|Atherosclerotic Aneurysm: Gross, an excellent example, natural color, external view of typical thoracic aortic aneurysms |
Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology
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An aortic aneurysm is a dilation of the aorta in which the aortic diameter is ≥ 3.0 cm if abdominal or >4 cm if thoracic, usually representing an underlying weakness in the wall of the aorta at that location. While the stretched vessel may occasionally cause discomfort, a greater concern is the risk of rupture which causes severe pain, massive internal hemorrhage which are often fatal. Aneurysms often are a source of blood clots (emboli) stemming from the most common etiology of atherosclerosis.
There are 2 types of aortic aneurysms: thoracic and abdominal. These can be further classified according to the respective part of the vessel that's been affected:
- Thoracic aortic aneurysm, which occur in the thoracic aorta (runs through the chest);
- Abdominal aortic aneurysm, which occur in the abdominal aorta, are the most common.
- Suprarenal - not as common, often more difficult to repair surgically due to the presence of many aortic branches;
- Infrarenal - often more easily surgically repaired and more common;
- Pararenal - aortic aneurysm is infrarenal but affects renal arteries;
- Juxtarenal - infrarenal aortic aneurysm that affects the aorta just below the renal arteries.
Aortic aneurysms may also be classified according to Crawford classification into 5 subtypes/groups:
- Type 1: from the origin of left subclavian artery in descending thoracic aorta to the supra-renal abdominal aorta.
- Type 2: from the left subclavian to the aorto-iliac bifurcation.
- Type 3: from distal thoracic aorta to the aorto-iliac bifurcation
- Type 4: limited to abdominal aorta below the diaphragm
- Type 5: from distal thoracic aorta to celiac and superior mesenteric origins, but not the renal arteries.
Aortic aneurysm was first recorded by Antyllus, a Greek surgeon, in the second century AD. In the Renaissaince era, in 1555, Vesalius first diagnosed an abdominal aortic aneurysm. The first publication on the pathology with case studies was published by Lancisi in 1728. Finally, in 1817, Astley Cooper was the first surgeon to ligate the abdominal aorta to treat a ruptured iliac aneurysm. In 1888, Rudoff Matas came up with the concept of endoaneurysmorrhaphy.
The aortic aneurysms are a multifactorial disease associated with genetic and environmental risk factors. Marfan's syndrome and Ehlers-Danlos syndrome are associated with the disease, but there are also rarer syndromes like the Loeys-Dietz syndrome that are associated as well. Even in patients that do not have genetic syndromes, it has been observed that genetics can also play a role on aortic aneurysms' development. There has been evidence of genetic heterogeneity as there has already been documented in intracranial aneurysms. The genetic alterations associated with these genetic syndromes are the following:
|Disease||Involved Cellular Pathway||Mutated Gene(s)||Affected Protein(s)|
|Ehlers-Danlos type IV syndrome||Extracellular Matrix Proteins||COL3A1||Collagen type III|
|Marfan's Syndrome||Extracellular Matrix Proteins||FBN1||Fibrillin-1|
|Loeys-Dietz syndrome||TGF-β Pathway||TGFBR1/TGFBR2|
|Autosomal Dominant Polycystic Kidney Disease||Ciliopathy||PKD1/PKD2||Polycystin 1|
|Turner Syndrome||Meiotic Error with Monosomy, Mosaicism, or De Novo Germ Cell Mutation||45X
|Partial or Complete Absence of X Chromosome|
|Bicuspid Aortic Valve with TAA||Neural Crest Migration||NOTCH1||Notch 1|
|Familial TAA||Smooth Muscle Contraction Proteins||ACTA2||α-Smooth Muscle Actin|
|Familial TAA with Patent Ductus Arteriosus||Smooth Muscle Contraction Proteins||MYH11||Smooth Muscle Myosin|
|Familial TAA||Smooth Muscle Contraction Proteins||MYLK||Myosin Light Chain Kinase|
|Familial TAA||Smooth Muscle Contraction Proteins||PRKG1||Protein Kinase c-GMP Dependent, type I|
|Loeys-Dietz Syndrome variants||TGF-β Pathway||TGF-βR1
These genetic diseases mostly affect either the synthesis of extracellular matrix protein or damage the smooth muscle cells both important component's of the aortic wall. Injury to any of these components lead to weakening of the aortic wall and dilation - resulting in aneurysm formation.
The aorta is the largest vessel of the body, but it is not homogenous. Its upper segment is composed by a larger proportion of elastin in comparison to collagen, therefore being more distensible. The lower segment has a larger proportion of collagen, therefore it is less distensible. It is also where most of the atherosclerotic plaques of the aorta are located. Historically it was thought that abdominal and thoracic aortic aneurysms were caused by the same etiology: atherosclerotic degeneration of the aortic wall, but recently it has been theorized that they are indeed different diseases.
