By Chris Wolski
Summary:
Lipoprotein(a), or Lp(a), is a genetically determined and under-recognized cardiovascular disease risk factor, but new diagnostic tools like Roche’s FDA-cleared molarity assay are enabling more accurate and widespread testing to guide prevention and future therapies.
Takeaways:
- Genetic Risk Factor: Lp(a) levels are determined primarily by genetics, remain stable throughout life, and are unaffected by lifestyle changes, making testing essential for identifying hidden cardiovascular risks.
- Improved Testing Available: Roche’s Tina-quant Lp(a) Gen.2 Molarity assay, the first FDA-cleared test measuring Lp(a) in molar units, offers consistent and accurate assessment to better predict ASCVD risk.
- Future-Ready Diagnostics: As Lp(a)-lowering therapies approach FDA approval, routine Lp(a) testing will become critical, and labs are encouraged to integrate this testing to support early intervention and personalized treatment strategies.
Cardiovascular disease is the leading cause of death for US men and women regardless of their ethnic or racial background. In fact one person dies every 33 seconds of cardiovascular disease, accounting for one in every five deaths annually1.
While many of the causes of cardiovascular disease are related to lifestyle choices—poor diet, lack of exercise, or smoking—some are not. Lipoprotein(a) [Lp(a)] is one of the factors influencing cardiovascular health that is somewhat out of our control.
But there’s good news—there’s testing available to help manage cardiovascular health related to Lp(a) levels, according to Alex Fohl, PharmD, scientific partner, Cardiometabolism at Roche Diagnostics. Prior to joining Roche, he was a clinical pharmacist at Indiana University Health in Indiana and Community Hospital in Indiana where he precepted students and residents.
In a recent conversation with CLP, Fohl outlined why Lp(a) testing is important for cardiovascular health, how labs can add it to their menus, and what the future holds for cardiovascular testing.
Fohl’s responses have been edited for length and clarity.
CLP: What is Lp(a) and why should healthcare providers be testing for it?
Alex Fohl: Lipoprotein(a), also known as Lp(a) or “L-p-little a”, is a type of lipoprotein whose concentration is primarily (90%) determined by genetics and is heritable. Genetics determines the size of the Lp(a) particle and the number of particles within the blood, with smaller particles tending to have a higher concentration than the larger particles. Lp(a) is emerging as an important, yet under-recognized, potential risk factor for cardiovascular disease (CVD), a major public health issue. Lp(a) is elevated in one in five people worldwide and can promote the development of plaques within artery walls, clot formation, and aortic valve calcification. Unlike other CVD risk factors, it remains unaffected by lifestyle changes such as diet and exercise.
CLP: Since LP(a) size is genetic in origin, is testing for Lp(a) levels different from cholesterol testing? If so, how?
Fohl: Although Lp(a) levels are determined at birth by genetics, approximately 20% of individuals live with elevated levels of this particle. Additionally, the Lp(a) concentration is present at a young age and remains relatively consistent throughout life. Liver disease, renal disease, thyroid disease, and menopause may affect Lp(a) levels, but diet and exercise do not affect Lp(a) levels like they do with other lipid concentrations, such as LDL. LDL and HDL measurements determine the amount of cholesterol contained within LDL and HDL particles. Although LDL is commonly measured and used as a target for therapy in cardiovascular outcome studies, the number of atherosclerotic particles in the blood may correlate better with atherosclerotic cardiovascular disease (ASCVD) risk than the cholesterol content. A simple blood test, similar to how practitioners test for LDL or HDL cholesterol, can be used to test for Lp(a) as well.
Traditionally, measurement of Lp(a) has been reported in mass-based (mg/dL) units. However, differences in the possible size of an individual’s Lp(a) will impact the weight of the particle. The different-sized particles can then create inconsistencies in the Lp(a) mass measurement, making it challenging to accurately determine the associated ASCVD risk. For this reason, there is a consensus in the scientific community that Lp(a) levels should be measured in terms of the number of particles per liter of blood (nmol/L) rather than mass units (mg/dL).
Importantly, the Tina-quant Lipoprotein (a) Gen.2 Molarity assay from Roche Diagnostics was recently FDA-cleared and is expected to be the first commercially available Lp(a) assay measuring in molar units in the United States. This Lp(a) Molarity assay is a simple diagnostic that will offer an opportunity to consistently and accurately measure Lp(a) in particle concentration units. When physicians have this information, they can work to provide patients with the appropriate support.
CLP: How does the Tina-quant Lipoprotein (a) Gen.2 Molarity assay work?
Fohl: The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is useful in evaluating lipid metabolism disorders and assessing ASCVD risk, when used in conjunction with clinical evaluation and other lipoprotein tests.
An Lp(a) test involves a routine blood draw, during which a small sample of blood is used for measurement. The measurement can be obtained from the Roche Diagnostics cobas c analyzers, which are widely available across the United States. This test measures the number of Lp(a) particles per liter in a person’s blood (serum and plasma). Results can enable clinicians to take actionable steps to reduce ASCVD risk in the future.
