發(fā)布時(shí)間：2018-08-28 12:30

【摘要】：基于UHPLC-QTOF/MS的冠心病非靶向代謝組學(xué)分析及代謝標(biāo)志物的探索目的:不同人群受到不同遺傳因素和環(huán)境危險(xiǎn)因素相互作用后將最終影響共同的生物代謝過(guò)程,因此通過(guò)代謝組學(xué)手段從小分子代謝物水平的變化研究冠心病動(dòng)脈粥樣硬化的病理形成機(jī)制已成為新的研究方向。本研究旨在通過(guò)非靶向代謝組學(xué)方法探索中國(guó)冠心病患者群體的血漿小分子代謝特點(diǎn)及其與疾病發(fā)生發(fā)展的關(guān)系。方法:經(jīng)過(guò)嚴(yán)格的冠脈造影資料審查,從中國(guó)醫(yī)學(xué)科學(xué)院國(guó)家心血管病中心阜外心血管病醫(yī)院的795位通過(guò)篩選的患者中抽取300位患者建立了一個(gè)獨(dú)立的代謝組學(xué)研究隊(duì)列:150人嚴(yán)重冠脈狹窄的冠心病患者組(severe coronary heart disease,sCHD)和年齡與性別1:1匹配的150人冠脈造影正常對(duì)照組(angiographically normal controls,ANC)。我們將冠狀動(dòng)脈造影顯示至少一支主支冠狀動(dòng)脈管腔直徑縮窄≥80%定義為sCHD組,將經(jīng)冠脈造影確認(rèn)冠狀動(dòng)脈管腔直徑縮窄≤ 20%定義為ANC組。抽取患者的靜脈血分離血漿,運(yùn)用超高效液相色譜-飛行時(shí)間質(zhì)譜聯(lián)用(UHPLC-QTOF/MS)的代謝組學(xué)檢測(cè)方法,從陽(yáng)離子相和陰離子相兩種電離模式進(jìn)行了血漿代謝組學(xué)分析。將篩選出的具有明確二級(jí)質(zhì)譜定性信息的小分子代謝物分別加入多元線性回歸模型(P0.05),分析校正傳統(tǒng)冠心病危險(xiǎn)因素(年齡、性別、體重指數(shù)、糖尿病、高血壓、高脂血癥、冠心病家族史、吸煙史)和檢測(cè)批次等因素。為了防止n次檢驗(yàn)可能帶來(lái)的Ⅰ類錯(cuò)誤,又進(jìn)行了 Bonferroni correction校正(P8.2×10-5(0.05/611)),并使用logistic回歸模型分析了這些小分子代謝物與冠心病患病風(fēng)險(xiǎn)關(guān)聯(lián)的方向和程度。結(jié)果:除年齡和性別進(jìn)行了匹配,冠心病傳統(tǒng)危險(xiǎn)因素在嚴(yán)重冠脈狹窄的冠心病患者組皆顯著高于冠脈造影正常對(duì)照組。300個(gè)血漿樣本上機(jī)檢測(cè)后我們一共獲得611個(gè)(466個(gè)陽(yáng)離子模式、145個(gè)陰離子模式)具有明確定性半定量信息的有效峰,多元線性回歸分析(P0.05)校正傳統(tǒng)冠心病危險(xiǎn)因素和檢測(cè)批次后我們一共篩選出105個(gè)差異代謝物(其中21個(gè)實(shí)為未知代謝物)在兩組間血漿水平具有顯著性差異:主要包含51種磷脂、10種肉毒堿、8種游離脂肪酸類、5種膽汁酸代謝中間產(chǎn)物、3種氨基酸和7種未統(tǒng)一分類代謝物(吲哚、己酮酸、4-吡哆酸、水楊尿酸、咖啡因、睪酮、對(duì)甲氧基苯乙酸)。經(jīng) Bonferroni correction 校正(P8.2×10-5(0.05/611))從 105種差異代謝物中篩選出了 6種組間差異最為顯著的血漿代謝物(吡哆酸、棕櫚酸、亞油酸、脂酰肉毒堿(14:1)、石膽酸、磷脂酰甘油(20:3/2:0)),且這些代謝物皆表現(xiàn)出與冠心病患病風(fēng)險(xiǎn)顯著的正相關(guān)(oddsratio,OR值范圍2.79-7.24)。結(jié)論:本研究借助非靶向代謝組學(xué)方法獲得了中國(guó)冠心病患者群體的代謝指紋圖譜,并首次報(bào)道了吡哆酸、石膽酸和磷脂酰甘油(20:3/2:0)這三種與冠心病病理生理過(guò)程有強(qiáng)關(guān)聯(lián)的潛在生物標(biāo)志物,為從整體水平探索冠心病動(dòng)脈粥樣硬化發(fā)病機(jī)制及尋求新的治療途徑提供了依據(jù)。吡哆酸對(duì)血管內(nèi)皮細(xì)胞增殖及單核巨噬細(xì)胞炎癥反應(yīng)的影響目的:我們前期的研究通過(guò)血漿代謝組學(xué)檢測(cè)發(fā)掘了一種在嚴(yán)重冠脈狹窄的冠心病患者組和冠脈造影正常對(duì)照組之間存在顯著性差異的小分子代謝物吡哆酸，并且發(fā)現(xiàn)血漿吡哆酸每增加1%冠心病患病風(fēng)險(xiǎn)就增加4.879倍。為了進(jìn)一步探討吡哆酸在動(dòng)脈粥樣硬化形成進(jìn)展過(guò)程中的作用，我們?cè)诩?xì)胞水平初步探索了吡哆酸可能對(duì)兩種冠狀動(dòng)脈粥樣硬化病理形成緊密相關(guān)的細(xì)胞(人臍靜脈內(nèi)皮細(xì)胞(HUVEC)，人單核細(xì)胞系(THP-1))產(chǎn)生的影響。方法:我們先后使用不同刺激濃度(20 nmol/L、50 nmol/L、100 nmol/L、200 nmol/L、500 nmol/L、1000 nmol/L、2000 nmol/L)的吡哆酸溶液刺激體外培養(yǎng)的人臍靜脈內(nèi)皮細(xì)胞(HUVEC)、人單核細(xì)胞系(THP-1)，于不同刺激時(shí)點(diǎn)(12h24h48h和72h)通過(guò)細(xì)胞活力檢測(cè)分析吡哆酸對(duì)人臍靜脈內(nèi)皮細(xì)胞產(chǎn)生的增殖影響，于吡哆酸刺激 48h 時(shí)通過(guò)實(shí)時(shí)熒光定量 PCR(Real-time quantitative Polymerase Chain ReactionqRT-PCR)的方法檢測(cè)白介素1β(IL-1β)、腫瘤壞死因子(TNF-α)和細(xì)胞粘附因子(ICAM)的表達(dá)變化以評(píng)估炎癥反應(yīng)變化。