Outcomes of Percutaneous Access to the First Versus Third Segment of Axillary Artery During Aortic Procedures.

PURPOSE: This article aims at investigating the outcomes of percutaneous access via the first versus third axillary artery (AXA) segments with closure devices during aortic procedures. MATERIALS AND METHODS: All patients receiving percutaneous AXA access closed with Perclose ProGlide device (Abbott, Santa Clara, California) from 2008 to 2021 were included in a retrospective multicenter registry (NCT: 04589962). Efficacy endpoint was the technically successful percutaneous procedure (no open conversion). Safety endpoints were stroke and access complications according to the Valve Academic Research Consortium-3 reporting standards. The first (AXA1) or third (AXA3) axillary puncture sites were compared. RESULTS: A total of 412 percutaneous AXA accesses were included: 172 (42%) in AXA1 and 240 (58%) in AXA3. Left AXA was catheterized in 363 cases (76% of AXA1 vs 97% of AXA3, p<0.001) and 91% of fenestrated/branched endovascular repair (F/BEVAR) procedures were conducted from the left. A ≥12F internal diameter (ID) sheath was used in 49% of procedures. Open conversion rate was 1%, no major vascular complications occurred, and only one major non-vascular complication was recorded. Primary closure failure occurred in 18 AXA1 (11%) and 32 AXA3 accesses (13%), treated by covered (8.3%) or bare-metal (2.7%) stenting. Bailout stent patency was 100% at median follow-up of 12 months, with 6 of 6 stents still patent after >36 months of follow-up. Stroke rate was 4.4%. An introducer sheath >12F was independently associated with both access complications (p<0.001) and stroke (p=0.005), while a right-side access was associated with stroke only (p=0.034). Even after adjustment for covariates, AXA1 versus AXA3 showed an equal success rate (odds ratio [OR]=0.537, 95% confidence interval [CI]=0.011-1.22 for AXA3, p=0.104). The combination of AXA3 and a >10F introducer sheath provided worse outcomes compared with >10F sheaths through AXA1 (OR for success=0.367, 95% CI=0.176-0.767, p=0.008). This was not confirmed for >12F sheaths, associated with similar outcomes (p=0.31 AXA 1 vs AXA 3). CONCLUSION: Major local complications with the percutaneous axillary approach and ≤12F sheaths are infrequent and solvable by complementary endovascular interventions. Stroke risk remains an issue. First and third AXA segments are both amenable for access with good results, but larger sheaths (12F) perform better in AXA1. CLINICAL IMPACT: Percutaneous access with vascular closure devices at the first or third axillary artery (AXA) segments during aortic procedures is burdened by a negligible risk of open conversion. Local complications with the percutaneous axillary approach are infrequent and solvable by complementary endovascular interventions. First and third AXA segments are both amenable to access with excellent results, but larger sheaths (12F) perform better in the wider first AXA segment. In this setting, bailout stenting does not appear to be associated with mid-term stent occlusion.

Influences of age and gender on operative risks following carotid endarterectomy: A systematic review and meta-analysis.

