The Impact of the COVID-19 Pandemic on a Dedicated Vascular Emergency Clinic.

BACKGROUND: Vascular Emergency Clinics (VEC) improve patient outcomes in chronic limb-threatening ischemia (CLTI). They provide a "1 stop" open access policy, whereby "suspicion of CLTI" by a healthcare professional or patient leads to a direct review. We assessed the resilience of the outpatient VEC model to the first year of the coronavirus disease (COVID-19) pandemic. METHODS: A retrospective review of a prospectively maintained database of all patients assessed in our VEC for lower limb pathologies between March 2020 and April 2021 was performed. This was cross-referenced to national and loco-regional Governmental COVID-19 data. Individuals with CLTI were further analysed to determine Peripheral Arterial Disease-Quality Improvement Framework compliance. RESULTS: Seven hundred and ninety one patients attended for 1,084 assessments (Male n = 484, 61%; Age 72.5 ± standard deviation 12.2 years; White British n = 645, 81.7%). In total, 322 patients were diagnosed with CLTI (40.7%). A total of 188 individuals (58.6%) underwent a first revascularization strategy (Endovascular n = 128, 39.8%; Hybrid n = 41, 12.7%; Open surgery n = 19, 5.9%; Conservative n = 134, 41.6%). Major lower limb amputation rate was 10.9% (n = 35) and mortality rate was 25.8% (n = 83) at 12 months of follow-up. Median referral to assessment time was 3 days (interquartile range: 1-5). For the nonadmitted patient with CLTI, the median assessment to intervention was 8 days (interquartile range: 6-15) and median referral to intervention time of 11 days (11-18). CONCLUSIONS: The VEC model has demonstrated strong resilience to the COVID-19 pandemic with rapid treatment timelines maintained for patients with CLTI.

Effect of high-pain versus low-pain structured exercise on walking ability in people with intermittent claudication: meta-analysis.

BACKGROUND: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC). METHODS: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms-structured low-pain exercise, structured high--pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome. RESULTS: Some 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, -0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA. CONCLUSION: There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).

Effects of Left Renal Vein Ligation During Open Abdominal Aortic Aneurysm Repair on Renal Function.

OBJECTIVE: Left renal vein (LRV) ligation is performed during open abdominal aortic aneurysm (AAA) repair to facilitate proximal anastomosis. Its impact on short, medium, and long term renal function has not been investigated in detail using appropriately validated endpoints. METHODS: This was a nested case control study using data from a prospectively maintained AAA institutional dataset (tertiary centre). A total of 76 patients who underwent elective open AAA repair and had LRV ligation (1 January 2012 to 1 January 2018) were individually case matched based on age (within two years), sex, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologist (ASA) score, chronic kidney disease (CKD) stage, and history of diabetes with 76 patients who had open AAA repair without LRV ligation. Renal outcomes were compared between groups, including proportion of patients developing acute kidney injury (AKI) using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, proportion developing major adverse kidney events (MAKE90) at 90 days (comprising mortality and/or decrease in eGFR >25%), and absolute decrease in eGFR at latest follow up. RESULTS: A higher proportion of patients developed AKI and MAKE90 in the LRV ligation group (AKI: 11 patients [14.8%] vs. 2 [2.6%], p = .009; MAKE90: 6 [7.9%] vs. 1 [1.3%] p = .053, in the LRV ligation and the non-LRV ligation groups, respectively) - even though the difference in the MAKE90 endpoint was not statistically significant. Changes in eGFR were not statistically different in the LRV ligation group at 90 days (4.0 ± 1.1 mL/min/1.73 m2vs. 4.4 ± 2.1, p = .64) or by the time of latest follow up (median: 28 months; 3.7 ± 1.6 vs. 2.6 ± 2.0, p = .55). CONCLUSION: Ligation of the LRV is associated with increased levels of AKI and renal deterioration in the early post-operative phase using validated reporting criteria; however, long term renal function does not seem to be affected.

Editor's Choice - The Impact of Endovascular Aneurysm Repair on Long Term Renal Function Based on Hard Renal Outcomes.

