无症状中低风险人群冠脉斑块CTA特征与血液生化标记物相关性研究及联合预测斑块稳定性模型的建立
发布时间：2018-08-31 10:19
【摘要】：[目的]回顾性分析无症状非糖尿病FRS中低风险人群冠状动脉粥样硬化斑块CTA特征和血液生化标记物(脂联素、可溶性细胞间粘附分子-1、可溶性血管细胞粘附分子-1、可溶性E-选择素、可溶性P-选择素、髓过氧化物酶和白细胞趋化蛋白-1)水平分布特点,探讨二者的相关性；尝试建立多种生化标记物联合预测冠脉斑块稳定性模型并验证,评价其对于斑块稳定性判断的可行性,为该组人群冠心病风险提供有效监测方案。[方法]随机抽取我院2014年3月-2015年1月期间健康体检或非心脏手术术前查体行冠状动脉CTA检查的连续人群,经纳入、排除标准筛选后,统一在CTA检查前1小时内抽取血液样本,采用流式荧光微球技术进行上述7种生化标记物检测；对CTA斑块特征进行定性及定量评价；以斑块稳定性分组,采用SPSS 19.0软件包分析上述CTA斑块特征与生化标记物水平的相关性,用判别分析的方法建立判别模型并进行模型验证。[结果]1.入组对象：共400例,年龄51.5±8岁(29-73岁),其中男性291例(75.5%)。FRS评分1-19%,其中中度风险(10-19%)85例(21.25%),低度风险(0-9%)315例。2.冠脉CTA特征：400例研究对象中,管腔狭窄程度≥50%的5例,152例无粥样硬化斑块形成,248例存在粥样硬化斑块,其中181例可见易损斑块,表现为管壁增厚以非钙化斑块为主并呈正性重构者108例(27%)、管腔内见低密度斑块者101例(25.25%)、低密度斑块内见点状钙化者60例(15%)、管壁增厚并呈“餐巾环征”者6例(1.5%)、同时具备正性重构、低密度斑块和斑块内点状钙化者23例(5.75%)。3.以斑块稳定性分组,经单因素及多因素Logistic逐步回归分析,结果显示：年龄(p=0.001)、高血脂病史(p=0.015)、 apoB(p=0.011), ADP(p=0.015)、sE-Selectin (p=0.019)是易损斑块的独立预测因素；其ROC曲线下面积为0.727,诊断敏感度81.6%,特异度56.3%,阳性预测值65.1%,阴性预测值75.4%。4.FRS联合上述指标(年龄、高血脂病史、apoB、HDL-C、ADP、sE-Selectin)预测易损斑块的价值：ROC曲线下面积为0.735,敏感度75%,特异度64.5%,阳性预测值67.9%,阴性预测值72.1%。5.7种特殊生化标记物(ADP,sICAM-1, sVCAM-1, sE-Selectin, sP-Selectin, MPO, MCP-1)与斑块负荷(SIS、SSS. DS. CS.受累血管数量、非钙化斑块数量、钙化斑块数量、混合斑块数量、易损斑块数量)均无相关性(p0.05)或p0.05,但相关系数r0.3,临床上可认为没有相关性。6.用判别分析法建立预测易损斑块的联合模型并验证6.1建立判别方程：第一分类函数：Z1=-28.099+8.991x1+0.947x2+1.602x3+2.511x4+1.126x5+0.423x6第二分类函数：Z2=-32.227+9.731x1+1.008x2+2.339x3+3.360x4+0.189x5+1.075x6(x1：男性,x2：年龄,x3：高血脂病史,X4:apoB, x5:ADP, X6: sE-Selectin)判别方法：将未知分类的个体的上述基线和生化指标分别代入第一和第二分类函数公式,若所得结果Z1Z2则归入对照组,反之,如Z1Z2则归入实验组。6.2模型验证,结果显示：采用"Casewise results"的方法得出的判别函数的正确判断率为67.0%,使用交互验证的方法得出判别函数的正确判断率为65.1%。[结论]1.在无症状非糖尿病FRS中低风险人群中,血清ADP、sE-Selectin水平与CTA所见斑块稳定性密切相关,尤其是有正性重构和低密度特征的易损斑块；血清sVCAM-1水平虽与斑块稳定性无关,但它是SC的独立预测因素,其病理生理机制还有待进一步研究；血清sICAM-1s在有粥样硬化斑块者中呈明显高表达,但与斑块稳定性无关；sP-Selectin、MCP-1和MPO与斑块稳定性无关.上述7种生化标记物水平均与CTA斑块负荷无关.2.在该组人群中,冠心病传统风险因素与多种生化标记物组成的联合模型在预测易损斑块中有一定价值,在无症状人群的冠心病CTA普查中可起到一定作用。传统FRS评分不能反映冠状动脉粥样病变,特别是易损斑块的情况,对于FRS中低风险人群中,冠状动脉粥样硬化发生情况、乃至冠心病风险的再分层冠脉CTA可发挥更大的作用。
[Abstract]:[Objective] To retrospectively analyze the characteristics of CTA and blood biochemical markers (adiponectin, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, soluble P-selectin, myeloperoxidase and leukocyte chemoattractant protein-1) in asymptomatic non-diabetic FRS patients To explore the correlation between the two factors and to establish a multi-biochemical markers model to predict the stability of coronary plaque, and to evaluate the feasibility of judging the stability of coronary plaque, so as to provide an effective monitoring program for the risk of coronary heart disease in this group. After excluding the criteria for screening, blood samples were taken within 1 hour before CTA and the seven biochemical markers were detected by flow cytometry. The plaque characteristics were evaluated qualitatively and quantitatively. PSS 19.0 software package analyzed the correlation between the above-mentioned CTA plaque characteristics and biochemical markers, and established a discriminant model with discriminant analysis method and validated the model. [Results] 1. Participants: 400 patients, aged 51.5 (+ 8 years) (29-73 years), including 291 males (75.5%). FRS score 1-19%, including moderate risk (10-19%) 85 cases (21.25%) and low wind (21.25%). Characteristic of coronary CTA: Of the 400 subjects, 5 had lumen stenosis greater than 50%, 152 had no atherosclerotic plaque, 248 had atherosclerotic plaque, 181 had vulnerable plaque, 108 had non-calcified plaque and positive remodeling, and 101 had low density plaque in lumen. There were 60 cases (15%) with punctate calcification in low-density plaques, 6 cases (1.5%) with thickened wall and "napkin ring sign" and 23 cases (5.75%) with positive remodeling. History of hyperlipidemia (p = 0.015), apoB (p = 0.011), ADP (p = 0.015), and sE-Selectin (p = 0.019) were independent predictors of vulnerable plaques; the area under the ROC curve was 0.727, sensitivity was 81.6%, specificity was 56.3%, positive predictive value was 65.1%, and negative predictive value was 75.4%. 