Related Experiment Video
Updated: Jun 27, 2025
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular
Allan D Sniderman1, Line Dufresne1, Karol M Pencina1,2
1Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, Department of Medicine, McGill University Health Centre-Royal Victoria Hospital, 1001 Boulevard Décarie, Montreal, Québec H4A 3J1, Canada.
Insights
Apolipoprotein B (apoB) is a superior marker for atherosclerotic cardiovascular disease (ASCVD) risk than LDL-C, non-HDL-C, and triglycerides. These standard lipid markers are insufficient for accurate ASCVD risk assessment in clinical practice.
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Preventive Cardiology
Background:
- Apolipoprotein B (apoB) is recognized as a more accurate marker for atherosclerotic cardiovascular disease (ASCVD) risk.
- Clinical adoption of apoB testing remains low, with routine care relying on low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides.
- This study investigates the sufficiency of standard lipid markers for cardiovascular risk assessment.
Purpose of the Study:
- To evaluate if LDL-C, non-HDL-C, and triglycerides are adequate surrogates for apoB in predicting ASCVD risk.
- To determine the variability of apoB across different levels of standard lipid markers.
- To assess the independent predictive value of apoB beyond standard lipid measurements.
Main Methods:
- Analysis of a large UK Biobank cohort (293,876 adults) with a median 11-year follow-up for new-onset ASCVD.
- Graphical examination of apoB distribution relative to LDL-C, non-HDL-C, and triglycerides.
- Construction of apoB residuals after accounting for standard lipids to assess independent predictive value for ASCVD events using proportional hazards regression.
Main Results:
- ApoB showed high correlation with LDL-C and non-HDL-C (r=.96), but lower with triglycerides (r=.42).
- Wide ranges of apoB values were observed at given levels of LDL-C, non-HDL-C, and triglycerides, indicating significant variability.
- Residual apoB independently predicted new-onset ASCVD events even after adjusting for LDL-C, non-HDL-C, and HDL-C, whereas standard lipid residuals did not remain significant when apoB was included.
Conclusions:
- Significant variability in apoB at standard lipid levels and its independent predictive power for ASCVD events demonstrate inadequacy of LDL-C, non-HDL-C, and triglycerides as sole risk assessment tools.
- ApoB provides crucial risk information not captured by conventional lipid profiles.
- Routine clinical care should consider apoB measurement for more accurate ASCVD risk stratification.
Background And Aims:
Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care.
Methods:
A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C.
Results:
ApoB was highly correlated with LDL-C and non-HDL-C (Pearson's r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model.
Conclusions:
High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.
Related Concept Videos
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:18Lipids: Dietary Sources and Requirements
01:31Lipid-derived Compounds in the Human Body
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...