From the Guidelines
LPA stands for lipoprotein(a), a type of cholesterol-carrying particle in the blood that's genetically determined and considered an independent risk factor for cardiovascular disease. Unlike other lipoproteins, LPA levels are primarily determined by genetics rather than lifestyle factors. High levels of LPA (typically above 50 mg/dL or 125 nmol/L) can increase the risk of heart attacks, strokes, and aortic valve stenosis, even in people with otherwise normal cholesterol levels. LPA is particularly concerning because it promotes both atherosclerosis (plaque buildup in arteries) and blood clotting. Traditional cholesterol-lowering medications like statins have minimal effect on LPA levels, as noted in studies such as 1. For those with elevated LPA, risk reduction focuses on aggressively controlling other cardiovascular risk factors like LDL cholesterol, blood pressure, and diabetes. Newer treatments specifically targeting LPA are in development, including PCSK9 inhibitors and antisense oligonucleotides, which may provide more direct treatment options in the future, as discussed in 1 and 1. Key points to consider about LPA include:
- LPA levels are mainly determined by genetic traits, with some influence from the APOE locus and PCSK9 R46L loss of function mutations, as explained in 1.
- 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 1.
- 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, as mentioned in 1 and 1. Given the most recent and highest quality evidence, the management of LPA should prioritize aggressive control of other cardiovascular risk factors and consideration of newer, targeted therapies, as supported by 1.
From the Research
Definition of Lp(a)
- Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle 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.
Significance of Lp(a) in Cardiovascular Disease
- Lp(a) is an established risk factor for multiple cardiovascular diseases, including atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis/calcific aortic valve disease (AS/CAVD) 4.
- Elevated Lp(a) levels are associated with an increased risk of cardiovascular disease, including myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and all-cause mortality 3.
- Lp(a) contributes to residual cardiovascular risk in patients receiving standard-of-care LDL-lowering therapy 5.
Measurement and Treatment of Lp(a)
- Plasma Lp(a) levels present a skewed distribution towards higher values and vary widely between individuals and according to ethnic background due to genetic variants in the LPA gene 3.
- Treatment guidelines have begun to advocate measurement of Lp(a) to identify patients with very high levels that have a family history of premature CVD or elevated Lp(a) 5.
- Currently, there are no approved pharmacologic therapies that specifically target Lp(a) concentrations, but some therapies that target primarily LDL cholesterol have also an influence on Lp(a) concentrations, such as PCSK9 inhibitors 3.
- Emerging nucleic acid-based therapies, such as antisense oligonucleotides (ASO) and small interfering RNA (siRNA), are generating interest due to their potent Lp(a)-lowering effects 2, 5.