‘Elevated Lp(a) is actionable now’: NLA issues updated recommendations
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Key takeaways:
- Lp(a) represents a “continuous gradient of risk” for heart disease and should be measured in adults at least once.
- Lipid-lowering therapies are appropriate for many patients with high Lp(a).
The National Lipid Association issued a focused update on its 2019 scientific statement on use of lipoprotein(a) in clinical practice, incorporating new evidence into recommendations for managing patients with high Lp(a).
“While specific Lp(a)-lowering therapies are not currently available, elevated Lp(a) is actionable now,” Christie M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, chief of the section of cardiovascular research and professor of medicine at Baylor College of Medicine, and colleagues wrote in the Journal of Clinical Lipidology.
The authors wrote that evidence from the UK Biobank has revealed that there is not a single threshold that signifies CV risk from elevated Lp(a). “The continuous gradient of risk with increased Lp(a) implies that clinical decision-making should be influenced by the degree of Lp(a) elevation and the patient’s other risk factors, not the mere presence of elevated Lp(a),” they wrote, noting that there is no evidence that Lp(a)’s impact on CV risk differs by race.
“There is a continuous relationship between levels of Lp(a) and your risk,” Ballantyne told Healio.
Address modifiable risk factors
The strongest links between elevated Lp(a) and CV outcomes are for atherosclerotic CVD, MI and calcified aortic valve stenosis, and although CV risk from high Lp(a) remains even after treatment with existing lipid-lowering therapies, “early and more-intensive management of modifiable risk factors, including LDL-C and non-HDL-C levels, is warranted in at-risk patients who have elevated Lp(a), as their risk is potentiated to a greater extent at a given Lp(a) concentration,” Ballantyne and colleagues wrote.
Given the impact of Lp(a) on CV risk, “we recommend measuring Lp(a) in every adult at least once for cardiovascular risk assessment,” the authors wrote.
For children with known elevated Lp(a), “treatment of conventional risk factors to guideline-based goals becomes particularly important, as these children are likely to be at higher risk compared with children with the same risk factors without elevated Lp(a),” they wrote.
Accurate measurement of Lp(a) is critical to determining a patient’s CV risk, and current methods are “sufficient” to assess Lp(a)-related risk in the general population, but completion of an effort by the International Federation of Clinical Chemistry and Laboratory Medicine to standardize Lp(a) measurement globally is awaited, the authors wrote. In addition, the National Lipid Association (NLA) recommends measurement of Lp(a) in nanomoles per liter as opposed to milligrams per deciliter, but prefers measurement in milligrams per deciliter to no measurement.
Genetic risk scores related to the LPA gene can be helpful to identify people with high Lp(a), but “Lp(a) genetic risk score appears to add no incremental value for CVD risk classification compared with Lp(a) concentrations alone,” Ballantyne and colleagues wrote.
A new risk scale
The NLA redefined the definition of “high risk” based on Lp(a) levels to account for evidence showing a continuous gradient of risk best represented real-world risk as opposed to exceeding to a specific threshold.
“In the risk continuum across Lp(a) levels, individuals with Lp(a) levels < 75 nmol/L (30 mg/dL) can be considered low risk and individuals with Lp(a) levels > 125 nmol/L (50 mg/dL) should be considered high risk,” the authors wrote. “This approach allows for the consideration of repeat measurement of Lp(a) in patients with levels within a ‘gray zone’ of intermediate risk between 75 and 125 nmol/L (30-50 mg/dL). Because Lp(a) levels are relatively stable in primary prevention patients, measurement of Lp(a) once for individuals in the low-risk or high-risk category in this population is reasonable; however, this needs to be verified in secondary prevention populations.”
“If you have a low level, that is not going to change and you will not have to repeat [a test],” Ballantyne told Healio. “It’s important that people get this information, and it has implications for health equity. It turns out that if you are African American, you have double the risk of having a high Lp(a) than someone who is white. We think it’s important that this information gets to the public.”
The panel wrote that lifestyle modification is recommended for all patients with high Lp(a).
“If someone has a high calcium score, you know that you need to be more aggressive on prevention,” Ballantyne told Healio. “What does that mean? Lifestyle, diet, exercise and smoking cessation. If someone has a very high Lp(a), the risk goes up the higher the number is, just like a calcium score, and you have to consider lifestyle measures and may want to consider whether to put the patient on a statin or be more aggressive with their blood pressure. Everyone seems to have gotten their arms around the concept of the calcium score, though it took a long time. I think we’re ready to have the same kind of concept for Lp(a). As with the calcium score, it needs to be looked at in the context of [a patient’s] total risk.”
According to the authors, Lp(a) level can help further guide treatment decisions as follows:
- In adults aged 40 to 75 years with a 10-year ASCVD risk of 7.5% to 19.9%, Lp(a) 125 nmol/L or 50 mg/dL is reasonable to be used as a risk-enhancing factor to favor initiation of a moderate- or high-intensity statin in those with on-treatment LDL 70 mg/dL or non-HDL-C 100 mg/dL.
- In patients with Lp(a) 125 nmol/L or 50 mg/dL at high or very high risk for CVD, it is reasonable to consider more intensive LDL lowering.
- In patients with Lp(a) 125 nmol/L or 50 mg/dL at high or very high risk for CVD, it is reasonable to add ezetimibe and/or a PCSK9 inhibitor to maximally tolerated statin therapy in those with on-treatment LDL 70 mg/dL or non-HDL-C 100 mg/dL.
- Lipoprotein apheresis is reasonable for high-risk patients with familial hypercholesterolemia and ASCVD whose Lp(a) level remains 60 mg/dL (approximately 150 nmol/L) and LDL-C 100 mg/dL on maximally tolerated lipid-lowering therapy.
- Niacin or hormone replacement therapy with estrogen and progesterone, which lower Lp(a) concentration, are not recommended to reduce ASCVD risk.
“In addition, identification of individuals with high levels of Lp(a) also identifies a family at risk, and cascade screening for elevated Lp(a) should be performed in first-degree family members,” the authors wrote.
For more information:
Christie M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, can be reached at cmb@bcm.edu; X (Twitter): @cballantynemd.
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