An Abdominal Aortic Aneurysm (AAA) is a localized swelling or bulge that develops in the aorta, the body’s largest blood vessel, as it passes through the abdomen. The abdominal aorta is normally about two centimeters wide, but it is classified as an aneurysm when it widens to three centimeters or more, and as a large aneurysm when it exceeds 5.5 centimeters. This weakening of the aortic wall is a serious condition because a large aneurysm risks rupture, which causes massive, life-threatening internal bleeding and is often rapidly fatal.
AAA Risk: Familial Tendency vs. Single-Gene Disorders
Abdominal aortic aneurysm has a substantial hereditary component, with heritability estimated to be as high as 70% in some studies. However, the condition does not typically follow the pattern of a simple Mendelian single-gene disorder, where a single mutation guarantees disease development.
Instead, AAA is considered a complex, polygenic disease, meaning that multiple genes contribute to an individual’s overall susceptibility. A person’s risk is significantly higher if they have a first-degree relative—a parent, sibling, or child—who has been diagnosed with the condition. This family history can increase a person’s risk of developing an AAA by four to six times compared to the general population. For male first-degree relatives of a patient, the prevalence of AAA can be as high as 21% to 25%.
Genome-wide association studies (GWAS) have identified numerous genetic variations, or single nucleotide polymorphisms (SNPs), that are associated with an increased predisposition for AAA. These genetic loci, such as regions on chromosome 9p21 (near the CDKN2BAS gene) and 12q13.3, each contribute a small amount to the overall risk. Researchers use these common variations to calculate a polygenic risk score, which estimates a person’s total genetic susceptibility to the condition.
In rare instances, AAA can be a feature of a more comprehensive connective tissue disorder, such as Marfan syndrome, Ehlers-Danlos syndrome, or Loeys-Dietz syndrome. These disorders are caused by mutations in a single gene, leading to widespread weakness in the body’s connective tissues, including the aortic wall.
Non-Genetic Factors That Increase Risk
While genetic predisposition lays the groundwork for AAA, environmental and acquired factors trigger the disease process. These non-genetic elements interact with inherited susceptibility, leading to the breakdown of structural proteins within the aortic wall. This combination of vulnerability and stress ultimately causes the aorta to weaken and bulge.
Advanced age is a primary non-modifiable risk factor, with the prevalence of AAA increasing significantly in individuals over 65 years old. Biological sex also plays a role, as men are four to five times more likely to develop an AAA than women. Smoking history is considered the single most important environmental factor, dramatically increasing the risk and often accounting for approximately 78% of all AAAs measuring 4.0 centimeters or more.
A history of high blood pressure (hypertension) places continuous stress on the aortic wall, contributing to its degradation over time. Similarly, high cholesterol levels (hyperlipidemia) promote the development of atherosclerosis, which is the hardening and narrowing of the arteries that further compromises the integrity of the aorta.
When Should Screening Be Considered?
Given the silent nature of AAA—most people have no symptoms until the aneurysm ruptures—screening with a simple imaging test is the most effective preventative strategy. Medical bodies, such as the U.S. Preventive Services Task Force (USPSTF), have established clear guidelines based on the strongest risk factors, including family history. The standard screening tool is a one-time abdominal ultrasound, which is a non-invasive and quick procedure.
Routine one-time screening is strongly recommended for all men between the ages of 65 and 75 who have any history of smoking, which is typically defined as having smoked 100 or more cigarettes in a lifetime. For men in this same age bracket who have never smoked, screening is offered selectively, with the decision often hinging on the presence of other risk factors, particularly a family history of AAA.
Family history is a separate and significant criterion that expands screening recommendations beyond just smoking status. Screening should be considered for men and women with a first-degree relative who had an AAA, regardless of whether the individual has ever smoked. Some organizations suggest offering this screening to male siblings and offspring of AAA patients as early as age 60.
While routine screening is not recommended for women who have never smoked and lack a family history, those women aged 65 to 75 who have a smoking history or a family history of AAA should discuss screening with their healthcare provider. Early detection aims to identify an aneurysm while it is small, allowing for regular monitoring or repair before it poses a significant risk of rupture.