining patients (RA-RC) who did not fulfil RC criteria. All patients were assessed for fat and fat-free mass, albumin (indicator of catabolism), disease activity/severity, novel and classical risk CVD factors and established CVD. Results. Fat-free mass (kg) and albumin (g/L) were significantly decreased in RA+RC vs. RA-RC patients: 37.3(33.9-41.6) vs. 45.9(41.2-55.5), p<0.001 and 39.6±6.7 vs. 42.4±4.9, p=0.001). Percent body fat was not significantly different. No significant differences were detected in either the classical or novel CVD risk factors, 10-year CVD risk or the prevalence of established CVD. Conclusions. RC does not appear to be associated with worse CVD profile in RA patients, but this needs to be confirmed in prospective studies. © Copyright Clinical and Experimental Rheumatology 2009.

Background: Cardiovascular morbidity and mortality are increased in rheumatoid arthritis (RA). Interleukin-6 (IL-6) is high in RA and, together with smoking and obesity, an important contributor to the development of cardiovascular disease (CVD). The present study examined the potential association of IL-6-174 G/C polymorphism, together with obesity and smoking, with the presence of CVD in RA patients. Methods and results: DNA samples were collected from 383 RA patients (who also had extensive clinical and laboratory evaluations). IL-6-174 G/C was identified using real time PCR and melting curve analysis. Serum IL-6 levels were measured in a subgroup of 135 RA patients to examine the functionality of the polymorphism. Carriers of the IL6-174C-allele demonstrated increased prevalence of CVD (26.2% vs. 17.0%, p = 0.041). There was a significant association with CVD, even after adjustment for traditional CVD risk factors (OR = 1.92, 95%CI: 1.03 to 3.58, p = 0.041). IL-6 levels were significantly increased in C-allele carriers [14.02 (3.21-38.81) vs. 4.48 (2.25-16.5), p = 0.028]. No significant interactions were observed between adiposity and IL6-174G/C genotypes. There was only a trend for an interaction between ever smoking and IL6 C-allele carriers on CVD. Conclusion: The IL-6-174C-allele may associate with CVD in RA patients and possibly exerts its effect via increased inflammation. This finding, if confirmed in future studies, may be used as a part of a genetic screening tool for RA patients at high CVD risk. © 2008 Elsevier Ireland Ltd. All rights reserved.

The physical demands placed on dancers make their physiology and fitness just as important as skill development. However, dancers’ muscular strength and bone and joint integrity seem to suffer as a result of the dance-only selection and training system. This partly reflects the unfounded view that exercise training that is not directly related to dance would diminish dancers’ aesthetic appearances and destroy muscle flexibility. Nevertheless, data on male and female dancers have demonstrated that supplemental strength training can lead to better dancing and reduced incidents of dance injuries without interfering with key artistic and aesthetic requirements. An awareness of these factors will assist dancers and their teachers in improving training techniques, employing more effective injury prevention program, and in determining better physical conditioning strategies.

This chapter explains the epidemiology, pathophysiology, and mechanisms of rheumatoid arthritis. It explores effects of exercise on rheumatoid arthritis symptoms and systemic manifestations. Rheumatoid arthritis (RA) was first described in the 1800s as a new form of gout under the designation 'primary asthenic gout'. Among RA patients, disability, often manifesting as premature work cessation, is a common feature. The aetiology of RA is not clear. It is believed that RA is triggered when an immunogenetically susceptible host is exposed to an antigen. Inflammation is considered the hallmark of RA and contributes to the main symptomatology of the disease, particularly pain, fatigue and functional disability. RA has significant systemic involvement: namely, skin, ocular, oral, gastrointestinal, pulmonary, renal, neurological and haematological manifestations that vary according to disease severity. Research studies investigating the effects of exercise on the aforementioned manifestations are currently lacking.

Physical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of known barriers and facilitators for engaging in PA, from the perspective of people living with RMD. Five hundred thirty-three people with RMD responded to a survey (nine questions) disseminated by the People with Arthritis and Rheumatism (PARE) network of the European Alliance of Associations for Rheumatology (EULAR). The survey required participants to rank — based on their perceived importance — known PA barriers and facilitators from the literature, and specifically RMD symptoms as well as healthcare and community factors that may affect PA participation. Of the participants, 58% reported rheumatoid arthritis as their primary diagnosis, 89% were female, and 59% were between 51 and 70 years of age. Overall, participants reported fatigue (61.4%), pain (53.6%) and painful/swollen joints (50.6%) as the highest ranked barriers for engaging in PA. Conversely, less fatigue (66.8%) and pain (63.6%), and being able to do daily activities more easy (56.3%) were identified as the most important facilitators to PA. Three literature identified PA barriers, i.e., general health (78.8%), fitness (75.3%) and mental health (68.1%), were also ranked as being the most important for PA engagement. Symptoms of RMDs, such as pain and fatigue, seem to be considered the predominant barriers to PA by people with RMD; the same barriers are also the ones that they want to improve through increasing PA, suggesting a bi-directional relationship between these factors.Key Points• Symptoms of rheumatic and musculoskeletal disease (RMD) are the predominant barriers for lack of physical activity engagement.• RMD symptoms are the factors that people with RMDs want to improve when engaging in PA.• The barriers that stop people living with RMDs to do more PA are the ones that can be significantly improved through PA engagement.

This randomized, double-blinded, experimental study investigated the effects of a four-week daily pre-workout supplementation (200 mg caffeine, 3.3 g creatine monohydrate, 3.2 g β-alanine, 6 g citrulline malate, and 5 g BCAA) vs. placebo (isocaloric maltodextrin) on anaerobic (jumping, sprinting, agility, and the running-based anaerobic sprint test: RAST) and aerobic (Yo-Yo intermittent recovery test level 1) performance, as well as on body composition and selective muscle damage/health-related blood markers in well-trained basketball players during the in-season period. Eighteen basketball players (age: 24.4 ± 6.3 years, height: 185.7 ± 8.0 cm, weight: 85.7 ± 12.8 kg, body fat: 16.5 ± 4.2%) were randomly assigned into two groups: pre-workout supplement (PWS, n = 10) or placebo (PL, n = 8). PWS consumption increased aerobic performance (PWS: 8 ± 6%; PL: −2 ± 6%; p = 0.004) compared to PL. A significant decrease was observed in peak (F = 7.0; p = 0.017), average (F = 10.7; p = 0.005), and minimum power (F = 5.1; p = 0.039) following 4 weeks of supplementation in both groups. No other significant changes were observed between groups (p > 0.05). In conclusion, the consumption of the current PWS over a four-week period appears to positively influence the aerobic performance of well-trained basketball players during the in-season period. However, it does not appear to mitigate the observed decline in anaerobic power, nor does it affect performance in jumping, sprinting, and agility, or alter body composition or selective muscle damage/health-related blood markers.

Objective. Rheumatoid arthritis (RA) associates with increased cardiovascular morbidity and mortality that is due to both traditional and novel cardiovascular risk factors. Hypertension (HT), one of the most common risk factors for cardiovascular disease, is highly prevalent in RA. The effects of long-term glucocorticoid (GC) therapy on blood pressure have not been established yet. This study examined whether GC exposure associates with HT in patients with RA. Methods. Four hundred consecutive RA patients with detailed clinical and laboratory assessments were categorized into three groups according to GC exposure: no or limited exposure (N/L-E); a low-dose (>7.5 mg) long-term exposure (LD/LT-E); and medium-dose (≥ 7.5 mg) long-term exposure (MD/LT-E). The association of GC exposure with HT was evaluated using logistic regression analysis. Results. HT was more prevalent in the MD/LT-E group (84.7%) than the LD/LT-E or N/L-E groups (70.7 and 67.3%, respectively, P = 0.028). Logistic regression revealed increased odds for HT when comparing MD/LT-E with N/L-E, after adjustment for HT risk factors [odds ratio (OR) = 2.57, 95% CI 1.01-6.56, P = 0.049] and RA disease characteristics (OR = 3.64, 95% CI: 1.36-9.77, P = 0.01). Conclusions. MD/LT GC exposure associates with a very high prevalence of HT. This appears to be independent of other risk factors for HT or of channelling bias due to disease severity, even though the latter cannot be excluded given the cross-sectional nature of our study. RA patients in this GC exposure group should be particularly targeted for early identification and aggressive management of HT. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Objectives. Resting energy expenditure (REE), one of the main components of total energy expenditure, can be measured via indirect calorimetry and/or predicted from equations. The latter may be misleading in RA, as they do not take into account the metabolic alterations occurring in RA. The objectives of this study are to evaluate the accuracy of widely used REE-predictive equations in RA patients against measured REE and to develop RA-specific equations. Methods. We assessed REE (via indirect calorimetry and several predictive equations), fat-free mass (FFM; via bioelectrical impedance) and disease activity (CRP) in RA patients and healthy controls. Data from 60 RA patients (experimental group) were used to assess the accuracy of existing REE equations and to develop new equations. The new equations were validated in an independent cross-validation group of 22 RA patients. These two groups were merged and two final equations were developed. Results. All equations significantly under-predicted measured REE (from 15% to 18.2%, all at P<0.001) in the RA experimental group, but not in the control group. After both equations demonstrated a high validity in the cross-validation group, the new final REE prediction equations developed from the total RA sample (n=82) were: Model 1: REE (kcal/ day)=126.1 × FFM