The aortic arch mostly derives from the neural crest cell which differentiate into smooth muscle cells. These smooth muscle cells are probably more adapted to remodel the thoracic aorta and manage the higher pulse pressure and ejection volume due to increased production of elastic lamellae during development and growth. The abdominal aorta remains with cells of mesodermal origin, which are more similar to that of the original primitive arterial. That difference results in the neural crest cell precursors of the thoracic aorta being able to respond differently to various cytokines and growth factors than the mesodermal precursors of the abdominal aorta, such as homocysteine and angiotensin II.
When neural crest vascular smooth muscle cells are treated with TGF-β they demonstrate increased collagen production, while mesodermal vascular smooth muscle cell did not. Not coincidently, mutations of the TGF-β receptor can cause thoracic aortic aneurysm but do not cause abdominal aortic ones.
The thoracic and abdominal aorta are very structurally different. While they both have three layers: intimal, medial and adventitia, the media of the thoracic aorta is comprised of approximately 60 units divided into vascular and avascular regions. The abdominal aorta consists of about 30 units and is entirely avascular, being dependent on trans-intimal diffusion of nutrients for its smooth muscle cells to survive. It is believed that both differences explain why the abdominal aorta is more likely to form aneurysms.
The development of aortic aneurysms is defined by: inflammation: infiltration of the vessel wall by lymphocytes and macrophage; extracellular matrix damage: destruction of elastin and collagen by proteases (also metalloproteinases) in the media and adventitia; cellular damage: loss of smooth muscle cells with thinning of the media; and insufficient repair: neovascularization.
Thoracic aortic aneurysms: The aneurysms tend to grow slowly and most of them will never rupture. As they grow, however, their symptoms become more evident and present with mass effects over surrounding structures and pain. They may present with thoracic symptoms: interscapular or central pain, ripping chest pain and dyspnea. Atypical presentations include hoarseness, dizziness and dysphagia, due to esophageal compression. Aneurysm rupture lead to massive internal bleeding, hypovolemic shock and it is usually fatal.
Abdominal aortic aneurysms: as the thoracic aneurysms, they begin asymptomatic but may cause symptoms as they grow and compress surrounding structures.Even though they usually remain asymptomatic, when they rupture they present with an ensuing mortality of 85 to 90%., and symptomatic patients require urgent surgical repair.
When symptomatic, abdominal aortic aneurysms present with:
- Pain: in the chest, abdomen, lower back, or flanks. It may radiate to the groin, buttocks, or legs. The pain characteristics vary and may be deep, aching, gnawing, or throbbing It may also last for hours or days, not affected by movement. Occasionally, certain positions can be more comfortable and alleviate the symptoms;
- Pulsating abdominal mass;
- Ischemia: "cold foot" or a black or blue painful toe. This is usually the presentation when an aneurysm forms a blood cloth and it releases emboli to the lower extremities;
- Fever or weight loss if caused by inflammatory states such as vasculitis.
If ruptured, the abdominal aortic aneurysm can present with sharp abdominal pain, often radiating to the back, discoloration of the skin and mucosa, tachycardia and low blood pressure due to hypovolemic shock.
Differentiating Aortic Aneurysm from other Diseases
Thoracic aortic aneurysms: differential diagnosis include other causes of chest pain: acute aortic dissection, acute pericarditis, aortic regurgitation, heart failure, hypertensive emergencies, infective endocarditis, myocardial Infarction, pulmonary embolism, superior vena cava syndrome. 
Abdominal aortic aneurysms: differential diagnosis include causes of pulsatile abdominal mass and/or abdominal pain such as ruptured viscus, strangulated hernia, ruptured visceral artery aneurysms, mesenteric ischemia, acute cholecystitis, ruptured hepatobiliary cancer, acute pancreatitis, lymphomas, and diverticular abscess.
These conditions can be easily differentiated using abdominal or thoracic imaging.
Epidemiology and Demographics
In the United States alone 15,000 people die yearly due to aortic aneurysms and it is the 13th leading cause of death. 1-2% of the population may have aortic aneurysms and prevalence rises up to 10% in older age groups. The disease varies according to where it takes place. In the thorax, the aortic arch is the less affected segment (10%) and the most common is the ascending aorta (50%). Regarding abdominal aneurysms, the infrarenal segment aortic aneurysms are three times more prevalent than the aortic aneurysms and dissections.
Regarding other factors as age, abdominal aortic aneurysms usually present 10 years later than thoracic aortic aneurysms. Both lesions are more present in men, but the proportion is much higher regarding abdominal aortic aneurysms (6:1 male:female ratio) in comparison to thoracic ones.
