Relationships of a disintegrin and metalloproteinase with thrombospondin motifs 1 in serum and tissue inhibitor of metalloproteinase 3 levels with in-stent restenosis
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摘要:目的
探讨血清含凝血酶敏感素1型基序的解聚素样金属蛋白酶（ADAMTS-1）、组织金属蛋白酶抑制因子3（TIMP3）水平与冠心病患者经皮冠状动脉介入治疗（PCI）后支架内再狭窄（ISR）的关系。
方法选取455例行PCI的冠心病患者作为研究对象，根据随访1年后冠状动脉造影的影像学观察结果分为ISR组43例和非ISR组412例。采用Gensini评分及狭窄支数评价狭窄程度，采用酶联免疫吸附试验（ELISA）法检测ADAMTS-1、TIMP3水平。采用Spearman相关分析法分析ADAMTS-1、TIMP3水平与造影后Gensini评分的相关性；采用Pearson相关系数法分析ADAMTS-1与TIMP3的相关性；采用Logistic回归分析法分析ISR发生的影响因素；采用受试者工作特征（ROC）曲线评估ADAMTS-1、TIMP3对ISR发生的预测价值。
结果与非ISR组相比，ISR组患者总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、ADAMTS-1水平升高，TIMP3水平降低，差异有统计学意义（P < 0.05）；ISR组血清ADAMTS-1水平与Gensini积分呈正相关（P < 0.05），TIMP3水平与Gensini积分呈负相关（P < 0.05）；ISR组ADAMTS-1水平与TIMP3水平呈负相关（r=-0.616，P < 0.001）；多因素Logistic回归分析发现，ADAMTS-1高水平、TIMP3低水平均为ISR发生的独立危险因素（P < 0.05）；ROC曲线显示，ADAMTS-1与TIMP3联合预测ISR发生的曲线下面积显著大于两者单独预测（P < 0.05）。
结论ADAMTS-1和TIMP3水平与冠心病患者PCI后ISR的发生密切相关，两者是ISR发生的独立危险因素，对预测ISR发生具有重要价值。
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关键词:
- 冠心病 /
- 经皮冠状动脉介入治疗 /
- 支架内再狭窄 /
- 组织金属蛋白酶抑制因子3 /
- 含凝血酶敏感素1型基序的解聚素样金属蛋白酶
Abstract:ObjectiveTo investigate relationships of the levels of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS-1) and tissue inhibitor of metalloproteinase 3 (TIMP3) in the serum with intrastent restenosis (ISR) in patients with coronary heart disease after percutaneous coronary intervention (PCI).
MethodsA total of 455 patients with coronary heart disease who underwent PCI were selected as study objects, and were divided into ISR group (43 cases) and non-ISR group (412 cases) according to the imaging observation results of coronary angiography after one year of follow-up; Gensini score and the number of stenotic branches were used to evaluate the degree of stenosis; Enzyme-Linked Immunosorbent Assay (ELISA) method was used to detect the levels of ADAMTS-1 and TIMP3; Spearman's method was used to analyze the correlations of ADAMTS-1 and TIMP3 levels with Gensini score after angiography; Pearson correlation coefficient method was used to analyze the correlation between ADAMTS-1 and TIMP3; Logistic regression was used to analyze the influencing factors of the occurrence of ISR; receiver operating characteristic (ROC) curve was used to evaluate the predictive value of ADAMTS-1 and TIMP3 for occurrence of ISR.
ResultsCompared with the non-ISR group, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ADAMTS-1 levels in the ISR group were significantly increased, while the level of TIMP3 was significantly decreased (P < 0.05); in the ISR group, the level of serum ADAMTS-1 was significantly positively correlated with Gensini score (P < 0.05); the level of TIMP3 was significantly negatively correlated with Gensini score (P < 0.05); the level of ADAMTS-1 was significantly negatively correlated with the level of TIMP3 in the ISR group(r=-0.616, P < 0.001); multivariate Logistic regression analysis showed that high level of ADAMTS-1 and low level of TIMP3 were independent risk factors for ISR (P < 0.05); compared with the single prediction of ADAMTS-1 or TIMP3, the area under the ROC curve of the combined prediction of ADAMTS-1 and TIMP3 for ISR was significantly increased (P < 0.05).
ConclusionThe levels of ADAMTS-1 and TIMP3 are closely related to the occurrence of ISR in patients with coronary heart disease after PCI. They are independent risk factors for the occurrence of ISR and have important value for predicting the occurrence of ISR.
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表 1 2组患者临床资料比较(x±s)[n(%)]
临床资料 分类 非ISR组(n=412) ISR组(n=43) t/χ2 P 年龄/岁 57.34±7.68 56.92±8.36 0.338 0.735 体质量指数/(kg/m2) 22.90±2.40 23.28±2.71 0.976 0.330 性别 男 201(48.79) 20(46.51) 0.015 0.902 女 211(51.21) 23(53.49) TC/(mmol/L) 3.69±0.76 4.97±0.88 10.347 < 0.001 TG/(mmol/L) 1.57±0.49 2.13±0.74 6.742 < 0.001 HDL-C/(mmol/L) 1.04±0.45 0.94±0.29 1.426 0.155 LDL-C/(mmol/L) 2.01±0.49 2.84±0.31 10.876 < 0.001 狭窄数目 单支 116(28.16) 12(27.91) 0.050 0.975 双支 185(44.90) 20(46.51) 3支及以上 111(26.94) 11(25.58) 狭窄部位 左前降支 60(14.56) 5(11.63) 0.619 0.892 左回旋支 105(25.49) 13(30.23) 右冠状动脉 162(39.32) 16(37.21) 右主干 85(20.63) 9(20.93) 吸烟 有 230(55.83) 21(48.84) 0.769 0.381 无 182(44.17) 22(51.16) 糖尿病 有 45(10.92) 5(11.63) 0.013 0.908 无 367(89.08) 38(88.37) 高血压病 有 150(36.41) 14(32.56) 0.250 0.617 无 262(63.59) 29(67.44) TC: 总胆固醇; TG: 甘油三酯; HDL-C: 高密度脂蛋白胆固醇; LDL-C: 低密度脂蛋白胆固醇。 
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表 2 2组患者PCI后血清ADAMTS-1、TIMP3水平比较(x±s)
组别 n ADAMTS-1/(μg/L) TIMP3/(ng/mL) 非ISR组 412 9.01±2.68 1.51±0.68 ISR组 43 12.84±3.90 0.75±0.30 t — 8.488 7.250 P — < 0.001 < 0.001 ADAMTS-1: 含凝血酶敏感素1型基序的解聚素样
金属蛋白酶; TIMP3: 组织金属蛋白酶抑制因子3。
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表 3 PCI后发生ISR影响因素的多因素Logistic回归分析
因素 wald χ2 β SE OR 95%CI P ADAMTS-1 6.774 0.351 0.135 1.421 1.091~1.851 0.009 TIMP3 7.960 0.403 0.143 1.497 1.131~1.981 0.004
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