0.638

0.045

2

0.47

-0.29

0.066

2

INTRODUCTION: Rheumatoid arthritis (RA) is associated with altered metabolism leading to muscle wasting. In the general population, cigarette smoking is known to affect body composition by reducing fat and inhibiting muscle synthesis. Even though smoking has been implicated in the pathophysiology and progression of RA, its possible effects on body composition of such patients have not been studied. This cross-sectional study aimed to identify potential associations of smoking with body weight and composition of RA patients. METHODS: A total of 392 patients (290 females) with RA were assessed for body mass index (BMI), body fat (BF), fat-free mass (FFM), and waist circumference. Erythrocyte sedimentation rate, C-reactive protein, Disease Activity Score-28, and Health Assessment Questionnaire score were used to assess disease activity and severity. Smoking habit (current smoker, ex-smoker, or never-smoker) and intensity (pack-years) were also noted. RESULTS: Current smokers had a significantly lower BMI compared with ex-smokers (mean difference: male -2.6, 95% confidence interval [CI]: -3.5 to -1.7; female: -2.6, 95% CI: -4.8 to -0.5) and never-smokers (mean difference: male -1.8, 95% CI: -3 to -0.6; female: -1.4, 95% CI: -2.4 to -0.4). Similarly, the BF of current smokers was lower compared with that of ex-smokers (mean difference: male: -4.3, 95% CI: -7.5 to -1.2; female: -3.4, 95% CI: -6.4 to -0.4) and never-smokers (mean difference: male: -3.3, 95% CI: -6.3 to -0.4; female: -2.1, 95% CI: -4 to -0.2). FFM did not differ between groups. Finally, current smokers had a significantly smaller waist circumference compared with ex-smokers only (mean difference: male: -6.2, 95% CI: -10.4 to -1.9; female: -7.8, 95% CI: -13.5 to -2.1). Following adjustments for age, disease duration, and HAQ score, smoking remained a significant predictor for BMI (P < 0.001), BF (P < 0.05), and waist circumference (P < 0.05). Pack-years were inversely correlated with BF (r = -0.46; P < 0.001), and heavy smokers exhibited a significantly lower FFM (P < 0.05) compared with all other participants. CONCLUSION: Within the limitations of a cross-sectional study, it appears that cigarette smoking associates with reduced BMI and BF in patients with RA and heavy smoking associates with lower muscle mass. Smoking cessation appears to associate with increased BMI, BF, and waist circumference in these patients. These results should be confirmed in prospective studies. Given the numerous adverse effects of smoking on general health and RA, patients should be actively advised against it. However, smoking cessation regimes in RA may need to include more general lifestyle counselling, particularly about weight control.

Background: Percentage of body fat (BF%) is a known risk factor for a range of healthcare problems but is difficult to measure. An easy to measure proxy is the weight/height

2

2

2

INTRODUCTION: Insulin resistance (IR), a risk factor for the development of cardiovascular disease, is common among patients with rheumatoid arthritis (RA). Inflammation, and especially tumour necrosis factor alpha (TNFα), has been associated with IR, and the administration of anti-TNFα agents is suggested to improve insulin sensitivity. However obesity, a potent contributor to IR, may limit the beneficial effects of anti-TNFα medication on IR. The aim of this study is to compare the effects of anti-TNFα therapy on IR between normal-weight and obese patients with RA. METHODS: Patients who were normal-weight with IR (N+IR) or obese with IR (O+IR) and had embarked on anti-TNFα treatment, participated. Assessments included body mass index (BMI), insulin sensitivity (Homeostasis Model Assessment of insulin resistance, HOMA and the Quantitative Insulin sensitivity Check Index, QUICKI), and RA disease characteristics before and following six months of anti-TNFα treatment. Their results were compared to matched (for age, gender, BMI, disease duration and smoking status) normal-weight patients without IR (N-IR) and obese without IR (N-IR), respectively. In total, 32 patients were assessed for this study, with 8 in each group. RESULTS: Following six months of treatment, disease activity was significantly reduced in all groups (P < 0.05) to a similar extent (P for differences between groups > 0.05 in all cases). In the total population, changes in HOMA (mean reduction at 6 m = -0.2 ± 0.1; P = 0.088) and QUICKI (mean increase at 6 m = 0.03 ± 0.022; P = 0.092) after treatment were not statistically significant, though a trend towards improvement was observed. However, N+IR patients showed a significant decrease in HOMA (mean reduction at 6 m = -0.54 ± 0.2; P = 0.002) and increase in QUICKI (mean increase at 6 m = 0.046 ± 0.02; P = 0.011). These changes were significantly different compared to the other groups (P < 0.05 in all cases). Multivariable analyses showed that the change in Erythrocyte Sedimentation Rate (ESR), and the change in C-Reactive Protein (CRP) associated with the improvement in HOMA (ESR: F₁₋₇ = 5.143, P = 0.019; CRP: F₁₋₇ = 3.122, P = 0.022) and QUICKI (ESR: F₁₋₇ = 3.814, P = 0.021; CRP: F₁₋₇ = 2.67; P = 0.041) only in the N+IR group. CONCLUSIONS: Anti-TNFα therapy, through controlling inflammation, seems to improve insulin sensitivity in normal-weight RA patients with insulin resistance, but is not sufficient to achieving the same beneficial effect in obese RA patients with insulin resistance.

Background and objectives: Low cardiorespiratory fitness (CRF) is a significant predictor of cardiovascular disease (CVD), and interventions aiming at increasing CRF are known to reduce CVD risk. The effects of such interventions on CVD risk have not been studied in patients with rheumatoid arthritis (RA). Methods: 40 age, gender, body mass index (BMI) and disease duration matched RA patients were allocated to either an exercise (receiving 6 months individualised aerobic and resistance high intensity exercise intervention, three times per week), or control (receiving advice on exercise benefits and lifestyle changes) arm. Participants were assessed at baseline, 3 and 6 months for aerobic capacity (VO2max), individual CVD risk factors (blood pressure, lipids, insulin resistance, body composition), 10-year CVD event probability and RA characteristics (C-reactive protein (CRP), Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ)). Results: There were no differences between groups at baseline in any of the assessed variables. VO2max (p=0.001), blood pressure (systolic: p<0.001; diastolic: p=0.003), triglycerides (p=0.030), high density lipoprotein (HDL; p=0.042), total cholesterol:HDL ratio (p=0.005), BMI (p=0.001), body fat (p=0.026), 10- year CVD event probability (p=0.012), CRP (p=0.042), DAS28 (p=0.008) and HAQ (p=0.003) were all significantly improved in the exercise versus the control group. The change in VO2max was the strongest predictor for the observed improvements in all of the assessed CVD risk factors and disease characteristics. Conclusions: Individualised aerobic and resistance exercise intervention can lead to significantly improved CRF, individual CVD risk factors, composite CVD risk, and disease activity and severity in RA patients.

Patients with rheumatoid arthritis (RA) are at high risk of cardiovascular events. Platelet biomarkers are involved in inflammation, atherosclerosis and thrombosis. Cardiovascular and RA-associated factors can alter the structure and function of platelets, starting from megakaryocytopoiesis. Reactive megakaryocytopoiesis increases circulating platelets count and triggers hyperactivity. Hyperactive platelets target synovial membranes with subsequent local rheumatoid inflammation. Hyperactive platelets interact with other cells, and target the vascular wall. Accumulating evidence suggests that disease modifying anti-rheumatic drugs (DMARD) decrease platelet activity. © Springer-Verlag 2010.

Childhood obesity is increasing alarmingly, and a strong association with chronic diseases has been established. Specific adipokines are released from the adipose tissue and relate with chronic diseases even in the pediatric population. Adiponectin levels are lower in obesity and increase with decreasing body weight. A few pediatric studies examining a possible relationship between resistin and obesity do not provide a clear picture. Most studies agree that visfatin levels appear elevated in childhood obesity. Exercise seems to increase adiponectin levels whereas resistin levels are reduced. The lack of data on the effects of acute and chronic exercise on visfatin levels precludes us from making safe conclusions as to what the effects of exercise (acute or chronic) would be on visfatin levels in children. Clearly, exercise has an impact on the adipose tissue and the release of adiponectin, resistin, and visfatin. However, other factors affect the secretion rate of these adipokines from the adipose tissue; these factors should also be taken into consideration when examining the effects of exercise on adipokines. Gender, age, body composition, physical activity levels, mode and intensity of exercise are some of the factors that should be looked into in future studies.

