Plasma Desmosine and Abdominal Aortic Aneurysm Disease

Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the breakdown of elastin within the aortic tunica media, leading to aortic dilatation and rupture. The aim of this study was to investigate the association of plasma desmosine (pDES), an elastin-specific degradation product, with disease severity and clinical outcome in patients with AAA. Methods and Results We measured pDES and serum biomarker concentrations in 507 patients with AAAs (94% men; mean age, 72.4±6.1 years; mean AAA diameter, 48±8 mm) and 162 control subjects (100% men; mean age, 71.5±4.4 years) from 2 observational cohort studies. In the longitudinal cohort study (n=239), we explored the incremental prognostic value of pDES on AAA events. pDES was higher in patients with AAA compared with control subjects (mean±SD: 0.46±0.22 versus 0.33±0.16 ng/mL; P<0.001) and had the strongest correlation with AAA diameter (r=0.39; P<0.0001) of any serum biomarker. After adjustment for baseline AAA diameter, pDES was associated with an AAA event (hazard ratio, 2.03 per SD increase [95% CI, 1.02-4.02]; P=0.044). In addition to AAA diameter, pDES provided incremental improvement in risk stratification (continuous net reclassification improvement, 34.4% [95% CI, -10.8% to 57.5%; P=0.09]; integrated discrimination improvement, 0.04 [95% CI, 0.00-0.15; P=0.050]). Conclusions pDES concentrations predict disease severity and clinical outcomes in patients with AAA. Clinical Trial Registration http://www.isrctn.com. Unique identifier: ISRCTN76413758

Improving cardiovascular health in patients with an abdominal aortic aneurysm:development of the cardiovascular risk reduction in patients with aneurysms (CRISP) behaviour change intervention

Background: Abdominal aortic aneurysm (AAA) is an important cardiovascular health problem. Ultrasound screening is proven to reduce AAA mortality and programmes have been implemented in some healthcare systems. Those who are identified as having a small AAA in screening enter into a surveillance programme to monitor AAA size. Individuals in AAA surveillance are at elevated risk of cardiovascular events, which is not currently addressed sufficiently. We aimed to develop a simple intervention to reduce cardiovascular risk, which could be embedded in AAA surveillance pathways. Methods: Intervention mapping methods were used to co-develop the intervention with individuals with AAA, families/carers, and healthcare staff. We identified “targets for change” by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We conducted a series of workshops to identify barriers to and facilitators of change and used taxonomies of behaviour change theories and techniques to match intervention strategies to each target. Further stakeholder involvement work helped refine the intervention. Results: The developed intervention focusses on assessment and individually tailored discussion of risk factors, exchanging information, building motivation and action planning, followed by review of progress and problem-solving. Workbooks covering physical activity, diet, stress management, alcohol, smoking, blood pressure and mental health are provided to support behaviour change. The intervention is facilitated by trained healthcare professionals during the patient’s AAA screening appointment for the duration that they are in surveillance. Discussion: The developed intervention will now be tested to assess whether it can be integrated with the current AAA screening programme. The developed intervention is a novel approach to reducing cardiovascular disease in the AAA population, it is also the first intervention which tries to do this in this population. Trial registration: International Clinical Trial Registration: ISRCTN93993995

New Horizons in Peripheral Artery Disease

Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams

Designing a platform/adaptive randomised controlled trial for peripheral arterial disease (PAD) - The PAEDIS international platform trial development project.

BACKGROUND: Peripheral artery disease (PAD) is a common health problem. There are several technologies, medications, and interventions that aim to improve or treat PAD in people with symptomatic disease. Most of these technologies, however, have been untested in high-quality randomised studies assessing effectiveness and their interactions remain unknown. We developed a proposed design for an international randomised controlled trial assessing multiple PAD treatments. METHODS: Over the course of 11 months (2023) several workshops and reviews of the literature took place. More specific, the proposed platform trial was designed with 44 people with PAD and 112 experts from across the world, in five work packages. The most relevant PAD treatment with unproven effectiveness were identified and key trial components as well as success criteria were defined. With input from five clinical trials units, the final format of a potential platform PAD trial in primary and secondary care was then proposed for funding. RESULTS: The proposed platform PAD randomised trial involved two major multi-arm multi-stage randomised studies, assessing PAD treatments in the community setting (1 st package) and then secondary care (2 nd package). The 1 st package involved people with claudication and the 2 nd package involves people with chronic limb threatening ischaemia (CLTI). CONCLUSIONS: A platform PAD trial involves many challenges in terms of both design and delivery. The proposed design involving both people with claudication and CLTI will hopefully act as a blueprint for future work in this area

