Predicting risk of rupture and rupture-preventing reinterventions following endovascular abdominal aortic aneurysm repair.

BACKGROUND: Clinical and imaging surveillance practices following endovascular aneurysm repair (EVAR) for intact abdominal aortic aneurysm (AAA) vary considerably and compliance with recommended lifelong surveillance is poor. The aim of this study was to develop a dynamic prognostic model to enable stratification of patients at risk of future secondary aortic rupture or the need for intervention to prevent rupture (rupture-preventing reintervention) to enable the development of personalized surveillance intervals. METHODS: Baseline data and repeat measurements of postoperative aneurysm sac diameter from the EVAR-1 and EVAR-2 trials were used to develop the model, with external validation in a cohort from a single-centre vascular database. Longitudinal mixed-effects models were fitted to trajectories of sac diameter, and model-predicted sac diameter and rate of growth were used in prognostic Cox proportional hazards models. RESULTS: Some 785 patients from the EVAR trials were included, of whom 155 (19·7 per cent) experienced at least one rupture or required a rupture-preventing reintervention during follow-up. An increased risk was associated with preoperative AAA size, rate of sac growth and the number of previously detected complications. A prognostic model using predicted sac growth alone had good discrimination at 2 years (C-index 0·68), 3 years (C-index 0·72) and 5 years (C-index 0·75) after operation and had excellent external validation (C-index 0·76-0·79). More than 5 years after operation, growth rates above 1 mm/year had a sensitivity of over 80 per cent and specificity over 50 per cent in identifying events occurring within 2 years. CONCLUSION: Secondary sac growth is an important predictor of rupture or rupture-preventing reintervention to enable the development of personalized surveillance intervals. A dynamic prognostic model has the potential to tailor surveillance by identifying a large proportion of patients who may require less intensive follow-up.

Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.

BACKGROUND: The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. METHODS: An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. RESULTS: The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. CONCLUSION: The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.

Long-term cost-effectiveness analysis of endovascular versus open repair for abdominal aortic aneurysm based on four randomized clinical trials.

BACKGROUND: A number of published economic evaluations of elective endovascular aneurysm repair (EVAR) versus open repair for abdominal aortic aneurysm (AAA) have come to differing conclusions about whether EVAR is cost-effective. This paper reviews the current evidence base and presents up-to-date cost-effectiveness analyses in the light of results of four randomized clinical trials: EVAR-1, DREAM, OVER and ACE. METHODS: Markov models were used to estimate lifetime costs from a UK perspective and quality-adjusted life-years (QALYs) based on the results of each of the four trials. The outcomes included in the model were: procedure costs, surveillance costs, reintervention costs, health-related quality of life, aneurysm-related mortality and other-cause mortality. Alternative scenarios about complications, reinterventions and deaths beyond the trial were explored. RESULTS: Models based on the results of the EVAR-1, DREAM or ACE trials did not find EVAR to be cost-effective at thresholds used in the UK (up to £30,000 per QALY). EVAR seemed cost-effective according to models based on the OVER trial. These results seemed robust to alternative model scenarios about events beyond the trial intervals. CONCLUSION: These analyses did not find that EVAR is cost-effective compared with open repair in the long term in trials conducted in European centres. EVAR did appear to be cost-effective based on the OVER trial, conducted in the USA. Caution must be exercised when transferring the results of economic evaluations from one country to another.

Observations from the IMPROVE trial concerning the clinical care of patients with ruptured abdominal aortic aneurysm.

