Is there a correlation between high lipoprotein(a) (Lp(a)) levels and the risk of cardiovascular events?

From the Guidelines

Yes, there is a strong correlation between high lipoprotein(a) (Lp(a)) levels and increased risk of cardiovascular events. Elevated Lp(a) levels, typically above 50 mg/dL or 125 nmol/L, are considered an independent risk factor for atherosclerotic cardiovascular disease, including heart attacks, strokes, and peripheral artery disease. This relationship is dose-dependent, meaning higher Lp(a) levels correspond to greater cardiovascular risk. Lp(a) promotes cardiovascular disease through multiple mechanisms: it contributes to atherosclerosis like LDL cholesterol, has pro-inflammatory effects, enhances blood clotting, and impairs the body's ability to dissolve clots. Unlike other lipid parameters, Lp(a) levels are primarily determined by genetics (up to 90%) and remain relatively stable throughout life, with minimal influence from diet or exercise. Currently, there are no FDA-approved medications specifically targeting Lp(a), though PCSK9 inhibitors may modestly reduce levels 1. For patients with elevated Lp(a), aggressive management of other cardiovascular risk factors is recommended, including optimizing LDL cholesterol with statins, maintaining healthy blood pressure, controlling diabetes if present, avoiding smoking, and following a heart-healthy lifestyle.

Some key points to consider:

• Lp(a) levels are highly prevalent, affecting 20-30% of the global population, with possibly higher incidence in patients with established CVD and CAVD 1.
• The European Society of Cardiology guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease and targeting levels below 50 mg/dL 1.
• Several observational studies, including meta-analyses, as well as genomic studies suggest a causal association between Lp(a) levels and CVD events 1.
• Niacin decreases Lp(a) levels, and PCSK9 inhibitors may also lower Lp(a) levels, although more research is needed to fully understand their effects 1.

Overall, managing elevated Lp(a) levels and associated cardiovascular risk factors is crucial to reducing the risk of cardiovascular events and improving patient outcomes. The most recent and highest quality study, published in 2020, highlights the importance of lipid management in patients with rheumatoid arthritis, including the treatment of other lipid abnormalities such as hyperlipoproteinaemia (a) 1. However, the study from 2018 provides the most comprehensive overview of Lp(a) biology, pathophysiology, and current therapies, making it the most relevant to this question 1.

From the Research

Correlation Between Lipoprotein(a) and Cardiovascular Events

There is evidence to suggest a correlation between high lipoprotein(a) (Lp(a)) levels and the risk of cardiovascular events.

• High levels of Lp(a) are considered an independent risk factor for cardiovascular disease, operating separately from other risk factors such as LDL cholesterol levels 2, 3.
• Studies have shown that Lp(a) is associated with an increased risk of ischemic cardiovascular disease, aortic valve stenosis, and heart failure 2, 4.
• The threshold value for Lp(a) has been set at 50 mg/dL, but the risk may increase at levels above 30 mg/dL 2.
• Lp(a) has been linked to a greater risk of coronary heart disease, peripheral arterial disease, and carotid atherosclerosis, although the evidence for the latter two is not as conclusive 2, 4.

Mechanisms and Treatment

• Lp(a) is thought to contribute to atherosclerotic cardiovascular disease through mechanisms associated with increased atherogenesis, inflammation, and thrombosis 3.
• Current treatments for high Lp(a) levels include apheresis, PCSK9 inhibitors, and emerging therapies such as antisense oligonucleotides and small interfering RNAs 2, 5.
• PCSK9 inhibitors have been shown to reduce Lp(a) levels by 25-30% and may provide greater coronary benefit for patients with higher baseline Lp(a) levels 5.

Clinical Implications

• High Lp(a) levels are associated with an increased risk of cardiovascular events, particularly in patients with established cardiovascular disease 5.
• Lp(a) may be a useful marker for identifying individuals at high risk of cardiovascular disease, particularly those with a family history of premature coronary heart disease 6.
• Further research is needed to establish standardized methods for measuring Lp(a) and to develop effective treatments for reducing Lp(a) levels and mitigating cardiovascular risk 3, 6.