Physicians' Academy for Cardiovascular Education

ApoC-III distribution in lipoproteins does not provide incremental predictive value for CAD

Relationship of lipoprotein-associated apolipoprotein C-III to lipid variables and coronary artery disease risk: The EPIC-Norfolk Prospective Population Study

Literature - van Capelleveen JC, Lee S-R, Verbeek R, et al. - J Clin Lipidol 2018; published online ahead of print

Introduction and methods

Apolipoprotein C-III (apoC-III) is a circulating apolipoprotein that inhibits the activation of lipoprotein lipase (LPL), thereby hindering triglyceride (TG) hydrolysis, and apoC-III plays an important role in the metabolism of triglyceride-rich lipoproteins (TRL).Several lines of evidence have suggested a causal relationship between apoC-III levels and coronary artery disease (CAD) [1-3]. The distribution of apoC-III among circulating lipoproteins and their respective predictive risk compared to apoC-III are unclear.

The association between lipoprotein-associated apoC-III levels and CAD risk was evaluated in a nested case-control analysis of the EPIC-Norfolk prospective population study [4]. For this purpose the apoC-III content on apolipoprotein B-100 (apoC-III-apoB), apolipoprotein A-I (apoC-III-apoAI), and lipoprotein(a) (apoC-III-Lp(a)) containing lipoproteins was determined in plasma samples (using the recently developed quantitative high-throughput sandwich chemiluminescent enzyme-linked immunoassays [ELISA]), and indices of “total apoC-III-apoB” and “total apoC-III-apoAI” were calculated by multiplying these measures with plasma apoB and apoA-I concentrations.

The EPIC-Norfolk cohort study includes 25,663 individuals, aged 45-79 years, who were recruited between 1993 and 1997. For the present analysis, 1,879 participants without a history of heart attack or stroke at baseline, who developed CAD during follow-up until 2003 were selected. Moreover, a control group (N=832) of apparently healthy study participants without CAD, was used for comparison. The duration of follow-up was 7.4 years.

Main results


Immuno-assay measurement of apoC-III on individual lipoproteins did not provide additional predictive information on the risk of CAD events in patients in the primary care setting, compared with total plasma apoC-III measurement. It remains to be established whether these biomarkers can predict future risk in individuals with established CVD.


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