OBJECTIVES: This review aims to undertake a comprehensive review of the literature and investigate associations of age and gender on 30 days post carotid endarterectomy (CEA) and up to 5 years post CEA stroke, death, and combined stroke and death. DESIGN: A systematic review and meta-analysis. METHODS: Three main electronic databases including the Cochrane Library, MEDLINE, and Embase were searched from their inception to July 2022. Studies examining operative risks (i.e., stroke, death, and combined stroke and death following CEA) linked to age or gender were included. Two independent reviewers were responsible for study selection, quality assessment, and data extraction. Odds ratio (OR) and 95% confidence interval (CI) of all outcomes were calculated. RESULTS: 44609 studies were retrieved from the search. There were 127 eligible studies (80 studies of age, 72 studies of gender, 25 studies of age and gender) for pooling in the meta-analysis. With regards to stroke and death risks within 30 days post CEA; patients aged ≥75 had higher death (OR 1.38; 95% CI 1.10-1.75) than patients aged <75. Patients aged ≥80 had higher stroke risk (OR 1.17; 95% CI 1.07-1.27) and death risk (OR 1.85; 95% CI 1.48-2.30) particular in asymptomatic patients (OR 2.4; 95% CI 1.56-3.81). Pooled effect estimates by gender, at 30 days post CEA, showed that female was associated with increased risk of stroke (OR 1.28; 95% CI 1.16-1.40), with more risk in asymptomatic female patients (OR 1.51; 95% CI 1.14-1.99). CONCLUSIONS: This meta-analysis highlights that older people is associated with increased stroke risk, particularly asymptomatic octogenarians who had higher likelihood of death within 30 days post CEA. In addition, female especially those with asymptomatic carotid stenosis had greater likelihood of stroke within 30 days post CEA surgery.

Safety of Carotid Endarterectomy for Symptomatic Stenosis by Age: Meta-Analysis With Individual Patient Data.

BACKGROUND: There is uncertainty whether elderly patients with symptomatic carotid stenosis have higher rates of adverse events following carotid endarterectomy. In trials, recurrent stroke risk on medical therapy alone increased with age, whereas operative stroke risk was not related. Few octogenarians were included in trials and there has been no systematic analysis of all study types. We aimed to evaluate the safety of carotid endarterectomy in symptomatic elderly patients, particularly in octogenarians. METHODS: We did a systematic review and meta-analysis of studies (from January 1, 1980 through March 1, 2022) reporting post carotid endarterectomy risk of stroke, myocardial infarction, and death in patients with symptomatic carotid stenosis. We included observational studies and interventional arms of randomized trials if the outcome rates (or the raw data to calculate these) were provided. Individual patient data from 4 prospective cohorts enabled multivariate analysis. RESULTS: Of 47 studies (107 587 patients), risk of perioperative stroke was 2.04% (1.94-2.14) in octogenarians (390 strokes/19 101 patients) and 1.85% (1.75-1.95) in nonoctogenarians (1395/75 537); P=0.046. Perioperative death was 1.09% (0.94-1.25) in octogenarians (203/18 702) and 0.53% (0.48-0.59) in nonoctogenarians (392/73 327); P<0.001. Per 5-year age increment, a linear increase in perioperative stroke, myocardial infarction, and death were observed; P=0.04 to 0.002. However, during the last 3 decades, perioperative stroke±death has declined significantly in octogenarians (7.78% [5.58-10.55] before year 2000 to 2.80% [2.56-3.04] after 2010); P<0.001. In Individual patient data multivariate-analysis (5111 patients), age ≥85 years was independently associated with perioperative stroke (P<0.001) and death (P=0.005). Yet, survival was similar for octogenarians versus nonoctogenarians at 1-year (95.0% [93.2-96.5] versus 97.5% [96.4-98.6]; P=0.08), as was 5-year stroke risk (11.93% [9.98-14.16]) versus 12.78% [11.65-13.61]; P=0.24). CONCLUSIONS: We found a modest increase in perioperative risk with age in symptomatic patients undergoing carotid endarterectomy. As stroke risk increases with age when on medical therapy alone, our findings support selective urgent intervention in symptomatic elderly patients.

Percutaneous transaxillary access for endovascular aortic procedures in the multicenter international PAXA registry.

