NEW YORK – While elevated lipoprotein(a) is an established risk factor for cardiovascular diseases, it's unclear how clinicians should identify and treat those patients, creating a care management gap for this at-risk population.
Despite a scientific statement from the American Heart Association (AHA) in 2021 calling Lp(a) a causal and prevalent risk factor for atherosclerotic cardiovascular disease (ASCVD), screening for Lp(a) remains rare. And even when patients are screened, "there's widespread variability" in how and why they're being tested, said Chiadi Ericson Ndumele, a cardiologist and associate professor of medicine at Johns Hopkins Medicine. Some clinicians may opt to screen patients who already demonstrate other cardiovascular risk factors, while others may screen patients based on family history, for example, and there aren't standard management approaches for treating patients with high Lp(a) once they're identified.
Ndumele is part of a three-year research project that the AHA kicked off last month to try to fill that gap. The effort, dubbed the Lp(a) Discovery Project, is seeking to create standard approaches for clinicians to screen and manage patients with high levels of Lp(a), a type of low-density lipoprotein cholesterol that's associated with increased inflammation, clotting, and other risk factors for cardiovascular diseases. Previous studies have estimated that 20 percent to 30 percent of people could have elevated levels of Lp(a).
High levels of Lp(a) are predominantly determined by variation in the LPA gene, with little influence from lifestyle factors, according to the AHA's scientific statement.
The Lp(a) Discovery Project, which launched in March with support from Novartis Pharmaceuticals, is in an early stage, according to Ndumele, so the team is still figuring out specific steps. But the AHA's goals include improving understanding of the genetic and biological basis for Lp(a) variations and its relationship with cardiovascular and stroke risk, and integrating information about Lp(a) into its Get With The Guidelines program.
The project's first steps likely will involve assessing the extent to which clinicians are currently screening for Lp(a) and the prevalence of elevated Lp(a) they're seeing, and subsequently defining strategies for standard use of such testing. From there, the AHA plans to launch a Lp(a) screening measure and quality improvement interventions that it will test at health systems across the country through the organization's current Integrated ASCVD Management Initiative, which was launched in 2021 to refine lipid management best practices.
Ndumele, who's a principal investigator on the Integrated ASCVD Management Initiative, noted that while Lp(a) may be a causal risk factor for ASCVD, it's not yet clear whether lowering Lp(a) will result in fewer cardiovascular disease events. That's an area where further study is needed, particularly as Lp(a) becomes an area of growing interest for the biopharmaceutical industry.
The Lp(a) Discovery Project is focused on implementation science and identifying barriers to Lp(a) testing, the AHA wrote in an email, and does not focus on therapeutics.
A few Lp(a) lowering strategies that could be on the horizon, according to Ndumele, are lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. There are also drugmakers developing targeted small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapies.
If any of those therapies show a reduction in cardiovascular disease events, that will "really change the landscape of Lp(a) management," he said. That's "the real question right now."
Novartis, which is providing financial support for the Lp(a) Discovery Project, considers the project an "integral part of our continued commitment to reduce cardiovascular disease morbidity and mortality," wrote Liviu Niculescu, the company's chief medical officer for the US, in an email. He declined to share how much funding Novartis contributed.
The company hopes the research project will drive awareness of high Lp(a) as a risk factor for cardiovascular disease, Niculescu said. It also intersects with Novartis' development of Pelacarsen (TQJ230), an ASO targeting Lp(a) that's being tested in a Phase III trial called Lp(a) HORIZON. The trial is assessing whether lowering Lp(a) leads to fewer major cardiovascular events for patients with cardiovascular disease and elevated Lp(a) levels.
Novartis is also a partner in a Lp(a) pilot program that 23andMe announced last month, in which people will be able to buy a blood-based screening test for Lp(a) levels. Novartis is providing financial support and disease-area expertise for the program but does not have access to test results or other personal information about participants, wrote Joyce Tung, VP of research at 23andMe, in an email. The program is managed by 23andMe, she added, and patients will have the option to discuss their test results with a clinician through 23andMe's Lemonaid Health telehealth service.
Care management for patients with elevated Lp(a) levels might involve counseling about the association between Lp(a) and cardiovascular disease and addressing other, modifiable risk factors, she said.
23andMe, which got its start in direct-to-consumer genetic testing, in recent years has been expanding into medical care, including acquiring Lemonaid Health in 2021. Today, it focuses on providing patients with health information to encourage proactive, preventive healthcare, primarily through its genetic testing services. The Lp(a) pilot is related to genetics through the link to the LPA gene, although it isn't reporting results on a genetic marker.
"Our hope is that this initiative will bring a greater understanding of Lp(a) and help those who might be at higher risk," Tung said. 23andMe will first roll out the Lp(a) test to a small number of customers, according to Tung, with plans to apply lessons from the pilot before making the test more widely available. Existing 23andMe customers who are at least 18 years of age and reside in the US will be randomly selected for the opportunity to participate in the pilot.