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What is the central question of this study? We sought to investigate whether peripheral and cerebrovascular function are impaired in early and late postmenopausal females compared with premenopausal females, while also accounting for nitric oxide and estradiol levels. What is the main finding and its importance? We observed no differences in peripheral vascular and cerebrovascular function between healthy and physically active premenopausal females and early and late postmenopausal females. Our findings contradict previous cross-sectional observations of vascular and cerebrovascular dysfunction across menopause. Longitudinal studies assessing vascular and cerebrovascular outcomes across the menopausal transition are warranted.The risk of cardiovascular and cerebrovascular disease increases in ageing females, coinciding with the onset of menopause. Differences in peripheral and cerebrovascular function across menopausal stages, however, are poorly characterized. The aim of this study was to compare peripheral and cerebrovascular function between healthy premenopausal (PRE), early (1-6 years after final menstrual period; E-POST) and late (6 years after final menstrual period; L-POST) postmenopausal females. We also explored the association between reproductive hormones, NO bioavailability and cerebrovascular function. In 39 females (40-65 years of age), we measured arterial stiffness, brachial artery flow-mediated dilatation, and cerebrovascular reactivity (CVR) to hypercapnia in the middle (MCAv) and internal (ICA) carotid arteries. Follicle-stimulating hormone, estradiol, progesterone and plasma nitrate and nitrite concentrations were also measured. Years since final menstrual period (PRE, 0 ± 0 years; E-POST, 3 ± 1 years; L-POST, 11 ± 4 years; P 0.001) and estradiol levels (PRE, 145.5 ± 65.6 pg ml

Purpose Our aim was to compare cerebrovascular and systemic vascular function between older adults with and without mild cognitive impairment (MCI), and to determine which measures of vascular function best predict the presence of MCI. Methods In 41 adults with MCI and 33 adults without MCI (control) we compared middle cerebral artery velocity (MCAv) and cerebrovascular pulsatility index (PI) at rest, cerebrovascular reactivity to CO2, and responsiveness to changes in blood pressure (%∆MCAv/%∆MAP). Systemic vascular function was assessed by flow-mediated dilation (FMD) and stiffness by pulse wave velocity (PWV). Results Cerebrovascular PI was higher in MCI compared with control (mean ± SD: 1.17 ± 0.27 vs. 1.04 ± 0.21), and MCI exhibited a lower %∆MCAv/%∆MAP (1.26 ± 0.44 vs. 1.50 ± 0.55%). Absolute (p = 0.76) and relative cerebrovascular reactivity to CO2 (p = 0.34) was similar between MCI and control. When age was included as a covariate the significant difference in cerebral PI between groups was lost. PWV was higher (13.2 ± 2.2 vs. 11.3 ± 2.5 m s−1) and FMD% (4.41 ± 1.70 vs. 5.43 ± 2.15%) was lower in MCI compared with control. FMD% was positively associated with PI across the cohort. Logistic regression analysis indicated that FMD and PWV significantly discriminated between MCI and controls, independent of age, whereas the inclusion of cerebrovascular measures did not improve the predictive accuracy of the model. Conclusion These findings raise the possibility that early changes in systemic vascular stiffness and endothelial function may contribute to altered cerebrovascular haemodynamics and impaired cognitive function, and present potential targets for prevention and treatment strategies in people with MCI.

Objectives To assess physical activity (PA), mental health and well-being of adults in the United Kingdom (UK), Ireland, New Zealand and Australia during the initial stages of National governments’ Coronavirus disease (COVID-19) containment responses. Design Observational, cross-sectional. Methods An online survey was disseminated to adults (n = 8,425; 44.5 ± 14.8y) residing in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government-mandated COVID-19 restrictions. Main outcome measures included: Stages of Change scale for exercise behaviour change; International Physical Activity Questionnaire (short-form); World Health Organisation-5 Well-being Index; and the Depression Anxiety and Stress Scale-9. Results Participants who reported a negative change in exercise behaviour from before initial COVID-19 restrictions to during the initial COVID-19 restrictions demonstrated poorer mental health and well-being compared to those demonstrating either a positive-or no change in their exercise behaviour (p < 0.001). Whilst women reported more positive changes in exercise behaviour, young people (18-29y) reported more negative changes (both p < 0.001). Individuals who had more positive exercise behaviours reported better mental health and well-being (p < 0.001). Although there were no differences in PA between countries, individuals in New Zealand reported better mental health and well-being (p < 0.001). Conclusion The initial COVID-19 restrictions have differentially impacted upon PA habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage PA should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation.

IntroductionRegular aerobic exercise is associated with improved cognitive function, implicating it as a strategy to reduce dementia risk. This is reinforced by the association between greater cardiorespiratory fitness and larger brain volume, superior cognitive performance and lower dementia risk. However, the optimal aerobic exercise dose, namely the intensity and mode of delivery, to improve brain health and lower dementia risk has received less attention. We aim to determine the effect of different doses of aerobic exercise training on markers of brain health in sedentary middle-aged adults, hypothesising that high-intensity interval training (HIIT) will be more beneficial than moderate-intensity continuous training (MICT).Methods and analysisIn this two-group parallel, open-label blinded endpoint randomised trial, 70 sedentary middle-aged (45–65 years) adults will be randomly allocated to one of two 12-week aerobic exercise training interventions matched for total exercise training volume: (1) MICT (n=35) or HIIT (n=35). Participants will perform ~50 min exercise training sessions, 3 days per week, for 12 weeks. The primary outcome will be measured as between-group difference in cardiorespiratory fitness (peak oxygen uptake) change from baseline to the end of training. Secondary outcomes include between-group differences in cognitive function and ultra-high field MRI (7T) measured markers of brain health (brain blood flow, cerebrovascular function, brain volume, white matter microstructural integrity and resting state functional brain activity) changes from baseline to the end of training.Ethics and disseminationThe Victoria University Human Research Ethics Committee (VUHREC) has approved this study (HRE20178), and all protocol modifications will be communicated to the relevant parties (eg, VUHREC, trial registry). Findings from this study will be disseminated via peer-review publications, conference presentations, clinical communications and both mainstream and social media.Trial registration numberANZCTR12621000144819.

