Aneurysms form when an artery wall weakens and bulges outward under the pressure of blood flow. The underlying cause is a breakdown of the structural proteins that give arteries their strength and flexibility, but what triggers that breakdown varies. Smoking, high blood pressure, genetic conditions, infections, and even the geometry of your blood vessels can all play a role.
How an Artery Wall Breaks Down
Healthy arteries have layers of muscle cells, elastic fibers, and collagen that allow them to stretch and snap back with every heartbeat. An aneurysm develops when those layers degrade. The key players are enzymes called matrix metalloproteinases, which act like molecular scissors, cutting through the collagen and elastin that hold the artery together. In a healthy artery, these enzymes are kept in check by natural inhibitors. When that balance tips, the enzymes chew through structural tissue faster than the body can rebuild it.
At the same time, the smooth muscle cells embedded in the artery wall begin to die off through a process called apoptosis. These cells are responsible for maintaining the wall’s tone and generating new structural proteins. As they disappear, the artery loses both its scaffolding and its ability to repair itself. The result is a thinned, weakened section that gradually stretches outward under normal blood pressure. This combination of protein destruction and muscle cell loss is the hallmark of aneurysm formation regardless of where it occurs in the body.
Smoking Is the Strongest Modifiable Risk Factor
Current smokers face a fivefold higher risk of developing an abdominal aortic aneurysm compared to people who have never smoked. Even former smokers carry roughly double the risk. The relationship is dose-dependent: the more you smoke and the longer you smoke, the greater the damage. Tobacco compounds accelerate the enzyme imbalance described above, promote chronic inflammation in artery walls, and stiffen the vessels in ways that compound over time.
The link is so well established that U.S. screening guidelines are built around it. The U.S. Preventive Services Task Force recommends a one-time ultrasound screening for abdominal aortic aneurysms in men aged 65 to 75 who have ever smoked. “Ever smoked” is defined as having smoked 100 or more cigarettes in a lifetime. Men in that age range who have never smoked may still be offered screening selectively, but it’s not routine.
High Blood Pressure and Atherosclerosis
Chronic high blood pressure forces artery walls to absorb more stress with every heartbeat. Over years, this accelerates the wear on elastic fibers and muscle cells, particularly in the aorta, the body’s largest artery. The damage compounds: as the wall weakens, it stretches, and a wider artery experiences even greater force from blood flow, creating a cycle that feeds further expansion.
Atherosclerosis, the buildup of fatty plaques inside arteries, shares nearly all the same risk factors as aneurysms: older age, male sex, smoking, high blood pressure, and elevated cholesterol. The two conditions frequently coexist, and the chronic inflammation triggered by plaque buildup contributes to the enzymatic breakdown of the artery wall. That said, atherosclerosis alone doesn’t fully explain aneurysm formation. Some patients develop aneurysms without significant plaque, pointing to an underlying vulnerability in connective tissue metabolism that atherosclerosis worsens but doesn’t necessarily start.
Brain Aneurysms and Blood Flow Geometry
Intracranial aneurysms, commonly called brain aneurysms, tend to form at specific locations: the branching points where arteries split into smaller vessels. The geometry of these forks determines how blood pressure and shear stress are distributed across the artery wall. When a branch is angled asymmetrically, high-pressure zones shift away from the reinforced apex of the fork and land instead on a thinner, more vulnerable section of the arterial wall. Over years, that sustained pressure damages the elastic layers and an aneurysm begins to form.
Brain aneurysms affect an estimated 2% to 4% of the global population, and most never rupture or cause symptoms. Women are disproportionately affected. In a pooled analysis of nearly 10,000 patients with unruptured brain aneurysms, 66% were women. Women also had a roughly 40% higher rate of rupture compared to men after adjusting for other factors. The reasons likely involve hormonal influences on blood vessel structure, particularly the drop in estrogen after menopause, which coincides with the age range when most brain aneurysms are detected.
Genetic Conditions That Weaken Arteries
Some people are born with a predisposition to aneurysms because of inherited defects in the proteins that build and maintain artery walls. The best-known example is Marfan syndrome, a connective tissue disorder that affects the body’s structural framework, including the aorta. People with Marfan syndrome produce abnormal fibrillin, a protein essential for elastic fiber integrity, which leaves the aortic wall prone to stretching and tearing.
