What is Lipoprotein(a) (Lp(a))?

From the Guidelines

Lipoprotein(a), or Lp(a), is a specialized type of cholesterol particle in the blood that combines LDL cholesterol with a protein called apolipoprotein(a), and high levels of Lp(a) are primarily determined by genetics, representing an independent risk factor for cardiovascular disease, including heart attacks and strokes, even when other cholesterol levels are normal.

Key Points

• High levels of Lp(a) are associated with an increased risk of cardiovascular disease, including heart attacks and strokes, as suggested by several observational studies, including meta-analyses, as well as genomic studies 1.
• Lp(a) levels remain relatively stable throughout life and aren't significantly affected by diet or exercise, but can be influenced by certain medications and medical conditions, such as niacin, which may modestly reduce levels 1.
• Testing for Lp(a) is not part of routine cholesterol screening but may be recommended for people with premature cardiovascular disease, family history of early heart disease, or those who don't respond well to standard cholesterol treatments, as recommended by the European consensus statement published in 2010 1.
• The primary approach for managing high Lp(a) focuses on aggressively controlling other cardiovascular risk factors through statins, healthy diet, regular exercise, blood pressure management, and avoiding smoking, as recommended by the European Society of Cardiology (ESC) guidelines 1.
• Lp(a) is particularly concerning because it promotes both atherosclerosis (plaque buildup) and blood clotting, creating a "double threat" to cardiovascular health, and its levels should be targeted below 50 mg/dL, as recommended by the ESC guidelines 1.

Management

• Aggressive control of other cardiovascular risk factors is crucial in managing high Lp(a) levels, including the use of statins, healthy diet, regular exercise, blood pressure management, and avoiding smoking 1.
• High-dose niacin (1-3 grams daily) may modestly reduce Lp(a) levels, but its use should be carefully considered due to potential side effects 1.
• Other medications, such as LDL apheresis, may also be used to lower Lp(a) levels in selected patients, but clinical evidence for this approach is still limited 1.

From the Research

Definition and Risk Factors

• Lipoprotein(a) (Lp(a)) is a risk factor for multiple cardiovascular (CV) disease phenotypes, including atherosclerosis and major CV events 2.
• Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization 3.
• Lp(a) is also associated with non-atherosclerotic endpoints such as venous thromboembolism and calcific aortic valve disease 2.

Measurement and Distribution

• 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 2.
• Lp(a) levels remain relatively constant throughout a person's life, and elevated Lp(a) (≥50 mg/dL) is a prevalent condition affecting >20% of the population 2.
• Measurement of Lp(a) is challenging given the structural heterogeneity of apolipoprotein a (apo(a)), for which isoform-insensitive immunoassays should be used 4.

Treatment and Therapies

• Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a), but PCSK9 inhibitors significantly reduce its level by up to 30% 2, 5.
• Specific lowering of Lp(a) with antisense oligonucleotides (ASO) shows good safety and strong efficacy with up to 90% reductions 2, 3.
• Lipoprotein apheresis (LA) efficiently lowers Lp(a) and was recently associated with a reduction of incident CV events 2.
• Aspirin therapy may be beneficial in individuals with elevated Lp(a) without clinical ASCVD, with an approximately 50% reduction in risk for coronary heart disease events and ASCVD mortality 6.

Guidelines and Recommendations

• 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) 2.
• Lp(a) should be measured in every patient at least once to identify patients with very high Lp(a) levels, who could benefit from Lp(a) lowering therapies when approved 3.
• Current guidelines do not recommend treatment to lower Lp(a) but rather focus on intensified preventive measures including low-density lipoprotein cholesterol (LDL-C) lowering in patients with high Lp(a) 4.