BACKGROUND: Single-centre series of the management of patients with ruptured abdominal aortic aneurysm (AAA) are usually too small to identify clinical factors that could improve patient outcomes. METHODS: IMPROVE is a pragmatic, multicentre randomized clinical trial in which eligible patients with a clinical diagnosis of ruptured aneurysm were allocated to a strategy of endovascular aneurysm repair (EVAR) or to open repair. The influences of time and manner of hospital presentation, fluid volume status, type of anaesthesia, type of endovascular repair and time to aneurysm repair on 30-day mortality were investigated according to a prespecified plan, for the subgroup of patients with a proven diagnosis of ruptured or symptomatic AAA. Adjustment was made for potential confounding factors. RESULTS: Some 558 of 613 randomized patients had a symptomatic or ruptured aneurysm: diagnostic accuracy was 91·0 per cent. Patients randomized outside routine working hours had higher operative mortality (adjusted odds ratio (OR) 1·47, 95 per cent confidence interval 1·00 to 2·17). Mortality rates after primary and secondary presentation were similar. Lowest systolic blood pressure was strongly and independently associated with 30-day mortality (51 per cent among those with pressure below 70 mmHg). Patients who received EVAR under local anaesthesia alone had greatly reduced 30-day mortality compared with those who had general anaesthesia (adjusted OR 0·27, 0·10 to 0·70). CONCLUSION: These findings suggest that the outcome of ruptured AAA might be improved by wider use of local anaesthesia for EVAR and that a minimum blood pressure of 70 mmHg is too low a threshold for permissive hypotension.

Incidence of cardiovascular events and death after open or endovascular repair of abdominal aortic aneurysm in the randomized EVAR trial 1.

BACKGROUND: The aim was to compare rates of myocardial infarction, stroke and cardiovascular death in patients with a large abdominal aortic aneurysm who had endovascular (EVAR) or open repair to determine whether cardiovascular mortality explains the convergence in survival curves after these procedures. METHODS: Between 1999 and 2004, 1252 patients were randomized to EVAR or open repair in the UK EVAR trial 1. All patients were followed for death, myocardial infarction or stroke until September 2009. Cox regression was used to compare cardiovascular events and deaths between the randomized groups during different time intervals. RESULTS: Over 5 years of follow-up, a total of 187 first non-fatal or fatal cardiovascular events (98 myocardial infarctions and 89 strokes) and 256 cardiovascular deaths occurred. Although the endovascular group had a lower cardiovascular event rate than the open repair group (2·6 versus 3·2 per 100 person-years respectively) this was not statistically significant (adjusted hazard ratio (HR) 0·83, 95 per cent confidence interval 0·62 to 1·10; P = 0·199). Overall, there was little difference in cardiovascular mortality between the randomized groups (adjusted HR 1·06, 0·83 to 1·36; P = 0·638), but a non-significant excess of cardiovascular deaths was apparent in the endovascular group during the 6-24-month interval (adjusted HR 1·44, 0·79 to 2·62; P = 0·237). CONCLUSION: Patients who had EVAR appeared to have a lower subsequent cardiovascular event rate during all time intervals. Cardiovascular mortality was similar between the two groups overall, but more cardiovascular deaths in the EVAR group appeared to contribute to the convergence in all-cause mortality during the first 2 years.

Use of baseline factors to predict complications and reinterventions after endovascular repair of abdominal aortic aneurysm.

BACKGROUND: It is uncertain which baseline factors are associated with graft-related complications and reinterventions after endovascular aneurysm repair (EVAR) in patients with a large abdominal aortic aneurysm. METHODS: Patients randomized to elective EVAR in EVAR Trial 1 or 2 were followed for serious graft-related complications (type 2 endoleaks excluded) and reinterventions. Cox regression analysis was used to investigate whether any prespecified baseline factors were associated with time to first serious complication or reintervention. RESULTS: A total of 756 patients who had elective EVAR were followed for a mean of 3.7 years, by which time there were 179 serious graft complications (rate 6.5 per 100 person years) and 114 reinterventions (rate 3.8 per 100 person years). The highest rate was during the first 6 months, with an apparent increase again after 2 years. Multivariable analysis indicated that graft-related complications increased significantly with larger initial aneurysm diameter (P < 0.001) and older age (P = 0.040). There was also evidence that patients with larger common iliac diameters experienced higher complication rates (P = 0.011). CONCLUSION: Graft-related complication and reintervention rates were common after EVAR in patients with a large aneurysm. Younger patients and those with aneurysms closer to the 5.5-cm threshold for intervention experienced lower rates.