Background: Rheumatoid arthritis (RA) is characterised by increased cardiovascular morbidity and mortality. Even though hypertension (HT) is highly prevalent in RA, the extent of target organ damage (TOD) caused by it remains unknown. Inflammation and sympathetic overdrive may also associate with TOD. We investigated the prevalence and associations of TOD in RA. Methods: In this cross-sectional, observational study, 251 RA patients with no overt cardiovascular or renal disease had extensive clinical and laboratory evaluations, including a 12-lead electrocardiogram and urine albumin:creatinine ratio. Pulse pressure (PP) was used as a proxy of arterial stiffness and heart rate (HR) of autonomic activity. TOD was defined as described in the European guidelines for the management of arterial hypertension. Binary logistic regression analysis was used to evaluate the independence of the variables that associated with the presence of TOD. Results: TOD prevalence was 23.5% (59/251). Of the 59 patients with TOD, 45.8% had suboptimally controlled HT, whereas 32.3% had undiagnosed HT. In univariable analysis, TOD was significantly associated with higher age (64.2 ± 11.7 years vs. 58.0 ± 12.4 years, p = 0.001), HT prevalence (89.8% vs. 60.4%, p < 0.001), systolic blood pressure (SBP) (150.3 ± 18.8 mmHg vs. 139.7 ± 20.7 mmHg, p = 0.001), PP (70.6 ± 16.6 mmHg vs. 60.3 ± 17.3 mmHg, p < 0.001), HR (77.1 ± 15.4 bpm vs. 72.2 ± 12.2 bpm, p < 0.001), serum uric acid (320.6 ± 88.8 μmol/l vs. 285.0 ± 74.9 μmol/l, p = 0.03) and type 2 diabetes mellitus prevalence (13.6% vs. 4.7%, p = 0.019). Binary logistic regression analysis revealed that only hypertension indices and HR associated independently with TOD. Conclusions: TOD is highly prevalent in patients with RA and associates independently with hypertension, arterial stiffness and heart rate. Further prospective studies are needed to confirm these findings and examine the role of beta-blockers in this particular population. © 2009 Elsevier Ireland Ltd. All rights reserved.

G-protein beta 3 subunit (GNB3) C825T (rs5443) single nucleotide polymorphism (SNP) has been implicated as a risk factor for essential hypertension in the general population. The effects of this SNP may be more prominent in subjects with endothelial dysfunction (ED). Rheumatoid arthritis (RA) is associated with ED and has a high prevalence of hypertension. Thus far, this SNP has not been studied in RA patients. We genotyped 383 RA patients and 432 controls. GNB3 C825T was identified using real-time polymerase chain reaction (PCR) and melting curve analysis. There were no differences in the frequencies of the GNB3 C825T genotype and alleles between RA and controls. Within RA patients, prevalence of hypertension did not differ across genotypes. The TT versus CC+CT contrast yielded an adjusted odds ratio (OR) of 0.92 (95% CI: 0.49 to 1.76, p 0.813), the contrast of TT+CT versus CC an adjusted OR of 2.17 (95% CI: 0.885 to 5.30, p 0.091), whereas that of the T allele versus C allele an adjusted OR of 1.11 (95% CI: 0.76 to 1.61, p 0.604). Systolic and diastolic blood pressure levels were not significantly different across the three genotypic groups. No significant interaction was observed between GNB3 825C/T polymorphism and serum endothelin levels. Data from the present study suggest that the T825 variant of the G protein β3 subunit gene is unlikely to constitute major susceptibility loci for essential hypertension in Caucasian RA patients. Further larger studies are required to confirm our findings and assess the interaction of rs5443 with environmental factors.

Objective: To assess whether physical activity, diet or inflammation is a more important determinant of body mass index (BMI) and body fat (BF) in patients with rheumatoid arthritis (RA).Methods: A total of 150 RA patients (102 female) were assessed for BMI and BF. Their habitual physical activity was assessed with the international physical activity questionnaire (IPAQ) and their energy intake with a 3-day food diary. Pro-inflammatory cytokines (interleukins, IL-1 and IL-6, and tumor necrosis factor-α), erythrocyte sedimentation rate, C-reactive protein, disease activity score-28 and physical function (Health Assessment QuestionnaireHAQ) were also measured.Results: BMI correlated inversely with IPAQ (r=0.511, P=0.000) and positively with energy intake (r=0.331, P=0.016) and HAQ (r=0.133, P=0.042). BF correlated inversely with IPAQ (r=0.575, P=0.000) and positively with HAQ (r=0.201, P=0.037). Normal weight patients were more physically active compared with those who were either overweight (P=0.006) or obese (P=0.000). Underweight patients consumed significantly fewer calories compared with other patients (P=0.05 in all cases). Cytokines or HAQ did not differ between weight groups. IPAQ was the sole predictor of obesity, whereas energy intake was the sole predictor of underweight.Conclusions: Inflammation does not seem to influence BMI and BF in RA. As in the general population, high levels of habitual physical activity associate with low BMI and BF in RA. Energy intake is a major determinant of being underweight in those who consume fewer calories. Further research is needed to investigate the suitability of exercise and diet modalities, and their effects on the body composition of RA patients. © 2010 Macmillan Publishers Limited All rights reserved.

Inflammation disturbs biochemical pathways involved in homeostasis of the endothelium. Research has established clear links between inflammatory mediators, particularly C-reactive protein and tumour necrosis factor alpha, endothelial dysfunction, and atherosclerosis. Endothelial dysfunction and atherosclerosis may be subclinical at early stages, and thus the ability to detect them with non-invasive techniques is crucially important, particularly in populations at increased risk for cardiovascular disease, such as those with rheumatoid arthritis. This may allow the identification of interventions that may reverse these processes early on. One of the best non-pharmacological interventions that may achieve this is physical activity. This review explores the associations between inflammation, endothelial dysfunction, and atherosclerosis and discusses the role of exercise in blocking specific pathways in the inflammation, endothelial dysfunction - atherosclerosis network.

Both cachexia and cardiovascular disease are strongly associated with rheumatoid arthritis (RA) and linked to the chronic inflammatory process. Typically, rheumatoid cachexia occurs in individuals with normal or increased BMI (reduced muscle mass and increased fat mass). Classic cachexia (reduced muscle mass and reduced fat mass) is rare in RA but is associated with high inflammatory activity and aggressive joint destruction in patients with a poor cardiovascular prognosis. Conversely, obesity is linked to hypertension and dyslipidemia but, paradoxically, lower RA disease activity and less cardiovascular disease-related mortality. Rheumatoid cachexia might represent the 'worst of both worlds' with respect to cardiovascular outcome, but until diagnostic criteria for this condition are agreed upon, its effect on cardiovascular disease risk remains controversial. © 2010 Macmillan Publishers Limited.

Obesity is a major threat for public health and its study has attracted significant attention in the general population, predominantly due to its association with significant metabolic and cardiovascular complications. In RA research, BMI is frequently reported as a demographical variable, but obesity, as such, has received little interest. This is surprising, in view of the clear associations of obesity with other arthritides, particularly OA, but also in view of the now-clear association of RA with increased cardiovascular morbidity and mortality. In this review, we summarize the studies that have looked into obesity in the RA population, evaluate their findings, identify knowledge gaps and propose directions for future research. We also pose a question of high clinical and research significance: is the use of BMI still a valid way of assessing obesity in RA? © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Introduction Rheumatoid arthritis (RA), a systemic inflammatory disease with complex genetic aetiology, associates with excess cardiovascular morbidity and mortality. Dyslipidaemia, a major cardiovascular risk factor has been reported to predate the onset of RA, thus suggesting a potential genetic link between the two conditions. The authors assessed whether RA susceptibility genes associate with the presence of dyslipidaemia in RA patients. Methods 400 well-characterised RA patients were included in this cross-sectional study. Fasting lipid profile (total cholesterol, high-density lipoproteins (HDL), lowdensity lipoproteins (LDL), triglycerides, apolipoproteins (ApoA and ApoB) and lipoprotein (a)) and four RA susceptibility genes ( PTPN22 , TRAF1/C5 , STAT4 and human leucocyte antigen shared epitope ( HLA-SE )) were assessed and associations were sought in both univariate and multivariate analyses. Results Following adjustment for age, sex and erythrocyte sedimentation rate, the G allele of TRAF1/C5 associated with lower total cholesterol (p=0.010), LDL (p=0.022) and ApoB (p=0.014); one or more copies of the shared epitope associated with lower ApoA (p=0.035) and higher ApoB:ApoA ratio (p=0.047); while STAT4 TT homozygotes had higher lipoprotein (a) (p=0.004). Conclusions RA susceptibility genes ( TRAF1/C5 , STAT4 and HLA-DRB1-SE ) may be involved in the regulation of lipid metabolism in RA patients, thus contributing to cardiovascular disease (CVD) risk and adverse outcome. If these findings are replicated, such genotyping could be used to identify and target for prevention those RA patients most at risk of CVD. It will also be interesting to study the association of these genes with lipid levels in the general population and identify mechanisms to explain the link.