The COVID-19 pandemic markedly changed how healthcare services are delivered and telehealth delivery has increased worldwide. Whether changes in healthcare delivery borne from the COVID-19 pandemic impact effectiveness is unknown. Therefore, we examined the effectiveness of exercise physiology services provided during the COVID-19 pandemic.This prospective cohort study included 138 clients who received exercise physiology services during the initial COVID-19 pandemic. Outcome measures of interest were EQ-5D-5L, EQ-VAS, patient-specific functional scale, numeric pain rating scale and goal attainment scaling.Most (59%, n = 82) clients received in-person delivery only, whereas 8% (n = 11) received telehealth delivery only and 33% (n = 45) received a combination of delivery modes. Mean (SD) treatment duration was 11 (7) weeks and included 12 (6) sessions lasting 48 (9) minutes. The majority (73%, n = 101) of clients completed 80% of exercise sessions. Exercise physiology improved mobility by 14% (β = 0.23, P = 0.003), capacity to complete usual activities by 18% (β = 0.29, P 0.001), capacity to complete important activities that the client was unable to do or having difficulty performing by 54% (β = 2.46, P 0.001), current pain intensity by 16% (β = - 0.55, P = 0.038) and goal attainment scaling t-scores by 50% (β = 18.37, P 0.001). Effectiveness did not differ between delivery modes (all: P 0.087).Exercise physiology services provided during the COVID-19 pandemic improved a range of client-reported outcomes regardless of delivery mode. Further exploration of cost-effectiveness is warranted.

Physical activity (PA) participation was substantially reduced at the start of the COVID-19 pandemic. The purpose of this study was to assess the association between PA, mental health, and wellbeing during and following the easing of COVID-19 restrictions in the United Kingdom (UK) and New Zealand (NZ). In this study, 3363 adults completed online surveys within 2–6 weeks of initial COVID-19 restrictions (April/May 2020) and once restrictions to human movement had been eased. Outcome measures included the International Physical Activity Questionnaire Short-Form, Depression Anxiety and Stress Scale-9 (mental health) and World Health Organisation-5 Wellbeing Index. There were no differences in PA, mental health or wellbeing between timepoints (p > 0.05). Individuals engaging in moderate or high volume of PA had significantly better mental health (−1.1 and −1.7 units, respectively) and wellbeing (11.4 and 18.6 units, respectively) than individuals who engaged in low PA (p < 0.001). Mental health was better once COVID-19 restrictions were eased (p < 0.001). NZ had better mental health and wellbeing than the UK (p < 0.001). Participation in moderate-to-high volumes of PA was associated with better mental health and wellbeing, both during and following periods of COVID-19 containment, compared to participation in low volumes of PA. Where applicable, during the current or future pandemic(s), moderate-to-high volumes of PA should be encouraged.

Community-based exercise programs for older adults play a potentially important role in mitigating the decline in functional outcomes, body composition, psychosocial outcomes, and cardiovascular health outcomes that commonly occurs with advancing age. There is a limited understanding of the characteristics and effectiveness of community-based exercise programs, particularly when those programs are offered outside metropolitan areas. Rural/regional settings face unique challenges, such as limited access to equipment/resources, transportation, and services, as well as significant costs to run programs. The objective of this scoping review was to characterise studies in the field that have aimed to implement community-based programs in settings identified as rural / regional. A secondary aim was to establish guidance for future exercise programs in this setting and highlight future research directions. A total of 12 studies were conducted in settings identified as rural/regional areas in various countries across the world were included. Of the included studies, five were randomised controlled trials. The majority of included studies reported on functional outcomes (83%) and psychosocial outcomes (75%), yet only 42% reported body composition, 17% reported cardiovascular health and 17% reported dietary outcomes. Low male representation was observed, with women outnumbering men in 7 of 12 studies. There was also minimal investigation of qualitative outcomes in existing community-based exercise programs in rural/regional settings, presenting a key gap for future research to address. Study Protocol: https://osf.io/txpm3/ . Date of registration: 20 July 2020.

Objective/background: Elevated arterial stiffness is a characteristic of abdominal aortic aneurysm (AAA), and is associated with AAA growth and cardiovascular mortality. A bout of exercise transiently reduces aortic and systemic arterial stiffness in healthy adults. Whether the same response occurs in patients with AAA is unknown. The effect of moderate- and higher intensity exercise on arterial stiffness was assessed in patients with AAA and healthy adults. Methods: Twenty-two men with small diameter AAAs (36 ± 5 mm; mean age 74 ± 6 years) and 22 healthy adults (mean age 72 ± 5 years) were included. Aortic stiffness was measured using carotid to femoral pulse wave velocity (PWV), and systemic arterial stiffness was estimated from the wave reflection magnitude (RM) and augmentation index (Alx75). Measurements were performed at rest and during 90 min of recovery following three separate test sessions in a randomised order: (i) moderate intensity continuous exercise; (ii) higher intensity interval exercise; or (iii) seated rest. Results: At rest, PWV was higher in patients with AAA than in healthy adults (p < .001), while AIx75 and RM were similar between groups. No differences were observed between AAA patients and healthy adults in post-exercise aortic and systemic arterial stiffness after either exercise protocol. When assessed as the change from baseline (delta, Δ), post-exercise ΔAIx75 was not different to the seated rest protocol. Conversely, post-exercise ΔPWV and ΔRM were both lower at all time points than seated rest (p < .001). ΔPWV was lower immediately after higher intensity than after moderate intensity exercise (p = .015). Conclusion: High resting aortic stiffness in patients with AAA is not exacerbated after exercise. There was a similar post-exercise attenuation in arterial stiffness between patients with AAA and healthy adults compared with seated rest. This effect was most pronounced following higher intensity interval exercise, suggesting that this form of exercise may be a safe and effective adjunctive therapy for patients with small AAAs.

Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyte fatty acid content in 43 AAA patients (diameter 3.0–4.5 cm) and 52 healthy controls. In addition, the effect of omega-3 PUFA (n-3 PUFA) supplementation on erythrocyte fatty acid content was examined in a cohort of 30 AAA patients as part of a 12 week randomized placebo-controlled clinical trial. Blood analyses identified associations between AAA and decreased linoleic acid (LA), and AAA and increased Δ6-desaturase activity and biosynthesis of arachidonic acid (AA) from LA. Omega-3 PUFA supplementation (1.5 g DHA + 0.3 g EPA/day) decreased red blood cell distribution width (14.8 ± 0.4% to 13.8 ± 0.2%; P = 0.003) and levels of pro-inflammatory n-6 PUFAs (AA, 12.46 ± 0.23% to 10.14 ± 0.3%, P < 0.001; adrenic acid, 2.12 ± 0.13% to 1.23 ± 0.09%; P < 0.001). In addition, Δ-4 desaturase activity increased (DHA/docosapentaenoic acid ratio, 1.85 ± 0.14 to 3.93 ± 0.17; P < 0.001) and elongase 2/5 activity decreased (adrenic acid/AA ratio, 0.17 ± 0.01 to 0.12 ± 0.01; P < 0.01) following supplementation. The findings suggest that n-3 PUFAs improve fatty acid profiles and ameliorate factors associated with inflammation in AAA patients.

We address two aims: Aim 1 (Fitness Review) compares the effect of higher cardiorespiratory fitness (CRF) (e.g., endurance athletes) with lower CRF (e.g., sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv), cerebrovascular reactivity and resistance, and global cerebral blood flow, as assessed by transcranial Doppler (TCD) or magnetic resonance imaging (MRI). Aim 2 (Exercise Training Review) determines the effect of exercise training on cerebrovascular outcomes. Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty studies (18 using TCD) met the eligibility criteria for Aim 1, and 14 studies (8 by TCD) were included for Aim 2. There was a significant effect of higher CRF compared with lower CRF on cerebrovascular resistance (effect size = -0.54, 95% confidence interval = -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41-1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance than mixed or female studies (male only: -0.69, -1.06 to -0.32; mixed and female studies: 0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31) but showed a small nonsignificant improvement in cerebrovascular reactivity (0.60, -0.08 to 1.28; P = 0.09). Exercise training showed heterogeneous effects on regional but little effect on global cerebral blood flow as measured by MRI. High CRF positively effects cerebrovascular function, including decreased cerebrovascular resistance and increased cerebrovascular reactivity; however, global cerebral blood flow and MCAv are primarily unchanged following an exercise intervention in healthy and clinical populations.NEW & NOTEWORTHY Higher cardiorespiratory fitness is associated with lower cerebrovascular resistance and elevated cerebrovascular reactivity at rest. Only adults with a true-high fitness based on normative data exhibited elevated middle cerebral artery velocity. The positive effect of higher compared with lower cardiorespiratory fitness on resting cerebrovascular resistance was more evident in male-only studies when compared with mixed or female-only studies. A period of exercise training resulted in negligible changes in middle cerebral artery velocity and global cerebral blood flow, with potential for improvements in cerebrovascular reactivity.

Endothelial function, assessed using brachial artery flow-mediated dilation (FMD), predicts future cardiovascular disease (CVD) risk. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. In a retrospective study design, we pooled brachial artery FMD (acquired according to expert-consensus guidelines for FMD protocol and analysis) and participant characteristics/medical history from 5362 individuals (4–84 years; 2076 females). Healthy individuals (n=1403 [582 females]) were used to generate age-/sex-specific percentile curves. Subsequently, we included individuals with CVD risk factors, without overt disease (unmedicated n=3167 [1247 females] and medicated n=792 [247 females]). Multiple linear regression tested the relation of CVD risk factors (body mass index, blood pressure, cholesterol, diabetes, dyslipidemia, and smoking) with FMD. Healthy males showed a negative, curvilinear relation between FMD and age, while females revealed a negative linear relation that started higher but declined at a faster rate than males. Age- and sex-specific differences in FMD relate, at least partly, to baseline artery diameter. FMD was related to CVD risk factors in unmedicated (eg, systolic/diastolic blood pressure) and medicated individuals (eg, diabetes/dyslipidemia). Sex mediated some of these effects ( P

NEW FINDINGS What is the topic of this review? We have conducted a systematic review and meta-analysis on the current evidence for the effect of heat therapy on blood pressure and vascular function. What advances does it highlight? We found that heat therapy reduced mean arterial, systolic and diastolic blood pressure. We also observed that heat therapy improved vascular function, as assessed via brachial artery flow-mediated dilatation. Our results suggest that heat therapy is a promising therapeutic tool that should be optimized further, via mode and dose, for the prevention and treatment of cardiovascular disease risk factors. ABSTRACT Lifelong sauna exposure is associated with reduced cardiovascular disease risk. Recent studies have investigated the effect of heat therapy on markers of cardiovascular health. We aimed to conduct a systematic review with meta-analysis to determine the effects of heat therapy on blood pressure and indices of vascular function in healthy and clinical populations. Four databases were searched up to September 2020 for studies investigating heat therapy on outcomes including blood pressure and vascular function. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. A total of 4522 titles were screened, and 15 studies were included. Healthy and clinical populations were included. Heat exposure was for 30-90 min, over 10-36 sessions. Compared with control conditions, heat therapy reduced mean arterial pressure [n = 4 studies; mean difference (MD): -5.86 mmHg, 95% confidence interval (CI): -8.63, -3.10; P

The endothelium is the single-cell monolayer that lines the entire vasculature. The endothelium has a barrier function to separate blood from organs and tissues but also has an increasingly appreciated role in anti-coagulation, vascular senescence, endocrine secretion, suppression of inflammation and beyond. In modern times, endothelial cells have been identified as the source of major endocrine and vaso-regulatory factors principally the dissolved lipophilic vosodilating gas, nitric oxide and the potent vascular constricting G protein receptor agonists, the peptide endothelin. The role of the endothelium can be conveniently conceptualized. Continued investigations of the mechanism of endothelial dysfunction will lead to novel therapies for cardiovascular disease. In this review, we discuss the impact of endothelial dysfunction on cardiovascular disease and assess the clinical relevance of endothelial dysfunction.