Does EVAR alter the rate of cardiovascular events in patients with abdominal aortic aneurysm considered unfit for open repair? Results from the randomised EVAR trial 2.

OBJECTIVES: To investigate whether endovascular aneurysm repair (EVAR) influences the rate of cardiovascular events (fatal or non-fatal myocardial infarction or stroke) in patients with abdominal aortic aneurysm (AAA) considered unfit for open repair. DESIGN: Randomised controlled trial. MATERIALS: Between 1999 and 2004, 404 patients with large AAA considered unfit for open repair were randomised to EVAR or no surgical intervention across 33 UK hospitals and followed until July 2009. METHODS: The Customised Probability Index was used to determine fitness for each patient and Cox regression was used to compare time to first cardiovascular event between randomised groups and levels of fitness. RESULTS: During an average of 2.8 years of follow-up, 67 first cardiovascular events occurred with a non-significantly higher event rate in the EVAR group compared to the no intervention group (6.6 versus 5.1 events per 100 person years); adjusted hazard ratio 1.42 [95% CI 0.87-2.34], p=0.156. There was no evidence to suggest that the hazard ratio between randomised groups changed with level of fitness (p=0.378). CONCLUSIONS: Cardiovascular event rates were high in these unfit patients and medical therapy was sub-optimal. Events rates were slightly higher in the EVAR group but this was not statistically significant.

Patient preference for surgical method of abdominal aortic aneurysm repair: postal survey.

OBJECTIVES: To determine whether men with small abdominal aortic aneurysm have a preference between either endovascular or open aneurysm repair for future treatment. DESIGN: Prospective study of self-declared treatment preference following receipt of a validated patient information pack. PARTICIPANTS: Men aged 65-84 years (n=237) with asymptomatic aneurysm (4.0-5.4 cm) detected by population-based screening. METHODS: An unbiased, validated patient information pack and questionnaire were developed to conduct a postal survey. RESULTS: One hundred sixty seven participants (70%) returned a completed questionnaire; 24 (10%) did not respond at all. Initially, only 38 (23%) declared a treatment preference. After reading the information pack, 130 participants (80%) declared a treatment preference: 30 preferred open repair (18%), 77 endovascular repair (46%), 23 were happy with either option (14%) and only 34 remained without any preference (20%). Nearly all (92%) thought that the information pack had prepared them well for future discussions with clinicians and with no single feature identified as influencing the preference-making process, 66 respondents (40%) still opted to 'take the advice of the doctor'. CONCLUSION: The patient information pack facilitated the development of treatment preferences with endovascular repair being preferred to open repair. Nevertheless for patient-centred care, vascular centres must continue to safely provide both open and endovascular repair.

Three-dimensional imaging core laboratory of the endovascular aneurysm repair trials: validation of methodology.

OBJECTIVE: The aim of this study was to establish and validate a three-dimensional imaging protocol for the assessment of Computed Tomography (CT) scans of abdominal aortic aneurysms in UK EVAR trials patients. Quality control and repeatability of anatomical measurements is important for the validity of any core laboratory. METHODS: Three different observers performed anatomical measurements on 50 preoperative CT scans of aortic aneurysms using the Vitrea 2 three-dimensional post-imaging software in a core laboratory setting. We assessed the accuracy of intra and inter observer repeatability of measurements, the time required for collection of measurements, 3 different levels of automation and 3 different automated criteria for measurement of neck length. RESULTS: None of the automated neck length measurements demonstrated sufficient accuracy and it was necessary to perform checking of the important automated landmarks. Good intra and limited inter observer agreement were achieved with three-dimensional assessment. Complete assessment of the aneurysm and iliacs took an average (SD) of 17.2 (4.1) minutes. CONCLUSIONS: Aortic aneurysm anatomy can be assessed reliably and quickly using three-dimensional assessment but for scans of limited quality, manual checking of important landmarks remains necessary. Using a set protocol, agreement between observers is satisfactory but not as good as within observers.

The Immediate Management of the Patient with Rupture: Open Versus Endovascular repair (IMPROVE) aneurysm trial--ISRCTN 48334791 IMPROVE trialists.