BACKGROUND: The aim of the study was to demonstrate the safety and effectiveness of a suture-mediated vascular closure device to perform hemostasis after an axillary artery access during endovascular procedures on the aortic valve, the aorta and its side branches. METHODS: A physician-initiated, international, multicenter, retrospective registry was designed to evaluate the success rate (VARC-2 reporting standards) of percutaneous transaxillary access closure with a suture-mediated closure device. Secondary end points were minor access vascular complications, transient peripheral nerve injury, stroke, and influence on periprocedural outcomes of puncture technique. RESULTS: Three hundred thirty-one patients (median age, 76 years; 69.2% males) in 11 centers received a percutaneous transaxillary access during endovascular cardiac (n = 166) or vascular (n = 165) procedures. The closure success rate was 84.6%, with 5 open conversions (1.5%), 45 adjunctive endovascular procedures (13.6%), and 1 nerve injury (0.3%). Secondary closure success was obtained in 325 patients (98%) after 7 bare stenting, 37 covered stenting, and 1 thrombin injection. Introducer sheaths 16F or larger (odds ratio, 3.70; 95% confidence interval, 1.22-11.42) and balloon-assisted hemostasis (odds ratio, 4.45; 95% confidence interval, 1.27-15.68) were associated with closure failure. A threshold of five percutaneous axillary accesses was associated with decreased rates of open conversion, but not with increased primary closure success. Primary closure success was 90.3% in the 175 patients with sheaths smaller than 16F, performed after the first 5 procedures in each center. Temporary nerve injury and stroke were observed in 2% and 4% of patients, respectively. CONCLUSIONS: Percutaneous transaxillary aortic procedures, in selected patients, can be performed with low rates of open conversion. The need for additional endovascular bailout procedures is not negligible when introducers sheaths 16F or larger are required.

Risk of stroke in relation to degree of asymptomatic carotid stenosis: a population-based cohort study, systematic review, and meta-analysis.

BACKGROUND: There is uncertainty around which patients with asymptomatic carotid stenosis should be offered surgical intervention. Although stroke rates were unrelated to the degree of stenosis in the medical-treatment-only groups in previous randomised trials, this could simply reflect recruitment bias and there has been no systematic analysis of a stenosis-risk association in cohort studies. We aimed to establish whether there is any association between the degree of asymptomatic stenosis and ipsilateral stroke risk in patients on contemporary medical treatment. METHODS: We did a prospective population-based study (Oxford Vascular Study; OxVasc), and a systematic review and meta-analysis. All patients in OxVasc with a recent suspected transient ischaemic attack or stroke, between April 1, 2002, and April 1, 2017, who had asymptomatic carotid stenosis were included in these analyses. We commenced contemporary medical treatment and determined ipsilateral stroke risk in this cohort by face-to-face follow-up (to Oct 1, 2020). We also did a systematic review and meta-analysis of all published studies (from Jan 1, 1980, to Oct 1, 2020) reporting ipsilateral stroke risk in patients with asymptomatic carotid stenosis. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and included both observational cohort studies and medical treatment groups of randomised controlled trials if the number of patients exceeded 30, ipsilateral stroke rates (or the raw data to calculate these) were provided, and were published in English. FINDINGS: Between April 1, 2002, and April 1, 2017, 2354 patients were consecutively enrolled in OxVasc and 2178 patients underwent carotid imaging, of whom 207 had 50-99% asymptomatic stenosis of at least one carotid bifurcation (mean age at imaging: 77·5 years [SD 10·3]; 88 [43%] women). The 5-year ipsilateral stroke risk increased with the degree of stenosis; patients with 70-99% stenosis had a significantly greater 5-year ipsilateral stroke risk than did those with 50-69% stenosis (six [14·6%; 95% CI 3·5-25·7] of 53 patients vs none of 154; p<0·0001); and patients with 80-99% stenosis had a significantly greater 5-year ipsilateral stroke risk than did those with 50-79% stenosis (five [18·3%; 7·7-29·9] of 34 patients vs one [1·0%; 0·0-2·9] of 173; p<0·0001). Of the 56 studies identified in the systematic review (comprising 13 717 patients), 23 provided data on ipsilateral stroke risk fully stratified by degree of asymptomatic stenosis (in 8419 patients). Stroke risk was linearly associated with degree of ipsilateral stenosis (p<0·0001); there was a higher risk in patients with 70-99% stenosis than in those with 50-69% stenosis (386 of 3778 patients vs 181 of 3806 patients; odds ratio [OR] 2·1 [95% CI 1·7-2·5], p<0·0001; 15 cohort studies, three trials) and a higher risk in patients with 80-99% stenosis than in those with 50-79% stenosis (77 of 727 patients vs 167 of 3272 patients; OR 2·5 [1·8-3·5], p<0·0001; 11 cohort studies). Heterogeneity in stroke risk between studies for patients with severe versus moderate stenosis (phet<0·0001) was accounted for by highly discrepant results (pdiff<0·0001) in the randomised controlled trials of endarterectomy compared with cohort studies (trials: pooled OR 0·8 [95% CI 0·6-1·2], phet=0·89; cohorts: 2·9 [2·3-3·7], phet=0·54). INTERPRETATION: Contrary to the assumptions of current guidelines and the findings of subgroup analyses of previous randomised controlled trials, the stroke risk reported in cohort studies was highly dependent on the degree of asymptomatic carotid stenosis, suggesting that the benefit of endarterectomy might be underestimated in patients with severe stenosis. Conversely, the 5-year stroke risk was low for patients with moderate stenosis on contemporary medical treatment, calling into question any benefit from revascularisation. FUNDING: NIHR Oxford Biomedical Research Centre, Wellcome Trust, Wolfson Foundation, and the British Heart Foundation.

