Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Comparison of peripheral and cerebral vascular function between premenopausal, early and late postmenopausal females.

NEW FINDINGS: 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. ABSTRACT: 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-1 ; E-POSTm 30.2 ± 81.2 pg ml-1 ; L-POST, 7.7 ± 11.3 pg ml-1 ; P < 0.001) were different between groups. All groups exceeded the guidelines for recommended physical activity. There were no group differences in blood pressure (P = 0.382), arterial stiffness (P = 0.129), flow-mediated dilatation (P = 0.696) or MCAv CVR (P = 0.442). The ICA CVR blood flow response was lower in PRE compared with L-POST (26.5 ± 19.2 vs. 47.8 ± 12.6%; P = 0.010), but after adjusting for age these differences were no longer present. Flow-mediated dilatation (r = 0.313, P = 0.105) and ICA CVR (r = -0.154, P = 0.495) were not associated with the estradiol concentration. There were no associations between the estradiol concentration and NO bioavailability. These results suggest that in healthy, physically active early and late postmenopausal females, vascular and cerebrovascular function is generally well preserved.

Economic evaluation of exercise interventions for individuals with cancer: A systematic review.

While there is good evidence that exercise is an effective adjunct therapy to cancer care, little is known about its value for money. The aim of this systematic review is to explore the available evidence pertaining to the cost-effectiveness of exercise interventions following cancer. A search of eight online databases (CINAHL, the Cochrane Library (NHSEED), Econlit, Embase, PsycInfo, PubMed, Scopus, Web of science) was first conducted on 26 March 2021 and updated on 8 March 2022. Only economic evaluations with results in the form of incremental cost-effectiveness ratio (ICER) were included. The Consolidated Health Economics Evaluation Reporting Standards (CHEERS) was used to appraise the quality of reporting in the studies. The study protocol was registered in PROSPERO. Sixteen studies comprising seven (44%) cost-utility analyses (CUA), one (6%) cost-effectiveness analyses (CEA) and eight (50%) combined CUA and CEA were identified. These studies explored exercise in five cancer types (breast, colon, lung, prostate, and blood), with half (50%) in breast cancer. Seven studies (44%) adopted societal perspectives. Exercise interventions were found to be cost-effective in five of ten (50%) trial-based economic evaluations and in five of the six (83%) model-based economic evaluations. Most exercise interventions included were supervised, while close supervision and individualized exercise sessions incurred higher costs. Exercise interventions in cancer care are cost-effective for various cancer types despite considerable heterogeneity in exercise delivery and the type of analysis used for economic evaluation. There is clear value in using decision-analytic modelling to account for the long-term benefits of exercise in cancer care.

Autonomic control of cerebral blood flow: fundamental comparisons between peripheral and cerebrovascular circulations in humans.

Understanding the contribution of the autonomic nervous system to cerebral blood flow (CBF) control is challenging, and interpretations are unclear. The identification of calcium channels and adrenoreceptors within cerebral vessels has led to common misconceptions that the function of these receptors and actions mirror those of the peripheral vasculature. This review outlines the fundamental differences and complex actions of cerebral autonomic activation compared with the peripheral circulation. Anatomical differences, including the closed nature of the cerebrovasculature, and differential adrenoreceptor subtypes, density, distribution and sensitivity, provide evidence that measures on peripheral sympathetic nerve activity cannot be extrapolated to the cerebrovasculature. Cerebral sympathetic nerve activity seems to act opposingly to the peripheral circulation, mediated at least in part by changes in intracranial pressure and cerebral blood volume. Additionally, heterogeneity in cerebral adrenoreceptor distribution highlights region-specific autonomic regulation of CBF. Compensatory chemo- and autoregulatory responses throughout the cerebral circulation, and interactions with parasympathetic nerve activity are unique features to the cerebral circulation. This crosstalk between sympathetic and parasympathetic reflexes acts to ensure adequate perfusion of CBF to rising and falling perfusion pressures, optimizing delivery of oxygen and nutrients to the brain, while attempting to maintain blood volume and intracranial pressure. Herein, we highlight the distinct similarities and differences between autonomic control of cerebral and peripheral blood flow, and the regional specificity of sympathetic and parasympathetic regulation within the cerebrovasculature. Future research directions are outlined with the goal to further our understanding of autonomic control of CBF in humans.

