Ultrasound screening for abdominal aortic aneurysm in high-risk women.

BACKGROUND: Population-wide ultrasound screening programmes for abdominal aortic aneurysm (AAA) for men have already been established in some countries. Women account for one third of aneurysm-related mortality and are four times more likely to experience an AAA rupture than men. Whole-population screening for AAA in women is unlikely to be clinically or economically effective. The aim of this study was to determine the outcomes of a targeted AAA screening programme for women at high risk of AAA. METHOD: Women aged 65-74 years deemed at high risk of having an AAA (current smokers, ex-smokers, or with a history of coronary artery disease) were invited to attend ultrasound screening (July 2016 to March 2019) for AAA in the Female Aneurysm screening STudy (FAST). Primary outcomes were attendance for screening and prevalence of AAA. Biometric data, medical history, quality of life (QoL) and aortic diameter on ultrasound imaging were recorded prospectively. RESULTS: Some 6037 women were invited and 5200 attended screening (86.7 per cent). Fifteen AAAs larger than 29 mm were detected (prevalence 0.29 (95 per cent c.i. 0.18 to 0.48) per cent). Current smokers had the highest prevalence (0.83 (95 per cent c.i. 0.34 to 1.89) per cent) but lowest attendance (75.2 per cent). Three AAAs greater than 5.5 cm were identified and referred for consideration of surgical repair; one woman underwent repair. There was a significant reduction in patient-reported QoL scores following screening. CONCLUSION: A low prevalence of AAA was detected in high-risk women, with lowest screening uptake in those at highest risk. Screening for AAA in high-risk women may not be beneficial.

Acute kidney injury following endovascular intervention for peripheral artery disease.

BACKGROUND: The incidence of, and risk factors for, acute kidney injury (AKI) after endovascular intervention for peripheral artery disease (PAD) remain unknown. The aim of this study was to assess the proportion of patients who develop AKI and explore the risk factors. METHODS: Prospectively collected data on patients undergoing femoropopliteal endovascular intervention for symptomatic PAD across three vascular centres were analysed. The proportion of patients developing AKI (according to the Kidney Disease Improving Global Outcomes definition) within 48 h, and the proportion developing the composite Major Adverse Kidney Events (MAKE) endpoints (death, dialysis, drop in estimated glomerular filtration rate at least 25 per cent) at 30 days (MAKE30) and remains 90 days (MAKE90) were calculated. Multivariable regression analysis was used to assess predictors of AKI, and the association between AKI and death. RESULTS: Some 2041 patients were included in the analysis. AKI developed in 239 patients (11.7 per cent), with 47 (2.3 per cent) requiring dialysis within 30 days, and 18 (0.9 per cent) requiring ongoing dialysis. The MAKE30 and MAKE90 composite endpoints were reached in 358 (17.5 per cent) and 449 (22.0 per cent) patients respectively. Risk factors for AKI were age, sex, congestive heart failure, chronic limb-threatening ischaemia, emergency procedure, and pre-existing chronic kidney disease. AKI, dementia, congestive heart failure, and major amputation were risk factors for medium-term mortality. CONCLUSION: AKI is a common complication after intervention for PAD and is associated with medium-term mortality.

Lack of an effective drug therapy for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. This review summarizes prior AAA pathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo-controlled drug trials in patients with small AAAs. Eleven previously published randomized-controlled clinical trials testing different drug therapies aimed at slowing AAA progression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta-analyses of these trials suggested that neither of these approaches limit AAA growth. Allocation to blood pressure-lowering medication was associated with a small reduction in AAA rupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00, P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow-up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.

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.

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.

Pre-operative Functional Cardiovascular Reserve Is Associated with Acute Kidney Injury after Intervention.

