Lipoprotein(a), or Lp(a), is a lipid particle that circulates in the blood. Its structure is similar to low-density lipoprotein (LDL), as it contains a cholesterol-rich core and a protein named apolipoprotein B (apoB). What makes Lp(a) distinct is the addition of a second, highly variable protein called apolipoprotein(a), or apo(a), which connects to the apoB protein. The complete Lp(a) particle is assembled in the liver. The size of the apo(a) protein varies among individuals due to genetic factors, which influences the concentration of Lp(a) in the bloodstream. While its exact functions are still being explored, it is thought to have roles in processes like wound healing.
Health Implications of High Lipoprotein(a)
Elevated levels of Lp(a) are an independent risk factor for several cardiovascular diseases. Its presence in high concentrations promotes the development of atherosclerosis, the buildup of plaque in artery walls. This process occurs because Lp(a) particles, like LDL particles, can deposit cholesterol into the arterial wall, contributing to the formation of these plaques. Over time, these deposits can narrow the arteries and restrict blood flow.
High Lp(a) levels are also associated with increased inflammation within blood vessels, which can make plaques unstable and more likely to rupture. Furthermore, the structure of the apo(a) protein is similar to a substance called plasminogen, which is involved in breaking down blood clots. By competing with plasminogen, Lp(a) can interfere with this process and promote a pro-thrombotic, or clot-forming, state.
This combination of plaque formation, inflammation, and increased clotting tendency elevates the risk for serious cardiovascular events, such as heart attacks and strokes. It is also strongly associated with a condition called calcific aortic valve stenosis, where inflammation and calcium buildup cause the heart’s aortic valve to narrow and stiffen.
Understanding Lipoprotein(a) Test Results
A simple blood test can measure the concentration of Lipoprotein(a) in your circulation. The results are reported in one of two units: milligrams per deciliter (mg/dL) or nanomoles per liter (nmol/L). It is important to know which unit is being used, as the numerical values for the same level of risk will differ.
While health organizations have slightly varying guidelines, a general consensus has formed around certain thresholds. Levels below 30 mg/dL (or approximately 75 nmol/L) are considered desirable. Concentrations between 30 and 50 mg/dL may be categorized as borderline or intermediate risk.
Levels that exceed 50 mg/dL (or 125 nmol/L) are widely considered to indicate a high risk for cardiovascular disease. Testing for Lp(a) is not always part of a standard lipid panel. A healthcare provider may recommend it for individuals who have a personal or strong family history of premature heart disease, a history of recurrent cardiovascular events despite management of other risk factors, or a diagnosis of familial hypercholesterolemia.
Genetic Influence on Lipoprotein(a) Levels
An individual’s Lp(a) level is overwhelmingly determined by genetics, with heritability estimates often exceeding 90%. The primary driver is the LPA gene, which provides the instructions for making the apolipoprotein(a) protein. A key feature of the LPA gene is a region containing a variable number of repeating segments known as “kringle IV type 2” (KIV-2) repeats. The number of these KIV-2 repeats varies greatly from person to person and is inversely related to the Lp(a) concentration in the blood; fewer repeats generally result in a smaller apo(a) protein and a higher Lp(a) level.
This is a major reason why Lp(a) levels can differ by more than 1,000-fold between individuals. Because of this strong genetic link, Lp(a) levels remain relatively stable throughout a person’s life. Unlike other lipid markers such as LDL cholesterol, Lp(a) is not significantly influenced by lifestyle factors like diet, exercise, or body weight.
Managing High Lipoprotein(a)
Currently, there are no medications approved by the FDA specifically for lowering high Lp(a) levels. Conventional lipid-lowering drugs like statins, fibrates, and bile acid sequestrants are not effective at reducing Lp(a) concentrations. The main strategy for managing the risk associated with high Lp(a) is to focus on controlling all other modifiable cardiovascular risk factors. This approach includes managing blood pressure and diabetes, stopping smoking, and lowering LDL cholesterol to very low targets, often using therapies like PCSK9 inhibitors.
While PCSK9 inhibitors can lower Lp(a) by about 20-30%, this is considered a modest reduction. For very specific high-risk patients, a procedure called lipoprotein apheresis may be used. Similar to dialysis, apheresis physically removes Lp(a) and LDL cholesterol from the blood, but it is a burdensome process requiring frequent sessions.
The future of Lp(a) management appears more targeted, with therapies in advanced stages of clinical development. These emerging treatments are designed to interfere with the production of the apo(a) protein. Two promising approaches are antisense oligonucleotides (ASOs) and small-interfering RNA (siRNA) therapies. These therapies work by “silencing” the LPA gene, blocking the messenger RNA that carries instructions for making the apo(a) protein, and have been shown in trials to reduce Lp(a) levels by 80% or more.