INTRODUCTION: Over the short term endovascular aneurysm repair (EVAR) is associated with superior outcomes compared with open repair; however, the progression of renal function after EVAR remains unknown because of the use of inconsistent reporting measures. The aim was to define long term renal decline following elective EVAR using estimated glomerular filtration rate (eGFR). METHODS: The prospectively maintained in house database was used to identify consecutive patients having elective EVAR who had been followed up for more than five years. Overall, 275 patients (23 females, 8%; mean age, 75 years) who were not previously on renal replacement therapy (RRT) were included (January 2000 to July 2010). Pre-operative, post-operative, and most recent eGFR values were evaluated using the chronic kidney disease epidemiology collaboration equation. The primary outcome was change in eGFR at latest follow up. RESULTS: Patients were followed up over a median of 9 years (range 5-17 years). Their mean eGFR dropped from a pre-operative value of 67 mL/min/1.73 m2 (standard deviation [SD]: 9.4) to 52 mL/min/1.73 m2 (SD 7.7), which amounts to a yearly loss of 1.7 units; six patients (2%) required RRT (dialysis) during late follow up. Patients requiring RRT and those with an eGFR loss exceeding 20% at latest follow up compared with baseline were more likely to die during late follow up (odds ratio 2.4 and 3.3 respectively, p < .001). CONCLUSION: This analysis, with some of the longest available follow up to date, suggests that patients undergoing EVAR may experience a significant long term decrease in renal function. This needs to be taken into account when offering EVAR in younger patients; renal follow up and preservation should be optimised in this patient group.

Post-carotid Endarterectomy Hypertension. Part 2: Association with Peri-operative Clinical, Anaesthetic, and Transcranial Doppler Derived Parameters.

OBJECTIVE/BACKGROUND: The first paper in this series observed that pre-operative baroreceptor dysfunction and poorly controlled hypertension were independently predictive for identifying patients who went on to require treatment for post-endarterectomy hypertension (PEH). The second paper examines the influence of intra-operative patient, transcranial Doppler (TCD) ultrasound, and anaesthetic variables on the incidence of PEH. METHODS: In total, 106 patients underwent carotid endarterectomy (CEA) under general anaesthesia. Systolic blood pressure (SBP) changes, anaesthetic and vasoactive agents, analgesia, and post-operative pain scores, as well as TCD derived changes in middle cerebral artery (MCA) velocity during surgery were recorded. Patients who met pre-existing unit criteria for treating PEH after CEA (SBP > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to an established and validated protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH following CEA (26 in theatre recovery [25%], 27 back on the vascular surgery ward [25%]), whereas seven (7%) had SBP surges > 200 mmHg on the ward. Patients requiring treatment for PEH had significantly higher pre-induction SBP (174 ± 21 mmHg vs. 153 ± 21 mmHg; p < .001), the greatest decreases in SBP after induction of anaesthesia (median decrease 100 ± 32 mmHg vs. 83 ± 24 mmHg; p = .01) and were significantly more likely to experience moderate/severe pain scores post-operatively (p = .003). Logistic regression analysis of the pre- and intra-operative data revealed that higher pre-induction mean SBP and lower pre-operative (impaired) BRS were the only independent predictors of PEH. CONCLUSION: This analysis of intra-operative variables has demonstrated that patients with poorly controlled and/or labile hypertension at induction of general anaesthesia were those at greatest risk of requiring treatment for PEH in the post-operative period after CEA. No other variables, including use of vasopressors, treatment of hypotension, anaesthetic agents, or changes in MCA velocity after clamp release and restoration of flow were able to predict who might go on to require treatment for PEH. Identification of at-risk individuals and aggressive blood pressure control in the post-operative period remains the mainstay of treatment.

Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.

