Objectives Embolizing an abdominal aortic aneurysm sac through a transcaval approach is a novel approach to treat type-II endoleaks that occur following aortic endografting. This study reviews the outcomes of this treatment in one of the few centres in Australia that offers this procedure. Methods A retrospective cohort study was conducted, including patients who had received transcaval embolisation of type-II endoleak over a 9-year period. The primary outcome was clinical success, defined as the absence of endoleak on post-procedural ultrasonography at 6-weeks, provided the procedure was successfully completed. Other outcomes included clinical success at 1-year, aneurysm size, rupture and aneurysm-related mortality. Results Twelve patients with type-II endoleak and AAA sac growth received transcaval embolisation. Technical success was achieved in 91.7% of cases, in which both Onyx 34 and coils were deployed into the sac. Clinical success, defined as an absence of endoleak on ultrasonography 6-weeks after a technically successful procedure, was achieved in 66.7% of patients, none of whom had evidence of endoleak at 1-year post-procedure. In patients whom clinical success was achieved, there was a decrease in sac size during follow-up, from 72.5 ± 13.1 at 6-weeks to 66.0 ± 12.1 at 1-year post-procedure. Aneurysm sac size continued to enlarge if clinical success was not observed, with an average sac size of 72.0 ± 14.1 at 6-weeks increasing to 76.9 ± 15.2 at 1-year. No patients suffered AAA rupture or AAA-related mortality during follow-up. Conclusions This study reports a high technical and clinical success rate, with outcomes that could suggest that this procedure could induce sac regression.

OBJECTIVE:Peripheral artery disease affects approximately 250 million people globally. Multiple randomised controlled trials have compared bypass and endovascular interventions but the optimum revascularisation approach remains unclear. The recently published BEST-CLI and BASIL-2 trials provide current and robust data addressing this question, however their findings are not concordant. This systematic review and meta-analysis provides an overview of the worldwide randomised evidence comparing bypass surgery and endovascular revascularisation in lower limb peripheral artery disease. METHODS:A comprehensive literature search of MEDLINE, Embase and CENTRAL databases was performed of all time periods up to 7 May 2023 to identify randomised controlled trials comparing bypass and endovascular revascularisation for treating lower limb peripheral artery disease. The primary outcome was major amputation. Secondary outcomes were mortality, re-intervention, 30-day adverse events and 30-day mortality. Odds ratios were calculated and pooled using the random-effects model. Risk of bias was assessed using the Cochrane risk of bias 2 tool. RESULTS:Fourteen cohorts were identified across thirteen studies, enrolling 3840 patients. There was no significant difference in major amputation (OR 1.12; 95% CI 0.80-1.57) or mortality (OR 0.96; 95% CI 0.79-1.17) between the bypass and endovascular groups. Bypass was associated with a significant reduction in re-intervention compared with endovascular treatment (OR 0.57, 95% CI 0.40-0.82). CONCLUSIONS:These findings suggest that rates of major amputation and mortality are similar following bypass and endovascular interventions. Patients who undergo bypass surgery have a significantly lower re-intervention rate post-operatively.

Objective: This retrospective cohort study investigated the anatomical distribution, severity, and outcome of peripheral artery disease (PAD) in Aboriginal and Torres Strait Islanders compared with non-indigenous Australians.Methods: The distribution, severity, and outcome of PAD were assessed using a validated angiographic scoring system and review of medical records in a cohort of Aboriginal and Torres Strait Islander and non-indigenous Australians. The relationship between ethnicity and PAD severity, distribution, and outcome were examined using non-parametric statistical tests, Kaplan-Meier and Cox proportional hazard analyses.Results: Seventy-three Aboriginal and Torres Strait Islanders and 242 non-indigenous Australians were included and followed for a median of 6.7 [IQR 2.7, 9.3] years. Aboriginal and Torres Strait Islander patients were more likely to present with symptoms of chronic limb threatening ischaemia (81% vs. 25%; p < .001), had greater median [IQR] angiographic scores for the symptomatic limb (7 [5, 10] vs. 4 [2, 7]) and tibial arteries (5 [2, 6] vs. 2 [0, 4]) and had higher risk of major amputation (HR 6.1, 95% CI 3.6 -10.5; p < .001) and major adverse cardiovascular events (HR 1.5, 95% CI 1.0 -2.3; p = .036) but not for revascularisation (HR 0.8, 95% CI 0.5 -1.3; p = .37) compared with non-indigenous Australians. The associations with major amputation and major adverse cardiovascular events were no longer statistically significant when adjusted for limb angiographic score.Conclusion: Compared with non-indigenous patients, Aboriginal and Torres Strait Islander Australians had more severe tibial artery disease and a higher risk of major amputation and major adverse cardiovascular events.

Objective: Carotid artery stenosis may present without the classical symptoms of transient ischaemic attack or stroke but the rates of stroke for these presentations is unknown. The aim of this study was to examine the rates of stroke in patients with different presentations of carotid artery stenosis.Methods: A multicentre prospective cohort study was conducted across three Australian vascular centres with low rates of surgical treatment of patients without transient ischaemic attack or stroke. Patients with a 50 99% carotid artery stenosis presenting with non-focal symptoms (e.g., dizziness or syncope; n = 47), prior contralateral carotid endarterectomy (n = 71), prior ipsilateral symptoms more than six months earlier (n = 82), and no symptoms (n = 304) were recruited. The primary outcome was ipsilateral ischaemic stroke. Secondary outcomes were any ischaemic stroke and cardiovascular death. Data were analysed using Cox proportional hazard and Kaplan-Meier analyses.Results: Between 2002 and 2020, 504 patients were enrolled (mean age 71 years, 30% women) and followed for a median of 5.1 years (interquartile range 2.5, 8.8; 2 981 person years). Approximately 82% were prescribed antiplatelet therapy, 84% were receiving at least one antihypertensive drug, and 76% were prescribed a statin at entry. After five years the incidence of ipsilateral stroke was 6.5% (95% confidence interval [CI] 4.3 - 9.5). There were no statistically significant differences in the annual rate of ipsilateral stroke among people with non-focal symptoms (2.1%; 95% CI 0.8 - 5.7), prior contralateral carotid endarterectomy (0.2%; 0.03 - 1.6) or ipsilateral symptoms > 6 months prior (1.0%; 0.4 - 2.5) compared with those with no symptoms (1.2%; 0.7 - 1.8; p = .19). There were no statistically significant differences in secondary outcomes across groups.Conclusion: This cohort study showed no large differences in stroke rates among people with different presentations of carotid artery stenosis.