INTRODUCTION: Substantial effort has been devoted for devising effective and safe interventions to reduce preventable hospital admissions in chronic disease patients. In rheumatoid arthritis (RA), identifying risk factors for admission has important health policy implications, but knowledge of which factors cause or prevent hospital admissions is currently lacking. We hypothesised that disease activity/severity and physical activity are major predictors for the need of hospitalisation in patients with RA. METHODS: A total of 244 RA patients were assessed for: physical activity (International Physical Activity Questionnaire), RA activity (C-reactive protein: CRP; disease activity score: DAS28) and disability (Health Assessment Questionnaire: HAQ). The number of hospital admissions and length of hospitalisation within a year from baseline assessment were collected prospectively. RESULTS: Disease activity and disability as well as levels of overall and vigorous physical activity levels correlated significantly with both the number of admissions and length of hospitalisation (P < 0.05); regression analyses revealed that only disease activity (DAS28) and physical activity were significant independent predictors of numbers of hospital admissions (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046)) and length of hospitalisation (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046). Sub-analysis of the data demonstrated that only 19% (n = 49) of patients engaged in recommended levels of physical activity. CONCLUSIONS: This study provides evidence that physical activity along with disease activity are important predictors of the number of hospital admissions and length of hospitalisation in RA. The combination of lifestyle changes, particularly increased physical activity along with effective pharmacological therapy may improve multiple health outcomes as well as cost of care for RA patients.

Objectives: The aim of the present study was to investigate if assymetric dimethylarginine (ADMA) is increased in patients with rheumatoid arthritis (RA) compared to healthy controls and to examine associations between ADMA, RA disease activity and in vivo assessments of microvascular and macrovascular endothelial function. Methods: Sixty-seven RA patients (age [mean ± standard deviation]: 56±12 years, disease duration median [25th-75th percentile]: 8 [3-15] years, 48 women) and 29 healthy controls (age [mean ± standard deviation]: 42±12, 21 women) underwent assessments of microvascular endothelial function (Laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) as well as arterial stiffness. ADMA levels were measured in contemporary specimens using an immunoassay ELISA kit. Results: ADMA levels were significantly higher (p=0.004) in RA patients compared with healthy controls after adjustment for age (difference=0.088, 95% confidence interval 0.029-0.147). ADMA levels did not correlate with demographic or disease characteristics. No correlation was found between ADMA and microvascular and macrovascular endothelial function or with arterial stiffness. Conclusion: ADMA levels are increased in patients with RA but there was no significant correlation with in vivo assessments of endothelial function. Further studies are needed to unfold the pathophysiological role of nitric oxide/ADMA pathway derangement in endothelial dysfunction and cardiovascular risk in RA. © Clinical and experimental rheumatology 2012.

Objective: To determine whether demographic, inflammatory, and metabolic factors predict elevated asymmetric dimethylarginine (ADMA) levels in rheumatoid arthritis (RA). Method: A total of 67 RA patients [mean age 56 ± 12 years, median disease duration 8 (3-15) years] were assessed. Routine biochemistry tests, lipid profile, glycaemic profile [glucose, insulin, homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI)], and inflammatory markers were measured in all patients. ADMA levels were measured by enzyme-linked immunosorbent assay (ELISA). Regression analyses were performed to identify predictors of ADMA in RA. Results: Regression analysis revealed that HOMA (β = 0.149, p = 0.003) was an independent predictor of ADMA in RA. From the drug factors, anti-hypertensive medication use was associated with lower ADMA levels (β =-0.081, p = 0.004). ADMA was not associated with RA disease-related parameters or any of the other cardiovascular risk factors that were assessed. Conclusions: HOMA, a strong indicator of insulin resistance, seems to be the main predictor of elevated ADMA levels in RA patients; ADMA may reflect an important pathway linking abnormal insulin metabolism with endothelial dysfunction in RA. © 2012 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation.

Objective: RA associates with an increased rate of sudden cardiac death (SCD). A prolonged QTc interval has been associated with arrhythmogenic and SCD in patients with long QT syndrome. Despite the previously reported contemporary association of CRP with SCD, thus far no studies have examined the association of QTc with mortality in RA, a condition characterized by high inflammatory burden. The aim of this study was to examine the role of electrocardiography (QT corrected interval) in predicting all-cause mortality in patients with RA who have an increased rate of SCD and a high inflammatory burden. Methods: Three hundred and fifty-seven RA patients with detailed baseline clinical characterization and 12-lead ECGs were followed up for a mean of 73.0 (S.D. 18.3) months. Linear and Cox regression analyses were used to identify variables that associate with QTc and examine its association with all-cause mortality. Results: The patients' mean age was 60.6 (S.D. 12.0) years, 267 (74.8%) were females and 54 (15.1%) died during the follow-up period. Age (ß = 0.231, P < 0.001), gender (ß = 0.137, P = 0.008) and CRP (ß = 0.144, P = 0.006) associated independently with QTc in RA patients. The crude hazard ratio (HR) for total mortality per 50-ms increase in QTc was 2.17 (95% CI 1.21, 3.90). This association remained significant [HR = 2.18 (95% CI 1.09, 4.35)] after adjustment for identified confounders (cardiovascular and RA specific), but was lost [HR = 1.73 (95% CI 0.83, 3.62)] when CRP was included in the model. Conclusion: A 50-ms increase in QTc interval associates with a doubling of the hazard for all-cause mortality in patients with RA. The observed contemporary association of QTc with CRP levels indicates a potentially hazardous interplay between inflammation and arrhythmogenesis. Future studies are needed to confirm the above findings and explore underlying mechanisms. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

INTRODUCTION: Asthma is a complex airways disease that affects over 350-million people worldwide. It is estimated that up to 10% of adults and 2.5% of children with asthma have severe disease, which is associated with reduced physical activity. The introduction of biological therapies has revolutionised the management of severe asthma; however, it remains to be determined whether this translates into improvements in physical activity status. METHOD: This 1-year retrospective study evaluated step-based physical activity (via a smartphone pedometer) in adults with severe asthma (n = 20) and two matched sub-groups (n = 20 mild asthma and n = 20 healthy controls). RESULTS: The annual daily step count was significantly less in adults with severe asthma (4698 ± 1927) versus mild asthma (7239 ± 1815) (P = 0.009) and healthy controls (8252 ± 2115) (P = 0.001). No difference in physical activity was observed between those with mild asthma and healthy controls (P > 0.05). CONCLUSION: Despite long-term treatment with biological therapies, physical activity remains significantly lower in adults with severe asthma. The development of personalised evidence-based interventions to promote physical activity in people with severe asthma remains a priority.

Objectives: We examined how opposing running slopes can modulate interval training effects on aerobic performance and reduction–oxidation (REDOX) determinants. Methods: Fourteen physically active volunteers, assigned to either the Uphill group (UG) or the Downhill group (DG), completed 16 workouts of ten 30-s runs, at either +10% or −10% grade, with a work-to-rest ratio of 1:2 at 90% of their Maximum Aerobic Speed (MAS) over 8 weeks. Maximal oxygen uptake (VO2max), MAS, Running Economy (RE), time to exhaustion at MAS (Tmax), respiratory exchange ratio (RER), and blood lactate at rest, 5th, and 10th runs were evaluated pre-, mid-, and post-training. Also, REDOX markers [Total Antioxidant Capacity (TAC), Protein Carbonyls (PCs) were assessed in blood samples taken at rest and 3 min post-exercise of the first and last workouts. Results: VO2max was unchanged in both groups; in the DG, MAS increased (from 14.2 ± 1.7 to 15.0 ± 1.5 km/h, d = 0.43), and post-training RER significantly increased (from 1.06 ± 0.07 to 1.12 ± 0.03). In the last training session, blood lactate levels increased in the UG (from 9.30 ± 2.69 mmοl/L to 13.34 ± 4.64 mmοl/L) but remained low and unchanged in DG (<2 mmοl/L). Post-training, resting TAC decreased in both groups, and the exercise-induced rise in PC levels was attenuated. Conclusions: Despite the brief intervention, VO2max levels were maintained in both groups, with divergent changes in metabolic, REDOX, and performance indicators; uphill HIIT may serve for enhancing lactate tolerance, while downhill intermittent running may improve running economy.

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/m 2 ), body fat (BF) and fat free mass (FFM), RA characteristics and CVD risk factors were assessed in 363 (262 female) 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. Body Mass Index 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 patients.

The physiological construct that is most widely known today as metabolic syndrome (MetS) was born in clinical practice almost a century ago when a Swedish physician recognized that hypertension, hyperglycemia, and gout commonly occurred together.1 Several years later, a French physician named Jean Vague recorded the keen observation that cardiovascular and metabolic dysfunctions were associated with an accumulation of upper body fat.2,3 Dr. Vague is credited with introducing the terms android and gynoid phenotypes to describe upper and lower body fat distribution and to document the greater health risk that appeared with the android pattern. The relationships between obesity, android adiposity, and the presence of hyperinsulinemia, hypertension, and elevated triglycerides gained greater recognition with the modernization of assays to reliably measure insulin, lipids, and other blood constituents.4-7 Prospective clinical studies, conducted just as obesity rates began to climb in the 1980s, con­rmed the greater health risks of abdominal fat that were ­rst observed by Vague. The waist circumference measurement was recognized to be a strong correlate of abdominal fat, and the waist-to-hip ratio was introduced as Origins of the Metabolic Syndrome ....................................................................... 311 Elusive De­nition of Metabolic Syndrome ........................................................... 313 Describing the Metabolic Syndrome in the United States of America .................. 318 Controversies of MetS in Science and Medicine ................................................... 319 Predicting Cardiometabolic Risk from MetS ......................................................... 321 Obesity and the Etiology of Insulin Resistance and MetS ..................................... 322 Screening and Evaluation for MetS ....................................................................... 325 Treatment and Management of MetS ..................................................................... 326 Lifestyle Behaviors: Healthy Diet, Physical Activity, and Weight Loss ........... 326 Dyslipidemia ..................................................................................................... 328 Blood Pressure .................................................................................................. 329 Blood Glucose Management ............................................................................. 330 Atherothrombosis and In°ammation ................................................................. 330 Summary ................................................................................................................ 331 References .............................................................................................................. 332 a surrogate marker of body fat phenotypes.8-14 Evidence to support the theory that insulin resistance15,16 and hyperinsulinemia17,18 were metabolic conditions linking obesity, hypertension, and type 2 diabetes was accumulating.