The UK population is growing, ageing and becoming increasingly inactive and unfit. Personalised and targeted exercise interventions are beneficial for ageing and the management of chronic and complex conditions. Increasing the uptake of effective exercise and physical activity (PA) interventions is vital to support a healthier society and decrease healthcare costs. Current strategies for exercise and PA at a population level mostly involve self-directed exercise pathways, delivered largely via the fitness industry. Even for those who opt-in and manage to achieve the current recommendations regarding minimum PA, this generic ‘one-size-fits-all’ approach often fails to demonstrate meaningful physiological and health benefits. Personalised exercise prescription and appropriate exercise testing, monitoring and progression of interventions for individuals with chronic disease should be provided by appropriately trained and recognised exercise healthcare professionals, educated in the cognate disciplines of exercise science (eg, physiology, biomechanics, motor control, psychology). This workforce has operated for >20 years in the Australian public and private healthcare systems. Accredited exercise physiologists (AEPs) are recognised allied health professionals, with demonstrable health and economic benefits. AEPs have knowledge of the risks and benefits of distinct forms of exercise, skills in the personalised prescription and optimal delivery of exercise, and competencies to support sustained PA behavioural change, based on the established scientific evidence. In this charter, we propose a road map for the training, accreditation and promotion of a clinical exercise physiology profession in the UK.

Intermittent claudication (IC) is pain or discomfort in the muscles of the calf, thigh or buttock that occurs during walking and is relieved by rest. It affects 4% of people over 60 years of age and is the most common symptom of peripheral arterial disease (PAD). For people with IC, the goals of treatment are twofold: (1) secondary prevention of cardiovascular disease through management of risk factors (eg, tobacco use, dyslipidaemia, diabetes, hypertension and physical inactivity); (2) improving functional status, with treatment options including exercise training, revascularisation and vasodilator therapy.1 In 2012, the UK’s National Institute for Health and Care Excellence published a clinical guideline on the diagnosis and …

Impairments in skeletal muscle microvascular function are frequently reported in patients with various cardiometabolic conditions for which older age is a risk factor. Whether aging per se predisposes the skeletal muscle to microvascular dysfunction is unclear. We used contrast‐enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. Test–retest reliability of CEU perfusion parameters was also assessed. Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after: (a) 5‐min of thigh‐cuff occlusion, and (b) 5‐min of submaximal intermittent isometric plantar‐flexion exercise (400 N) using CEU. Whole‐leg blood flow was measured using strain‐gauge plethysmography. Repeated measures were obtained with a 15‐min interval, and averaged responses were used for comparisons between age groups. There were no differences in post‐occlusion whole‐leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole‐leg blood flow during exercise and post‐exercise peak muscle microvascular perfusion did not differ between groups (p > .05). The overall level of agreement between the test–retest measures of calf muscle perfusion was excellent for measurements taken at rest (intraclass correlation coefficient [ICC] 0.85), and in response to cuff occlusion (ICC 0.89) and exercise (ICC 0.95). Our findings suggest that healthy aging does not affect muscle perfusion responses to cuff‐occlusion and submaximal leg exercise. CEU muscle perfusion parameters measured in response to these provocation tests are highly reproducible in both young and older adults., We used contrast‐enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. There were no differences in post‐occlusion whole‐leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole‐leg blood flow during exercise and post‐exercise peak muscle microvascular perfusion did not differ between groups (p > .05).

Macrophages are implicated in the pathogenesis of abdominal aortic aneurysm (AAA). This study examined the environmentally conditioned responses of AAA macrophages to inflammatory stimuli. Plasma- and blood-derived monocytes were separated from the whole blood of patients with AAA (30&ndash, 45 mm diameter, n = 33) and sex-matched control participants (n = 44). Increased concentrations of pro-inflammatory and pro-oxidant biomarkers were detected in the plasma of AAA patients, consistent with systemic inflammation and oxidative stress. However, in monocyte-derived macrophages, a suppressed cytokine response was observed in AAA compared to the control following stimulation with lipopolysaccharide (LPS) (tumor necrosis factor alpha (TNF-&alpha, ) 26.9 &plusmn, 3.3 vs. 15.5 &plusmn, 3.2 ng/mL, p &lt, 0.05, IL-6 3.2 &plusmn, 0.6 vs. 1.4 &plusmn, 0.3 ng/mL, p &lt, 0.01). LPS-stimulated production of 8-isoprostane, a biomarker of oxidative stress, was also markedly lower in AAA compared to control participants. These findings are consistent with developed tolerance in human AAA macrophages. As Toll-like receptor 4 (TLR4) has been implicated in tolerance, macrophages were examined for changes in TLR4 expression and distribution. Although TLR4 mRNA and protein expression were unaltered in AAA, cytosolic internalization of receptors and lipid rafts was found. These findings suggest the inflamed, pro-oxidant AAA microenvironment favors macrophages with an endotoxin-tolerant-like phenotype characterized by a diminished capacity to produce pro-inflammatory mediators that enhance the immune response.

