From the Guidelines
Lipoprotein(a), or Lp(a), is a type of cholesterol particle in the blood that is primarily determined by genetics and is considered an independent risk factor for cardiovascular disease, including heart attacks and strokes. Lp(a) is composed of an apolipoprotein B (apoB)-containing low-density lipoprotein (LDL)-like particle, covalently linked to the plasminogen-like glycoprotein apolipoprotein(a) (apo(a)) 1. It's levels are largely set by birth and remain relatively stable throughout life, with more than one billion people globally having elevated levels of Lp(a) 1. Some key points about Lp(a) include:
- Lp(a) levels are mainly determined by genetic traits, and it is postulated that Lp(a) particles have pro-atherogenic and pro-thrombotic properties 1
- Lp(a) is considered an independent risk factor for cardiovascular disease, including heart attacks and strokes, even in people with otherwise normal cholesterol levels
- Currently, there are no FDA-approved medications specifically targeting Lp(a), though PCSK9 inhibitors and niacin may modestly reduce levels
- For people with elevated Lp(a), doctors typically focus on aggressively managing other cardiovascular risk factors like LDL cholesterol, blood pressure, and diabetes
- Screening for Lp(a) is increasingly recommended, especially for those with premature cardiovascular disease, family history of early heart disease, or when standard risk assessments don't explain cardiovascular events 1.
From the Research
What is Lipoprotein(a) (LPA)
- Lipoprotein(a) (Lp(a)) is a type of low-density lipoprotein (LDL) cholesterol-like particle that is bound to apolipoprotein(a) 2
- It is an atherogenic lipoprotein with a strong genetic regulation, with up to 90% of its concentrations explained by a single gene, the LPA gene 3
- Lp(a) is composed of two major protein components: apoB100 and apolipoprotein(a) 4
Risk Factors Associated with LPA
- High levels of Lp(a) are an independent and causal risk factor for atherosclerotic cardiovascular diseases, including myocardial infarction, stroke, aortic valve stenosis, heart failure, and peripheral arterial disease 4, 2, 3, 5
- Lp(a) levels above 30 mg/dL and even more above 50 mg/dL are associated with an increased risk for cardiovascular disease 3
- Approximately 20% of the global population have Lp(a) levels of 50 mg/dL or higher, which is noted to confer increased cardiovascular risk 2
Current Understanding and Treatment
- There are currently no approved pharmacologic therapies that specifically target Lp(a) concentrations, but some therapies that target LDL cholesterol also have an influence on Lp(a) concentrations 3
- Emerging nucleic acid-based therapies, such as antisense oligonucleotides and small interfering RNA, are being developed to lower Lp(a) levels and may potentially reduce cardiovascular risk 2, 3
- Lifestyle modification, statins, and ezetimibe are ineffective in lowering Lp(a) levels, while proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis have a modest effect on Lp(a) reduction 2, 3