多种心脏标志物与冠状动脉狭窄的相关性及临床意义

Correlation Between Levels of Cardiac Markers and Coronary Artery Stenosis and Its Clinical Significance

目的：探讨性别、年龄、吸烟等临床基线资料和总胆固醇、甘油三酯等常规生化指标及胰岛素样生长因子1（IGF-1）、结缔组织生长因子（CTGF）、氧化低密度脂蛋白（ox-LDL）、转化生长因子β1（TGF-β1）、脂蛋白脂肪酶A2（Lp-PLA2）、可溶性细胞间黏附分子1（sICAM-1）、基质蛋白金属酶9（MMP-9）、髓过氧化物酶（MPO）、热休克蛋白70（HSP-70）等多种心脏标志物与冠状动脉粥样硬化性狭窄相关性及其临床诊断价值。方法：将200例行冠状动脉造影的患者按造影结果分为冠脉狭窄轻度组（狭窄：1%-50%）、中度组（狭窄：51%-75%）、重度组（狭窄：〉75%）和冠脉正常对照组;采用单因素方差分析探讨狭窄各组与对照组间临床基线资料、一般生化指标和心脏标志物的差异,采用二元Logistic逐步回归方法探讨冠状动脉粥样硬化性狭窄程度与多种心脏标志物的相关性,并绘制其ROC曲线,评价其临床诊断价值。结果：冠状动脉粥样硬化性狭窄轻度组、中度组、重度组与对照组在性别、年龄、吸烟、血总胆固醇、高密度脂蛋白胆固醇、载脂蛋白B及细胞因子IGF-1、CTGF、Ox-LDL、TGF-β1、LpPLA2、sICAM-1、MMP-9、MPO、HSP-70中的比较,差异有统计学意义,其中Lp-PLA2、MMP-9、CTGF三个标志物在对照组、轻度组、中度组和重度组之间相互比较,均为差异显著,诊断价值较大;将每个心脏标志物变量纳入二元Logistic逐步回归模型,也显示了Lp-PLA2、MMP-9、CTGF进入最优逻辑回归方程,表明Lp-PLA2、MMP-9、CTGF可以作为冠状动脉粥样硬化性狭窄的独立危险因素,分析Lp-PLA2、MMP-9和CTGF诊断冠脉狭窄的ROC曲线,它们的诊断临界值、曲线下面积、敏感度、特异度分别为：15.67ng/ml,0.95,85.30%,96.00%;12.20ng/ml,0.96,94.70%,90.00%;503.65pg/ml,0.973,92%,94.00%。结论：性别、年龄、吸烟、总胆固醇、高密度脂蛋白胆固醇、载脂蛋白B100、IGF-1、CTGF、Ox-LDL、TGF-β1、LP-PLA2、MMP-9、sICAM-1、MPO、HSP-70是冠脉狭窄的指标,临床工作中检测Lp-PLA2、MMP-9和CTGF可以作为评估冠状动脉狭窄及独立危险因素指标。

Objective：To investigate the clinical baseline data of gender,age,smoking and total cholesterol,triglyceride and other routine biochemical indicators as well as insulin-like growth factor1（IGF-1）,connective tissue growth factor（CTGF）,oxidized low density lipoprotein（ox-LDL）,transforming growth factor beta 1（TGF-beta 1）,lipoprotein lipase（Lp-PLA2）A2,soluble intercellular adhesion molecule 1（sICAM-1）,metal matrix protein 9（MMP-9）,myeloperoxidase enzyme（MPO）,heat shock protein 70（HSP-70）and other cardiac markers of coronery heart disease patients,and to analyze the correlation between these markers and coronary artery stenosis and explore its clinical diagnostic value.Methods：Two hundred patients undergoing coronary angiography were divided into mild group（stenosis：1%-50%）,moderate group（stenosis：51%-75%）,severe group（stenosis：75%）,and control group（normal coronary artery）according to the result of angiogmphy.The differences of clinical baseline data,general biochemical indexes and cardiac markers between stenosis groups and control group were analyzed by single factor analysis of variance.The binary logistic stepwise regression method was used to investigate the relationship between coronary atherosclerosis degree of stenosis and a variety of cardiac markers,and the ROC curve was drawn to evaluate its clinical diagnostic value.Results：It is statistically significant among the mild group,moderate group,severe group and control group by comparison of coronary atherosclerotic stenosis in gender,age,smoking,blood total cholesterol,high density lipoprotein cholesterol,apolipoprotein B,as well as cytokine proteins IGF-1,CTGF,OxLDL,TGF-β1,Lp-PLA2,sICAM-1,MMP-9,MPO and HSP-70.Among these indexes,LpPLA2,MMP-9,and CTGF showed more diagnostic value;when each heart marker variable was included in binary logistic stepwise regression model,it also showed that Lp-PLA2,MMP-9,and CTGF entered the optimal logistic regression equation,which implied that Lp-PLA2,MMP-9,and CTGF could be used as independent risk factors for coronary atherosclerotic stenosis.By analyzing the performance of Lp-PLA2,MMP-9,and CTGF in the ROC curve of coronary artery stenosis,their diagnostic thresholds,area under the curve,sensitivities and specificities were 15.67 ng/ml,0.95,85.30%,96.00%;12.20 ng/ml,0.96,94.70%,90.00%;503.65 pg/ml,0.973,92%,94.00%,respectively.Conclusion：Gender,age,smoking,blood total cholesterol,high density lipoprotein cholesterol,apolipoprotein B,as well as cytokine proteins IGF-1,CTGF,OxLDL,TGF-β1,Lp-PLA2,sICAM-1,MMP-9,MPO and HSP-70 are clinical markers,and LpPLA2,MMP-9 and CTGF may be independent risk factors for diagnosis of coronary atherosclerotic stenosis.