結(jié)果:研究發(fā)現(xiàn)給予吡哆酸刺激48小時(shí)，人臍靜脈內(nèi)皮細(xì)胞增殖活力開(kāi)始發(fā)生了顯著下降且隨著吡哆酸濃度增加而逐漸降低2000nmol/L濃度刺激時(shí)最低可下降10.7%。給予吡哆酸刺激72小時(shí)，人臍靜脈內(nèi)皮細(xì)胞增殖活力從刺激濃度20nmol/L起即表現(xiàn)出增殖活力顯著下降，隨著吡哆酸濃度增加而逐漸降低，1000nmol/L濃度刺激時(shí)最低可下降10.56%。低濃度的吡哆酸刺激沒(méi)有誘發(fā)單核細(xì)胞的炎癥反應(yīng)，而當(dāng)吡哆酸濃度為1000nmol/L和2000nmol/L時(shí)，THP-1細(xì)胞IL-1β、TNF-α和ICAM表達(dá)顯著高于空白對(duì)照組細(xì)胞，，IL-1β表達(dá)量最高升高到1.22倍、TNF-α的表達(dá)量最高升高到1.4倍、ICAM的表達(dá)量最高升高到1.74倍。結(jié)論:吡哆酸能夠誘導(dǎo)人臍靜脈內(nèi)皮細(xì)胞出現(xiàn)增殖抑制、人單核細(xì)胞系炎癥因子(IL-1β、TNF-α、ICAM)表達(dá)上調(diào)，因此推測(cè)血漿吡哆酸水平升高與動(dòng)脈粥樣硬化的形成、發(fā)展相關(guān)。混合置入藥物洗脫支架和金屬裸支架治療多處病變冠心病患者的遠(yuǎn)期療效和安全性評(píng)價(jià)目的:藥物洗脫支架(DES)有效降低了金屬支架置入后的再狹窄發(fā)生率及靶血管或靶病變的血運(yùn)重建率,但其涂層藥物能夠?qū)е掳醒軆?nèi)皮修復(fù)延遲以及致死性支架內(nèi)血栓形成風(fēng)險(xiǎn)升高,引起了學(xué)界對(duì)DES使用安全性的關(guān)注與探討。因此針對(duì)冠狀動(dòng)脈多處病變患者,術(shù)者們開(kāi)始嘗試藥物洗脫支架和金屬裸支架混合置入(Hybrid支架)的介入治療策略,以期通過(guò)適度減少藥物支架置入數(shù)量來(lái)提高PCI治療安全性并獲得最佳的臨床效果。本研究旨在評(píng)估混合置入藥物洗脫支架(Hybrid支架)和金屬裸支架治療多處病變冠心病患者的遠(yuǎn)期療效和安全性。方法:本研究入選了 2004年4月至2006年10月期間,在我院行擇期經(jīng)皮冠狀動(dòng)脈介入治療(PCI)的冠狀動(dòng)脈多處病變患者共計(jì)6495例,并根據(jù)支架置入種類分為藥物洗脫支架和金屬裸支架混合置入組(Hybrid組,848例)和單純藥物洗脫支架置入組(5647例)。按1:1的比例進(jìn)行傾向性評(píng)分匹配后,共823對(duì)患者最終納入研究。臨床隨訪資料包括術(shù)后30天、1年和2年的死亡、心肌梗死、靶病變血運(yùn)重建、靶血管血運(yùn)重建、主要心臟不良事件和支架內(nèi)血栓形成。研究對(duì)比分析了兩組術(shù)后2年內(nèi)的各種臨床事件的累積發(fā)生率差異,并通過(guò)Cox比例風(fēng)險(xiǎn)模型對(duì)臨床事件風(fēng)險(xiǎn)進(jìn)行了評(píng)估。結(jié)果:經(jīng)過(guò)傾向性評(píng)分匹配后COX比例風(fēng)險(xiǎn)模型分析顯示術(shù)后2年Hybrid支架治療組靶病變血運(yùn)重建(風(fēng)險(xiǎn)比2.38,95%可信區(qū)間1.50-3.70)、靶血管血運(yùn)重建(風(fēng)險(xiǎn)比1.61,95%可信區(qū)間1.15-2.27)以及主要心臟不良事件(風(fēng)險(xiǎn)比1.37,95%可信區(qū)間1.02-1.85)的風(fēng)險(xiǎn)顯著高于單純DES支架治療組,兩組間全因死亡、心肌梗死和全因死亡/心肌梗死差異無(wú)統(tǒng)計(jì)學(xué)意義。術(shù)后2年Hybrid支架治療組累積晚期血栓發(fā)生率顯著低于單純DES支架治療組(P=0.0112),而2年累積支架內(nèi)其他血栓形成事件:肯定的血栓、肯定+可能血栓、早期血栓及極晚期血栓發(fā)生率無(wú)明顯差異。結(jié)論:對(duì)于冠狀動(dòng)脈多處病變需置入多支架的患者而言,單純藥物洗脫支架置入的遠(yuǎn)期有效性明顯優(yōu)于混合置入藥物洗脫支架和金屬裸支架,兩種支架置入策略安全性相當(dāng)。冠狀動(dòng)脈介入治療后圍術(shù)期心肌梗死風(fēng)險(xiǎn)模型及評(píng)分系統(tǒng)研究目的:既往國(guó)內(nèi)外關(guān)于經(jīng)皮冠狀動(dòng)脈介入治療(PCI)后圍術(shù)期心肌梗死的發(fā)生風(fēng)險(xiǎn)并無(wú)系統(tǒng)、全面的研究,本研究旨在針對(duì)美國(guó)心血管介入學(xué)會(huì)(SCAI)制定的PMI定義,系統(tǒng)的篩選出圍術(shù)期心肌梗死的獨(dú)立危險(xiǎn)因素,并建立PMI風(fēng)險(xiǎn)模型及評(píng)分系統(tǒng),用于全面評(píng)估多個(gè)危險(xiǎn)因素共同作用下圍術(shù)期心肌梗死的風(fēng)險(xiǎn)。方法:本研究入選了 2013年1月至2013月12月間在中國(guó)醫(yī)學(xué)科學(xué)院阜外醫(yī)院成功行擇期PCI治療并具備圍術(shù)期心臟損傷標(biāo)志物監(jiān)測(cè)資料的患者共3371例(3516次PCI治療)。根據(jù)患者術(shù)后是否發(fā)生SCAI所定義的圍術(shù)期心肌梗死(PMI),分為圍術(shù)期心肌梗死組和無(wú)圍術(shù)期心肌梗死組。篩選可能影響圍術(shù)期心肌梗死的危險(xiǎn)因素:患者臨床基線資料、心肌損傷標(biāo)志物等生化指標(biāo)、冠狀動(dòng)脈造影特點(diǎn)、介入操作特點(diǎn)等,納入Logistic多元回歸分析識(shí)別出圍術(shù)期心肌梗死的獨(dú)立危險(xiǎn)因子并建立圍術(shù)期心肌梗死風(fēng)險(xiǎn)模型。