The relationships between age, sex, and cerebrovascular reactivity to hypercapnia using traditional and kinetic-based analyses in healthy adults.

The effect of age and sex on intracranial and extracranial cerebrovascular function is poorly understood. We investigated the relationships between age, sex, and cerebrovascular reactivity (CVR) to hypercapnia in 73 healthy adults (18-80 yr, n = 39 female). CVR to hypercapnia was assessed in the middle cerebral artery (MCA) using transcranial Doppler ultrasound and at the internal carotid artery (ICA) using duplex ultrasound. MCA CVR was characterized by peak MCA velocity (MCAv) response per mmHg increase in end-tidal CO2 and by using a monoexponential model to characterize the kinetics (time constant) of the MCAv response. ICA reactivity was assessed as the relative peak increase in artery diameter. Hierarchical multiple regression determined the relationships between age, sex, and the age-by-sex interaction on all baseline and CVR outcomes. There was no relationship between ICA reactivity (%) with age (P = 0.07), sex (P = 0.56), or a moderator effect of sex on the age effect (P = 0.24). MCAv CVR showed no relationship with age (P = 0.59), sex (P = 0.09), or an age-by-sex moderator effect (P = 0.90). We observed a positive relationship of MCAv CVR time constant with age (P = 0.013), such that the speed of the MCA response was slower with advancing age. The present study provides comprehensive data on age- and sex-specific relationships with intracranial and extracranial cerebrovascular responses to hypercapnia. Despite similar MCAv CVR and ICA reactivity between sexes, kinetic responses of the MCA revealed a slower rate of adjustment with advancing age.NEW & NOTEWORTHY We observed similar MCA CVR and ICA reactivity in males and females. However, kinetic responses of the MCA to hypercapnia suggest that advancing age slows down the rate at which MCA velocity increases in response to hypercapnia. These data indicate distinct regulatory differences, and an impaired vasomotor control of the cerebrovasculature with advancing age, not detected by traditional methods.

The physiological and clinical importance of cardiorespiratory fitness in people with abdominal aortic aneurysm.

NEW FINDINGS: What is the topic of this review? This review focuses on the physiological impact of abdominal aortic aneurysm (AAA) on cardiorespiratory fitness and the negative consequences of low fitness on clinical outcomes in AAA. We also discuss the efficacy of exercise training for improving cardiorespiratory fitness in AAA. What advances does it highlight? We demonstrate the negative impact of low fitness on disease progression and clinical outcomes in AAA. We highlight potential mechanistic determinants of low fitness in AAA and present evidence that exercise training can be an effective treatment strategy for improving cardiorespiratory fitness, postoperative mortality and disease progression. ABSTRACT: An abdominal aortic aneurysm (AAA) is an abnormal enlargement of the aorta, below the level of the renal arteries, where the aorta diameter increases by >50%. As an aneurysm increases in size, there is a progressive increase in the risk of rupture, which ranges from 25 to 40% for aneurysms >5.5 cm in diameter. People with AAA are also at a heightened risk of cardiovascular events and associated mortality. Cardiorespiratory fitness is impaired in people with AAA and is associated with poor (postoperative) clinical outcomes, including increased length of hospital stay and postoperative mortality after open surgical or endovascular AAA repair. Although cardiorespiratory fitness is a well-recognized prognostic marker of cardiovascular health and mortality, it is not assessed routinely, nor is it included in current clinical practice guidelines for the management of people with AAA. In this review, we discuss the physiological impact of AAA on cardiorespiratory fitness, in addition to the consequences of low cardiorespiratory fitness on clinical outcomes in people with AAA. Finally, we summarize current evidence for the effect of exercise training interventions on cardiorespiratory fitness in people with AAA, including the associated improvements in postoperative mortality, AAA growth and cardiovascular risk. Based on this review, we propose that cardiorespiratory fitness should be considered as part of the routine risk assessment and monitoring of people with AAA and that targeting improvements in cardiorespiratory fitness with exercise training might represent a viable adjunct treatment strategy for reducing postoperative mortality and disease progression.

