Apolipoprotein E-Containing High-Density Lipoprotein is Independently Associated with Atherosclerotic Plaque Progression

Mounting evidence suggests apolipoprotein E-containing high-density lipoprotein cholesterol (APOE-HDLC) as an indicator of the anti-atherogenic function of HDLC, but data are lacking on whether or not APOE-HDLC is involved in the development of atherosclerosis in humans. This study was performed to explore whether or not APOE-HDLC is associated with atherosclerotic plaque progression in humans. Among 823 participants 45 to 74 years old who were free of cardiovascular disease, we assessed nuclear magnetic resonance spectroscopy-measured HDL particle concentrations, APOE-HDLC levels and HDLC levels at baseline, and performed carotid ultrasound measurements in surveys conducted in 2002 and again in 2007 after a 5-year interval. The ratio of APOE-HDLC to total HDLC (APOE-HDLC/HDLC ratio) was calculated to assess the relative proportion of APOE-HDLC in total HDLC, given the strong correlation between them. The baseline APOE-HDLC/HDLC ratio was significantly associated with the risk of 5-year plaque progression (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.53-0.95), which is independent of the ratio of HDLC to the HDL particle number (HDLC/P ratio). In particular, participants with an HDLC/P ratio ≥ 44.8 (denoted very high level of cholesterol content per HDLP, a marker of dysfunctional HDL) had a 36% reduced 5-year plaque progression risk (RR = 0.64; 95% CI = 0.43-0.97) if combined with the highest APOE-HDLC/HDLC ratio, as compared with the lowest APOE-HDLC/HDLC ratio. These results highlight the potential utility of APOE-containing HDL as a candidate emerging biomarker for the anti-atherosclerotic function of HDL particles.