Objective: Observational studies demonstrate an inverse association between type II diabetes and abdominal aortic aneurysm (AAA) for reasons that are unclear. The aim of this study was to clarify the causal association between type II diabetes predisposition and AAA using Mendelian randomisation. Methods: Effect estimates for single nucleotide polymorphisms (SNPs) associated with diabetes were obtained from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) consortium to construct a genetic instrumental variable. Corresponding effect estimates for associations of these SNPs with AAA were obtained from the International Aneurysm Consortium comprising six separate AAA genomewide association studies (4 972 cases and 99 858 controls). Mendelian randomisation estimates were calculated using inverse variance, weighted median, and MR-Egger methods, and compared against recently published observational estimates. Results: A genetic risk score was constructed from 206 SNPs associated with diabetes. All three Mendelian randomisation models showed no effect of genetic liability to diabetes and risk of AAA (inverse variance: odds ratio 1.04 per unit higher log odds, 95% 0.98 - 1.11, p = .19; MR-Egger slope p = .33; weighted median p = .50). Results were similar after excluding the TCF7L2 locus (inverse variance p = .075). Findings from the Mendelian randomisation analysis differed from previous observational reports of an inverse association (p(dif) < .001). Conclusion: Lifelong genetic predisposition to diabetes does not appear to protect against AAA. These findings differ from traditional epidemiological studies showing an inverse association between diabetes and AAA, for reasons that remain unclear.

Objective: Asymptomatic carotid stenosis (ACS) is associated with an increased risk of ischaemic stroke and myocardial infarction. Risk scores have been developed to detect individuals at high risk of ACS, thereby enabling targeted screening, but previous external validation showed scope for refinement of prediction by adding additional predictors. The aim of this study was to develop a novel risk score in a large contemporary screened population. Methods: A prediction model was developed for moderate (>= 50%) and severe (>= 70%) ACS using data from 596 469 individuals who attended screening clinics. Variables that predicted the presence of >= 50% and >= 70% ACS independently were determined using multivariable logistic regression. Internal validation was performed using bootstrapping techniques. Discrimination was assessed using area under the receiver operating characteristic curves (AUR005) and agreement between predicted and observed cases using calibration plots. Results: Predictors of >= 50% and >= 70% ACS were age, sex, current smoking, diabetes mellitus, prior stroke/ transient ischaemic attack, coronary artery disease, peripheral arterial disease, blood pressure, and blood lipids. Models discriminated between participants with and without ACS reliably, with an AUROC of 0.78 (95% confidence interval [CI] 0.77-0.78) for >= 50% ACS and 0.82 (95% CI 0.81-0.82) for >= 70% ACS. The number needed to screen in the highest decile of predicted risk to detect one case with >= 50% ACS was 13 and that of >= 70% ACS was 58. Targeted screening of the highest decile identified 41% of cases with >= 50% ACS and 51% with >= 70% ACS. Conclusion: The novel risk model predicted the prevalence of ACS reliably and performed better than previous models. Targeted screening among the highest decile of predicted risk identified around 40% of all cases with >= 50% ACS. Initiation or intensification of cardiovascular risk management in detected cases might help to reduce both carotid related ischaemic strokes and myocardial infarctions. Conclusion: The novel risk model predicted the prevalence of ACS reliably and performed better than previous models. Targeted screening among the highest decile of predicted risk identified around 40% of all cases with >= 50% ACS. Initiation or intensification of cardiovascular risk management in detected cases might help to reduce both carotid related ischaemic strokes and myocardial infarctions.

Background: "Structural factors" relating to organization of hospitals may affect procedural outcomes. This study's aim was to clarify associations between structural factors and outcomes after carotid endarterectomy (CEA) and carotid endarterectomy stenting (CAS). Methods: A systematic review of studies published in English since 2005 was conducted. Structural factors assessed were as follows: population size served by the vascular department; number of hospital beds; availability of dedicated vascular beds; established clinical pathways; surgical intensive care unit (SICU) size; and specialty of surgeon/interventionalist. Primary outcomes were as follows: mortality; stroke; cardiac complications; length of hospital stay (LOS); and cost. Results: There were 11 studies (n = 95,100 patients) included in this systematic review. For CEA, reduced mortality (P < 0.0001) and stroke rates (P = 0.001) were associated with vascular departments serving > 75,000 people. Larger hospitals were associated with lower mortality, stroke rate, and cardiac events, compared with smaller hospitals (less than 130 beds). Provision of vascular beds after CEA was associated with lower mortality (P = 0.0008) and fewer cardiac events (P = 0.03). Adherence to established clinical pathways was associated with reduced stroke and cardiac event rates while reducing CEA costs. Large SICUs (>= 7 beds) and dedicated intensivists were associated with decreased mortality after CEA while a large SICU was associated with reduced stroke rate (P = 0.001). Vascular surgeons performing CEA were associated with lower stroke rates and shorter LOS (P = 0.0001) than other specialists. CAS outcomes were not influenced by specialty but costless when performed by vascular surgeons (P < 0.0001). Conclusions: Structural factors affect CEA outcomes, but data on CAS were limited. These findings may inform reconfiguration of vascular services, reducing risks and costs associated with carotid interventions.

