Lipoprotein (a), or Lp(a), is a distinct particle in the bloodstream that transports cholesterol. Its structure consists of a particle similar to low-density lipoprotein (LDL), or “bad” cholesterol, with an additional protein known as apolipoprotein(a), or apo(a), attached by a disulfide bond. This composition makes it different from other frequently measured cholesterol components.
Lp(a) has been identified as an independent factor contributing to cardiovascular disease risk, separate from traditional factors like high blood pressure or smoking. The concentration of Lp(a) is not significantly influenced by lifestyle, a key difference from other cholesterol types. This makes it an important part of assessing a person’s overall cardiovascular health profile.
The Role of Lipoprotein a in Cardiovascular Disease
Elevated levels of Lipoprotein (a) contribute to the progression of atherosclerosis, the process where plaque accumulates inside arteries. The LDL-like component of the Lp(a) particle facilitates the deposition of cholesterol into the artery wall. Lp(a) particles are also more prone to oxidation than standard LDL particles, accelerating their uptake by immune cells and leading to the formation of foam cells, a component of atherosclerotic plaques.
The structure of the apo(a) protein gives Lp(a) prothrombotic, or clot-promoting, properties. Apo(a) is remarkably similar in structure to plasminogen, a substance the body uses to break down blood clots. Because of this similarity, Lp(a) can interfere with the normal clot-dissolving process by competing with plasminogen for binding sites on fibrin. This interference increases the risk of a heart attack or stroke.
Lp(a) also fosters inflammation within the blood vessel walls. It can stimulate the expression of adhesion molecules on the surface of endothelial cells, which line the arteries. This action encourages inflammatory cells to stick to and penetrate the artery wall, further driving the atherosclerotic process.
These mechanisms link high Lp(a) to several specific cardiovascular conditions. It is a causal risk factor for coronary artery disease, myocardial infarction (heart attack), and stroke. A strong association has also been established between elevated Lp(a) and calcific aortic valve disease, a condition where the heart’s aortic valve stiffens and narrows.
Measuring and Interpreting Lipoprotein a Levels
Lipoprotein (a) concentration is determined through a blood test that is not part of a standard lipid panel and often needs to be specifically requested. Testing may be recommended for individuals with a personal or significant family history of early-onset cardiovascular disease. It is also considered for patients who experience recurrent cardiovascular events despite their other risk factors being well-managed.
The results of an Lp(a) test are reported in one of two units: milligrams per deciliter (mg/dL) or nanomoles per liter (nmol/L). It is important to note which unit is being used, as the numerical values are not interchangeable. The conversion between these units is complex because the size of the apo(a) protein varies among individuals, affecting the mass-to-mole ratio.
While there is an ongoing discussion regarding the exact thresholds for risk, general guidelines exist. Many experts consider an Lp(a) level above 30 mg/dL or 75 nmol/L to be elevated. Some guidelines, including those from the European Atherosclerosis Society, use a higher cutoff of >50 mg/dL to define high risk.
Genetic Factors Determining Lipoprotein a
An individual’s Lipoprotein (a) level is overwhelmingly determined by genetics. It is estimated that between 70% and 90% of the variation in Lp(a) levels among people is attributable to inherited factors. The primary genetic determinant is the LPA gene on chromosome 6, which contains the instructions for making the apolipoprotein(a) protein.
The LPA gene contains a specific sequence called a “kringle IV type 2” repeat, and the number of these repeats can vary significantly. An inverse relationship exists between the number of these repeats and the resulting Lp(a) concentration. Individuals with a lower number of repeats produce smaller apo(a) proteins, which are more efficiently secreted from liver cells, leading to higher Lp(a) levels.
A significant consequence of this strong genetic control is that lifestyle choices have very little impact on Lp(a) levels. Modifications to diet, exercise, or body weight do not meaningfully change Lp(a) concentration. This is a distinction from other lipoproteins like LDL cholesterol, which can be managed through lifestyle adjustments. Genetic ancestry also plays a role, with average Lp(a) levels varying among different ethnic populations.
Approaches to Managing Elevated Lipoprotein a
Currently, there are limited options for directly lowering high Lipoprotein (a) levels with standard medications. Statins are highly effective for reducing LDL cholesterol but do not lower Lp(a); in some cases, they may cause a slight increase. This means the risk from high Lp(a) can remain even with well-controlled LDL cholesterol.
Other existing medications have shown only modest or inconsistent effects. Niacin, a B vitamin, can reduce Lp(a) by approximately 20-30%, but its use is often limited by side effects. A class of injectable drugs called PCSK9 inhibitors can lower Lp(a), but this is not their main purpose, and the reduction is variable. Low-dose aspirin may be considered to counteract the prothrombotic tendency of Lp(a), though it does not lower the level itself.
For patients with very high Lp(a) levels and progressive cardiovascular disease, lipoprotein apheresis is an option. This process is similar to dialysis and involves physically filtering Lp(a) particles from the blood. It is an invasive, time-consuming, and expensive treatment reserved for the most severe cases. The primary focus for most individuals with high Lp(a) is aggressive management of all other modifiable cardiovascular risk factors.
The future of Lp(a) management appears more targeted, with several new therapies in advanced stages of clinical development. These emerging treatments, such as antisense oligonucleotides and small interfering RNA (siRNA) therapies, are designed to inhibit the production of the apo(a) protein. Clinical trials have shown these approaches can lower Lp(a) levels significantly, and research is aimed at confirming if this reduction will lead to a decrease in heart attacks and strokes.