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
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 . 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.
- At baseline, apoC-III-apoB, apoC-III-Lp(a), apoC-III-apoAI, and blood lipid values were significantly higher in CAD cases, compared with controls (all P values ≤0.005).
- ApoCIII-apoAI was significantly associated with CAD risk (OR for highest compared to lowest quintile: 1.42; 95%CI: 1.09-1.84), but significance was lost after adjustment for CAD risk factors (OR: 1.14; 95%CI: 0.86-1.52).
- ApoC-III-apoB was also associated with CAD risk when comparing highest to lowest quintile (OR: 1.46; 95%CI: 1.12-1.89), but significance was lost after adjusting for CAD risk factors (OR: 1.28; 95%CI: 0.96-1.70).
- ApoC-III-Lp(a) was significantly associated with CAD risk before and after adjustment for CAD risk factors (OR: 1.66; 95%CI: 1.29-2.15; ORadj: 1.35; 95%CI: 1.02-1.78), but this significance was lost after additional adjustment for lipid variables and apoC-III.
- ApoC-III content in apoA-I-containing lipoproteins was not associated with CAD risk (OR: 1.22; 95%CI: 0.92-1.63), while apoC-III content in apoB-containing lipoproteins was significantly associated with CAD risk (OR: 1.81; 95%CI: 1.38-2.38; OR adjusted for CAD risk factors: 1.57; 95%CI: 1.16-2.12), but the association lost its significance after further adjustment for lipid values.
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.