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Results: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease

Preoperative exercise training for adults undergoing elective major vascular surgery: A systematic review

Patients undergoing major vascular surgery may have an increased risk of postoperative complications due to poor ‘fitness for surgery’. Prehabilitation aims to optimise physical fitness and risk factors before surgery to improve outcomes. The role of exercise-based prehabilitation in vascular surgery is currently unclear. Therefore, the aim of this systematic review was to assess the benefits and harms of preoperative exercise training in adults undergoing elective vascular surgery. We searched MEDLINE, Embase, CINAHL, and CENTRAL databases, trial registries, and forward and backward citations for studies published between January 2008 and April 2021. We included randomised trials that compared patients receiving exercise training with those receiving usual care or no training before vascular surgery. Outcomes included mortality, complications, and health-related quality of life (HRQOL). Three trials with 197 participants were included. All studies involved people undergoing abdominal aortic aneurysm (AAA) repair. Low-certainty evidence could not differentiate between rates of all-cause mortality. Moderate-certainty evidence indicated that postoperative cardiac and renal complications were less likely to occur in people who participated in preoperative exercise training compared with those who did not. Low-certainty evidence also indicated better postoperative HRQOL outcomes in people who undertook prehabilitation. There were no serious exercise-related adverse events. The evidence on preoperative exercise training for AAA patients is promising, but currently insufficiently robust for this intervention to be recommended in clinical guidelines. High-quality trials are needed to establish its clinical and cost-effectiveness. Research is also needed to determine the feasibility and effects of prehabilitation before lower-limb revascularisation

A Community and Hospital cAre Bundle to improve the medical treatment of severe cLaudIcation and critical limb iSchaemia (CHABLIS)

This article relates to a research study that included patients or members of the workforce as study participants from GP practices in Nottingham and Nottinghamshire.Background: Patients with peripheral artery disease (PAD) often do not receive optimal best medical therapy (BMT). Through interaction with patients and healthcare-professionals (HCPs) we developed the LEaflet Gp letter Structured checklist (LEGS) complex clinical intervention to support HCPs in providing guideline-compliant PAD BMT. Methods: This was a prospective multicentre study assessing the feasibility and fidelity of delivering the LEGS intervention in primary and secondary care over six months. Intervention fidelity was scored based on the proportion of intervention components used correctly at discharge, 30 days, and six months. Results: Overall, 129 individuals were screened and 120 took part (33% female, 74% with chronic limb threatening ischaemia; 93% recruitment rate). Of those, 118 (98% retention rate) completed follow-up. Mean intervention fidelity score at discharge (primary outcome measure) was 63% [95% Confidence Interval (CI): 39-68%, SD: 5%], exceeding the success criteria set at 60% by a panel of HCPs and patients. This, however, declined to 51% at six months. Eight patients (6.7%) died (all cardiovascular deaths), four (3.3%) had a major lower limb amputation, 12 (10%) had a cardiovascular event, and 13 (11%) were admitted due to limb ischaemia at six months. Incomplete lipid therapy prescriptions and LEGS intervention documents not received by primary care CHPs were the most common reasons for not complying with the LEGS intervention. Conclusions: The LEGS intervention can be delivered in PAD care pathways across different hospitals, primary, and community healthcare settings with acceptable fidelity, to streamline and improve PAD BMT short- and medium-term

A feasibility study of the CRISP intervention; a cardiovascular risk reduction intervention in patients with an abdominal aortic aneurysm:[version 2; peer review: 2 approved, 1 approved with reservations, 1 not approved]