Loeys-Dietz syndrome is another inherited condition that increases aortic aneurysm risk significantly. It affects signaling pathways involved in blood vessel growth and repair, leading to fragile, aneurysm-prone arteries throughout the body. Vascular Ehlers-Danlos syndrome, caused by defective collagen production, carries a particularly high risk of arterial rupture, often at younger ages than typical aneurysms.
Beyond these named syndromes, researchers have identified variants in genes responsible for cross-linking collagen and elastin. One example is the gene for lysyl oxidase, an enzyme that creates the chemical bonds holding these structural proteins together. When this enzyme doesn’t function properly, the aortic wall lacks the tensile strength to withstand normal blood pressure over a lifetime.
Family History Doubles the Risk
Even without a diagnosable genetic syndrome, having a first-degree relative (parent, sibling, or child) with an aortic aneurysm roughly doubles your own risk. Interestingly, the inherited risk is stronger when the affected relative is female. Having a mother or sister with an abdominal aortic aneurysm raises your odds more than fourfold, while having a father or brother with one raises it by about 60%. This suggests that when women develop aneurysms despite being generally lower-risk, a stronger genetic component is at play.
Bicuspid Aortic Valve and Thoracic Aneurysms
A bicuspid aortic valve, where the heart’s aortic valve has two flaps instead of the usual three, is the most common congenital heart defect, present in 1% to 2% of the population. About half of people with this valve abnormality develop a thoracic aortic aneurysm, making it the second most frequent complication after valve dysfunction itself. They also face an eightfold higher risk of aortic dissection, a life-threatening tear in the artery wall.
Two mechanisms drive the connection. First, the abnormal valve creates turbulent, asymmetric blood flow that hits the wall of the ascending aorta with uneven force, accelerating wear on one side. Second, the same developmental process that produced the abnormal valve may have also left the aortic wall with an inherent structural weakness. Research shows that greater aortic stiffness in these patients is independently associated with faster aneurysm growth, suggesting that as the vessel loses its natural elasticity, expansion accelerates.
Polycystic Kidney Disease
Autosomal dominant polycystic kidney disease (ADPKD) is primarily known for causing cysts in the kidneys, but it also affects blood vessel walls. The prevalence of brain aneurysms in people with ADPKD ranges from 9% to 23%, compared to 2% to 4% in the general population. The gene mutations responsible for ADPKD disrupt proteins involved in cell structure and signaling throughout the body, including in the smooth muscle cells that line cerebral arteries. People with ADPKD and a family history of brain aneurysms are typically offered screening with brain imaging.
Infections and Physical Trauma
Infected aneurysms, historically called mycotic aneurysms, develop when bacteria reach the artery wall and trigger localized destruction. This can happen through a bloodstream infection or when infected material from the heart, such as fragments from infected heart valves, lodges in a vessel wall. The infection weakens the artery from the inside, and the resulting aneurysm tends to expand rapidly and carries a high rupture risk. Pre-existing aneurysms can also become secondarily infected, which dramatically worsens the outlook.
Blunt or penetrating trauma to a blood vessel can damage the artery wall directly, creating a weak point that may balloon outward immediately or develop into an aneurysm over weeks to months. Traumatic aneurysms are less common than those caused by chronic risk factors but can occur at any age and in arteries that wouldn’t typically be affected.
Age, Sex, and Overall Risk
Age is one of the strongest non-modifiable risk factors for all types of aneurysms. The structural proteins in artery walls naturally degrade over decades, and the cumulative effects of blood pressure, inflammation, and other stressors compound with time. Most abdominal aortic aneurysms are diagnosed in people over 60, and most brain aneurysms are found in people between their 40s and 60s.
Men are significantly more likely to develop abdominal aortic aneurysms, which is why screening guidelines focus on men. Brain aneurysms, however, are more common in women, who also face a higher rupture rate. In a large meta-analysis, women with unruptured brain aneurysms ruptured at a rate of about 1% per year, compared to 0.74% per year in men. Women in these studies were also older on average (62 versus 60 years) and had slightly larger aneurysms at the time of detection, both of which contribute to rupture risk.