Aortic aneurysms develop when the wall of the aorta weakens and bulges outward, and the causes range from gradual wear driven by smoking and high blood pressure to inherited genetic conditions that compromise the vessel wall from birth. Smoking is the single strongest modifiable risk factor, raising the likelihood of an aortic aneurysm by three to six times compared to nonsmokers. Understanding what triggers this weakening helps explain why some people develop aneurysms and others don’t.
How the Aortic Wall Breaks Down
The aorta is built in layers, and the middle layer (the media) contains elastic fibers that allow the vessel to stretch and recoil with every heartbeat. In people who develop aneurysms, these elastic fibers become fragmented and depleted. Specimens from aneurysm tissue consistently show reduced elastin content, impaired cross-linking between fibers, and extensive fragmentation. Once enough elastic scaffolding is lost, mechanical stress shifts onto stiffer collagen fibers at lower pressures, raising the peak stress on the wall and accelerating further enlargement.
The breakdown is driven by a family of enzymes that digest elastin. Immune cells, particularly macrophages and neutrophils, infiltrate the aortic wall and release these enzymes in large quantities. One enzyme produced almost exclusively by macrophages is responsible for roughly 95% of macrophage-driven elastin destruction. At the same time, the smooth muscle cells that normally maintain and repair the vessel wall begin to die off and malfunction. As these cells are lost, less new elastin is produced and more destructive enzymes are released, creating a self-reinforcing cycle of damage.
Neutrophils add another layer of harm by generating bursts of reactive oxygen species, highly reactive molecules that directly damage elastic fibers, disable the body’s natural protease inhibitors, and prime destructive enzymes to become more active. The result is an imbalance: too many enzymes breaking down the wall and too few inhibitors to stop them.
Thoracic vs. Abdominal: Different Locations, Different Drivers
Aortic aneurysms are broadly split into two types based on where they occur, and the causes differ meaningfully between them. Abdominal aortic aneurysms (AAAs), which form below the diaphragm, are strongly tied to lifestyle and cardiovascular risk factors like smoking, high blood pressure, and high cholesterol. Thoracic aortic aneurysms (TAAs), which form in the chest, have a much stronger genetic component. An estimated 20% to 25% of TAA patients have a familial form of the disease, often following an autosomal dominant inheritance pattern. AAAs do not typically show this kind of inheritance.
Comparative analyses at the cellular level confirm that the two types involve different biological pathways and distinct sets of genes. This is why screening guidelines, risk profiles, and management strategies differ depending on which part of the aorta is affected.
Genetic and Inherited Causes
At least 29 genes have been linked to thoracic aortic aneurysm and dissection, and roughly one in four patients with a thoracic aneurysm carries a mutation in one of them. Most of these genes encode proteins involved in three areas: the structural matrix of the vessel wall, smooth muscle cell contraction, or a key growth-signaling pathway called TGF-beta.
The best-known genetic cause is Marfan syndrome, caused by mutations in the FBN1 gene, which produces a protein critical to connective tissue integrity. Loeys-Dietz syndrome, caused by mutations in several TGF-beta pathway genes, is another well-recognized cause. Together, Marfan and Loeys-Dietz gene mutations account for about 10% of familial thoracic aneurysms. Mutations in ACTA2, a gene involved in smooth muscle contraction, are even more common, causing an estimated 12% to 21% of familial cases.
Several forms of Ehlers-Danlos syndrome also predispose to aneurysms, particularly the vascular type caused by mutations in COL3A1. Other rare conditions linked to aortic aneurysms include Shprintzen-Goldberg syndrome, arterial tortuosity syndrome, and cutis laxa. Even people without a named syndrome can carry mutations that raise their risk. If a first-degree relative had a thoracic aortic aneurysm or dissection, the probability of carrying a relevant gene variant is significantly higher.
Smoking and High Blood Pressure
Smoking is the most potent modifiable risk factor for aortic aneurysm. Current smokers face a relative risk of 3 to 6 for aneurysm-related events, a stronger association than smoking has with coronary artery disease (relative risk of 1 to 2) or stroke (also 1 to 2). In fact, the link between smoking and aortic aneurysm is 2.5 times stronger than the link between smoking and heart disease, and 3.5 times stronger than its link to cerebrovascular disease. Of the major smoking-related conditions, only chronic obstructive pulmonary disease (COPD) has a stronger association.
