Carotid intima-media thickness and flow-mediated dilation do not predict acute in-hospital outcomes in patients hospitalized with COVID-19.

Studies have suggested a potential role of endothelial dysfunction and atherosclerosis in the pathophysiology of COVID-19. Herein, we tested whether brachial flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT) measured upon hospital admission are associated with acute in-hospital outcomes in patients hospitalized with COVID-19. A total of 211 patients hospitalized with COVID-19 were submitted to assessments of FMD and mean and maximum cIMT (cIMTmean and cIMTmax) within the first 72 h of hospital admission. Study primary outcome was a composite of intensive care unit admission, mechanical ventilation, or death during the hospitalization. These outcomes were also considered independently. Thrombotic events were included as a secondary outcome. Odds ratios (ORs) and confidence intervals (CIs) were calculated using unadjusted and adjusted multivariable logistic regression models. Eighty-eight (42%) participants demonstrated at least one of the composite outcomes. cIMTmean and cIMTmax were predictors of mortality and thrombotic events in the univariate analysis (cIMTmean and mortality: unadjusted OR 12.71 [95% CI 1.71-94.48]; P = 0.014; cIMTmean and thrombotic events: unadjusted OR 11.94 [95% CI 1.64-86.79]; P = 0.015; cIMTmax and mortality: unadjusted OR 8.47 [95% CI 1.41-51.05]; P = 0.021; cIMTmax and thrombotic events: unadjusted OR 12.19 [95% CI 2.03-73.09]; P = 0.007). However, these associations were no longer present after adjustment for potential confounders (P > 0.05). In addition, FMD% was not associated with any outcome. In conclusion, cIMT and FMD are not independent predictors of clinical outcomes in patients hospitalized with COVID-19. These results suggest that subclinical atherosclerosis and endothelial dysfunction may not be the main drivers of COVID-19 complications in patients hospitalized with COVID-19.NEW & NOTEWORTHY Studies have suggested a role of endothelial dysfunction and atherosclerosis in COVID-19 pathophysiology. In this prospective cohort study, we assessed the prognostic value of carotid intima-media thickness (IMT) and flow-mediated dilation (FMD) in patients with COVID-19. Carotid IMT and FMD were not independent predictors of major outcomes. These results suggest that other risk factors may be the main drivers of clinical outcomes in patients with COVID-19.

Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activation in post-menopausal women with rheumatoid arthritis.

KEY POINTS: Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved.  This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA.  Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain.  The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. ABSTRACT: Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3 min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAPexercise  = 16 ± 11 vs. 9 ± 6 mmHg, P = 0.03; ΔMAPPEI  = 15 ± 10 vs. 5 ± 5 mmHg, P = 0.001; ΔMSNAexercise  = 17 ± 14 vs. 7 ± 9 bursts min-1 , P = 0.04; ΔMSNAPEI  = 14 ± 10 vs. 6 ± 4 bursts min-1 , P = 0.04). Autonomic responses to exercise showed significant (P < 0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.

Acute cardiometabolic effects of brief active breaks in sitting for patients with rheumatoid arthritis.

Exercise is a treatment in rheumatoid arthritis, but participation in moderate-to-vigorous exercise is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. We compared the acute effects of active breaks in sitting with those of moderate-to-vigorous exercise on cardiometabolic risk markers in patients with rheumatoid arthritis. In a crossover fashion, 15 women with rheumatoid arthritis underwent three 8-h experimental conditions: prolonged sitting (SIT), 30-min bout of moderate-to-vigorous exercise followed by prolonged sitting (EX), and 3-min bouts of light-intensity walking every 30 min of sitting (BR). Postprandial glucose, insulin, c-peptide, triglycerides, cytokines, lipid classes/subclasses (lipidomics), and blood pressure responses were assessed. Muscle biopsies were collected following each session to assess targeted proteins/genes. Glucose [-28% in area under the curve (AUC), P = 0.036], insulin (-28% in AUC, P = 0.016), and c-peptide (-27% in AUC, P = 0.006) postprandial responses were attenuated in BR versus SIT, whereas only c-peptide was lower in EX versus SIT (-20% in AUC, P = 0.002). IL-1ß decreased during BR, but increased during EX and SIT (P = 0.027 and P = 0.085, respectively). IL-1ra was increased during EX versus BR (P = 0.002). TNF-α concentrations decreased during BR versus EX (P = 0.022). EX, but not BR, reduced systolic blood pressure (P = 0.013). Lipidomic analysis showed that 7 of 36 lipid classes/subclasses were significantly different between conditions, with greater changes being observed in EX. No differences were observed for protein/gene expression. Brief active breaks in sitting can offset markers of cardiometabolic disturbance, which may be particularly useful for patients who may find it difficult to adhere to exercise.NEW & NOTEWORTHY Exercise is a treatment in rheumatoid arthritis but is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. Our findings show beneficial, but differential, cardiometabolic effects of active breaks in sitting and exercise in patients with rheumatoid arthritis. Breaks in sitting mainly improved glycemic and inflammatory markers, whereas exercise improved lipidomic and hypotensive responses. Breaks in sitting show promise in offsetting aspects of cardiometabolic disturbance associated with prolonged sitting in rheumatoid arthritis.