The within- and between-day reliability of cerebrovascular reactivity using traditional and novel analytical approaches.

NEW FINDINGS: What is the central question of the study? What is the reliability of middle cerebral artery velocity cerebrovascular reactivity (CVR) when using traditional and novel outcomes, as measured by transcranial Doppler? What is the main finding and its importance? Traditional CVR approaches presented acceptable reproducibility but should be expressed as an absolute CVR. Large within- and between-individual differences in the middle cerebral artery velocity response profile support using a dynamic peak, rather than a set time point, for the most reliable interpretation. The study highlights the utility of novel kinetic CVR outcomes, but due to increased variability in time-based metrics, this analysis requires larger sample sizes than traditional methods. ABSTRACT: Cerebrovascular reactivity (CVR) of middle cerebral artery velocity (MCAv) to CO2 is a common method to assess cerebrovascular function. Yet, the approaches used to calculate CVR outcomes vary. The aim of this study was to explore the within- and between-day reliability of traditional CVR outcomes. The second aim was to explore the reliability of novel kinetic-based analyses. Healthy adults (n = 10, 22.3 ± 3.4 years) completed assessments of CVR over 4 min using a fixed fraction of inspired CO2 (6%). This was repeated across four separate visits (between-day), and on one visit measures were repeated 2.5 h later (within-day). No mean biases were present between assessments for traditional CVR metrics, expressed as absolute (cm/s/mmHg) or relative (%/mmHg) outcomes (minute 3, minute 4, peak 1 s, peak 30 s) (between-day: P > 0.14, ηp2 < 0.20; within-day: P > 0.22, d > 0.27). Absolute, rather than relative, CVR yielded the most reproducible parameters (coefficient of variation: 8.1-13.2% vs. 14-83%, respectively). There were significant differences between CVR outcomes (P < 0.001, ηp2 > 0.89) dependent on the time point used to determine CVR, as a steady state MCAv response was rarely observed. Furthermore, the MCAv response was not reproducible within an individual (κ = 0.15, P = 0.09). No mean differences were present for novel kinetic outcomes (amplitude, time-delay, time constant) (between-day: P > 0.05, d < 0.33; within-day: P > 0.38, d < 0.25). The results support the need for standardisation and indicate CVR should be defined as a dynamic peak, rather than a set time point for increased reliability. For novel kinetic outcomes variability was greater (CV: 8.7-120.9%) due to the nature of time-based metrics.

Comparison of high intensity interval training with standard cardiac rehabilitation on vascular function.

OBJECTIVES: To compare the short- and long-term effects of high-intensity interval training (HIIT) with usual care moderate intensity continuous training (MICT) on systemic vascular function and stiffness in patients with coronary artery disease undergoing a cardiac rehabilitation program. DESIGN: Randomized controlled trial. METHODS: Fifty-four patients (age = 63 ± 8 years, 93% male) were randomized to complete 3 sessions/week (2 supervised, 1 home-based) of either (1) 4 × 4-min HIIT or (2) 40-min MICT, for 4 weeks. Patients then continued 3 unsupervised home-based sessions/week of their allocated training for 11 months. Brachial artery flow-mediated dilation, pulse wave velocity, and blood pressure were measured at baseline, 4 weeks, 3 months, 6 months, and 12 months. Data were analyzed using linear mixed modeling and are presented as mean change from baseline (95% CI). RESULTS: HIIT showed a greater improvement in flow-mediated dilation compared to MICT after 4 weeks [1.5% (0.9, 2.1) vs 0.1% (-0.5, 0.8); p = 0.004) but not 12 months [1.2% (-0.2, 2.5) vs 0.4% (-0.8, 1.7); p = 0.153). There were no short- or long-term group differences for changes in pulse wave velocity, peripheral or central blood pressure between HIIT and MICT after 4 weeks, or over 12 months. CONCLUSIONS: A 4-week HIIT program was superior to MICT for improving vascular function, but not arterial stiffness or blood pressure. Over 12 months, changes in vascular function, blood pressure, and arterial stiffness were similar for HIIT and MICT.

