NLA Expert Consensus Examines Role of ApoB in ASCVD Risk Assessment

Daniel E. Soffer, MD

Credit: University of Pennsylvania

A new expert clinical consensus from the National Lipid Association (NLA) explored the role of apolipoprotein B (apoB) measurement in cardiovascular management in adults, particularly for atherosclerotic cardiovascular disease (ASCVD) risk assessment.¹

The NLA writing committee summarized the available scientific evidence on apoB measurement in routine and specialty clinic lipid management, in order to improve ASCVD assessment and determine the need for initiation or intensification of lipid-lowering therapies (LLTs), compared with low-density lipoprotein cholesterol (LDL-C).

“ApoB is a well-validated clinical measurement that augments the information provided by a standard lipoprotein lipid panel,” wrote the committee, led by Daniel E. Soffer, MD, clinical lipidology, division of human genetics and translational medicine at the University of Pennsylvania. “Ideally, it would be included in every lipid panel, but there are presently practical limitations to doing so, including gaps in understanding its role in care and the present high charges for performing the test.”

ApoB is the main structural protein identified on all atherogenic lipoproteins and the principal ligand for the LDL receptor.² ApoB concentrations represent a direct measure of the circulating burden of atherogenic lipoprotein particles. As a result, data indicate that ApoB is a precise, accurate, and well-validated measurement.

On a population level, LDL-C, non-HDL-C, and apoB concentrations are highly correlated—the relationship is typically stronger for non-HDL-C and apoB than LDL-C and apoB. However, despite this correlation, there can be discordance between LDL-C and apoB measurements, leading to undertreatment with LLTs and misclassification of ASCVD risk.¹

Recent evidence found higher-than-expected apoB levels common among individuals with metabolic risk factors.³ However, even among metabolically healthy adults, a wide range of apoB levels was observed for any given LDL-C.

Compared with LDL-C, this guidance suggested apoB levels more accurately reflect the atherogenic impact of lipoproteins before and during lipid-altering treatment with LLTs.¹ Noting the potential for discordance between LDL-C and apoB, the committee indicated that apoB and non-HDL-C stratify ASCVD risk more accurately to guide therapeutic intervention.

In the presence of discordance, they denoted apoB as the strongest predictor of ASCVD risk, followed by non-HDL-C and LDL-C as the least predictive of the three measures.

The consensus statement indicated the foundation of ASCVD risk reduction remains a healthy lifestyle, with nutritional interventions effect in reducing LDL-C, non-HDL-C, and apoB levels. Statins continue to serve as a guideline-directed first-line pharmacotherapy to reduce these levels, based on decades of evidence, including tolerability, affordability, and population accessibility.

Compared with LDL-C and non-HDL-C, thresholds for initiating or intensifying pharmacotherapy for apoB are not well-established. Based on evidence from untreated populations and randomized controlled trials involving LLT use, the commute suggested apoB thresholds of 60, 70, and 90 mg/dL for patients at very high, high, and borderline to intermediate risk for ASCVD. They noted these correspond with available treatment thresholds for LDL-C and non-HDL-C.

Overall, the committee emphasized that apoB is an important measurement enabling lipidologists and other specialists to identify lipid and lipoprotein syndromes and to provide information relevant to prognosis and treatment expectations. They called for further attention to address and minimize barriers to apoB testing and allow equitable access to optimize ASCVD care strategies.

To address these issues, the committee noted the NLA plan to educate clinicians and the public about the role of apoB in cardiovascular risk management, with this expert clinical consensus serving as a first-line resource and educational tool for healthcare professionals.

“We support the view that apoB testing is underutilized in clinical practice, and that it should be reclassified by payers are a routine (non-experimental) test to improve access,” they wrote. “...we strongly recommend that RCTs that are conducted to evaluate lipid-altering interventions for lowering ASCVD risk include measurement of apoB to further elucidate its role in patient care.”

References

1. _{Soffer DE, Marston NA, Maki KC, et al. Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An expert clinical consensus from the national lipid association. J Clin Lipidol. Published online September 5, 2024. doi:10.1016/j.jacl.2024.08.013}
2. _{Sayed A, Peterson ED, Virani SS, Sniderman AD, Navar AM. Individual Variation in the Distribution of Apolipoprotein B Levels Across the Spectrum of LDL-C or Non–HDL-C Levels. JAMA Cardiol. 2024;9(8):741–747. doi:10.1001/jamacardio.2024.1310}
3. _{APOB test may be more accurate measure of heart disease risk. UT Southwestern Medical Center. August 13, 2024. Accessed September 27, 2024. https://www.utsouthwestern.edu/newsroom/articles/year-2024/aug-apob-test.html.}