Abdominal Aortic Aneurysm

The abdominal aorta has three distinct tissue layers: intima, media, and adventitia. The intima is composed of the classic endothelial layer. The media consists of smooth-muscle cells surrounded by elastin, collagen, and proteoglycans; to a great extent, this layer is responsible for the structural and elastic properties of the artery. The adventitia consists primarily of collagen but also contains a variety of cells (including fibroblasts and immunomodulatory cells), as well as adrenergic nerves.

The diameter of the aorta decreases from its thoracic portion to its abdominal and infrarenal portions. A normal aorta shows a reduction in medial elastin layers from the thoracic portion to the abdominal portion. Elastin content and collagen content are also reduced.

Most AAAs begin below the renal arteries and end above the iliac arteries. The size, shape, and extent of AAAs vary considerably. Like thoracic aortic aneurysms (TAAs), AAAs may be broadly described as either fusiform (circumferential) or saccular (more localized). However, these descriptions represent two points on a continuum, and lesions that fall between the two points exist.

The important surgical and endovascular anatomic considerations include associated renal and visceral artery involvement (either in occlusive disease or involved in the aneurysm process) and the iliac artery (occlusive disease or aneurysm). The length of the infrarenal aortic neck is important in helping determine the surgical approach (ie, open or endovascular) and the location of the aortic cross-clamp.

Consideration of hypogastric artery (internal iliac) outflow is important in planning surgical repair. Loss of blood flow from the hypogastric artery may result in buttock claudication, impotence in males and sigmoid colon ischemia with necrosis.

Finally, inflammatory aneurysms represent a subsegment of AAAs and are characterized by a thick inflammatory peel. These aneurysms are associated with retroperitoneal fibrosis and adhesion of the duodenum (see the image below).

AAAs arise as a result of a destruction of the major structural proteins of the aorta (elastin and collagen). The inciting factors are not known, but a genetic predisposition clearly exists. Although aneurysms involve a dilatation in all three layers of the vessel wall, AAAs develop after degeneration of the media. The degeneration ultimately may lead to widening of the vessel lumen and loss of structural integrity.

After age 50 years, the normal diameter of the infrarenal aorta is 1.5 cm in women and 1.7 cm in men. An infrarenal aorta that is 3 cm or more in diameter is considered an AAA, even if asymptomatic. Approximately 90% of AAAs are infrarenal, and 30% of all aortic aneurysms occur in the infrarenal portion.

A multidisciplinary research program supported by the US National Heart, Lung, and Blood Institute identified the following as mechanisms important in the development of AAA ^[9] :

• Proteolytic degradation of aortic-wall connective tissue
• Inflammation and immune responses
• Biomechanical wall stress
• Molecular genetics

Similarly, surgical specimens of AAA have revealed the following (see the image below):

• Inflammation, with infiltration by lymphocytes and macrophages
• Thinning of the media
• Marked loss of elastin

Elastin

Elastin is the principal load-bearing element in the aorta. The aortic wall contains smooth muscle, elastin, and collagen arranged in concentric layers in order to withstand arterial pressure. The number of medial elastin layers is markedly reduced from the proximal thoracic aorta to the infrarenal aorta, with medial thinning and intimal thickening.

Elastin fragmentation and degeneration are observed in aneurysm walls. The decrease in content coupled with the histologic changes of this matrix protein in aneurysms may explain the propensity for aneurysm formation in the infrarenal aorta.

Proteolysis, metalloproteinases, and inflammation

In AAA, the aortic media appears to degrade by way of a proteolytic process. This implies an increase in the concentration of proteolytic enzymes relative to the concentration of their inhibitors in the abdominal aorta as the individual ages.

Some research has focused on the role of the metalloproteinases, a group of zinc-dependent enzymes responsible for tissue remodeling. Reports have documented increased expression and activity of matrix metalloproteinases (MMPs) in people with AAAs. MMPs and other proteases have been shown to be secreted into the extracellular matrix of AAAs by macrophages and aortic smooth-muscle cells.

MMPs and their inhibitors are present in normal aortic tissue and are responsible for vessel-wall remodeling. Aneurysmal tissue tends to demonstrate increased MMP activity and decreased inhibitor activity, which favor the degradation of elastin and collagen. The mechanism that tips the balance in favor of degradation of elastin and collagen in the aortic wall of AAAs by MMPs and other proteases is not yet known.

Upon histologic examination, AAAs demonstrate a chronic adventitial and medial inflammatory infiltrate. Infiltration of AAAs with lymphocytes and macrophages may trigger protease activation via various cytokines (eg, interleukin [IL]-1, IL-6, IL-8, and tumor necrosis factor [TNF]-α).

