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BACKGROUND: Regular physical activity is associated with a reduced stroke risk. However, this relationship might be attenuated in the presence of hypertension and antihypertensive medication use. We examined the dose-response relationship between physical activity and stroke in normotensive and hypertensive individuals. METHODS: A Dutch population-based cohort including 139 930 individuals (41% men; mean age, 44±13) was performed (median follow-up, 6.75 years). Participants were stratified at baseline as hypertensive (44%) or normotensive (56%) and categorized into quartiles of the lowest (Q1) to the highest (Q4) moderate-to-vigorous, self-reported physical activity. The primary outcome was incident stroke (fatal and nonfatal). Cox regression estimated hazard ratios and 95% CIs. The main analyses were stratified on baseline blood pressure and adjusted for confounders. Hypertensives were stratified into medicated (21%) or non-medicated (79%). RESULTS: Compared with Q1, adjusted hazard ratios were 0.87 (0.69-1.10; P=0.23), 0.75 (0.59-0.95; P=0.02), and 0.94 (0.74-1.20; P=0.64) for Q2 to Q4, respectively in the total population. Hazard ratios for normotensives were 0.79 (0.50-1.25; P=0.32), 0.75 (0.48-1.18; P=0.22), 0.97 (0.62-1.51; P=0.90) for Q2 to Q4, respectively. In hypertensives, hazard ratios were 0.89 (0.68-1.17; P=0.41), 0.74 (0.56-0.98; P=0.03), 0.92 (0.69-1.23; P=0.56) for Q2 to Q4, respectively. There was no significant interaction between hypertension status for the relation between physical activity and stroke risk. The stratified analysis revealed a smaller benefit of moderate-to-vigorous physical activity in medicated hypertensives compared with nonmedicated hypertensives, but no significant interaction effect was found. CONCLUSIONS: Regular moderate-to-vigorous physical activity is beneficial for stroke risk reduction (Q3 compared with Q1), which is not affected by hypertension. Antihypertensive medication may be associated with a smaller benefit of moderate-to-vigorous physical activity on the risk of stroke, but further research is warranted.
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Ejercicio Físico , Hipertensión , Accidente Cerebrovascular , Humanos , Masculino , Hipertensión/epidemiología , Hipertensión/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular/epidemiología , Adulto , Estudios de Cohortes , Antihipertensivos/uso terapéutico , Países Bajos/epidemiología , Presión Sanguínea/fisiología , Estudios de Seguimiento , AncianoRESUMEN
PURPOSE: We used a within-subject, cross-over study to determine the relationship between the intra-individual adaptations to four weeks' resistance (RT) versus four weeks' endurance (END) training, and we investigated whether three single nucleotide polymorphisms (SNPs) were associated with these adaptations. METHODS: Thirty untrained, healthy, young men completed a cycling test to exhaustion to determine peak oxygen uptake (VÌO2peak), and a knee extension (KE) maximum voluntary isometric contraction (MVIC) of the right leg before and after four weeks' supervised RT (four sets of 10 repetitions at 80% single repetition maximum unilateral KE exercise, three times weekly) and four weeks' supervised END (30 min combined continuous/interval cycling, three times weekly), separated by a three-week washout phase. Participants were genotyped for the ACTN3 rs1815739, NOS3 rs2070744 and VEGFA rs2010963 SNPs. RESULTS: The intra-individual adaptations regarding percentage changes in MVIC force and VÌO2peak following RT and END, respectively, were unrelated (r2 = 0.003; P = 0.79). However, a VEGFA genotype × training modality interaction (P = 0.007) demonstrated that VEGFA GG homozygotes increased their MVIC force after RT (+ 20.9 ± 13.2%) more than they increased their VÌO2peak after END (+ 8.4 ± 9.1%, P = 0.005), and more than VEGFA C-allele carriers increased their MVIC force after RT (+ 12.2 ± 8.1%, P = 0.04). There were no genotype × training modality interactions for the ACTN3 or NOS3 SNPs. CONCLUSION: High/low responders to RT were not consequently high/low responders to END or vice versa. However, preferential adaptation of VEGFA rs2010963 GG homozygotes to RT over END, and their greater adaptation to RT compared to VEGFA C-allele carriers, indicate a novel genetic predisposition for superior RT adaptation.