Background Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. Methods MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). Discussion Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. Trial registration Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018

Background Recommendations for screening patients with lower-extremity arterial disease (LEAD) to detect asymptomatic carotid stenosis (ACS) are conflicting. Prediction models might identify patients at high risk of ACS, possibly allowing targeted screening to improve preventive therapy and compliance. Methods A systematic search for prediction models for at least 50 per cent ACS in patients with LEAD was conducted. A prediction model in screened patients from the USA with an ankle : brachial pressure index of 0.9 or less was subsequently developed, and assessed for discrimination and calibration. External validation was performed in two independent cohorts, from the UK and the Netherlands. Results After screening 4907 studies, no previously published prediction models were found. For development of a new model, data for 112 117 patients were used, of whom 6354 (5.7 per cent) had at least 50 per cent ACS and 2801 (2.5 per cent) had at least 70 per cent ACS. Age, sex, smoking status, history of hypercholesterolaemia, stroke/transient ischaemic attack, coronary heart disease and measured systolic BP were predictors of ACS. The model discrimination had an area under the receiver operating characteristic (AUROC) curve of 0.71 (95 per cent c.i. 0.71 to 0.72) for at least 50 per cent ACS and 0.73 (0.72 to 0.73) for at least 70 per cent ACS. Screening the 20 per cent of patients at greatest risk detected 12.4 per cent with at least 50 per cent ACS (number needed to screen (NNS) 8] and 5.8 per cent with at least 70 per cent ACS (NNS 17). This yielded 44.2 and 46.9 per cent of patients with at least 50 and 70 per cent ACS respectively. External validation showed reliable discrimination and adequate calibration. Conclusion The present risk score can predict significant ACS in patients with LEAD. This approach may inform targeted screening of high-risk individuals to enhance the detection of ACS.

Background: Among patients with severe carotid artery stenosis but no recent symptoms from it, carotid surgery involves hazards, but then reduces long-term stroke rates. Triple-drug therapy (statin, anti-thrombotic, anti-hypertensive) also reduces long-term stroke rates in these asymptomatic patients. Past trials of carotid endarterectomy (CEA) can help assess the proportional reduction by carotid surgery in long-term stroke rates before and since triple-drug therapy became common. Methods: Intention-to-treat analyses used individual data from all 3 properly randomised trials among asymptomatic patients of immediate CEA vs deferral of any CEA until definitely indicated. Analyses of long-term stroke rates, censored at non-stroke death, used Kaplan-Meier life-tables and logrank methods. Findings: 2599 patients were allocated immediate CEA vs 2627 allocated deferral, with 89% vs 7% operated on within 1 year. Non-perioperative stroke rates were halved by allocation to immediate CEA (10-year stroke rate ratio [RR]=0.54, 95%CI 0.46-0.65, p<0.0001; 5.8% vs 11.7% by year 5); for fatal/disabling strokes, RR=0.55 (0.40-0.77, p<0.0001). Proportional reductions depended little on gender, or other patient characteristics. Ipsilateral and contralateral strokes were both reduced. In analyses restricted to strokes occurring on triple-drug therapy, absolute hazards and long-term stroke rates were lower than in the overall findings, but allocation to immediate CEA still halved long-term stroke rates (RR=0.56, 0.41-0.76; p=0.0002; 3.5% vs 7.0% by year 5). Of all CEAs undertaken, 3.1% involved perioperative stroke/death (71/3348; 40 dead/disabled, 31 not). Interpretation: Successful CEA halves long-term stroke rates. Net benefits will depend on surgical risks, long-term stroke rates without surgery, and life expectancy.Trial Registration: The trial is registered with the ISRCTN registry, ISRCTN21144362.Funding: MRC.Declaration of Interest: None to declare.

INTRODUCTION:Mendelian randomisation (MR) has been suggested to be able to overcome biases of observational studies, but no meta-analysis is available on MR studies on abdominal aortic aneurysm (AAA). This systematic review and Meta-analysis examined the evidence of causal risk factors for AAA identified in MR studies. METHODS:Publicly available databases were systematically searched for MR studies that reported any causal risk factors for AAA diagnosis. Meta-analyses were performed using random effect models and reported as odds ratio (OR) and 95% confidence intervals (CI). Study quality was assessed using a modified version of Strengthening the Reporting of Mendelian Randomisation Studies (STROBE-MR) guidelines. RESULTS:Sixteen MR studies involving 34,050 patients with AAA and 2,205,894 controls were included. Meta-analyses suggested that one standard deviation increase in high density lipoprotein (HDL) significantly reduced (OR: 0.66, 95% CI: 0.61, 0.72) and one standard deviation increase in low density lipoprotein (LDL) significantly increased the risk (OR: 1.68, 95%, CI: 1.55, 1.82) of AAA. One standard deviation increase in triglycerides did not significantly increase the risk of AAA (OR: 1.21, 95% CI: 0.86, 1.71). Quality assessment suggested that ten and five studies were of low and moderate risk of bias respectively, with one study considered as high risk of bias. CONCLUSION:This meta-analysis suggests LDL and HDL are positive and negative casual risk factors for AAA.