Editor's Choice - Influence of Proximal Aortic Neck Diameter on Durability of Aneurysm Sealing and Overall Survival in Patients Undergoing Endovascular Aneurysm Repair. Real World Data from the Gore Global Registry for Endovascular Aortic Treatment (GREAT).

OBJECTIVES: Aortic neck diameter is an independent anatomical feature that is poorly understood, yet potentially linked to proximal seal failure and adverse outcome following standard EVAR. The aim of this study was to assess whether large proximal aortic neck (LAN) diameter is associated with adverse outcome using prospectively collected individual patient data from The Global Registry for Endovascular Aortic Treatment (GREAT). METHODS: A total of 3166 consecutive patients, from 78 global centres, receiving Gore Excluder stent grafts for infrarenal abdominal aortic aneurysm repair between 2011 and 2017 were included. Patient demographics, biometrics, operative details, and clinical outcome were analysed. Patients were divided into two groups: normal baseline proximal aortic neck (NAN) diameter (<25 mm on computed tomography aortography), and LAN (≥25 mm). Clinical follow up (including imaging) was available for 76.5% of patients 5 years post-intervention. Primary endpoints analysed were Type IA endoleak and any aortic re-intervention up to 5 years post-procedure. A composite endpoint of Type IA endoleak, re-intervention, aortic rupture, or aortic related mortality was also assessed. RESULTS: A total of 1977 (62.4%) patients were classified NAN and 1189 (37.6%) were LAN. Immediate technical success was achieved in 3164 out of 3166 (>99.9%) of cases. Freedom from Type IA endoleak was achieved in 99.3% at 1 year and 97.3% at 5 years (lower in LAN vs. NAN: 96.8% [CI 93.7-98.4] vs. 98.6% [CI 94.5-99.6], p = .007). Freedom from aortic re-intervention was 93.7% at 1 year and 83.2% at 5 years (78.6% [CI 66.0-87.0] LAN vs. 86.0% [CI 81.8-89.3] NAN, p = .11). Freedom from primary composite endpoint was 95.9% at 1 year and 84.9% at 5 years (81.3% [CI 69.2-89.0] LAN vs. 87.0% [CI 81.6-91.0] NAN, p = .066). Five year survival was lower in the LAN group; 64.6% (CI 50.1-75.7) vs. 76.5% (CI 70.7-81.3), p = .03). CONCLUSION: LAN is associated with delayed Type IA endoleak occurrence and lower overall survival.

