CETP is an enzyme responsible for moving cholesterol esters and triglycerides between VLDL, LDL, and HDL. Lower CETP levels promote HDL formation. Since higher HDL levels are associated with decreased risk of atherosclerosis, the activity of CETP is thought to promote development of the disease by reducing HDL levels. Likewise, rare variants in the CETP gene leading to increased CETP activity are associated with increased risk of atherosclerosis. Paradoxically, a D442G variant of CETP that decreases its activity and increases HDL levels is also associated with more severe atherosclerosis. Although there is much hope that CETP inhibition will raise HDL levels and reduce atherosclerosis, initial CETP inhibitor trials led to augmented HDL levels without improvement in atherosclerosis-related endpoints.
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