Background Large studies are required for reliable estimates of important risk factors for abdominal aortic aneurysm ( AAA ). This could guide targeted AAA screening programs, particularly in subgroups like women who are currently excluded from such programs. Method and Results In a cross‐sectional study, 1.5 million women and 0.8 million men without known vascular disease attended commercial screening clinics in the United Kingdom or United States from 2008 to 2013. Measurements of vascular risk factors were related to AAA using logistic regression with correction for regression dilution bias. Screening detected 12 729 new AAA cases (0.6%). Compared with never smoking, current smoking was associated with 15 times the risk of AAA among women (risk ratio 15.0, 95% CI 13.2–17.0) and 7 times among men (7.3, 6.4–8.2). In women aged <75 years, the risk of AAA was nearly 30 times greater in current smokers (26.4, 20.3–34.2). In every age group, the prevalence of AAA in female smokers was greater than in male never‐smokers. Positive log‐linear associations with AAA for women and men were also observed for usual body mass index, usual systolic blood pressure, height, usual low‐density lipoprotein cholesterol, and usual triglycerides. Conclusions Log‐linear increases in the risks of AAA with traditional vascular risk factors should be considered when evaluating populations that may be at‐risk for the development of AAA , and when considering potential treatments. However, at any given age, female smokers are at higher risk of AAA than male never‐smokers, and a policy of screening male never‐smokers but not higher‐risk female smokers is questionable.

Key PointsQuestionDoes telmisartan reduce the growth of small abdominal aortic aneurysms? FindingsIn this placebo-controlled randomized trial of 210 participants, a significant effect of telmisartan on abdominal aortic aneurysm growth rates was not shown. Telmisartan had no effect on requirement for abdominal aortic aneurysm repair or aneurysm rupture. MeaningFurther adequately powered trials are needed to assess the efficacy of medical therapies to slow abdominal aortic aneurysm growth. ImportanceCurrently there is no drug therapy for abdominal aortic aneurysm (AAA). ObjectiveTo test the efficacy of the angiotensin receptor blocker telmisartan in slowing AAA growth in the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. Design, Setting, and ParticipantsA randomized, double-blind, placebo-controlled trial recruited participants between September 6, 2011, and October 5, 2016, to evaluate the efficacy of telmisartan treatment in patients with AAA. Participants with 35- to 49-mm AAAs recruited from Australia, the Netherlands, and the US were randomized 1:1 to receive telmisartan, 40 mg, or identical placebo. Analyses were conducted according to intention-to-treat principles. Final follow-up was conducted on October 11, 2018, and data analysis was performed between June and November 2019. InterventionTelmisartan, 40 mg, or identical placebo. Main Outcomes and MeasuresThe primary outcome of the difference in AAA growth, assessed on core imaging laboratory-read ultrasonographic scanning, was tested with linear mixed-effects models. Other outcomes included effects on blood pressure, computed tomographic (CT)-measured AAA diameter and volume, time to AAA-related events (AAA repair or mortality due to AAA rupture), and health-related quality of life. ResultsOf 300 intended participants, 210 were enrolled and randomized to receive telmisartan (n=107) or placebo (n=103). Of patients included in the intention-to-treat analysis (telmisartan: n=106, placebo: n=101), 183 were men (88%); mean (SD) age was 73.5 (7.9) years. At 1 year, participants receiving telmisartan had mean lower systolic (8.9; 95% CI, 4.1-13.8 mm Hg; P<.001) and diastolic (7.0; 4.3-9.8 mm Hg; P<.001) blood pressure levels compared with participants receiving placebo. A total of 188 participants (91%) received at least 2 ultrasonographic scans and 133 participants (64%) had at least 2 CT scans. There was no significant difference in ultrasonographic-assessed AAA growth rates among those assigned telmisartan (1.68 mm/y) or placebo (1.78 mm/y): mean difference, -0.11 mm/y (95% CI, -0.60 to 0.38 mm/y; P=.66). Telmisartan had no significant effects on AAA growth assessed by CT-measured AAA diameter (mean difference, -0.01 mm/y; 95% CI, -0.02 to 0.01 mm/y; P=.23) or volume (mean difference, -0.02 cm(3)/y; 95% CI, -0.04 to 0.00 cm(3)/y; P=.11), AAA-related events (relative risk, 1.35; 95% CI, 0.54-3.35; P=.52), or health-related quality of life (mean difference in physical component score at 24 months, 0.4; 95% CI, 0.4-0.4; P=.80). Hypotensive symptoms (eg, syncope) were twice as common among participants receiving telmisartan compared with placebo (28 [26%] vs 13 [13%]; P=.02), but overall adverse event rates were otherwise similar for both groups. Conclusions and RelevanceThis underpowered study did not show a treatment effect for telmisartan on small AAA growth. Future trials will need to ensure adequate sample size and duration of follow-up. Trial Registrationsanzctr.org.au Identifier: ACTRN12611000931976; ClinicalTrials.gov Identifier: NCT01683084 This randomized clinical trial examines the efficacy of telmisartan therapy slowing the growth of abdominal aortic aneurysm in patients with that condition.

Background Significant asymptomatic carotid stenosis ( ACS ) is associated with higher risk of strokes. While the prevalence of moderate and severe ACS is low in the general population, prediction models may allow identification of individuals at increased risk, thereby enabling targeted screening. We identified established prediction models for ACS and externally validated them in a large screening population. Methods and Results Prediction models for prevalent cases with ≥50% ACS were identified in a systematic review (975 studies reviewed and 6 prediction models identified [3 for moderate and 3 for severe ACS ]) and then validated using data from 596 469 individuals who attended commercial vascular screening clinics in the United States and United Kingdom. We assessed discrimination and calibration. In the validation cohort, 11 178 (1.87%) participants had ≥50% ACS and 2033 (0.34%) had ≥70% ACS . The best model included age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, vascular and cerebrovascular disease, measured blood pressure, and blood lipids. The area under the receiver operating characteristic curve for this model was 0.75 (95% CI, 0.74–0.75) for ≥50% ACS and 0.78 (95% CI, 0.77–0.79) for ≥70% ACS . The prevalence of ≥50% ACS in the highest decile of risk was 6.51%, and 1.42% for ≥70% ACS . Targeted screening of the 10% highest risk identified 35% of cases with ≥50% ACS and 42% of cases with ≥70% ACS . Conclusions Individuals at high risk of significant ACS can be selected reliably using a prediction model. The best‐performing prediction models identified over one third of all cases by targeted screening of individuals in the highest decile of risk only.

