From the Guidelines
Lipoprotein(a) is a highly prevalent, genetic risk factor for cardiovascular disease and calcific aortic valve disease, composed of an apolipoprotein B-containing low-density lipoprotein-like particle covalently linked to the plasminogen-like glycoprotein apolipoprotein(a). Lipoprotein(a), often abbreviated as Lp(a), is primarily produced in the liver and circulates in the bloodstream, with levels largely determined by genetics, as stated in the study by 1. High levels of Lp(a) are considered an independent risk factor for cardiovascular disease, including heart attacks and strokes, separate from other lipid abnormalities like high LDL cholesterol.
Key Characteristics of Lipoprotein(a)
- Lp(a) levels are mainly determined by genetic traits, with approximately 70-90% of a person's Lp(a) concentration being inherited, as mentioned in the study by 1.
- 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.
- Unlike other lipoproteins, Lp(a) levels aren't significantly affected by diet, exercise, or standard cholesterol-lowering medications like statins.
- 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, as stated in the study by 1.
Clinical Implications
- Screening for Lp(a) may be recommended for individuals with premature cardiovascular disease, family history of early heart disease, or those not responding well to standard lipid-lowering therapy.
- Currently, specialized treatments targeting Lp(a) specifically are being developed, including PCSK9 inhibitors and antisense oligonucleotides, though these aren't yet widely available, as mentioned in the study by 1.
- The management of Lp(a) levels is crucial in reducing the risk of cardiovascular disease and calcific aortic valve disease, and further research is needed to fully understand the role of Lp(a) in these conditions, as stated in the study by 1.
From the Research
Definition and Composition of Lipoprotein(a)
- Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a) 2, 3, 4, 5, 6
- 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 4
Association with Cardiovascular Disease
- 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 2, 3, 4, 5, 6
- Lp(a) levels above 30 mg/dL and even more above 50 mg/dL are associated with an increased risk for cardiovascular disease 4
- Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics 2, 5
Current Therapies and Emerging Treatments
- Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels 5
- Some therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis, have a modest effect on Lp(a) reduction 2, 4
- Emerging RNA-based therapeutics, such as antisense oligonucleotides and small interfering RNA, have shown promising results in reducing Lp(a) levels 2, 4, 5