Observational study of the medical management of patients with peripheral artery disease.

BACKGROUND: Previous research has suggested that patients with peripheral artery disease (PAD) are not offered adequate risk factor modification, despite their high cardiovascular risk. The aim of this study was to assess the cardiovascular profiles of patients with PAD and quantify the survival benefits of target-based risk factor modification. METHODS: The Vascular and Endovascular Research Network (VERN) prospectively collected cardiovascular profiles of patients with PAD from ten UK vascular centres (April to June 2018) to assess practice against UK and European goal-directed best medical therapy guidelines. Risk and benefits of risk factor control were estimated using the SMART-REACH model, a validated cardiovascular prediction tool for patients with PAD. RESULTS: Some 440 patients (mean(s.d.) age 70(11) years, 24·8 per cent women) were included in the study. Mean(s.d.) cholesterol (4·3(1·2) mmol/l) and LDL-cholesterol (2·7(1·1) mmol/l) levels were above recommended targets; 319 patients (72·5 per cent) were hypertensive and 343 (78·0 per cent) were active smokers. Only 11·1 per cent of patients were prescribed high-dose statin therapy and 39·1 per cent an antithrombotic agent. The median calculated risk of a major cardiovascular event over 10 years was 53 (i.q.r. 44-62) per cent. Controlling all modifiable cardiovascular risk factors based on UK and European guidance targets (LDL-cholesterol less than 2 mmol/l, systolic BP under 140 mmHg, smoking cessation, antiplatelet therapy) would lead to an absolute risk reduction of the median 10-year cardiovascular risk by 29 (20-38) per cent with 6·3 (4·0-9·3) cardiovascular disease-free years gained. CONCLUSION: The medical management of patients with PAD in this secondary care cohort was suboptimal. Controlling modifiable risk factors to guideline-based targets would confer significant patient benefit.

Impact of abdominal aortic aneurysm screening on quality of life.

BACKGROUND: Screening for abdominal aortic aneurysm (AAA) is known to reduce AAA-related mortality; however, the psychological impact of population AAA screening is unclear. The aim was to assess the impact of AAA diagnosis on quality of life (QoL) using data from an established AAA screening programme. METHODS: Mental and physical QoL scores for men diagnosed with AAA through participation in the English and Welsh AAA screening programmes were compared with no-AAA controls. Participants were identified through the United Kingdom Aneurysm Growth Study (UKAGS), a nationwide prospective cohort study of men with an AAA of less than 55 mm diagnosed through voluntary participation in screening. The UKAGS participants completed QoL questionnaires at the time of screening and annually thereafter. RESULTS: A transient reduction in mental QoL scores was observed following the diagnosis of AAA, returning to baseline levels after 12 months. Physical QoL remained consistently lower in the AAA cohort. Participants thought about their AAA and the AAA growth progressively less 12 months after the initial screening diagnosis. AAA growth rate had no influence over QoL parameters. DISCUSSION: This study suggests that screening for AAA does reduce mental QoL; however, this effect is transient (less than 12 months). Men diagnosed with AAA have a consistently worse physical QoL compared with controls.

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.

Multi-Centre Study on Cardiovascular Risk Management on Patients Undergoing AAA Surveillance.

BACKGROUND: The risk of cardiovascular events and death in patients with abdominal aortic aneurysms (AAA) is high. Screening has been introduced to reduce AAA related mortality; however, after AAA diagnosis, cardiovascular modification may be as important to patient outcomes as surveillance. The aim of this study was to assess cardiovascular risk reduction in patients with small AAA. METHODS: Institutional approval was granted for The Vascular and Endovascular Research Network (VERN) to retrospectively collect data pertaining to cardiovascular risk reduction from four tertiary vascular units in England. Patients with small AAA (January 2013-December 2015) were included. Demographic details, postcode, current medications, and smoking status were recorded using a bespoke electronic database and analysed. In a secondary analysis VERN contacted all AAA screening units in England and Wales to assess their current protocols relating to CV protection. RESULTS: In total, 1053 patients were included (mean age 74 ± 9 years, all men). Of these, 745 patients (70.8%) had been prescribed an antiplatelet agent and 787 (74.7%) a statin. Overall, only 666 patients (63.2%) were prescribed both a statin and antiplatelet. Two hundred and sixty eight patients (32.1%) were current smokers and the proportion of patients who continued to smoke decreased with age. Overall, only 401 patients (48.1%) were prescribed a statin, antiplatelet, and had stopped smoking. In the secondary analysis 38 AAA screening units (84% national coverage) replied. Thirty-one units (82%) suggest changes to the patient's prescription; however, none monitor compliance with these recommendations or assess whether the general practitioner has been made aware of the AAA diagnosis or prescription advice. CONCLUSION: Many patients with small AAA are not prescribed an antiplatelet/statin, and still smoke cigarettes, and therefore remain at high risk of cardiovascular morbidity and mortality. National guidance to ensure this high risk group of patients is adequately protected from poor cardiovascular outcomes is lacking.

