Correlation Between Galectin-4 And The Degree Of Coronary Artery Disease In Patients With Coronary Heart Disease

Background and objective:Coronary Heart Disease(CHD),its core pathogenesis is myocardial ischemia,hypoxia and even necrosis caused by coronary artery lesions.Therefore,the evaluation of the degree of coronary artery lesions is of great significance in the occurrence,development,and prognosis of CHD.At present,the discovered biomarkers like myocardial enzyme,myocardial troponin and myoglobin have high specificity and selectivity in the diagnosis of myocardial infarction,but cannot evaluate the degree of coronary artery disease.Therefore,it is particularly important to find more reliable biomarkers to evaluate the degree of coronary artery stenosis.Galectin-4(Gal-4)interacts with vascular endothelial cells,stimulating monocyte chemoattractant protein(MCP-1),granulocyte colony-stimulating factor(G-CSF),interleukin-6(IL-6)and other cytokines and chemokines secreted,promote the transformation of monocytes into macrophages,mediate the infiltration of macrophages and enhance their adhesion to the coronary artery wall,which may play an important role in the occurrence and development of coronary atherosclerosis.But the effect on the degree of coronary stenosis is unknown.This study evaluated the potential of Gal-4 as a novel biomarker to predict the degree of coronary artery disease in patients with CHD by analyzing the correlation between Gal-4 level and the degree of coronary artery disease in patients with CHD,and provided scientific basis for the early detection,diagnosis and treatment of CHD.Method:A total of 159 inpatients with CHD who were admitted to the Department of Cardiology of the Second Hospital of Jilin University from December 2021 to December 2022 were selected,and 35 patients with normal coronary vessels who were hospitalized during the same period were selected as controls.The general information and clinical data of all selected patients were collected.Fasting venous blood of selected patients was collected on the second day of admission,and the serum Gal-4 level was measured by enzyme linked immunosorbent assay(ELISA).In the first step,the general data of patients with CHD and controls were analyzed and compared.In the second step,patients with CHD and controls were compared for the presence of differences in Gal-4 concentrations.In order to control the interference of confounding factors,the indicators with statistical differences in the first step were included in the regression model for multivariate logistic regression analysis.For the indicators that were still statistically significant after multivariate analysis,the correlation between the two levels was analyzed alone with Gal-4.The third step was to analyze the correlation between the levels of Gal-4 and the degree of coronary artery lesions.Firstly,the correlation between serum Gal-4 levels and Gensini scores in patients with CHD was analyzed.Second,the patients with CHD were divided into three subgroups according to the number of coronary artery lesions involving the left anterior descending artery,left circumflex artery or right coronary artery.The levels of Gal-4 were compared between the three subgroups.CHD patients were divided into the first,second,third and fourth quartile subgroups according to the quartile method of Gensini scores.Pairwise comparisons of Gal-4 levels in patients between the four subgroups were performed.The fourth step was to evaluate the diagnostic value of Gal-4 in patients with acute myocardial infarction(AMI)and unstable angina pectoris(UA)using ROC curve.Results:1.The degree of coronary artery lesions and the grouping of severity of disease in all enrolled patientsAll enrolled patients meeting the criteria were divided into CHD(at least one coronary artery stenosis ≥50%,n=159 cases)and controls(normal coronary artery,n=35 cases)according to the degree of coronary artery stenosis.The CHD group included 68 patients with AMI,67 patients with UA,and 24 patients with stable angina pectoris(SAP).2.Comparison of general clinical data and biochemical parameters between CHD and controlsThe results showed that compared with controls,patients with CHD were more