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Entrenamiento Aeróbico , Entrenamiento de Fuerza , Masculino , Humanos , Estudios Cruzados , Fuerza Muscular/genética , Genotipo , Adaptación Fisiológica/genética , Músculo Esquelético , Factor A de Crecimiento Endotelial Vascular/genética , Actinina/genéticaRESUMEN
PURPOSE: Endothelial dysfunction is an early and integral event in the development of atherosclerosis and coronary artery disease (CAD). Reduced NO bioavailability, oxidative stress, vasoconstriction, inflammation and senescence are all implicated in endothelial dysfunction. However, there are limited data examining associations between these pathways and direct in vivo bioassay measures of endothelial function in CAD patients. This study aimed to examine the relationships between in vivo measures of vascular function and the expression of atherogenic risk-modulating proteins in endothelial cells (ECs) isolated from the radial artery of CAD patients. METHODS: Fifty-six patients with established CAD underwent trans-radial catheterization. Prior to catheterization, radial artery vascular function was assessed using a) flow-mediated dilation (FMD), and b) exercise-induced dilation in response to handgrip (HE%). Freshly isolated ECs were obtained from the radial artery during catheterization and protein content of eNOS, NAD(P)H oxidase subunit NOX2, NFκB, ET-1 and the senescence markers p53, p21 and p16 were evaluated alongside nitrotyrosine abundance and eNOS Ser1177 phosphorylation. RESULTS: FMD was positively associated with eNOS Ser1177 phosphorylation (r = 0.290, P = 0.037), and protein content of p21 (r = 0.307, P = 0.027) and p16 (r = 0.426, P = 0.002). No associations were found between FMD and markers of oxidative stress, vasoconstriction or inflammation. In contrast to FMD, HE% was not associated with any of the EC proteins. CONCLUSION: These data revealed a difference in the regulation of endothelium-dependent vasodilation measured in vivo between patients with CAD compared to previously reported data in subjects without a clinical diagnosis, suggesting that eNOS Ser1177 phosphorylation may be the key to maintain vasodilation in CAD patients.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Humanos , Células Endoteliales , Fuerza de la Mano , Dilatación , Endotelio Vascular , Vasodilatación/fisiología , Inflamación , Arteria BraquialRESUMEN
PURPOSE: In this study, we examined whether the decrease in endothelial function associated with short-term exposure to elevated retrograde shear rate (SR), could be prevented when combined with a concurrent drop in transmural pressure in humans. METHODS: Twenty-five healthy individuals reported to our laboratory on three occasions to complete 30-min experimental conditions, preceded and followed by assessment of endothelial function using flow-mediated dilation (FMD). We used cuff inflation for 30-min to manipulate retrograde SR and transmural pressure in the brachial artery. Subjects underwent, in randomised order: (1) forearm cuff inflation to 60 mmHg (distal cuff; causing increase in retrograde SR), (2) upper arm cuff inflation to 60 mmHg (proximal cuff; causing increase in retrograde SR + decrease in transmural pressure), and (3) no cuff inflation (Control). RESULTS: The distal and proximal cuff conditions both increased brachial artery retrograde SR (p < 0.001) and oscillatory shear index (p < 0.001). The Control intervention did not alter SR patterns or FMD (p > 0.05). A significant interaction-effect was found for FMD (p < 0.05), with the decrease during distal cuff (from 6.9 ± 2.3% to 6.1 ± 2.5%), being reversed to an increase with proximal cuff (from 6.3 ± 2.0 to 6.9 ± 2.0%). The proximal cuff-related increase in FMD could not be explained by the decrease in antegrade or increase in retrograde shear. CONCLUSION: This study suggests that a decrease in transmural pressure may ameliorate the decline in endothelial function that occurs following exposure to elevated retrograde shear in healthy individuals.
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Arteria Braquial/fisiología , Vendajes de Compresión , Endotelio Vascular/fisiología , Precondicionamiento Isquémico/métodos , Adulto , Hemodinámica , Humanos , Precondicionamiento Isquémico/instrumentación , Masculino , Distribución AleatoriaRESUMEN
PURPOSE: Animal studies have shown that endothelial denudation abolishes vasodilation in response to increased shear stress. Interestingly, shear-mediated dilation has been reported to be reduced, but not abolished, in coronary artery disease (CAD) patients following catheterization. However, it is not known whether this resulted from a priori endothelial dysfunction in this diseased population. In this study, we evaluated shear-mediated dilation following catheterization in healthy young men. METHODS: Twenty-six (age: 24.4 ± 3.8 years, BMI: 24.3 ± 2.8 kg m-2, VO2peak: 50.5 ± 8.8 ml/kg/min) healthy males underwent unilateral transradial catheterization. Shear-mediated dilation of both radial arteries was measured using flow-mediated dilation (FMD) pre-, and 7 days post-catheterization. RESULTS: FMD was reduced in the catheterized arm [9.3 ± 4.1% to 4.3 ± 4.1% (P < 0.001)] post-catheterization, whereas no change was observed in the control arm [8.4 ± 3.8% to 7.3 ± 3.8% (P = 0.168)]. FMD was completely abolished in the catheterized arm in five participants. Baseline diameter (P = 0.001) and peak diameter during FMD (P = 0.035) were increased in the catheterized arm 7 days post-catheterization (baseline: 2.3 ± 0.3 to 2.6 ± 0.2 mm, P < 0.001, peak: 2.5 ± 0.3 to 2.7 ± 0.3 mm, P = 0.001), with no change in the control arm (baseline: 2.3 ± 0.3 to 2.3 ± 0.3 mm, P = 0.288, peak: 2.5 ± 0.3 to 2.5 ± 0.3 mm, P = 0.608). CONCLUSION: This is the first study in young healthy individuals with intact a priori endothelial function to provide evidence of impaired shear-mediated dilation following catheterization. When combined with earlier studies in CAD patients, our data suggest the catheterization impairs artery function in humans.