Cerebrovascular function and its association with systemic artery function and stiffness in older adults with and without mild cognitive impairment.

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.

Effects of cardiorespiratory fitness and exercise training on cerebrovascular blood flow and reactivity: a systematic review with meta-analyses.

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.

The effect of heat therapy on blood pressure and peripheral vascular function: A systematic review and meta-analysis.

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 < 0.0001], systolic blood pressure (n = 10; MD: -3.94 mmHg, 95% CI: -7.22, -0.67; P = 0.02) and diastolic blood pressure (n = 9; MD: -3.88 mmHg, 95% CI: -6.13, -1.63; P = 0.0007) and improved flow-mediated dilatation (n = 5; MD: 1.95%, 95% CI: 0.14, 3.76; P = 0.03). Resting heart rate was unchanged (n = 10; MD: -1.25 beats/min; 95% CI: -3.20, 0.70; P = 0.21). Early evidence also suggests benefits for arterial stiffness and cutaneous microvascular function. The certainty of evidence was moderate for the effect of heat therapy on systolic and diastolic blood pressure and heart rate and low for the effect of heat therapy on mean arterial pressure and flow-mediated dilatation. Heat therapy is an effective therapeutic tool to reduce blood pressure and improve macrovascular function. Future research should aim to optimize heat therapy, including the mode and dose, for the prevention and management of cardiovascular disease.

The Role of Exercise in Patients with Obesity and Hypertension.

PURPOSE OF REVIEW: This review sought to evaluate the role of exercise in patients with obesity and comorbid hypertension, with a focus on contemporary literature (since January 2015). RECENT FINDINGS: No reviews have included patients classified with both obesity and hypertension and there is a paucity of randomised controlled trials examining the benefits of exercise in this population. Moreover, just one of 19 reviews examining the role of exercise on blood pressure included studies that met pre-defined inclusion criterion for hypertension, although seven conducted subgroup analyses stratified by mean baseline blood pressure. These demonstrated significantly larger reductions in blood pressure in hypertensive than pre-hypertensive and normotensive samples. There is a significant research-practice gap for understanding and influencing the role of exercise for patients with obesity and hypertension. This review provides recommendations for future research and consensus-based recommendations that promote exercise as a principle therapy for patients with obesity and hypertension.

Participation in sports/recreational activities and incidence of hypertension, diabetes, and obesity in adults.

Evidence of prospective associations between participation in sports and recreational activities (SRAs) and health outcomes at the population level is scarce. We investigated the associations between participation in SRAs and 6-year incidence of hypertension, diabetes, and obesity in a cohort of mid-age Australian adults. We analyzed data from the HABITAT study (n = 8784), a cohort of adults aged 40+ years living in Brisbane, Australia. Mail surveys in 2007, 2009, 2011, and 2013 were used to collect data on participation in 11 SRAs in the past 12 months, as well as self-reported hypertension, diabetes, height, and weight. Obesity was defined as BMI ≥ 30.0 kg/m2 . Logistic generalized estimating equation models with a 2-year lag were used. Participation in SRAs in 2007, 2009, and 2011 was matched with outcomes measured in 2009, 2011, and 2013. From 2007 to 2013, the cumulative incidence of hypertension, diabetes, and obesity was 14.9%, 3.2%, and 11%, respectively. Running, tennis, team sports, exercise classes, and resistance training were associated with reduced odds of hypertension. Running, cycling, resistance training, and yoga/tai chi were associated with reduced odds of diabetes. Cycling, tennis, home-based exercises, resistance training, and yoga/tai chi were associated with lower odds of obesity. Participation in SRAs was associated with lower incidence of hypertension, diabetes, and obesity in mid-age adults over six years. These findings support current efforts to promote wider and continuing participation in SRAs at this life stage.

n-3 PUFAs improve erythrocyte fatty acid profile in patients with small AAA: a randomized controlled trial.

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.

Does respiratory drive modify the cerebral vascular response to changes in end-tidal carbon dioxide?

