The assessment of lipid-related cardiovascular risk has traditionally focused on low-density lipoprotein cholesterol (LDL-C), but debate continues over the relative atherogenicity of different apolipoprotein B-containing lipoprotein particles (apoB-P). A large prospective analysis published in the European Heart Journal provides clarity, suggesting that the total count of apoB-P and lipoprotein(a) (Lp(a)) are the most critical measures for predicting coronary artery disease (CAD) risk, superseding the importance of particle type or size.¹

Researchers, led by Dr Jakub Morze from Chalmers University of Technology, Gothenburg, Sweden, conducted a prospective analysis of 207,368 participants from the UK Biobank. The cohort included individuals with no prior history of atherosclerotic disease, diabetes, or active lipid-lowering therapy. Using nuclear magnetic resonance (NMR) spectroscopy, the study examined the association between various lipid parameters—including apoB-P, concentrations of very-low-density lipoprotein (VLDL) and LDL, size subclasses, and immunoassay-measured Lp(a)—and the primary endpoint of incident CAD over a median follow-up of 13.7 years.

The analysis revealed that a one standard deviation (SD) increase in the total count of apoB-P was associated with a 33% higher risk of CAD (hazard ratio [HR]: 1.33; 95% CI: 1.30–1.36). While VLDL particles demonstrated a higher per-particle risk compared to LDL particles, this was offset by the fact that LDL particles constitute the vast majority (91%) of circulating apoB-P. Consequently, after accounting for total apoB-P concentration, neither particle size, average particle diameter, nor the specific type of apoB-P (VLDL vs LDL) significantly improved risk prediction.

In contrast, the risk associated with Lp(a) was substantial and independent of other lipoproteins. A 1-SD increase in Lp(a) was linked to an 18% higher CAD risk (HR: 1.18; 95% CI: 1.16–1.20) even after adjusting for apoB-P. The addition of Lp(a) to a model with clinical covariates and apoB-P significantly improved the predictive performance for CAD (area under curve: 0.769 vs 0.774; p<0.001).

These findings reinforce the central role of the total number of atherogenic particles in driving atherosclerosis, a concept supported by other major studies.² The study suggests that for routine clinical risk assessment, focusing on the total apoB-P count provides a comprehensive measure of risk from VLDL and LDL particles combined. The independent, additive risk from Lp(a) highlights the need for its separate measurement to fully capture an individual's lipid-mediated risk. "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," the authors concluded, adding that "adequate assessment of atherogenic risk from dyslipidemia is best accomplished by consideration of both apoB-P and Lp(a) concentrations."¹

While this study clarifies risk prediction, the authors note that definitive evidence on the clinical benefit of specifically targeting VLDL and Lp(a) will come from ongoing and future clinical trials of novel therapies. Further research is also warranted to see if these findings hold true in higher-risk populations, such as patients with diabetes or those already on statin therapy.

References

1. Morze J, Melloni GEM, Wittenbecher C, et al. ApoB-containing lipoproteins: count, type, size, and risk of coronary artery disease. Eur Heart J. 2025;46(27):2691–2701. https://doi.org/10.1093/eurheartj/ehaf207.

2. Marston NA, Giugliano RP, Melloni GEM, et al. Association of apolipoprotein B-containing lipoproteins and risk of myocardial infarction in individuals with and without atherosclerosis: distinguishing between particle concentration, type, and content. JAMA Cardiol. 2022;7(3):250–256. https://doi.org/10.1001/jamacardio.2021.5083.

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