Initial results of ultrasound screening for aneurysm of the abdominal aorta in Western Australia: relevance for endoluminal treatment of aneurysm disease

Background. Increased life expectancy in men during the last thirty years is largely due to the decrease in mortality from cardiovascular disease in the age group 29-69 yr. This change has resulted in a change in the disease profile of the population with conditions such as aneurysm of the abdominal aorta (AAA) becoming more prevalent. The advent of endoluminal treatment for AAA has encouraged prophylactic intervention and fuelled the argument to screen for the disease. The feasibility of inserting an endoluminal graft is dependent on the morphology and growth characteristics of the aneurysm. This study used data from a randomized controlled trial of ultrasound screening for AAA in men aged 65-83 yr in Western Australia for the purpose of determining the norms of the living anatomy in the pressurized infrarenal aorta. Aims. To examine (1) the diameters of the infra-renal aorta in aneurysmal and non-aneurysmal cases, (2) the implications for treatment modalities, with particular reference to endoluminal grafting, which is most dependent on normal and aneurysmal morphology, and (3) any evidence to support the notion that northern Europeans are predisposed to aneurysmal disease. Methods. Using ultrasound, a randomized control trial was established in Western Australia to assess the value of a screening program in males aged 65-83 yr, The infra-renal aorta was defined as aneurysmal if the maximum diameter was 30 mm or more. Aortic diameter was modelled both as a continuous tin mm) and as a binary outcome variable, for those men who had an infra-renal diameter of 30 mm or more. ANOVA and linear regression were used for modelling aortic diameter as a continuum, while chi-square analysis and logistic regression were used in comparing men with and without the diagnosis of AAA. Findings. By December 1998, of 19.583 men had been invited to undergo ultrasound screening for AAA, 12.203 accepted the invitation (corrected response fraction 70.8%). The prevalence of AAA increased with age from 4.8% at 65 yr to 10.8% at 80 yr (chi (2) = 77.9, df = 3, P<0.001). The median (IQR) diameter for the non-aneurysmal group was 21.4 mm (3.3 mm) and there was an increase (<chi>(2) = 76.0, df = 1, P<0.001) in the diameter of the infra-renal aorta with age. Since 27 mm is the 95th centile for the non-aneurysmal infra-renal aorta, a diameter of 30 mm or more is justified as defining an aneurysm. The risk of AAA was higher in men of Australian (OR = 1.0) and northern European origin (OR = 1.0, 95%CL: 0.9. 1.2) compared with those of Mediterranean origin (OR = 0.5, 99%CL: 0.4, 0.7). Conclusion. Although screening has not yet been shown to reduce mortality from AAA. these population-based data assist the understanding of aneurysmal disease and the further development and use of endoluminal grafts for this condition. (C) 2001 Published by Elsevier Science Ltd on behalf of The International Society for Cardiovascular Surgery.

C-reactive protein levels and the expansion of screen-detected abdominal aortic aneurysms in men

Background-C- reactive protein (CRP) levels have been shown to predict a number of cardiovascular outcomes. CRP levels have also been found to be elevated in patients with abdominal aortic aneurysms (AAAs). The aim of this study was to assess the relation between CRP levels and rates of expansion of small AAAs. Methods and Results-A cohort of men with small aneurysms was identified in a trial of screening with ultrasound scanning. After initial screening, men were rescanned at 6- to 12-month intervals. CRP levels were measured at the first follow-up visit. Rates of expansion and risk factors for expansion were assessed with the use of data from 545 men who attended for at least 1 scan after CRP levels were measured. These men were followed for a median of 48 (range, 5 to 69) months. The mean annual rate of expansion was 1.6 mm. The median CRP level was 2.6 mg/L in men with the smaller AAAs (30 to 39 mm, n=433) compared with 3.5 mg/L in men with larger AAAs (40 to 54 mm, n=112) (P=0.007). The multivariate age-adjusted logistic model confirmed initial aortic diameter to be the only factor associated with rapid expansion with an odds ratio of 7.2 (95% CI, 4.3,12.2) for an initial diameter of 40 to 54 mm relative to one of 30 to 39 mm. Conclusions-Most small aneurysms expand slowly. CRP levels are elevated in larger aneurysms but do not appear to be associated with rapid expansion. The most useful predictor of aneurysmal expansion in men is aortic diameter.

