Long-Term Cardiovascular Risks Linked to Lp(a) Levels

Introduction to Lp(a) and Cardiovascular Disease Risks

Lipoprotein(a), commonly referred to as Lp(a), is a lipoprotein subclass that has garnered significant attention as a potential independent risk factor for cardiovascular diseases (CVD). Elevated Lp(a) levels are associated with an increased risk of various cardiovascular conditions, including coronary artery disease (CAD), calcific aortic valve stenosis (CAVS), and ischemic stroke (IS). The structure of Lp(a) is unique, comprising a low-density lipoprotein (LDL) component linked to apolipoprotein(a), which exhibits structural similarities to plasminogen, implicating it in both atherogenesis and thrombosis processes. Elevated levels of Lp(a) are genetically determined and remain relatively stable throughout an individual’s life, which has led researchers to investigate its role in long-term CVD risks, particularly in populations with pre-existing conditions.

Relationship Between Lp(a) Levels and Ischemic Heart Disease

Research has established a strong correlation between elevated Lp(a) levels and the incidence of ischemic heart disease (IHD). A large-scale genetic study indicated that each 10 mg/dL increase in genetically-predicted Lp(a) correlates with a 6% heightened risk of CAD, further supporting Lp(a) as a causal risk factor (Zhang et al., 2025). Moreover, individuals with both elevated Lp(a) and high LDL cholesterol (LDL-C) levels experience even greater risks for cardiovascular events, underscoring the need for comprehensive lipid management strategies in patients with high Lp(a) concentrations (Hadidchi et al., 2025).

Table 1: Summary of Studies on Lp(a) and Ischemic Heart Disease

Impact of Lp(a) on Coronary Artery Disease and Calcific Aortic Valve Stenosis

In addition to its role in IHD, elevated Lp(a) levels are implicated in the development of CAVS. Studies suggest that Lp(a) may contribute to the calcification of aortic valve leaflets through its oxidized phospholipid content, promoting local inflammation and endothelial dysfunction. Notably, men exhibit a stronger Lp(a)-associated risk of CAVS compared to women, indicating a potential sex-based difference in the pathophysiological mechanisms at play (Zhang et al., 2025). This information is crucial, as it may inform targeted screening and therapeutic strategies for individuals at risk.

Table 2: Lp(a) and CAVS Risk Factors

Interactions of Lp(a) with Other Cardiovascular Risk Factors

The interaction of Lp(a) with traditional cardiovascular risk factors, such as LDL-C, triglycerides (TG), and body mass index (BMI), is complex. Evidence shows that individuals with higher levels of Total-C, LDL-C, and TG experience amplified risks associated with elevated Lp(a) levels for CAD. However, no significant interactions were noted with BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP) (Zhang et al., 2025). Understanding these interactions is vital for optimizing treatment approaches for patients with elevated Lp(a).

Clinical Implications and Future Research Directions on Lp(a)

The clinical implications of elevated Lp(a) levels are profound. Current guidelines suggest that individuals with high Lp(a) levels should undergo regular cardiovascular risk assessments. However, the clinical benefits of lowering Lp(a) levels remain to be fully established. Ongoing clinical trials, such as the HORIZON trial exploring the effects of pelacarsen on cardiovascular outcomes, aim to clarify the role of Lp(a) reduction in preventing major adverse cardiovascular events (MACE) (Hadidchi et al., 2025). Such research is critical for developing effective treatment protocols that address the unique risk profiles of patients with high Lp(a).

Table 3: Ongoing Clinical Trials Targeting Lp(a)

FAQs

What is Lp(a)?

Lp(a) or lipoprotein(a) is a subclass of lipoprotein that carries cholesterol and is associated with increased risks of cardiovascular diseases.

How does Lp(a) contribute to cardiovascular disease?

Elevated Lp(a) levels are linked to increased risks of coronary artery disease, calcific aortic valve stenosis, and ischemic stroke, primarily through mechanisms involving inflammation and thrombosis.

Are there treatments available to lower Lp(a)?

Currently, treatments specifically targeting Lp(a) levels are in clinical trials, including therapies such as pelacarsen, olpasiran, and lepodisiran, aimed at assessing their effectiveness in reducing cardiovascular events.

How can I check my Lp(a) levels?

Lp(a) levels can be assessed through a blood test. It is advisable to discuss with a healthcare provider whether testing is appropriate based on individual risk factors.

What should I do if I have elevated Lp(a)?

If you have elevated Lp(a) levels, it is essential to work with your healthcare provider to assess your overall cardiovascular risk and develop a comprehensive management plan, which may include lifestyle modifications and monitoring.

References

1. Zhang, T., et al. (2025). The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank. Am Heart J Plus: Cardiology Research and Practice. https://doi.org/10.1016/j.ajpc.2025.101008

2. Hadidchi, R., et al. (2025). Long-term outcomes of patients with pre-existing coronary artery disease after SARS-CoV-2 infection. eBioMedicine. https://doi.org/10.1016/j.ebiom.2025.105778

3. Xie, J., et al. (2024). Current trends in stroke events, mortality, and case fatality in Switzerland: an epidemiologic update. Int J Epidemiol