Lipoprotein (a) and the aortic heart valve

Lipoprotein A is a lipid particle composed of LDL cholesterol, which forms the deposits that make up atherosclerotic plaque, and is associated with a component—a side chain—that promotes thrombosis. It is less well known that elevated levels of this substance also contribute to calcification of the aortic valve; this is the valve that opens to allow the left ventricle to eject blood into the ascending aorta during contraction and closes to prevent backflow (acting as a sort of “check valve”). This three-leaflet valve can be impaired in the form of a narrowing or aortic stenosis under several circumstances: congenital anomaly, infection, aging. It is known that in Familial (genetic) Hypercholesterolemia, there is early damage to this heart valve, with the likelihood of replacement at a very young age.
Elevated Lp(a) levels promote the development of valvular calcifications
Unsurprisingly, there is a relationship between elevated Lp(a) levels and the development of calcified aortic stenosis. The deposition of Lp(a) and its oxidized forms within the aortic valve triggers a pro-inflammatory and pro-calcifying cascade. This inflammatory cascade contributes to the accumulation of fibrous tissue and the progressive deposition of calcium within the valve leaflets. This process is similar to that observed in atherosclerosis, with a progressive deposition of lipid material and calcium, impairing valve function and leading to obstruction of cardiac blood flow—causing the patient to experience shortness of breath on exertion, chest pain, dizziness, or even loss of consciousness.
What about patients who have undergone surgery and have a prosthetic valve?
For these patients, valve degeneration is the primary cause of late failure of bioprosthetic valves. Lp(a) contributes to the calcification of the native aortic valve, but its role in patients with prosthetic valves remains uncertain.
Some authors investigated whether elevated Lp(a) levels are associated with deterioration following aortic valve replacement with a bioprosthesis.
The study included 174 patients who underwent aortic valve replacement with a bioprosthesis and were followed up with echocardiography for an average of 7.3 years (1,372 examinations).
Lp(a) levels were assessed using a binary classification: ≤ or > 125 nmol/L.
During follow-up, 40 patients developed a valvular abnormality: 22 stenoses, 9 regurgitations (backflow), and 9 mixed. The cumulative rate at 15 years was 51%.
When comparing the two groups, a high Lp(a) level was associated with a significantly increased risk of atherosclerotic disease (62% vs. 47%). After adjusting for other parameters, a high Lp(a) level remained an independent predictor of prosthetic dysfunction (stenotic or mixed) with a threefold increased risk.
There is also a linear dose-response relationship, with each 25 nmol/L increase in Lp(a) conferring a 13% increased risk.

In practice and in conclusion:
Elevated Lp(a) levels are independently associated with the long-term risk of valvular disease.
Although this is not included in the European guidelines for Lp(a) management, the following recommendations can be made:
- Perform a cardiac ultrasound to screen for valvular lesions in patients with elevated levels.
- Monitor these same patients more closely following surgery.
The development of new therapies aimed at reducing Lp(a) levels should, in addition to reducing complications related to atherothrombosis, improve the durability of cardiac bioprostheses.
- Routinely measure Lp(a) levels in patients at cardiovascular and/or lipid risk to tailor cardiovascular follow-up

Reference:

Boute M. et al: Lipoprotein(a) and long-term structural valve
degeneration of aortic bioprostheses
European Heart Journal - Cardiovascular Imaging (2026) 27, 264–273.