Reporting individual surgeon outcomes does not lead to risk aversion in abdominal aortic aneurysm surgery.

INTRODUCTION Reporting surgeons' outcomes has recently been introduced in the UK. This has the potential to result in surgeons becoming risk averse. The aim of this study was to investigate whether reporting outcomes for abdominal aortic aneurysm (AAA) surgery impacts on the number and risk profile (level of fitness) of patients offered elective treatment. METHODS Publically available National Vascular Registry data were used to compare the number of AAAs treated in those centres across the UK that reported outcomes for the periods 2008-2012, 2009-2013 and 2010-2014. Furthermore, the number and characteristics of patients referred for consideration of elective AAA repair at a single tertiary unit were analysed yearly between 2010 and 2014. Clinic, casualty and theatre event codes were searched to obtain all AAAs treated. The results of cardiopulmonary exercise testing (CPET) were assessed. RESULTS For the 85 centres that reported outcomes in all three five-year periods, the median number of AAAs treated per unit increased between the periods 2008-2012 and 2010-2014 from 192 to 214 per year (p=0.006). In the single centre cohort study, the proportion of patients offered elective AAA repair increased from 74% in 2009-2010 to 81% in 2013-2014, with a maximum of 84% in 2012-2013. The age, aneurysm size and CPET results (anaerobic threshold levels) for those eventually offered elective treatment did not differ significantly between 2010 and 2014. CONCLUSIONS The results do not support the assumption that reporting individual surgeon outcomes is associated with a risk averse strategy regarding patient selection in aneurysm surgery at present.

Role of Simulation in Endovascular Aneurysm Repair (EVAR) Training: A Preliminary Study.

BACKGROUND: Endovascular aneurysm repair (EVAR) requires a high-level of technical-competency to avoid device-related complications. Virtual reality simulation-based training (SBT) may offer an alternative method of psychomotor skill acquisition; however, its role in EVAR training is undefined. This study aimed to: a) benchmark competency levels using EVAR SBT, and b) investigate the impact of supervised SBT on trainee performance. METHODS: EVAR procedure-related metrics were benchmarked by six experienced consultants using a Simbionix Angiomentor EVAR simulator. Sixteen vascular surgical trainees performing a comparable EVAR before and after structured SBT (>4 teaching sessions) were assessed utilising a modified Likert-scale score. These were benchmarked for comparison against the standard set by the consultant body. RESULTS: Median procedural-time for consultants was 43.5 min (IQR 7.5). A significant improvement in trainee procedural-time following SBT was observed (median procedural time 77 min [IQR 20.75] vs. 56 min [IQR: 7.00], p < .0001). The mean (SD) trainee Likert score pre- and post-SBT improved (16.6 [SD 1.455] vs. 28.63 [SD 2.986], p < .0001). Fewer endoleaks were observed (p = .0063) and trainees chose an appropriately sized device more often after SBT. CONCLUSION: This study suggests that EVAR-SBT should be considered as an adjunct to standard psychomotor skill teaching techniques for EVAR within the vascular surgery training curricula.

Patients with Small Abdominal Aortic Aneurysm are at Significant Risk of Cardiovascular Events and this Risk is not Addressed Sufficiently.

BACKGROUND: Patients with abdominal aortic aneurysm (AAA) are at significant risk of cardiovascular (CV) events. Recent implementation of AAA-screening means thousands of patients are now diagnosed with small-AAA; however, CV risk factors are not always addressed. This study aimed at assessing and quantifying the CV characteristics of patients with small AAA following the introduction of screening programmes. METHODS: CV profiles of 384 men with a small AAA (<55 mm diameter) were assessed through the United Kingdom Aneurysm Growth Study (UKAGS), a nationwide prospective cohort study of men with small AAA. A prospective local cohort of an additional 142 patients with small AAA with available blood pressure (BP) and lipid profiles was also included and followed-up for 1 year. RESULTS: In the UKAGS population, 54% were current and 30% ex-smokers; 58% were hypertensive and 54% hypercholesterolaemic. In the local group, 54% were current and 40% were ex-smokers, and 94% were hypertensive. Patients were not more likely to receive CV medication after entering AAA surveillance in either group. All local patients were clustered "high-risk" for future CV events based on the Framingham score (mean 21.8%, 95% CI 20.0-23.6), JBS-2 (16.3%, 14.7-17.9) and ASSIGN (25.2%, 22.7-27.7). No change was seen in systolic BP levels between baseline and 1 year (140.9 mmHg vs. 142.5 mmHg, p=.435). A rise was seen in cholesterol (4.0 mmol-4.2 mmol, p<.0001) values at 1 year. CONCLUSIONS: This study suggests that patients with small AAA are at significant risk for developing CV events and this is not currently addressed, which is evident by the "high-risk" CV risk profiles of these patients despite being in AAA surveillance. Design and implementation of a CV risk reduction programme tailored for this population is necessary.

