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.

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.

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.

Factors influencing short- and long-term mortality after lower limb amputation.

Mortality after lower limb amputation is high, with UK 30-day mortality rates of 9-17%. We performed a retrospective analysis of factors affecting early and late outcome after lower limb amputation for peripheral vascular disease or diabetic complications at a UK tertiary referral vascular centre between 2003 and 2010. Three hundred and thirty-nine patients (233 male), of median (IQR [range]) age 73 (62-79 [26-92]) years underwent amputation. Thirty-day mortality was 12.4%. On regression modelling, the risk of 30-day mortality was increased in patients of ASA grade ≥ 4 (OR 4.23, 95% CI 2.07-8.63), p < 0.001 and age between 74 and 79 years (OR 3.8, 95% CI 1.10-13.13), p = 0.04 and older than 79 years (OR 4.08, 95% CI 1.25-13.25), p = 0.02. Peri-operative (30-day) mortality for these groups was 23.2%, 13.7% and 18.8%, respectively. Survival and Cox regression analysis demonstrated that long-term mortality was associated with: age 74-79 years (HR 2.15, 95% CI 1.38-3.35), p = 0.001; age > 79 years (HR 2.78, 95% CI 1.82-4.25), p < 0.001; ASA grade ≥ 4 (HR 2.04, 95% CI 1.51-2.75), p < 0.001; out-of-hours operating (HR 1.51, 95% CI 1.08-2.10), p = 0.02; and chronic kidney disease stage 4-5 (1.57, 95% CI 1.07-2.30), p = 0.02. Anaesthetic technique was associated with long-term mortality on survival analysis (p = 0.04), but not when analysed using regression modelling. Mortality after lower limb amputation relates to patient age, ASA, out-of-hours surgery and renal dysfunction. These data support lower limb amputations' being performed during daytime hours and after modification replace with 'of ' correctable risk factors.

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.

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 after endovascular aneurysm repair.

BACKGROUND: The aim was to assess the risk of rupture, and determine the benefits of intervention for the treatment of type II endoleak after endovascular abdominal aortic aneurysm repair (EVAR). METHODS: This systematic review was done according to PRISMA guidelines. Outcome data included incidence, spontaneous resolution, sac expansion, interventions, clinical success, and complications including conversion to open repair, and rupture. RESULTS: Thirty-two non-randomized retrospective studies were included, totalling 21 744 patients who underwent EVAR. There were 1515 type II endoleaks and 393 interventions. Type II endoleak was seen in 10·2 per cent of patients after EVAR; 35·4 per cent resolved spontaneously. Fourteen patients (0·9 per cent) with isolated type II endoleak had ruptured abdominal aortic aneurysm; six of these did not have known aneurysm sac expansion. Of 393 interventions for type II endoleak, 28·5 per cent were unsuccessful. Translumbar embolization had a higher clinical success rate than transarterial embolization (81 versus 62·5 per cent respectively; P = 0·024) and fewer recurrent endoleaks were reported (19 versus 35·8 per cent; P = 0·036). Transarterial embolization also had a higher rate of complications (9·2 per cent versus none; P = 0·043). CONCLUSION: Aortic aneurysm rupture after EVAR secondary to an isolated type II endoleak is rare (less than 1 per cent), but over a third occur in the absence of sac expansion. Translumbar embolization had a higher success rate with a lower risk of complications.