Association of cholesterol synthesis/absorption markers with the cholesterol-lowering efficacy of atorvastatin


  In November 2013,Professor Qi Yue and Professor Zhao Dong of Beijing Anzhen Hospital Affiliated to Capital Medical University conducted a study to explore whether the synthesis/absorption status of cholesterol affects the cholesterol-lowering effect of statins and whether it can predict the cholesterol-lowering effect of statins.

  This study is based on a specific clinical problem:many patients with conventional or even higher dose statin therapy,blood cholesterol reduction is not significant or difficult to achieve.The possible reasons are as follows:Cholesterol in human blood circulation mainly comes from the body's own synthesis and intestinal absorption and reabsorption,and there is a negative feedback regulation between cholesterol synthesis and absorption.Statin therapy only lowers the cholesterol produced by the body.A considerable number of patients with hypercholesterolemia may be caused by increased cholesterol absorption,and the effect of statin therapy is inevitably poor.The combination therapy of statins and selective cholesterol absorption inhibitors provides a new means to effectively reduce cholesterol levels.It is important for clinicians to understand the individual's cholesterol synthesis and absorption status before treatment,and to select statin monotherapy or combination therapy in a targeted manner.

  We designed a 4-week,open,before and after controlled clinical trial.In this study,306 patients at high risk of coronary heart disease who were treated with statins for the first time were treated with 20mg/d atorvastatin for 4 weeks,and the levels and changes of cholesterol synthesis and absorption markers and low density lipoprotein cholesterol(LDL-C)were observed before and after treatment.

  The study found significant individual differences in the efficacy of atorvastatin in lowering LDL-C,ranging from a maximum reduction of 74.5%to an increase in LDL-C levels of 31.9%,with an average reduction of 36.8%.The LDL-C lowering effect of atorvastatin is influenced by the level of endogenous cholesterol synthesis marker(7-encholestol)and cholesterol absorption marker(canolasterol)before treatment.The effect of atorvastatin on lowering LDL-C was significantly correlated with the level of synthesis before treatment,and the higher the endogenous synthesis before treatment,the better the effect of lowering LDL-C.However,the absorption level of cholesterol before treatment is also closely related to the effect of statins on lowering LDL-C.In patients with low absorption level before treatment,the absorption level was significantly increased after statin treatment to inhibit synthesis,which significantly opposed the effect of statins on lowering LDL-C.Patients with high levels of synthesis but low levels of absorption before treatment had the least reduction in LDL-C.This study demonstrates from multiple perspectives that the synthesis/absorption status of cholesterol has a combined effect on the cholesterol-lowering effect of statins and can predict the efficacy of statins.The results of this study provide evidence for the targeted selection of lipid-lowering drugs and the realization of individualized treatment,in order to bring more clinical benefits to patients.

  Source:Journal of Lipid Research

  Zhongyou Pharmaceutical Industry