Exercise intensity as a mediator of central and peripheral vascular integrity

Vascular homeostasis is a vital element of health. Exercise plays a role in maintaining the integrity of the vascular endothelium via transient increases in endothelial shear stress that accompany exercise-induced hyperaemia. This hyperaemia and stimulus it presents to the vasculature is governed by exercise intensity. Exercise is the primary therapy in cardiac rehabilitation contexts, a population with typically elevated cardiovascular risk factors and compromised vascular integrity. In the UK, cardiac rehabilitation may be ineffective for improving long-term health outcomes. This thesis demonstrates that the exercise intensities achieved by patients in UK cardiac rehabilitation were variable and generally low. The exercise performed had no impact upon indices of peripheral vascular structure or function and little effect upon short-term health outcomes. A service-level intervention was implemented to increase the dose of exercise achieved by patients via an increase in intensity and examine its effects upon the vasculature. In a subsequent cohort, the intervention was unsuccessful at modifying the exercise intensities that were achieved or indices of peripheral vascular structure or function. However, a positive relationship between the intensity achieved at the end of the programme and changes in vascular function was found. Although peripheral vascular integrity is easily studied it is perhaps less relevant to health compared to central vascular integrity. Assessments of the central circulation during exercise have previously relied upon high-risk, invasive techniques. Therefore, to understand the stimulus presented to the central vasculature by exercise at intensities akin to those achieved in cardiac rehabilitation, a novel technique was applied: using cardiac magnetic resonance imaging during cycling in a healthy cohort. This technique was unable to capture the changes in perfusion of the central circulation that should have occurred with exercise at different intensities but successfully demonstrated reproducible assessments of cardiac dynamics during exercise of different intensities

Extracorporeal Shockwave for Intermittent Claudication and Quality of Life: A Randomized Clinical Trial

Importance Intermittent lower limb claudication limits function and quality of life. Supervised exercise programs are not readily available, and a noninvasive alternative is needed.Objective To assess extracorporeal corporeal shockwave therapy in improving quality of life in patients with claudication.Design, Setting, and Participants In this double-blind, placebo-controlled randomized clinical trial, patients in the outpatient setting at a single tertiary center for vascular surgery were randomized in a 1:1 ratio to extracorporeal shockwave therapy or placebo therapy with no shockwaves delivered. Recruitment was between June 2015 and January 2020, with 12-week follow-up ending in March 2020. A convenience sample of patients with claudication and conservative treatment requirements who refused or were unable to participate in supervised exercise were eligible. Patients receiving anticoagulation therapy or with an active cancer were excluded. Of 522 patients screened, 389 were eligible, 138 were enrolled, and 110 completed follow-up and were included in the primary analysis. Statistical analysis was completed by May 2021.Intervention In the intervention group, patients received 100 impulses of 0.1mJ/mm/cm2 in an area of the gastrocnemius muscle 3 times weekly for 3 weeks. The steps for treatment were replicated for the control group without delivering the treatment.Main Outcomes and Measures The primary outcome was the Physical Functioning domain of the 36-item Short-Form Quality of Life Questionnaire at 12-week follow-up. Secondary outcomes included walking distances, ankle brachial pressure index, and other quality-of-life measures.Results Of 138 patients recruited and randomized, 92 (67%) were male, and the mean (SD) age of the study population was 67 (9.6) years. The intervention group had a significantly higher physical function score at 12 weeks (estimated median difference 3.8; 95% CI, 0.0-7.7; P = .03). However, this significance did not remain when adjusting for covariates. At 12 weeks, the intervention group had significantly longer pain-free and maximum walking distances (pain-free estimated median difference, 34.1, 95% CI, 11.4-56.8; P = .004; maximum estimated median difference, 51.4; 95% CI, 10.7-86.5; P = .01).Conclusions and Relevance To our knowledge, this is the first double-blind, placebo-controlled, randomized clinical trial to consider extracorporeal shockwave therapy for the management of intermittent claudication. It demonstrated efficacy for walking distances, may have a positive effect on quality of life, and may provide a safe, noninvasive alternative therapy for patients with intermittent claudication

A systematic review of exercise intervention reporting quality and dose in studies of intermittent claudication