NEW FINDINGS: What is the central question of this study? There is an interaction between the regulatory systems of respiration and cerebral blood flow, because the mediator (CO2 ) is the same for both physiological systems. We examined whether the traditional method for determining cerebrovascular reactivity to CO2 is modified by changes in respiration. What is the main finding and its importance? Cerebrovascular reactivity was modified by voluntary changes in respiration during hypercapnia. This finding suggests that an alteration in the respiratory system may result in under- or overestimation of cerebrovascular reactivity determined by traditional methods in healthy adults. ABSTRACT: The cerebral vasculature is sensitive to changes in the arterial partial pressure of CO2 . This physiological mechanism has been well established as a cerebrovascular reactivity to CO2 (CVR). However, arterial CO2 may not be an independent variable in the traditional method for assessment of CVR, because the cerebral blood flow response is also affected by the activation of respiratory drive or higher centres in the brain. We hypothesized that CVR is modified by changes in respiration. To test our hypothesis, in the present study, 10 young, healthy subjects performed hyper- or hypoventilation to change end-tidal CO2 ( PET,CO2 ) with different concentrations of CO2 in the inhaled gas (0, 2.0 and 3.5%). We measured middle cerebral artery mean blood flow velocity by transcranial Doppler ultrasonography to identify the cerebral blood flow response to change in PET,CO2 during each set of conditions. In each set of conditions, PET,CO2 was significantly altered by changes in ventilation, and middle cerebral artery mean blood flow velocity changed accordingly. However, the relationship between changes in middle cerebral artery mean blood flow velocity and PET,CO2 as a response curve of CVR was reset upwards and downwards by hypo- and hyperventilation, respectively, compared with CVR during normal ventilation. The findings of the present study suggest the possibility that an alteration in respiration might lead to under- or overestimation of CVR determined by the traditional methods.

Aortic and Systemic Arterial Stiffness Responses to Acute Exercise in Patients With Small Abdominal Aortic Aneurysms.

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.

Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease.

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.

Effects of acute exercise on endothelial function in patients with abdominal aortic aneurysm.

Endothelial dysfunction is observed in patients with abdominal aortic aneurysm (AAA), who have increased risk of cardiovascular events and mortality. This study aimed to assess the acute effects of moderate- and higher-intensity exercise on endothelial function, as assessed by flow-mediated dilation (FMD), in AAA patients (74 ± 6 yr old, n = 22) and healthy adults (72 ± 5 yr old, n = 22). Participants undertook three randomized visits, including moderate-intensity continuous exercise [40% peak power output (PPO)], higher-intensity interval exercise (70% PPO), and a no-exercise control. Brachial artery FMD was assessed at baseline and at 10 and 60 min after each condition. Baseline FMD was lower [by 1.10% (95% confidence interval: 0.72-.81), P = 0.044] in AAA patients than in healthy adults. There were no group differences in FMD responses after each condition ( P = 0.397). FMD did not change after no-exercise control but increased by 1.21% (95% confidence interval: 0.69-1.73, P < 0.001) 10 min after moderate-intensity continuous exercise in both groups and returned to baseline after 60 min. Conversely, FMD decreased by 0.93% (95% confidence interval: 0.41-1.44, P < 0.001) 10 min after higher-intensity interval exercise in both groups and remained decreased after 60 min. We found that the acute response of endothelial function to exercise is intensity-dependent and similar between AAA patients and healthy adults. Our findings provide evidence that regular exercise may improve vascular function in AAA patients, as it does in healthy adults. Improved FMD after moderate-intensity exercise may provide short-term benefit. Whether the decrease in FMD after higher-intensity exercise represents an additional risk and/or a greater stimulus for vascular adaptation remains to be elucidated. NEW & NOTEWORTHY Abdominal aortic aneurysm patients have vascular dysfunction. We observed a short-term increase in vascular function after moderate-intensity exercise. Conversely, higher-intensity exercise induced a prolonged reduction in vascular function, which may be associated with both short-term increases in cardiovascular risk and signaling for longer-term vascular adaptation in abdominal aortic aneurysm patients.

Effects of exercise intensity and cardiorespiratory fitness on the acute response of arterial stiffness to exercise in older adults.