AIMS: To quantify the difference in long-term survival and cardiovascular morbidity between women and men undergoing elective abdominal aortic aneurysm (AAA) repair at National Health Service hospitals in England. METHODS AND RESULTS: Patients having elective repair of AAA were reviewed using the Hospital Episode Statistics and Office for National Statistics (ONS) datasets. The primary outcome measure was 30-day mortality and the secondary outcomes were 1-year, 5-year, and aortic-related mortality and post-operative complication rates. We used logistic regression and survival models to assess risk factors on the primary and secondary outcomes. Between 1 April 2002 and 31 March 2013, a total of 31 090 patients (4795 women and 26 295 men) underwent open AAA repair. Between 1 January 2006 and 31 March 2013, a total of 16 777 patients (2036 women and 14 741 men) underwent endovascular aneurysm repair (EVAR). All-cause and aortic-related mortalities at 30 days, 1 year, and 5 years were all higher in women, despite a lower prevalence of pre-operative cardiovascular risk factors. Female sex was a significant independent risk factor for 30-day mortality in both open repair [odds ratio (OR) 1.39; 95% confidence interval (CI) 1.25-1.56; P < 0.001] and EVAR (OR 1.57; 95% CI 1.23-2.00; P < 0.001) groups. Based on an all-cause long-term survival model, conditional on 30-day survival, the estimated hazard for women in the open repair group was significantly (P = 0.006) higher than men, but the sex difference was not significant in the EVAR group (P = 0.356). In the open repair group, women had significantly (P < 0.001) higher cumulative incidence probabilities for both aortic-related mortality and other-cause mortality. In the EVAR group, women had significantly (P < 0.001) higher mean cumulative incidence probabilities for the aortic-related mortality compared with men, but not for the other-cause mortality (P = 0.235). CONCLUSION: Women undergoing elective AAA repair at National Health Service hospitals in England had increased short- and long-term mortality and post-operative morbidity compared with men. These findings can be used to improve pre-operative counselling for women undergoing AAA repair, and highlight the need for female-specific pre-, peri-, and post-operative management strategies.

Renal Function is the Main Predictor of Acute Kidney Injury after Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Postoperative acute kidney injury (AKI) may occur in up to 18% of elective endovascular abdominal aortic aneurysm repair (EVAR) and has been associated with poor outcome; however, it is not clear which patients are at highest risk, to target renoprotection effectively. We sought to determine the predictive factors of AKI after elective EVAR. METHODS: Overall, 947 patients undergoing elective EVAR between January 2004 and December 2014 were analyzed, using prospectively collected data. Postoperative AKI was defined by serum creatinine change within 48 hr, as per the Kidney Disease Improving Global Outcomes guidelines. Cardiovascular and kidney-disease risk factors were entered in univariate and multivariate analyses to assess influence on AKI development. RESULTS: Overall, 167 (17.6%) patients developed AKI but only 2 patients required dialysis perioperatively. At multivariate analysis, adjusted for established AKI-risk factors and parameters that differed between groups at baseline, preoperative estimated glomerular filtration rate (eGFR; as per the chronic kidney disease epidemiology [CKD] formula); odds ratio (OR): 1.02 (per unit decrease); 95% confidence interval (CI): 1.003-1.041; P = 0.025; and chronic kidney disease (CKD) stage > 2 (OR: 1.28; 95% CI: 1.249-2.531, P = 0.001) were associated with development of AKI. CONCLUSIONS: AKI was common after elective infrarenal EVAR and preoperative renal function appears to be the main factor associated with AKI. Patients with a low eGFR need to be targeted with more aggressive renal protection.

Mortality from thoracic aortic diseases and associations with cardiovascular risk factors.

BACKGROUND: Temporal trends in mortality from thoracic aortic disease are unclear. This study examined trends in mortality from thoracic aortic aneurysm (TAA) and aortic dissection (AD) with the aim of identifying associations with trends in established cardiovascular risk factors. METHODS AND RESULTS: TAA and AD mortality (1994-2010) using International Classification of Diseases codes was extracted from the World Health Organization mortality database and age standardized. World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Eighteen World Health Organization member states were included (Europe=13, Australasia=2, North America=2, Asia=1). Ecological regression was performed of temporal trends in cardiovascular risk factors (1946-2010) and independent correlations to mortality trends. TAA and AD mortality trends show substantial heterogeneity but are generally declining. TAA mortality has increased in Hungary, Romania, Japan, and Denmark, and AD mortality has increased in Romania and Japan; therefore, the mortality decline is not universal. A linear relationship exists between trends in systolic blood pressure, cholesterol, and body mass index and mortality from TAA. Body mass index demonstrated a negative linear association with female AD mortality, whereas trends in systolic blood pressure demonstrated a positive linear relationship with male AD mortality. Trends in smoking prevalence were not associated with TAA or AD mortality trends. CONCLUSIONS: This population-level ecological regression provides evidence that mortality secondary to TAA and mortality secondary to AD are both in decline. Differences between countries could be explained by population-level changes in common cardiovascular risk factors. Public health measures could further reduce mortality from TAA and AD.