Abdominal aortic aneurysms also affect patients differently regarding race, as they are more prevalent among whites than blacks, asians and hispanics. It also seems to be declining in prevalence as evidenced by a Swedish study that found out a 2% prevalence of abdominal aortic aneurysms in comparison to earlier studies which reported 4-8%, probably due to risk-factor modification. 
Many risk factors are common between both forms of aortic aneurysms, but some are specific for each presentation:
- Abdominal aortic aneurysm: smoking, male gender, age (>65 years), race (white), family history, other aneurysms.
- Thoracic aortic aneurysm: smoking, age (>65 years), hypertension, atherosclerosis, family history, Marfan's syndrome, bicuspid aortic valve. 
Natural History, Complications and Prognosis
Even though the majority of the aortic aneurysms remain asymptomatic for years, their natural history is dissection or rupture. According to Laplace's law, as the aneurysms grow larger they have a higher rate of expansion. Due to that, the frequency of monitoring changes with the diameter of the abdominal aortic aneurysm, being every 3 years for aneurysms with a 3-3.4cm diameter, yearly for diameters of 3.5-4.4cm, and every 6 months for larger than 4.5cm. For the thoracic one, up to 80% of the aneurysms will eventually rupture, and patients present with a 10-20% five-year survival rate if they remain untreated. Risk of rupture doubles every 1cm in growth over the 5cm diameter in descending thoracic aorta.
Besides rupturing and dissection of the aorta, aortic aneurysms can also present with systemic embolization and aortic regurgitation (if the thoracic aortic aneurysm is located in the ascending aorta). The altered blood flow in the aneurysm can also lead to the formation of blood cloths and embolization. 
Abdominal aortic aneurysm: begin asymptomatic but may cause pain, pulsating abdominal mass, peripheral ischemia, fever or weight loss. When they rupture, they cause acute abdominal pain and hypovolemic shock.
- There are no specific laboratory findings associated withaortic aneurysms.
- Anemia can be seen in ruptured aortic aneurysms.
- An abdominal ultrasound can be diagnostic of abdominal aortic aneurysms and is the imaging tool used to screen for aortic aortic aneurysms.
- CTA/MRA can accurately demonstrate aortic aneurysms extent.
Other Diagnostic Studies
- Conventional angiogram can be used to diagnose aortic aneurysms.
- Beta-blockers may help in reducing the rate of expansion of the aortic aneurysm, reducing shear stress - studies have been mostly on Marfan patients and they found a low compliance with propranolol due to a significant effect on quality of life;
- Tetracyclines inhibit the MMP endopeptidases, and has been used in conditions in which MMP are overexpressed such as rheumatoid arthritis. There are studies in humans showing that doxycycline reduced the rate of expansion of aortic aneurysms. Roxithromycin, a macrolide has been also show to reduce the expansion of the aortic aneurysms.
- Statins may also be helpful due to their pleiotropic effecs, reducing the oxidative stress by blocking the reactive oxygen species on aneurysms, suppressing the NADH/NADPH oxidase system.
- Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers promotes vascular hypertrophy, cell proliferation and production of extracellular matrix. It also activates the NADH/NADPH oxidase system, both stimulating and inhibiting MMPs and degradation of extracellular matrix. There is a controversy of which class is more effective, and ongoing trials are being run to further clarify these questions.
Decision to perform elective surgery to prevent aneurysm rupture is complicated as there must be an appropriate patient selection and timing for repair of the aneurysm which demands selecting patients at the greatest risk of aneurysm rupture. Once rupture occurs, mortality is extremely high. Fatality rates of emergency surgical repair is 50% if the patient manages to reach the hospital, in comparison to 1-5% fatality rate in elective surgical repair.
According to the 2005 AHA/ACC guidelines - it is recommended surgical repair of abdominal aortic aneurysms:
- 5.5 cm in diameter or greater in asymptomatic patients;
- Increase by 0.5 cm or greater in diameter in 6 months;
- Symptomatic aneurysms.
Endovascular repair may be performed with better short-term morbidity and mortality rates but with failed long-term benefits over surgical repair. Endovascular is preferred in high-risk patients while surgical repair is generally indicated for low/average-risk patients.
In thoracic aortic aneurysms, surgery is indicated in Marfan's syndrome when the aortic diameter reaches 5.0cm, or the rate of increase of the aortic root diameter approaches 1.0 cm per year, or progressive and severe aortic regurgitation. If family history is positive for aortic aneurysms, aggressive therapy may be indicated in individuals with Marfan and Loeys Dietz syndrome. Surgery consists in replacing the affected portion of the aorta. 
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