Table of Contents

ABSTRACT

Cholesterol is one of the major components of cholesteryl esters, which possesses cholesteryl ester transfer protein (CETP) that circulates widely in the blood. It is possible that the concentration of CETP in the blood is a potential determinant for increased risk of cardiovascular diseases (CVDs), including stroke. The low risk of CVDs among Japanese may be explained by genetic deficiency of CETP activity and its association with an improved lipid profile, resulting in a decrease in cholesterol accompanied with a high level of high-density lipoprotein (HDL), leading to lower premature atherosclerosis low-density lipoprotein (LDL) in Japanese. The activity of CETP tends to result in a net mass transfer of cholesteryl esters from HDL to very low-density lipoprotein (VLDL) and LDL, and a net mass transfer of triglycerides from VLDL to LDL and HDL. Inhibiting CETP can reduce these exchanges, resulting in increased concentrations of HDL cholesterol and decreased concentrations of cholesterol in apolipoprotein (Apo) B-containing particles of VLDL and LDL. It is possible that treatment with CETP inhibitors, such as obicetrapib, may reverse an atherogenic lipid profile by lowering LDL-C, non-HDL-C, ApoB, LDL particle levels. This is specific to small LDL particles and lipoprotein(a) (Lp(a)) and thus, raises pre-beta HDL as well as mature HDL particles and ApoA-1 and ApoE, which are protective against CVDs.

Keywords: Cholesterol, LDL, antioxidants, low HDL, atherosclerosis, dyslipidemia