Short-Term Outcomes of Management of Endovascular Aneurysm Repair in Patients With Dilated Iliacs.

OBJECTIVES: This study aims to evaluate outcomes following endovascular aneurysm repair (EVAR) in patients with dilated but not aneurysmal common iliac arteries. METHODS: Data prospectively collected from 342 elective EVARs were analyzed retrospectively. Dilated common iliac anatomy was defined as 21 to 24 mm. Patients with iliac aneurysms or external iliac artery (EIA) extension were excluded. Patients were followed up using clinical review, plain radiographs, duplex imaging, and selective computed tomography scanning. RESULTS: Median age was 75 years with a mean follow-up of 3.6 years. In all, 33 patients had dilated common iliac arteries (DCIAs) and 309 had non-dilated common iliac arteries (NDCIA). There was no difference in aneurysm diameter or neck characteristics (length, diameter, angulation, thrombus, and flare) between the subgroups. There was no significant difference in technical success, 30-day mortality, late mortality, aneurysm-related mortality, 30-day reinterventions, stent graft migration, limb occlusion, sac expansion, graft rupture, type 1 endoleaks, type 3 endoleaks, and total reinterventions (all Ps > .05). There was a significant decrease in type II endoleaks in patients with DCIA compared to NDCIA (NDCIA 12.9% and DCIA 0.0%; P = .02). CONCLUSION: Patients presenting with abdominal aortic aneurysms with DCIA can be successfully treated with EVAR with no increase in complications without extension into the EIA.

Systematic review of cardiovascular disease and cardiovascular death in patients with a small abdominal aortic aneurysm.

BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has reduced the rate of AAA rupture. However, cardiovascular disease is still a major cause of death in men with an AAA. The aim of this study was to assess cardiovascular risk in patients with a small AAA. METHODS: Standard PRISMA guidelines were followed. Analysis was performed of studies reporting cardiovascular outcomes in patients with a small AAA (30-54 mm). Weighted metaregression was performed for cardiovascular death in patients with a small AAA, and the prevalence of cardiovascular disease was reviewed. RESULTS: Twenty-one articles were identified describing patients with an AAA, and the prevalence of, and death from, cardiovascular disease. Ten of these reported cardiovascular death rates in patients with a small AAA. Some 2323 patients with a small AAA were identified; 335 cardiovascular deaths occurred, of which 37 were due to AAA rupture. Metaregression demonstrated that the risk of cardiovascular death was 3·0 (95 per cent c.i. 1·7 to 4·3) per cent per year in patients with a small AAA (R(2) = 0·902, P < 0·001). The prevalence of ischaemic heart disease (44·9 per cent), myocardial infarction (26·8 per cent), heart failure (4·4 per cent) and stroke (14·0 per cent) was also high in these patients. CONCLUSION: The risk of cardiovascular death in patients with a small AAA is high and increases by approximately 3 per cent each year after diagnosis. Patients with a small AAA have a high prevalence of cardiovascular disease. Patients a small AAA should be considered for lifestyle modifications and secondary cardiovascular protection.

Identification of microRNAs associated with abdominal aortic aneurysms and peripheral arterial disease.