根據(jù)各個(gè)危險(xiǎn)因素對(duì)圍術(shù)期心肌梗死的危險(xiǎn)度分配相應(yīng)的分?jǐn)?shù),形成PMI風(fēng)險(xiǎn)評(píng)分系統(tǒng)。通過(guò)Bootstrap方法從入選患者中內(nèi)部驗(yàn)證評(píng)分系統(tǒng)(樣本量n=3516,再抽樣次數(shù)B=1000),進(jìn)一步驗(yàn)證風(fēng)險(xiǎn)模型和評(píng)分系統(tǒng)的預(yù)測(cè)能力和有效性。結(jié)果:在所有成功實(shí)施經(jīng)皮冠狀動(dòng)脈介入治療的3371例患者患者中,有107例患者(3.1%)對(duì)應(yīng)108次PCI治療發(fā)生了圍術(shù)期心肌梗死。通過(guò)多因素Logistic回歸分析發(fā)現(xiàn),影響圍術(shù)期心肌梗死的獨(dú)立危險(xiǎn)因素有:年齡(比值比(OR)為1.037,95%置信區(qū)間(CI):1.016-1.058;P0.01)、多支血管治療(OR 為 1.697,95%CI:1.095-2.629;P=0.02)、至少一處分叉病變治療(OR 為 1.869,95%CI:1.213-2.878;P0.01)、靶病變總長(zhǎng)度(OR為1.016,95%CI:1.009-1.024;P0.01)。由此建立的PMI評(píng)分系統(tǒng) ROC 曲線下面積為 0.71(95%CI:0.66-0.76),H-L p=0.5;經(jīng) Bootstrap 方法內(nèi)部驗(yàn)證得到PMI風(fēng)險(xiǎn)評(píng)分系統(tǒng)平均ROC曲線下面積為0.707,中位ROC曲線下面積為0.708;根據(jù)PMI評(píng)分的四分位數(shù),將前三個(gè)四分位Q1-Q3合并定義為非PMI高危組(對(duì)應(yīng)風(fēng)險(xiǎn)評(píng)分10分)而第四四分位Q4定義為為PMI高危組(對(duì)應(yīng)風(fēng)險(xiǎn)評(píng)分≥10分),圍術(shù)期心肌梗死風(fēng)險(xiǎn)在PMI高危組顯著高于非PMI高危組(P0.01)。結(jié)論:本研究全面系統(tǒng)的篩選出了影響圍術(shù)期心肌梗死的獨(dú)立危險(xiǎn)因素:年齡、靶病變總長(zhǎng)度、多支血管治療、至少一處分叉病變治療,并建立了簡(jiǎn)便易用的PCI后圍術(shù)期心肌梗死風(fēng)險(xiǎn)評(píng)分,準(zhǔn)確劃分出圍術(shù)期心肌梗死的高風(fēng)險(xiǎn)患者,為臨床決策提供客觀依據(jù)。
[Abstract]:Untargeted metabolomic analysis and exploration of metabolic markers for coronary heart disease based on UHPLC-QTOF/MS Objective: Different populations will eventually affect the common metabolic processes after interaction between different genetic and environmental risk factors, so the changes of small molecular metabolites in coronary heart disease atherosclerosis will be studied by metabonomics. The aim of this study was to explore the characteristics of plasma small molecule metabolism and its relationship with the occurrence and development of coronary heart disease in Chinese population by non-targeted metabonomics. An independent metabonomic cohort of 795 selected patients from the Cardiovascular Hospital outside Heart Fuwai was established: 150 patients with severe coronary heart disease (sCHD) and 150 age-and sex-matched normal coronary angiographic con. Trols, ANC. We defined coronary artery angiography showing at least one main coronary artery lumen narrowing (> 80%) as the sCHD group and coronary artery lumen narrowing (< 20%) as the ANC group. METABOLOGICAL DETECTION METABOLOGICAL METABOLISM METABOLOGICAL ANALYSIS OF PLASMA FROM IONIZATION MODELS OF CATIONIC AND ANIONIC PHASES. The selected small molecular metabolites with definite qualitative information of secondary mass spectrometry were added to the multiple