BACKGROUND: Acute kidney injury (AKI) is a common complication after endovascular intervention, associated with poor short and long-term outcomes. However, the mechanisms underlying AKI development remain poorly understood. The impact of pre-existing cardiovascular disease and low cardiovascular reserve (CVR) in AKI is unclear; it remains unknown whether AKI is primarily related to pre-existing comorbidity or to procedural parameters. The association between CVR and AKI after EVAR was therefore assessed. METHODS: This is a case control study. From a database of 484 patients, 292 undergoing elective endovascular aneurysm repair (EVAR) of an infrarenal abdominal aortic aneurysm (AAA) in two tertiary centres were included. Of these, 73 patients who had developed AKI after EVAR were case matched, based on pre-operative estimated glomerular filtration rate (eGFR; within 5 mL/min/1.73 m2) and age, with patients who had not developed AKI. Cardiopulmonary exercise testing (CPET) was used to assess CVR using the anaerobic threshold (AT). Development of AKI was defined using the Kidney Disease Improving Outcomes (KDIGO) guidance. Associations between CVR (based on AT levels) and AKI development were then analysed. RESULTS: Pre-operative AT levels were significantly different between those who did and did not develop AKI (12.1±2.9 SD vs. 14.8±3.0 mL/min/kg, p < .001). In multivariate analysis, a higher level of AT (per 1 mL/min/kg) was associated with a lower odds ratio (OR) of 0.72 (95% CI, 0.63-0.82, p < .001), relative to AKI development. A pre-operative AT level of < 11 mL/min/kg was associated with post-operative AKI development in adjusted analysis, with an OR of 7.8 (95% CI, 3.75-16.51, p < .001). The area under the curve (receiver operating characteristic) for AT as a predictor of post-operative AKI was 0.81 (standard error, 0.06, 95% CI, 0.69-0.93, p < .001). CONCLUSIONS: Poor CVR was strongly associated with the development of AKI. This provides pathophysiological insights into the mechanisms underlying AKI.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women.

BACKGROUND: Although women represent an increasing proportion of those presenting with abdominal aortic aneurysm (AAA) rupture, the current prevalence of AAA in women is unknown. The contemporary population prevalence of screen-detected AAA in women was investigated by both age and smoking status. METHODS: A systematic review was undertaken of studies screening for AAA, including over 1000 women, aged at least 60 years, done since the year 2000. Studies were identified by searching MEDLINE, Embase and CENTRAL databases until 13 January 2016. Study quality was assessed using the Newcastle-Ottawa scoring system. RESULTS: Eight studies were identified, including only three based on population registers. The largest studies were based on self-purchase of screening. Altogether 1 537 633 women were screened. Overall AAA prevalence rates were very heterogeneous, ranging from 0·37 to 1·53 per cent: pooled prevalence 0·74 (95 per cent c.i. 0·53 to 1·03) per cent. The pooled prevalence increased with both age (more than 1 per cent for women aged over 70 years) and smoking (more than 1 per cent for ever smokers and over 2 per cent in current smokers). CONCLUSION: The current population prevalence of screen-detected AAA in older women is subject to wide demographic variation. However, in ever smokers and those over 70 years of age, the prevalence is over 1 per cent.

Meta-analysis of Outcomes Following Aneurysm Repair in Patients with Synchronous Intra-abdominal Malignancy.

OBJECTIVES: The management of concomitant intra-abdominal malignancy (IAM) and abdominal aortic aneurysm (AAA) remains a challenge, even though malignancy is common in an elderly population. By means of systematic review and meta-analysis, the aim was to investigate outcomes in patients undergoing open (OAR) or endovascular AAA repair (EVAR) that have a concomitant malignancy. METHODS: A systematic literature review was performed (Medline and EMBASE databases) to identify all series reporting outcomes of AAA repair (OAR or EVAR) in patients with concomitant IAM. Meta-analysis was applied to assess mortality and major morbidity at 30 days and long term. RESULTS: The literature review identified 36 series (543 patients) and the majority (18 series) reported on patients with colorectal malignancy and AAA. Mean weighted mortality for OAR at 30 days was 11% (95% CI: 6.6% to 17.9%); none of the EVAR patients died peri-operatively. The weighted 30-day major complication rate for EVAR was 20.4% (10.0-37.4%) and for OAR it was 15.4% (7.0-30.8%). Most patients had their AAA and malignancy treated non-simultaneously (56.6%, 95% CI, 42.1-70.1%). In the EVAR cohort, three patients (4.6%) died at last follow-up (range 24-64 months). In the OAR cohort 23 (10.6%) had died at last follow up (range from 4 to 73 months). CONCLUSION: In this meta-analysis, OAR was associated with significant peri-operative mortality in patients with an IAM. EVAR should be the first-line modality of AAA repair. The majority of patients were not treated simultaneously for the two pathologies, but further investigation is necessary to define the optimal timing for each procedure and malignancy.

