Unlocking New Insights into Cardiovascular Risk with Accurate Lp(a) Measurement

Despite decades of progress in identifying cardiovascular risk factors and prevention efforts, cardiovascular disease (CVD) remains the leading cause of death worldwide.1 A growing body of evidence has underscored the role of Lipoprotein(a) [Lp(a)] in CVD risk. In addition to its independent contribution to atherosclerosis, thrombosis, and aortic valve calcification, high Lp(a) levels can also exacerbate the impact of more well-known CVD risk factors, such as smoking, diabetes, and obesity.2

A neglected risk factor

While an estimated 1 in 5 people worldwide live with high Lp(a), it is generally under-recognized as a CVD risk factor.3 Unlike modifiable lifestyle factors contributing to CVD risk, genetics determine up to 90% of individual variation in plasma Lp(a) levels, and they cannot be reduced through diet, exercise, statin therapies, or other means.4

Lp(a) levels largely remain constant throughout a person’s lifetime, so screening guidelines from the National Lipid Association (NLA) recommend that all adults undergo Lp(a) testing at least once.5 There is much work to be done in meeting this recommendation: A recent study of US adults found that ≤ 0.3% of patients underwent Lp(a) testing between 2012 and 2021.6

Why are we falling short? Although Lp(a) levels can be detected through a simple blood test, traditional measurement approaches have critical limitations.

The Lp(a) molecule is comprised of 2 components: apolipoprotein B100 (apo-B100) and apolipoprotein a [apo(a)]. Due to a coding copy number variation in the LPA gene that determines the size of the apo(a) molecule, > 40 different isoforms of Lp(a) exist.7

Tests of plasma Lp(a) have traditionally yielded measurements in milligrams per deciliter of total Lp(a) mass, which assumes Lp(a) concentration based on constant particle size. Because of the wide size variation across different Lp(a) isoforms, mass measurement cannot reflect Lp(a) levels in an accurate, standardized way.

Overcoming persistent challenges in Lp(a) assessment

More recent approaches measuring Lp(a) in nanomoles per liter have enabled determination of the total number of Lp(a) particles, irrespective of size variability. In 2024, the NLA updated its guidelines on the use of Lp(a) assessment in clinical practice to endorse molar over mass-based measurement.

Some labs running mass-based Lp(a) testing elect to convert mass measurements to molar units, though the NLA cautions against this approach due to the diversity of Lp(a) isoforms.5 However, without an available in vitro diagnostic (IVD) test, US clinicians could not incorporate updated Lp(a) assessment guidance into clinical practice and decision-making.

In January 2025, the Roche Diagnostics Tina-quant Lipoprotein (a) Gen.2 Molarity assay received FDA 510(k) clearance, making it the first IVD test available for reporting Lp(a) levels in molar units.8 This new version of the biomarker test, standardized according to International Federation of Clinical Chemistry (IFCC) guidelines, will help mitigate any concerns about the impact of particle size on the accuracy of Lp(a) measurement.

The future of Lp(a) in clinical practice

The growing availability of molar Lp(a) biomarker tests is only part of its evolving future in care. While there are currently no available Lp(a)-lowering pharmacological agents, several therapeutics in development show early promise for reducing Lp(a).9

For now, Lp(a) screening results can guide both the clinician and the patient to prioritize the mitigation of other CVD risk factors and adopt lifestyle modifications earlier to improve CV outcomes. Understanding that an elevated Lp(a) level is both an independent and causal CVD risk factor means that steps can and should be taken now to address risk through optimal management of hypertension, diabetes, obesity, and smoking cessation. Through actionable diagnostic insights, and potentially pharmacological intervention, the field is moving closer to reducing the deleterious impact of this genetic risk factor.

References

1. World Health Organization. The Top 10 Causes of Death. Published 7 August 2024. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed 13 May 2025.

2. Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement from the American Heart Association. Arterioscl Throm Vas. 2021;42:1. https://doi.org/10.1161/ATV.0000000000000147.

3. Rendler J, Murphy M, Yeang C. Lipoprotein(a) is a Prevalent yet Vastly Underrecognized Risk Factor for Cardiovascular Disease. Health Care Curr Rev. 2024;12(2):397. http://dx.doi.org/10.54615/2231-7805.397

4. Schmidt K, Noureen A, Kronenberg F, Utermann G. Structure, function, and genetics of lipoprotein (a). J Lipid Res. 2016;57(8):1339-1359. doi:10.1194/jlr.R067314

5. Koschinsky ML, Bajaj A, Boffa MB, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice. J Clin Lipidol. 2024;18(3):e308-e319. doi:10.1016/j.jacl.2024.03.001

6. Bhatia HS, Hurst S, Desai P, et al.. Lipoprotein(a) Testing Trends in a Large Academic Health System in the United States. J Am Heart Assoc. 2023;12(18):e031255. doi:10.1161/JAHA.123.031255

7. Matveyenko A, Matienzo N, Ginsberg H, et al. Relationship of apolipoprotein(a) isoform size with clearance and production of lipoprotein(a) in a diverse cohort. J Lipid Res. 2023;64(3):100336. doi:10.1016/j.jlr.2023.100336

8. Roche Diagnostics. Roche receives FDA 510(k) clearance for the first blood test in the U.S. measuring Lp(a) in molar units. Published 29 January 2025. https://diagnostics.roche.com/us/en/news-listing/2025/roche-receives-fda-510k-clearance-for-the-first-blood-test-in-the-us-measuring-lpa-in-molar-units.html. Accessed 13 May 2025.

9. Thau H, Neuber S, Emmert MY, Nazari-Shafti TZ. Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease?. Cardiol Ther. 2024;13(1):39-67. doi:10.1007/s40119-024-00353-w.