Abstract 023: Presence of Apolipoprotein C-III Defines a High Density Lipoprotein Subtype that is not Inversely Associated with Incident Coronary Events
Background: High density lipoprotein (HDL; as measured by concentrations of either cholesterol [C] in HDL or by its major apolipoprotein [apo] AI), is inversely associated with risk of CHD. However, recent clinical trials question the cardioprotective benefits of raising HDL-C. Since HDLs comprise a structurally and metabolically diverse group of lipoproteins, it is possible that subpopulations of HDL could have different cardioprotective potential. ApoC-III is a small pro-inflammatory protein that resides on the surface of some lipoproteins. We previously found that apoC-III enhances the atherogenicity of VLDL and LDL particles. Here we investigated whether the presence or absence of apoC-III on HDL defines subtypes with differential associations with risk of future CHD.
Methods and Results: We measured the concentrations of apoAI and HDL-C in plasma separated according to apoC-III (by immunoaffinity chromatography) from initially healthy women and men from in a case-cohort nested within the Danish Diet, Cancer and Health Study. Between baseline (1993-1997) and the 2010, 1980 incident cases of CHD occurred (536 in women and 1444 in men). A random sample of the cohort (n=1720) was used for reference. In multivariable Cox regression models, the concentration of apoAI without apoC-III was inversely associated with risk of CHD (HR per 1 SD increase = 0.77; 95% CI: 0.67-0.88) whereas apoAI with apoC-III was not associated with CHD (HR=1.07; 0.95-1.20) (p heterogeneity= 0.002). Similarly, HDL-C without apoC-III was inversely associated with risk of CHD (HR=0.77; 0.67-0.89) and HDL-C with apoC-III was not associated (HR=0.98; 0.86-1.12) (p heterogeneity= 0.02). ApoC-III was found on approximately 9% of apoAI and 15% of HDL-C.
Conclusions: The presence of apoC-III may mark a dysfunctional HDL particle that does not protect against CHD. Novel measures of HDL subpopulations that better capture HDL function rather than absolute levels may be more relevant as therapeutic targets and for evaluation of cardiovascular risk.
- © 2013 by American Heart Association, Inc.