Aetiology

Traditionally, arterial aneurysms were thought to arise from atherosclerotic disease, and certainly intimal atherosclerosis reliably accompanies AAA.[21] Subsequent data suggest that altered tissue metalloproteinases may diminish the integrity of the arterial wall.[7]

Smoking remains the most significant risk factor.[1][9][13][14][22][23][24]​​[25]​​ 

Evidence suggests that diabetes may protect against the growth and enlargement of AAA.[26][27][28]​ However, the protective mechanism is yet to be determined.[27]​ Data demonstrate that operative and long-term survival is lower among AAA repair patients with diabetes than those without, suggesting an increased cardiovascular burden.[26][29]

Pathophysiology

Histologically there is obliteration of collagen and elastin in the media and adventitia, smooth muscle cell loss with resulting tapering of the medial wall, infiltration of lymphocytes and macrophages, and neovascularisation.[21][30]​ There are 4 mechanisms relevant to AAA development:[31]

  • Proteolytic degradation of aortic wall connective tissue: matrix metalloproteinases (MMPs) and other proteases are derived from macrophages and aortic smooth muscle cells and secreted into the extracellular matrix. Disproportionate proteolytic enzyme activity in the aortic wall may promote deterioration of structural matrix proteins (e.g., elastin and collagen).[30]​ One meta-analysis reported significant AAA risk associated with the expression of certain MMP-2, MMP-3, and MMP-13 polymorphisms (and MMP-9 in a hospital patient subgroup), indicating possible future clinical applications for determining prognosis and suitability of patients for surgery.[32]

  • Inflammation and immune responses: an extensive transmural infiltration by macrophages and lymphocytes is present on aneurysm histology and these cells may release a cascade of cytokines that subsequently activate many proteases.[21] Additionally, deposition of immunoglobulin G into the aortic wall supports the hypothesis that AAA formation may be an autoimmune response. There is research interest in the role of reactive oxygen species and antioxidants in AAA formation.[33][34][35][36][37]

  • Biomechanical wall stress: elastin levels and the elastin-collagen ratio decrease progressively distal down the aorta. Diminished elastin is associated with aortic dilation, and collagen degradation predisposes to rupture.[31]​ Additionally, data support increased MMP-9 expression and activity, disordered flow and an increase in wall tension, and relative tissue hypoxia in the distal aorta (i.e., infrarenal).[33][38]​​

  • Molecular genetics: AAA exhibits significant heritability (the proportion of phenotype due to genotype). A Swedish Twin Registry study found that the twin of a monozygotic twin with AAA had a risk of AAA approximately 70 times greater than that of the twin of a monozygotic twin without AAA.[39] While there is no single genetic defect or polymorphism responsible, familial clustering suggests a polygenic aetiology. Genome-wide approaches have identified 10 risk loci for AAA, 4 of which are not shared with other cardiovascular diseases.[40][41]​

Classification

Types of AAA[6][7][8]

  • Congenital: while medial degeneration occurs naturally with age, it is accelerated in patients with bicuspid aortic valves and Marfan syndrome.

  • Infectious: infection of the aortic wall (‘mycotic aneurysm’ or ‘infectious aortitis’) is a rare aetiology. Staphylococcus, Pneumococcus, Escheria coli, and Salmonella are the most common pathogens.[9] Chlamydia pneumoniae has been postulated as an infectious aetiology for conventional aneurysms.[10]​ Tertiary syphilis may manifest as aortic aneurysm, but this is an exceptionally rare presentation.[9][11]​​ Fungal infection and tuberculous aortitis are rare and most often occur in the setting of immunocompromise.[9]

  • Inflammatory: the aetiology of inflammatory AAAs remains controversial. This variant is characterised by an abnormal accumulation of macrophages and cytokines in diseased tissue. Pathologically there is perianeurysmal fibrosis, thickened walls, and dense adhesions.[7]​ The most common causes of inflammatory aortitis are the large vessel vasculitides Takayasu's arteritis and giant cell arteritis. Other known causes include immunoglobulin G4-related disease, sarcoidosis, Behcet's disease, and granulomatosis with polyangiitis.[9]

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