Immunoreactive proteins are found more conspicuously in the abdominal aorta, and this may contribute to the increased frequency of aneurysms in this region. Studies have defined a matrix protein that is immunoreactive with immunoglobulin G in the aneurysm wall. This autoantigen appears to be a collagen-associated microfibril. Certain infectious agents (eg, Chlamydia pneumoniae and Treponema pallidum) have been associated with the development of this protein; however, no direct cause-and-effect relation has been demonstrated.

Insights from molecular genetics

Through gene microarray analysis, various genes involved in extracellular matrix degradation, inflammation, and other processes observed in AAA formation have been shown to be upregulated, whereas others that may serve to prevent this occurrence are downregulated. The combination of proteolytic degradation of aortic-wall connective tissue, inflammation and immune responses, biomechanical wall stress, and molecular genetics represents a dynamic process that leads to aneurysmal deterioration of aortic tissue.

Atherosclerosis

Most AAAs occur in individuals with advanced atherosclerosis. Atherosclerosis may induce AAA formation by causing mechanical weakening of the aortic wall with loss of elastic recoil, along with degenerative ischemic changes, through obstruction of the vasa vasorum.

Many patients with advanced atherosclerosis do not develop AAA, and some patients with no evidence of atherosclerosis do. The observed association between atherosclerosis and AAA probably is not causative; however, atherosclerosis may represent a nonspecific secondary response to vessel-wall injury that is induced by multiple factors.

AAA is thought to be a degenerative process of the aorta, the cause of which remains unclear. It is often attributed to atherosclerosis because these changes are observed in the aneurysm at the time of surgery. However, a study by Blanchard et al found that the risk factors for AAA differ from those for atherosclerosis, with no association between cholesterol and AAA. ^[1] In addition, atherosclerosis fails to explain the development of occlusion, which is observed in the disease process.

Patients at greatest risk for AAA are men who are older than 65 years and have peripheral atherosclerotic vascular disease. A history of smoking often is elicited. Accordingly, in 2005, the United States Preventive Services Task Force (USPSTF) recommended screening with US in men aged 65-75 years who had ever smoked. ^[10] These recommendations were subsequently updated ^[11] on the basis of evidence from a 2014 study by Guirguis-Blake et al. ^[12]

Subsequently, the Society for Vascular Surgery (SVS) recommended screening for AAA not only according to the previous USPSTF guidelines but also in patients with first-degree relatives with history of AAA and in healthy men or women older than 75 years with a history of smoking. ^{[7, 3]}

A Swedish study showed that instances of AAA in elderly men have been decreasing, a phenomenon that can be attributed to a nationwide decline in smoking for the past 30 years, as well as the significantly improved longevity of the elderly population. ^[13] A one-time US scan is recommended for men once they reach age 65 years to detect and prevent possible occurrences of AAA.

Other risk factors for AAA include the following:

• Chronic obstructive pulmonary disease (COPD)
• Previous aneurysm repair or peripheral aneurysm (popliteal prevalence at 62% or femoral prevalence at 85%)
• Coronary artery disease
• Hypertension (1-15% of cases)

Less frequent causes of AAA include Marfan syndrome, Ehlers-Danlos syndrome, and other collagen-vascular diseases. In fewer than 5% of cases, AAA is caused by a mycotic aneurysm of hematogenous origin. In these cases, local invasion of the intima and media gives rise to abscess formation and aneurysmal dilation of the vessel. Gram-positive organisms most commonly cause mycotic aneurysms. Other uncommon causes include cystic medial necrosis, arteritis, trauma, and anastomotic disruption producing pseudoaneurysms.

Persons who have first-degree relatives with AAA are at increased risk for AAA. The familial prevalence rate of AAA has been estimated at 15-25%. Studies by Majumder et al suggested that the genetic predisposition is isolated to a single dominant gene with low penetrance that increases with age. ^[14]

Tilson et al described the potential for an autoimmune basis for the development of AAA involving the DRB1 major histocompatibility locus. ^[15] This locus has been identified as a basis for inflammatory AAA.