Background: Abdominal aortic aneurysm (AAA) screening/surveillance is implemented widely. Those in AAA-surveillance are at high-risk of cardiovascular-events. We developed an intervention, called CRISP, using intervention-mapping, to reduce cardiovascular-risk in AAA-surveillance. This study tested the CRISP intervention in routine clinical-care. Methods: The CRISP intervention, consisting of a nurse-led cardiovascular risk assessment and subsequent lifestyle change support using a self-care workbook and low-intensity nurse input was delivered in two screening/surveillance programmes. Those consenting to take part were followed-up with cardiovascular-assessments. Fidelity of intervention-delivery was assessed quantitatively/qualitatively. Results: 40 men (mean age 75 ± 7 years) took part over four months and followed-up for a minimum six months. A sub-group of 25 patients and nine Health Care Professionals (HCPs) were interviewed. The median number of risk-factors that patients chose to focus on was two (range 0 to 4), with physical activity (n=17) being the most popular. Participants who had a ‘red light’ risk factor for stress, low mood, smoking or alcohol intake were offered a referral to appropriate services. Two were offered referral to mental-health services and took it up, three declined referrals to smoking or alcohol support services. The fidelity of intervention-delivery (a score intervention components delivered to each patient based on a score from 0 to 5, with 5 being highest delivery fidelity) was generally low. The highest mean score (on a 0-5 scale) for the nurse assessment was 1.5 for engaging the participant, lowest 0.5 for exploring the importance for selected lifestyle behaviours. In qualitative interviews, the intervention was liked by patients/HCPs. Based on qualitative interviews and observations, the low fidelity of intervention-delivery was due to intervention-training not being detailed. Conclusions: CRISP can be delivered in AAA-surveillance, but fidelity of delivery is low. The intervention and its training need to be refined/tested before wider implementation. Registration: ISRCTN9399399518/11/20).</p

Sex differences in mortality after abdominal aortic aneurysm repair in the UK

Background The UK abdominal aortic aneurysm (AAA) screening programmes currently invite only men for screening because the benefit in women is uncertain. Perioperative risk is critical in determining the effectiveness of screening, and contemporary estimates of these risks in women are lacking. The aim of this study was to compare mortality following AAA repair between women and men in the UK. Methods Anonymized data from the UK National Vascular Registry (NVR) for patients undergoing AAA repair (January 2010 to December 2014) were analysed. Co-variables were extracted for analysis by sex. The primary outcome measure was in-hospital mortality. Secondary outcome measures included mortality by 5-year age groups and duration of hospital stay. Logistic regression was performed to adjust for age, calendar time, AAA diameter and smoking status. NVR-based outcomes were checked against Hospital Episode Statistics (HES) data. Results A total of 23 245 patients were included (13·0 per cent women). Proportionally, more women than men underwent open repair. For elective open AAA repair, the in-hospital mortality rate was 6·9 per cent in women and 4·0 per cent in men (odds ratio (OR) 1·48, 95 per cent c.i. 1·08 to 2·02; P = 0·014), whereas for elective endovascular AAA repair it was 1·8 per cent in women and 0·7 per cent in men (OR 2·86, 1·72 to 4·74; P < 0·001); the results in HES were similar. For ruptured AAA, there was no sex difference in mortality within the NVR; however, in HES, for ruptured open AAA repair, the in-hospital mortality rate was higher in women (33·6 versus 27·1 per cent; OR 1·36, 1·16 to 1·59; P < 0·001). Conclusion Women have a higher in-hospital mortality rate than men after elective AAA repair even after adjustment. This higher mortality may have an impact on the benefit offered by any screening programme offered to women.D.A.S. and A.S. are funded by the UK NIHR. This paper was written in collaboration with members of the SWAN project, a modelling study to examine the potential clinical benefit and cost-effectiveness of AAA screening in women (www.nets.nihr.ac.uk/projects/hta/1417901). The SWAN project was funded by the UK NIHR HTA programme (project number 14/179/01). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health. The aspect of this paper relating to the analysis of HES presents independent research funded by the NIHR under the Programme Grants for Applied Research programme (RP-PG-1210-12009). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health