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Cateterismo/efectos adversos , Arteria Radial/fisiología , Dispositivos de Acceso Vascular/efectos adversos , Vasodilatación , Adulto , Cateterismo/métodos , Endotelio Vascular/fisiología , Voluntarios Sanos , Humanos , MasculinoRESUMEN
KEY POINTS: Obesity and sedentary behaviour are associated with capillary rarefaction and impaired muscle microvascular vasoreactivity, due to reduced nitric oxide bioavailability. Low-volume high-intensity interval training (HIT) is a time-efficient alternative to traditional moderate-intensity continuous training (MICT), but its effect on the muscle microvasculature has not been studied. The applicability of current laboratory- and gym-based HIT protocols for obese individuals with low fitness and mobility has been disputed by public health experts, who cite the strenuous nature and complex protocols as major barriers. Therefore, we developed a virtually supervised HIT protocol targeting this group that can be performed at home without equipment (Home-HIT). This study is the first to show that 12 weeks of virtually supervised Home-HIT in obese individuals with elevated cardiovascular disease risk leads to similar increases in capillarisation and eNOS/NAD(P)Hoxidase protein ratio within the muscle microvascular endothelium as virtually supervised home-based MICT and laboratory-based HIT, while reducing many of the major barriers to exercise. ABSTRACT: This study investigated the effect of a novel virtually supervised home-based high-intensity interval training (HIT) (Home-HIT) intervention in obese individuals with elevated cardiovascular disease (CVD) risk on capillarisation and muscle microvascular eNOS/NAD(P)Hoxidase ratio. Thirty-two adults with elevated CVD risk (age 36 ± 10 years; body mass index 34.3 ± 5 kg m-2 ; VÌO2peak 24.6 ± 5.7 ml kg min-1 ), completed one of three 12-week training programmes: Home-HIT (n = 9), laboratory-based supervised HIT (Lab-HIT; n = 10) or virtually supervised home-based moderate-intensity continuous training (Home-MICT; n = 13). Muscle biopsies were taken before and after training to assess changes in vascular enzymes, capillarisation, mitochondrial density, intramuscular triglyceride content and GLUT4 protein expression using quantitative immunofluorescence microscopy. Training increased VÌO2peak (P < 0.001), whole-body insulin sensitivity (P = 0.033) and flow-mediated dilatation (P < 0.001), while aortic pulse wave velocity decreased (P < 0.001) in all three groups. Immunofluorescence microscopy revealed comparable increases in total eNOS content in terminal arterioles and capillaries (P < 0.001) in the three conditions. There was no change in eNOS ser1177 phosphorylation (arterioles P = 0.802; capillaries P = 0.311), but eNOS ser1177 /eNOS content ratio decreased significantly following training in arterioles and capillaries (P < 0.001). Training decreased NOX2 content (arterioles P < 0.001; capillaries P < 0.001), but there was no change in p47phox content (arterioles P = 0.101; capillaries P = 0.345). All measures of capillarisation increased (P < 0.05). There were no between-group differences. Despite having no direct supervision during exercise, virtually supervised Home-HIT resulted in comparable structural and endothelial enzymatic changes in the skeletal muscle microvessels to the traditional training methods. We provide strong evidence that Home-HIT is an effective novel strategy to remove barriers to exercise and improve health in an obese population at risk of CVD.