BACKGROUND: Systematic reviews have suggested a survival advantage for patients with ruptured abdominal aortic aneurysm (AAA), who are managed by endovascular repair. These reviews are based on single centre experiences of selected patients. OBJECTIVE: To determine whether a policy of endovascular repair improves the survival of all patients with ruptured AAA. METHODS: A randomized controlled trial, IMPROVE (ISRCTN 48334791) will randomize patients with a clinical diagnosis of rAAA, made in hospital, either to immediate CT scan and endovascular repair whenever anatomically suitable (endovascular first), or to open repair, with CT scan being optional (normal care), The trial is set on a background of guidelines for emergency care, CT scanning and anaesthesia, which incorporate the protocol of permissive hypotension. Recruitment started in October 2009 and 600 patients are required to show a 14% survival benefit at 30 days (primary outcome) for the endovascular first policy. Recruitment will be from the UK and Europe. Secondary outcomes include 24h, in-hospital and 1 year survival, complications, major morbidities, costs and quality of life. DISCUSSION: This is a "real life" trial that will answer the fundamental relevant clinical dilemma, namely, do patients who present with ruptured AAA derive benefit from treatment in a system, which offers a preferential strategy of endovascular repair? The trial addresses whether the anticipated reduced mortality and morbidity associated with endovascular repair is offset by the relatively greater ease of access and speed to conventional surgery. This issue is pivotal to future patient care and provision of services.

Modelling the long-term cost-effectiveness of endovascular or open repair for abdominal aortic aneurysm.

BACKGROUND: Recent randomized trials have shown that endovascular abdominal aortic aneurysm repair (EVAR) has a 3 per cent aneurysm-related survival benefit in patients fit for open surgery, but it also has uncertain long-term outcomes and higher costs. This study assessed the cost-effectiveness of EVAR. METHODS: A decision model was constructed to estimate the lifetime costs and quality-adjusted life years (QALYs) with EVAR and open repair in men aged 74 years. The model includes the risks of death from aneurysm, other cardiovascular and non-cardiovascular causes, secondary reinterventions and non-fatal cardiovascular events. Data were taken largely from the EVAR trial 1 and supplemented from other sources. RESULTS: Under the base-case (primary) assumptions, EVAR cost 3800 pounds sterling (95 per cent confidence interval (c.i.) 2400 pounds sterling to 5200 pounds sterling) more per patient than open repair but produced fewer lifetime QALYs (mean -0.020 (95 per cent c.i. -0.189 to 0.165)). These results were sensitive to alternative model assumptions. CONCLUSION: EVAR is unlikely to be cost-effective on the basis of existing devices, costs and evidence, but there remains considerable uncertainty.

Do abdominal aortic aneurysm necks increase in size faster after endovascular than open repair?

INTRODUCTION: Progression of aneurysmal disease in the aortic neck poses a threat to durable abdominal aortic aneurysm (AAA) repair. We tested the hypothesis that 2 years after AAA repair the size of the aortic neck increased more after endovascular (EVAR) than open repair. PATIENTS AND METHODS: For a subset of EVAR 1 trial patients, true outer-wall area at three levels of the aortic neck was measured using a Vitrea2 workstation, and rate of change over 2 years analysed. RESULTS: The 67 EVAR patients and 56 open repair patients were well-matched, very similar to the total EVAR 1 cohort. The mean area change over 2 years at the superior mesenteric artery was small for both groups. However at the caudal renal artery (CRA), adjusted regression coefficient was 0.68 cm(2)/y greater after EVAR (p<0.001) and 0.77 cm(2)/y at a level 15 mm distal to it (p<0.001). The area at the CRA of 45 available post-procedure scans showed a large proportion of the increase had occurred by 3 months (mean 4.8 cm(2) to 5.9 cm(2) versus 6.7 cm(2) at 2 years). CONCLUSIONS: The increase in aortic neck size was much greater 2 years after EVAR versus open repair. Further research is ongoing to establish whether the dilatation is progressive after stent-graft placement.