National audit of anaesthesia for major abdominal surgery

A postal survey was conducted of all hospitals in Australia known to have a department of anaesthesia and an intensive care or high dependency unit. Each hospital was asked to report the anaesthetic and postoperative analgesic techniques used for the last ten cases of four common major surgical procedures-aorto-femoral bypass, repair of an abdominal aortic aneurysm, hemicolectomy and anterior resection of the rectum. Half of 76 hospitals sent a survey form completed and returned it. Responding hospitals were larger on average, than non-responding ones, but otherwise typical of them in terms of university affiliation and metropolitan versus rural location. For each of the procedures studied the proportion of cases in which epidural block was used intra- or postoperatively varied from 0% to 100%. Depending on the procedure, between 65% and 85% of hospitals used epidural block sometimes, with between 10% and 90% of patients in these hospitals being managed with this technique. There is wide variation in the use of epidural block, intra- and postoperatively, in Australia, variation that is unlikely to be explained by systematic differences between institutions in the patients seen or their suitability for one or other technique. This pattern of practice mirrors the lack of agreement about the proper place for epidural techniques evident in the recent literature. There is a widespread belief among clinicians that this is a question of great importance. Accordingly, we believe that anaesthetists and surgeons share an ethical responsibility to enter suitable patients in an appropriately designed randomized controlled trial in order to resolve this question.

Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm

Background - Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)- 2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results - Aneurysm tissue was obtained from patients undergoing surgery ( MS: 4 M, 1 F, age 27 - 45 years; BAV: 3 M, 2 F, age 28 - 65 years). Normal aorta from subjects with nonaneurysm disease was also collected ( 4 M, 1 F, age 23 - 93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS ( 27 +/- 8%) and BAV ( 32 +/- 14%) compared with control ( 7 +/- 5%). Conclusions - In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

Overexpression of transforming growth factor-beta is associated with increased hyaluronan content and impairment of repair in Marfan syndrome aortic aneurysm

Background-Marfan syndrome (MFS), a condition caused by fibrillin-1 gene mutation is associated with aortic aneurysm that shows elastic lamellae disruption, accumulation of glycosaminoglycans, and vascular smooth muscle cell (VSMC) apoptosis with minimal inflammatory response. We examined aneurysm tissue and cultured cells for expression of transforming growth factor-beta1 to -beta3 (TGF beta 1 to 3), hyaluronan content, apoptosis, markers of cell migration, and infiltration of vascular progenitor cells (CD34). Methods and Results-MFS aortic aneurysm (6 males, 5 females; age 8 to 78 years) and normal aorta (5 males, 3 females; age 22 to 56 years) were used. Immunohistochemistry showed increased expression of TGF beta 1 to 3, hyaluronan, and CD34-positive microcapillaries in MFS aneurysm compared with control. There was increased expression of TGF beta 1 to 3 and hyaluronan in MFS cultured VSMCs, adventitial fibroblasts (AF), and skin fibroblasts (SF). Apoptosis was increased in MFS (VSMC: mean cell loss in MFS 29%, n of subjects = 5, versus control 8%, n = 3, P < 0.05; AF: 28%, n = 5 versus 7%, n = 5, P < 0.05; SF: 29%, n = 3 versus 4%, n = 3, not significant). In MFS, there was a 2-fold increase in adventitial microcapillaries containing CD34-positive cells compared with control tissue. Scratch wound assay showed absence of CD44, MT1-MMP, and beta-3 integrin at the leading edge of migration in MFS indicating altered directional migration. Western blot showed increased expression of TGF beta 1 to 3 in MFS but no change in expression of CD44, MT1-MMP, or beta-3 integrin compared with controls. Conclusions-There was overexpression of TGF-beta in MFS associated with altered hyaluronan synthesis, increased apoptosis, impaired progenitor cell recruitment, and abnormal directional migration. These factors limit tissue repair and are likely to contribute to aneurysm development.

Prevalence of peripheral arterial disease: persistence of excess risk in former smokers