Aneurysm global epidemiology study: public health measures can further reduce abdominal aortic aneurysm mortality.

BACKGROUND: Contemporary data from Western populations suggest steep declines in abdominal aortic aneurysm (AAA) mortality; however, international trends are unclear. This study aimed to investigate global AAA mortality trends and to analyze any association with common cardiovascular risk factors. METHODS AND RESULTS: AAA mortality (1994-2010) using International Classification of Diseases codes were extracted from the World Health Organization mortality database and age standardized. The World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Nineteen World Health Organization member states were included (Europe, 14; Australasia, 2; North America, 2; Asia, 1). Regression analysis of temporal trends in cardiovascular risk factors (1946-2010) was done independently for correlations to AAA mortality trends. Global AAA mortality trends show substantial heterogeneity, with the United States and United Kingdom recording the greatest national decline, whereas internationally, male individuals and those <75 years of age demonstrated the greatest reductions. AAA mortality has increased in Hungary, Romania, Austria, and Denmark; therefore, the mortality decline is not universal. A positive linear relationship exists between global trends in systolic blood pressure (P≤0.03), cholesterol (P≤0.03), and smoking prevalence (P≤0.02) in males and females. Body mass index demonstrated a negative linear association with AAA mortality (P≤0.007), whereas fasting blood glucose showed no association. CONCLUSIONS: AAA mortality has not declined globally, and this study reveals that differences between nations can be explained by variations in traditional cardiovascular risk factors. Declines in smoking prevalence correlate most closely with declines in AAA mortality, and a novel obesity paradox has been identified that requires further investigation. Public health measures could therefore further reduce global AAA mortality, with greatest benefits in the younger age group.

A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated heritability (0.7); however, only a small number of associated genetic loci have been reported to date. In contrast, over 100 loci have now been reproducibly associated with either blood lipid profile and/or coronary artery disease (CAD) (both risk factors for AAA) in large-scale meta-analyses. This study employed a staged design to investigate whether the loci for these two phenotypes are also associated with AAA. Validated CAD and dyslipidaemia loci underwent screening using the Otago AAA genome-wide association data set. Putative associations underwent staged secondary validation in 10 additional cohorts. A novel association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839 G allele, which has been previously associated with both dyslipidaemia and CAD, reached genome-wide significance in 11 combined independent cohorts (meta-analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76-0.85, P = 7.2 × 10(-14)). Modelling for confounding interactions of concurrent dyslipidaemia, heart disease and other risk factors suggested that this marker is an independent predictor of AAA susceptibility. In conclusion, a genetic marker associated with cardiovascular risk factors, and in particular concurrent vascular disease, appeared to independently contribute to susceptibility for AAA. Given the potential genetic overlap between risk factor and disease phenotypes, the use of well-characterized case-control cohorts allowing for modelling of cardiovascular disease risk confounders will be an important component in the future discovery of genetic markers for conditions such as AAA.

Intervention Associated Acute Kidney Injury and Long-Term Cardiovascular Outcomes.

BACKGROUND: Acute kidney injury (AKI) has been associated with all-cause short- and long-term mortality. However, its association with cardiovascular (CV) events remains unclear. We sought to investigate this in patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm repair, as they are likely to develop both AKI and CV morbidity. A meta-analysis was subsequently performed to confirm this in other CV-interventions. METHODS: AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing EVAR (947 individuals) or OAR electively using the 'Acute Kidney Injury Network' criteria. A composite-endpoint was used, consisting of non-fatal myocardial infarction (MI), stroke, vascular event, hospitalisation due to heart failure and CV death. A systematic literature review identified studies reporting AKI-incidence and CV events. Risk ratios (RRs) at 1 and 5 years were combined using meta-analysis. RESULTS: During a median follow-up of 62 months (range 11-121), AKI was associated with CV events on adjusted (for CV risk-factors) analyses (Incidence 36% of EVAR, 32% of OAR patients; hazard ratio 1.73, 95% CI 1.06-3.39, p=0.03) for the overall population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year after coronary intervention (PCI) with a pooled RR of 1.76 (95% CI 1.45-2.83, p<0.001); at 2 years, 3 studies reported MI incidence on 17,773 patients after PCI with a pooled RR of 1.34 (95% CI 1.10-1.63, p=0.003). MI-incidence was reported 5 years after cardiac surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95% CI 1.43-1.81). CONCLUSION: AKI is associated with long-term CV events after surgery or endovascular intervention.

