Women have a lower age-matched cardiovascular risk than men, largely due to estrogen’s protective role in endothelial function. While exercise improves vascular health, acute vascular responses are influenced by factors such as age, fitness level, metabolic status, and exercise modality. In premenopausal women, fluctuations in estrogen levels during the menstrual cycle may further affect vascular reactivity. Here, we review current evidence on acute exercise-induced vascular responses in women, emphasizing menstrual phase influences and key biomarkers such as flow-mediated dilation (FMD), along with others including vascular conductance and pulse wave velocity (PWV). Despite limited and heterogeneous evidence, shear-induced vascular responses, (including FMD) following acute exercise, appear to be relatively stable across menstrual cycle phase, suggesting that strict phasic control may not always be necessary. However, future high-quality studies are needed to further clarify this response. In contrast, other vascular assessments that rely more heavily on neural components—such as vascular conductance and PWV—show greater estrogen sensitivity. Nonetheless, the inconsistencies between studies again underscore the need for future research with hormonal verification. Morever, adequate sample sizes, and standardized exercise protocols will improve both consistency and help develop and promote the inclusion of women in vascular research.

Introduction Development of clinical skills in areas, such as exercise risk stratification, testing, prescription, monitoring and outcome assessment, is vital for patient safety and clinical effectiveness in clinical exercise physiology (CEP). This study explored how current CEP courses are being taught and assessed and to identify potential best practice recommendations from a variety of stakeholdersMethods Qualitative methods were employed to explore the thoughts of CEPs, academics and current students regarding the teaching and assessment of CEPs in the UK. Research design involved (1) semistructured interviews with students (n=16) and (2) focus groups with academics (n=8) and CEP (n=5) stakeholders. Data obtained were audio recorded using a portable Dictaphone and transcribed verbatim, then thematically analysed manually.Results Three themes: (1) in situ learning/real-world practice (working with patients and specialist practitioners); (2) programme design (scaffold learning and integrated modules) and (3) teaching approach (simulated learning and research competency) were generated concerning teaching methods and approaches across CEP postgraduate degrees. The current use of simulated tasks for the delivery of taught content was identified as lacking effectiveness, with clinical placements identified as being the most important source of knowledge and skill attainment due to the real-world exposure to patients and practitioners. Clinical placements and simulated learning were recognised as the two main methods of problem-based learning used to develop student knowledge, skills and competency to practice. Two themes (placement tariffs/assessors in situ and role play/simulation) were identified for the assessment of students.Conclusion Clinical placements remain the optimal method for developing the knowledge, skills and competency to practice for student CEPs. However, suitable placements remain limited, and novel approaches such as university-led exercise services require consideration for student competency development. A standardised and accredited training pathway from undergraduate through to postgraduate level should be explored to allow student competency to be developed over a longer period, to enhance knowledge, skills and competency on graduation and registration.

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.

ABSTRACT Background In the UK Academy of Healthcare Science, registered clinical exercise physiologists (CEPs) receive specialist, master’s-level education and training in the knowledge and skills required to work with chronic and complex medical conditions based on a curriculum that was benchmarked against Australian standards. The aim of this study was to explore the perspectives of multiple stakeholders to identify the key knowledge and skills required for a registered CEP to work effectively in the United Kingdom and inform future iterations of the accredited curriculum. Methods Semistructured interviews of academics (n = 5), CEPs (n = 5) and service users (n = 5) explored perspectives of the key knowledge and skills required of a CEP in UK health care. Reflexive thematic analysis was performed to identify the key knowledge and skills of a UK-registered CEP that all the stakeholders deemed important. Results Six themes were identified from the interviews. The CEP-specific themes were identified as pathophysiology, physiological assessments, exercise prescription, exercise delivery, and behavior change and education. Clinical practice was recognized as the overarching concept that linked all the CEP-specific themes together. Conclusion This study provides the first understanding of the knowledge and skills required for a CEP to work effectively in the UK health care system, in addition to providing research evidence and insight to the next iterations of the Clinical Exercise Physiology UK (CEP-UK) curriculum framework. Future research should focus on establishing a more comprehensive, definitive list of the knowledge and skills of a UK CEP that will contribute to subsequent versions of the CEP-UK curriculum framework.

