Clinical Significance Of Amino Acids And Carnitine Alteration In The Plasma Of Patients With Coronary Artery Heart Disease

ObjectiveTo investigate the plasma amino acids and carnitine alteration in patients with coronary artery heart disease(CAD),and to find potential biomarkers for the early diagnosis and prevention of CAD.MethodsA total of 158 CAD patients were collected in the Department of Cardiology of the First Affiliated Hospital of Jinzhou Medical University from September 2015 to April 2017,and a total of 124 non CAD volunteers were collected in the physical examination center of the hospital at the same period.All subjects were excluded from the clear CAD risk factors of hypertension,hyperlipidemia and diabetes.The general clinical data of the subjects were recorded in detail.Tandem mass spectrometry(MS/MS)was used to detect the levels of 23 amino acids,5 carnitineand 12 ratios of metabolites.A series of multivariate statistical analysis were used.Principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA)and orthogonal partial least square discriminant analysis(OPLS-DA)were used to establish the model.Based on the contribution of variable importance for the projection(VIP),metabolic biomarkers with statistical difference between groups were chosen.From the CAD group and the control group,80% samples were randomly selected as training cohort to establish the Logistic regression model.The accuracy of the regression model was tested by receiver operating characteristic curve(ROC curve)and tested by the validation cohort(the remaining 20% samples).ResultsThe CAD group included 90 males and 68 females with an average age of 57.9±11.3 years.The control group included 70 males and 54 females with an average age of 57.3±10.8 years.There was no significant difference in the general clinical data between the CAD group and the control group(P> 0.05).The PCA model established by the two groups was well fitted,but the predictive ability of the model was not good(R2X=64.7%,Q2Y=29.3%).The PLS-DA model indicated that there was a significant difference between the two groups(R2Y=0.527,Q2Y=0.464).Permutation test was used to verify that the PLS-DA model is stable and effective(R2=0.062,Q2=-0.149).The OPLS-DA model made the difference between groups more significant(R2Y=0.572,Q2Y=0.492).Under the criteriaof VIP value > 1,a total of 12 differential metabolites were found between the two groups(P< 0.05),and then a total of 6 differential metabolites were obtained by multiple factor Logistic regression analysis with Forward LR,which finally entered the optimal regressionmodel.The levels of homocysteine,histidine,valine,phenylalanine and isoamyl carnitine in the plasma of CAD patients were higher than those in the control group,and ornithine/citrulline was lower than the control group.The model made it possible to correctly classify 89.7%of patients with CAD and 81.8% of controls,with an area under the curve(AUC)of 0.917.Important moreover was the fact that the model was convincing,which was demonstrated by validation in the independent cohort with a sensitivity of 78.5%,a specificity of 83.6% and an area under the curve of 0.896.It indicated that the regression model had good accuracy and can be used to predict the incidence of CAD.Conclusions1.Compared with non CAD population,the plasma levels of alanine,histidine,valine,homocysteine,glutamine,serine,aspartic acid,phenylalanine,isoamyl carnitine,and the ornithine : citrulline ratio and C26:C20 ratio in patients with CAD were all increased,and the citrullinine: arginine ratio was decreased.2.The equation,Y=1.483 x homocysteine +0.051 x histidine-0.113 x phenylalanine +0.037 x valine +20.623 x isoamyl carnitine +0.927 x ornithine / citrulline-20.623,can be used to predict the incidence of CAD.