linear regression model (P 0.05) to analyze and correct the traditional risk factors of coronary heart disease (age, sex, body mass index, diabetes mellitus). Bonferroni correction (P8.2 x 10-5 (0.05/611)) was used to prevent class I errors caused by n tests, and logistic regression model was used to analyze the direction and course of the association between these small molecular metabolites and coronary heart disease risk. Results: Except for age and sex matching, the traditional risk factors of coronary heart disease in patients with severe coronary stenosis were significantly higher than those in the normal control group. A total of 105 metabolites (21 of which were unknown metabolites) were screened out after adjusting for the risk factors and batches of traditional coronary heart disease (P 0.05). There were significant differences in plasma levels between the two groups: 51 phospholipids, 10 carnitines, 8 free fatty acids, and 5 bile acid metabolites. Products, 3 amino acids and 7 undifferentiated metabolites (indole, pentoxylic acid, 4-pyridoxic acid, salicyluric acid, caffeine, testosterone, p-methoxyphenylacetic acid). The plasma metabolites (pyridoxic acid, palmitic acid, subunit) with the most significant difference were screened from 105 different metabolites by Bonferroni correction. Oleic acid, lipoacyl carnitine (14:1), cholic acid, phosphatidylglycerol (20:3/2:0), and these metabolites all showed significant positive correlation with the risk of coronary heart disease (odds ratio, OR value range 2.79-7.24). Conclusion: The metabolic fingerprints of CHD patients in China were obtained by non-targeted metabonomics method, and piperidine was reported for the first time. These three potential biomarkers, namely, oxalic acid, cholic acid and phosphatidylglycerol (20:3/2:0), are strongly associated with the pathophysiological process of coronary heart disease. These biomarkers provide a basis for exploring the pathogenesis of coronary atherosclerosis at the overall level and for seeking new therapeutic approaches. Pyridoxic acid has effects on vascular endothelial cell proliferation and inflammation of mononuclear macrophages. Impact Objectives: Our previous study identified a small molecule metabolite pyridoxine with significant differences between patients with severe coronary artery stenosis and normal controls on coronary angiography, and found that the risk of coronary heart disease increased by 4.879 times for each 1% increase in plasma pyridoxine. To investigate the role of pyridoxine in the development of atherosclerosis, we initially explored the effect of pyridoxine on two types of cells (human