High blood pressure contributes by placing chronic mechanical stress on an already vulnerable wall. Every heartbeat pushes blood against the aorta, and sustained hypertension amplifies the force on weakened segments. This doesn’t just initiate damage; it accelerates expansion of existing aneurysms. High cholesterol plays a supporting role by promoting atherosclerotic plaque buildup, which triggers local inflammation in the vessel wall and further contributes to structural weakening.
Inflammatory and Autoimmune Causes
Conditions that inflame the aortic wall directly, collectively called aortitis, can cause aneurysms even without traditional cardiovascular risk factors. Takayasu arteritis is a prime example: the immune system mounts a T-cell response against components of the aortic wall, starting with inflammation in the outer layers and small blood vessels (vasa vasorum) that supply the aorta itself. As inflammation spreads inward through the full thickness of the wall, smooth muscle cells are destroyed, the media weakens, and the vessel dilates or forms a frank aneurysm.
Giant cell arteritis follows a similar pattern and is the most common form of large-vessel vasculitis in older adults. Chronic idiopathic periaortitis represents another inflammatory pathway, where inflammation begins in the vasa vasorum and can progress to a spectrum of disease ranging from inflammatory abdominal aortic aneurysm to retroperitoneal fibrosis. A notable proportion of these cases show a specific type of immune cell infiltrate associated with IgG4-related disease.
Infection as a Cause
Infected (mycotic) aneurysms are uncommon but dangerous. They develop when bacteria colonize the arterial wall, triggering rapid inflammation and structural breakdown. In Western countries, the most common culprits are Staphylococcus aureus (28% of cases), Salmonella species (15%), and Pseudomonas (10%). In Asian countries, Salmonella is more frequently identified. Fungal causes are rare and largely confined to people with compromised immune systems, such as those with diabetes, HIV, or undergoing chemotherapy.
Bacteria can reach the aortic wall through several routes. Bloodstream infections can seed an already damaged segment of artery. Intravenous drug use, trauma, or medical procedures involving needles or catheters can introduce bacteria directly into the vessel wall. Nearby infections, such as spinal bone infections or abdominal conditions like appendicitis, can also spread to the aorta by direct extension. Once bacteria penetrate the inner lining, infection moves rapidly into deeper layers, and an aneurysm can form quickly.
Who Is Most at Risk
Men develop aortic aneurysms far more often than women. Women account for only about 23% of thoracic aneurysm repairs, though they represent a disproportionate 45% of aorta-related deaths, suggesting that aneurysms in women may be detected later or behave more aggressively. Age is a major factor: the vast majority of aneurysms are diagnosed after age 60, and prevalence rises steeply with each decade.
The U.S. Preventive Services Task Force recommends a one-time ultrasound screening for abdominal aortic aneurysm in men aged 65 to 75 who have ever smoked. “Ever smoked” is defined as having smoked 100 or more cigarettes in a lifetime, a threshold that includes many people who consider themselves former light smokers. For men in that age range who have never smoked, screening is offered selectively based on other risk factors. Routine screening is not recommended for women who have never smoked and have no family history.
Slowing Aneurysm Growth
Once an aneurysm is found, slowing its expansion becomes the primary goal if it hasn’t yet reached a size requiring repair. Cholesterol-lowering statin medications show a meaningful effect. In one study, patients taking statins had an aneurysm growth rate of just 0.9 mm per year, compared to 3.2 mm per year in those not on statins. For an aneurysm starting at the median size of 4.1 cm, statin users saw essentially no net growth over a year (a change of negative 0.3 mm), while non-users grew by 3.1 mm.
Interestingly, neither beta blockers nor ACE inhibitors showed a significant effect on growth rate in the same analysis. Quitting smoking, controlling blood pressure, and regular imaging surveillance remain the cornerstones of managing a small aneurysm that hasn’t yet reached the threshold for surgical intervention.