Circulating Markers of Abdominal Aortic Aneurysm Presence and Progression

Abstract

Over the last decade abdominal aortic aneurysm (AAA) has increasingly been recognised as an important cause of mortality in older persons. In 1999 for example AAA was noted to be the 15th leading cause of mortality in the USA [1]. Exact estimates of AAA-related fatalities are hampered by the low rate of post-mortems when sudden death occurs in elderly subjects, however, recent figures suggest that AAA accounts for approximately 15,000 deaths annually in the USA despite the increasing numbers of elective AAA repairs [2,3]. Approximately 25,000 endovascular and open AAA repairs are performed annually in the USA [3]. Ultrasound screening of men >65 years has been demonstrated to reduce AAA-related mortality and selective screening (of men aged ≥65 who have ever smoked) has been introduced in the USA [4]. Most screen-detected AAAs are of small size (<55mm) and surgery for these AAAs has not been demonstrated to improve outcome [5-7]. In an screening study of 12,203 men ≥65 years performed in Australia for example, 814 (6.7%) had a small AAA measuring 30-54mm but only 61 (0.5%) a large AAA (≥55mm) [8]. The increase in identification of small AAAs resulting from screening programs, in association with an ageing population, will highlight the number of deficiencies in current diagnosis and management of this condition. Firstly, there are no accurate non-imaging methods of diagnosing small AAAs, with clinical examination being inaccurate [9]. Secondly, prognostic determinants for AAA are relatively poorly defined [10]. Approximately 70% of 40-55mm AAAs expand within 10 years to a size requiring treatment [6,7]. There are however large intra and inter-patient variations in rates of expansion of small AAAs during follow-up [10]. To date only initial aortic diameter has been consistently shown to predict subsequent increase in aortic diameter [10-13]. Smoking has been associated with increased, and diabetes with decreased, AAA expansion in some, but not all studies [10-13]. More accurate prognostic predictors would offer the possibility of selecting patients for different management pathways rather than relying on aortic diameter alone [10]. Finally the management of small AAAs remains controversial despite randomised controlled trials indicating that open surgical repair of 40-55mm AAAs does not reduce mortality [6,7]. Many centres manage all AAAs ≤55mms conservatively. Estimates based on the UK small aneurysm trial support repeat imaging for 30-40, 41-45, 46-50 and 51-55mm AAAs at 24, 12, 6 and 3 monthly intervals respectively [10]. The increasingly utilisation of endovascular repair of AAA, with its lower peri-operative mortality, has been suggested as more appropriate management for small AAAs, particularly those in the 50-55mm range [14,15]. At present however no randomised controlled trial has been completed examining the outcome of endovascular repair of small AAAs, although one such study is expected to report soon [16]. The lack of any proven medical therapy for prevention of progression and rupture of AAAs represents an important challenge [17]. Only one randomised trial has examined the value of a medication (propranolol) for small AAAs in a cohort of reasonable size (>500 subjects) [18].