The Effect Of Metformin On Blood Lipids And Lipoprotein Subfraction Distribution In Non-diabetic Patients With Coronary Heart Disease

Background: Coronary heart disease(CHD)is one of the most common diseases leading to death in the world.Dyslipidemia is the pathogenic risk factor,in which low-density lipoprotein cholesterol(LDL-C)is the key target for lipid control.Despite achieving optimal LDL-C levels,cardiovascular events still remain,which is refered as residual cardiovascular risk.High lipoprotein(a)[Lp(a)] levels can partly explain the residual risk.Statins,the basic lipid-lowering medications,may produce an increase in circulating Lp(a).The drug which can reduce the concentration of Lp(a)is limited and inconvenient to use.Objective: To explore the effect of statins combined with metformin on blood lipids with Lp(a)as the core in non-diabetic patients with CHD.To find optimal management of residual risk-related dyslipidemia in patients with coronary heart disease.Methods: A total of 200 non-diabetic patients with CHD and high Lp(a)levels were admitted to our hospital,and 80 patients were included and randomized.The patients were divided into control group and metformin group.9 patients were excluded and eventually 71 patients were included in the analysis: 55 males and 16 females with average(58.85±11.08)years old.Patients in the control group were treated with statins ± ezetimibe for lipid-lowering,while patients in the metformin group were treated with metformin 850 mg twice a day on the basis of statins ± ezetimibe.The body weight,blood lipids,blood sugar and other biochemical elements were recorded and measured at baseline and one month of treatment.Meanwhile,blood samples were collected for the detection of Lp(a)level,proprotein converting enzyme subtilisin 9(PCSK9)concentration,and lipoprotein subfraction distribution.Result: 1)The concentration of Lp(a)in the treatment of metformin for one month did not change compared with the control group.2)There was no difference in triglyceride,triglyceride and cholesterol in triglyceride-rich lipoproteins and remnant cholesterol levels between the metformin and control group within one month of treatment.3)During the one-month follow-up,LDL-C and low-density lipoprotein particles in the metformin group significantly decreased because of the decreasing of small and dense low-density lipoprotein particles and cholesterol levels.At the same time,plasma PCSK9 levels decreased and correlated with small and dense low-density lipoprotein particles and cholesterol concentrations.4)At one month,the cholesterol and phospholipids level in large high-density lipoprotein(HDL)particles in the metformin group decreased,but it was unchanged in small HDL particles.Furthermore,the decrease of triglyceride levels in HDL particles was more prominent than that in the control group.Conclusions: In non-diabetic patients with CHD,metformin did not alter the level of lipid components associated with residual cardiovascular risk,including Lp(a),triglyceride-rich lipoprotein cholesterol,and remnant cholesterol.But it can decrease the concentration of small and dense LDL particles and their cholesterol content to decline the concentration of total low-density lipoprotein particles and LDL-C.The lipid-lowering effect of metformin is attributed to the decrease in plasma PCSK9 levels.