Lipid management is a key step in reduction of cardiovascular disease, which is a major cause of morbidity and mortality worldwide. In the 2018 multi-society guideline on the management of blood cholesterol, there were a few major themes that directly impact laboratory testing. In this afternoon’s scientific session, “Updates on Diagnostics and Therapeutics for Lipid Management of Cardiovascular Disease,” four experts will delve into the key steps in lipid management, from laboratory testing to potential new therapies.

Jeff Meeusen, PhD, DABCC, will kick off the session with a review of the 2018 multi-society guideline used in the U.S., and compare it to the European guidelines. The latest guideline makes specific mention of several laboratory tests to be considered risk enhancing factors, including lipoprotein (a) [Lp(a)] and apolipoprotein B. “A big takeaway from the latest guideline is the continued emphasis on statin benefit groups,” says Meeusen.

Historically, the laboratory reporting of LDL cholesterol (LDL-C) was framed in the context of the National Cholesterol Education Program treat-to-target strategy, whereby a patient’s LDL-C goal was either <160, <130, or <100 mg/dL, determined according to their baseline cardiovascular risk. The 2018 guideline broke from this strategy and introduced statin-benefit groups, which individualized each patient’s target LDL-C to a percentage reduction from their personal baseline. “Thus, an LDL-C <100 mg/dL may not be the desirable goal in all cases. This is already playing out with many patients achieving an on-treatment LDL-C of <70 mg/dL or even <40 mg/dL,” explains Meeusen.

This has led to another major lab impact included in the guideline. “The standard practice for 50 years has been to calculate LDL-C using the Friedewald equation. However, this equation performs very poorly at low concentrations of LDL-C. The 2018 guideline specifically calls this out and suggests using more modern equations with an LDL-C <70 mg/dL,” says Meeusen.

Many cardiovascular risk biomarkers can be measured with a standard automated chemistry analyzer. In addition to a basic lipid panel, Lp(a), and high-sensitivity C-reactive protein, additional methods have become available, such as small dense LDL-C. However, “when considering implementing novel FDA approved reagents, the laboratory director must make sure the clinical demand warrants test implementation. With a wide variety of biomarkers available for detection of residual cardiovascular risk, the judicious selection of the most clinically relevant and useful biomarkers with physician endorsement is crucial,” says speaker Leslie Donato, PhD, DABCC.

The next speaker, Alicia Lyle, PhD, will explain the analytical aspects and biology of Lp(a), a risk-enhancing factor that can help guide patient management in the clinic. “Lp(a) is a highly heterogeneous analyte due to variations in size, which can lead to over- or underestimation of Lp(a) quantities by some assay types,” explains Lyle. Another limitation of the Lp(a) assays is the lack of standardization. To address this issue, Lyle explains that “the IFCC Working Group on Apolipoproteins is working to establish a mass spectrometry-based reference measurement system that will quantify Lp(a) concentrations in molar units, and will be Lp(a) size-independent. The CDC Clinical Standardization Program is working in collaboration with the IFCC to help manufacturers and laboratories make the transition to the new IFCC reference system.”

Alan Remaley, MD, PhD, is the moderator and the final speaker of the session. He will discuss the existing lipid lowering therapies, including PCSK9 inhibitors, bempedoic acid, and eicosapentaenoic acid (EPA). Among these three groups, the PCSK9 inhibitors were the first to be approved by FDA, which was in 2015. Bempedoic acid was approved early in 2020 for the treatment of adults with heterozygous familial hypercholesterolemia —or established atherosclerotic cardiovascular disease—who require additional lowering of LDL-C. EPA—found in cold-water fatty fish such as salmon, as well as fish oil supplements—is an omega-3 fatty acid that helps lower risk of heart disease. Remaley will also review several potential new lipid-lowering therapies that are in late-stage clinical trials.

Attendees will leave this scientific session with a better understanding of the new multi-society guidelines and laboratory assays for lipid management.