umbilical vein endothelial cells (HUVEC) and human monocyte line (THP-1) closely related to the pathological formation of coronary atherosclerosis at the cellular level. Human umbilical vein endothelial cells (HUVEC) and human monocyte lines (THP-1) were stimulated by pyridoxic acid at concentrations (20 nmol/L, 50 nmol/L, 100 nmol/L, 200 nmol/L, 500 nmol/L, 1000 nmol/L, 2000 nmol/L) in vitro. The proliferation of human umbilical vein endothelial cells (HUVEC) and human monocyte lines (THP-1) at different stimulation points (12 h, 24 h, 48 h and 72 h) was analyzed by cell viability assay. Reproductive effects were assessed by real-time quantitative polymerase chain reaction (Real-time quantitative polymerase Chain ReactionqRT-PCR) with the expression of interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and cell adhesion factor (ICAM) at 48 h after pyridoxine stimulation. The proliferative activity of human umbilical vein endothelial cells (HUVECs) began to decrease markedly and decreased by 10.7% when the concentration of pyridoxine increased, and decreased by 2 000 nmol/L. After 72 hours of stimulation with pyridoxine, the proliferative activity of HUVECs decreased markedly from 20 nmol/L to 20 nmol/L, and with pyridoxine, the proliferative activity of HUVECs decreased significantly. The expression of IL-1beta, TNF-alpha and ICAM in THP-1 cells was significantly higher than that in blank control cells, and the expression of IL-1beta and ICAM in THP-1 cells was up to 1.5% when the concentration of pyridoxine was 1000 nmol/L and 2000 nmol/L. Conclusion: Pyridoxic acid can induce the proliferation inhibition of human umbilical vein endothelial cells, and the expression of human monocyte inflammatory factors (IL-1 beta, TNF-a, ICAM) is up-regulated. Therefore, it is speculated that the increase of plasma pyridoxic acid level and the formation and development of atherosclerosis. Long-term efficacy and safety of drug-eluting stents and bare metal stents in the treatment of multiple coronary artery disease Objective: Drug-eluting stents (DES) can effectively reduce the incidence of restenosis after metal stent implantation and the revascularization rate of target vessel or target lesion, but their coated drugs can lead to target vessel endothelial repair. Delayed and increased risk of fatal stent thrombosis has attracted attention and discussion in academia on the safety of DES use. Therefore, for patients with multiple coronary artery lesions, surgeons have begun to try the intervention strategy of drug-eluting stent and metal bare stent implantation (Hybrid stent), with a view to reducing drug-eluting stent