Clinical safety of blood flow-restricted training? A comprehensive review of altered muscle metaboreflex in cardiovascular disease during ischemic exercise.

Blood flow restriction training (BFRT) is an increasingly widespread method of exercise that involves imposed restriction of blood flow to the exercising muscle. Blood flow restriction is achieved by inflating a pneumatic pressure cuff (or a tourniquet) positioned proximal to the exercising muscle before, and during, the bout of exercise (i.e., ischemic exercise). Low-intensity BFRT with resistance training promotes comparable increases in muscle mass and strength observed during high-intensity exercise without blood flow restriction. BFRT has expanded into the clinical research setting as a potential therapeutic approach to treat functionally impaired individuals, such as the elderly, and patients with orthopedic and cardiovascular disease/conditions. However, questions regarding the safety of BFRT must be fully examined and addressed before the implementation of this exercise methodology in the clinical setting. In this respect, there is a general concern that BFRT may generate abnormal reflex-mediated cardiovascular responses. Indeed, the muscle metaboreflex is an ischemia-induced, sympathoexcitatory pressor reflex originating in skeletal muscle, and the present review synthesizes evidence that BFRT may elicit abnormal cardiovascular responses resulting from increased metaboreflex activation. Importantly, abnormal cardiovascular responses are more clearly evidenced in populations with increased cardiovascular risk (e.g., elderly and individuals with cardiovascular disease). The evidence provided in the present review draws into question the cardiovascular safety of BFRT, which clearly needs to be further investigated in future studies. This information will be paramount for the consideration of BFRT exercise implementation in clinical populations.

Increased Prolonged Sitting in Patients with Rheumatoid Arthritis during the COVID-19 Pandemic: A Within-Subjects, Accelerometer-Based Study.

BACKGROUND: Social distancing measures designed to contain the COVID-19 pandemic can restrict physical activity, a particular concern for high-risk patient groups. We assessed rheumatoid arthritis patients' physical activity and sedentary behavior level, pain, fatigue, and health-related quality of life prior to and during the social distancing measures implemented in Sao Paulo, Brazil. METHODS: Post-menopausal females diagnosed with rheumatoid arthritis were assessed before (from March 2018 to March 2020) and during (from 24 May to 7 July 2020) social distancing measures to contain COVID-19 pandemic, using a within-subjects, repeated-measure design. Physical activity and sedentary behavior were assessed using accelerometry (ActivPAL micro). Pain, fatigue, and health-related quality of life were assessed by questionnaires. RESULTS: Mean age was 60.9 years and BMI was 29.5 Kg/m2. Disease activity ranged from remission to moderate activity. During social distancing, there were reductions in light-intensity activity (13.0% [-0.2 h/day, 95% CI: -0.4 to -0.04; p = 0.016]) and moderate-to-vigorous physical activity (38.8% [-4.5 min/day, 95% CI: -8.1 to -0.9; p = 0.015]), but not in standing time and sedentary time. However, time spent in prolonged bouts of sitting ≥30 min increased by 34% (1.0 h/day, 95% CI: 0.3 to 1.7; p = 0.006) and ≥60 min increased by 85% (1.0 h/day, 95% CI: 0.5 to 1.6). There were no changes in pain, fatigue, and health-related quality of life (all p > 0.050). CONCLUSIONS: Imposed social distancing measures to contain the COVID-19 outbreak were associated with decreased physical activity and increased prolonged sedentary behavior, but did not change clinical symptoms sitting among patients with rheumatoid arthritis.