Purpose A priori cardiovascular (CV) health status may impact reductions in risk factors and CV mortality and morbidity following exercise training, although this is not fully understood. Therefore, the purpose of the study was to examine if endothelial function (assessed via flow mediated dilation; FMD%), predicts the magnitude of change in CV risk factors or fitness following exercise training. Methods We pooled data from 338 individuals who underwent supervised exercise training (8–26 weeks). Using recent sex- and age-specific reference values for flow-mediated dilation (FMD%), we categorised participants as having preserved endothelial function (P-EF) (> 50th percentile of reference value, 56 females, 67 males, 46 ± 17 years) or reduced endothelial function (R-EF) (< 50th percentile of reference value, 67 females, 148 males, 48 ± 17 years). The effects of exercise training on cardiovascular risk factors (BMI, cholesterol, glucose and triglycerides), cardiorespiratory fitness (VO 2peak ) and vascular function (FMD%) were examined using a two-way mixed design general linear model. Results Exercise training significantly improved physical fitness ( P < 0.001), with no difference in the magnitude of improvement between P-EF and R-EF. Modest but significant reductions were present in BMI, blood pressure and total cholesterol (all P < 0.005), with no difference between P-EF and R-EF groups in the magnitude of changes in these variables with training. Exercise training did not significantly alter glucose, triglycerides, high density lipoprotein (HDL) and low-density lipoprotein (LDL) (all P > 0.05). Conclusion Individuals with reduced and preserved a priori endothelial function status can obtain benefits from exercise in terms of risk factor modification and fitness change. Therefore, exercise has the potential to be beneficial in all clinical groups.

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.

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).

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.

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. 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

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; 30 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.

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. Thirty untrained, healthy, young men completed a cycling test to exhaustion to determine peak oxygen uptake (V̇O2peak), 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

Cardiovascular disease (CVD) is highly prevalent and contributes to disease burden and mortality in older adults. 1 American Heart Association2019 heart disease & stroke statistical update fact sheet: older Americans & cardiovascular diseases. https://www.heart.org/idc/groups/ahamah-public/@wcm/@sop/@smd/documents/downloadable/ucm_502138.pdf?utm_campaign=sciencenews17-18&utm_source=science-news&utm_medium=heart&utm_content=heart07-25-18Date: 2019 Date accessed: July 13, 2020 Google Scholar The American Heart Association concluded that CVD is the leading cause of death in octogenarians, followed by cancer and Alzheimer's disease. 1 American Heart Association2019 heart disease & stroke statistical update fact sheet: older Americans & cardiovascular diseases. https://www.heart.org/idc/groups/ahamah-public/@wcm/@sop/@smd/documents/downloadable/ucm_502138.pdf?utm_campaign=sciencenews17-18&utm_source=science-news&utm_medium=heart&utm_content=heart07-25-18Date: 2019 Date accessed: July 13, 2020 Google Scholar Studies questioned the validity of traditional CVD risk factors to predict CVD-related events in older adults. 2 Odden M.C. Shlipak M.G. Whitson H.E. et al. Risk factors for cardiovascular disease across the spectrum of older age: The Cardiovascular Health Study. Atherosclerosis. 2014; 237: 336-342 Abstract Full Text Full Text PDF PubMed Google Scholar ,3 de Ruijter W. Westendorp R.G.J. Assendelft W.J.J. et al. Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study. BMJ. 2009; 338: a3083 Crossref PubMed Scopus (243) Google Scholar Therefore, we explored differences in nontraditional risk factors between octogenarians with vs without cardiovascular events across a 4.5-year follow-up.

An understanding of physical activity (PA) and related health benefits remains limited in adults with Cystic Fibrosis (CF). Raw acceleration data metrics may improve the quality of assessment and further this understanding. The study aimed to compare PA between people with CF (pwCF) and non-CF peers and examine associations between PA, vascular function and health outcome measures. PA was assessed in 62 participants (31 pwCF) using ActiGraph accelerometers. Vascular function (a marker of cardiovascular disease risk) was assessed using flow-mediated dilatation (FMD) in sub-groups of pwCF (n = 12) and matched controls. Average Euclidean norm minus one (ENMO) (total PA) was significantly lower (p = 0.005) in pwCF (35.09 +/- 10.60 mg), than their non-CF peers (44.62 +/- 13.78 mg). PwCF had PA profiles (intensity gradient) indicative of more time in lower intensity activity (-2.62 +/- 0.20, -2.37 +/- 0.23). Vigorous activity was positively associated with lung function (r(s) = 0.359) and Quality of Life (r = 0.412). There were no significant differences (p = 0.313) in FMD% between pwCF (5.29 +/- 2.76%) and non-CF peers (4.34 +/- 1.58%) and no associations with PA. PwCF engaged in less moderate-to-vigorous PA and demonstrated a steeper PA profile than their non-CF peers.