CLP: How do Lp(a) testing results inform potential treatments?
Fohl: Whether testing for Lp(a) or other biomarkers, like NTproBNP, consistent and accurate testing holds the potential to refine risk prediction and improve an individual’s cardiovascular health management. Lp(a) is an independent, causal, linear risk factor for ASCVD risk, meaning that an elevated Lp(a) value can cause ASCVD regardless of the individual’s other risk factors. The American Heart Association (AHA) has dubbed the primary risk factors contributing to CVD as “Life’s Essential Eight,” which include managing blood pressure, cholesterol, blood sugar, weight, exercise, sleep habits, smoking cessation, and diet. An Lp(a) value can help identify individuals at risk of ASCVD. Healthcare providers can, in turn, encourage healthy lifestyles to reduce the risk factors which are modifiable. The good news is that Lp(a)-lowering pharmaceutical agents currently in development are showing encouraging results in preliminary studies, which may be another option for patients in the future.
CLP: How and why should labs push to have LP(a) testing added to the diagnostic menu?
Fohl: Lp(a) testing rates throughout the United States are markedly low. Some estimates suggest that less than 1% of the population has had their Lp(a) concentration measured despite understanding the risks associated with elevated Lp(a) values. With the clearance of the Tina-quant Lipoprotein (a) Gen.2 Molarity assay, this test can be run on a fully automated analyzer with other commonly ordered blood tests. The addition of the test to a lab’s diagnostic menu can reduce the time needed to obtain a result and enable practitioners to recommend lifestyle modifications for their patients. The sooner individuals with risk factors for cardiovascular disease can be identified, the sooner they can work to reduce those risk factors and potentially delay or prevent adverse outcomes.
It will become increasingly important to have Lp(a) testing added to diagnostic menus as therapies become available. Currently, there are Lp(a)-lowering therapies in development by several pharmaceutical companies, which hope to gain FDA approval in the coming years. These therapies are expected to dramatically reduce the Lp(a) concentrations in individuals with the objective of preventing or delaying the progression of cardiovascular diseases. As part of a separate FDA submission, the Roche Tina-quant Lp(a) RxDx assay, which is in development and is expected to be intended to support the selection of patients who may benefit from an innovative Lp(a)-lowering therapy, has received a Breakthrough Device Designation from the FDA and is currently in development.
CLP: With all of the new understanding of genetics and biomarkers, how do you expect cardiovascular testing to evolve in the next 5 to 10 years?
Fohl: Cardiovascular disease remains the leading cause of death both in the United States and globally. Roche is committed to advancing innovation in cardiac biomarker testing and ensuring that physicians have the diagnostic tools they need to improve patient care.
In partnership with the scientific community, Roche strives to understand disease processes, identify risk factors, and ultimately reduce the burden of cardiovascular disease for individuals and healthcare systems. Most recently, the concept of the Cardiovascular-Kidney-Metabolic syndrome, a theory where risk factors and disease progression in one organ system can lead to a cascade of health issues in other organ systems, has been developed to reflect the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and their profound impacts on morbidity and mortality. Over the next five to 10 years, we can expect to see advances in biomarkers that aid in the identification of high-risk individuals and are applied to help mitigate or prevent subsequent disease progression.
The concept of disease progression across risk factors is already coming to fruition for patients with diabetes who are at increased risk for heart failure or kidney disease. The American Diabetes Association (ADA) updated its Standards of Care in Diabetes in 2024 to advocate for the use of natriuretic peptide (i.e. NT-proBNP and BNP) biomarker tests for annual heart failure testing. These cross-functional collaborations will continue to expand in an attempt to improve health outcomes for other related risk factors.
Roche’s Lp(a) Molarity assay is another example of how Roche’s innovation in cardiovascular biomarkers can evolve cardiovascular testing in the coming years. This test can accelerate access to more standardized testing and equip more patients and healthcare providers with important information to better understand an individual’s risk for cardiovascular disease. Professional societies around the world, including the National Lipid Association, have recommended that Lp(a) measurement should be considered at least once in every adult person’s life. With these recommendations and ongoing clinical trials, Lp(a) will be included in more routine evaluations to help identify individuals at high risk in the future and may help stratify individuals who could benefit from future therapies already in development.
Laboratories can expect an increased volume of cardiac biomarker tests in conjunction with biomarkers for renal function, inflammation and liver function to identify risk factors for disease as early as possible. Laboratorians will play a pivotal role in providing critical insights for patients, ranging from those experiencing a cardiac event to individuals undergoing routine testing.
Chris Wolski is chief editor of CLP.
Featured Image: Lp(a) testing can be performed on the Roche Diagnostics cobas c analyzers, which are widely available across the United States. Image: Roche Diagnostics
Reference
- “Heart Disease Facts.” Centers for Disease Control and Prevention. October 24, 2024. https://www.cdc.gov/heart-disease/data-research/facts-stats/index.html#:~:text=Heart%20disease%20in%20the%20United%20States&text=One%20person%20dies%20every%2033,1%20in%20every%205%20deaths.