Background: Exercise therapy is an important treatment option for people with intermittent claudication (IC). Appropriate reporting of exercise interventions in populations with IC within randomised controlled trials (RCTs) is important to ensure that research can be translated into clinical practice. Therefore, the purpose of our review is to evaluate the reporting of exercise interventions in RCTs of exercise therapy in patients with IC. Methods: A systematic search was performed to identify relevant trials in patients with IC published until May 2020. Studies including only participants with critical-limb ischemia or asymptomatic peripheral artery disease were excluded. Each trial was scored using the recently developed ‘Consensus on Exercise Reporting Template’ (CERT) which has a maximum obtainable score of 19. Results: Of 1489 unique records identified from the search, 73 trials were included reporting 107 exercise interventions. Overall, the average CERT score was 10/19. The exercise equipment used, the use of supervision and a description of whether the exercise prescription was tailored or generic were the most frequently reported intervention components. The motivational strategies used, intervention adherence, and intervention fidelity were the most under reported CERT components. There was no trend indicating that CERT scores were higher in more recent publications. Conclusions: We have identified that important details about exercise interventions are frequently missing from the published literature. These missing data hinder replication of research findings and limit the translation of evidence into clinical practice

Provision of exercise services in patients with peripheral artery disease in the United Kingdom

OBJECTIVES: Supervised exercise programmes (SEPs) are a vital treatment for people with intermittent claudication, leading improvements in walking distance and quality of life and are recommended in multiple national and international guidelines. We aimed to evaluate the use and structure of SEPs in the United Kingdom (UK). DESIGN: We conducted an anonymous online survey using the Jisc platform comprising of 40 questions. The survey was designed to address key areas such as access, provision, uptake and delivery of SEPs in the United Kingdom. Ethical approval was obtained from Coventry University (P108729). METHODS: The list of trusts providing vascular services was obtained from the National Vascular Registry (NVR) report. The survey was disseminated via social media, The Vascular Society of Great Britain and Ireland and the Society for Vascular Technology. Data were exported to a Microsoft Excel document and analysed using simple descriptive statistics. RESULTS: Of 93 vascular units identified, we received response from 48. Of these, 23 had access to an exercise programme (48%). The majority of SEPs were exclusively for PAD patients (77%), with 21% using integrated services. 67% of respondents were providing a circuit-based programme, and 5 out of 23 were meeting the dose recommendations in the UK National Institute for Health and Care Excellence (NICE) guidelines. Respondents felt that programmes were moderately to extremely important to patients, slightly to very important to clinicians and not at all important to slightly important to commissioning/funding bodies. CONCLUSION: SEPs are a well-established first-line treatment for patients with IC and they are recommended by NICE guidelines. Despite this, many patients still do not have access to an exercise programme, and clinicians do not feel that they have support from commissioning/funding bodies to develop them. There is an urgent need for funding, development and delivery of SEPs in the United Kingdom

A preoperative supervised exercise program potentially improves long-term survival after elective abdominal aortic aneurysm repair

Objective: A preoperative supervised exercise program (SEP) improves cardiorespiratory fitness and perioperative outcomes for patients undergoing elective abdominal aortic aneurysm (AAA) repair. The aim of this study was to assess the effect of a preoperative SEP on long-term survival of these patients. A secondary aim was to consider long-term changes in cardiorespiratory fitness and quality of life. Methods: Patients scheduled for open or endovascular AAA repair were previously randomized to either a 6-week preoperative SEP or standard management, and a significant improvement in a composite outcome of cardiac, pulmonary, and renal complications was seen following SEP. For the current analysis, patients were followed up to 5 years post-surgery. The primary outcome for this analysis was all-cause mortality. Data were analyzed on an intention to treat (ITT) and per protocol (PP) basis, with the latter meaning that patients randomized to SEP who did not attend any sessions were excluded. The PP analysis was further interrogated using a complier average causal effect (CACE) analysis on an all or nothing scale, which adjusts for compliance. Additionally, patients who agreed to follow-up attended the research center for cardiopulmonary exercise testing and/or provided quality of life measures. Results: ITT analysis demonstrated that the primary endpoint occurred in 24 of the 124 participants at 5 years, with eight in the SEP group and 16 in the control group (P =.08). The PP analysis demonstrated a significant survival benefit associated with SEP attendance (4 vs 16 deaths; P =.01). CACE analysis confirmed a significant intervention effect (hazard ratio, 0.36; 95% confidence interval, 0.16-0.90; P =.02). There was no difference between groups for cardiorespiratory fitness measures and most quality of life measures. Conclusions: These novel findings suggest a long-term mortality benefit for patients attending a SEP prior to elective AAA repair. The underlying mechanism remains unknown, and this merits further investigation

