ACS患者血浆vWF、ADAMTS13水平与冠脉病变程度的相关性研究
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摘要
目的：研究血管性血友病因子（vWF）、血管性血友病因子裂解蛋白酶（ADAMTS13）水平在急性冠脉综合征(ACS)患者中的差异，探讨ACS患者冠状动脉粥样硬化病变程度与血浆vWF、ADAMTS13水平之间的相关性，探讨其临床意义，为ACS的发生发展与指导治疗提供新的理论依据。
方法：收集苏州大学附属第一人民医院2012年2月至2013年2月入院并接受冠脉造影的急性冠脉综合征(ACS)患者共119例，其中UA患者17例，NSTEMI患者31例，STEMI患者71例。根据冠状动脉造影结果，按病变累及左前降支、回旋支和右冠脉等相关冠脉支数，分为单支病变组（42例），双支病变组（43例），多支病变组（34例）。依据Gensini积分分组：Gensini积分≤20分(28例)，Gensini积分21-40分（33例），Gensini积分≥41分（58例）。另设SA对照组患者20例，冠脉正常健康对照组患者20例。入院后抽静脉血检测vWF和ADAMTS13水平，冠状动脉病变的严重程度用病变的血管支数及Gensini评分表示，不同冠脉病变组进行比较，并观察行PCI术患者术前术后vWF及ADAMTS13水平的动态变化。
结果：1.ACS患者在vWF、hs-CRP、WBC及应激血糖水平上均高于SA组及对照组，ADAMTS13水平变化与上述相反，差异具有显著统计学意义(P<0.05)；SA组患者vWF、ADAMTS、hs-CRP、WBC及应激血糖水平与对照组患者两组之间比较差异无统计学意义(P>0.05)。
2.ACS患者不同临床类型亚组之间的vWF、ADAMTS13水平比较差异无统计学意义(P>0.05)。
3.不同冠脉病变支数组间vWF、ADAMTS13水平的比较，单支病变、双支病变、三支病变及对照组各组间比较，差异具有显著统计学意义(P<0.001)。
4.将ACS患者按冠脉病变程度Gensini积分分为轻、中、重三组，比较三组及对照组患者vWF和ADAMTS13水平，差异具有显著统计学意义(P<0.01)。
5.血浆vWF水平与冠状动脉病变支数呈显著正相关(r=0.686， P<0．001)；ADAMTS13水平与冠状动脉病变支数呈显著负相关(r=-0.642，P<0．01)；血浆vWF水平与冠状动脉造影Gensini积分呈显著正相关(r=0.7539，P<0.0001)；血浆ADAMTS13水平与冠状动脉造影Gensini积分呈显著负相关(r=-0.7318，P<0.0001）；血浆vWF/ADAMTS13（两者比值）与冠状动脉造影Gensini积分呈显著正相关(r=0.7214，P<0.0001)；血浆vWF水平与ADAMTS水平呈显著负相关(r=-0.9165，P<0.0001）。
6.以vWF抗原含量、vWF活性、ADAMTS13活性为检验变量，以冠脉病变程度（冠脉造影Gensini积分标准划分）为状态变量，统计分析绘制ROC曲线，列出曲线下面积，结果表明vWF活性水平曲线下面积最大（0.924）。
7.经皮冠状动脉介入治疗（PCI）的ACS患者，按术后采血时间点不同分组，即术后采血时间≤24h组和＞24h组，≤48h组和＞48h组，观察各组术前、术后vWF及ADAMTS13水平变化值。vWF水平方面，术后≤24h组及≤48h组患者vWF水平较术前增高（P<0.01），差异有统计学意义；术后＞24h组及＞48h组，患者vWF水平较术前降低（P<0.01），差异有统计学意义。ADAMTS13方面，两组不同采血时间点在术前、术后比较，差异无统计学意义（P>0.05）。
结论：1.ACS患者的vWF水平明显高于SA组及正常对照组，ADAMTS13水平明显低于SA组及正常对照组，两者作为血栓标志物与冠脉病变的严重程度相关，对临床评价ACS患者危险分层及指导治疗有一定参考价值。
2.经皮冠状动脉介入治疗（PCI）可使ACS患者心肌再灌注，改善预后，但心血管介入术中也可能会引起血管内皮受损，内皮细胞功能失调，术后vWF水平可能先较前升高，之后逐渐降低。
Objective: To study the diversity of levels of Von willebrand factor (vWF) and vonwillebrand factor cracking protease (ADAMTS13) in patients of acute coronarysyndrome(ACS),meanwhile,to investigate the correlation between plasma von Willebrandfactor,von willebrand factor cracking protease (ADAMTS13) levels and the extent ofcoronary lesion in acute coronary syndrome,and to assess the clinical value．
Method: A total of119patients of acute coronary syndrome(ACS) admitted weredivided into three clinical types including17patients with UA,31patients with NSTEMIand71patients with STEMI.20stable angina patients and20normal volunteers weredesignated as control groups.The severity of coronary artery lesions was evaluated by thenumber of diseased arteries and Gensini score for a decision of coronaryangiography(CAG) after admission.The venous blood samples were takenfrom the patient immediately after admission for detection of Von willebrand factor (vWF)and von willebrand factor cracking protease (ADAMTS13).To observe the dynamic changeof vWF and ADAMTS13before and after PCI.