Objective: To determine the age-standardised prevalence of peripheral arterial disease (PAD) and associated risk factors, particularly smoking. Method: Design: Cross-sectional survey of a randomly selected population. Setting: Metropolitan area of Perth, Western Australia. Participants: Men aged between 65-83 years. Results: The adjusted response fraction was 77.2%. Of 4,470 men assessed, 744 were identified as having PAD by the Edinburgh Claudication Questionnaire and/or the ankle-brachial index of systolic blood pressure, yielding an age-standardised prevalence of PAD of 15.6% (95% confidence intervals (CI): 14.5%, 16.6%). The main risk factors identified in univariate analyses were increasing age, smoking current (OR=3.9, 95% CI 2.9-5.1) or former (OR=2.0, 95% CI 1.6-2.4), physical inactivity (OR=1.4, 95% CI 1.2-1.7), a history of angina (OR=2.2, 95% CI 1.8-2.7) and diabetes mellitus (OR=2.1, 95% CI 1.7-2.6). The multivariate analysis showed that the highest relative risk associated with PAD was current smoking of 25 or more cigarettes daily (OR=7.3, 95% CI 4.2-12.8). In this population, 32% of PAD was attributable to current smoking and a further 40% was attributable to past smoking by men who did not smoke currently. Conclusions: This large observational study shows that PAD is relatively common in older, urban Australian men. In contrast with its relationship to coronary disease and stroke, previous smoking appears to have a long legacy of increased risk of PAD. Implications: This research emphasises the importance of smoking as a preventable cause of PAD.

The effect of spatial definition on the allocation of clients to screening clinics

We compared four strategies for inviting 91,456 women aged 50-69 years to one of six clinics for mammography screening and 40,142 men aged 60-79 years to one of 10 clinics for abdominal aortic aneurysm (AAA) screening. The strategies were invitation to the clinic nearest to the client and invitation to the clinic nearest to the client's area of residence defined by census small area, postcode and local government area. For each strategy we calculated the expected demand at each clinic and the travel distances for clients. We found that when women were allocated to mammography clinics on the basis of the local government area instead of their individual address, expected demand at one clinic increased by 60%, and 19% of clients were invited to attend a more remote clinic, entailing 99,000 km of additional travel. Similar results were obtained for men allocated to AAA clinics by their postcode of residence instead of their individual address: 55% difference in expected demand, 13% to a more remote clinic and 60,000 km of extra travel. Allocation on the basis of small areas did not show such great differences, except for travel distance, which was about 5% higher for each clinic type. We recommend that allocation of clients to screening clinics be made according to residential address, that assessment of the location of clinics be based on distances between residences and nearest clinic, but that planning new locations for clinics be aided with spatial analysis tools using small area demographic and social data. (C) 1997 Elsevier Science Ltd.

Lifestyle still predicts mortality in older men with established vascular disease

Background. It is uncertain whether accepted associations between health behaviors and mortality are pertinent to elderly people. No previous studies have examined the patterns of lifestyle in elderly men with and without clinically evident vascular disease by using a lifestyle score to predict survival. Methods. We measured prevalence of a healthy lifestyle (four or more healthy behaviors out of eight) and examined survival in 11,745 men aged 65-83 years participating in a randomized population-based trial of screening for abdominal aortic aneurysm in Perth, Western Australia. After stratifying participants into five groups according to history and symptoms of vascular disease, we compared survival of men in each subgroup with that of 'healthy' men with no history or symptoms of vascular disease. Results. Invitations to screening produced a corrected response of 70.5%. After adjusting for age and place of birth, having an unhealthy lifestyle was associated with an increase of 20% in the likelihood of death from any cause within 5 years (95% CI: 10-30%). This pattern was consistently evident across subgroups defined by history of vascular disease, but was less evident for deaths from vascular disease. Conclusions. Our results highlight the importance of maintaining a healthy lifestyle through to old age, regardless of history of vascular disease. (c) 2005 Elsevier Inc. All rights reserved.

Successful mental health aging: Results from a longitudinal study of older Australian men

Objective: The authors investigated the associations of medical and lifestyle factors with the mental health of men in their 80s. Methods: This was a prospective study of a community-representative cohort of older men. Successful mental health aging was defined as reaching age 80 years with Mini-Mental State Examination score (MMSE) of 24 or more and Geriatric Depression Scale-15 items (GDS-15) score of 5 or less. Results: Of 601 men followed for 4.8 years, 76.0% enjoyed successful mental health aging. Successful mental health aging was inversely associated with age (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.81 - 0.94), non-English-speaking background (HR = 0.42; 95% CI: 0.21 - 0.85), and the consumption of full-cream milk (HR = 0.63; 95% CI: 0.45 - 0.89), and directly associated with high school or university education (HR = 1.92; 95% CI: 1.34 - 2.75) and vigorous (HR = 1.89; 95% CI: 1.17 - 3.05) and nonvigorous physical activity (HR = 1.50; 95% CI: 1.05 - 2.14). Marital status, smoking and alcohol use, weekly consumption of meat or fish, and a medical history of hypercholesterolemia, hypertension, diabetes, myocardial infarction, and stroke were not associated with mental health outcomes in men aged 80 years or over. Conclusion: Three in four men who reach age 80 years undergo successful mental health aging. Factors associated with successful mental health aging include education and lifestyle behaviors such as physical activity. Lifestyle modification by means of increasing physical activity and reducing saturated fat intake may prove to be a safe, inexpensive, and readily available strategy to help maximize the successful mental health aging of the population.

