National Lipid Association

National Lipid Association

May 17, 2019
5 min read

NLA: Lp(a) can help assess ASCVD risk in several patient populations

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Peter H. Jones
Peter H. Jones

MIAMI — A statement from the National Lipid Association focused on the standardization of lipoprotein(a) measurement, in addition to measuring Lp(a) to reclassify atherosclerotic CVD risk and to aid in decision making for pharmacotherapy, according to a presentation at the NLA Scientific Sessions.

Lp(a) testing is appropriate in certain primary and secondary prevention populations, and Lp(a) should be measured in accordance with particle concentration instead of mass concentration, according to the statement, which was simultaneously published in the Journal of Clinical Lipidology.

Lp(a) measurement

Some of the major issues involved with measuring Lp(a) include the units of measurement, lack of harmonization and standardization of assays and the absence of evidence-based cut points, Marlys L. Koschinsky, PhD, FAHA, FNLA, scientific and executive director of Robarts Research Institute in London, Ontario, said during the presentation. Although there is a potential for isoform-dependent bias, it can be minimized through the use of a calibrator that contains several different isoforms, she said.

The statement recommends, if possible, the use of a particle concentration unit of measurement — nmol/L — rather than a mass concentration unit of measurement, or mg/dL.

“You cannot interconvert between the two units,” Koschinsky said during the presentation. “That’s just not possible. ... Why can’t you interconvert? Because if you use a common conversion factor to go from mg/dL to nmol/L, you will almost always underestimate the smaller isoform sizes which happen to be associated with the highest Lp(a) levels.”

Using nmol/L as a unit of measurement allows for standardization and harmonization of assays, facilitates the establishment of evidence-based guidelines and harmonizes future clinical trial data, Koschinsky said.

The statement recommends selecting an assay that reports results in nmol/L, uses a five-point calibrator or similar and is calibrated against secondary reference material from WHO and the International Federation of Clinical Chemistry and Laboratory Medicine.

Different cut points for risk assessment may need to be determined for specific populations based on ethnic groups, sex, primary vs. secondary prevention and comorbidities.

“The evidence base on this particular aspect of things is, to say the least, incomplete at this time,” Koschinsky said during the presentation.

Primary prevention

A statement from the National Lipid Association focused on the standardization of lipoprotein(a) measurement, in addition to measuring Lp(a) to reclassify atherosclerotic CVD risk and to aid in decision making for pharmacotherapy, according to a presentation at the NLA Scientific Sessions.
Source: Adobe Stock

With regards to the use of Lp(a) testing for primary prevention, shared decision making is important when discussing the potential for statin therapy in patients who have borderline risk for atherosclerotic CVD, Peter H. Jones, MD, FNLA, associate professor at Baylor College of Medicine in Houston and chief science officer of the NLA, said during the presentation. To aid in this, the measurement of Lp(a) may be reasonable to refine risk assessment for ASCVD events in patients with a family history of premature ASCVD, those who have borderline 10-year ASCVD risk in whom the decision for statin therapy is uncertain, family history of Lp(a), less-than-expected LDL reductions despite adherence to therapy, recurrent or progressive ASCVD despite lipid-lowering therapy and calcific valvular aortic stenosis.

Carl E. Orringer
Carl E. Orringer

“We all know that Lp(a) is stable throughout life,” Jones said during the presentation. “It is genetically determined and therefore one measurement once in your lifetime can create a reasonable decision. It came up in this discussion that maybe we can recommend universal screening because of that possibility, but as you’ll read through this [statement], ... because of some lack of evidence on whether specifically treating that Lp(a) makes a difference vs. just using it as a risk-enhancing factor in the right patients, we decided that right now, we cannot make a recommendation for universal screening of Lp(a). We did recognize that there is little harm from the universal screening approach; however, we felt that we would wait for more data to become available and then we would reassess as a group whether the possibility of universal screening might be reevaluated.”

Testing for secondary prevention

The measurement of Lp(a) may be reasonable in patients with ASCVD who are also younger with ACS, have recurrent coronary events or have recurrent ischemic stroke, Carl E. Orringer, MD, FNLA, associate professor of medicine at University of Miami Miller School of Medicine, said during the presentation. In addition, patients on statin therapy with elevated Lp(a) levels may have an increased risk for ASCVD that has not been addressed by the statin therapy.