New Findings: What is the central question of the study? Cuff-occlusion duration may influence contrast-enhanced ultrasound (CEUS) assessments of skeletal muscle microvascular blood flow responsiveness: what are the effects of 1, 3 and 5 min cuff-occlusion on the magnitude and reliability of calf muscle microvascular blood flow responsiveness in older adults? What is the main finding and its importance? Calf muscle microvascular blood flow responsiveness was enhanced following 5 min cuff-occlusion compared with 1 min. The reliability of post-occlusion CEUS measurements was also improved following 5 min occlusion. The use of a standardized 5 min occlusion period should therefore be considered in future studies and clinical practice. Abstract: Contrast-enhanced ultrasound (CEUS) is increasingly used in assessments of skeletal muscle microvascular blood flow responsiveness. In response to limb cuff-occlusion, some studies have reported significant impairments in CEUS measurements of microvascular blood flow in older adults with cardiovascular or metabolic disease, whereas others have failed to detect significant between-group differences, which has brought the reliability of the technique into question. In the absence of a standardized CEUS protocol, there is variance in the duration of cuff-occlusion used, which is likely to influence post-occlusion measurements of muscle microvascular blood flow. We aimed to determine the effect of cuff-occlusion duration by comparing the magnitude and reliability of CEUS measurements of calf muscle microvascular blood flow responsiveness in older adults (n = 15, 67 ± 11 years) following 1, 3 and 5 min occlusion periods. Microvascular blood flow (= microvascular volume × microvascular velocity) within the calf muscle was measured using real-time destruction–replenishment CEUS. Measurements were made following thigh cuff-occlusion (200 mmHg) periods of 1, 3 and 5 min in a random order. Microvascular blood flow was higher following 3 min (3.71 ± 1.46 aU s−1) and 5 min (3.47 ± 1.48 aU s−1) compared with 1 min (2.42 ± 1.27 aU s−1, P = 0.002), which corresponded with higher microvascular volumes after 3 and 5 min compared with 1 min. Reliability was good following 5 min (intraclass correlation coefficient (ICC) 0.49) compared with poor following 1 min (ICC 0.34) and 3 min (ICC 0.35). This study demonstrates that the magnitude and reliability of calf muscle microvascular responsiveness is enhanced using a 5 min cuff-occlusion protocol compared with 1 min in older adults.

ObjectivesTo assess how the early stages of National governments Coronavirus disease (COVID-19) containment strategies impacted upon the physical activity, mental health and well-being of adults in the UK, Ireland, New Zealand and AustraliaDesignObservational, cross-sectionalSettingOnline survey disseminated in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government mandated COVID-19 restrictionsParticipantsAdults (n = 8,425; 44.5 ± 14.8 y), ≥ 18 y who were residing in the surveyed countriesMain outcome measuresStages of Change scale for exercise behaviour change, International Physical Activity Questionnaire (short-form), World Health Organisation-5 Well-being Index and the Depression Anxiety and Stress Scale-9ResultsParticipants who reported a negative change in exercise behaviour between pre- and during the early COVID-19 restrictions demonstrated poorer mental health and well-being compared to those who had either a positive change- or no change in their exercise behaviour (ppppConclusionThe COVID-19 restrictions have differentially impacted upon the physical activity habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage physical activity should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation.

BackgroundIncomplete restoration of myocardial blood flow (MBF) is reported in up to 30% of ST-segment elevation myocardial infarction (STEMI) despite prompt mechanical revascularization. Experimental hyperinsulinemic euglycemia (HE) increases MBF reserve (MBFR). If fully exploited, this effect may also improve MBF to ischemic myocardium. Using insulin-dextrose infusions to induce HE, we conducted four experiments to determine (1) how insulin infusion duration, dose, and presence of insulin resistance affect MBFR response; and (2) the effect of an insulin-dextrose infusion given immediately following revascularization of STEMI on myocardial perfusion.MethodsThe MBFR was determined using myocardial contrast echocardiography. Experiment 1 (insulin duration): 12 participants received an insulin-dextrose or saline infusion for 120 minutes. MBFR was measured at four time intervals during infusion. Experiment 2 (insulin dose): 22 participants received one of three insulin doses (0.5, 1.5, 3.0 mU/kg/minute) for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 3 (insulin resistance): five metabolic syndrome and six type 2 diabetes (T2DM) participants received 1.5 mU/kg/minute of insulin-dextrose for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 4 (STEMI): following revascularization for STEMI, 20 patients were randomized to receive either 1.5 mU/kg/minute insulin-dextrose infusion for 120 minutes or standard care. Myocardial contrast echocardiography was performed at four time intervals to quantify percentage contrast defect length.ResultsExperiment 1: MBFR increased with time through to 120 minutes in the insulin-dextrose group and did not change in controls. Experiment 2: compared with baseline, MBFR increased in the 1.5 (2.42 ± 0.39 to 3.25 ± 0.77, P = .002), did not change in the 0.5, and decreased in the 3.0 (2.64 ± 0.25 to 2.16 ± 0.33, P = .02) mU/kg/minute groups. Experiment 3: compared with baseline, MBFR increase was only borderline significant in metabolic syndrome and T2DM participants (1.98 ± 0.33 to 2.59 ± 0.45, P = .04, and 1.67 ± 0.35 to 2.14 ± 0.21, P = .05). Experiment 4: baseline percentage contrast defect length was similar in both groups but with insulin decreased with time and was significantly lower than in controls at 60 minutes (2.8 ± 5.7 vs 13.7 ± 10.6, P = .02).ConclusionsPresence of T2DM, insulin infusion duration, and dose are important determinants of the MBFR response to HE. When given immediately following revascularization for STEMI, insulin-dextrose reduces perfusion defect size at one hour. Hyperinsulinemic euglycemia may improve MBF following ischemia, but further studies are needed to clarify this.