Hospital and Institutionalisation Care Costs after Limb and Visceral Ischaemia Benchmarked Against Stroke: Long-Term Results of a Population Based Cohort Study.

OBJECTIVE/BACKGROUND: There are few published data on the acute care or long-term costs after acute/critical limb or visceral ischaemia (ACLVI) events. Using data from patients with acute events in a population based incidence study (Oxford Vascular Study), the present study aimed to determine the long-term costs after an ACLVI event. METHODS: All patients with first ever incident ACLVI from 2002 to 2012 were included. Analysis was based on follow up until January 2017, with all patients having full 5 year follow up. Multivariate regressions were used to assess baseline and subsequent predictors of total 5 year hospital care costs. Overall costs after an ACLVI event were benchmarked against those after stroke in the same population, during the same period. RESULTS: Among 351 patients with an ACLVI event, mean 5 year total care costs were €35,211 (SD 50,500), of which €6443 (18%) were due to long-term institutionalisation. Costs differed by type of event (acute visceral ischaemia €16,476; acute limb ischaemia €24,437; critical limb ischaemia €46,281; p < 0.001). Results of the multivariate analyses showed that patients with diabetes and those undergoing above knee amputations incurred additional costs of €11,804 (p = 0.014) and €25,692 (p < 0.001), respectively. Five year hospital care costs after an ACLVI event were significantly higher than after stroke (€28,768 vs. €22,623; p = 0.004), but similar after including long-term costs of institutionalisation (€35,211 vs. €35,391; p = 0.957). CONCLUSION: Long-term care costs after an ACLVI event are considerable, especially after critical limb ischaemia. Hospital care costs were significantly higher than for stroke over the long term, and were similar after inclusion of costs of institutionalisation.

Recent time trends in incidence, outcome and premorbid treatment of atrial fibrillation-related stroke and other embolic vascular events: a population-based study.

BACKGROUND: Prevalence of atrial fibrillation (AF) is increasing, due partly to the ageing population. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) Trial, published in 2007, provided strong evidence of the effectiveness of warfarin at age≥80 years, but the impact on incidence of AF-related stroke and peripheral embolic vascular events is uncertain. METHODS: We studied age-specific incidence and outcome of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study. RESULTS: Of 3096 acute cerebral or peripheral vascular events, 748 (24.2%) were AF-related. Of the 597 disabling/fatal incident ischaemic strokes, 369 occurred at age ≥80 years, of which 124 (33.6%) were in non-anticoagulated patients with known prior AF. There was no reduction in incident AF-related events after 2007 at all ages (n=231 vs 211; adjusted RR=1.11, 0.91 to 1.36, p=0.29) or at age ≥80 (137 vs 135, RR=1.15, 0.94 to 1.40, p=0.17). Scope for improved prevention at older ages was considerable. Among 208 patients with incident AF-related events at age ≥80 and known prior AF, only 19 (9.1%) were anticoagulated. Of the 189 patients not anticoagulated, 166 (87.8%) had no major disability prior to the event and 167 (88·4%) had a high embolism risk score, of whom 139 (83.2%) were also at low risk of complications. Yet, 125/167 (74.9%) were dead or institutionalised after the event. Potentially preventable embolic events outnumbered warfarin-related intracerebral haemorrhages by about 15-fold (280 vs 19), rising to 50-fold (189 vs 4) at age ≥80 years. CONCLUSIONS: We found no reduction in incidence of AF-related vascular events since publication of the BAFTA trial. A third of all disabling/fatal strokes occur in non-anticoagulated patients with known prior AF.

Population-Based Study of Incidence, Risk Factors, Outcome, and Prognosis of Ischemic Peripheral Arterial Events: Implications for Prevention.

