Influence of CETP on High-Density Lipoprotein Subclasses in Patients with Coronary Heart Disease

Background: Inhibition of plasma cholesteryl ester transfer protein (CETP) can effectively reduce the risk of atherosclerotic cardiovascular disease by increasing high-density lipoprotein cholesterol (HDL-C) levels, but the effect of CETP on the distributions of HDL subclasses in patients with coronary heart disease (CHD) is still elusive. Methods: To investigate the correlation between the level of CETP and the distributions of HDL subclasses, 121 healthy controls and 139 patients with CHD were selected as study subjects. The plasma levels of CETP and each HDL subclass were respectively determined by enzyme-linked immunosorbent assay and two-dimensional gel electrophoresis associated with the immunodetection method. At the same time, blood biochemical data from all subjects were collected, including the levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C, apoA1, and apoB100. Correlation analysis and multiple regression analysis among the plasma HDL subclass values and biochemical parameters in subjects with CHD were conducted. Results: As the plasma level of CETP increases, the contents of TC, TG, and apoB100/A1 were obviously elevated, while the levels of HDL-C and apoA1 decreased significantly. For distributions of HDL subclasses, large-sized HDL2a and HDL2b were markedly decreased in the middle CETP group (p < 0.05) and the high CETP group (p < 0.001) compared to the low CETP group, while the small-sized pre beta(1)-HDL was obviously increased. Intriguingly, when the plasma concentration of TC or TG in patients with CHD was higher, the elevated pre beta(1)-HDL and reduced HDL2a were more dependent on the increase in CETP. Furthermore, correlation analysis and multiple regression analysis also confirmed that plasma CETP was positively correlated with prefil-HDL levels and negatively correlated with HDL2b levels. Conclusions: The distributions of HDL subclasses were associated with CETP in patients with CHD, especially in those with high levels of TC and TG. CETP levels were associated with an increase in small-sized prefil-HDL and a decrease in large-sized HDL subclasses, which indicated that CETP might be a limiter of reverse cholesterol transport and HDL maturation.