Impact of Fenestrated Endovascular Abdominal Aortic Aneurysm Repair on Renal Function.

PURPOSE: To investigate the impact of fenestrated endovascular aneurysm repair (fEVAR) on renal function perioperatively and at midterm. METHODS: A case-controlled study was performed involving 58 patients (mean age 75±7 years; 51 men) who underwent elective fEVAR for a juxtarenal or short-necked abdominal aortic aneurysm (AAA) matched on age, sex, smoking, diabetes, and baseline estimated glomerular filtration rate (eGFR) with a contemporaneous group undergoing open aneurysm repair (OAR) for the same indications. Perioperative incidence of acute kidney injury (AKI) and levels of eGFR at 30 days and 1 year were compared. A systematic literature review was performed to identify studies that had used eGFR as renal outcome after fEVAR; the pooled data were meta-analyzed using an eGFR drop >30% at 1 month and the latest follow-up as endpoints. Results are reported as the pooled proportion and 95% confidence interval (CI). RESULTS: The incidence of AKI after fEVAR was 28% compared to 10% after OAR (p=0.03). Following fEVAR, the mean eGFR dropped from 78±8 to 74±9 mL/min/1.73 m(2) at 30 days compared to a change from 79±8 to 80±16 mL/min/1.73 m(2) after OAR (p<0.01). However, the absolute drop in eGFR between fEVAR and OAR at 1 year was similar (7 mL/min/1.73 m(2); p=0.53); 7% of the fEVAR patients had an eGFR drop >30% at that point compared with none for OAR (p=0.12). The systematic literature review identified eGFR outcomes for 193 fEVAR patients. Combining these patients with the 58 from our cohort study, the pooled proportions of eGFR drop >30% were 20% (95% CI 9% to 39%) at 30 days and 8% (95% CI 0.5% to 13%) at the end of follow-up. CONCLUSION: fEVAR has a significant perioperative impact on renal function, but 1-year results are similar to OAR. fEVAR patients may benefit from targeted AKI prevention strategies that need to be assessed in relevant studies.

Hydrogen sulfide reduces inflammation following abdominal aortic occlusion in rats.

BACKGROUND: Remote renal ischemia-reperfusion injury (IRI) following infra-renal aortic occlusion leads to acute kidney injury and systemic inflammation. Hydrogen sulfide is a mediator of IRI and can ameliorate tissue injury in many organ systems. Its role in vascular surgery has yet to be established. We assessed the role of hydrogen sulfide in a rodent model of aortic occlusion. METHODS: Wistar rats were divided into sham, control, and treatment groups (n = 6). Inflammation was assessed using a nonrecovery protocol. The infra-renal aorta was cross-clamped for 60 min and animals were reperfused for 120 min. Ten minutes before clamp release, treatment animals received hydrogen sulfide (10, 30, or 50 µg/kg) and control animals received 0.9% saline injected into the retroperitoneum. Renal injury and histology were assessed by a recovery protocol. The procedure was identical to the nonrecovery arm but with a single dose of hydrogen sulfide (30 µg/kg) and animals were recovered for 7 days. RESULTS: There was no difference in animal weight between the groups (P = 0.337). In the nonrecovery arm, there was a reduction in serum levels of tumor necrosis factor alpha in sulfide-treated animals compared with controls (909 ± 98 vs. 607 ± 159 pg/mL; P = 0.0038). There was also a reduction in myeloperoxidase-positive cells in renal tissue in the sulfide-treated animals compared with controls (8 ± 4 vs. 17 ± 9; P = 0.03). There was no difference in histological injury score or endothelin-1 levels. In the recovery arm, there was no difference in renal function, Kidney Injury Molecule-1 levels, or histological injury scores. CONCLUSION: Hydrogen sulfide has systemic and renal anti-inflammatory effects in remote IRI following aortic occlusion in rats.

International trends in patient selection for elective endovascular aneurysm repair: sicker patients with safer anatomy leading to improved 1-year survival.