BACKGROUND: There are few published data on the incidence and long-term outcomes of critical limb ischemia, acute limb ischemia, or acute visceral ischemia with which to inform health service planning, to monitor prevention, and to enable risk prediction. METHODS AND RESULTS: In a prospective population-based study (Oxfordshire, UK; 2002-2012), we determined the incidence and outcome of all acute peripheral arterial events in a population of 92,728. Risk factors were assessed by comparison with the underlying population. A total of 510 acute events occurred in 386 patients requiring 803 interventions. Two hundred twenty-one patients (59.3%) were ≥75 years of age, and 98 (26.3%) were ≥85 years old. Two hundred thirty patients (62.3%) were independent before the event, but 270 (73.4%) were dead or dependent at the 6-month follow-up, and 328 (88.9%) were dead or dependent at 5 years. The 30-day survival was lowest for patients with acute visceral ischemia (28.2%) compared with acute limb ischemia (75.3%) and critical limb ischemia (92.6%; P<0.001). Risk factors (all P<0.001) were hypertension (age- and sex-adjusted risk ratio, 2.75; 95% confidence interval, 1.95-3.90), smoking (adjusted risk ratio, 2.14; 95% confidence interval, 1.37-3.34), and diabetes mellitus (adjusted risk ratio, 3.01; 95% confidence interval, 1.69-5.35), particularly for critical limb ischemia (adjusted risk ratio, 5.96; 95% confidence interval, 3.15-11.26). Two hundred eighty-eight patients (77.2%) had known previous cardiovascular disease, and 361 (96.8%) had vascular risk factors, but only 203 (54.4%) were on an antiplatelet and only 166 (44.5%) were on a statin. Although 260 patients (69.7%) were taking antihypertensives, 42.9% of all blood pressures recorded during the 5 years before the event were >140/90 mm Hg. Of 88 patients (23.6%) with incident cardioembolic events, 62 had known atrial fibrillation (diagnosed before the event), of whom only 14.5% were anticoagulated despite 82.3% having a CHA2DS2VASC score ≥2 without contraindications. CONCLUSIONS: The clinical burden of peripheral arterial events is substantial. Although the vast majority of patients have known vascular disease in other territories and multiple treatable risk factors, premorbid control is poor.

Population-Based Study of Incidence of Acute Abdominal Aortic Aneurysms With Projected Impact of Screening Strategy.

BACKGROUND: Current abdominal aortic aneurysm (AAA) screening in men age 65 might have limited impact on overall AAA death rates if incidence is moving to older ages. Up-to-date population-based studies of age-specific incidence, risk factors, and outcome of acute AAA are needed to inform screening policy. METHODS AND RESULTS: In a prospective, population-based study (Oxfordshire, UK, 2002-2014), the incidence and outcome of acute AAA events were determined. Based on population projections and current incidence trends, the impact of screening strategies in the UK was estimated. Over the 12-year period, 103 incident acute AAA events occurred in the study population of 92 728. Incidence/100 000/year was 55 in men ages 65 to 74 years, but increased to 112 at 75 to 85 and 298 at ≥85, with 66.0% of all events occurring at age ≥75 years. Incidence at ages 65 to 74 was highest in male smokers (274), with 96.4% of events in men <75 years occurring in ever-smokers. Extrapolating rates to the UK population, using trial evidence of screening efficacy, the current UK screening program would prevent 5.6% of aneurysm-related deaths (315 200 scans/year: 1426/death prevented, 121/year-of-life saved). Screening only male smokers age 65 and then all men at age 75 would prevent 21.1% of deaths (247 900 scans/year; 297/death prevented, 34/year-of-life saved). By 2030, 91.0% of deaths will occur at age ≥75, 61.6% at ≥85, and 28.6% in women. CONCLUSIONS: Given that two thirds of acute AAA occurred at ≥75 years of age, screening older age groups should be considered. Screening nonsmokers at age 65 is likely to have very little impact on AAA event rates.

Age-specific incidence, outcome, cost, and projected future burden of atrial fibrillation-related embolic vascular events: a population-based study.