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Entrenamiento de Intervalos de Alta Intensidad , Microvasos/fisiología , Músculo Esquelético/irrigación sanguínea , NADPH Oxidasas/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Obesidad , Adulto , Enfermedades Cardiovasculares/prevención & control , Femenino , Regulación Enzimológica de la Expresión Génica , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Humanos , Masculino , NADPH Oxidasas/genética , Óxido Nítrico Sintasa de Tipo III/genética , Fosforilación , Factores de Riesgo , Conducta Sedentaria , Triglicéridos/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Muscle weakness is a defining characteristic of Muscular Dystrophy (MD); however, yet while speculated, objective measures of muscle weakness has not been reported in relation to quality of life in adults with MD. OBJECTIVES: 1) compare the self-reported QoL of adults with Duchenne MD (DMD), Beckers MD (BMD), Limb-Girdle MD (LGMD) and Fascioscapulohumeral MD (FSHD, and a non-MD (CTRL) group; 2) present and compare between groups measures of Impairment (Muscle Strength and Activities of Daily Living) and Perception (Fatigue, Pain and Self-Efficacy); and 3) identify associations between QoL domains and measures of Impairment and Perception (See above). METHODS: Seventy-Five males, including MD classifications DMD, BMD, LGMD, FSHD and CTRL, completed measures for QoL, Knee-Extension Maximal Voluntary Contraction (KEMVC), Fatigue, Pain, Self-Efficacy and Activities of Daily Living (ADL). RESULTS: QoL was lower across many domains in MD than CTRL. FSHD scored lower than DMD for mental wellbeing domains. KEMVC associated with Physical-Function domain for BMD. Pain, Self-Efficacy and ADLs associated with QoL domains, with Fatigue the most consistently associated. CONCLUSION: The present study identified differences between MD classifications within self-perceptions of mental-health. Muscle weakness is a defining feature of MD; however, it doesn't define QoL in adults with MD. A greater understanding of mental wellbeing, independence, and management of fatigue and pain, are required to improve QoL for adults with MD.
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Actividades Cotidianas/psicología , Fuerza Muscular , Distrofia Muscular de Duchenne/psicología , Calidad de Vida , Adulto , Estudios Transversales , Fatiga/psicología , Humanos , Masculino , Persona de Mediana Edad , Debilidad Muscular , Dolor/psicología , Autoeficacia , Autoinforme , Adulto JovenRESUMEN
PURPOSE: No previous study has explored the importance of exercise-induced changes in vascular function to prolonged adaptations. Therefore, the purpose was to explore the within-subject relationship between the acute post-exercise change in brachial artery endothelial function (flow-mediated dilation, FMD) and the change in resting FMD after a 2-week exercise training in healthy volunteers. METHODS: Twenty one healthy, young men (24 ± 5 years) underwent assessment of brachial artery FMD using high-resolution ultrasound before and after 30-min of moderate-intensity cycle exercise (80% maximal heart rate). Subsequently, subjects performed five 30-min cycle exercise bouts at 80% maximal heart rate across a 2-week period, followed by repeat assessment of resting brachial FMD post-training. RESULTS: Correcting for changes in diameter and shear, FMD did not change after the initial exercise bout (P = 0.26). However, a significant correlation was found between post-exercise changes in FMD and adaptation in resting FMD after training (r = 0.634, P = 0.002), where an acute decrease in post-exercise FMD resulted in a decrease in baseline FMD after 2 weeks and vice versa. We also found a positive correlation between antegrade shear rate during exercise and change in FMD% after acute exercise and after exercise training (r = 0.529 and 0.475, both P < 0.05). CONCLUSION: Our findings suggest that acute post-exercise changes in vascular function are related to changes in resting FMD after a 2-week endurance exercise training period in healthy men, an effect that may be related to exercise-induced increases in antegrade shear rate. This provides further insight into the relevance of acute changes in shear and FMD for subsequent adaptation.
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Adaptación Fisiológica , Arteria Braquial/fisiología , Endotelio Vascular/fisiología , Ejercicio Físico , Adulto , Humanos , Masculino , VasodilataciónRESUMEN
PURPOSE: Exercise training induces adaptation in conduit and resistance arteries in humans, partly as a consequence of repeated elevation in blood flow and shear stress. The stimuli associated with intrinsic cutaneous microvascular adaptation to exercise training have been less comprehensively studied. METHODS: We studied 14 subjects who completed 8-weeks cycle ergometer training, with partial cuff inflation on one forearm to unilaterally attenuate cutaneous blood flow responses during each exercise-training bout. Before and after training, bilateral forearm skin microvascular dilation was determined using cutaneous vascular conductance (CVC: skin flux/blood pressure) responses to gradual localised heater disk stimulation performed at rest (33, 40, 42 and 44 °C). RESULTS: Cycle exercise induced significant increases in forearm cutaneous flux and temperature, which were attenuated in the cuffed arm (2-way ANOVA interaction-effect; P < 0.01). We found that forearm CVC at 42 and 44 °C was significantly lower in the uncuffed arm following 8-weeks of cycle training (P < 0.01), whereas no changes were apparent in the contralateral cuffed arm (P = 0.77, interaction-effect P = 0.01). CONCLUSIONS: Lower limb exercise training in healthy young men leads to lower CVC-responses to a local heating stimulus, an adaptation mediated, at least partly, by a mechanism related to episodic increases in skin blood flow and/or skin temperature.