Introduction Aging is associated with impaired cerebrovascular blood flow and function, attributed to reduced vasodilatory capacity of the cerebrovascular network. Older adults may also have an impaired relationship between changes in blood pressure and cerebral blood flow; however, previous reports conflict. This study aimed to compare the blood pressure and cerebral blood flow responses to both repeated and sustained stand‐to‐sit transitions in young and older adults, and to assess the relationship with cerebrovascular reactivity. Methods In 20 young (age: 24 ± 4 years) and 20 older (age: 71 ± 7 years) adults we compared middle cerebral artery flow velocity (MCAv), end‐tidal partial pressure of carbon dioxide (PETCO2), and blood pressure (mean arterial blood pressure [MAP]) during repeated stand‐to‐sit (10 s standing and 10 s sitting) and sustained stand‐to‐sit (3 min standing followed by 2 min sitting) transitions. Cerebrovascular reactivity to changes in carbon dioxide levels was assessed using a repeated breath‐hold test. Results The % change in MCAv per % change in MAP (%∆MCAv/%∆MAP) was higher in the older adults than in the young adults during repeated stand‐to‐sit transitions. During the sustained protocol the %∆MCAv/%∆MAP response was similar in both age groups. A high %∆MCAv/%∆MAP response during the repeated stand‐to‐sit protocol was associated with low cerebrovascular reactivity to CO2 (r = −.39; p, Aging and age‐related cerebrovascular diseases are associated with impaired cerebrovascular function. The novel finding of this study is that older adults showed higher pressure–flow responses during repeated stand–sit transitions compared to younger adults, and that a high pressure–flow response was associated with low cerebrovascular reactivity to CO2. These results suggest that impaired vascular function and increased arterial stiffness may contribute to the pressure–flow responses observed in the older adults.

Peripheral artery disease (PAD) is caused by atherosclerotic narrowing of the arteries supplying the lower limbs often resulting in intermittent claudication, evident as pain or cramping while walking. Supervised exercise training elicits clinically meaningful benefits in walking ability and quality of life. Walking is the modality of exercise with the strongest evidence and is recommended in several national and international guidelines. Alternate forms of exercise such as upper- or lower-body cycling may be used, if required by certain patients, although there is less evidence for these types of programmes. The evidence for progressive resistance training is growing and patients can also engage in strength-based training alongside a walking programme. For those unable to attend a supervised class (strongest evidence), home-based or ‘self-facilitated’ exercise programmes are known to improve walking distance when compared to simple advice. All exercise programmes, independent of the mode of delivery, should be progressive and individually prescribed where possible, considering disease severity, comorbidities and initial exercise capacity. All patients should aim to accumulate at least 30 min of aerobic activity, at least three times a week, for at least 3 months, ideally in the form of walking exercise to near-maximal claudication pain.

Background: Assessment of endothelial function using brachial artery flow-mediated dilation (FMD) predicts future cardiovascular disease (CVD) risk. However, poor adherence to protocol guidelines and lack of reference values hinders widespread FMD use. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. Methods: Collected according to expert-consensus guidelines, we combined brachial artery FMD and subject characteristics/medical history from 5,362 individuals (4–84 years; 2,076 females). We first examined healthy individuals (n = 1,403 [582 females]) to generate age-/sex-specific percentile curves. Subsequently, we included subjects with CVD risk factors but without disease (un-medicated n = 3,167 [1,247 females], and medicated n = 792 [247 females]). Multiple linear regression tested the relation of CVD risk factors with FMD. Results: Healthy men showed a negative, curvilinear relation between FMD and age, whilst females revealed a linear relation that started higher, but declined at a faster rate. Age-/sex-related differences in FMD, at least partly, relate to baseline artery diameter. FMD was affected by CVD risk factors in un-medicated (e.g. systolic-/diastolic blood pressure, diabetes) and medicated subjects (e.g. dyslipidaemia). Importantly, sex mediated these effects (p < 0.05), with (supra) normalisation of FMD in medicated men, but not in women (except for blood pressure). Conclusion: Sex alters the age-related decline in FMD, which is partly explained through differences in artery diameter. Sex also altered the effect of some CVD risk factors and medication on FMD. This work improves interpretation and future use of the FMD technique when strictly adhering to FMD protocol guidelines.

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. Although leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole leg blood flow and calf muscle microvascular perfusion after cuff occlusion and submaximal leg exercise between patients with PAD ( n = 12, 69 ± 9 yr) and healthy age-matched control participants ( n = 12, 68 ± 7 yr). Microvascular blood flow (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after the following: 1) 5 min of thigh-cuff occlusion, and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400 N) using real-time contrast-enhanced ultrasound. Whole leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Postocclusion whole leg blood flow and calf muscle microvascular perfusion were lower in patients with PAD than control participants, and these parameters were strongly correlated ( r = 0.84, P < 0.01). During submaximal exercise, total whole leg blood flow and vascular conductance were not different between groups. There were also no group differences in postexercise calf muscle microvascular perfusion, although microvascular blood volume was higher in patients with PAD than control participants (12.41 ± 6.98 vs. 6.34 ± 4.98 arbitrary units, P = 0.03). This study demonstrates that the impaired muscle perfusion of patients with PAD during postocclusion hyperemia is strongly correlated with disease severity and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in patients with PAD, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise. NEW & NOTEWORTHY This study suggests that peripheral arterial disease (PAD) has different effects on the microvascular perfusion responses to cuff occlusion and submaximal leg exercise. Patients with PAD have impaired microvascular perfusion after cuff occlusion, similar to that previously reported after maximal exercise. In response to submaximal exercise, however, the microvascular flow volume response was elevated in patients with PAD compared with control. This finding may reflect a compensatory mechanism to maintain perfusion and oxygen delivery during recovery from exercise.

