van Capelleveen Julian C, Bernelot Moens Sophie J, Yang Xiaohong, Kastelein John J P, Wareham Nicholas J, Zwinderman Aeilko H, Stroes Erik S G, Witztum Joseph L, Hovingh G Kees, Khaw Kay-Tee, Boekholdt S Matthijs, Tsimikas Sotirios
From the Department of Vascular Medicine (J.C.v.C., S.J.B.M., J.J.P.K., E.S.G.S., G.K.H.), Department of Clinical Epidemiology and Biostatistics (A.H.Z.), and Department of Cardiology (S.M.B.), Academic Medical Center, Amsterdam, The Netherlands; Vascular Medicine Program, Division of Cardiology (X.Y., S.T.) and Division of Endocrinology and Metabolism (J.L.W.), Department of Medicine, University of California San Diego, La Jolla; Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.J.W.); and Department of Public Health and Primary Care, University of Cambridge, United Kingdom (K.-T.K.).
Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1206-1212. doi: 10.1161/ATVBAHA.117.309007. Epub 2017 May 4.
Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk.
Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48-2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11-1.94). ApoC-III levels were positively correlated with triglyceride levels, (=0.39), particle numbers of very-low-density lipoprotein (=0.25), intermediate-density lipoprotein (=0.23), small dense low-density lipoprotein (=0.26), and high-sensitivity C-reactive protein (=0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number (=-0.11), <0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by triglyceride elevation (triglyceride, very-low-density lipoprotein, and intermediate-density lipoprotein particles), small low-density lipoprotein particle size, and high-sensitivity C-reactive protein.
ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association.
载脂蛋白C-III（apoC-III）是甘油三酯代谢的关键调节因子。富含甘油三酯的脂蛋白水平升高和apoC-III水平与冠状动脉疾病（CAD）风险存在因果联系。apoC-III增加CAD风险的机制在很大程度上仍不清楚。本研究旨在证实apoC-III血浆水平与CAD风险之间的关联，并探讨哪些脂蛋白亚组分促成了apoC-III与CAD风险之间的这种关系。
在欧洲癌症前瞻性调查（EPIC）-诺福克研究的一项巢式病例对照研究的基线样本中测量血浆apoC-III水平。该研究包括2711名表面健康的研究参与者，其中832人随后患上了CAD。我们研究了基线apoC-III水平与CAD发病风险、通过核磁共振光谱测量的脂蛋白亚组分以及炎症生物标志物之间的关联。apoC-III水平与CAD风险显著相关（最高五分位数与最低五分位数相比，比值比为1.91；95%置信区间为1.48-2.48），在对传统CAD风险因素进行调整后仍具有显著性（比值比为1.47；95%置信区间为1.11-1.94）。apoC-III水平与甘油三酯水平（r=0.39）、极低密度脂蛋白颗粒数（r=0.25）、中间密度脂蛋白（r=0.23）、小而密低密度脂蛋白（r=0.26）以及高敏C反应蛋白（r=0.15）呈正相关，而与大低密度脂蛋白颗粒数呈负相关（r=-0.11），各相关性均P<0.001。中介分析表明，apoC-III与CAD风险之间的关联可由甘油三酯升高（甘油三酯、极低密度脂蛋白和中间密度脂蛋白颗粒）、小低密度脂蛋白颗粒大小以及高敏C反应蛋白来解释。
apoC-III水平与CAD发病风险显著相关。残余脂蛋白、小而密低密度脂蛋白水平升高以及低度炎症可能解释了这种关联。