Results：1.Significant differences in vWF、ADAMTS13、hs-CRP、WBC and stressblood glucosewere found between ACS group and SA group、normal group（P<0.05);Nosignificant differences in vWF、ADAMTS13、hs-CRP、WBC and stress blood glucose werefound between SA group and normal group（P>0.05).
2.No significant differences in vWF、ADAMTS13were found among three ACSclinical types（P>0.05).
3.Significant differences between vWF、ADAMTS13levels and coronary vascular lesion count（P<0.001).
4.Significant differences between vWF、 ADAMTS13levels and Gensini score（P<0.01）.
5.There is a correlation between level of vWF,ADAMTS13and coronary vascularlesion count and Gensini score.There is a positive correlation between the ratio ofvWF/ADAMTS13and coronary vascular lesion count and Gensini score(r=0.7214，P<0.0001).There is a correlation between level of vWFAct and vWF-cp activity(r=-0.9165，P<0.0001）.
6.The ROC curve show that the corresponding area under the ROC of vWFAg、vWFAct and ADAMTS13were0.902,0.924and0.889.
7.Plasma levels of vWF in ACS patients when admitted were marked higher than thatafter PCI within24hours or48hours(P<0.01),lower than that after PCI moer than24hours or48hours(P<0.01);but no significant differences vWF-cp activity in ACS patientsbefore and after PCI（P>0.05).
Conclusions:1.The level of vWF in patients of ACS were much higher than SAgroup and normal group,The levels of ADAMTS13were much lower than SA group andnormal group,there is a correlation between levels of vWF,ADAMTS13in ACS patientsand different degrees of coronary artery lesions.It can offer us the reference of clinical riskstratification and treatment of the hospitalized patients with ACS.
2.Percutaneous coronary interention (PCI) may lead to myocardial reperfusion inpatients with ACS, and improve the prognosis, but also it can lead to vascular endothelialdamage, endothelial dysfunction, postoperative vWF levels may increases, then graduallydecreases.
方法：收集苏州大学附属第一人民医院2012年2月至2013年2月入院并接受冠脉造影的急性冠脉综合征(ACS)患者共119例，其中UA患者17例，NSTEMI患者31例，STEMI患者71例。根据冠状动脉造影结果，按病变累及左前降支、回旋支和右冠脉等相关冠脉支数，分为单支病变组（42例），双支病变组（43例），多支病变组（34例）。依据Gensini积分分组：Gensini积分≤20分(28例)，Gensini积分21-40分（33例），Gensini积分≥41分（58例）。另设SA对照组患者20例，冠脉正常健康对照组患者20例。入院后抽静脉血检测vWF和ADAMTS13水平，冠状动脉病变的严重程度用病变的血管支数及Gensini评分表示，不同冠脉病变组进行比较，并观察行PCI术患者术前术后vWF及ADAMTS13水平的动态变化。
结果：1.ACS患者在vWF、hs-CRP、WBC及应激血糖水平上均高于SA组及对照组，ADAMTS13水平变化与上述相反，差异具有显著统计学意义(P<0.05)；SA组患者vWF、ADAMTS、hs-CRP、WBC及应激血糖水平与对照组患者两组之间比较差异无统计学意义(P>0.05)。
2.ACS患者不同临床类型亚组之间的vWF、ADAMTS13水平比较差异无统计学意义(P>0.05)。
3.不同冠脉病变支数组间vWF、ADAMTS13水平的比较，单支病变、双支病变、三支病变及对照组各组间比较，差异具有显著统计学意义(P<0.001)。
4.将ACS患者按冠脉病变程度Gensini积分分为轻、中、重三组，比较三组及对照组患者vWF和ADAMTS13水平，差异具有显著统计学意义(P<0.01)。
5.血浆vWF水平与冠状动脉病变支数呈显著正相关(r=0.686， P<0．001)；ADAMTS13水平与冠状动脉病变支数呈显著负相关(r=-0.642，P<0．01)；血浆vWF水平与冠状动脉造影Gensini积分呈显著正相关(r=0.7539，P<0.0001)；血浆ADAMTS13水平与冠状动脉造影Gensini积分呈显著负相关(r=-0.7318，P<0.0001）；血浆vWF/ADAMTS13（两者比值）与冠状动脉造影Gensini积分呈显著正相关(r=0.7214，P<0.0001)；血浆vWF水平与ADAMTS水平呈显著负相关(r=-0.9165，P<0.0001）。
6.以vWF抗原含量、vWF活性、ADAMTS13活性为检验变量，以冠脉病变程度（冠脉造影Gensini积分标准划分）为状态变量，统计分析绘制ROC曲线，列出曲线下面积，结果表明vWF活性水平曲线下面积最大（0.924）。
7.经皮冠状动脉介入治疗（PCI）的ACS患者，按术后采血时间点不同分组，即术后采血时间≤24h组和＞24h组，≤48h组和＞48h组，观察各组术前、术后vWF及ADAMTS13水平变化值。vWF水平方面，术后≤24h组及≤48h组患者vWF水平较术前增高（P<0.01），差异有统计学意义；术后＞24h组及＞48h组，患者vWF水平较术前降低（P<0.01），差异有统计学意义。ADAMTS13方面，两组不同采血时间点在术前、术后比较，差异无统计学意义（P>0.05）。