Cardiovascular disease is associated with increased risk for cognitive decline and dementia, but it is unclear whether this risk varies across disease states or occurs in the absence of symptomatic stroke. To examine the evidence of increased risk for cognitive decline and dementia following non-stroke cardiovascular disease we conducted two independent meta-analyses in accordance with PRISMA guidelines. The first review examined cardiovascular diagnoses (atrial fibrillation, congestive heart failure, periphery artery disease and myocardial infarction) while the second review assessed the impact of atherosclerotic burden (as indicated by degree of stenosis, calcification score, plaque morphology or number of plaques). Studies eligible for review longitudinally assessed risk for clinically significant cognitive decline and/or dementia and excluded stroke and cognitive impairment at baseline. Summary statistics were computed via the inverse variance weighted method, utilising Cox Proportional Hazards data (Hazard Ratios, HR). Both atrial fibrillation (n = 5, HR = 1.26, 95% CI [1.12, 1.43]) and severe atherosclerosis (n = 4, HR = 1.59, 95% CI [1.12, 2.26]) emerged as significant risk factors for cognitive decline and/or dementia. A small set of studies reviewed, insufficient for meta-analysis, examining congestive heart failure, peripheral artery disease and myocardial infarction suggested that these conditions may also be associated with an increased risk of cognitive decline/dementia. In the absence of stroke, patients with atrial fibrillation or generalised atherosclerosis are at heightened risk for cognitive deterioration. Nonetheless, this paper highlights the need for methodologically rigorous and prospective investigation of the relationship between CVD and dementia.

Abdominal aortic aneurysm (AAA) is associated with inflammation and oxidative stress, the latter of which contributes to activation of macrophages, a prominent cell type in AAA. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to limit oxidative stress in animal models of AAA. The aim of this study was to evaluate the effect of the n-3 PUFA docosahexaenoic acid (DHA) on antioxidant defence in macrophages from patients with AAA. Cells were obtained from men with small AAA (diameter 3.0–4.5 cm, 75 ± 6 yr, n = 19) and age- matched male controls (72 ± 5 yr, n = 41) and incubated with DHA for 1 h before exposure to 0.1 µg/mL lipopolysaccharide (LPS) for 24 h. DHA supplementation decreased the concentration of tumour necrosis factor-α (TNF-α; control, 42.1 ± 13.6 to 5.1 ± 2.1 pg/ml, p

Background Sprint interval training (SIT) can be as effective, or more effective, than continuous moderate intensity exercise (CMIE) for improving a primary risk factor for cardiometabolic disease, low cardiorespiratory fitness (CRF). However, there has been no direct comparison in inactive individuals, of the acute effects of a session of SIT with a work-matched session of CMIE on local oxygen utilisation, which is a primary stimulus for increasing CRF. Furthermore, post-exercise blood pressure (BP) and enjoyment, if symptomatic and low, respectively, have implications for safety and adherence to exercise and have not been compared between these specific conditions. It was hypothesised that in young inactive men, local oxygen utilisation would be higher, while post-exercise BP and enjoyment would be lower for SIT, when compared to CMIE. Methods A total of 11 inactive men (mean ± SD; age 23 ± 4 years) completed a maximal ramp-incremental exercise test followed by two experiment conditions: (1) SIT and (2) work-matched CMIE on a cycle ergometer on separate days. Deoxygenated haemoglobin (∆HHb) in the pre-frontal cortex (FH), gastrocnemius (GN), left vastus lateralis (LVL) and the right vastus lateralis (RVL) muscles, systemic oxygen utilisation (VO2), systolic (SBP) and diastolic (DBP) blood pressure and physical activity enjoyment scale (PACES) were measured during the experiment conditions. Results During SIT, compared to CMIE, ∆HHb in FH (p = 0.016) and GN (p = 0.001) was higher, while PACES (p = 0.032) and DBP (p = 0.043) were lower. No differences in SBP and ∆HHb in LVL and RVL were found between conditions. Conclusions In young inactive men, higher levels of physiological stress occurred during SIT, which potentially contributed to lower levels of post-exercise DBP and enjoyment, when compared to CMIE.

Aging is often associated with reduced leg blood flow, increased arterial stiffness, and endothelial dysfunction, all of which are related to declining nitric oxide (NO) bioavailability. Flow mediated dilatation (FMD) and passive leg movement (PLM) hyperaemia are two techniques used to measure NO-dependent vascular function. We hypothesised that acute dietary nitrate (NO3&minus, ) supplementation would improve NO bioavailability, leg FMD, and PLM hyperaemia. Fifteen healthy older men (69 &plusmn, 4 years) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice (800 mg NO3&minus, ) or placebo (NO3&minus, depleted beetroot juice) in a randomised, double blind, cross-over design study. Plasma nitrite (NO2&minus, ) and NO3&minus, blood pressure (BP), augmentation index (AIx75), pulse wave velocity (PWV), FMD of the superficial femoral artery, and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO3&minus, and placebo. Placebo had no effect but NO3&minus, led to an 8.6-fold increase in plasma NO2&minus, which was accompanied by an increase in FMD (NO3&minus, +1.18 &plusmn, 0.94% vs. placebo: 0.23 &plusmn, 1.13%, p = 0.002), and a reduction in AIx75 (NO3&minus, &minus, 8.7 &plusmn, 11.6% vs. placebo: &minus, 4.6 &plusmn, 5.5%, p = 0.027). PLM hyperaemia, BP, and PWV were unchanged during both trials. This study showed that a dose of dietary NO3&minus, improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD. These findings provide insight into the specific central and peripheral vascular responses to dietary NO3&minus, supplementation in older adults.

Purpose Aging is associated with impaired cerebral blood flow (CBF) and increased risk of cerebrovascular disease. Acute increases in CBF during exercise may initiate improvements in cerebrovascular health, but the CBF response is diminished during continuous exercise in older adults. The effect of interval exercise for promoting increases in CBF in young and old adults is unknown. Methods We compared middle cerebral artery blood velocity (MCAv), end-tidal CO (PCO) and blood pressure (mean arterial pressure [MAP]) during intensity- and work-matched bouts of continuous (10-min 60%W, followed by 10-min rest) and interval cycling (10 × 1-min 60%W, separated by 1-min rest) in 11 young (25 ± 3 yr) and 10 old (69 ± 3 yr) men. Results Middle cerebral artery velocity was higher during continuous compared with interval exercise in the young (P < 0.001), but not in the old. This trend was also seen for changes in PCO. Although absolute MAP was higher in the old, the relative rise (%Δ) in MAP was similar between age groups and was greater during continuous exercise than interval. When we assessed the total accumulated change in MCAv (area under curve: exercise + recovery), it was higher with interval compared with continuous exercise in both groups (P = 0.018). Conclusion These findings suggest that interval exercise may be an effective alternative for promoting acute increases in CBF velocity, particularly in those older adults who may have difficulty sustaining continuous exercise.

