From the Guidelines
Lipoprotein(a) (Lp(a)) is a specialized type of lipoprotein particle in the blood that combines a low-density lipoprotein (LDL) particle with a protein called apolipoprotein(a), and it is considered an independent risk factor for cardiovascular disease, including heart attacks and strokes, regardless of other cholesterol levels. Lp(a) levels are largely determined by genetics, with approximately 80-90% of a person's Lp(a) concentration being inherited 1. High levels of Lp(a) are associated with an increased risk of cardiovascular disease, and it is estimated that 20-30% of the global population has elevated levels of Lp(a) 1.
Some key points about Lp(a) include:
- Lp(a) promotes atherosclerosis (plaque buildup in arteries) through multiple mechanisms: it can deposit cholesterol in artery walls, promote inflammation, interfere with blood clot breakdown, and enhance blood clotting 1.
- Unlike other lipoproteins, Lp(a) levels aren't significantly affected by diet, exercise, or standard cholesterol-lowering medications like statins 1.
- Currently, there are limited treatment options specifically targeting Lp(a), though PCSK9 inhibitors and specialized therapies like antisense oligonucleotides are being developed 1.
- Measuring Lp(a) levels can be valuable for assessing cardiovascular risk, especially in people with a family history of early heart disease or those who develop cardiovascular disease despite having otherwise normal cholesterol levels 1.
It's worth noting that the European Society of Cardiology (ESC) guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) and to target levels below 50 mg/dL 1. Additionally, several observational studies, including meta-analyses, as well as genomic studies suggest a causal association between Lp(a) levels and CVD events, also including emergent outcomes in the elderly, such as heart failure and calcific aortic valve stenosis 1.
From the Research
Definition and Structure of Lipoprotein(a) (Lp(a))
- Lipoprotein(a) (Lp(a)) is a molecule that induces inflammation of the blood vessels, atherogenesis, valvular calcification, and thrombosis 2.
- Lp(a) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a) 3.
- It is a complex polymorphic lipoprotein with a glycoprotein, apolipoprotein(a) (apo(a)), attached to the apolipoprotein B-100 component 4.
- Lp(a) has many functions, which include proatherosclerotic, prothrombotic, and pro-inflammatory roles 5.
Association with Cardiovascular Disease
- High Lp(a) levels are associated with a persisting risk for atherosclerotic cardiovascular diseases despite optimization of established risk factors, including low-density lipoprotein cholesterol (LDL-C) levels 2.
- Approximately 20-25% of the global population have Lp(a) levels of 50 mg/dL or higher, a level noted to confer increased cardiovascular risk 3, 2.
- Elevated Lp(a) levels are associated with increased risk of heart disease, including atherosclerotic cardiovascular disease and calcific aortic stenosis 6.
- The risk associated with elevations in Lp(a) appears to be independent of other lipid markers 6.
Treatment Options
- Lifestyle modification, statins, and ezetimibe do not effectively lower Lp(a) levels 2, 3.
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and niacin only lower Lp(a) levels modestly 2, 3.
- Emerging nucleic acid-based therapies, such as antisense oligonucleotides and small interfering RNA (siRNA), offer a targeted approach with the potential for safe and robust Lp(a)-lowering 2, 3.
- Gene-based therapies that affect transcription and translation of apolipoprotein(a) mRNA are also being developed 5.