结论：1.ACS患者的vWF水平明显高于SA组及正常对照组，ADAMTS13水平明显低于SA组及正常对照组，两者作为血栓标志物与冠脉病变的严重程度相关，对临床评价ACS患者危险分层及指导治疗有一定参考价值。
2.经皮冠状动脉介入治疗（PCI）可使ACS患者心肌再灌注，改善预后，但心血管介入术中也可能会引起血管内皮受损，内皮细胞功能失调，术后vWF水平可能先较前升高，之后逐渐降低。
Objective: To study the diversity of levels of Von willebrand factor (vWF) and vonwillebrand factor cracking protease (ADAMTS13) in patients of acute coronarysyndrome(ACS),meanwhile,to investigate the correlation between plasma von Willebrandfactor,von willebrand factor cracking protease (ADAMTS13) levels and the extent ofcoronary lesion in acute coronary syndrome,and to assess the clinical value．
Method: A total of119patients of acute coronary syndrome(ACS) admitted weredivided into three clinical types including17patients with UA,31patients with NSTEMIand71patients with STEMI.20stable angina patients and20normal volunteers weredesignated as control groups.The severity of coronary artery lesions was evaluated by thenumber of diseased arteries and Gensini score for a decision of coronaryangiography(CAG) after admission.The venous blood samples were takenfrom the patient immediately after admission for detection of Von willebrand factor (vWF)and von willebrand factor cracking protease (ADAMTS13).To observe the dynamic changeof vWF and ADAMTS13before and after PCI.
Results：1.Significant differences in vWF、ADAMTS13、hs-CRP、WBC and stressblood glucosewere found between ACS group and SA group、normal group（P<0.05);Nosignificant differences in vWF、ADAMTS13、hs-CRP、WBC and stress blood glucose werefound between SA group and normal group（P>0.05).
2.No significant differences in vWF、ADAMTS13were found among three ACSclinical types（P>0.05).
3.Significant differences between vWF、ADAMTS13levels and coronary vascular lesion count（P<0.001).
4.Significant differences between vWF、 ADAMTS13levels and Gensini score（P<0.01）.
5.There is a correlation between level of vWF,ADAMTS13and coronary vascularlesion count and Gensini score.There is a positive correlation between the ratio ofvWF/ADAMTS13and coronary vascular lesion count and Gensini score(r=0.7214，P<0.0001).There is a correlation between level of vWFAct and vWF-cp activity(r=-0.9165，P<0.0001）.
6.The ROC curve show that the corresponding area under the ROC of vWFAg、vWFAct and ADAMTS13were0.902,0.924and0.889.
7.Plasma levels of vWF in ACS patients when admitted were marked higher than thatafter PCI within24hours or48hours(P<0.01),lower than that after PCI moer than24hours or48hours(P<0.01);but no significant differences vWF-cp activity in ACS patientsbefore and after PCI（P>0.05).
Conclusions:1.The level of vWF in patients of ACS were much higher than SAgroup and normal group,The levels of ADAMTS13were much lower than SA group andnormal group,there is a correlation between levels of vWF,ADAMTS13in ACS patientsand different degrees of coronary artery lesions.It can offer us the reference of clinical riskstratification and treatment of the hospitalized patients with ACS.
2.Percutaneous coronary interention (PCI) may lead to myocardial reperfusion inpatients with ACS, and improve the prognosis, but also it can lead to vascular endothelialdamage, endothelial dysfunction, postoperative vWF levels may increases, then graduallydecreases.
引文
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