Short‐term changes in arterial stiffness with exercise are proposed to better reflect vascular impairments than resting measures alone and are suggested as a prognostic indicator of cardiovascular risk in older adults. Arterial stiffness indices are reliable at rest, but the time‐course and reliability of postexercise changes in arterial stiffness in older adults are unknown. The precision of postexercise changes in arterial stiffness should be determined prior to their use in large prospective trials. This study assessed the between‐day reliability of the changes in pulse wave velocity (PWV), augmentation index (AIx75) and reflection magnitude (RM) following an exercise bout in older adults. Ten older adults (71 ± 5 years) were tested on three separate days, 7 days apart. PWV, AIx75 and RM were assessed at rest, immediately post and at 20, 40 and 60 min during recovery after moderate‐intensity cycling. Intraclass correlation coefficient (ICC) and reliability coefficient (RC) were used to assess the relative and absolute reliability of arterial stiffness responses. PWV increased, and RM decreased immediately after exercise (P

Background and purposeAging leads to alterations in cerebrovascular function, and these are thought to contribute to cognitive decline/dementia. Disturbances to cerebral blood flow regulation have been reported, but the findings are inconsistent and to date no study has comprehensively tested the collective and independent contribution of these parameters in the same age range. Such lines of enquiry are vital since aging is a heterogeneous and complex process, with cerebrovascular parameters being differentially affected depending on the individual. A multicomponent comprehensive measure of cerebrovascular function, which accounts for such diversity, is needed to differentiate between healthy young and old adults.MethodsWe tested the effect of aging on cerebrovascular function by comparing healthy young adults aged 18-30 and older adults aged 60-75, without cognitive impairments. Cerebrovascular blood flow velocity was assessed using transcranial Doppler ultrasound. Parameters included resting middle cerebral artery velocity (MCAv), neurovascular coupling, cerebrovascular reactivity to CO2 (hypercapnia and hypocapnia), and the pressure-flow response during a sit-to-stand procedure.ResultsMANOVA revealed that collectively, the parameters discriminated the groups (p < .001). MCAv and pressure-flow responses were lower in the older group (p < .001). While there were no differences in hypercapnic responses (p = .908) and neurovascular coupling (p = .517), hypocapnic responses were elevated in the old (p = .002).ConclusionsCollectively, cerebrovascular parameters can distinguish between healthy young and older adults, with aging leading to reductions in MCAv, and altering cerebrovascular reactivity and pressure-flow responses under hypotensive conditions.

To investigate the effects of compression socks worn during exercise on performance and physiological responses in elite wheelchair rugby athletes.In a non-blinded randomized crossover design, participants completed two exercise trials (4 × 8 min bouts of submaximal exercise, each finishing with a timed maximal sprint) separated by 24 hr, with or without compression socks.National Sports Training Centre, Queensland, Australia.Ten national representative male wheelchair rugby athletes with cervical spinal cord injuries volunteered to participate.Participants wore medical grade compression socks on both legs during the exercise task (COMP), and during the control trial no compression was worn (CON).The efficacy of the compression socks was determined by assessments of limb blood flow, core body temperature, heart rate, and ratings of perceived exertion, perceived thermal strain, and physical performance.While no significant differences between conditions were observed for maximal sprint time, average lap time was better maintained in COMP compared to CON (P0.05). Lower limb blood flow increased from pre- to post-exercise by the same magnitude in both conditions (COMP: 2.51 ± 2.34; CON: 2.20 ± 1.85 ml.100 ml.(-1)min(-1)), whereas there was a greater increase in upper limb blood flow pre- to post-exercise in COMP (10.77 ± 8.24 ml.100 ml.(-1)min(-1)) compared to CON (6.21 ± 5.73 ml.100 ml.(-1)min(-1); P 0.05).These findings indicate that compression socks worn during exercise is an effective intervention for maintaining submaximal performance during wheelchair exercise, and this performance benefit may be associated with an augmentation of upper limb blood flow.

Abdominal aortic aneurysm (AAA) is a vascular disease involving permanent focal dilation of the abdominal aorta (&ge, 30 mm) that can lead to catastrophic rupture. Destructive remodeling of aortic connective tissue in AAA contributes to wall stiffening, a mechanical parameter of the arterial system linked to a heightened risk of cardiovascular morbidity and mortality. Since aortic stiffening is associated with AAA progression, treatment options that target vascular inflammation would appear prudent. Given this, and growing evidence indicating robust anti-inflammatory and vasoprotective properties for long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), this study evaluated the impact of these nutrients (1.8 g/day for 12 weeks) on indices of vascular stiffness in patients with AAA. At baseline, pulse wave velocity (PWV) and augmentation index normalized to a heart rate of 75 bpm (AIx75) were significantly higher in patients with AAA compared to control participants (PWV: 14.2 &plusmn, 0.4 m.s&minus, 1 vs. 12.6 &plusmn, 1, p = 0.014, AIx75: 26.4 &plusmn, 1.7% vs. 17.3 &plusmn, 2.7%, p = 0.005). Twelve-week LC n-3 PUFA supplementation significantly decreased PWV (baseline: 14.2 &plusmn, 0.6 m.s&minus, 1, week 12: 12.8 &plusmn, 0.7 m.s&minus, 1, p = 0.014) and heart rate (baseline: 63 &plusmn, 3 bpm, week 12: 58 &plusmn, 3 bpm, p = 0.009) in patients with AAA. No change was observed for patients receiving placebo capsules. While this raises the possibility that LC n-3 PUFAs provide improvements in aortic stiffness in patients with AAA, the clinical implications remain to be fully elucidated.