4. FRS combined with the above indicators (age, history of hyperlipidemia, apoB, HDL-C, ADP, sE-Selectin). Value of vulnerable plaque: area under ROC curve was 0.735, sensitivity 75%, specificity 64.5%, positive predictive value 67.9%, negative predictive value 72.1%. 5.7 special biochemical markers (ADP, sICAM-1, sVCAM-1, sE-Selectin, sP-Selectin, MPO, MCP-1) and plaque load (SIS, SSS.DS.CS. number of involved vessels, number of non-calcified plaques, number of calcified plaques There was no correlation (p0.05) or P0.05 between the quantity, the number of mixed plaques and the number of vulnerable plaques, but the correlation coefficient r0.3 was not considered to be correlated clinically. 6. A joint model for predicting vulnerable plaques was established by discriminant analysis and a discriminant equation was established by validating 6.1. The first classification function: Z1 = - 28.099 + 8.991x1 + 0.947x2 + 1.602x3 + 2.511x4 + 1.126x5 + 0.423x6. The second classification function: Z2 = - 32.227 + 9.731x1 + 1.008x2 + 2.339x3 + 3.360x4 + 0.189x5 + 1.075x6 (x1: male, x2: age, x3: history of hyperlipidemia, X4: apoB, x5: ADP, X6: sE - Selectin). The baseline and biochemical indices of the unknown individuals were substituted in the first and second classification function formulas respectively. If the results were Z1Z2, they would be classified into the first and second classification function formulas. In the control group, on the contrary, Z1Z2 was included in the experimental group. 6.2 model validation, the results showed that: the correct judgment rate of the discriminant function obtained by the "Casewise results" method was 67.0%, and the correct judgment rate of the discriminant function obtained by the cross-validation method was 65.1%. [Conclusion]1. In the asymptomatic non-diabetic FRS low-risk population, serum ADP The level of sE-Selectin is closely related to the stability of plaques seen by CTA, especially the vulnerable plaques with positive remodeling and low density. The level of sVCAM-1 in serum is an independent predictor of SC, but its pathophysiological mechanism remains to be further studied. High expression but not plaque stability; sP-Selectin, MCP-1 and MPO were not associated with plaque stability. The above seven biochemical markers were not associated with CTA plaque load. The traditional FRS score can not reflect the condition of coronary atherosclerosis, especially vulnerable plaque. For the low-risk group of FRS, the occurrence of coronary atherosclerosis, and even the risk of coronary heart disease, the stratified coronary CTA can play a greater role.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.4;R816.2
[Abstract]:[Objective] To retrospectively analyze the characteristics of CTA and blood biochemical markers (adiponectin, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, soluble P-selectin, myeloperoxidase and leukocyte chemoattractant protein-1) in asymptomatic non-diabetic FRS patients To explore the correlation between the two factors and to establish a multi-biochemical markers model to predict the stability of coronary plaque, and to evaluate the feasibility of judging the stability of coronary plaque, so as to provide an effective monitoring program for the risk of coronary heart disease in this group. After excluding the criteria for screening, blood samples were taken within 1 hour before CTA and the seven biochemical markers were detected by flow cytometry. The plaque characteristics were evaluated qualitatively and quantitatively. PSS 19.0 software package analyzed the correlation between the above-mentioned CTA plaque characteristics