Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study.
Arteriosclerosis, thrombosis, and vascular biology 2017 ; 37: 1206-1212.
van Capelleveen JC, Bernelot Moens SJ, Yang X, Kastelein JJP, Wareham NJ, Zwinderman AH, Stroes ESG, Witztum JL, Hovingh GK, Khaw KT, Boekholdt SM, Tsimikas S
DOI : 10.1161/ATVBAHA.117.309007
PubMed ID : 28473441
PMCID : PMC5484077
URL : https://www.ahajournals.org/doi/10.1161/ATVBAHA.117.309007
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.