Abdominal Aortic Aneurysms

Aneurysm disease burden and pathophysiology. Abdominal aortic aneurysms (AAAs) primarily affect elderly males with a prevalence of 3%. In England, rupture of aortic aneurysms cause 6,500 deaths per year [1]. Many risk factors have been associated with aneurysmal rupture eg., high diastolic blood pressure, smoking, family history of AAA and chronic obstructive pulmonary disease but the principle determinant of rupture is the maximum diameter of the aneurysm, which increases with age [2].Initiation of the lesion is associated with inflammation and modulation of proteolytic enzymes, causing the early loss of elastin and a compensatory increase in the expression of collagen [2,3].Subsequent formation of thrombus, which can cause alterations of blood flow as well as creating ischaemia, is most likely to induce new blood vessel development and changes in the expression of ischemia-induced genes [4,5].Angiogenesis further exacerbates the inflammatory process by providing a conduit for infiltration of immune-responsive cells.The combination of conditions which are anti-proliferative and pro-apoptotic result in cellular losses [6,7].Ultimately the aortic wall is thickened, non-compliant, matrix-rich and cell poor.Our recent studies suggest that bursts of subsequent medial neo-angiogenesis may provide the final differential weakening across the structurally compromised lesion, leading to aneurysmal rupture [8].

Current status of aortic aneurysm treatment. There is no known pharmacotherapeutic drug licensed for stabilisation or regression of AAA.Results of the UK small aneurysm study, which evaluated the benefits of surgery, concluded that the benefits outweighed the risks when vessel dilatation was greater than 5.0 - 5.5 cm [2].Recent studies have evaluated the benefits of endovascular arterial repair (EVAR) by stenting compared to open repair in fit patients (EVAR I) and compared to conservative management in unfit patients (EVAR II) [9]. Patients with small aneurysms undergo ultrasound surveillance and are generally treated for co-morbidities.Patients with large aneurysms often have no alternative to open-repair, which carries a high risk of mortality.The introduction of aneurysm screening over the age of 65 years will result in the diagnosis of significantly more aneurysms.

1. Thompson MM.(2003). Infrarenal Abdominal Aortic Aneurysms. Curr Treat Options Cardiovasc Med. 5:137-146.

2. Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. (1998) The UK Small Aneurysm Trial Participants. Lancet .352:1649-1655.

3. Wills A, Thompson MM, Crowther M, Sayers RD, Bell PR.(1996) Pathogenesis of abdominal aortic aneurysms--cellular and biochemical mechanisms. Eur J Vasc Endovasc Surg . 12(4):391-400.

4. Sho E, Sho M, Nanjo H, Kawamura K, Masuda H, Dalman RL. (2004) Hemodynamic regulation of CD34+ cell localisation and differentiation in experimental aneurysms. Arterioscler Thromb Vasc Biol.24;1916-1921.

5. Thompson MM, Jones L, Nasim A, Sayer RD, Bell PR. (1996) Angiogenesis in abdominal aortic aneurysm. Eur J Vasc Endovasc Surg.11;464-469.

6. Tang PC, Coady MA, Lovoulos L, Dardik A, Aslan M, Elefteriades JA, Tellides A. (2005) Hyperplastic cellular remodelling if the media in ascending thoracic aortic aneurysms. Circ.112;1098-1105.

7. Sinha I, Sinha-Hakim AP, Hannawa KK, Henke PK, Eagleton MJ, Stanley JC, Upchurch GR Jr. (2005) Mitochondrial-dependent apoptosis in experimental rodent abdominal aortic aneurysms. Surgery.138:806-811.

8. Choke E, Dawson J, Wilson WR, Loftus IM, Thompson MM, Cockerill GW.(2006) Upregulation of pro-angiogenic mediators and increased angiogenesis at the site of abdominal aortic aneurysm rupture. Arterioscler Thromb Vasc Biol.26:2077-2082.

9.Greenhalgh RM, Brown LC, Kwong GP, Powell JT, Thompson SG, EVAR trial participants. (2004) 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. Lancet.364:843-848.