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Discordance analyses comparing LDL cholesterol, Non-HDL cholesterol, and apolipoprotein B for cardiovascular risk
Camilla Ditlev Lindhardt Johannesen1, Martin Bødtker Mortensen2, Børge Grønne Nordestgaard1
1Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Denmark; The Copenhagen City Heart Study, Copenhagen University Hospital - Bispebjerg Frederiksberg, Denmark; Institute of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Denmark.
Insights
Identifying the best cholesterol marker for atherosclerotic cardiovascular disease (ASCVD) risk is complex. Discordance analyses reveal that elevated LDL, non-HDL cholesterol, or apoB indicate risk, especially in treated patients.
Area of Science:
- Cardiology and Atherosclerosis Research
- Biomarker Discovery and Validation
- Clinical Risk Assessment
Background:
- Identifying optimal cholesterol markers for atherosclerotic cardiovascular disease (ASCVD) risk has been a long-standing challenge.
- High correlation between low-density-lipoprotein (LDL) cholesterol, non-high-density-lipoprotein (non-HDL) cholesterol, and apolipoprotein B (apoB) complicates direct comparison.
- Discordance analyses, examining disagreements between these markers, have emerged as a key approach.
Purpose of the Study:
- To review and compare different methods of discordance analysis for cholesterol markers in ASCVD risk assessment.
- To discuss the complexities and interpretation challenges associated with discordance analyses.
- To evaluate the clinical applicability of various discordance approaches, particularly in treated versus untreated individuals.
Main Methods:
- Review of studies employing discordance analyses based on cut-points, percentiles, or residuals.
- Examination of the association between discordant lipid levels and ASCVD risk, using concordant levels as reference.
- Analysis of how lipid-lowering medication influences discordance between cholesterol markers.
Main Results:
- Concordant low lipid levels are associated with the lowest ASCVD risk, while concordant high levels indicate the highest risk, showing heterogeneity across methods.
- Discordance between cholesterol markers is more prevalent in patients treated with lipid-lowering medication.
- Discordance by cut-points is intuitive; elevated LDL, non-HDL, or apoB indicate risk in untreated individuals, while non-HDL and apoB best predict residual risk in treated patients.
Conclusions:
- Direct comparison of results from different discordance approaches is limited due to heterogeneity in reference groups.
- Lipid-lowering medication significantly impacts cholesterol marker discordance and risk prediction.
- The cut-point method for discordance analysis offers clinical applicability, with specific markers indicating risk differently in treated and untreated populations.
Abstract:
For decades, studies have tried to identify the cholesterol marker that best reflects risk of atherosclerotic cardiovascular disease(ASCVD). Comparing low-density-lipoprotein(LDL) cholesterol, non-high-density-lipoprotein(non-HDL) cholesterol, and apolipoprotein B(apoB) as ASCVD risk markers has been challenged by high correlation between them. Thus, discordance analyses, directly addressing disagreements between the cholesterol markers, have emerged. Approaches adopted to define discordance originate in one of three methods: discordance by cut-points, discordance by percentiles, or discordance by residuals. Commonly, concordant lipid levels serve as reference examining the association between discordant lipid levels with risk of ASCVD. Importantly, concordant reference groups present heterogeneity of clinical relevance across different discordance methods as concordant low lipid levels associate with lowest ASCVD risk while concordant high lipid levels associate with highest risk. Thus, results from different discordance approaches cannot be directly compared. Moreover, discordance between cholesterol markers is more frequently seen in individuals treated with lipid-lowering medication than in individuals not treated with lipid-lowering medication. Accordingly, studies performing discordance analyses have reported inconsistent and even conflicting results. Discordance by cut-points appears the most intuitive and clinically applicable method; results from these analyses suggest that elevated LDL cholesterol, non-HDL cholesterol, or apoB levels in individuals not treated with lipid-lowering medication confer increased ASCVD risk while in individuals treated with lipid-lowering medication, elevated non-HDL cholesterol and apoB levels best indicate residual risk. Results from discordance analyses comparing LDL cholesterol, non-HDL cholesterol, and apoB in risk of ASCVD as well as complexities of discordance analyses and considerations regarding interpretations are discussed in this review.
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