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Adaptación Fisiológica/fisiología , Ejercicio Físico/fisiología , Antebrazo/irrigación sanguínea , Flujo Sanguíneo Regional/fisiología , Adulto , Arteria Braquial/fisiología , Endotelio Vascular/fisiología , Femenino , Calor , Humanos , Masculino , Piel/irrigación sanguínea , Estrés Mecánico , Vasodilatación/fisiología , Adulto JovenRESUMEN
BACKGROUND: Physical activity (PA) is associated with reduced hospitalisations and maintenance of lung function in patients with Cystic Fibrosis (CF). PA is therefore recommended as part of standard care. Despite this, there is no consensus for monitoring of PA and little is known about perceptions of PA monitoring among children and young people with CF. Therefore, the research aimed to explore patients' perceptions of PA and the acceptability of using PA monitoring devices with children and young people with CF. METHODS: An action research approach was utilised, whereby findings from earlier research phases informed subsequent phases. Four phases were utilised, including patient interviews, PA monitoring, follow-up patient interviews and health care professional (HCP) interviews. Subsequently, an expert panel discussed the study to develop recommendations for practice and future research. RESULTS: Findings suggest that experiences of PA in children and young people with CF are largely comparable to their non-CF peers, with individuals engaging in a variety of activities. CF was not perceived as a barrier per se, although participants acknowledged that they could be limited by their symptoms. Maintenance of health emerged as a key facilitator, in some cases PA offered patients the opportunity to 'normalise' their condition. Participants reported enjoying wearing the monitoring devices and had good compliance. Wrist-worn devices and devices providing feedback were preferred. HCPs recognised the potential benefits of the devices in clinical practice. Recommendations based on these findings are that interventions to promote PA in children and young people with CF should be individualised and involve families to promote PA as part of an active lifestyle. Patients should receive support alongside the PA data obtained from monitoring devices. CONCLUSIONS: PA monitoring devices appear to be an acceptable method for objective assessment of PA among children and young people with CF and their clinicians. Wrist-worn devices, which are unobtrusive and can display feedback, were perceived as most acceptable. By understanding the factors impacting PA, CF health professionals will be better placed to support patients and improve health outcomes.
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Actitud del Personal de Salud , Actitud Frente a la Salud , Fibrosis Quística/psicología , Fibrosis Quística/rehabilitación , Ejercicio Físico , Monitores de Ejercicio , Humanos , Entrevistas como Asunto , Cooperación del Paciente , PercepciónRESUMEN
BACKGROUND: Skin microvascular responses to local heating are frequently used to assess microvascular function. Several local heating protocols have been developed, all varying slightly in execution. The aim of this study was to determine the inter-day reproducibility of the four most commonly used local heating protocols in healthy young subjects. METHODS: Fifteen, healthy males (28±5yrs, BMI 25±2kg/m2) attended two experimental trials 2-7days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5s), 2. Rapid 42°C (0.5°C/5s) 3. Gradual 42°C (0.5°C/2min 30s) and 4. Slow 42°C (0.5°C/5min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). RESULTS: Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (all 21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. CONCLUSION: This is the first study examining inter-day reproducibility across four local heating protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols support their (simultaneous) use to assess microvascular function. Using Rapid 39°C may require a greater number of subjects to detect differences within subjects.
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Hipertermia Inducida/métodos , Microcirculación , Microvasos/fisiología , Temperatura Cutánea , Piel/irrigación sanguínea , Adulto , Velocidad del Flujo Sanguíneo , Humanos , Flujometría por Láser-Doppler , Masculino , Flujo Sanguíneo Regional , Reproducibilidad de los Resultados , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: Gradual local heating of the skin induces a largely NO-mediated vasodilatation. However, use of this assessment of microvascular health is limited because little is known about its reproducibility. METHODS: Healthy volunteers (n = 9) reported twice to the laboratory. CVC, derived from laser Doppler flux and mean arterial pressure, was examined in response to a standardized local heating protocol (0.5°C per 150 second from 33°C to 42°C, followed by 20 minutes at 44°C). Skin responses were examined at two locations on the forearm (between-site). Heating was repeated after a break of 24-72 hours (between-day). Reproducibility of skin responses at 33-42°C is presented for absolute CVC and relative CVC responses corrected for maximal CVC at 44°C (%CVCmax ). RESULTS: Between-day reproducibility of baseline CVC and %CVCmax for both sites was relatively poor (22-30%). At 42°C, CVC and %CVCmax responses showed less variation (9-19%), whilst absolute CVC responses at 44°C were 14-17%. Between-day variation for %CVCmax increased when using data from site 1 on day 1, but site 2 on the subsequent day (25%). CONCLUSION: Day-to-day reproducibility of baseline laser Doppler-derived skin perfusion responses is poor, but acceptable when absolute and relative skin perfusion to a local gradual heating protocol is utilized and site-to-site variation is minimized.
