Morze Jakub, Melloni Giorgio E M, Wittenbecher Clemens, Ala-Korpela Mika, Rynkiewicz Andrzej, Guasch-Ferré Marta, Ruff Christian T, Hu Frank B, Sabatine Marc S, Marston Nicholas A
SciLifeLab, Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Eur Heart J. 2025 Jul 14;46(27):2691-2701. doi: 10.1093/eurheartj/ehaf207.
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.
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)].
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).
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.
载脂蛋白B浓度反映致动脉粥样硬化脂蛋白的数量，被认为是关键的脂质风险标志物。载脂蛋白B颗粒（apoB-P）的类型或大小是否能增加冠状动脉疾病（CAD）的预测价值尚不清楚。
对207368名英国生物银行参与者进行前瞻性分析，这些参与者具有全面的脂蛋白谱，且无动脉粥样硬化疾病、糖尿病或积极降脂治疗的既往史。多变量调整的Cox回归模型用于检验以下每种脂质参数与CAD发生之间的关联：（i）核磁共振测量的apoB-P，（ii）各脂蛋白类别的浓度[极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）]，（iii）大小亚类，（iv）平均颗粒直径，以及（v）免疫测定法测量的脂蛋白（a）[Lp（a）]。
apoB-P每增加一个标准差（SD），CAD风险升高33%[风险比（HR）：1.33，95%置信区间：1.30-1.36]。尽管观察到VLDL颗粒每颗粒的风险（每100 nmol/L的HR：1.22，1.11-1.34）高于LDL（每100 nmol/L的HR：1.07，1.05-1.08），但在考虑相对颗粒丰度后（LDL占总apoB-P的91%，VLDL占9%），这种差异被抵消。因此，每1-SD的相应HR分别为1.09（1.05-1.14）和1.24（1.19-1.30）。在调整apoB-P后，颗粒直径或大小亚类与CAD无关。即使在调整apoB-P后，Lp（a）的关联仍然很强（HR：1.18，1.16-1.20），并且为CAD增加了独立的预后价值（曲线下面积：0.769对0.774，P<.001）。
脂质相关的动脉粥样硬化风险最准确地由apoB-P的总数反映，并且在很大程度上不受主要颗粒类型（VLDL、LDL）或大小的影响。Lp（a）计数升高会增加额外风险，因此通过同时考虑apoB-P和Lp（a）浓度，能最好地完成对血脂异常所致动脉粥样硬化风险的充分评估。