The study aimed to establish the test-retest reliability of detrended fluctuation analysis of heart rate variability (DFA-α1) based exercise intensity thresholds, assess its agreement with ventilatory- and lactate-derived thresholds and the moderating effect of sex and cardiorespiratory fitness (CRF) on the agreement. Intensity thresholds for thirty-seven participants (17 females) based on blood lactate (LT1/LT2), gas-exchange (VT1/VT2) and DFA-α1 (αTh1/αTh2) were assessed. Heart rate (HR) at αTh1 and αTh2 showed good test-retest reliability (coefficient of variation [CV] < 6%), and moderate to high agreement with LTs (r = 0.40 - 0.57) and VTs (r = 0.61 - 0.66) respectively. Mixed effects models indicated bias magnitude depended on CRF, with DFA-α1 overestimating thresholds versus VTs for lower fitness levels (speed at VT1 <8.5 km⋅hr-1), while underestimating for higher fitness levels (speed at VT2 >15 km⋅hr-1; VO2max >55 mL·kg-1·min-1). Controlling for CRF, sex significantly affected bias magnitude only at first threshold, with males having higher mean bias (+2.41 bpm) than females (-1.26 bpm). DFA-α1 thresholds are practical and reliable intensity measures, however it is unclear if they accurately represent LTs/VTs from the observed limits of agreement and unexplained variance. To optimise DFA-α1 threshold estimation across different populations, bias should be corrected based on sex and CRF.

PURPOSE: Pre-participation health screening is recommended to detect individuals susceptible to serious adverse cardiovascular complications during exercise. Although expert opinion and best available scientific evidence have informed recent modifications, there remains limited experimental data to support or refute current practice. We therefore aimed to quantify the impact of change to the ACSM pre-participation health screening guidelines on risk classification and referral for medical clearance in a large cohort of undergraduate university students. METHODS: Participants attended the laboratory on a single occasion to undergo pre-participation health screening. Information concerning health status was obtained via self-report questionnaire and objective physiological assessment with all data recorded electronically and evaluated against ACSM screening guidelines (9 and 10 Edition). RESULTS: Five-hundred and fifty-three students completed the study. The 9th Edition screening guidance resulted in eighty-two (15%) subjects classified as high-risk, almost one quarter (24%) classified as moderate-risk, and almost two-thirds (61%) classified as low-risk. In comparison, the updated 10 Edition screening guidance resulted in a significant reduction in those previously classified as either high-risk (5%) or moderate risk (2%), respectively. The majority of subjects (93%) were therefore cleared to begin a structured exercise programme. Taken together, approximately one-third (32%) fewer medical referrals were required when applying the updated 10 Edition guidance (χ (4) = 247.7, P<0.001). CONCLUSION: The updated ACSM 10 Edition pre-participation screening guidance reduces medical referrals by approximately one-third. These findings are in keeping with previous reports and thus serve to consolidate and justify recent modification - particularly when applied to young adult or adolescent populations. The findings and arguments presented should be used to refine and inform future guidance.

Abstract

Background Cardiovascular rehabilitation (CR) is a crucial element in the management of coronary heart disease (CHD). However, only 52% of those eligible for CR participate in it, with lower engagement among females and minority ethnic groups. Despite reported barriers to participation, healthcare professionals’ (HCPs) perspectives on referral and attendance remains unexplored. Aim To explore the perspectives of HCPs on factors influencing referral and attendance to CR services in the UK. Methods A three-round Delphi study (May to September 2023) involved 38 HCPs recruited via snowball sampling. In Round One, 12 open-ended questions enquired about participants’ views on staff competencies, core components of CR, referral criteria, referral pathways, and the associations between sex and ethnicity related to referral and attendance. Content analysis informed a structured five-point Likert scale questionnaire used in Round Two. Consensus was defined a priori as ≥ 70% agreement among the participants. In Round Three, participants were asked to retake the questionnaire after receiving feedback for individual and group responses. Results Consensus was achieved on 53 of the 108 statements, covering 10 key aspects of CR. HCPs acknowledged significant disparities in UK CR programmes, attributing these to knowledge gaps. HCPs emphasised the need for educational initiatives within general practitioner (GP) surgeries and direct referral pathways as effective strategies for enhancing sex-specific referrals to phase III CR. Furthermore, HCPs suggested education for hospital ward staff on inclusion and cultural training, alongside building relationships with local communities, to improve ethnic-specific referrals to CR (table 1). Conclusion This study highlights HCPs perspectives on referral and attendance to CR programmes in the UK, focusing on sex and ethnicity. HCPs emphasised the urgent need for initiatives to enhance clinicians’ knowledge and ensure inclusivity in CR services. Future research should build on these findings to promote equitable access to CR for diverse UK populations.

Purpose The aim was to develop and validate an individualised internal training exposure method by deriving weighting factors for each heart rate (HR) from detrended fluctuation analysis of heart rate variability (DFA-α1) during a graded exercise test. Methods Thirty-seven participants (17 females; 32.72 ± 9.26 years; maximal oxygen uptake, O2max = 48.32 ± 7.95 mL kg−1 min−1) completed a step- and a ramp incremental test to measure blood lactate (BLa), DFA-α1, and cardiorespiratory fitness (CRF) variables, i.e. speed at lactate, ventilatory thresholds (LTs/VTs), and O2max. Exponential fitting of the fractional elevation of HR (ΔHR) with BLa (individualised training impulse; iTRIMP) or DFA-α1 (αTRIMP) generated individualised coefficients for both methods. The TRIMP weightings were interpolated values of BLa or DFA-α1 derived at each ΔHR through coefficients to represent individualised physiological intensity. Principal component regression evaluated the relationship between combined CRF variables and the TRIMP coefficients or weightings. Results Large inter-individual variation was observed at the same physiological thresholds (ΔHR at LT1/VT1 = 0.51–0.83 and LT2/VT2 = 0.63–0.96), underscoring the need for TRIMP methods to weight ΔHR and account for different exposure at similar intensity. CRF had a moderate relationship with coefficients for iTRIMP and αTRIMP methods (R2average = 0.52–0.67), but a moderate to strong relationship with their weightings at a fixed ΔHR (R2average = 0.67–0.78). Conclusion αTRIMP is a valid and practically accessible method for quantifying internal training exposure using ECG-based HR monitors, which individualises physiological intensity through DFA-α1-derived weightings among individuals of varied fitness exercising at same percentages of HR.

Physical inactivity is common in people with chronic airways disease (pwCAD) and associated with worse clinical outcomes and impaired quality of life. We conducted a systematic review and meta-analysis to characterise and evaluate the effectiveness of interventions promoting step-based physical activity (PA) in pwCAD. We searched for studies that included a form of PA promotion and step-count outcome measure. A random-effects model was used to determine the overall effect size using post-intervention values. 38 studies (n=32 COPD; n=5 asthma; n=1 bronchiectasis; study population: n=3777) were included. Overall, implementing a form of PA promotion resulted in a significant increase in step-count: median (IQR) 705 (183-1210) when compared with usual standard care: -64 (-597-229), standardised mean difference (SMD) 0.24 (95% CI: 0.12-0.36), p<0.01. To explore the impact of specific interventions, studies were stratified into subgroups: PA promotion+wearable activity monitor-based interventions (n=17) (SMD 0.37, p<0.01); PA promotion+step-count as an outcome measure (n=9) (SMD 0.18, p=0.09); technology-based interventions (n=12) (SMD 0.16, p=0.01). Interventions promoting PA, particularly those that incorporate wearable activity monitors, result in a significant and clinically meaningful improvement in daily step-count in pwCAD.