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Calor , Microcirculación , Óxido Nítrico/metabolismo , Piel/irrigación sanguínea , Vasodilatación , Adolescente , Adulto , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Piel/metabolismoRESUMEN
PURPOSE: Previous studies that have examined the impact of exercise intensity on conduit artery endothelial function have involved large muscle group exercise which induces local and systemic effects. The aim of this study was to examine flow-mediated dilation (FMD) before and after incremental intensities of handgrip exercise (HE), to assess the role of local factors such as blood flow and shear rate on post-exercise brachial artery function. METHODS: Eleven healthy men attended the laboratory on three occasions. Subjects undertook 30 min of handgrip exercise at three intensities (5, 10 or 15 % MVC). Brachial artery FMD, shear and blood flow patterns were examined before, immediately after and 60 min post exercise. RESULTS: Handgrip exercise increased mean and antegrade shear rate (SR) and blood flow (BF) and reduced retrograde SR and BF (all P < 0.01). Exercise intensity was associated with a dose-dependent increase in both mean and antegrade BF and SR (interaction, P < 0.01). Post-hoc tests revealed that, whilst handgrip exercise did not immediately induce post-exercise changes, FMD was significantly higher 60 min post-exercise following the highest exercise intensity (5.9 ± 2.8-10.4 ± 5.8 %, P = 0.01). CONCLUSIONS: Handgrip exercise leads to intensity-and time-dependent changes in conduit artery function, possibly mediated by local increases in shear, with improvement in function evident at 1 h post-exercise when performed at a higher intensity.
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Arteria Braquial/fisiología , Fuerza de la Mano/fisiología , Entrenamiento de Fuerza , Vasodilatación/fisiología , Adulto , Presión Arterial/fisiología , Arteria Braquial/anatomía & histología , Endotelio Vascular/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Modelos Lineales , Masculino , Contracción Muscular/fisiología , Especies Reactivas de Oxígeno/metabolismo , Flujo Sanguíneo Regional/fisiología , Adulto JovenRESUMEN
CONTEXT: Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights. OBJECTIVE: The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED. DATA SOURCES: CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date. DATA EXTRACTION: Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (<26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. DATA ANALYSIS: Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies. CONCLUSION: Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD 42023398774.
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BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia worldwide and is linked to a higher risk of mortality and morbidity. To predict AF and AF-related complications, clinical risk scores are commonly employed, but their predictive accuracy is generally limited, given the inherent complexity and heterogeneity of patients with AF. By classifying different presentations of AF into coherent and manageable clinical phenotypes, the development of tailored prevention and treatment strategies can be facilitated. In this study, we propose an artificial intelligence (AI)-based methodology to derive meaningful clinical phenotypes of AF in the general and critical care populations. METHODS: Our approach employs generative topographic mapping, a probabilistic machine learning method, to identify micro-clusters of patients with similar characteristics. It then identifies macro-cluster regions (clinical phenotypes) in the latent space using Ward's minimum variance method. We applied it to two large cohort databases (UK-Biobank and MIMIC-IV) representing general and critical care populations. FINDINGS: The proposed methodology showed its ability to derive meaningful clinical phenotypes of AF. Because of its probabilistic foundations, it can enhance the robustness of patient stratification. It also produced interpretable visualisation of complex high-dimensional data, enhancing understanding of the derived phenotypes and their key characteristics. Using our methodology, we identified and characterised clinical phenotypes of AF across diverse patient populations. INTERPRETATION: Our methodology is robust to noise, can uncover hidden patterns and subgroups, and can elucidate more specific patient profiles, contributing to more robust patient stratification, which could facilitate the tailoring of prevention and treatment programs specific to each phenotype. It can also be applied to other datasets to derive clinically meaningful phenotypes of other conditions. FUNDING: This study was funded by the DECIPHER project (LJMU QR-PSF) and the EU project TARGET (10113624).
