High Blood Pressure Education Month: Targeting Lp(a)

For High Blood Pressure Education Month, we’re highlighting the work of experts focused on raising awareness and improving screening for elevated Lp(a), a factor that can contribute to hypertension. In 2021, the American Heart Association issued a scientific statement defining lipoprotein(a) (Lp[a]) as an independent, causal risk factor for heart disease. 1 Lp(a) is strongly driven by genetics and has proven links to atherogenesis, inflammation, hypertension, and thrombosis. Even after effectively controlling LDL cholesterol and apoB100, Lp(a) continues to pose a significant threat to the 20% of people in the United States with elevated levels. 2 To address this concern, the American Heart Association partnered with Novartis to launch the Lp(a) Discovery Project. A key aspect of the project is the Lp(a) Data Challenge, which awards valuable contributions to Lp(a) research. “ Even though we don’t have an approved treatment for elevated Lp(a) yet, identifying high-risk patients can allow us to intensify cardiovascular risk management. Arya Aminorroaya, MD, MPH We spoke with Wenjun Fan, MD, PhD, assistant professor of teaching in the Department of Epidemiology and Biostatistics at UC Irvine, and Arya Aminorroaya, MD, MPH, a postdoctoral research fellow at Yale University. Both Dr Fan and Dr Aminorroaya are leading experts in the study of Lp(a). Dr Fan’s team won the AHA’s Lp(a) Data Challenge for assessing the impact of Lp(a) on long-term cardiovascular disease risk. 3 Dr Aminorroaya was recognized as a finalist for his work developing the Algorithmic Risk Inspection for Screening Elevated Lp(a) (ARISE) model to optimize Lp(a) screening. 4 Here’s how they responded to our questions about the current and future role of Lp(a) in cardiovascular care.

Do you think patients receive sufficient Lp(a) screening? If not, why?

Dr Fan: The current rate of Lp(a) screening in clinical practice is insufficient. Despite accumulating evidence establishing Lp(a) as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD), testing remains markedly underutilized. In a recent global cohort analysis encompassing 90 million patients across 87 health care organizations, the Lp(a) testing rate was only 0.1% between 2015 and 2024. Key barriers to broader implementation include limited awareness among health care providers and patients, the historical absence of targeted therapeutic interventions, variability in guideline recommendations, and restricted insurance coverage. A persistent misconception contributing to clinical inertia is the belief that the lack of specific Lp(a)-lowering therapies limits its clinical utility. However, this notion is misleading. Although targeted Lp(a)-lowering therapies are not yet widely available, the identification of elevated Lp(a) levels provides valuable prognostic information. Elevated Lp(a) is associated with increased atherogenic lipoprotein burden and heightened cardiovascular risk, which can only be identified through direct measurement. Patients with elevated Lp(a) may benefit from intensified risk factor management, including aggressive lifestyle modification, long-term cardiovascular monitoring, and consideration of more intensive lipid-lowering strategies such as statins and potentially PCSK9 inhibitors . Dr Aminorroaya: I don’t think patients are getting enough Lp(a) screening right now. In fact, in our study, we showed that only 0.4% of patients in a US health system actually undergo Lp(a) testing. There are a few key reasons for this. First, some clinicians aren’t fully aware of how critical elevated Lp(a) is as a cardiovascular risk factor. The second issue is the lack of clear guidelines on when to test, so the screening often gets overlooked or is only done in very select cases, usually when patients already have cardiovascular disease or other traditional risk factors. Another challenge is that we still don’t have a specific treatment for elevated Lp(a) approved, though there are promising therapies in the pipeline. We’re waiting for the cardiovascular outcome trials of these Lp(a)-lowering therapeutics to really see their impact. However, even without a specific treatment, we can still intensify cardiovascular risk management for patients with high Lp(a). Our machine learning tool, ARISE, helps with this by identifying individuals at high risk of elevated Lp(a) based on their health records. This makes it easier to know who should get tested and ultimately improves how we prioritize screening, helping to overcome some of the barriers that limit its uptake.

What do you feel would be the best practice for Lp(a) screening criteria?