The adjuvant benefit of angioplasty in patients with mild to moderate intermittent claudication (MIMIC) managed by supervised exercise, smoking cessation advice and best medical therapy: results from two randomised trials for stenotic femoropopliteal and aortoiliac arterial disease.

BACKGROUND: Uncertainty exists on whether there is adjuvant benefit of percutaneous transluminal angioplasty (PTA) over supervised exercise and best medical therapy in the treatment of intermittent claudication. METHODS: Patients with symptoms of stable mild to moderate intermittent claudication (MIMIC) were randomised in two multi-centre trials, for femoropopliteal and aortoiliac arterial disease, to receive either PTA or no PTA against a background of supervised exercise and best medical therapy and followed up for 24 months. Initial claudication distance (ICD) and absolute walking distance (AWD) on treadmill were compared between randomised groups adjusting for the corresponding measure at baseline. Secondary outcomes included ankle-brachial pressure index (ABPI) and quality of life. FINDINGS: A total of 93 patients were randomised into the femoropopliteal trial (48 into PTA) and 34 into the aortoiliac trial (19 to PTA). The mean (standard deviation, SD) age was 66(9) years for the femoropopliteal trial (63% male) and 63(9) for the aortoiliac trial (65% male). At 24 months, there were significant improvements in both AWD and ICD in the PTA groups for both trials. The adjusted AWD was 38% greater in the PTA group for the femoropopliteal trial (95%; CI 1-90) (p=0.04) and 78% greater in the PTA group for the aortoiliac trial (95%; CI 0-216) (p=0.05). Further benefits were demonstrated for ABPI but not for quality of life. INTERPRETATION: PTA confers adjuvant benefit over supervised exercise and best medical therapy in terms of walking distances and ABPI 24 months after PTA in patients with stable mild to moderate intermittent claudication.

Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms.

BACKGROUND: Two clinical trials, one British and one American, have shown that early, prophylactic elective surgery does not improve five-year survival among patients with small abdominal aortic aneurysms. We report long-term outcomes in the United Kingdom Small Aneurysm Trial. METHODS: We randomly assigned 1090 patients, 60 to 76 years of age, with small abdominal aortic aneurysms (diameter, 4.0 to 5.5 cm) to one of two groups: 563 were assigned to undergo early elective surgery, and 527 were assigned to undergo surveillance by ultrasonography. Patients were followed in the trial until June 1998 and thereafter until August 2001; the mean duration of follow-up was 8 years (range, 6 to 10). RESULTS: The mean duration of survival was 6.5 years among patients in the surveillance group, as compared with 6.7 years among patients in the early-surgery group (P=0.29). The adjusted hazard ratio for death from any cause in the early-surgery group as compared with the surveillance group was 0.83 (95 percent confidence interval, 0.69 to 1.00; P=0.05). The 30-day operative mortality in the early-surgery group (5.5 percent) led to an early disadvantage in terms of survival. The survival curves crossed at three years, and at eight years, mortality in the early-surgery group was 7.2 percentage points lower than that in the surveillance group (P=0.03). There was no evidence that age, sex, or the initial size of the aneurysm modified the hazard ratio or that delayed surgery in the surveillance group increased 30-day postoperative mortality. Death was attributable to a ruptured aneurysm in 19 of the 411 men who died (5 percent) and in 12 of the 85 women who died (14 percent) (P=0.001). The rate of early cessation of smoking was higher in the early-surgery group than in the surveillance group. CONCLUSIONS: Among patients with a small abdominal aortic aneurysm, we found no long-term difference in mean survival between the early-surgery and surveillance groups, although after eight years, total mortality was lower in the early-surgery group. This difference may be attributed in part to beneficial changes in lifestyle adopted by members of the early-surgery group.

Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms.

