The emerging concept of "individualized cholesterol-lowering therapy": A change in paradigm

Abstract

High LDL-cholesterol concentrations constitute a risk for atherosclerotic cardiovascular disease. By consensus, cholesterol-lowering therapy is initiated with a statin that reduces endogenous cholesterol synthesis, upregulates hepatic LDL receptor activity, increases LDL clearance and lowers LDL-cholesterol concentrations in the bloodstream. The efficacy of statin treatment is dose dependent and achieves a risk reduction of up to 50%. However, a substantial body of evidence suggests that a quarter of statin-treated patients do not respond adequately as a result of low endogenous cholesterol synthesis. In humans fractional cholesterol absorption varies from 20% to 80%. High cholesterol absorbers, which are characterized by a low-to-normal cholesterol synthesis, exhibit poor responsiveness to statin treatment. On the other hand, the cholesterol absorption inhibitor ezetimibe effectively reduces serum cholesterol levels in these patients. On this background, we suggest to "get personal" and individualize cholesterol-lowering therapies, according to the individual's status of cholesterol synthesis and absorption.

Keywords: Acute coronary syndrome; Cholesterol balance; Cholesterol synthesis; Coronary artery disease; Lipid metabolism; Sterol absorption.