BACKGROUND: Prevalence of atrial fibrillation (AF) is >10% at age ≥80 years, but the impact of population aging on rates of AF-related ischemic events is uncertain. METHODS AND RESULTS: We studied age-specific incidence, outcome, and cost of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study (OXVASC). We determined time trends in incidence of AF-related stroke in comparison with a sister study in 1981 to 1986, extrapolated numbers to the UK population and projected future numbers. Of 3096 acute cerebral or peripheral vascular events in the 92 728 study population, 383 incident ischemic strokes and 71 systemic emboli were related to AF, of which 272 (59.9%) occurred at ≥80 years. Of 597 fatal or disabling incident ischemic strokes, 262 (43.9%) were AF-related. Numbers of AF-related ischemic strokes at age ≥80 years increased nearly 3-fold from 1981-1986 to 2002-2012 (extrapolated to the United Kingdom: 6621 to 18 176 per year), due partly to increased age-specific incidence (relative rate 1.52, 95% confidence interval 1.31-1.77, P=0.001), with potentially preventable AF-related events at age ≥80 years costing the United Kingdom £374 million per year. At current incidence rates, numbers of AF-related embolic events at age ≥80 years will treble again by 2050 (72 974/year), with 83.5% of all events occurring in this age group. CONCLUSIONS: Numbers of AF-related incident ischemic strokes at age ≥80 years have trebled over the last 25 years, despite the introduction of anticoagulants, and are projected to treble again by 2050, along with the numbers of systemic emboli. Improved prevention in older people with AF should be a major public health priority.

Type 2 diabetes is not associated with an altered plaque phenotype among patients undergoing carotid revascularization. A histological analysis of 1455 carotid plaques.

AIMS: Diabetes accelerates progression of atherosclerotic disease, but data on associations between diabetes and advanced atherosclerotic plaque composition are scarce. METHODS AND RESULTS: We used one of the largest biobanks, the Athero-Express study (n=1455) at carotid endarterectomy (CEA). All plaques were subjected to histological analysis to assess lipid core size, collagen, macrophages, smooth muscle cells, micro-vessel density and calcifications. In addition, within a subset of patients cytokines and chemokines were assessed. The 295 patients (20%) with type-2 diabetes showed a higher proportion of previous cardiovascular interventions and more stringent treatment for hypertension and hypercholesterolaemia compared with patients without type-2 diabetes. Surprisingly, no associations between diabetes and histological plaque characteristics were observed. In addition, no differences were observed in the expression of inflammatory chemokines, cytokines or advanced glycation end products in plaques of diabetic and non-diabetic patients. CONCLUSION: In patients suffering from significant carotid artery disease, diabetes does not appear to be associated with specific atherosclerotic plaque characteristics.

Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study.

BACKGROUND: Acute aortic dissection is a preventable life-threatening condition. However, there have been no prospective population-based studies of incidence or outcome to inform an understanding of risk factors, strategies for prevention, or projections for future clinical service provision. METHODS AND RESULTS: We prospectively determined incidence and outcomes of all acute aortic dissections in a population of 92 728 in Oxfordshire, United Kingdom, from 2002 to 2012. Among 155 patients with 174 acute aortic events, 54 patients had 59 thoracoabdominal aortic dissections (52 incident events: 6/100 000, 95% confidence interval, 4-7; 37 Stanford type A, 15 Stanford type B; 31 men, mean age=72.0 years). Among patients with type A incident events, 18 (48.6%) died before hospital assessment (61.1% women). The 30-day fatality rate was 47.4% for patients with type A dissections who survived to hospital admission and 13.3% for patients with type B dissections, although subsequent 5-year survival rates were high (85.7% for type A; 83.3% for type B). Even though 67.3% of patients were on antihypertensive drugs, 46.0% of all patients had at least 1 systolic BP ≥180 mm Hg in their primary care records over the preceding 5 years, and the proportion of blood pressures in the hypertensive range (>140/90 mm Hg) averaged 56.0%. Premorbid blood pressure was higher in patients with type A dissections that were immediately fatal than in those who survived to admission (mean/standard deviation pre-event systolic blood pressure=151.2/19.3 versus 137.9/17.9; P<0.001). CONCLUSIONS: Uncontrolled hypertension remains the most significant treatable risk factor for acute aortic dissection. Prospective population-based ascertainment showed that hospital-based registries will underestimate not only incidence and case fatality, but also the association with premorbid hypertension.