Objective; Currently there is no drug therapy for abdominal aortic aneurysm (AAA) and most previous investigations have focused on imaging rather than clinical outcomes. The aim of this study was to assess whether AAA related clinical events were lower in patients prescribed metformin. Methods: This was a prospective cohort observational study performed in three cities in Australia, which was designed to study risk factors for clinical events not simply to focus on metformin. Patients with an asymptomatic unrepaired AAA of any diameter >= 30 mm were recruited from hospital outpatient clinics and surveillance programs run at four centres. The main outcome was the requirement for AAA repair or AAA related mortality (AAA events). The association between metformin prescription and AAA events was assessed using Kaplan-Meier analysis and Cox proportional hazard analysis. Results: Patients (1,080) with a mean (SD) initial AAA diameter of 46.1 (11.3) mm were followed for a mean (SD) of 2.5 (3.1) years until an AAA event (n = 454), death (n = 176), loss to follow up (n = 128), or completion of current follow up (n = 322). Patients with diabetes who were prescribed metformin (adjusted HR 0.63, 95% CI 0.44-0.93), but not patients with diabetes who were not prescribed metformin (adjusted HR 1.15, 95% CI 0.83-1.59), had a lower incidence of AAA events compared with those without diabetes. Findings were similar in sensitivity analyses restricted to patients with an initial AAA diameter <= 50 mm and patients with a minimum follow up of six months before an AAA event. Conclusions: These findings suggest that clinically important AAA events may be reduced in patients with diabetes who are prescribed metformin, but not those with diabetes receiving other treatments. A randomised controlled trial is needed to definitively test whether metformin reduces AAA related clinical events in patients with small AAAs who do not have diabetes.

BACKGROUND:Supervised exercise is recommended for the management of peripheral artery disease (PAD); however, the uptake is limited. Structured home exercise programmes may be more feasible, but their effectiveness is unclear. This systematic review and meta-analysis examined the benefit of structured home exercise programmes for treating PAD in comparison to controls not receiving an exercise programme.METHODS:A literature search was conducted to identify RCTs comparing structured home exercise with controls not receiving an exercise programme among patients with PAD. To be included, studies had to report outcomes from treadmill or corridor walking tests, or objective assessment of physical activity. Inverse variance-weighted meta-analysis was performed to compare changes in maximum walking distance and intermittent claudication onset distance in treadmill tests, walking distance during a 6-min walking test, and physical activity measured using a pedometer or accelerometer. Summarized results are presented in terms of standard deviation differences.RESULTS:Eleven randomized trials involving 807 patients were included. Follow-up ranged from 2 to 24 months; only one trial included follow-up beyond 12 months. Meta-analyses showed that structured home exercise programmes led to significant improvements in maximum walking distance (mean difference (MD) 0·32, 95 per cent c.i. 0·15 to 0·50; P < 0·001), intermittent claudication onset distance (MD 0·45, 0·27 to 0·62; P < 0·001), walking distance in a 6-min walking test (MD 0·28, 0·09 to 0·47; P = 0·004) and physical activity (MD 0·27, 0·11 to 0·43; P = 0·001).CONCLUSION:This meta-analysis suggests that structured home exercise programmes are effective at improving walking performance and physical activity in the short term for patients with PAD.

Introduction: Effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. Detailed analysis of the timing of procedural events offers the possibility for the surgical team to adjust their treatment protocol by implementing preventive measures to lower the risk of periprocedural complications. We aimed to assess frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. Methods: Individual patient data (N=8,752) were obtained from four large trials: VA, ACAS, ACST-1, and GALA. Timeframe of recruitment was 1983 to 2007. In these four trials, 4,462 patients underwent CEA for asymptomatic carotid artery stenosis. Patients with a stroke or death after CEA were included. Timing of procedural stroke and death was stratified into day 0 intraoperative, day 0 postoperative, days 1-3, days 4-30. Results: In total, 126 (2.8%) patients had a procedural complication. Of these, 67% were male and median age was 70. Twenty-two (17.5%) were fatal strokes and 84 (66.7%) were non-fatal strokes (29 disabling and 55 non-disabling), 12 (9.5%) were fatal myocardial infarctions, and 8 (6.3%) were deaths from other causes. Eighty-five (80.2%) strokes were ipsilateral with regard to the operated artery, 19 (17.9%) were contralateral, and two (1.9%) were vertebrobasilar. Fifty-two (49.1%) were ischaemic strokes, 9 (8.5%) were haemorrhagic strokes, and in 45 (42.5%) the stroke subtype was not determined. Fifth-five (43.7%) strokes and deaths occurred on day 0 (of which 26 intraoperative, 19 postoperative, and 10 with unclear timing). Twenty-five (19.8%) occurred on days 1-3, and 46 (36.5%) occurred on days 4-30. Conclusion: Half of the procedural deaths and strokes occurred on the day of operation. Of these, at least one fifth were intraoperative and at least 15% were postoperative. One third occurred after day 3 when most patients will have been discharged. This analysis of procedural complications may help in planning strategies to reduce procedural complications after CEA. Disclosure: Nothing to disclose

