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

Accepted version
Peer-reviewed

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Article

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Authors

van Capelleveen, JC 
Bernelot Moens, SJ 
Yang, X 
Kastelein, JJP 
Wareham, NJ 

Abstract

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.

Description

Keywords

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

Journal Title

Arteriosclerosis, Thrombosis, and Vascular Biology

Conference Name

Journal ISSN

1079-5642
1524-4636

Volume Title

37

Publisher

American Heart Association
Sponsorship
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MR/N003284/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)