and biochemical markers, and established a discriminant model with discriminant analysis method and validated the model. [Results] 1. Participants: 400 patients, aged 51.5 (+ 8 years) (29-73 years), including 291 males (75.5%). FRS score 1-19%, including moderate risk (10-19%) 85 cases (21.25%) and low wind (21.25%). Characteristic of coronary CTA: Of the 400 subjects, 5 had lumen stenosis greater than 50%, 152 had no atherosclerotic plaque, 248 had atherosclerotic plaque, 181 had vulnerable plaque, 108 had non-calcified plaque and positive remodeling, and 101 had low density plaque in lumen. There were 60 cases (15%) with punctate calcification in low-density plaques, 6 cases (1.5%) with thickened wall and "napkin ring sign" and 23 cases (5.75%) with positive remodeling. History of hyperlipidemia (p = 0.015), apoB (p = 0.011), ADP (p = 0.015), and sE-Selectin (p = 0.019) were independent predictors of vulnerable plaques; the area under the ROC curve was 0.727, sensitivity was 81.6%, specificity was 56.3%, positive predictive value was 65.1%, and negative predictive value was 75.4%. 4. FRS combined with the above indicators (age, history of hyperlipidemia, apoB, HDL-C, ADP, sE-Selectin). Value of vulnerable plaque: area under ROC curve was 0.735, sensitivity 75%, specificity 64.5%, positive predictive value 67.9%, negative predictive value 72.1%. 5.7 special biochemical markers (ADP, sICAM-1, sVCAM-1, sE-Selectin, sP-Selectin, MPO, MCP-1) and plaque load (SIS, SSS.DS.CS. number of involved vessels, number of non-calcified plaques, number of calcified plaques There was no correlation (p0.05) or P0.05 between the quantity, the number of mixed plaques and the number of vulnerable plaques, but the correlation coefficient r0.3 was not considered to be correlated clinically. 6. A joint model for predicting vulnerable plaques was established by discriminant analysis and a discriminant equation was established by validating 6.1. The first classification function: Z1 = - 28.099 + 8.991x1 + 0.947x2 + 1.602x3 + 2.511x4 + 1.126x5 + 0.423x6. The second classification function: Z2 = - 32.227 + 9.731x1 + 1.008x2 + 2.339x3 + 3.360x4 + 0.189x5 + 1.075x6 (x1: male, x2: age, x3: history of hyperlipidemia, X4: apoB, x5: ADP, X6: sE - Selectin). The baseline and biochemical indices of the unknown individuals were substituted in the first and second classification function formulas respectively. If the results were Z1Z2, they would be classified into the first and second classification function formulas. In the control group, on the contrary, Z1Z2 was included in the experimental group. 6.2 model validation, the results showed that: the correct judgment rate of the discriminant function obtained by the "Casewise results" method was 67.0%, and the correct judgment rate of the discriminant function obtained by the cross-validation method was 65.1%. [Conclusion]1. In the asymptomatic non-diabetic FRS low-risk population, serum ADP The level of sE-Selectin is closely related to the stability of plaques seen by CTA, especially the vulnerable plaques with positive remodeling and low density. The level of sVCAM-1 in serum is an independent predictor of SC, but its pathophysiological mechanism remains to be further studied. High expression but not plaque stability; sP-Selectin, MCP-1 and MPO were not associated with plaque stability. The above seven biochemical markers were not associated with CTA plaque load. The traditional FRS score can not reflect the condition of coronary atherosclerosis, especially vulnerable plaque. For the low-risk group of FRS, the occurrence of coronary atherosclerosis, and even the risk of coronary heart disease, the stratified coronary CTA can play a greater role.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.4;R816.2
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