BACKGROUND: MicroRNAs are crucial in the regulation of cardiovascular disease and represent potential therapeutic targets to decrease abdominal aortic aneurysm (AAA) expansion. The aim of this study was to identify circulating microRNAs associated with AAA. METHODS: Some 754 microRNAs in whole-blood samples from 15 men with an AAA and ten control subjects were quantified using quantitative reverse transcriptase-PCR. MicroRNAs demonstrating a significant association with AAA were validated in peripheral blood and plasma samples of men in the following groups (40 in each): healthy controls, controls with peripheral arterial disease (PAD), men with a small AAA (30-54 mm), those with a large AAA (over 54 mm), and those following AAA repair. MicroRNA expression was also assessed in aortic tissue. RESULTS: Twenty-nine differentially expressed microRNAs were identified in the discovery study. Validation study revealed that let-7e (fold change (FC) -1·80; P = 0·001), miR-15a (FC -2·24; P < 0·001) and miR-196b (FC -2·26; P < 0·001) were downregulated in peripheral blood from patients with an AAA, and miR-411 was upregulated (FC 5·90; P = 0·001). miR-196b was also downregulated in plasma from the same individuals (FC -3·75; P = 0·029). The same miRNAs were similarly expressed differentially in patients with PAD compared with healthy controls. Validated and predicted microRNA targets identified through miRWalk revealed that these miRNAs were all regulators of AAA-related genes (vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, DAB2 interacting protein, α1-antitrypsin, C-reactive protein, interleukin 6, osteoprotegerin, methylenetetrahydrofolate reductase, tumour necrosis factor α). CONCLUSION: In this study, circulating levels of let-7e, miR-15a, miR-196b and miR-411 were differentially expressed in men with an AAA compared with healthy controls, but also differentially expressed in men with PAD. Modulation of these miRNAs and their target genes may represent a new therapeutic pathway to affect the progression of AAA and atherosclerosis.

A retrospective study: Factors associated with the risk of abdominal aortic aneurysm rupture.

INTRODUCTION: Literature regarding pharmacological manipulation of aneurysm development and progression is abundant; however studies looking at preventing rupture are sparse. Moreover, best medical therapy is ill-instituted, and continued in this high-risk cohort. This paper aims to identify factors which affect the risk of AAA-rupture. MATERIALS & METHODS: A retrospective review of patients undergoing non-screen detected AAA-repair at a single tertiary-referral centre was performed. Age, cardiovascular history, medication use and the nature of surgical repair (elective or emergency) were converted to binary characteristics and a binomial logistic regression performed. RESULTS: We included 315 admissions for ruptured AAA, and 668 referrals for elective repair of large aneurysms (n=983). Multifactorial analysis showed that the cohort which was prescribed statins experienced fewer ruptured AAA ([OR] 0.50, [95% CI] 0.32-0.77). Factors associated with increased risk of rupture include female gender (2.49, 1.63-3.80), history of hypertension (3.5, 1.6-3.8) or renal failure (8.08, 4.15-15.4), age over 80 (2.77, 1.79-4.27) and current smoking (1.80, 1.09-2.96). DISCUSSION AND CONCLUSIONS: This is the largest study, interrogating individual patient data, to suggest an association between statins and prevention of large AAA-rupture. As patients with AAA are at high risk of cardiovascular events, and statins may decrease the risk of the devastating consequence of the condition, healthcare teams should maintain pharmaco-vigilance in instituting and continuing best medical therapy, including a statin.

Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm.

BACKGROUND: Many studies have investigated the systemic and local expression of biomarkers in patients with abdominal aortic aneurysm (AAA). The natural history of AAA varies between patients, and predictors of the presence and diameter of AAA have not been determined consistently. The aim of this study was to perform a systematic review, meta-analysis and meta-regression of studies comparing biomarkers in patients with and without AAA, with the aim of summarizing the association of identified markers with both AAA presence and size. METHODS AND RESULTS: Literature review identified 106 studies suitable for inclusion. Meta-analysis demonstrated a significant difference between matrix metalloproteinase (MMP) 9, tissue inhibitor of matrix metalloproteinase 1, interleukin (IL) 6, C-reactive protein (CRP), α1-antitrypsin, triglycerides, lipoprotein(a), apolipoprotein A and high-density lipoprotein in patients with and without AAA. Although meta-analysis was not possible for MMP-2 in aortic tissue, tumour necrosis factor α, osteoprotegerin, osteopontin, interferon γ, intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1, systematic review suggested an increase in these biomarkers in patients with AAA. Meta-regression analysis identified a significant positive linear correlation between aortic diameter and CRP level. CONCLUSION: A wide variety of biomarkers are dysregulated in patients with AAA, but their clinical value is yet to be established. Future research should focus on the most relevant biomarkers of AAA, and how they could be used clinically.

Type II endoleak: conservative management is a safe strategy.

