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.

Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/-, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.

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.

Report of a Delphi exercise to inform the design of a research programme on screening for thoracic aortic disease.

OBJECTIVES: To inform the design of a clinical trial of a targeted screening programme for relatives of individuals affected by thoracic aortic disease, we performed a consensus exercise as to the acceptability of screening, the optimal sequence and choice of tests, long-term patient management, and choice of trial design. METHODS: Working with the Aortic Dissection Awareness UK & Ireland patient association, we performed a Delphi exercise with clinical experts, patients, and carers, consisting of three rounds of consultation followed by a final multi-stakeholder face-to-face workshop. RESULTS: Thirty-five experts and 84 members of the public took part in the surveys, with 164 patients and clinicians attending the final workshop. There was substantial agreement on the need for a targeted screening pathway that would employ a combined approach (imaging + genetic testing). The target population would include the first- and second-degree adult (> 15 years) relatives, with no upper age limit of affected patients. Disagreement persisted about the screening process, sequence, personnel, the imaging method to adopt, computed tomography (CT) scan vs magnetic resonance imaging (MRI), and the specifics of a potential trial, including willingness to undergo randomisation, and measures of effectiveness and acceptability. CONCLUSION: A Delphi process, initiated by patients, identified areas of uncertainty with respect to behaviour, process, and the design of a targeted screening programme for thoracic aortic disease that requires further research prior to any future trial.

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.

The Impact of Suprarenal Fixation on Renal Function Following Endovascular Abdominal Aortic Aneurysm Repair: Meta-analysis Based on Estimated Glomerular Filtration Rate.

BACKGROUND: Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is currently used routinely to treat AAA. Suprarenal fixation (SRF) of EVAR grafts can lead to renal dysfunction. A meta-analysis of studies using estimated glomerular filtration rate (eGFR) as a measure of renal injury to assess the effect of SRF on renal function was performed. METHODS: An electronic search was carried out to identify all articles that reported on renal injury following SRF versus infrarenal fixation (IRF) EVAR, and 24 studies were identified. Formal meta-analysis was used to assess eGFR drop at 1 and 5 years. The primary outcome measure was a drop in eGFR >20% at 1 year; secondary measures included eGFR drop >20% at 5 years and "renal dysfunction" based on the definition used in each publication. RESULTS: Five series reported eGFR reduction >20% at 1 year. The weighted odds ratio (OR) was 1.53 (95% CI 0.67-3.51, p = .31, I2 = 53.2%); 9.3% for SRF versus 7.4% for IRF. One study reported eGFR based renal dysfunction at 5 years: OR 1.77 (95% CI 1.04-3.02, p = .03); 16.9% for SRF versus 10.3% for IRF. Nineteen series reported some form of renal dysfunction (5287 SRF vs. 4386 IRF patients, mean follow up: 20.5 months, range 72 h to 5 years). The weighted OR was 1.32 (95% CI 1.01-1.71, p = .03, I2 = 28.4%); 5.1% for SRF versus 4.6% for IRF. "Renal dysfunction" definitions varied greatly and were based on creatinine or other inaccurate methods. CONCLUSION: EVAR using SRF does not lead to a significant drop in renal function at 1 year, based on eGFR. Long-term results are limited. Authors should report long-term renal injury using eGFR and not inaccurate arbitrary measures, which are currently common in the literature.

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.

Cardiovascular Risk Reduction is Important for Improving Patient and Graft Survival After Ligation and Bypass Surgery for Popliteal Artery Aneurysm.

OBJECTIVES: To report outcomes following ligation and bypass (LGB) surgery for popliteal artery aneurysm (PAA) and study factors influencing patient and graft survival. MATERIALS AND METHODS: A retrospective review of patients undergoing LGB surgery for PAA between September 1999 and August 2012 at a tertiary referral vascular unit was performed. Primary graft patency (PGP), primary-assisted graft patency (PAGP), and secondary graft patency (SGP) rates were calculated using survival analyses. Patient, graft aneurysm-free survival (GAFS), aneurysm reperfusion-free survival (ARFS), and amputation-free survival (AFS) rates were also calculated. Log-rank testing and Cox proportional hazards modeling were used to perform univariate and multivariate analysis of influencing factors, respectively. RESULTS: Eighty-four LGB repairs in 69 patients (mean age 71.3 years, 68 males) were available for study. The 5-year PGP, PAGP, SGP, and patient survival rates were 58.1%, 84.4%, 85.2%, and 81.1%, respectively. On multivariate analysis, the principal determinants of PGP were urgency of operation ( P = .009) and smoking status ( P = .019). The principal determinants of PAGP were hyperlipidemia status ( P = .048) and of SGP were hyperlipidemia ( P = .042) and cerebrovascular disease (CVD) status ( P = .045). The principal determinants of patient survival were previous myocardial infarction ( P = .004) and CVD ( P = .001). The 5-year GAFS, ARFS, and AFS rates were 87.9%, 91.6%, and 96.1%, respectively. CONCLUSION: This study has shown that traditional cardiovascular risk factors, such as a smoking and ischemic heart disease, are the most important predictors of early graft failure and patient death following LGB surgery for PAA.

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.

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.

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.

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.

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.

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.

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.

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.