BACKGROUND: To review the trends in patient selection and early death rate for patients undergoing elective endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) in 3 countries. For this study, audit data from 4,163 patients who had undergone elective infrarenal EVAR were amalgamated. The data originated from Australia, Canada (Ontario), and England (London, Cambridge, and Leicester). METHODS: Statistical analyses were undertaken to determine whether patient characteristics and early death rate varied between and within study groups and over time. The study design was retrospective analysis of data collected prospectively between 1999 and 2012. RESULTS: One-year survival improved over time (P = 0.0013). Canadian patients were sicker than those in Australia or England (P < 0.001). American Society of Anesthesiologists classification (ASA) increased over time across all countries although more significantly in Canada. Age at operation remained constant, although older patients were treated more recently in London (P < 0.001). English centers treated larger aneurysms compared with Australia and Canada (P < 0.001). Australian centers treated a much larger proportion of aneurysms that were <55 mm than other countries. Preoperative creatinine levels decreased over time for all countries and centers (P < 0.001). Infrarenal neck angles have significantly decreased over time (P < 0.001). Recent data from London (UK) showed that operations were performed on longer (P < 0.001) and wider (P < 0.001) infrarenal necks than elsewhere. CONCLUSIONS: In this international comparison, several trends were noted including improved 1-year survival despite declining patient health (as measured by increasing ASA status). This may reflect greater knowledge regarding EVAR that centers from different countries have gained over the last decade and improved medical management of patients with aneurysmal disease.

A systematic review and meta-analysis of the association between markers of hemostasis and abdominal aortic aneurysm presence and size.

OBJECTIVE: The purpose of this study was to summarize the current evidence of the association between markers of hemostasis and both the presence and size of abdominal aortic aneurysms (AAAs). METHODS: A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines by use of the search terms "aneurysm AND abdominal AND aortic AND coagulation" NOT "thoracic." Outcome data including concentration of hemostatic marker, number of patients, and significance level were recorded. RESULTS: A total of 22 nonrandomized studies were included in the analysis, with a total of 9862 patients. Fibrinogen mean difference (MD) (0.43 g/L; 95% confidence interval [CI], 0.28-0.58 g/L; P ≤ .00001), D-dimer MD (325.82 ng/mL; 95% CI, 199.74-451.89 ng/mL; P ≤ .00001), and thrombin-antithrombin III complex MD (5.58 g/L; 95% CI, 3.34-7.83 g/L; P ≤ .0001) were significantly elevated in the presence of AAAs. Tissue plasminogen activator, prothrombin fragments F1+F2, and platelet count were not shown to be significantly different between patients with and those without AAAs. Meta-regression of studies reporting plasma D-dimer concentration and aneurysm diameter suggests a strong and significant association (r(2) = 0.94; P ≤ .0001). CONCLUSIONS: This study suggests that the presence of AAAs is associated with increased fibrin turnover, fibrinolysis, and thrombin generation, as shown by increased levels of fibrinogen, D-dimer, and thrombin-antithrombin III complex. This is clinically relevant because markers of hemostasis are independent risk factors for cardiovascular events, highlighting the necessity of addressing all modifiable cardiovascular risk factors in patients with AAAs. Furthermore, the finding that plasma D-dimer concentration appears to have a linear relationship with aneurysm diameter may be useful as a future biomarker of AAAs.

