Study On The Application Value Of Lipoprotein Particles In The Prediction And Treatment Of Coronary Heart Disease

Objective:Low-density lipoprotein cholesterol(LDL-C)is the primary target of therapy in patients with acute coronary syndromes(ACS)in guidelines worldwide.Recent clinical trial evidence confirms that there is substantial incremental reduction in risk for acute cardiovascular events when LDL-C is reduced to very low levels(< 50 mg/dl)in patients with established coronary artery disease,however,risk for events among these treated patients remained substantial.Data from multiple epidemiological studies have proven that LDL-P is better than LDL-C in predicting cardiovascular events,especially in patients with inconsistent of LDL-P and LDL-C.The measurement of LDL-P can provide a better risk indicator of coronary heart disease.In this study,NMR was used to evaluate the predictive value of lipoprotein particles and subfraction in the diagnosis and treatment of coronary heart disease,and to provide new ideas and new methods for clinical diagnosis and treatment.PCSK9 inhibitor,as a new lipid-lowering drug,has rarely been studied on lipoprotein particles and subfraction,especially in the Chinese population.To assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor(evolocumab)on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.Methods:1,569 patients admitted to Tianjin Chest Hospital from December 2018 to October2019 were enrolled.According to the results of coronary angiography,the patients were divided into CHD group and non-CHD group.Traditional risk factors,routine lipids,lipoprotein particles and subfractions of all patients were analyzed.Logistic multivariate regression model was used to screen the risk factors related to CHD.A total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group(n = 54)or the control group(n = 45).The combination therapy of PCSK9 inhibitor(Repatha(?),140 mg,q2w)and moderate statin(Rosuvastatin,10 mg,qn)was administered in the experimental group,with statin monotherapy(Rosuvastatin,10 mg,qn)in the control group.The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment,and the achievement of LDL-C therapeutic target in both groups were analyzed.Results:1.The age,gender,history of hypertension,diabetes mellitus and smoking history of CHD group were significantly higher than those of non-CHD group.The difference was statistically significant(P < 0.05).The triglyceride,IDL-C and VLDL-C in CHD group were significantly higher than those in non-CHD group(P < 0.05).There was no significant difference in cholesterol and LDL-C between two groups(P > 0.05).The levels of IDL-P,VLDL-P,LDL-P3,LDL-P4 and LDL-P6 in CHD group were significantly higher than those in non-CHD group(P < 0.05).2.Multivariate regression analysis showed that the traditional risk factors gender,diabetes,hypertension,smoking,age and the risk of CHD were significantly positive correlation,and they were independent risk factors for CHD.Lp(a),VLDL-P and LDL-P6 were independent risk factors for CHD.There was no significant correlation between other lipoprotein particles and CHD.3.The area under the ROC curve(AUC)of age,gender,smoking,hypertension and diabetes as the traditional risk factors for predicting CHD was 0.711.The area under the ROC curve(AUC)of traditional risk factors combined with LP(a),VLDL-P,and LDL-P6(small particles)for predicting CHD was 0.711.4.In the experimental group,after 8 weeks of evolocumab combination treatment,the concentrations of blood lipids(TC,LDL-C and its subfractions [LDL-1 to 6],VLDLC and its subfractions [VLDL-1 to 5],IDL-C,and HDL-C),lipoprotein particles,and their subfractions [VLDL-P,IDL-P,LDL-P,and its subfractions [LDL-P1 to 6],apo B,and LP(a)] demonstrated therapeutic benefits with statistical significance(P <0.05).The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles(LDL-P 5 + 6),which was significantly more prominent than the decrease in medium-sized LDL-P(LDL-P3 + 4)and largesized LDL-P(LDL-P1 + 2)(P < 0.001).According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019,after 8 weeks treatment,96.3% patients in the experimental group and 13.3%in the control group had achieved the LDL-C therapeutic target(P < 0.01).Conclusions:1.In addition to the traditional risk factors,LDL-P6,VLDL-P and LP(a)were all independent risk factors for CHD.When traditional risk factors are combined with LDL-P6,VLDL-P and Lp(a),their predictive value can be further improved.2.Evolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients,and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.3.The detection of lipoprotein particles and subfrctions by NMR spectroscopy has certain application value in the diagnosis and treatment of coronary heart disease,and provides new ideas and new methods for clinical diagnosis and treatment.