Elevated Lp(a) Levels Associated with Residual Cardiovascular Risk
Lipoprotein(a), or Lp(a), is a cholesterol-carrying lipoprotein in the blood that is mostly inherited and remains stable throughout life. Elevated levels of Lp(a) are an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, and calcific aortic valve stenosis (CAVS). High Lp(a) levels affect approximately 1 in 5 people worldwide and can increase the risk of heart attack or stroke even when standard treatments have lowered LDL cholesterol.
What Is Lipoprotein(a)?
Lipoprotein(a) is a low-density lipoprotein (LDL) particle to which apolipoprotein(a) [apo(a)] is covalently bound. The presence of apo(a) confers proatherogenic, proinflammatory, and prothrombotic properties. Plasma concentrations of Lp(a) are approximately 70-90% genetically determined and do not change significantly with lifestyle modifications or most lipid-lowering therapies.
How High Lp(a) Increases Cardiovascular Risk
Elevated Lp(a) contributes to cardiovascular disease through several mechanisms:
- Lp(a)-cholesterol can build up in the walls of blood vessels, forming plaques that narrow arteries and reduce blood flow to the heart, brain, and other organs.
- These plaques can become unstable and rupture, leading to blood clots that block vessels and cause heart attacks or strokes.
- Lp(a) promotes increased clotting, which can lead to rapidly formed blockages in blood vessels.
- Lp(a) promotes inflammation, increasing the likelihood that plaques will rupture.
- Because of its role in inflammation, high Lp(a) can lead to narrowing of the aortic valve, known as aortic stenosis, due to calcium buildup on the valve leaflets.
Who Should Be Tested for Lp(a)?
The American Heart Association recommends that every adult be tested for Lp(a) at least once in their lifetime. Testing is especially critical for individuals with:
- A family or personal history of premature heart disease (before age 55 for men and before age 65 for women).
- A known family history of high Lp(a).
- A diagnosis of familial hypercholesterolemia (FH), an inherited condition characterized by very high LDL levels.
The only way to know your Lp(a) level is through a simple blood test ordered by a healthcare professional. High Lp(a) levels usually cause no symptoms, so testing is essential for detection.
Current Treatment Options for High Lp(a)
Current treatments for high Lp(a) are limited. While statins effectively lower LDL cholesterol, they do not significantly reduce Lp(a) levels and may even slightly increase them in some individuals. Other lipid-lowering therapies, such as ezetimibe and PCSK9 inhibitors, have minimal impact on Lp(a). However, PCSK9 inhibitors may lower Lp(a) by approximately 20-30% in some patients. Emerging therapies specifically targeting Lp(a), including antisense oligonucleotides and small interfering RNA (siRNA) approaches, are currently under investigation in clinical trials and show promise for significantly reducing Lp(a) levels.
Key Takeaways
- Lipoprotein(a) is an inherited, cholesterol-carrying particle that significantly increases the risk of heart attack, stroke, and aortic stenosis when elevated.
- High Lp(a) affects about 20% of the global population and often goes undetected because it causes no symptoms.
- Lp(a) levels are mostly genetically determined and remain stable over a person’s lifetime, making a single lifetime test sufficient for most individuals.
- Elevated Lp(a) contributes to cardiovascular risk through plaque buildup, increased clotting, and inflammation, independent of LDL cholesterol levels.
- Current therapies have limited effect on Lp(a), but novel treatments are in development and may offer new options for lowering this risk factor.
- Individuals with a family history of early heart disease or familial hypercholesterolemia should discuss Lp(a) testing with their healthcare provider.
Frequently Asked Questions
What is considered a high Lp(a) level?
According to the American Heart Association, an Lp(a) level of 125 nmol/L or higher (equivalent to approximately 50 mg/dL) is considered high and associated with increased cardiovascular risk.
Can lifestyle changes lower Lp(a) levels?
No. Lp(a) levels are primarily determined by genetics and are not significantly affected by diet, exercise, or other lifestyle modifications.
Is Lp(a) testing covered by insurance?
Coverage for Lp(a) testing varies by insurance provider and plan. Many insurers cover the test when ordered for individuals with a personal or family history of premature cardiovascular disease or familial hypercholesterolemia. Patients should check with their insurance company and healthcare provider regarding coverage and potential out-of-pocket costs.
Should children be tested for Lp(a)?
Lp(a) levels are largely established by age 5 and remain stable throughout life. Testing may be considered for children with a strong family history of premature cardiovascular disease or familial hypercholesterolemia, but decisions should be made in consultation with a pediatrician or lipid specialist.