In late 2018, the FDA issued a warning that fluoroquinolone use can increase the risk of aortic aneurysm and urged healthcare providers to avoid prescribing these antibiotics to patients with or at risk for an aortic aneurysm, such as those with peripheral atherosclerotic vascular disease, hypertension, or certain genetic conditions (eg, Marfan syndrome and Ehlers-Danlos syndrome), as well as the elderly. ^[16]

Risk factors for rupture

Aneurysm diameter is an important risk factor for rupture. In general, AAAs gradually enlarge (0.2-0.8 mm/y) and eventually rupture. Hemodynamic factors play an important role. Areas of high stress have been found in AAAs and appear to correlate with the site of rupture. Computer-generated geometric models have demonstrated that aneurysm volume is a better predictor of areas of peak wall stress than aneurysm diameter. This may have implications for determining which AAAs require surgical repair.

AAA rupture is believed to occur when the mechanical stress acting on the wall exceeds the strength of the wall tissue. Wall tension can be calculated by applying Laplace’s law, as follows:

• P × R/W

where P is the mean arterial pressure (MAP), R is the radius of the vessel, and W is the thickness of the vessel wall. AAA-wall tension is a significant predictor of pending rupture. The actual tension in the AAA wall appears to be a more sensitive predictor of rupture than aneurysm diameter alone. For these reasons, the clinician may wish to achieve acute blood pressure control in patients with AAA and elevated blood pressure.

United States statistics

In autopsy studies, the frequency rate of AAA has ranged from 0.5% to 3.2%. In a large US Veterans Affairs screening study, the prevalence was 1.4%. ^[2] The likelihood of development has ranged from 3 to 117 cases per 100,000 person-years.

Ruptured AAA is the 13th-leading cause of death in the United States, causing an estimated 15,000 deaths per year. The frequency of rupture has been reproted to be 4.4 cases per 100,000 persons. The reported incidence of rupture has ranged from 1 to 21 cases per 100,000 person-years. Despite increased survival following diagnosis, incidence and crude mortality and morbidity seem to be increasing.

International statistics

The frequency of asymptomatic AAA has been reported to be 8.2% in the United Kingdom, 8.8% in Italy, 4.2% in Denmark, and 8.5% in Sweden (in males only). The reported frequency of AAA in females has been much lower, 0.6-1.4%. The frequency of AAA rupture has been reported to be 6.9 cases per 100,000 persons in Sweden, 4.8 cases per 100,000 in Finland, and 13 cases per 100,000 in the United Kingdom.

Age-, sex-, and race-related demographics

The incidence of AAA begins to increase sharply after 50 years of age and peaks in the eighth decade of life (see the image below). In women, the onset of this increase is delayed and appears to occur at approximately age 60 years.

The male-to-female incidence ratio in people younger than 80 years is 2:1. In those older than 80 years, the ratio is 1:1. After menopause, women may experience faster AAA growth (particularly of fusiform aneurysms) and at smaller sizes than men do; this suggests that it might be advisable to carry out surveillance in postmenopausal women at shorter intervals than those specified in SVS guidelines. ^[17]

White men have the highest incidence of AAA (~3.5 times that in Black men). AAAs are uncommon in African Americans, Asians, and persons of Hispanic heritage.

For patients who suffer rupture of an AAA before hospital arrival, the prognosis is guarded. More than 50% do not survive to reach the emergency department (ED); for those who do, the survival rate drops by about 1% per minute. However, in the subset of patients who are not in severe shock and who receive expert surgical intervention in a timely manner, the survival rate is more favorable.

In 1988, 40,000 surgical reconstructions for AAA were performed in the United States, and substantial mortality differences between elective and emergency operations were noted. Because the mortality associated with elective aneurysm repair is drastically lower than that associated with repair of a ruptured AAA, the emphasis must be on early detection and repair free from complications.

In 2014, Ambler et al, in association with the Audit and Quality Improvement Committee of the Vascular Society of Great Britain and Ireland, used data collected during a 15-month period in the United Kingdom National Vascular Database to develop a model for assessing the risk of in-hospital mortality after AAA repair. ^[18]

A retrospective study by Leyba et al (N = 22,395; 16,125 male, 6270 female; 18,655 White, 1555 Black, 1095 Hispanic, 470 Asian or Pacific Islander, 80 Native American) examined sex- and race-related disparities in inpatient outcomes for patients with ruptured AAAs in the United States. ^[19]  Compared with male patients, female patients were less likely to undergo EVAR and more likely to die while hospitalized. Despite having a higher rate of comorbidity, Black patients were less like to die during hospitalization than White patients.

The long-term prognosis is related to associated comorbidities. Long-term survival is shortened by chronic heart failure and COPD. Rupture of associated TAAs is also an important cause of late death. Overall, AAA repair is very durable, with few long-term complications (< 5% false aneurysm). In general, the survival rate of patients with successful AAA repair is comparable to that of people in the age-matched population at large who have never had an aneurysm. ^{[20, 21]}