BACKGROUND: There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. METHODS AND RESULTS: Aneurysm biopsies were used for explant cultures, the preparation of smooth muscle cell cultures, and isolation of macrophages. Tissue macrophages stained strongly for cyclooxygenase 2. Prostaglandin E2 (PGE2) concentrations in aneurysm tissue homogenates, conditioned medium from explants, and isolated macrophages were 49+/-22 ng/g, 319+/-38 ng/mL, and 22+/-21 ng/mL, respectively. PGE2 inhibited DNA synthesis and proliferation in normal aortic smooth muscle cells (IC50, 23.2+/-3.8 and 23.6+/-4.5 ng/mL, respectively). In smooth muscle cells derived from aneurysmal aorta, PGE2 also caused cell death, with generation of oligonucleosomes. Conditioned medium from the mixed smooth muscle and monocyte cultures derived from explants also had potent growth-inhibitory effects, and fractionation of this medium showed that the growth-inhibitory molecule(s) coeluted with PGE2. In explants, indomethacin 10 micromol/L or mefenamic acid 10 micromol/L abolished PGE2 secretion and significantly reduced IL-1beta and IL-6 secretion. In a separate case-control study, the expansion of abdominal aortic aneurysms was compared in 15 patients taking nonsteroidal anti-inflammatory drugs and 63 control subjects; median growth rates were 1.5 and 3.2 mm/y, respectively, P=0.001. CONCLUSIONS: The adverse effects of PGE2 on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE2 synthesis could be an effective treatment to curtail aneurysm expansion.

Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased. METHODS AND RESULTS: We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6. We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the -174 G-->C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, P=0.01). In 466 patients with small aneurysms, the frequency of the -174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis P=0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), P=0.036, and 0.51 (95% CI 0.25 to 1.00), P=0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth. CONCLUSIONS: Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the -174 G-->C IL-6 genotype predicts future cardiovascular mortality.

The influence of diabetes on the vasomotor responses of saphenous vein and the development of infra-inguinal vein graft stenosis.

There has been a prejudice that diabetes modulates the function of saphenous vein in a manner that predisposes to bypass graft failure, although most of the evidence accrues from animal studies. We have investigated the effect of diabetes on the vasodilator responses and ultrastructure of saphenous vein harvested from patients undergoing infrainguinal bypass surgery for limb salvage and the development of stenoses within the vein grafts. Of 55 consecutive patients undergoing vein bypass surgery for critical ischemia, 16 (29%) were diabetic: diabetes was not a risk factor for graft stenosis, which occurred in 17 of 56 (30%) grafts. Endothelium-dependent relaxation by nitric oxide pathways stimulated after receptor activation (bradykinin and thrombin) was not different in vein rings from diabetic (n = 12) and nondiabetic patients (n = 12). Prostarioid-mediated vasorelaxation was absent in vein rings from diabetic patients, and the production of 6-keto prostaglandin F(1alpha) (PGF(1alpha)) from diabetic vein was only 66 +/- 27 pg x cm-2 x min-1 compared with 112 +/- 20 pg x cm-2 x min-1 from control vein (P = 0.011). Fibrinogen-mediated vasorelaxation, normally inhibited by K+ channel blockers, was negligible in vein from diabetic patients. No ultrastructural differences were observed between the endothelium of saphenous vein harvested from diabetic and nondiabetic patients. However, diabetes was associated significantly with the presence of spiraled collagen in media. The maintenance of receptor-activated stimulation of nitric oxide pathways and the damping of the response to fibrinogen in saphenous vein endothelium may provide, in part, for the good prognosis of vein graft surgery in diabetic patients: diabetes is not a risk factor for early (12 months) infrainguinal vein graft stenosis.

Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial.

