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

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2017 May 6

PMID 28473441

Citations 32

Authors

Julian C van Capelleveen

Sophie J Bernelot Moens

Xiaohong Yang

John J P Kastelein

Nicholas J Wareham

Aeilko H Zwinderman

Erik S G Stroes

Joseph L Witztum

G Kees Hovingh

Kay-Tee Khaw

S Matthijs Boekholdt

Sotirios Tsimikas

Affiliations

Soon will be listed here.

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, (=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.

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.

Citing Articles

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