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<0.05), with normalization of FMD in medicated men, but not women with dyslipidemia. In conclusion, sex alters the age-related decline in FMD, which may partly be explained through differences in baseline diameter. Sex also alters the influence of some CVD risk factors and medication on FMD. This work improves interpretation and future use of the FMD technique.

We used a within‐subject, cross‐over design study to compare the impact of 4‐weeks' resistance (RT) versus endurance (END) training on vascular function. We subsequently explored the association of intra‐individual effects of RT versus END on vascular function with a single nucleotide polymorphism (SNP) of theNOS3gene. Thirty‐five healthy males (21 ± 2 years old) were genotyped for theNOS3rs2070744 SNP and completed both training modalities. Participants completed 12 sessions over a 4‐week period, either RT (leg‐extension) or END (cycling) training in a randomized, balanced cross‐over design with a 3‐week washout period. Participants performed peak oxygen uptake (peak VO2) and leg‐extension single‐repetition maximum (1‐RM) testing, and vascular function assessment using flow‐mediated dilation (FMD) on 3 separated days pre/post‐training. Peak VO2increased after END (p < 0.001), while 1‐RM increased after RT (p < 0.001). FMD improved after 4‐weeks’ training (time effect:p = 0.006), with no difference between exercise modalities (interaction effect:p = 0.92). No relation was found between individual changes (delta, pre‐post) in FMD to both types of training (R2 = 0.06,p = 0.14). Intra‐individual changes in FMD following END and RT were associated with theNOS3SNP, with TT homozygotes significantly favoring only END (p = 0.016) and TC/CC tending to favor RT only (p = 0.056). Although both training modes improved vascular function, significant intra‐individual variation in the adaptation of FMD was found. The association withNOS3genotype suggests a genetic predisposition to FMD adapting to a specific mode of chronic exercise. This study therefore provides novel evidence for personalized exercise training to optimize vascular health.

We found that resistance and endurance exercise modalities lead to different endothelial function responses after a single bout of exercise. Endothelial function increased after an acute bout of resistance exercise, whereas it decreased after an acute bout of endurance exercise. Four weeks of chronic exercise training did not affect the acute endothelial function response.

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. 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). 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. 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.

Abstract Purpose Muscular dystrophy (MD) is an umbrella term for muscle wasting conditions, for which longitudinal changes in function and body composition are well established in children with Duchenne (DMD), however, changes in adults with DMD and Beckers (BMD), respectively, remain poorly reported. This study aims to assess 12-month changes in lower-limb strength, muscle size, body composition and physical activity in adults with Muscular Dystrophy (MD). Methods Adult males with Duchenne MD (DMD; N = 15) and Beckers MD (BMD; N = 12) were assessed at baseline and 12-months for body composition (Body fat and lean body mass (LBM)), Isometric maximal voluntary contraction (Knee-Extension (KEMVC) and Plantar-Flexion (PFMVC)) and physical activity (tri-axial accelerometry). Results 12-Month change in strength was found as −19% (PFMVC) and −14% (KEMVC) in DMD. 12-Month change in strength in BMD, although non-significant, was explained by physical activity (R 2=0.532–0.585). Changes in LBM (DMD) and body fat (BMD) were both masked by non-significant changes in body mass. Discussion 12-Month changes in adults with DMD appear consistent with paediatric populations. Physical activity appears important for muscle function maintenance. Specific monitoring of body composition, and potential co-morbidities, within adults with MD is highlighted. Implications for rehabilitation Quantitative muscle strength assessment shows progressive muscle weakness in adults with Duchenne Muscular Dystrophy is comparable to paediatric reports (−14 to −19%). Physical activity should be encouraged in adults with Beckers Muscular Dystrophy, anything appears better than nothing. Body composition, rather than body mass, should be monitored closely to identify any increase in body fat.