RESUMEN
Exercise training is associated with rapid changes in endothelium-dependent vasodilation, which occur within days of training. Whilst long-term physical inactivity has potent effects on vascular structure, little is known about the immediate impact of inactivity on vascular function. Aim of this study was to measure vascular function before, during (day 4) and after 8 days of unilateral forearm inactivity. Thirteen healthy male subjects (22 ± 1 years) were instructed to wear a sling on the non-dominant arm to induce local inactivity. Before, during (at 4 days) and after the 8-day intervention, we used echo Doppler to measure bilateral brachial artery dilator response to 5-min ischaemia [i.e. flow-mediated dilation (FMD)], ischaemic handgrip exercise (iEX) and endothelium-independent dilation to a NO donor [i.e. glyceryl trinitrate (GTN)]. Maximal handgrip strength of the inactive forearm significantly decreased after 8 days (t tests P = 0.03 for Day 0 vs. Day 8), confirming physical deconditioning in the inactive forearm. A significant decrease in peak blood flow was found in the intervention arm (sling: 539 ± 236, 528 ± 184, 384 ± 142 ml/min) relative to the control arm (559 ± 181, 591 ± 219, 613 ± 169 ml/min; 2-way ANOVA interaction: P = 0.05). Analysis revealed no significant change in brachial artery baseline diameter, FMD %, iEX or GTN across the 8 days in either arm (P > 0.05). Eight days of forearm physical inactivity induced a significant decrease in post-ischaemic limb blood flow, suggestive of remodelling of forearm resistance vessels. However, measures of conduit artery endothelium-dependent vasodilation were not altered across an 8-day period of inactivity, suggesting that initial remodelling occurs at distal ends of the vascular tree.
Asunto(s)
Arteria Braquial/fisiopatología , Endotelio Vascular/fisiopatología , Contracción Muscular , Músculo Esquelético/irrigación sanguínea , Vasodilatación , Análisis de Varianza , Velocidad del Flujo Sanguíneo , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/efectos de los fármacos , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/efectos de los fármacos , Antebrazo , Fuerza de la Mano , Humanos , Inmovilización , Isquemia/fisiopatología , Masculino , Donantes de Óxido Nítrico/administración & dosificación , Nitroglicerina/administración & dosificación , Flujo Sanguíneo Regional , Factores de Tiempo , Ultrasonografía Doppler , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificación , Adulto JovenRESUMEN
Acute exercise can result in temporary decrease in endothelial functions, which may represent a transient period of risk. Numerous mechanisms underpinning these responses included release of extracellular vesicles (EVs) derived from apoptotic or activated endothelial cells and platelets. This study aims to compare the time course of endothelial responses to moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) and the associations with EV release. Eighteen young healthy males (age: 22.6 ± 3.7 years, BMI: 25.6 ± 2.5 m2/kg, and VO2peak: 38.6 ± 6.5 mL/kg/min) completed two randomly assigned exercises: HIIE (10 × 1 min-@-90% heart rate reserve (HRR) and 1 min passive recovery) and MICE (30 min-@-70% HRR) on a cycle ergometer. Flow-mediated dilation (FMD) was used to assess endothelial function and blood samples were collected to evaluate endothelial cell-derived EV (CD62E+) and platelet-derived EV (CD41a+), 10, 60, and 120 min before and after exercise. There were similar increases but different time courses (P = 0.017) in FMD (increased 10 min post-HIIE, P < 0.0001 and 60 min post-MICE, P = 0.038). CD62E+ remained unchanged (P = 0.530), whereas overall CD41a+ release was reduced 60 min post-exercise (P = 0.040). FMD was not associated with EV absolute release or change (P > 0.05). Acute exercise resulted in similar improvements, but different time course in FMD following either exercise. Whilst EVs were not associated with FMD, the reduction in platelet-derived EVs may represent a protective mechanism following acute exercise.