BACKGROUND: Endovascular aneurysm repair (EVAR) is a new technology to treat patients with abdominal aortic aneurysm (AAA) when the anatomy is suitable. Uncertainty exists about how endovascular repair compares with conventional open surgery. EVAR trial 1 was instigated to compare these treatments in patients judged fit for open AAA repair. METHODS: Between 1999 and 2003, 1082 elective (non-emergency) patients were randomised to receive either EVAR (n=543) or open AAA repair (n=539). Patients aged at least 60 years with aneurysms of diameter 5.5 cm or more, who were fit enough for open surgical repair (anaesthetically and medically well enough for the procedure), were recruited for the study at 41 British hospitals proficient in the EVAR technique. The primary outcome measure is all-cause mortality and these results will be released in 2005. The primary analysis presented here is operative mortality by intention to treat and a secondary analysis was done in per-protocol patients. FINDINGS: Patients (983 men, 99 women) had a mean age of 74 years (SD 6) and mean AAA diameter of 6.5 cm (SD 1). 1047 (97%) patients underwent AAA repair and 1008 (93%) received their allocated treatment. 30-day mortality in the EVAR group was 1.7% (9/531) versus 4.7% (24/516) in the open repair group (odds ratio 0.35 [95% CI 0.16-0.77], p=0.009). By per-protocol analysis, 30-day mortality for EVAR was 1.6% (8/512) versus 4.6% (23/496) for open repair (0.33 [0.15-0.74], p=0.007). Secondary interventions were more common in patients allocated EVAR (9.8% vs 5.8%, p=0.02). INTERPRETATION: In patients with large AAAs, treatment by EVAR reduced the 30-day operative mortality by two-thirds compared with open repair. Any change in clinical practice should await durability and longer term results.

Chlamydia pneumoniae does not influence atherosclerotic plaque behavior in patients with established carotid artery stenosis.

BACKGROUND AND PURPOSE: Research for infectious agents in the etiology of atherosclerosis has identified Chlamydia pneumoniae as a possible candidate. While there is evidence of an association between presence of this microorganism and atherosclerosis, it is unclear whether infection has a genuinely etiologic role in this disease, whether its presence influences clinical outcomes, and, if so, at which stages of disease this occurs. We have approached this issue in patients with advanced carotid artery atherosclerosis using molecular biological detection methods and clinically relevant indicators of pathology in carotid artery atheroma to determine whether the presence of C pneumoniae correlates with plaque instability. METHODS: C pneumoniae was detected with the use of a sensitive nested polymerase chain reaction. Preoperative embolization and preoperative infarcts were recorded with the use of transcranial Doppler insonation of the middle cerebral artery and cerebral CT, respectively. RESULTS: C pneumoniae DNA was detected in 25.5% of a cohort of 98 symptomatic patients. There was no significant difference in plaque stability as measured by embolization rates between the chlamydial-positive and -negative specimens. There was also no correlation between the number of ipsilateral hemispheric infarcts in the territory of the middle cerebral artery and chlamydial status. CONCLUSIONS: This study confirms that C pneumoniae is a common finding in atherosclerotic plaques of the carotid artery but suggests that the presence of the infectious organism has little detectable impact on plaque instability when measured by clinically significant markers. This raises important questions for the rationale of antibiotic therapy in atherosclerosis.

Diagnosis and initial management of stroke and transient ischemic attack across UK health regions from 1992 to 1996: experience of a national primary care database.

BACKGROUND AND PURPOSE: The aim of this study was to establish the difference in burden of cerebrovascular disease across the different health regions of the United Kingdom and to determine whether the initial management of new cases of stroke and transient ischemic attack (TIA) was uniform across the United Kingdom: METHODS: The General Practice Research Database (GPRD) is a national database used for epidemiological studies. This was a cohort study identifying incident cases of stroke and TIA over a 5-year study period between 1992 and 1996. The population studied was patients registered with general practitioners contributing to the GPRD across the different health regions of the United Kingdom: Outcome measures were new diagnoses of stroke and TIA, new prescriptions for antiplatelet and anticoagulant agents, and referrals made for specialist opinion. RESULTS: The age-adjusted annual incidence rate across all regions was 151 per 100 000 for stroke and 190 per 100 000 for TIA. There was almost a 2-fold difference in the incidence of cerebrovascular disease between the regions. The management of stroke and TIA in terms of antiplatelet prescription and of referral onward for further opinion to hospital specialists varied significantly between regions. CONCLUSIONS: Reported stroke and TIA incidence on the GPRD was comparable to that of other European studies. There were striking regional differences in the incidence of disease. The primary care management, both in prescription and referral rates, varied significantly between the different regions. There was a marked underuse of antiplatelet and anticoagulant agents, and referral rates for specialists' opinions were low.