Infrarenal aortic diameter predicts all-cause mortality

Objective - To assess the relationship between infrarenal aortic diameter and subsequent all-cause mortality in men aged 65 years or older. Methods and Results - Aortic diameter was measured using ultrasound in 12 203 men aged 65 to 83 years as part of a trial of screening for abdominal aortic aneurysms. A range of cardiovascular risk factors was also documented. Mortality over the next 3 to 7 years was assessed using record linkage. Initial aortic diameter was categorized into 10 intervals, and the relationship between increasing diameter and subsequent mortality was explored using Cox proportional hazard models. Median diameter increased from 21.4 mm in the youngest men to 22.1 mm in the oldest men. The cumulative all-cause mortality increased in a graded fashion with increasing aortic diameter. Using the diameter interval 19 to 22 mm as the reference, the adjusted hazard ratio for all-cause mortality increased from 1.26 (95% CI: 1.09, 1.44; P = 0.001) for aortic diameters of 23 to 26 mm to 2.38 (95% CI: 1.22, 4.61; P = 0.011) for aortic diameters of 47 to 50 mm. Analysis of causes of death indicated that cardiovascular disease was an important contributor to this increase. Conclusion - Infrarenal aortic diameter is an independent marker of subsequent all-cause mortality.

Design of the multicenter Australian study of epidural anesthesia and analgesia in major surgery: The MASTER Trial

The Multicenter Australian Study of Epidural Anesthesia and Analgesia in Major Surgery (The MASTER Trial) was designed to evaluate the possible benefit of epidural block in improving outcome in high-risk patients. The trial began in 1995 and is scheduled to reach the planned sample size of 900 during 2001. This paper describes the trial design and presents data comparing 455 patients randomized in 21 institutions in Australia, Hong Kong, and Malaysia, with 237 patients from the same hospitals who were eligible but not randomized. Nine categories of high-risk patients were defined as entry criteria for the trial. Protocols for ethical review, informed consent, randomization, clinical anesthesia and analgesia, and perioperative management were determined following extensive consultation with anesthesiologists throughout Australia. Clinical and research information was collected in participating hospitals by research staff who may not have been blind to allocation. Decisions about the presence or absence of endpoints were made primarily by a computer algorithm, supplemented by blinded clinical experts. Without unblinding the trial, comparison of eligibility criteria and incidence of endpoints between randomized and nonrandomized patients showed only small differences. We conclude that there is no strong evidence of important demographic or clinical differences between randomized and nonrandomized patients eligible for the MASTER Trial. Thus, the trial results are likely to be broadly generalizable. Control Clin Trials 2000;21:244-256 (C) Elsevier Science Inc. 2000.

Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial

Background Epidural block is widely used to manage major abdominal surgery and postoperative analgesia, but its risks. and benefits are uncertain. We compared adverse outcomes in high-risk patients managed for major surgery with epidural block or alternative analgesic regimens with general anaesthesia in a multicentre randomised trial. Methods 915 patients undergoing major abdominal surgery with one of nine defined comorbid states to identify high-risk status were randomly assigned intraoperative epidural anaesthesia and postoperative epidural analgesia for 72 h with general anaesthesia (site of epidural selected to provide optimum block) or control. The primary endpoint was death at 30 days or major postsurgical morbidity. Analysis by intention to treat involved 447 patients assigned epidural and 441 control. Findings 255 patients (57.1%) in the epidural group and 268 (60.7%) in the control group had at least one morbidity endpoint or died (p=0.29). Mortality at 30 days was low in both groups (epidural 23 [5.1%], control 19 [4.3%], p=0.67). Only one of eight categories of morbid endpoints in individual systems (respiratory failure) occurred less frequently in patients managed with epidural techniques (23% vs 30%, p=0.02). Postoperative epidural analgesia was associated with lower pain scores during the first 3 postoperative days. There were no major adverse consequences of epidural-catheter insertion. Interpretation Most adverse morbid outcomes in high-risk patients undergoing major abdominal surgery are not reduced by use of combined epidural and general anaesthesia and postoperative epidural analgesia. However, the improvement in analgesia, reduction in respiratory failure, and the low risk of serious adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperative epidural analgesia.