Asunto(s)
Vesículas Extracelulares , Vasodilatación , Humanos , Masculino , Vasodilatación/fisiología , Endotelio Vascular/fisiología , Células Endoteliales , Terapia por EjercicioRESUMEN
Although evidence demonstrates the fundamental role of shear stress in vascular health, predominantly through the release of nitric oxide (NO), the mechanisms by which endothelial cells (EC)s sense and transduce shear are poorly understood. In cultured ECs tyrosine phosphorylation of PECAM-1 has been shown to activate eNOS in response to shear stress. However, in the human skeletal muscle microcirculation PECAM-1 was not activated in response to exercise or passive leg movement. Given this contradiction, this study aimed to assess the effect of exercise on conduit artery PECAM-1 and eNOS activation in humans. Eleven males were randomised to two groups; 30â min of handgrip exercise (n = 6), or a time-control group (n = 5). Protein content of eNOS and PECAM-1, alongside eNOS Ser1177 and PECAM-1 Tyr713 phosphorylation were assessed in ECs obtained from the radial artery pre- and post-intervention. Handgrip exercise resulted in a 5-fold increase in mean shear rate in the exercise group, with no change in the control group (group*time, P < 0.001). There was a 54% increase in eNOS Ser1177 phosphorylation in the exercise group, when compared to control group (group*time, P = 0.016), but no change was reported in PECAM-1 Tyr713 phosphorylation in either group (group*time, P > 0.05). eNOS and PECAM-1 protein content were unchanged (group*time, P > 0.05). Our data show that exercise-induced elevations in conduit artery shear rate increase eNOS Ser1177 phosphorylation but not PECAM-1 Tyr713 phosphorylation. This suggests PECAM-1 phosphorylation may not be involved in the vascular response to acute but prolonged elevations in exercise-induced shear rate in conduit arteries of healthy, active men.
Asunto(s)
Células Endoteliales , Fuerza de la Mano , Humanos , Masculino , Arterias , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Óxido Nítrico/metabolismo , Fosforilación , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Estrés MecánicoRESUMEN
Reduced hepatic lactate elimination initiates blood lactate accumulation during incremental exercise. In this study, we wished to determine whether renal lactate elimination contributes to the initiation of blood lactate accumulation. The renal arterial-to-venous (a-v) lactate difference was determined in nine men during sodium lactate infusion to enhance the evaluation (0.5 mol x L(-1) at 16 ± 1 mL x min(-1); mean ± s) both at rest and during cycling exercise (heart rate 139 ± 5 beats x min(-1)). The renal release of erythropoietin was used to detect kidney tissue ischaemia. At rest, the a-v O(2) (CaO(2)-CvO(2)) and lactate concentration differences were 0.8 ± 0.2 and 0.02 ± 0.02 mmol x L(-1), respectively. During exercise, arterial lactate and CaO(2)-CvO(2) increased to 7.1 ± 1.1 and 2.6 ± 0.8 mmol x L(-1), respectively (P < 0.05), indicating a -70% reduction of renal blood flow with no significant change in the renal venous erythropoietin concentration (0.8 ± 1.4 U x L(-1)). The a-v lactate concentration difference increased to 0.5 ± 0.8 mmol x L(-1), indicating similar lactate elimination as at rest. In conclusion, a -70% reduction in renal blood flow does not provoke critical renal ischaemia, and renal lactate elimination is maintained. Thus, kidney lactate elimination is unlikely to contribute to the initial blood lactate accumulation during progressive exercise.
Asunto(s)
Ciclismo/fisiología , Ejercicio Físico/fisiología , Riñón/metabolismo , Lactatos/metabolismo , Adulto , Arterias/metabolismo , Eritropoyetina/sangre , Humanos , Isquemia/sangre , Riñón/irrigación sanguínea , Lactatos/sangre , Masculino , Consumo de Oxígeno , Flujo Sanguíneo Regional , Descanso , Lactato de Sodio/metabolismo , Adulto JovenRESUMEN
BACKGROUND: There are few examples of interventions designed to promote physical activity (PA) in adults with Cystic fibrosis (CF). Increasing levels of habitual PA may be more feasible and result in greater compliance than conventional exercise training inventions which give little or no attention to long-term PA behaviour. Despite this there is limited research exploring perceptions of PA among adults with CF. The study aimed to understand the ecological correlates of PA in adults with CF and to involve individuals with CF, their families (where applicable) and clinicians in a formative process to inform the development of an ecological approach to PA promotion in this population. METHODS: An iterative approach was utilised, whereby findings from earlier phases of the research informed subsequent phases. Semi-structured interviews were conducted to explore patients' perceptions of PA, devised using the PRECEDE component of the PRECEDE-PROCEED model. Followed by, focus groups to discuss the perceived barriers, facilitators and opportunities for PA participation and how this information could inform the development and delivery of a PA intervention. Separate focus groups were conducted with individuals with CF (n = 11) and their families and CF MDT members. Thematic analysis was used to construct themes. RESULTS: Physical and mental wellbeing manifested as both barriers and facilitators of PA. CF is characterised by a progressive decline in physical function, which presents as a number of challenging symptoms and set-backs for an individual with CF. PA represents an opportunity for participants to slow the rate of this decline and manage the symptoms associated with the condition. Enjoyment was an important facilitator of PA. Exercise professionals and family reinforce PA behaviour, particularly during adolescence. CONCLUSIONS: PA promotion should form part of routine CF care with additional exercise professional support during adolescence.