frequently male(66%>37.1%,P=0.001),had a higher prevalence of hypertension(55.3%>22.9%,P=0.001),higher serum creatinine(75μmol/L>64.5μmol/L,P=0.01),and higher NT-proBNP(109.7pg/mL>55.1pg/mL,P=0.001)were statistically significant.There were no significant statistical differences in age,BMI,smoking rate,prevalence of diabetes mellitus,blood glucose,total cholesterol,total triglycerides,HDL cholesterol,LDL cholesterol,homocysteine,and LVEF between the two groups.3.Differential expression levels of Gal-4 in CHD and controlsThe results showed that the serum Gal-4 expression levels were significantly increased in the CHD group compared with controls(2.50ng/mL>0.66ng/mL,P<0.001),which was statistically significant.4.Multivariate analysis of Gal-4 expression levels in CHD patients and controlsThe results showed that:(1)Gal-4 expression levels were different between CHD and controls(OR=1.34,P<0.05);(2)On logistic multivariate analysis,NT-proBNP expression levels were different between CHD and controls(OR=1.003,P=0.041);Gender may have an impact on the occurrence of CHD(OR=0.262,P=0.004),with no statistically significant differences in the prevalence of hypertension or serum creatinine.5.Univariate analysis of the difference between Gal-4 levels and NT-proBNP levels and gender in all enrolled patientsThere was no significant correlation between Gal-4 concentrations and NT-proBNP in all enrolled patients(r=-0.048,P=0.543).There was no significant correlation between Gal-4 concentration and gender of enrolled patients(r=-0.056,P=0.440),which was not statistically significant.6.Correlation between Gal-4 levels and Gensini scores of CHD patientsPearson’s correlation was performed between the degree scores of coronary lesions obtained by Gensini scoring system and Gal-4 levels(r= 0.521,P<0.001).7.Differential comparison of Gal-4 levels among different subgroups of CHD patients7.1 Comparison of Gal-4 levels among three groups in single-vessel disease,double-vessel disease and three-vessel diseaseFor pairwise comparison,the results showed that regarding serum Gal-4 levels,Gal-4 levels were lower in the single-vessel disease group than in the two-vessel disease group(1.21 ng/mL<2.23ng/mL,P=0.01),lower in the single-vessel disease group than in the threevessel disease group(1.21ng/mL<4.27ng/mL,P<0.001),and lower in the two-vessel disease group than in the three-vessel disease group(2.23ng/mL<4.27ng/mL,P=0.005),with statistical significance(Kruskal-Wallis H test).7.2 Comparison of Gal-4 levels among subgroups from the first quartile to the fourth quartile of Gensini scoresPairwise comparison among groups showed that the first quartile array was lower than the second quartile array(0.94ng/mL<1.99ng/mL,P=0.014),the first quartile array was lower than the third quartile array(0.94ng/mL<2.44ng/mL,P<0.001),the first quartile array was lower than the fourth quartile array(0.94ng/mL<4.15ng/mL,P<0.001),the second quartile array was lower than the fourth quartile array(1.99ng/mL<4.15ng/mL,P<0.001),the third quartile array was lower than the fourth quartile array(2.44ng/mL<4.15ng/mL,P=0.028),the second quartile array was lower than the third quartile array(1.99ng/mL<2.44ng/mL,P=1.000),but not statistically significant,the remaining indexes were all statistically significant(Kruskal-Wallis H test).8.Diagnostic value of Gal-4 levels for UA and AMI in CHD patientsROC curve analysis,the results showed: compared with controls,the ROC curve area of Gal-4 under AMI was 0.904,P<0.001,95%Cl(0.848,0.961),which predicted AMI with a sensitivity of 75%,specificity of 91.4%,and maximum Youden index of 0.664;The ROC curve area under UA was 0.731,P<0.001,95%Cl(0.636,0.827),which predicted UA with a sensitivity of 61.3%,specificity of 77.1%,and maximum Youden index of 0.384.When Gal-4 levels were compared between UA and AMI groups,the results showed that UA group was lower than AMI group(1.85ng/mL<3.66ng/mL,P<0.001),with statistical significance.Conclusion:1.The expression levels of Gal-4 increased gradually with the severity of coronary stenosis in CHD patients.2.Gal-4 may be an independent predictor of the extent of coronary lesions in CHD patients.3.Gal-4 may serve as a biomarker for UA and AMI diagnosis.