Aortic stenosis (AS) is a progressive heart disease defined by the narrowing of the aortic valve opening. This narrowing limits the flow of oxygenated blood from the heart’s main pumping chamber to the rest of the body, forcing the heart to work harder and potentially leading to serious complications. The causes of AS are complex, involving an interplay of inherited conditions affecting the valve’s structure and acquired factors that cause wear and tear over decades. Understanding the role of genetics versus lifestyle factors is important for assessing personal risk.
The Direct Answer: Genetic and Inherited Causes
The hereditary nature of Aortic Stenosis is strongly tied to Bicuspid Aortic Valve (BAV), the most common congenital heart defect. A normal aortic valve has three leaflets, but a BAV forms with only two. This structural abnormality changes blood flow dynamics, causing the valve to fail prematurely and is the most frequent genetic precursor to AS, often leading to significant narrowing in patients under 70 years old.
BAV is primarily inherited in an autosomal dominant pattern, meaning only one copy of the altered gene is needed from one parent. However, the inheritance has incomplete penetrance, meaning not everyone who inherits the genetic change will develop the condition. Heritability for BAV is very high, estimated at nearly 89%, and approximately one in ten first-degree relatives of an affected person also has the condition.
Genetic studies have identified several genes implicated in BAV, including NOTCH1 and GATA5, though these account for only a small percentage of cases. The genetic architecture is complex, suggesting many interacting genes contribute to the valve malformation. In rare instances, AS is part of a broader genetic syndrome, such as Turner Syndrome or familial hypercholesterolemia, but these syndromic causes are less common than isolated BAV.
Acquired Causes of Aortic Stenosis
While a genetic predisposition exists, the most common cause of AS, particularly in older adults, is Calcific Aortic Stenosis (CAS). This acquired form results from a slow process of calcification and thickening of a structurally normal, three-leaflet valve over a lifetime. CAS is often referred to as degenerative AS, and its development shares many risk factors with atherosclerosis (hardening of the arteries).
Traditional cardiovascular risk factors accelerate this acquired process, including high blood pressure, elevated cholesterol levels, diabetes, and chronic kidney disease. The deposition of calcium on the valve leaflets involves active cellular changes similar to bone formation. Advanced age and male sex are consistently associated with an increased risk of developing CAS.
Rheumatic heart disease, typically resulting from untreated strep throat, is another acquired cause of AS, though it is rare in developed countries. The inflammation damages the heart valves, causing the leaflets to fuse and scar. These acquired forms of AS are not passed directly from parent to child, although the underlying risk factors, like hypertension or high cholesterol, can have a familial component.
Understanding Risk for Family Members
The hereditary link, particularly with BAV, underscores the importance of screening first-degree relatives (parents, siblings, and children of an affected individual). This screening is typically performed using a non-invasive test called a transthoracic echocardiogram (TTE). The goal of this imaging is to detect BAV or any early signs of aortic widening before complications arise.
Experts recommend that first-degree relatives undergo a baseline echocardiogram to check for the structural abnormality. If BAV is detected, regular monitoring can be established to track the valve’s function and the size of the aorta. Early detection allows for timely intervention, which can prevent life-threatening events like aortic dissection.
If a family has a history of BAV or early-onset AS, genetic counseling can be beneficial for interpreting complex inheritance patterns. Counselors can help estimate individual risk and explain the implications of testing for known gene mutations, although a causative gene is identified in only a minority of families. Managing acquired risk factors is a preventive strategy, particularly for those with a genetic predisposition. Controlling blood pressure, lowering cholesterol, and maintaining a heart-healthy lifestyle can slow the progression of valve disease and delay the need for intervention.