C-reactive protein polymorphism rs3091244 is associated with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) formation involves an inflammatory process with a strong genetic background. C-reactive protein (CRP) regulates inflammation and is elevated in patients with AAA. The aim of this study was to investigate the association of the triallelic (C, A, and T alleles) rs3091244 functional CRP single nucleotide polymorphism (SNP) with AAA. METHODS: This was a case-control study involving two independent populations: 351 AAA patients (mean aortic diameter, 6.25 ± 1.47 cm) and 391 controls (mean diameter, 2.4 ± 0.2 cm) were recruited from Greece (the main cohort); and 371 patients (mean diameter, 5.4 ± 1.0 cm) and 362 controls (mean diameter, 2.4 ± 0.6 cm) were recruited from the United Kingdom (replication cohort). The frequency of the functional triallelic (C, T, and A alleles) rs3091244 polymorphism was analyzed in univariate and adjusted (for cardiovascular risk factors) analyses, assuming that the rare T and A alleles have similar functional properties (pooled analysis for T and A). Three groups were constructed: group A included those with the rare T and A alleles (genotypes TT, AA, and TA), group B included heterozygotes for the C allele (CT, CA), and group C included C allele homozygotes (CC, reference genotype). Finally, meta-analysis of the two populations was performed together with previously reported results. RESULTS: Genotype distributions differed significantly between cases and controls in both cohorts (P < .001 and P = .001). Adjusted analysis (for all aneurysm-related risk-factors) showed an estimated odds ratio of 4.88 (95% confidence interval [CI], 2.96-8.04) for SNP group A and 2.38 (95% CI, 1.69-3.36) for SNP group B (P < .001 in both cases) in the initial cohort and 2.07 (95% CI, 1.33-3.21) for SNP group A and 1.70 (95% CI, 1.21-2.39) for SNP group B (P = .001 and .002) in the replication cohort. The SNP group A patients among the main cohort also had higher CRP levels (median, 26; interquartile range, 17-52 mg/L vs median, 4; interquartile range, 4-12 mg/L; P < .001). Aneurysms >5.5 cm were significantly more frequent among the SNP groups A and B compared with C allele homozygotes both in the main and the replication cohorts (P < .001 and P = .001, respectively). Meta-analysis of the two populations with previously reported results showed a positive association between minor-allele and aneurysm presence with an odds ratio of 1.47 (95% CI, 1.01-2.14; I(2) = 83.1%; P = .04). CONCLUSIONS: The rare T and A alleles were significantly related with AAA presence in both populations and correlated with higher CRP levels and AAA diameter.

Effect of anticoagulation and antiplatelet therapy on incidence of endoleaks and sac size expansions after endovascular aneurysm repair.

BACKGROUND: The effects of anticoagulation or antiplatelet therapy on the incidence of endoleak and aneurysm sac size after endovascular aneurysm repair (EVAR) are unclear. This study aims to determine whether these therapies affect the incidence of endoleaks or sac size expansions after EVAR. METHODS: The case notes of 407 patients (367 men and 40 women, mean age 74.7 years) who underwent elective EVAR between January 2006 and November 2011 were reviewed for medication history and EVAR-related outcomes. RESULTS: The median follow-up period was 18 months. There were 45 (11.1%) patients on warfarin (WA), 292 (71.7%) on antiplatelet therapy (AT) (aspirin, clopidogrel, or dipyridamole modified release), and 70 (17.2%) on no anticoagulation or antiplatelet therapy (NA). During the study period, 51 (12.5%) endoleaks were documented, 8 type I (AT = 6, NA = 0, and WA = 2) and 42 type II (AT = 31, NA = 9, and WA = 2). Medication did not significantly affect the incidence of type I (P = 0.24) (based on chi-squared analysis), type II (P = 0.33), or type III (P = 0.82) endoleaks, or sac expansions (P = 0.95). CONCLUSIONS: Warfarin and antiplatelet therapies are not associated with increased incidence of postoperative endoleaks or aneurysm sac expansion after EVAR. The data in this study support safe use of anticoagulant and antiplatelet medications in patients undergoing EVAR.

Changing epidemiology of abdominal aortic aneurysms in England and Wales: older and more benign?

BACKGROUND: Recent studies from Australia, New Zealand, and Sweden have reported declines in abdominal aortic aneurysm (AAA) incidence, prevalence, and mortality. This finding may have important implications for screening programs. This study determined trends in AAA incidence and mortality in England and Wales. METHODS AND RESULTS: Cause-specific mortality data for England and Wales were obtained from UK Office for National Statistics, and hospital admissions and procedures data for England were obtained from Hospital Episode Statistics from 2001 to 2009. Poisson regression models were constructed to estimate the relative change over time. Age-standardized rates for AAA mortality in England and Wales fell significantly by 35.7% from 2001 to 2009, which was largely due to a 35.3% drop in age-standardized ruptured AAA deaths. During the same period, ruptured AAA admissions and emergency AAA repairs in England declined by 29.3% and 35.5%, respectively. In contrast, nonruptured AAA admissions remained static, and nonemergency AAA repairs increased by 17.2%. The average ages for hospital admissions for nonruptured AAAs and ruptured AAAs increased by 0.19 years of age per annum (P<0.001) and 0.09 years of age per annum (P<0.001), respectively. Nonruptured AAA admissions increased by 21.4% in age band 75 years or more but declined by 11.7% in ages <75 years. CONCLUSIONS: AAA mortality, ruptured AAA admission, and emergency AAA repair have declined in England and Wales. However, nonruptured AAA admission has remained steady, with an increasing rate in older population offsetting a decreasing rate in younger population. This suggests a shift in AAA presentation to the older population. Present screening strategies may need reassessment to include consideration for increasing the age at which to screen men for AAAs.

