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A Translational Tool to Facilitate Use of Apolipoprotein B for Clinical Decision-Making
Justine Cole1, James Dorian Otvos2, Alan Thomas Remaley3
1Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Insights
Apolipoprotein B (apoB) better predicts atherosclerotic cardiovascular disease (ASCVD) risk than LDL-C. This study developed a method to translate apoB values into LDL-C equivalents, aiding ASCVD risk management.
Area of Science:
- Cardiovascular Medicine
- Clinical Chemistry
- Biomarker Discovery
Background:
- Apolipoprotein B (apoB) is a superior predictor of atherosclerotic cardiovascular disease (ASCVD) risk compared to low-density lipoprotein cholesterol (LDL-C).
- Current US guidelines still recommend LDL-C for guiding lipid-lowering treatments, despite evidence favoring apoB.
- A significant barrier to adopting apoB is the absence of established guideline treatment targets.
Purpose of the Study:
- To develop a method for translating apoB values into population-equivalent LDL-C units.
- To enable apoB-based treatment decisions using existing LDL-C targets.
- To facilitate the adoption of apoB for improved ASCVD risk management.
Main Methods:
- Utilized population-based samples (n=15,153) excluding those with triglycerides >1000 mg/dL.
- Performed standard lipid panel analysis and apoB testing via immunoassay.
- Employed linear regression to establish an equation for converting apoB to percentile-equivalent LDL-C units.
Main Results:
- Developed the conversion equation: LDL-C equivalents = 1.38(apoB) - 29 (R²=0.999).
- Found significant discordance between LDL-C and apoB levels across various risk strata.
- Highlighted that 40% of individuals with very low LDL-C had discordantly higher apoB, indicating elevated ASCVD risk.
Conclusions:
- The developed translation method allows apoB values to be interpreted within the framework of LDL-C targets.
- Visibility of discrepancies between apoB, LDL-C, and non-HDL-C is crucial for clinical practice.
- Widespread adoption of apoB for ASCVD risk management can be accelerated by addressing current guideline limitations.
Background:
Despite recent large-scale discordance studies showing definitively that atherosclerotic cardiovascular disease (ASCVD) risk correlates better with apolipoprotein B (apoB) than with low-density lipoprotein cholesterol (LDL-C), the latter remains the recommended metric for guiding lipid-lowering treatment decisions in the United States. A major barrier to change, in this regard, is the lack of guideline-recommended apoB treatment targets. We developed a simple method to "translate" apoB values into population-equivalent LDL-C units, allowing apoB-based treatment decisions to be made using LDL-C targets.
Methods:
Sequentially collected, population-based samples underwent standard lipid panel analysis and apoB testing by immunoassay. Those with triglycerides greater than 1000 mg/dl were excluded, leaving a study cohort of 15 153 individuals.
Results:
Linear regression of calculated LDL-C values against percentile-equivalent apoB values yielded an equation to convert apoB into percentile-equivalent LDL-C units: [LDL-C equivalents = 1.38(apoB) - 29] (R2 = 0.999). The extent of discordance between LDL-C and apoB was examined in subgroups with similar LDL-C, ranging from very low (55-70 mg/dL) to very high (175-190 mg/dL). Among individuals with very low LDL-C, 40% had discordantly higher apoB, indicating higher ASCVD risk. Of those with very high LDL-C, 49% had discordantly lower apoB. Across the range, a minority of patients (25%-40%) had concordant levels of apoB, confirming that discordance between these biomarkers is highly prevalent. Similar results were found in discordance analysis between apoB and non-high-density lipoprotein cholesterol (HDL-C).
Conclusions:
Providing visibility to discrepancies among LDL-C, non-HDL-C, and apoB should help to facilitate more rapid and widespread adoption of apoB for managing ASCVD risk.
