Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk The EPIC-Norfolk Prospective Population Study

作者：van Capelleveen Julian C; Moens Sophie J Bernelot; 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

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37(6): 1206-+.

DOI：10.1161/ATVBAHA.117.309007

• apolipoprotein CIII
• C-reactive protein
• coronary artery disease
• lipoproteins
• triglycerides

Objective-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.
Approach and Results-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, (r=0.39), particle numbers of very-low-density lipoprotein (r=0.25), intermediate-density lipoprotein (r=0.23), small dense low-density lipoprotein (r=0.26), and high-sensitivity C-reactive protein (r=0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number (r=-0.11), P<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.
Conclusions-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.

• 出版日期2017-6