Potential role for anti-angiogenic therapy in abdominal aortic aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a condition that mainly affects elderly men. At present, there is no effective medical therapy that can retard aneurysm growth or prevent aneurysm rupture. There is evidence that angiogenesis within the wall of an aortic aneurysm may play key roles in aneurysm progression as well as rupture. The use of anti-angiogenic therapy as potential medical therapy in AAA is a promising strategy but has never been studied in detail. DESIGN: This paper discusses the basic mechanisms of angiogenesis, the role played by angiogenesis in aortic aneurysms and the potential therapeutic role of anti-angiogenic drugs against aneurysm expansion or rupture. RESULTS: Angiogenesis is a multi-step process which is fundamental for growth and differentiation of various tissues within a multi-cellular organism. Hypoxia and inflammation are key stimuli for activation of neoangiogenesis. Investigations in both human tissues and animal models of AAA have shown that angiogenesis is a pathological hallmark of AAA and appears to play a role in the development and progression of the condition. Pre-clinical studies have shown that anti-angiogenic drugs can potentially be effective in reducing the intensity of aneurysm formation, suggesting that such drugs may potentially be useful as novel drug therapy for AAA in humans. CONCLUSION: Current evidence suggests that angiogenesis contributes to the destructive processes within aneurysmal aortic wall. As novel drug therapy for aortic aneurysms (for use in humans) is still eluding researchers, anti-angiogenic pathway appears to be an attractive approach.

Endovascular aortic aneurysm repair in patients with hostile neck anatomy.

PURPOSE: To report a systematic review and meta-analysis of outcomes following endovascular aneurysm repair (EVAR) in patients with hostile neck anatomy (HNA) vs. those with favorable neck anatomy (FNA). METHODS: Systematic review and meta-analysis of data on EVAR in patients with HNA and FNA was performed by 2 reviewers in February 2013. An eligible study was required to have at least 50 participants and to incorporate one or more of the HNA criteria of neck length <15 mm, neck diameter >28 mm, and/or angulation >60°. Of the 24 full-length articles ultimately reviewed, 8 were excluded, resulting in 16 articles that were suitable for inclusion in the meta-analysis. The study size ranged from 55 to 5183 participants, with a total of 8920 patients in the FNA group and 3039 patients in the HNA group. Mean follow-up ranged from 9 to 49 months. RESULTS: Analysis of the pooled data revealed a significant increase in 30-day mortality (2.4% FNA vs. 3.5% HNA; OR 1.60, 95% CI 1.13 to 2.27; p<0.01), intraoperative adjuncts (8.8% FNA vs. 15.4% HNA; OR 1.88, 95% CI 1.15 to 3.07; p=0.01), and 30-day migration (0.9% FNA vs. 1.6% HNA; OR 2.08, 95% CI 1.20 to 3.62; p=0.009) in patients with HNA. A decrease in primary technical success (97.5% FNA vs. 93.8% HNA; OR 0.41, 95% CI 0.18 to 0.93; p=0.03) was significant when all 3 criteria were used to define HNA. For outcomes at >30 days, the increase in secondary interventions (OR 1.29, 95% CI 1.00 to 1.66; p=0.05) approached significance, but aneurysm-related mortality, all-cause mortality, migration, and aortic rupture did not achieve statistical significance. There was no difference in rates of sac expansion. Analysis of endoleak rates revealed a significant increase in 30-day type I endoleaks (OR 2.92, 95% CI 1.61 to 5.30; p<0.001) and late type I endoleaks (OR 1.71, 95% CI 1.31 to 2.23; p<0.0001) in patients with HNA. CONCLUSION: These results suggest that performing EVAR in patients with HNA increases the technical difficulty and results in poorer short-term outcomes. The higher rates of early and late type I endoleaks, along with secondary interventions, suggest that increased monitoring should be performed in this category of patient to ensure rapid treatment.