Influence of Adherence to Social Distancing Due to the COVID-19 Pandemic on Physical Activity Level in Post-bariatric Patients.

We assessed physical activity using accelerometers and a questionnaire in 33 post-bariatric patients who reported to be adherent (n = 15) or not (n = 18) to social distancing due to the COVID-19 pandemic. Patients adherent to social distancing spent more time in sedentary behavior (1.1 h/day, 0.1, 2.2; p = 0.045) and less time in moderate-to-vigorous physical activity (- 12.2 min/day, - 23.8, - 0.6; p = 0.040) vs. non-adherent ones. Bland-Altman analysis comparing objective and subjective physical activity estimates showed a bias for time spent in sedentary behavior and moderate-to-vigorous activity of 2.8 h/day and 8.5 min/day. In conclusion, post-bariatric patients who were adherent to social distancing measures were more inactive and sedentary than non-adherent ones. Strategies to increase physical activity in post-bariatric patients exposed to social distancing are necessary during the COVID-19 pandemic.

Acute effects of moderate-intensity and high-intensity exercise on hemodynamic and autonomic reactivity to the cold pressor test in young adults with excess body weight.

OBJECTIVE: To investigate the effects of a single session of moderate-intensity and high-intensity interval exercise in cardiovascular reactivity to the cold pressor test in young adults with excess body weight. METHODS: Twenty-two subjects with excess body weight (23 ± 2 years; 30.0 ± 3.4 kg·m) performed three sessions: (1) moderate-intensity exercise (30-minute cycling at 50%-60% of heart rate reserve); (2) high-intensity exercise (four series of 3-minute cycling at 80%-90% of heart rate reserve, interspersed by 2-minute recovery) and (3) control (i.e. 30-minute seated). Before and 30 minutes after the interventions, subjects undertook assessments of SBP/DBP and heart rate in response to the cold pressor test (1-minute rest + 1-minute hand immersed in 4°C water). Reactivity was calculated as the absolute response of SBP, DBP and heart rate to cold pressor test and compared between interventions using a two-way analysis of variance (P < 0.05). RESULTS: Neither moderate-intensity exercise or high-intensity interval exercise attenuated SBP/DBP reactivity to cold pressor test compared with control. On the other hand, heart rate reactivity was reduced after moderate-intensity exercise compared with control (1.36 ± 8.35 bpm vs. 5.18 ± 9.45 bpm). Furthermore, moderate-intensity exercise reduced absolute levels of SBP/DBP from pre- to post-intervention. CONCLUSION: A single session of moderate-intensity exercise or high-intensity interval exercise did not reduce the SBP/DBP reactivity to cold pressor test. However, absolute levels of SBP/DBP were lower after moderate-intensity exercise, indicating a hypotensive effect promoted by a single session of moderate-intensity exercise in young adults with excess body weight.

A randomized controlled trial to reduce sedentary time in rheumatoid arthritis: protocol and rationale of the Take a STAND for Health study.

BACKGROUND: Patients with rheumatoid arthritis spend most of their daily hours in sedentary behavior (sitting), a predisposing factor to poor health-related outcomes and all-cause mortality. Interventions focused on reducing sedentary time could be of novel therapeutic relevance. However, studies addressing this topic remain scarce. We aim to investigate the feasibility and efficacy of a newly developed intervention focused on reducing sedentary time, and potential clinical, physiological, metabolic and molecular effects in rheumatoid arthritis. METHODS: The Take a STAND for Health study is a 4-month, parallel-group, randomized controlled trial, in which postmenopausal patients with rheumatoid arthritis will set individually tailored, progressive goals to replace their sedentary time with standing and light-intensity activities. Patients will be recruited from the Clinical Hospital (School of Medicine, University of Sao Paulo) and will be assessed at baseline and after a 4-month follow up. Outcomes will include objectively measured sedentary behavior (primary outcome) and physical activity levels, clinical parameters, anthropometric parameters and body composition; aerobic fitness, muscle function, blood pressure, cardiovascular autonomic function, vascular function and structure, health-related quality of life, and food intake. Blood and muscle samples will be collected for assessing potential mechanisms, through targeted and non-targeted approaches. DISCUSSION: Findings will be of scientific and clinical relevance with the potential to inform new prescriptions focused on reducing sedentary behavior, a modifiable risk factor that thus far has been overlooked in patients with rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03186924. Registered on 14 June 2017.