Introduction: Regular physical activity and structured exercise are often reported to be associated with improved asthma control - however the majority of published evidence is limited by short-term studies employing subjective measures of assessment (i.e. self-report / questionnaires). Modern smartphones typically include built-in activity sensors (i.e. possess the capability to monitor daily step-count) and thus may offer a cost-effective and pragmatic solution to the assessment of physical activity in clinical practice and/or research trials. The primary aim of this proof-of-concept study was therefore to evaluate the validity of the iPhone® (Apple Inc, USA) step-counter in adults with asthma and healthy controls. Methods: The study was conducted as a cross-sectional laboratory based-trial. Ten healthy adults with no prior history of respiratory disease and ten adults with a prior physician diagnosis of asthma were enrolled. All completed baseline clinical assessment followed by a standardised walking treadmill challenge consisting of 3 x 3-minute stages at pre-determined speeds: 2.5kph, 5.0kph and 7.5kph. Steps were recorded using the following devices: (i) Yamax Digiwalker™ SW-200 Pedometer (Yamax, UK), (ii) iPhone® step-counter (upper body arm-band), (iii) iPhone® step-counter (lower body trouser pocket) - and evaluated against a video-verified manual step-count (i.e. gold-standard comparator) conducted by the investigator (CR). Results: No difference was observed in manual total step-count between individuals with asthma (1018 steps) and healthy controls (1038 steps) (P=0.44). The iPhone® step-counter (both upper and lower body) provided close agreement with video-verified manual step-count, and importantly, outperformed the Yamax Digiwalker® SW-200 Pedometer across the majority of test stages. Specifically, the iPhone® (lower body) correlated strongly (r = 0.96; P<0.006) and produced the highest level of agreement with video-verified total step-count (mean bias: -11; limits of agreement: -43 to 21) (Table 1). Conclusion: Our findings indicate that the iPhone® provides an accurate estimate of step-count in adults with asthma and healthy controls completing a standardised laboratory-based treadmill test. Prior to implementation, further research is required to determine the validity and reliability of this approach during daily active / free living conditions.

Background Impaired vascular health is prevalent in type 1 diabetes (T1D); however, it remains unknown whether di!erent insulin treatment regimens mediate indices of vascular structure or function. Methods Sixteen individuals with T1D receiving either multiple daily injection therapy (MDI; n=8; age: 32±13years; BMI:26.0±5.9kg.m2; HbA1c:53.7±11.2mmol/mol [7.1±3.2%]) or continuous subcutaneous insulin infusion (CSII; n=8; age:35±18years; BMI:26.3±4.6kg.m2; HbA1c: 58.6±9.7mmol/mol [7.5±3.0%]) and ten matched controls (CON; age:31±13years; BMI: 24.3±2.9kg.m2) consumed two high fat (HF) meals at 4-hour intervals. Carotid artery intima-media thickness (CIMT) and flow mediated dilation (FMD) was assessed at baseline, with further FMD assessment at 3-hrs following the ingestion of each meal using high resolution B-mode ultrasound. Bolus insulin dose was standardised using the carbohydrate-counting method. Results CIMT was significantly higher in individuals with T1D compared to controls (p=0.039); treatment stratification within T1D revealed MDI mediated this e!ect (MDI vs. CON: p=0.049; CSII vs. CON: p=0.112). FMD remained unchanged following the first meal (p=0.204) but was significantly impaired following the second meal (p=<0.001); post- hoc analysis revealed MDI mediated this e!ect of impaired FMD after the second meal (MDI vs. CON: p=0.048; CSII vs. CON: p=0.416). Conclusions Our findings indicate that patients treated with MDI therapy have higher CIMT (a structural marker of subclinical atherosclerosis) compared to controls but not CSII therapy. FMD was impaired following a second HF meal irrespective of a diabetes status. Considering the pre-existing heightened cardiovascular disease risk in T1D therapeutic strategies to reduce postprandial risk warrants further research.

PURPOSE: Preparticipation health screening is recommended to detect individuals susceptible to serious adverse cardiovascular complications during exercise. Although expert opinion and best available scientific evidence have informed recent modifications, there remain limited experimental data to support or refute current practice. We therefore aimed to quantify the impact of change to the preparticipation health screening guidelines of the American College of Sports Medicine (ACSM) on risk classification and referral for medical clearance in a large cohort of undergraduate university students. METHODS: Participants attended the laboratory on a single occasion to undergo preparticipation health screening. Information concerning health status was obtained via self-report questionnaire and objective physiological assessment with all data recorded electronically and evaluated against the ACSM screening guidelines (9th and 10th editions). RESULTS: Five hundred and fifty-three students completed the study. The 9th edition screening guidance resulted in 82 subjects (15%) classified as high risk, almost one-quarter (24%) classified as moderate risk, and almost two-thirds (61%) classified as low risk. In comparison, the updated 10th edition screening guidance resulted in a significant reduction in those previously classified as either high risk (5%) or moderate risk (2%), respectively. The majority of subjects (93%) were therefore cleared to begin a structured exercise program. Taken together, approximately one-third (32%) fewer medical referrals were required when applying the updated 10th edition guidance (χ4 = 247.7, P < 0.001). CONCLUSIONS: The updated ACSM 10th edition preparticipation screening guidance reduces medical referrals by approximately one-third. These findings are in keeping with previous reports and thus serve to consolidate and justify recent modification-particularly when applied to young adult or adolescent populations. The findings and arguments presented should be used to refine and inform future guidance.

Background: The benefits of exercise for people with rheumatoid arthritis (RA) are now widely recognised [1]. However, exercise participation among people with RA remains low. A key reason for that could be the commonly held belief that exercise, may exacerbate disease activity while acutely increasing levels of joint pain. The association of acute exercise with pain has not been established in RA and especially in people with a recent diagnosis. Objectives: This study investigated the impact of acute aerobic-and resistance-type exercise on perceptions of pain in people with early RA. Methods: Following local NHS ethical approval, ten people with RA volunteered for the study (Age=46±13years; BMI=29.4±8.6kg/m2, RA diagnosis= 13±9months, mean±SD). Inclusion criteria were RA diagnosis (2010 EULAR criteria) within the last two years and not engaging in regular physical activity (i.e. no participation in structured exercise >2 times per week). They were assessed for maximal aerobic capacity and maximal strength at chest press, leg press and wide-grip lateral pulldown to determine intensities for exercise conditions. Thereafter they completed one no-exercise control trial (CON) and four exercise trials: 30 minutes of sub-maximal cycling at a workload equivalent to 65% VO2max (CYCLE); high intensity interval exercise consisting of 10x1 minutes cycling intervals at a workload equivalent to 95% VO2max (HIIE); resistance exercise consisting of three sets of 12-15 repetitions at 70%1RM (RES-70); resistance exercise consisting of three sets of repetitions to failure at 30%1RM (RES-30). All trials were randomised and separated by a washout period of 3-7 days. Participants completed a a visual analogue scale (VAS) for pain at baseline then 2-and 24-hours post exercise; they also completed a questionnaire related to exercise enjoyment 2-and 24-hours post exercise. Results: Currently four RA participants have completed the study and all participants completed the prescribed exercises in full. Perceived pain was low at 2 hours (0.7±0.4) and 24 hours post-exercise (1.2±0.8) for all exercise conditions (see table 1). Importantly, a difference in heart rate between the aerobic conditions (heart rate during HIIE was 16% higher than during CYCLE), and a difference in workload between the resistance conditions (RES-30 was 117% higher than RES-70) did not result in a difference in pain perception. One participant reported increased pain at 24 hours (7cm vs 1cm at 2 hours) post RES-30, but claimed that this was purely muscular and not joint pain. Interestingly, all participants enjoyed the exercises with comparable high results across the exercise conditions (see table 1). Conclusion: This study identified minimal exercise effect on perceived pain at 2 hours-and 24 hours-post exercise among participants with early RA. This suggests that exercise did not exacerbate pain and importantly, high intensities and high loads did not cause additional pain. Nevertheless, further larger studies are required to examine the role of acute exercise on disease activity, e.g. inflammation, and the association with perceived pain in people with early RA. References: [1]Combe B, et al. 2016 update of the EULAR recommendations for the management of early arthritis. Annals of the Rheumatic Diseases 2016; 76: 948-959. Disclosure of Interests: None declared Table 1 Pain and Enjoyment Descriptives Trial Baseline VAS pain (cm) 2-hour VAS pain (cm) 24-hour VAS pain (cm) 2-hour exercise enjoyment (1-119) 24-hour exercise enjoyment (1-119) CON 0.1±0.3 0.1±0.3 0.3±0.3 63.8±13.0 63.8±13.0 CYCLE 0.1±0.3 0.5±0.4 0.9±1.2 86.8±11.0 88.0±8.8 HIIE 0.1±0.3 1.3±1.9 1.1±1.7 85.0±27.8 88.3±19.1 RES-70 0.1±0.3 0.4±0.4 0.5±0.4 91.3±13.0 88.3±6.6 RES-30 0.1±0.3 0.4±0.5 2.4±3.1 88.5±17.1 85.0±13.1 (mean±SD)

