An Underrecognized Risk Factor for Heart Disease

Most people know what cholesterol is, and that low-density lipoproteins, or LDLs, carry cholesterol through the blood. Cholesterol carried by LDL is commonly called LDL cholesterol or "LDL–C," and it's a major risk factor for heart disease. However, about 20 percent of the global population lives with high levels of another type of lipoprotein called Lp(a), and its association with cardiovascular disease is widely underrecognized.¹

Lp(a) – pronounced "L-P-little a" and alternately known as lipoprotein(a) –  has a structure similar to LDL and also carries cholesterol like LDL. However, it has an additional protein coil called apo(a), which causes it to be "extra sticky" and contributes to the formation of plaque buildups and blood clots in the arteries.^2,3 With high levels of Lp(a), these blockages could be more frequent, potentially increasing the risk for cardiovascular events such as a heart attack or stroke.²

Having elevated Lp(a) is almost entirely genetic, and lifestyle changes such as diet and exercise cannot reduce Lp(a).⁴ Similar to LDL cholesterol, people living with high Lp(a) often don't have any symptoms and are unaware they are living with a heart disease risk factor.² A person's Lp(a) level is seldom considered until a cardiovascular event occurs, which is why proactive testing for high Lp(a) is vital, especially for those who have a known family history of elevated levels or cardiovascular events. 

The Importance of Accurate Lp(a) Testing

The Lp(a) field is rapidly evolving, and the cardiovascular ecosystem is adding emphasis to its importance, especially for testing, which is a critical piece to understanding Lp(a) prevalence and impact. The National Lipid Association recently recommended that every adult have their Lp(a) tested at least once in their lifetime, yet today testing rates are markedly low, and lab tests used do not consistently and accurately measure Lp(a) levels.^5,6

When it comes to Lp(a) tests, there are two common types: mass- and molarity-based. Mass-based testing measures the total mass of Lp(a) in the blood in milligrams per deciliter (mg/dL), while molarity-based testing measures in nanomoles per liter (nmol/L). Mass-based testing can be inaccurate, as Lp(a) particles may differ in mass depending on a person's genetics.⁷ Molarity-based testing is deemed more precise and desirable as it indicates the number of particles in the blood, regardless of their mass.^7,8 Lp(a) levels are considered high if greater than or equal to 50 mg/dL or 125 nmol/L.²  

Physicians and researchers have emphasized the need for more accurate, standardized tests that are molarity-based to not only better identify high-risk patients, but also support research into the connection between Lp(a) and cardiovascular disease.

An Important Next Step

Amgen has partnered with Roche Diagnostics to develop a molarity-based diagnostic test intended to measure Lp(a). Amgen is also committed to exploring the potential of Lp(a) inhibition and recently completed enrollment of a phase 3 clinical trial evaluating an investigational therapy targeting Lp(a) in patients with ASCVD and elevated Lp(a). On April 16, Roche Diagnostics and Amgen's new diagnostic test, or assay, received Breakthrough Device Designation from the U.S. Food and Drug Administration (FDA) for use in patient selection for this ongoing trial.

Amgen is proud to collaborate with Roche to accelerate access to more standardized testing. The FDA designation of the investigational assay reinforces the urgency and importance of improving Lp(a) testing methods in the U.S. The FDA's Breakthrough Devices Program is intended to provide patients and health care providers with timely access to medical devices by speeding up development, assessment, and review for approval.⁹

Working with Roche on the assay demonstrates Amgen's dedication to cardiometabolic care and provides hope for a future of greater awareness and understanding of underlying risk factors that may contribute to cardiovascular disease.

References

1. Wilson, D. P., et al. (2022). Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association. Journal of clinical lipidology, S1933-2874(22)00244-6. Advance online publication. https://doi.org/10.1016/j.jacl.2022.08.007.
2. American Heart Association. Lipoprotein (a). https://www.heart.org/en/health-topics/cholesterol/genetic-conditions/lipoprotein-a. Accessed May 2024.
3. U.S. National Library of Medicine. (n.d.). Lipoprotein (a) blood test: Medlineplus medical test. MedlinePlus. https://medlineplus.gov/lab-tests/lipoprotein-a-blood-test/. Accessed May 2024.
4. American Heart Association. AHA names top heart disease and stroke research advances of 2020. (2021, December 16). https://www.heart.org/en/around-the-aha/aha-names-top-heart-disease-and-stroke-research-advances-of-2020. Accessed May 2024.
5. National Lipid Association. National Lipid Association Releases Official Scientific Statement on a Focused Update to the 2019 Scientific Statement on Use of Lipoprotein(a) in Clinical Practice. Press Release. https://www.lipid.org/nla/focused-update-2019-nla-scientific-statement-use-lipoproteina-clinical-practice. Accessed May 2024.
6. Family Heart Foundation. Lipoprotein(a). https://familyheart.org/high-lipoprotein-a. Accessed May 2024.  
7. Cegla, J., et al. (2021). Lp(a): When and how to measure it. Annals of clinical biochemistry, 58(1), 16–21. https://doi.org/10.1177/0004563220968473.
8. Kronenberg F., et al. Lipoprotein(a) measurement issues: Are we making a mountain out of a molehill?, Atherosclerosis, Volume 349, 2022, https://doi.org/10.1016/j.atherosclerosis.2022.04.008.
9. U.S. Food & Drug Administration. Breakthrough Devices Program. Accessed May 2024. https://www.fda.gov/medical-devices/how-study-and-market-your-device/breakthrough-devices-program