無癥狀中低風(fēng)險人群冠脈斑塊CTA特征與血液生化標(biāo)記物相關(guān)性研究及聯(lián)合預(yù)測斑塊穩(wěn)定性模型的建立
發(fā)布時間：2018-08-31 10:19
【摘要】：[目的]回顧性分析無癥狀非糖尿病FRS中低風(fēng)險人群冠狀動脈粥樣硬化斑塊CTA特征和血液生化標(biāo)記物(脂聯(lián)素、可溶性細胞間粘附分子-1、可溶性血管細胞粘附分子-1、可溶性E-選擇素、可溶性P-選擇素、髓過氧化物酶和白細胞趨化蛋白-1)水平分布特點,探討二者的相關(guān)性；嘗試建立多種生化標(biāo)記物聯(lián)合預(yù)測冠脈斑塊穩(wěn)定性模型并驗證,評價其對于斑塊穩(wěn)定性判斷的可行性,為該組人群冠心病風(fēng)險提供有效監(jiān)測方案。[方法]隨機抽取我院2014年3月-2015年1月期間健康體檢或非心臟手術(shù)術(shù)前查體行冠狀動脈CTA檢查的連續(xù)人群,經(jīng)納入、排除標(biāo)準(zhǔn)篩選后,統(tǒng)一在CTA檢查前1小時內(nèi)抽取血液樣本,采用流式熒光微球技術(shù)進行上述7種生化標(biāo)記物檢測；對CTA斑塊特征進行定性及定量評價；以斑塊穩(wěn)定性分組,采用SPSS 19.0軟件包分析上述CTA斑塊特征與生化標(biāo)記物水平的相關(guān)性,用判別分析的方法建立判別模型并進行模型驗證。[結(jié)果]1.入組對象：共400例,年齡51.5±8歲(29-73歲),其中男性291例(75.5%)。FRS評分1-19%,其中中度風(fēng)險(10-19%)85例(21.25%),低度風(fēng)險(0-9%)315例。2.冠脈CTA特征：400例研究對象中,管腔狹窄程度≥50%的5例,152例無粥樣硬化斑塊形成,248例存在粥樣硬化斑塊,其中181例可見易損斑塊,表現(xiàn)為管壁增厚以非鈣化斑塊為主并呈正性重構(gòu)者108例(27%)、管腔內(nèi)見低密度斑塊者101例(25.25%)、低密度斑塊內(nèi)見點狀鈣化者60例(15%)、管壁增厚并呈“餐巾環(huán)征”者6例(1.5%)、同時具備正性重構(gòu)、低密度斑塊和斑塊內(nèi)點狀鈣化者23例(5.75%)。3.以斑塊穩(wěn)定性分組,經(jīng)單因素及多因素Logistic逐步回歸分析,結(jié)果顯示：年齡(p=0.001)、高血脂病史(p=0.015)、 apoB(p=0.011), ADP(p=0.015)、sE-Selectin (p=0.019)是易損斑塊的獨立預(yù)測因素；其ROC曲線下面積為0.727,診斷敏感度81.6%,特異度56.3%,陽性預(yù)測值65.1%,陰性預(yù)測值75.4%。4.FRS聯(lián)合上述指標(biāo)(年齡、高血脂病史、apoB、HDL-C、ADP、sE-Selectin)預(yù)測易損斑塊的價值：ROC曲線下面積為0.735,敏感度75%,特異度64.5%,陽性預(yù)測值67.9%,陰性預(yù)測值72.1%。5.7種特殊生化標(biāo)記物(ADP,sICAM-1, sVCAM-1, sE-Selectin, sP-Selectin, MPO, MCP-1)與斑塊負荷(SIS、SSS. DS. CS.受累血管數(shù)量、非鈣化斑塊數(shù)量、鈣化斑塊數(shù)量、混合斑塊數(shù)量、易損斑塊數(shù)量)均無相關(guān)性(p0.05)或p0.05,但相關(guān)系數(shù)r0.3,臨床上可認為沒有相關(guān)性。6.用判別分析法建立預(yù)測易損斑塊的聯(lián)合模型并驗證6.1建立判別方程：第一分類函數(shù)：Z1=-28.099+8.991x1+0.947x2+1.602x3+2.511x4+1.126x5+0.423x6第二分類函數(shù)：Z2=-32.227+9.731x1+1.008x2+2.339x3+3.360x4+0.189x5+1.075x6(x1：男性,x2：年齡,x3：高血脂病史,X4:apoB, x5:ADP, X6: sE-Selectin)判別方法：將未知分類的個體的上述基線和生化指標(biāo)分別代入第一和第二分類函數(shù)公式,若所得結(jié)果Z1Z2則歸入對照組,反之,如Z1Z2則歸入實驗組。6.2模型驗證,結(jié)果顯示：采用"Casewise results"的方法得出的判別函數(shù)的正確判斷率為67.0%,使用交互驗證的方法得出判別函數(shù)的正確判斷率為65.1%。[結(jié)論]1.在無癥狀非糖尿病FRS中低風(fēng)險人群中,血清ADP、sE-Selectin水平與CTA所見斑塊穩(wěn)定性密切相關(guān),尤其是有正性重構(gòu)和低密度特征的易損斑塊；血清sVCAM-1水平雖與斑塊穩(wěn)定性無關(guān),但它是SC的獨立預(yù)測因素,其病理生理機制還有待進一步研究；血清sICAM-1s在有粥樣硬化斑塊者中呈明顯高表達,但與斑塊穩(wěn)定性無關(guān)；sP-Selectin、MCP-1和MPO與斑塊穩(wěn)定性無關(guān).上述7種生化標(biāo)記物水平均與CTA斑塊負荷無關(guān).2.在該組人群中,冠心病傳統(tǒng)風(fēng)險因素與多種生化標(biāo)記物組成的聯(lián)合模型在預(yù)測易損斑塊中有一定價值,在無癥狀人群的冠心病CTA普查中可起到一定作用。傳統(tǒng)FRS評分不能反映冠狀動脈粥樣病變,特別是易損斑塊的情況,對于FRS中低風(fēng)險人群中,冠狀動脈粥樣硬化發(fā)生情況、乃至冠心病風(fēng)險的再分層冠脈CTA可發(fā)揮更大的作用。
[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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R541.4;R816.2
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