Dr Fan: Given its predominantly genetic determination, Lp(a) should be measured at least once in everyone’s lifetime, as recommended by current expert consensus. Repeat testing is typically unnecessary unless clinical indications evolve or therapeutic monitoring becomes relevant. Screening is especially warranted for individuals with a personal or family history of premature ASCVD, particularly when traditional lipid profiles such as LDL-C are within normal limits. Dr Aminorroaya: I believe the best practice would be to screen for Lp(a) at least once in a lifetime for every adult. That’s what the guidelines are starting to recommend, and it makes sense, given how much Lp(a) can influence cardiovascular risk. Additionally, Lp(a) levels are largely genetically determined and tend to remain stable throughout a person’s life, so a one-time test should be sufficient. What ARISE does really well is help focus on those who are most likely to have elevated Lp(a) based on their health records. It helps us prioritize testing by identifying individuals at higher risk, making screening more efficient. The goal is to ensure that we’re testing the right people without missing those who would benefit most from it. Additionally, ARISE allows us to conduct large-scale, health system-based screenings. In our study, we demonstrated the feasibility of deploying ARISE within electronic health records, which makes it easier to implement this kind of screening across a large population.

What are the most important takeaways of your research for cardiologists?

Dr Fan: Our AHA Data Challenge project demonstrates that incorporating Lp(a) into ASCVD risk prediction models using real-world electronic health record data improves the accuracy of 10-year risk estimation. A 25 mg/dL increment in Lp(a) was associated with a 23% increased risk of incident ASCVD . Although the enhancement in model discrimination (C-statistic) was modest, the inclusion of Lp(a) resulted in significant risk reclassification. Specifically, 21.3% of individuals at borderline or intermediate risk were correctly reclassified into a more appropriate risk category, underscoring the clinical relevance of integrating Lp(a) into risk assessment frameworks for personalized prevention strategies. Dr Aminorroaya: Elevated Lp(a) is a critical, yet often overlooked, cardiovascular risk factor. Despite its strong association with cardiovascular disease, Lp(a) testing is still not widely performed, with fewer than 0.5% of patients getting tested in health systems. This highlights the need for more widespread screening. Our research, particularly with the ARISE model, shows how we can optimize Lp(a) screening using data already available in electronic health records. ARISE helps identify individuals at high risk of having elevated Lp(a), making it easier to prioritize testing and ensuring that we’re focusing on those who would benefit most from early identification. Even though we don’t have an approved treatment for elevated Lp(a) yet, identifying high-risk patients can allow us to intensify cardiovascular risk management. As cardiologists, it’s important to recognize that ARISE enables large-scale, efficient screening , helping us address the significant gap in Lp(a) testing and improve patient care, particularly as new Lp(a)-lowering therapies become available.

What future research would you like to see conducted on Lp(a)?

Dr Fan: Our future research directions include the following areas: Implementation Science : Investigate barriers to Lp(a) testing in real-world practice and develop strategies to improve clinical uptake, ensuring that forthcoming therapies reach high-risk individuals. Population-Based Studies : Characterize Lp(a) distribution and its associated risk across diverse racial and ethnic populations, as current data predominantly reflect European ancestry cohorts. Therapeutic Effectiveness : Once Lp(a)-lowering therapies are available, evaluate their effectiveness in broader, real-world populations beyond clinical trial participants to inform guideline development and optimize patient care. Dr Aminorroaya: Another important area is exploring the integration of ARISE into real-world clinical practice. We’ve shown in our study that ARISE can be deployed effectively in health systems, but we need further research on the operational and economic feasibility of scaling this up across various health systems, especially in resource-constrained environments. Understanding how ARISE can be implemented at scale will be crucial for widespread adoption. With new therapies for lowering Lp(a) in the pipeline, we need to identify and enroll the patients who will benefit the most from these treatments. It would be incredibly useful to adopt ARISE for trial enrollment, helping to target the right patient populations and streamline the process. Additionally, studying the impact of ARISE on clinical outcomes in these trials will allow us to evaluate not only the effectiveness of the Lp(a)-lowering therapies but also the efficiency of using ARISE to accelerate patient recruitment and improve trial timelines. This article originally appeared on The Cardiology Advisor