High INtensity Interval Training In pATiEnts with intermittent claudication (INITIATE): protocol for a multicentre, proof-of-concept, prospective interventional study

INTRODUCTION: The first-line recommended treatment for patients with intermittent claudication (IC) is a supervised exercise programme (SEP), which includes a minimum of 2-hours of exercise per week over a 12-week period. However, provision, uptake and adherence rates for these SEP programmes are poor, with time constraints cited as a common participant barrier. High-intensity interval training (HIIT) is more time-efficient and therefore has the potential to overcome this barrier. However, evidence is lacking for the role of HIIT in those with IC. This proof-of-concept study aims to consider the safety, feasibility, tolerability and acceptability of a HIIT programme for patients with IC. METHODS AND ANALYSIS: This multicentre, single-group, prospective, interventional feasibility study will recruit 40 patients with IC, who will complete 6 weeks of HIIT, 3 times a week. HIIT will involve a supervised programme of 10×1 min high-intensity cycling intervals at 85%-90% peak power output (PPO), interspaced with 10×1 min low intensity intervals at 20%-25% PPO. PPO will be determined from a baseline cardiopulmonary exercise test (CPET) and it is intended that patients will achieve ≥85% of maximum heart rate from CPET, by the end of the second HIIT interval. Primary outcome measures are safety (occurrence of adverse events directly related to the study), programme feasibility (including participant eligibility, recruitment and completion rates) and HIIT tolerability (ability to achieve and maintain the required intensity). Secondary outcomes include patient acceptability, walking distance, CPET cardiorespiratory fitness measures and quality of life outcomes. ETHICS AND DISSEMINATION: Ethical approval was obtained via a local National Health Service research ethics committee (Bradford Leeds - 18/YH/0112) and recruitment began in August 2019 and will be completed in October 2020. Results will be published in peer-reviewed journals and presented at international conferences and are expected to inform a future pilot randomised controlled trial of HIIT versus usual-care SEPs. TRIAL REGISTRATION NUMBER: NCT04042311; Pre-results

High-intensity interval training in patients with intermittent claudication: Presented at the 2022 Vascular Society of Great Britain and Ireland Annual Scientific Meeting, Brighton, United Kingdom, November 23-25, 2022; presented at the 2023 Surgical Research Society Meeting, Nottingham, United Kingdom, March 22-24, 2023; and presented at the 2023 Vascular Annual Meeting of the Society for Vascular Surgery, National Harbor, MD, June 14-17, 2023

Objective: Provision, uptake, adherence, and completion rates for supervised exercise programs (SEP) for intermittent claudication (IC) are low. A shorter, more time-efficient, 6-week, high-intensity interval training (HIIT) program may be an effective alternative that is more acceptable to patients and easier to deliver. The aim of this study was to determine the feasibility of HIIT for patients with IC. Methods: A single arm proof-of-concept study, performed in secondary care, recruiting patients with IC referred to usual-care SEPs. Supervised HIIT was performed three times per week for 6 weeks. The primary outcome was feasibility and tolerability. Potential efficacy and potential safety were considered, and an integrated qualitative study was undertaken to consider acceptability. Results: A total of 280 patients were screened: 165 (59%) were eligible, and 40 (25%) were recruited. The majority (n = 31; 78%) of participants completed the HIIT program. The remaining nine patients were withdrawn or chose to withdraw. Completers attended 99% of training sessions, completed 85% of sessions in full, and performed 84% of completed intervals at the required intensity. There were no related serious adverse events. Maximum walking distance (+94 m; 95% confidence interval, 66.6-120.8 m) and the SF-36 physical component summary (+2.2; 95% confidence interval, 0.3-4.1) were improved following completion of the program. Conclusions: Uptake to HIIT was comparable to SEPs in patients with IC, but completion rates were higher. HIIT appears feasible, tolerable, and potentially safe and beneficial for patients with IC. It may provide a more readily deliverable, acceptable form of SEP. Research comparing HIIT with usual-care SEPs appears warranted