HomeCirculationVol. 140, No. 3Opposite Associations of Aortic Aneurysm With Blood Glucose and With Diabetes Mellitus Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBOpposite Associations of Aortic Aneurysm With Blood Glucose and With Diabetes Mellitus Dylan R. Morris, MBBS, Paul Sherliker, BA, Rachel Clack, BA, David Preiss, PhD, Kin Bong Hubert Lam, PhD, Jennifer Carter, PhD, Alison Halliday, FRCS, Richard Peto, FRS, Sarah Lewington, DPhil and Richard Bulbulia, FRCS Dylan R. MorrisDylan R. Morris Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. , Paul SherlikerPaul Sherliker Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. MRC Population Health Research Unit (P.S., D.P., S.L., R.B.), University of Oxford, United Kingdom. , Rachel ClackRachel Clack Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. , David PreissDavid Preiss MRC Population Health Research Unit (P.S., D.P., S.L., R.B.), University of Oxford, United Kingdom. , Kin Bong Hubert LamKin Bong Hubert Lam Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. , Jennifer CarterJennifer Carter Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. , Alison HallidayAlison Halliday Nuffield Department of Population Health, and Nuffield Department of Surgical Sciences (A.H.), University of Oxford, United Kingdom. , Richard PetoRichard Peto Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. , Sarah LewingtonSarah Lewington Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. MRC Population Health Research Unit (P.S., D.P., S.L., R.B.), University of Oxford, United Kingdom. and Richard BulbuliaRichard Bulbulia Richard Bulbulia, FRCS, CTSU, Richard Doll Building, Old Road Campus, Oxford OX3 7LF, UK. Email E-mail Address: [email protected] Clinical Trial Service Unit and Epidemiological Studies Unit (D.R.M., P.S., R.C., D.P., K.B.H.L., J.C., R.P., S.L., R.B.), University of Oxford, United Kingdom. MRC Population Health Research Unit (P.S., D.P., S.L., R.B.), University of Oxford, United Kingdom. Originally published15 Jul 2019https://doi.org/10.1161/CIRCULATIONAHA.119.040398Circulation. 2019;140:264–266The prevalence of aortic aneurysm is inversely associated with the prevalence of diabetes mellitus, but the reasons for this inverse relationship remain unclear.1 The 2 main hypotheses to explain it are the following: (1) high blood glucose, or some other aspect of diabetes mellitus, has a direct fibrotic or other effect on the aortic wall that inhibits aneurysm development (in which case prediabetes could well have a protective effect); or (2) some common diabetes treatment protects against aneurysm development.1 These hypotheses predict different relationships of prediabetes to aneurysm development, yet no large studies have assessed the associations of blood glucose with subclinical aortic aneurysm among people without diabetes mellitus. The aim of this study was to assess the associations of blood glucose with screen-detected aortic aneurysm in a large population of otherwise healthy adults without diabetes mellitus.The population comprised self-referred adults who attended commercial vascular screening clinics in the United Kingdom/United States from 2008 to 2013. They underwent ultrasound screening for aortic aneurysm, carotid stenosis, and peripheral artery disease. Diabetes mellitus was defined by previous diagnosis or antihyperglycemic treatment. Blood glucose was measured in capillary blood samples at point-of-care (Cholestech LDX) by using the oxidase/peroxidase method,2 of which >90% were fasting samples. The LDX method has a mean bias of –0.8 mmol/L (SD 0.6) and a percentage bias of –17.6% (SD 13.4) for the measurement of blood glucose in comparison with standard methods.2 Vascular screening was conducted using dedicated vascular ultrasound instruments (GE LOGIQ e). Aortic aneurysm was defined as a maximum infrarenal aortic diameter ≥3 cm. Analyses were restricted to findings at the first screening examination, and, to minimize the influence of reverse causation, excluded participants who reported a previous diagnosis of ischemic heart disease, stroke, transient cerebral ischemia, peripheral artery disease, or aortic aneurysm. Participants were not representative of the general population, but this should not materially bias any associations between screen-detected arterial lesions and either diabetes mellitus or blood glucose.Multivariable logistic regression was used to assess the associations of blood glucose (among people without diagnosed diabetes mellitus) and of diabetes mellitus itself (in the entire population) with screen-detected vascular disease. Analyses were adjusted for age, sex, body mass index group, systolic blood pressure, smoking, and region, and for the use of aspirin, antihypertensive therapy, and low-density lipoprotein cholesterol–lowering therapy. Odds ratios in 4 categories defined by blood glucose measurements at the first screening invitation were plotted against the usual blood glucose levels in those categories (ie, the mean glucose values including the first resurvey measurement, to correct for regression dilution).3 The results are therefore referred to in terms of usual blood glucose differences, as opposed to differences in baseline blood glucose levels that may underestimate the magnitude of risk factor associations. The University of Oxford Inter-Divisional Research Ethics Committee approved the study. Attendees provided written consent to the collecting organization for research use of deidentified data.Among 3 276 139 people screened in 2008 to 2013, 2 065 432 (63%) were eligible and included in the analysis. Ninety-eight percent were from the United States, mean age was 64 (SD 10) years, and two-thirds were women. Approximately 11% (224 840) had a prior diagnosis of diabetes mellitus, and most of those reported current antihyperglycemic treatment (84%; 43 200 of 51 550 who were asked). Blood glucose measurements were available for 396 023 attendees, including 29 919 with diagnosed diabetes mellitus and 366 104 without (of whom 344 had a resurvey). Those with diagnosed diabetes mellitus had a mean blood glucose level of 6.9 mmol/L (SD 2.8), in comparison with 5.0 mmol/L (SD 1.0) among those without.Diabetes mellitus was associated with ≈50% higher prevalence of carotid stenosis (odds ratio, 1.45; 95% CI, 1.40–1.50; P<0.0001) and peripheral artery disease (odds ratio, 1.53; 95% CI, 1.49–1.57; P<0.0001). In contrast, diabetes mellitus was associated with a 22% lower prevalence of aortic aneurysm (odds ratio, 0.78; 95% CI, 0.74–0.83; P<0.0001). Yet, among people without diagnosed diabetes mellitus, higher blood glucose was significantly positively associated with a higher prevalence of all 3 of these screen-detected vascular conditions, including aortic aneurysm. Each 2 mmol/L higher usual blood glucose was associated with a higher prevalence of carotid stenosis (odds ratio, 1.36; 95% CI, 1.23–1.51; P<0.0001), peripheral artery disease (odds ratio, 1.36; 95% CI, 1.26–1.47; P<0.0001), and aortic aneurysm (odds ratio, 1.22; 95% CI, 1.04–1.43; P=0.017).The Figure shows that for both carotid stenosis and peripheral artery disease, prevalence was higher with higher usual blood glucose, and was highest among those with diabetes mellitus. It also shows, however, that although the prevalence of aortic aneurysm was higher with higher blood glucose in the nondiabetic range, the lowest prevalence was among people who had diabetes mellitus. The results were unchanged after restricting blood glucose measurements to fasting samples.Download figureDownload PowerPointFigure. Associations of usual blood glucose with 3 screen-detected vascular diseases. Odds ratios are adjusted for age, sex, region, body mass index group, systolic blood pressure, and smoking, and the use of aspirin, antihypertensive therapy, and low-density lipoprotein cholesterol–lowering therapy, and are scaled so that the odds ratios for those with diabetes mellitus are compared against those without diabetes mellitus. Black squares: people without diabetes mellitus, plotted against the means of the resurvey glucose values. Quartiles are defined by equal numbers of cases in each group. White squares: previously diagnosed diabetes mellitus or antihyperglycemic treatment, plotted against the mean blood glucose (of those who had it measured). In each group, the number of cases is given and the area of the square is inversely proportional to the variance of the log odds in that group. ABI indicates ankle-brachial index; and PSV, peak systolic velocity.In conclusion, among people without diabetes mellitus, increased blood glucose levels were positively associated with a higher prevalence of aortic aneurysm. These findings make it unlikely that the inverse association between diabetes mellitus and aortic aneurysm is mediated by hypothetical protective effects of glycemia or of other metabolic aspects of diabetes mellitus. Instead, some common treatment for diabetes mellitus may well have a protective effect against aortic aneurysm.AcknowledgmentsThe authors acknowledge J. Reizes, M. Chabok, and A. Manganaro (Life Line Screening) and S. Weisman (Innovative Science Solutions), who facilitated this research.Sources of FundingThis study was supported by core funding to the UK Medical Research Council Population Health Research Unit, which receives direct support from the British Heart Foundation and Cancer Research UK. Dr Morris is supported by a General Sir John Monash Scholarship and an Avant Doctor in Training Research Scholarship. Dr Preiss is supported by a British Heart Foundation Centre of Research Excellence Senior Transition Fellowship (RE/13/1/30181). Dr Halliday is supported by the UK National Institute of Health Research Oxford Biomedical Research Centre. Drs Lewington and Bulbulia are supported by the UK Medical Research Council, and a Goodger and Schorstein Scholarship from the University of Oxford Medical Sciences Division.DisclosuresData were analyzed and interpreted by the investigators independently of Life Line Screening and all funding sources.Footnotes*Drs Lewington and Bulbulia are joint senior authors.Data sharing: The Nuffield Department of Population Health, University of Oxford, has a data access and sharing policy to facilitate data access to bona fide researchers, available from https://www.ctsu.ox.ac.uk/.Richard Bulbulia, FRCS, CTSU, Richard Doll Building, Old Road Campus, Oxford OX3 7LF, UK. Email richard.[email protected]ox.ac.ukReferences1. Lederle FA, Johnson GR, Wilson SE, Chute EP, Littooy FN, Bandyk D, Krupski WC, Barone GW, Acher CW, Ballard DJ. Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group.Ann Intern Med. 1997; 126:441–449.CrossrefMedlineGoogle Scholar2. Whitehead SJ, Ford C, Gama R. A combined laboratory and field evaluation of the Cholestech LDX and CardioChek PA point-of-care testing lipid and glucose analysers.Ann Clin Biochem. 2014; 51(pt 1):54–67. doi: 10.1177/0004563213482890CrossrefMedlineGoogle Scholar3. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.Lancet. 1990; 335:765–774.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Liu H, Wei P, Fu W, Xia C, Li Y, Tian K, Li Y, Cheng D, Sun J, Xu Y, Lu M, Xu B, Zhang Y, Wang R, Wang W, Xu B, Liu E, Zhao S and Yu Q (2022) Dapagliflozin Ameliorates the Formation and Progression of Experimental Abdominal Aortic Aneurysms by Reducing Aortic Inflammation in Mice, Oxidative Medicine and Cellular Longevity, 10.1155/2022/8502059, 2022, (1-11), Online publication date: 28-Jan-2022. Morris D, Jones G, Holmes M, Bown M, Bulbulia R, Singh T and Golledge J (2022) Genetic Predisposition to Diabetes and Abdominal Aortic Aneurysm: A Two Stage Mendelian Randomisation Study, European Journal of Vascular and Endovascular Surgery, 10.1016/j.ejvs.2021.10.038, 63:3, (512-519), Online publication date: 1-Mar-2022. Sterpetti A and Bozzani A (2022) Factors Involved in the Etiology of Abdominal Aortic aneurysm, European Journal of Vascular and Endovascular Surgery, 10.1016/j.ejvs.2022.05.035, Online publication date: 1-May-2022. Obel L, Diederichsen A, Steffensen F, Frost L, Lambrechtsen J, Busk M, Urbonaviciene G, Egstrup K, Karon M, Rasmussen L, Gerke O, Bovling A and Lindholt J (2021) Population-Based Risk Factors for Ascending, Arch, Descending, and Abdominal Aortic Dilations for 60-74–Year-Old Individuals, Journal of the American College of Cardiology, 10.1016/j.jacc.2021.04.094, 78:3, (201-211), Online publication date: 1-Jul-2021. Kunath A, Unosson J, Friederich-Persson M, Bjarnegård N, Becirovic-Agic M, Björck M, Mani K, Wanhainen A and Wågsäter D (2021) Inhibition of angiotensin-induced aortic aneurysm by metformin in apolipoprotein E–deficient mice, JVS-Vascular Science, 10.1016/j.jvssci.2020.11.031, 2, (33-42), . Golledge J, Arnott C, Moxon J, Monaghan H, Norman R, Morris D, Li Q, Jones G, Roake J, Bown M and Neal B (2021) Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm, Trials, 10.1186/s13063-021-05915-0, 22:1, Online publication date: 1-Dec-2021. Unosson J, Wågsäter D, Bjarnegård N, De Basso R, Welander M, Mani K, Gottsäter A and Wanhainen A (2021) Metformin Prescription Associated with Reduced Abdominal Aortic Aneurysm Growth Rate and Reduced Chemokine Expression in a Swedish Cohort, Annals of Vascular Surgery, 10.1016/j.avsg.2020.06.039, 70, (425-433), Online publication date: 1-Jan-2021. July 16, 2019Vol 140, Issue 3 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.040398PMID: 31306072 Originally publishedJuly 15, 2019 Keywordsaortic aneurysmdiabetes mellitusblood glucoseprediabetic statePDF download Advertisement SubjectsAneurysmDiabetes, Type 2Epidemiology

