Aortic stenosis is most commonly caused by a gradual buildup of calcium on the aortic valve, the gate that opens and closes with every heartbeat to let blood flow from the heart into the body. This process stiffens the valve over decades, narrowing the opening and forcing the heart to work harder. The condition affects roughly 2 to 3% of people over age 65 and 7% of those over 80, making it the most common valve disease in older adults. While age-related calcification is the leading cause, several other factors can trigger or accelerate it.
How Calcium Builds Up on the Valve
For years, doctors assumed calcified valves were simply “wearing out” from age. That view has changed. Aortic valve calcification is now understood as an active, inflammatory disease with a biological chain of events that mirrors how bone forms in the skeleton.
It starts with damage to the thin layer of cells lining the valve leaflets. Mechanical stress from billions of heartbeats, high blood pressure, and deposits of LDL cholesterol (the same “bad” cholesterol involved in clogged arteries) all injure this lining. Once damaged, immune cells, including macrophages and T cells, flood the area and release inflammatory signals. These signals push the valve’s own structural cells through a transformation: they shift from their normal repair role into cells that behave like bone-building cells. Those transformed cells then begin laying down calcium and even forming tiny bone-like deposits directly within the valve tissue.
Several molecular pathways drive this transformation. One involves a signaling system called RANK, which normally regulates bone turnover in the skeleton. Another involves a pathway that interacts with LDL receptors on cell surfaces and promotes bone production inside the valve. Shear stress on the valve also activates a growth factor that triggers fibrosis and calcification. Once these processes start, they tend to accelerate: early calcium deposits change how blood flows across the valve, creating more turbulence and more damage, which feeds more calcification.
Being Born With a Bicuspid Valve
A normal aortic valve has three thin flaps (leaflets) that open and close symmetrically. Between 0.5% and 2% of people are born with only two leaflets, a condition called bicuspid aortic valve. It’s the most common congenital heart defect.
Two leaflets don’t open as evenly or handle stress as well as three. The uneven flow creates more turbulence and wears down the valve faster, triggering the same calcification cascade described above but at a younger age. People with a bicuspid valve who develop stenosis typically need treatment a decade or more earlier than those whose valve started with three leaflets. Younger patients with a bicuspid valve are more likely to first develop a leaky valve (regurgitation), while older patients with this anatomy more commonly progress to narrowing.
Rheumatic Fever and Valve Scarring
In parts of the world where strep throat goes untreated, rheumatic fever remains a major cause of aortic stenosis. The immune response to the strep bacteria mistakenly attacks the body’s own tissues, including the heart valves. Repeated bouts of rheumatic fever cause progressive scarring that thickens and stiffens the valve leaflets, eventually fusing them together and narrowing the opening.
Rheumatic heart disease has been largely eliminated in high-income countries through antibiotic treatment of strep infections, but it remains prevalent in sub-Saharan Africa, the Middle East, central and south Asia, and the south Pacific. It also still appears among Indigenous populations and older adults in wealthier nations, and among immigrants from regions where the disease is common.
Cholesterol and Lipoprotein(a)
The early stages of valve calcification share striking similarities with atherosclerosis, the process that clogs arteries. LDL cholesterol deposits on damaged valve tissue help spark the inflammatory cascade that leads to calcification. However, large clinical trials of cholesterol-lowering statins have not successfully slowed stenosis progression once it’s established, suggesting that cholesterol plays a bigger role in initiating the disease than in driving it forward.
A different blood fat called lipoprotein(a), or Lp(a), has emerged as a particularly strong risk factor. Lp(a) levels are largely genetic, meaning they don’t change much with diet or exercise. A study published in the Journal of the American Heart Association found that patients with calcific aortic stenosis who had Lp(a) levels at or above 125 nmol/L were 58% more likely to need valve replacement within five years and 43% more likely to experience valve replacement or cardiac death compared to those with lower levels. Unlike standard cholesterol, Lp(a) isn’t part of routine blood panels, so many people don’t know their level.
Kidney Disease Speeds Things Up
Chronic kidney disease dramatically accelerates valve calcification. Failing kidneys can’t properly regulate minerals in the blood, leading to elevated calcium and phosphate levels. That excess mineral load is a strong predictor of valve calcification in dialysis patients, and even modestly elevated phosphate levels within the “normal” range are associated with increased calcification risk in the general population.
Beyond mineral imbalance, kidney disease creates a perfect storm for valve damage. Uremic toxins (waste products the kidneys can no longer clear) accumulate in the blood, chronic low-grade inflammation persists, and the body loses protective compounds like pyrophosphate and fetuin A that normally prevent calcium from depositing in soft tissues. Elevated parathyroid hormone, common in kidney disease, also promotes the transformation of valve cells into bone-like cells. The vast majority of stenosis cases in kidney disease patients (about 91%) are degenerative rather than congenital, but the disease progresses faster than in people with healthy kidneys.
How the Disease Differs in Men and Women
Aortic stenosis doesn’t develop identically in men and women. Men’s valves tend to accumulate more calcium, while women’s valves develop more fibrosis, a thickening and stiffening of the tissue through excess collagen rather than mineral deposits. This distinction matters because women can reach the same degree of valve obstruction with significantly less visible calcium on imaging. For the same amount of calcification seen on a CT scan, women tend to have more severe functional narrowing than men.
The reasons trace back to cellular differences. Valve cells in women show higher activation of the proteins that drive conversion into collagen-producing cells. The heart’s response also differs: men develop myocardial fibrosis mainly in proportion to how severe the stenosis is and how thickened the heart muscle has become. In women, the pattern of heart muscle remodeling is more variable and driven by multiple factors beyond stenosis severity alone. These differences have practical implications for diagnosis, since calcium scoring alone may underestimate disease severity in women.
Other Contributing Risk Factors
Several conditions overlap with the mechanisms above and raise your overall risk:
- High blood pressure increases the mechanical stress on valve leaflets with every heartbeat, accelerating the damage that starts the calcification process.
- Diabetes promotes chronic inflammation and abnormal calcium metabolism, both of which feed into valve disease.
- Age is the single strongest risk factor. Decades of cumulative wear, combined with the gradual inflammatory changes that come with aging, explain why prevalence more than doubles between ages 65 and 80.
- Genetics play a role beyond Lp(a) levels. Mutations in a gene called NOTCH1 cause both congenital valve abnormalities and severe calcification by removing a natural brake on bone-forming activity within the valve.
- Radiation therapy to the chest, commonly used for lymphoma or breast cancer, can damage valve tissue and accelerate calcification years or even decades after treatment.
Why It Matters Which Cause You Have
The underlying cause shapes how quickly stenosis progresses and when it becomes a problem. Someone born with a bicuspid valve may develop significant narrowing in their 50s or 60s. A person with three normal leaflets and no kidney disease might not reach that point until their 70s or 80s. Someone with advanced kidney disease on dialysis may see rapid progression over just a few years.
The cause also influences what, if anything, can slow things down. Managing blood pressure, treating kidney disease, and controlling phosphate levels may help reduce the rate of calcification in people with those specific risk factors. No medication has been proven to reverse or halt stenosis once moderate or severe narrowing is established. Once the valve area shrinks below about 1 square centimeter (roughly a third of normal), or blood velocity across the valve exceeds 4 meters per second on echocardiography, the stenosis is classified as severe and treatment focuses on replacing the valve rather than modifying risk factors.