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Non-HDL Cholesterol and Apolipoprotein B Measures and Risk of Atherosclerotic Cardiovascular Disease
Camilla Ditlev Lindhardt Johannesen1,2,3,4, Anne Langsted1,2,3,4, Børge Grønne Nordestgaard1,2,3,4
1Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev Gentofte, Herlev, Denmark.
Insights
Non-high-density-lipoprotein (non-HDL) cholesterol and apolipoprotein B (apoB) independently predict atherosclerotic cardiovascular disease (ASCVD) risk. Both markers provide unique information, suggesting cholesterol content and particle number are crucial for risk assessment.
Area of Science:
- Cardiology
- Biochemistry
- Epidemiology
Background:
- Non-high-density-lipoprotein (non-HDL) cholesterol and apolipoprotein B (apoB) are established biomarkers for atherosclerotic cardiovascular disease (ASCVD) risk.
- The relative superiority and independent predictive value of non-HDL cholesterol versus apoB for ASCVD risk remain subjects of investigation.
- Understanding the distinct contributions of non-HDL cholesterol and apoB is crucial for refining cardiovascular risk stratification.
Purpose of the Study:
- To determine if non-high-density-lipoprotein (non-HDL) cholesterol provides incremental information on ASCVD risk beyond apolipoprotein B (apoB).
- To assess whether apolipoprotein B (apoB) offers additional ASCVD risk prediction beyond non-high-density-lipoprotein (non-HDL) cholesterol.
- To evaluate the combined and independent predictive power of non-HDL cholesterol and apoB for major adverse cardiovascular events.
Main Methods:
- Analysis of the Copenhagen General Population Study, a large contemporary cohort of Danish individuals (n=94,398) without lipid-lowering medication.
- Prospective assessment of myocardial infarction (MI) and ASCVD events over a median follow-up of 13.2 years using Cox proportional hazards regression.
- Evaluation of non-HDL cholesterol and apoB as continuous variables and categorized by concordance/discordance relative to median values.
Main Results:
- Higher levels of both non-HDL cholesterol and apoB were independently associated with increased risk of MI and ASCVD.
- For a 1-SD increase, the multivariable-adjusted hazard ratio for ASCVD was 1.16 for non-HDL cholesterol and 1.14 for apoB.
- Concordantly high levels of both non-HDL cholesterol and apoB conferred the highest ASCVD risk (HR=1.36), while discordant levels also showed significant risk elevation.
Conclusions:
- Non-high-density-lipoprotein (non-HDL) cholesterol and apolipoprotein B (apoB) provide complementary information for ASCVD risk prediction in individuals not on lipid-lowering therapy.
- Both cholesterol content (reflected by non-HDL) and particle number (reflected by apoB) are important determinants of cardiovascular risk.
- These findings underscore the value of assessing both non-HDL cholesterol and apoB for comprehensive cardiovascular risk assessment.
Importance:
Non-high-density-lipoprotein (non-HDL) cholesterol and apolipoprotein B (apoB) are better markers of atherosclerotic cardiovascular disease (ASCVD) risk than low-density-lipoprotein cholesterol, but whether non-HDL cholesterol or apoB is superior to the other is less clear.
Objective:
To assess if non-HDL cholesterol provides information on ASCVD beyond apoB, and vice versa.
Design, Setting, And Participants:
The Copenhagen General Population Study, a population-based contemporary cohort study in Danish individuals recruited in 2003-2015 with a median of 13.2 (IQR, 10.3-15.8) years of follow-up, included women and men not taking lipid-lowering medication and with non-HDL cholesterol and apoB measurements at baseline. Data were analyzed from January 3 through June 23, 2025.
Exposures:
Continuous non-HDL cholesterol and apoB assessed as absolute levels and SDs as well as categories of concordance/discordance between non-HDL cholesterol and apoB defined by medians-(1) concordant low: non-HDL cholesterol and apoB less than the median; (2) discordant high apoB: non-HDL cholesterol less than the median and apoB greater than the median; (3) discordant high non-HDL cholesterol: non-HDL cholesterol greater than the median and apoB less than the median; and (4) concordant high: non-HDL cholesterol and apoB greater than median values.
Main Outcomes And Measures:
Myocardial infarction and ASCVD events estimated by Cox proportional hazards regressions using age as 19 years the underlying time scale and delayed entry (left truncation) at baseline.
Results:
This cohort study in 94 398 individuals (53 042 women [56%]) with a total of 2462 first myocardial infarction (MI) and 5723 first ASCVD events found that any higher levels of non-HDL cholesterol or apoB on continuous scales were associated with similar increased risk of MI and ASCVD; for 1-SD higher levels, the multivariable-adjusted hazard ratio (HR) for ASCVD was 1.16 (95% CI, 1.13-1.19) for non-HDL cholesterol (39 mg/dL) and 1.14 (95% CI, 1.12-1.17) for apoB (30 mg/dL). Further adjusting for non-HDL cholesterol in the apoB model, and vice versa, attenuated the HRs, although the findings were still significant. Compared with concordant low non-HDL cholesterol and apoB, the HR for MI was 1.32 (95% CI, 1.10-1.59) for discordant high apoB, 1.30 (95% CI, 1.05-1.60) for discordant high non-HDL cholesterol, and 1.69 (95% CI, 1.53-1.85) for concordant high non-HDL cholesterol and apoB; corresponding values for ASCVD were 1.14 (95% CI, 1.01-1.29), 1.21 (95% CI, 1.06-1.38), and 1.36 (95% CI, 1.28-1.44).
Conclusions And Relevance:
In this study, in individuals not taking lipid-lowering medication, non-HDL cholesterol provides information on ASCVD risk beyond apoB, and vice versa, indicating that both cholesterol content and particle number are important for risk.
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