Background and Purpose- This analysis was performed to assess the association between perioperative and clinical variables and the 30-day risk of stroke or death after carotid endarterectomy for symptomatic carotid stenosis. Methods- Individual patient-level data from the 5 largest randomized controlled carotid trials were pooled in the Carotid Stenosis Trialists' Collaboration database. A total of 4181 patients who received carotid endarterectomy for symptomatic stenosis per protocol were included. Determinants of outcome included carotid endarterectomy technique, type of anesthesia, intraoperative neurophysiological monitoring, shunting, antiplatelet medication, and clinical variables. Stroke or death within 30 days after carotid endarterectomy was the primary outcome. Adjusted risk ratios (aRRs) were estimated in multilevel multivariable analyses using a Poisson regression model. Results- Mean age was 69.5±9.2 years (70.7% men). The 30-day stroke or death rate was 4.3%. In the multivariable regression analysis, local anesthesia was associated with a lower primary outcome rate (versus general anesthesia; aRR, 0.70 [95% CI, 0.50-0.99]). Shunting (aRR, 1.43 [95% CI, 1.05-1.95]), a contralateral high-grade carotid stenosis or occlusion (aRR, 1.58 [95% CI, 1.02-2.47]), and a more severe neurological deficit (mRS, 3-5 versus 0-2: aRR, 2.51 [95% CI, 1.30-4.83]) were associated with higher primary outcome rates. None of the other characteristics were significantly associated with the perioperative stroke or death risk. Conclusions- The current results indicate lower perioperative stroke or death rates in patients operated upon under local anesthesia, whereas a more severe neurological deficit and a contralateral high-grade carotid stenosis or occlusion were identified as potential risk factors. Despite a possible selection bias and patients not having been randomized, these findings might be useful to guide surgeons and anesthetists when treating patients with symptomatic carotid disease.