OBJECTIVE: Type II endoleak is the most common complication after endovascular abdominal aortic aneurysm repair (EVAR); however, its natural history is unclear. The aim of this study was to examine the incidence and outcomes of type II endoleak, at a single institution after EVAR. METHODS: A total of 904 consecutive patients who underwent EVAR between September 1995 and July 2013 at a single centre were entered onto a prospective database. All patients were followed up by duplex ultrasound (DUSS). Patients who developed type II endoleak were compared for preoperative demographics, mortality, and sac expansion. RESULTS: A total of 175(19%) patients developed type II endoleak over a median follow-up of 3.6 years (1.5-5.9 years); 54% of type II endoleaks spontaneously resolved within 6 months (0.25-1.2 years). No difference was found in preoperative demographics or choice of endograft between the two groups. Survival was significantly higher in the group with type II endoleak (94.1% vs. 85.6%; p = .01) and this effect was most pronounced in those with late type II endoleaks (97.7% vs. 85.6% p = .004). No difference was seen in aneurysm-related mortality or rate of type I endoleak between the two groups. Freedom from sac expansion (>5 mm from preoperative diameter) was significantly lower in the group of patients with type II endoleak (82.5% vs. 93.2%, p = .0001); however, at a threshold of >10 mm from preoperative diameter no difference was seen. CONCLUSIONS: Patients with isolated type II endoleak demonstrate equivalent aneurysm-related mortality and an improved survival.

National Vascular Registry Report on surgical outcomes and implications for vascular centres.

BACKGROUND: The National Vascular Registry Report on Surgical Outcomes (NVSRO) coincided with the update of the National Health Service Standard Contract for Specialized Vascular Services in Adults (NHSSCSVS). The latter promises patients minimum standards for vascular centres. The present study aimed to determine whether current data support the standards proposed in the NHSSCSVS. METHODS: Numbers of abdominal aortic aneurysm (AAA) repairs and carotid endarterectomies (CEAs) performed by hospital Trust and surgeon, and their outcomes were obtained from the NVRSO. These were assessed against NHSSCSVS recommendations that included: more than 60 AAA repairs per year per Trust, over 50 CEAs per year per Trust and at least six vascular surgeons per Trust. RESULTS: Based on NVRSO data, 107 hospital Trusts (92.2 per cent) would fail to meet the minimum standards required to achieve vascular centre status. Outcomes were poorer in these hospitals (overall mortality rate after AAA: 2.7 versus 1.3 per cent; P = 0.007). There were strong associations between number of AAA repairs or CEAs per Trust and better outcomes (AAA repair, P < 0.001; CEA, P = 0.004). These remained significant when analysed by individual surgeon (AAA repair, P < 0.001; CEA, P < 0.001). Trusts undertaking 60 or fewer elective AAA repairs per year had significantly higher elective AAA mortality rates (2.7 versus 1·7 per cent; P = 0.010). Trusts performing a minimum of 50 CEAs per year had significantly lower perioperative mortality/morbidity rates (1.9 versus 3.0 per cent; P = 0.032). Trusts with seven or more surgeons demonstrated lower AAA-related mortality rates (1.7 versus 2.7 per cent; P = 0.018). CONCLUSION: Data from the NVRSO suggest that the majority of hospital Trusts presently fail to meet the standards for vascular centre status. NVRSO data support a standard of more than 60 elective AAA repairs and 50 CEAs per Trust per year. A minimum of seven vascular surgeons per unit was associated with better outcomes. These data support the ongoing remodelling of vascular services in the UK.

A review of current reporting of abdominal aortic aneurysm mortality and prevalence in the literature.

BACKGROUND: It is common for authors to introduce a paper by demonstrating the importance of the clinical condition being addressed, usually by quoting data such as mortality and prevalence rates. Abdominal aortic aneurysm (AAA) epidemiology is changing, and therefore such figures for AAA are subject to error. The aim of this study was to analyse the accuracy of AAA prevalence and mortality citations in the contemporaneous literature. METHODS: Two separate literature searches were performed using PubMed to identify studies reporting either aneurysm prevalence or mortality. The first 40 articles or those published over the last 2 years were included in each search to provide a snapshot of current trends. For a prevalence citation to be appropriate, a paper had to cite an original article publishing its own prevalence of AAA or a national report. In addition, the cited prevalence should match that published within the referenced article. These reported statistics were compared with the most recent data on aneurysm-related mortality. RESULTS: The prevalence of AAA was reported to be as low as 1% and as high as 12.7% (mean 5.7%, median 5%). Only 47.5% of studies had referenced original articles, national reports or NICE, and only 32.4% of cited prevalences matched those from the referenced article. In total 5/40 studies were completely accurate. 80% of studies cited aneurysm mortality in the USA, with the majority stating 15,000 deaths per year (range 9,000 to 30,000). Current USA crude AAA mortality is 6,289 (2010). CONCLUSION: References for AAA mortality and prevalence reported in the current literature are often inaccurate. This study highlights the importance of accurately reporting mortality and prevalence data and using up-to-date citations.