Microarray-based Gene Expression Profiling of Abdominal Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Microarray-based gene expression profiling studies may detect transcriptional signatures carrying prognostic value in abdominal aortic aneurysms (AAA). A gene expression profiling study was conducted to compare individuals with AAA with screened controls. METHODS: The peripheral blood transcriptome was compared between 12 individuals with AAA and 12 age- and sex-matched controls using microarray. Validation by Taqman real-time quantitative (qPCR) was performed in an independent group as described. Peripheral blood RNA was hybridized to Illumina microarrays, each representing 37,846 genes, allowing comparison of gene expression between cases and controls. Eleven differentially expressed genes were re-quantified by qPCR in the independent group with AAA (n = 95), controls (n = 92), pre- and postendovascular AAA repair (EVAR, n = 31); or open AAA repair (n = 13), AAA wall biopsies (n = 11), and in matched smooth muscle cultures (n = 7). RESULTS: Microarray detected 47 significantly differentially expressed genes in AAA after correction for multiple testing (p < .05). These genes conferred roles in regulation of apoptosis, proteolysis, the electron transport chain, leukocyte migration, and the humoral immune response. Gene quantification in the independent group demonstrated three genes to be downregulated in AAA compared with controls: MSN, PSMB10, and STIM1; however, their expression remained unchanged post-AAA repair. PSMB10 was the only gene conferring a consistent direction of effect in both the discovery and validation analyses (downregulated). EIF3G, SIVA, PUF60, CYC1, FIBP, and CARD8 were downregulated post-EVAR. Expression of all 11 genes of interest was detected in aortic biopsies and matched smooth muscle cultures. CONCLUSION: This study demonstrates differential expression of transcripts in peripheral blood of individuals with AAA, with functional roles in proteolysis, inflammation, and apoptotic processes. These were modulated by aneurysm exclusion from the circulation and expressed in matched aortic biopsies and smooth muscle cultures. These observations further support the key roles for these pathways in the pathogenesis of AAA.

Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in Unstable Carotid Atherosclerotic Plaques.

OBJECTIVE/BACKGROUND: The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level. METHODS: Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort. RESULTS: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p < .001). Cathepsin G expression was upregulated in histologically unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p = .03). CCL19 also co-localised with CD3+ T-cell lymphocytes in the core region, around where CCL19 was expressed. CONCLUSIONS: CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated.

Survey of ankle-brachial pressure index use and its perceived barriers by general practitioners in the UK.

BACKGROUND: Peripheral arterial disease (PAD) is often undetected until complications arise, despite it being a major healthcare burden and an independent risk factor for cardiovascular death and systemic atherosclerosis. Appropriate diagnostic tools are as important as clinical knowledge and skill to investigate patients for PAD. Currently, the ankle-brachial pressure index (ABPI) is the recommended diagnostic tool for PAD. PURPOSE: We explore current opinions on ABPI by general practitioners (GPs) and the limitations to its implementation in primary care practice. METHODS: GPs attending a regional 1-day study event, were surveyed in October 2014. Survey questionnaires were placed at the top of each conference pack for each attendee. The survey questionnaire was modelled from the ankle-brachial index (ABI) usage survey questionnaire used in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) preceptorship study. RESULTS: All respondents were GPs, with a survey response rate of 77.1%. All respondents regarded ABPI as an important test, that is primarily performed by nursing staff (79.5%) in their respective GP surgeries. 70% and 97% of GPs found ABPI useful for the diagnosis of asymptomatic and symptomatic PAD, respectively. 69% of GPs regarded ABPI as a feasible test in primary care practice. Time constraints (84%), staff availability (89%) and staff training (72%) were cited as the main limitations to its use. CONCLUSIONS: Targeted training of nursing staff may improve ABPI usage, although a less time-consuming test for PAD may be another option.

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.

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.

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.

What is the best option for elective repair of an abdominal aortic aneurysm in a young fit patient?

OBJECTIVE: The lower procedural risk associated with endovascular aneurysm repair (EVAR) compared with open aneurysm repair (OAR) is well known. Younger patients are likely to represent a group at low perioperative risk. The long-term durability and late complications following EVAR may have more significance when considering the optimal treatment for young patients with a longer life expectancy. This study examined perioperative and long-term outcomes of young patients undergoing aneurysm repair by either open surgical or endovascular means. METHODS: A retrospective review of a prospectively collated database was performed. Patients undergoing elective aneurysm repair at the age of 65 years or younger between January 2000 and September 2010 were included. All EVAR patients were followed up in a nurse-led clinic. Data regarding long-term outcomes for patients undergoing open repair were gathered from case note review. RESULTS: There were 99 patients who underwent open repair and 59 patients who underwent endovascular repair. Groups were well matched in terms of demographics and co-morbidities. 30-day mortality was 1% after open repair. There were no perioperative deaths after endovascular repair. Overall, 30-day complication rates were 15% after open repair and 12% after EVAR. The nature of complications differed between the two groups with the EVAR group experiencing endoleaks and the OAR group demonstrating more cardiorespiratory complications. Mean follow-up was 75.5 months and there was a 14% reintervention rate after EVAR compared with 7% after OAR. CONCLUSION: Young patients are likely to have a lower procedural risk for EVAR and OAR than described in published figures. Although mortality and complication rates in these two groups were similar, the nature of complications occurring following open surgery were often more significant than those occurring after EVAR. There remains a risk of late reintervention following either form of repair.

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.