Histological features of carotid plaque in patients with ocular ischemia versus cerebral events.

BACKGROUND AND PURPOSE: Patients with carotid artery stenosis and ocular ischemic events have a much lower risk of future ipsilateral ischemic stroke on medical treatment and lower procedural risks for endarterectomy and stenting than patients with cerebral ischemic events, and are closer in risk to patients with asymptomatic stenosis. The reasons for this difference in prognosis are not fully understood, but may reflect differences in carotid plaque pathology. METHODS: In consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis (Oxford Plaque Study, Athero-Express Study), we compared carotid plaque histology (using validated semiquantitative scales) in those who had cerebral events within the last 6 months (n=1317) versus those with ocular events only (n=323). RESULTS: Compared with plaques from patients with ocular events only, those from patients with cerebral events had significantly more large lipid core (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.05-1.82; P=0.02), inflammation (OR, 1.32; 95% CI, 1.02-1.72; P=0.04) and overall plaque instability (OR, 1.37; 95% CI, 1.05-1.80; P=0.02), and less fibrous content (OR, 0.71; 95% CI, 0.54-0.92; P=0.01), and calcification (OR, 0.70; 95% CI, 0.54-0.91; P=0.008). The overall number of histological features known to be associated with vulnerable plaque was greater in patients with cerebral events than in those with ocular events (P=0.002). CONCLUSIONS: Carotid plaques from patients undergoing endarterectomy for previous ocular ischemic events have fewer vulnerable plaque features than those from patients with recent cerebral ischemic events, possibly explaining some of the differences in risk of stroke between these groups.

Basolateral adrenoceptor activation mediates noradrenaline-induced Cl- secretion in M-1 mouse cortical collecting duct cells.

Noradrenaline (NA) released from efferent renal sympathetic nerves may directly affect renal tubular transport. Here we examined the effect of NA on transepithelial ion transport of cultured M-1 mouse cortical collecting duct cells using equivalent short-circuit current ( I(SC)) measurements. Steady-state I(SC) averaged 87.5+/-2.9 microA cm(-2) (n=185) and was reduced by 97.1+/-0.1% (n=80) by apical amiloride (100 microM) confirming that the predominant electrogenic transport across M-1 monolayers is sodium absorption via the epithelial sodium channel (ENaC). Basolateral addition of NA (10 microM) induced a biphasic change in I(SC) characterized by an initial transient peak increase of 18.1+/-0.9 microA cm(-2) with a subsequent decline to a plateau 1.4+/-0.3 microA cm(-2) (n=20) above baseline. Apical application of NA had no effect. The response to basolateral NA was concentration dependent and was preserved in the presence of apical amiloride. In contrast, the response was largely reduced in the presence of apical diphenylamine-2-carboxylic acid (1 mM) and in the absence of extracellular Cl(-). The peak response to NA was reduced in the presence of the alpha-adrenoceptor antagonist phentolamine (100 microM), whereas the beta-antagonist propranolol (100 microM) reduced the secondary plateau phase while failing to influence the peak response. The alpha(1)-adrenoceptor-selective antagonists prazosin (10 nM) and corynanthine (1 microM) reduced the NA-induced peak response by about 75% and 70%, respectively, while the alpha(2)-adrenoceptor antagonist yohimbine (100 nM) was ineffective. We conclude that in M-1 cells NA stimulates Cl(-) secretion probably involving both alpha(1)- and beta-adrenoceptors located basolaterally.