Several drug therapies in patients with high or very high risk for ASCVD had varied results. Both statin therapy and ezetimibe have been shown to minimally increase Lp(a). As for the PCSK9 inhibitors, evolocumab (Repatha, Amgen) reduced Lp(a) by 27% and had a greater treatment effect in patients with high Lp(a) compared with lower levels, and alirocumab (Praluent, Sanofi Aventis) improved ASCVD outcomes in patients with high Lp(a) due to Lp(a) reduction independent of LDL reduction, Orringer said.

Based on the available evidence, niacin, despite its ability to lower Lp(a), is not recommended for the reduction of ASCVD risk in patients on moderate-to-high intensity statins with or without ezetimibe and an LDL of less than 80 mg/dL while on the treatment. In addition, it is reasonable to consider more intensive LDL reduction in patients with high or very-high risk who have a Lp(a) level greater than 100 nmol/L. Adding ezetimibe to maximally tolerated statins may also be reasonable in patients with very high risk or high risk, Lp(a) greater than 100 nmol/L and an on-treatment LDL greater than 70 mg/dL. It may also be reasonable to add a PCSK9 inhibitor for patients with very high ASCVD risk who are on maximally tolerated statin and ezetimibe, according to the presentation.

Marlys L. Koschinsky
Marlys L. Koschinsky

Testing in young patients

The majority of Lp(a) concentration can be explained through an autosomal dominant pattern of inheritance, Catherine J. McNeal, MD, PhD, FNLA, associate professor of internal medicine and pediatrics and director of the nutrition and weight management program for Baylor Scott and White Health in Temple, Texas, said during the presentation. By 1 to 2 years of age, the gene is fully expressed and by 5 years of age, it can reach adult levels and remains stable throughout the patient’s lifetime independent of sex, age or lifestyle habits.

The statement recommends screening siblings and parents of patients younger than 20 years of age with elevated Lp(a) levels. In addition, a lifelong heart-healthy lifestyle should be encouraged in these young patients even though there are no medications that have been approved to lower Lp(a) levels, according to the presentation. Smoking avoidance or cessation should be emphasized in these patients.

Lp(a) should also be measured in young patients with a history of ischemic stroke, according to the presentation.

“To answer these and a myriad of other questions, it is encouraging that a randomized, placebo-controlled, double blind trial of Lp(a) reduction using antisense oligonucleotides to block the production of Lp(a) via LPA gene silencing is anticipated to start in 2020,” Don Wilson, MD, FNLA, endowed chair of pediatric cardiovascular health and risk prevention at Cook Children’s Medical Center in Fort Worth, Texas, and colleagues wrote. “Other pharmaceutical companies are developing other promising Lp(a)-lowering therapies such as small interfering RNA inhibitor technology. Thus, if these early studies continue to show both safety and efficacy, it is likely that more randomized trials will also be conducted with the aim of reducing ASCVD and possibly [aortic valve stenosis] progression through novel targeted Lp(a) reduction.” – by Darlene Dobkowski


Jones PH.

Koschinsky ML.

McNeal CJ.

Orringer CE. Manuscripts for the Clinical Setting. All presented at: National Lipid Association Scientific Sessions; May 16-19, 2019; Miami.

Wilson DP, et al. J Clin Lipidol. 2019;doi:10.1016/j.jacl.2019.04.010.

Disclosures: Jones reports he received advisory board honorarium from Amgen, AstraZeneca and Sanofi/Regeneron. Koschinsky reports she received speaker and consulting honorarium from Eli Lilly, speaker honorarium from Pfizer and independent contractor fees from Cardiovax, Eli Lilly, Ionis and Pfizer. McNeal and Orringer report no relevant financial disclosures. Wilson reports he received speaking honorarium from Osler Institute, research grants from Merck Sharp and Dohme and Novo Nordisk and participated on the advisory board for Alexion Pharmaceuticals. Please see the statement for all other authors’ relevant financial disclosures.