Background: Acute sarcopenia is sarcopenia lasting less than six months, typically following acute illness or injury. It may impact patient recovery and quality of life, advancing to chronic sarcopenia. However, its development and assessment remain poorly understood, particularly during hospitalisation. This systematic review aimed to elucidate the incidence of acute sarcopenia and examine changes in muscle parameters during hospitalisation. Methods: Eighty-eight papers were included in the narrative synthesis; 33 provided data for meta-analyses on the effects of hospitalisation on handgrip strength (HGS), rectus femoris cross-sectional area (RFCSA) and various muscle function tests. Meta-regressions were performed for length of hospital stay (LoS) and age for all meta-analyses; sex was also considered for HGS. Results: Acute sarcopenia development was assessed in four studies with a pooled incidence of 18% during hospitalisation. Incidence was highest among trauma patients in intensive care (59%) while it was lower among medical and surgical patients (15-20%). Time of development ranged from 4-44 days. HGS remained stable during hospitalisation (SMD = 0.05, 95% CI = -0.18:0.28, P = 0.67) as did knee extensor strength. LoS affected HGS performance (θ = 0.04, 95% CI = 0.001:0.09, P = 0.045) but age (P = 0.903) and sex (P = 0.434) did not. RFCSA, reduced by 16.5% over 3 to 21 days (SMD = -0.67, 95% CI = -0.92:-0.43, P <0.001); LoS or time between scans did significantly predict the reduction (θ = -0.04, 95% CI = -0.077:-0.011, P = 0.012). Indices of muscle quality also reduced. Muscle function improved when assessed by the short physical performance battery (SMD = 0.86, 95% CI = 0.03:1.69, P = 0.046); there was no change in 6-minute walk (P = 0.22), timed up-and-go (P = 0.46) or gaitspeed tests (P = 0.98). The only significant predictor of timed up-and-go performance was age (θ = -0.11, 95% CI = -0.018:-0.005, P = 0.009). Conclusions: Assessment and understanding of acute sarcopenia in clinical settings is limited. Incidence varies between clinical conditions and muscle parameters are affected differently. HGS and muscle function tests may not be sensitive enough to identify acute changes during hospitalisation. Currently, muscle health deterioration may be underdiagnosed impacting recovery, quality of life and overall health following hospitalisation. Further evaluation is necessary to determine the suitability of existing diagnostic criteria of acute sarcopenia. Muscle mass and quality indices might need to become the primary determinants for muscle health assessment in hospitalised populations.

Objectives. Rheumatoid arthritis (RA) associates with excessive cardiovascular morbidity and mortality. Hypertension (HT) contributes significantly to the development of cardiovascular disease (CVD). Little is known about the factors that influence blood pressure (BP) in patients with RA. In this study, we assessed the prevalence of HT in a secondary care cohort of RA patients, and aimed to identify factors associated with its presence and inadequate control. Methods. A total of 400 consecutive RA patients were studied. HT was defined as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or current use of antihypertensive drugs. The association of HT with several demographic and RA-related factors, comorbidities and drugs was evaluated using logistic regression. Results. HT was present in 282 (70.5%) patients. Of those, 171 (60.6%) received anti-hypertensive therapy, but 111 (39.4%) remained undiagnosed. Of those treated, only 37/171 (21.8%) were optimally controlled. Multivariable logistic regression revealed age (OR = 1.054, CI: 1.02 to 1.07, P = 0.001), body mass index [BMI (OR = 1.06, CI: 1.003-1.121, P = 0.038)] and prednisolone use (OR = 2.39, CI: 1.02-5.6, P = 0.045) to be independently associated with the presence of HT. BMI (OR = 1.11, CI: 1.02-1.21, P = 0.002) and the presence of CVD (OR = 4.01, CI: 1.27-12.69, P = 0.018) associated with uncontrolled HT. Conclusions. HT is highly prevalent in RA, under-diagnosed particularly in the young, and under-treated particularly in old RA patients with CVD. RA patients receiving steroids should be specifically targeted for screening and treatment; those with any cardiovascular comorbidity may require particularly aggressive monitoring and treatment strategies. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

INTRODUCTION: MicroRNAs (miRNAs) are non-coding RNAs that have an important role in regulating gene expression. Although circulating miRNAs are considered good markers of response to acute resistance training (RT) (1), change in expression according to the applied stimulus (e.g. high-intensity low-volume vs. low-intensity high-volume) has yet to be investigated. The aim of this study was therefore to evaluate the impact of RT protocols on circulating miRNA levels. We selected miRNA 29a, 128a, 486 as they have been previously shown to be implicated in skeletal muscle regeneration and structural adaptation (i.e. hypertrophy)

INTRODUCTION: MicroRNAs (miRNAs) are non-coding RNAs that have an important role in regulating gene expression. Although circulating miRNAs are considered good markers of response to acute aerobic exercise (1) change in expression according to workload has yet to be investigated. The aim of this study was therefore to determine the impact of maximal vs. sub-maximal intensity aerobic exercise on plasma concentrations of circulating miRNAs associated with inflammation, vascular adaptation and cardio-protection (miRNA 146a, miRNA 222, miRNA 21) (2).

Background: Exercise is advocated in the treatment of rheumatoid arthritis (RA). However, uncertainty around the acute effects of exercise on pain and inflammation may be stopping people with RA from exercising more regularly. Objectives: To determine the acute effects of exercise on pain symptoms, clinical inflammatory markers, and inflammatory cytokines in RA. Design: A systematic review of the literature. Data sources and methods: Five databases were searched (PubMed, Cochrane Library, CINAHL, Scopus and SPORTDiscus); inclusion criteria were studies with acute exercise, a definite diagnosis of RA and disease characteristics assessed by clinical function (i.e., disease activity score, health assessment questionnaire and self-reported pain), clinical markers associated with inflammation (i.e., c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and inflammatory cytokines (i.e., interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)). Results: From a total of 1544 articles, initial screening and full text assessment left 11 studies meeting the inclusion criteria. A total of 274 people were included in the studies (RA = 186; control = 88). Acute bouts of aerobic, resistance, and combined aerobic and resistance exercise did not appear to exacerbate pain symptoms in people with RA. Conclusion: Post-exercise responses for pain, clinical inflammatory markers and inflammatory cytokines were not different between people with or without RA. Exercise prescription was variable between studies, which limited between-study comparisons. Therefore, future investigations in people with RA are warranted, which combine different exercise modes and intensities to examine acute effects on pain symptoms and inflammatory markers. Registration: The PROSPERO international prospective register of systematic reviews - CRD42018091155.

OBJECTIVE: The aim of this pilot validation study was to determine the accuracy of a smartphone (iPhone®) pedometer in adults with and without asthma. METHODS: : Ten adults with asthma and ten healthy controls underwent clinical assessment prior to completing two separate trials. Phase 1. standardized treadmill and self-paced walking tests. Total steps were recorded via: (i) Yamax Digiwalker™ SW800 pedometer positioned on the waistband, (ii) iPhone® pedometer positioned on the upper body, (iii) iPhone® pedometer positioned on the lower body and evaluated against a video-verified manual step-count. Phase 2. step-count was evaluated over seven-days during habitual free-living conditions via Yamax Digiwalker™ SW800 and iPhone® pedometers. RESULTS: : During treadmill walking, the iPhone® positioned on the lower body correlated strongly (r = 0.96) and produced the highest level of agreement (mean bias: -11 steps, LOA: -43 to 21 steps) in comparison to video-verified manual step-count. During self-paced walking, all devices provided an excellent step-count estimate. During free-living conditions, no difference was observed between the Yamax Digiwalker™ SW800 pedometer and iPhone® (P = 0.10) and a strong correlation (r = 0.94) and acceptable agreement (mean bias: -343, LOA: -1963 to 1276 steps) was observed. CONCLUSION: : Our findings indicate that an in-built iPhone® pedometer offers a practical approach to physical activity assessment in adults with and without asthma. Future research is now required to further validate the precision of this approach and evaluate the efficacy and effectiveness of smartphone pedometers to monitor and promote physical activity when employed during medical consultation and/or clinical research trials.

The COVID-19 pandemic and social distancing restrictions have significantly reduced population-wide physical activity (PA) levels. However, the impact of the pandemic and relevant restrictions on PA participation, and any potential barriers to it, in people with rheumatoid arthritis (RA) are not clear. Furthermore, we are unsure if any such PA changes have affected their body weight, mental wellbeing, and/or quality of life (QoL). Thus, the aim of this study was to examine the impact of the lockdown on PA participation in people with RA, versus people without RA. Participants (n = 128; RA = 27, non-RA = 101) completed a self-administered online survey, which included questions on PA, body weight, mental wellbeing and QoL. PA participation during lockdown was significantly lower among RA versus non-RA participants (p < 0.001). Additionally, a similar profile of results was found where more RA participants vs non-RA participants reported reduced habitual PA (59% vs 33%) and increased body weight (59% vs 35%). Mental wellbeing scores were similarly low in both groups during lockdown (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, p = 0.080). Matched group comparisons identified similar trends to full sample analyses. In the first months of the lockdown, more people with RA reported decreased PA participation and increased body weight than their non-RA counterparts. Access to exercise equipment and facilities appears to be the main cause for these results. Looking beyond COVID-19, specific PA promotion for people with RA will be required to prevent a pandemic of inactivity.

MicroRNAs (miRNAs) are endogenously generated single-stranded RNAs that play crucial roles in numerous biological processes, such as cell development, proliferation, differentiation, metabolism and apoptosis. They negatively regulate target gene expression by repressing translation of messenger RNA into a functional protein. Several miRNAs have been implicated in the development and progression of RA. They are involved in inflammatory and immune processes and are associated with susceptibility to RA and disease activity. They are also considered to be potential markers of disease activity or even therapeutic targets. Likewise, several miRNAs are affected acutely by exercise and regulate exercise-related adaptations in the skeletal muscle and cardiovascular system and aerobic fitness. Interestingly, some miRNAs affected by exercise are also important in the context of RA. Investigating these might increase our understanding of the effects of exercise in RA and improve exercise prescription and, potentially, disease management. In this review, we focus on the miRNAs that are associated with both RA and exercise and discuss their roles in (and potential interactions between) RA and exercise-induced adaptations.

Fatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (>35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P > 0.05). Insulin sensitivity decreased following HFD (SMD = –0.34; 95% CI: –0.52, –0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (>35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984.

Background Cardiac rehabilitation (CR) provides proven benefits, yet only 50% of eligible individuals participate, with females and ethnic minority groups being particularly underrepresented. This study aimed to explore healthcare professionals’ (HCPs) views on factors influencing referral and attendance to phase III CR services in the United Kingdom (UK), with the purpose of identifying evidence-based recommendations and strategies to enhance access and participation. Methods Thirty-eight HCPs involved in the cardiac care or rehabilitation of patients with coronary heart disease (CHD) participated in a three-round Delphi study. Participants were asked about staff competencies, CR core components, referral criteria, referral pathways, and the impact of sex and ethnicity on referral and attendance. Results 108 statements were proposed by the participants. Consensus was achieved on 53 statements covering 10 key aspects of CR. HCPs identified significant disparities in referral practices and attendance, attributing these to HCP knowledge gaps, lack of streamlined referral pathways, and non-inclusive referral processes. They emphasised the need for educational initiatives within general practitioner surgeries and the development of direct referral pathways to improve CR access. Additionally, HCPs highlighted the importance of educating ward staff on inclusive practices and cultural sensitivity to improve referrals, particularly for females and ethnic minority groups. Conclusions The study highlights disparities in CR referral and attendance, particularly by sex and ethnicity. It provides evidence-based recommendations to ensure equitable access to CR services. Future interventions should focus on tailored education for HCPs and streamlined, direct referral pathways to ensure inclusive access for diverse populations in the UK.

Introduction Acute exposure to very high altitude (>3500m) is associated with a suppression of appetite, acylated ghrelin (AG) and energy intake. Appetite suppression at altitude is likely caused by the reduction in arterial oxygen saturation (SpO2), consequent to the low oxygen tensions present at altitude. Beetroot juice (BRJ) has shown to minimise the altitude-related reductions in SpO2 and may therefore provide relief of altitude-induced suppression of AG and appetite. The present study investigated the effects of BRJ supplementation on appetite, AG and energy intake at 4300m simulated altitude. Methods Ten healthy males (mean(SD); age 24(7) years, body mass index 25(3)kg·m-2) completed two 6h 30mins experimental trials in normobaric hypoxia, simulating an altitude of 4300m (~11.7% FiO2). Trials were conducted in a randomised, double blind, counter-balanced fashion. After an overnight fast, participants arrived at the laboratory and completed baseline measures. Following cannulation, participants consumed a porridge breakfast accompanied by 140ml concentrated BRJ (Beet It, James White Ltd., UK) or placebo. Participants entered the hypoxic chamber 90mins after breakfast, where they rested for 2h 30mins. Participants then completed a 60min treadmill walk at 10% gradient and 50% of relative V̇O2max, whilst carrying a 10kg rucksack. After exercise, participants consumed a snack and 70ml concentrated BRJ or placebo. Participants then rested inside the chamber until 6h 30mins. After leaving the chamber, the participants were given an ad-libitum homogenous pasta meal. Fractional exhaled nitric oxide (FeNO) provided a marker of nitric oxide bioavailability. Composite appetite score (CAS) and AG were measured throughout; results are presented for four area under the curve (AUC) periods: pre-hypoxic, hypoxic rest, exercise and post-exercise. Results At baseline there were no differences in any variables between conditions (P≥0.382). There was no significant difference in FeNO between conditions upon entry to the chamber (P=0.110), however FeNO was significantly elevated in BRJ immediately prior to exercise, compared with placebo (P=0.034). There were no differences between conditions during any of the AUC periods for SpO2 (P≥0.746), AG (P≥0.231), or CAS (P≥0.730). Energy intake at the ad-libitum buffet meal did not differ between BRJ (3542±1306kJ) and placebo (3980±1342kJ; P=0.270). Discussion This study suggests that acute BRJ supplementation has no effect on appetite, AG, or energy intake at 4300m simulated altitude. However, other methodological approaches which may elevate SpO2, such as chronic BRJ loading, require further investigation.

We appreciate the opportunity to respond to the comments raised by Silva and Cipriano [1] regarding our recently published systematic review and meta-analysis on acute sarcopenia [2]. Constructive discussions such as this help clarify methodological considerations and enhance scientific understanding. Firstly, regarding knee extensor strength measurement, Silva and Cipriano [1] note that our review stated their study [3] did not assess knee extensor strength. We acknowledge that they measured strength using neuromuscular electrical stimulation to evoke peak force. However, our review excluded studies using electrically evoked contractions, as voluntary contractions are the recognised standard for sarcopenia assessments. This exclusion criterion was applied consistently across all studies, ensuring methodological alignment. Although we did not explicitly state this in our inclusion/exclusion criteria, we appreciate the opportunity to clarify this point. To further justify our stance on excluding this, we would like to highlight conclusions from Jenkins et al. [4] who acknowledged that voluntary and evoked contractions offer unique information to each other and should not be used interchangeably. Secondly, with reference to the sample size inclusion, we included only the control group from Silva et al.'s study, as per our inclusion criteria that specified that only control groups from intervention studies would be included. Although their total sample size was 60 participants, we reported only the control group (n = 30) as our review focused on muscle changes during hospitalisation independent of interventions. We acknowledge that this distinction could have been stated more clearly. We respectfully disagree with the claim that our review contains inaccuracies that could compromise the integrity of the scientific record. Our methodological decisions were carefully considered, transparent, and aligned with standard sarcopenia assessment practices. The exclusion of electrically evoked contraction measures was a deliberate methodological choice, as voluntary contractions are the established standard. Although this criterion was not explicitly outlined in our inclusion/exclusion criteria, it reflects a methodological decision rather than an inaccuracy. We appreciate the opportunity to clarify this and believe our approach remains clear to researchers familiar with standard assessment methods. We thank Silva et al. for their engagement and the opportunity to address these points.

To establish the criterion-assessed energy and fluid requirements of female netball players, 13 adult players from a senior Netball Super League squad were assessed over 14 days in a cross-sectional design, representing a two- and one-match microcycle, respectively. Total energy expenditure (TEE) and water turnover (WT) were measured by doubly labeled water. Resting and activity energy expenditure were measured by indirect calorimetry and Actiheart, respectively. Mean 14-day TEE was 13.46 ± 1.20 MJ day−1 (95% CI, 12.63–14.39 MJ day−1). Resting energy expenditure was 6.53 ± 0.60 MJ day−1 (95% CI, 6.17–6.89 MJ day−1). Physical activity level was 2.07 ± 0.19 arbitrary units (AU) (95% CI, 1.95–2.18 AU). Mean WT was 4.1 ± 0.9 L day−1 (95% CI, 3.6–4.7 L day−1). Match days led to significantly greater TEE than training (+2.85 ± 0.70 MJ day−1; 95% CI, +1.00– +4.70 MJ day−1; p = 0.002) and rest (+4.85 ± 0.70 MJ day−1; 95% CI, +3.13–+6.56 MJ day−1; p < 0.001) days. Matches led to significantly greater energy expenditure (+1.85 ± 1.27 MJ; 95% CI, +0.95–+2.76 MJ day−1; p = 0.001) than court-based training sessions. There was no significant difference in TEE (+0.03 ± 0.35 MJ day−1; 95% CI, −0.74–+0.80 MJ day−1; p = 0.936) across weeks. Calibrated Actiheart 5 monitors underestimated TEE (−1.92 ± 1.21 MJ day−1). Energy and fluid turnover were greatest on match days, followed by training and rest days, with no difference across weeks. This study provides criterion-assessed energy and fluid requirements to inform dietary guidance for female netball players.

This narrative review examines the mechanisms underlying the development of cardiovascular (CVD) and metabolic diseases (MDs), along with their association with sarcopenia. Furthermore, non-pharmacological interventions to address sarcopenia in patients with these conditions are being suggested. The significance of combined training in managing metabolic disease and secondary sarcopenia in type II diabetes mellitus is emphasized. Additionally, the potential benefits of resistance and aerobic training are being explored. This review emphasises the role of nutrition in addressing sarcopenia in patients with CVD or MDs, focusing on strategies such as optimising protein intake, promoting plant-based protein sources, incorporating antioxidant-rich foods and omega-3 fatty acids, and ensuring sufficient vitamin D levels. Moreover, the potential benefits of targeting gut microbiota through probiotics and prebiotic fibres in sarcopenic individuals are being considered. Multidisciplinary approaches that integrate behavioural science are explored to enhance the uptake and sustainability of behaviour-based sarcopenia interventions. Future research should prioritise high-quality randomized controlled trials to refine exercise and nutritional interventions and investigate the incorporation of behavioural science into routine practices. Ultimately, a comprehensive and multifaceted approach is essential to improve health outcomes, well-being, and quality of life in older adults with sarcopenia and coexisting cardio-vascular and metabolic diseases.