Introduction - Carotid Endarterectomy (CEA) and Carotid Artery Stenting (CAS) effectively reduce long-term stroke risk. Peri-procedural factors affecting outcome have been studied extensively. However, factors relating to the organisation of hospitals (structural factors) may also impact on the quality of patient care. The aim of this study was to examine the evidence that hospital structural factors may affect outcome following CEA or CAS. Methods - A systematic review was conducted of published studies from 2005 onwards. Three independent reviewers screened titles, abstracts and extracted data from papers, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Structural factors assessed were: Size of the population served by the Vascular Unit; number of hospital beds; availability of dedicated Vascular beds; impact of clearly defined pathways of care; size of the Surgical Intensive Care Unit (SICU) as a proxy for availability of care; and specialty of doctors performing the vascular procedure. Primary outcomes were: mortality; stroke; combined mortality/stroke; serious cardiac complications; length of hospital stay (LOS); and procedural cost. Results - Seventeen retrospective cohort studies from six countries, with a total of 95,100 patients, were included. CEA outcomes were reported in fourteen studies, CAS outcomes in two studies and both CEA and CAS outcomes in one study. Vascular Units providing services to larger populations (>75,000 people) had reduced mortality (p<0.0001) and stroke rates (p=0.001) following CEA, compared with those serving smaller populations. Larger hospitals providing CEA also had significantly reduced mortality (p<0.0001), stroke rate (p=0.0008) and cardiac events (p=0.01), compared with smaller hospitals (up to 130 beds). Provision of dedicated Vascular beds was associated with reduced mortality (p=0.0008) and fewer cardiac events (p=0.03) following CEA. Clearly defined pathways of care also appeared to reduce stroke and cardiac event rates (p=0.004) and the costs of CEA (by more than $600 (USD) per patient). Larger SICU availability (>6 beds) was associated with decreased mortality (p<0.0001) and stroke rate (p=0.001) compared with smaller units, whilst the presence of a dedicated Intensivist was also associated with significantly lower mortality (p=0.0002) following CEA. Patients treated by Vascular Surgeons versus non-Vascular Surgeons (Neuro-, Cardio-thoracic and 'General' Surgeons) had significantly lower stroke and mortality/stroke rates, as well as shorter LOS, following CEA. CAS outcomes were not influenced by interventionalist's specialty but CAS was significantly cheaper when performed by a Vascular Surgeon (p<0.0001). Conclusion - Hospital structural factors significantly affect outcomes of Carotid intervention, but data on CAS were limited. These findings can improve the future configuration of Vascular services and may help reduce the procedural risks and costs of CEA and CAS.