Lp(a) ‘should be measured at least once’ in adults to target CV risk
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BOSTON — There is strong evidence for a casual association between lipoprotein(a) concentration and CV outcomes across ethnicities, and Lp(a) “should be measured at least once” in all adults to identify high CV risk, according to a speaker.
Elevated Lp(a) levels are an independent risk factor for the development of atherosclerotic diseases, including peripheral artery disease (PAD), and the interpretation of Lp(a) concentration should be done in the context of absolute CVD risk, Patrick M. Moriarty, MD, FACC, FACP, professor of medicine and director of clinical pharmacology and the Atherosclerosis/Lipoprotein-Apheresis Center at the University of Kansas Medical Center, said during a presentation at the Cardiometabolic Health Congress. Lp(a) levels greater than 50 mg/dL contribute to a higher risk for heart disease, with several ethnicities being more genetically predisposed to this risk factor, he said; however, Lp(a) is still not routinely measured in the U.S.
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“The risk for CVD based exclusively on Lp(a) levels is incredibly high, whereas the lack of testing for Lp(a) in the United States is, as quoted by Winston Churchill, ‘a riddle, wrapped in a mystery, inside an enigma,’ Moriarty told Healio.
High Lp(a) predicts CV events, death
The LPA gene makes messenger RNA, which then makes apolipoprotein A, which then forms lipoprotein(a) particles, Moriarty said during the presentation.
In a study examining the prognostic impact of elevated Lp(a) published in the Journal of the American College of Cardiology in July, researchers assessed more than 1,100 patients who underwent successful endovascular therapy for symptomatic PAD; a high Lp(a) was defined as at least 30 mg/dL. Among patients with elevated Lp(a), the cumulative incidence rate of major adverse CV events, including all-cause and CV death, and major adverse limb events, including major amputation, were nearly two times and four times higher, respectively, compared with patients with lower Lp(a) concentrations; the associations were not influenced by LDL levels or statin administration.
“We recommend that Lp(a) should be measured at least once in adults to identify those with high CV risk,” Moriarty said. “We are not doing it. We should be. And we will be.”
What to do
There are currently no approved pharmacological therapies for targeted treatment of Lp(a), though there are promising candidates in phase 1 and 2 development. Current treatments include aspirin, statins, PCSK9 inhibitors and lipoprotein-apheresis, Moriarty said.
Diet and exercise have “little to no effect” on Lp(a) concentration, Moriarty said; however, lifestyle modification should still be recommended along with medications to intensify risk factor management.
New research suggests that low-dose aspirin for primary prevention of CV events may benefit older adults aged at least 65 years with elevated lipoprotein(a)-associated genotypes, Moriarty said. In a new analysis of the ASPREE trial published in September that assessed participants who carry genotypes associated with elevated Lp(a) levels, researchers found that in rs3798220-C and high Lp(a) genomic risk score subgroups, aspirin reduced major adverse CV events 11.4 and 3.3 events per 1,000 person-years, respectively, without significantly increasing bleeding risk.
Targeted therapies coming
New treatments may be available soon to help patients at very high risk, Moriarty said. RNA therapeutics targeting hepatic synthesis of apolipoprotein(a) are under development; multiple trials, including the phase 3 HORIZON trial, are in progress to test the hypothesis that lowering Lp(a) could reduce CV risk, Moriarty said. There are two therapies targeting Lp(a) in phase 2 or 3 development: pelacarsen (Akcea/Ionis), an antisense therapy, and olpasiran (Amgen), a small interfering RNA (siRNA) therapy. Additionally, in the phase 1 APOLLO study, a short interfering RNA therapy, SLN360 (Silence Therapeutics) lowered Lp(a) by a maximum of more than 90% in certain doses.
“These specific Lp(a)-lowering medications are currently in phase 2/3 trials and hopefully will be very effective,” Moriarty said.
References:
- Lacaze P, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2022.07.027.
- Tomoi Y, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jcin.2022.05.050.
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Moriarty P. The evolving story of lipoprotein(a). Presented at: Cardiometabolic Health Congress; Oct. 19-22, 2022; Boston.
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