PURPOSE: Increased arterial stiffness is observed with ageing and in individuals with low cardiorespiratory fitness ([Formula: see text]O2peak), and associated with cardiovascular risk. Following an exercise bout, transient arterial stiffness reductions offer short-term benefit, but may depend on exercise intensity. This study assessed the effects of exercise intensity on post-exercise arterial stiffness in older adults with varying fitness levels. METHODS: Fifty-one older adults (72 ± 5 years) were stratified into fitness tertiles ([Formula: see text]O2peak: low-, 22.3 ± 3.1; mid-, 27.5 ± 2.4 and high-fit 36.3 ± 6.5 mL kg-1 min-1). In a randomised order, participants underwent control (no-exercise), moderate-intensity continuous exercise (40% of peak power output; PPO), and higher-intensity interval exercise (70% of PPO) protocols. Pulse wave velocity (PWV), augmentation index (AIx75) and reflection magnitude (RM) were assessed at rest and during 90 min of recovery following each protocol. RESULTS: After control, delta PWV increased over time (P < 0.001) and delta RM was unchanged. After higher-intensity interval exercise, delta PWV (P < 0.001) and delta RM (P < 0.001) were lower to control in all fitness groups. After moderate-intensity continuous exercise, delta PWV was not different from control in low-fit adults (P = 0.057), but was lower in the mid- and higher-fit older adults. Post-exercise AIx75 was higher to control in all fitness groups (P = 0.001). CONCLUSIONS: In older adults, PWV increases during seated rest and this response is attenuated after higher-intensity interval exercise, regardless of fitness level. This attenuation was also observed after moderate-intensity continuous exercise in adults with higher, but not lower fitness levels. Submaximal exercise reveals differences in the arterial stiffness responses between older adults with higher and lower cardiorespiratory fitness.

Exercise training reduces the acute physiological severity of post-menopausal hot flushes.

KEY POINTS: A post-menopausal hot flush consists of profuse physiological elevations in cutaneous vasodilatation and sweating that are accompanied by reduced brain blood flow. These responses can be used to objectively quantify hot flush severity. The impact of an exercise training intervention on the physiological responses occurring during a hot flush is currently unknown. In a preference-controlled trial involving 21 post-menopausal women, 16 weeks of supervised moderate intensity exercise training was found to improve cardiorespiratory fitness and attenuate cutaneous vasodilatation, sweating and the reductions in cerebral blood flow during a hot flush. It is concluded that the improvements in fitness that are mediated by 16 weeks of exercise training reduce the severity of physiological symptoms that occur during a post-menopausal hot flush. A hot flush is characterised by feelings of intense heat, profuse elevations in cutaneous vasodilatation and sweating, and reduced brain blood flow. Exercise training reduces self-reported hot flush severity, but underpinning physiological data are lacking. We hypothesised that exercise training attenuates the changes in cutaneous vasodilatation, sweat rate and cerebral blood flow during a hot flush. In a preference trial, 18 symptomatic post-menopausal women underwent a passive heat stress to induce hot flushes at baseline and follow-up. Fourteen participants opted for a 16 week moderate intensity supervised exercise intervention, while seven participants opted for control. Sweat rate, cutaneous vasodilatation, blood pressure, heart rate and middle cerebral artery velocity (MCAv) were measured during the hot flushes. Data were binned into eight equal segments, each representing 12.5% of hot flush duration. Weekly self-reported frequency and severity of hot flushes were also recorded at baseline and follow-up. Following training, mean hot flush sweat rate decreased by 0.04 mg cm(2) min(-1) at the chest (95% confidence interval 0.02-0.06, P = 0.01) and by 0.03 mg cm(2) min(-1) (0.02-0.05, P = 0.03) at the forearm, compared with negligible changes in control. Training also mediated reductions in cutaneous vasodilatation by 9% (6-12%) at the chest and by 7% (4-9%) at forearm (P ≤ 0.05). Training attenuated hot flush MCAv by 3.4 cm s(-1) (0.7-5.1 cm s(-1) , P = 0.04) compared with negligible changes in control. Exercise training reduced the self-reported severity of hot flushes by 109 arbitrary units (80-121, P < 0.001). These data indicate that exercise training leads to parallel reductions in hot flush severity and within-flush changes in cutaneous vasodilatation, sweating and cerebral blood flow.