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ApoB-containing lipoproteins: count, type, size, and risk of coronary artery disease
Jakub Morze1,2,3, Giorgio E M Melloni4, Clemens Wittenbecher1
1SciLifeLab, Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
Insights
Apolipoprotein B particle count accurately predicts coronary artery disease (CAD) risk, regardless of particle type or size. Lipoprotein(a) [Lp(a)] levels provide additional, independent risk information for CAD.
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Biomarkers
Background:
- Apolipoprotein B (apoB) concentration is a key marker for atherogenic lipoproteins and coronary artery disease (CAD) risk.
- The independent predictive value of apoB particle (apoB-P) type or size for CAD risk is not well-established.
Purpose of the Study:
- To investigate whether apoB particle type or size adds predictive value for incident CAD.
- To determine the combined prognostic value of apoB-P and lipoprotein(a) [Lp(a)] for CAD risk assessment.
Main Methods:
- Prospective analysis of 207,368 UK Biobank participants without prior cardiovascular disease or diabetes.
- Cox regression models assessed associations between various lipid parameters (apoB-P, VLDL, LDL, particle size, Lp(a)) and incident CAD.
Main Results:
- A one SD increase in apoB-P was associated with a 33% higher CAD risk.
- While VLDL particles had higher per-particle risk than LDL, their contribution to overall risk was similar after accounting for particle abundance.
- Particle size did not predict CAD independently of apoB-P; Lp(a) provided additional independent prognostic value.
Conclusions:
- Total apoB-P count is the most accurate reflection of lipid-related atherosclerotic risk, unaffected by major particle type or size.
- Elevated Lp(a) levels independently increase CAD risk.
- Optimal assessment of dyslipidemia-related atherogenic risk requires considering both apoB-P and Lp(a) concentrations.
Background And Aims:
Apolipoprotein B concentration reflects the number of atherogenic lipoproteins and is recognized as a key lipid risk marker. Whether the type or size of apoB particle (apoB-P) adds predictive value for coronary artery disease (CAD) remains unclear.
Methods:
A prospective analysis of 207 368 UK Biobank participants with comprehensive lipoprotein profiling and no prior history of atherosclerotic disease, diabetes, or active lipid-lowering therapy was conducted. Multivariable-adjusted Cox regression models were used to examine the association between each of the following lipid parameters with incident CAD: (i) nuclear magnetic resonance-measured apoB-P, (ii) concentrations of individual lipoprotein classes [very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL)], (iii) size subclasses, (iv) average particle diameter, and (v) immunoassay-measured lipoprotein(a) [Lp(a)].
Results:
A one standard deviation (SD) increase in apoB-P was associated with a 33% higher CAD risk [hazard ratio (HR): 1.33, 95% CI: 1.30-1.36]. Although VLDL particles were observed to carry a higher per-particle risk (HR per 100 nmol/L: 1.22, 1.11-1.34) compared with LDL (HR per 100 nmol/L: 1.07, 1.05-1.08), this difference was counterbalanced after considering relative particle abundance (LDL 91% vs VLDL 9% of total apoB-P). Thus the respective HR per 1-SD were 1.09 (1.05-1.14) and 1.24 (1.19-1.30). Particle diameter or size subclasses were not associated with CAD after apoB-P adjustment. The association of Lp(a) was robust even after apoB-P adjustment (HR:1.18, 1.16-1.20) and added independent prognostic value for CAD (area under curve: 0.769 vs 0.774, P < .001).
Conclusions:
Lipid-related atherosclerotic risk is most accurately reflected by the total count of apoB-P and is largely unaffected by the major particle type (VLDL, LDL) or size. Elevated count of Lp(a) adds additional risk, and thus adequate assessment of atherogenic risk from dyslipidemia is best accomplished by consideration of both apoB-P and Lp(a) concentrations.
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