implantation appropriately. The aim of this study was to evaluate the long-term efficacy and safety of a combination of drug-eluting stents (Hybrid stents) and bare metal stents in the treatment of multiple lesions of coronary artery disease. A total of 6495 patients with multiple coronary artery lesions underwent coronary interventional therapy (PCI) were divided into drug-eluting stent and bare metal stent implantation groups (Hybrid group, 848 cases) and drug-eluting stent implantation group (5647 cases). Clinical follow-up data included 30-day, 1-year and 2-year mortality, myocardial infarction, revascularization of target lesions, revascularization of target vessels, major adverse cardiac events and stent thrombosis. The cumulative incidence of various clinical events during the 2-year follow-up period was compared between the two groups, and the clinical events were analyzed by Cox proportional hazard model. Results: The COX proportional hazard model after propensity score matching showed target revascularization (risk ratio 2.38,95% CI 1.50-3.70), target revascularization (risk ratio 1.61,95% CI 1.15-2.27) and major adverse cardiac events (risk ratio 1.37,95% Cocoa) in the Hybrid stent group 2 years after surgery. The risk of all-cause mortality, myocardial infarction, and all-cause mortality / myocardial infarction was not significantly different between the two groups. The cumulative incidence of late thrombosis in the Hybrid stent group was significantly lower than that in the DES stent group at 2 years after surgery (P = 0.0112), while other stent thrombosis was cumulative in 2 years. Events: There was no significant difference in the incidence of positive thrombosis, positive + possible thrombosis, early thrombosis and very late thrombosis. Conclusion: For patients with multiple coronary lesions requiring multi-stent implantation, the long-term efficacy of drug-eluting stent implantation alone was significantly better than that of drug-eluting stent and bare metal stent implantation. The risk model and scoring system for perioperative myocardial infarction after percutaneous coronary intervention (PCI) Objective: There was no systematic and comprehensive study on the risk of perioperative myocardial infarction after PCI at home and abroad. This study was aimed at PMI formulated by American Society of Cardiovascular Intervention (SCAI). Definition, systematic screening of independent risk factors for perioperative myocardial infarction, and establishment of a PMI risk model and scoring system for a comprehensive assessment of the risk of perioperative myocardial infarction under the combined effects of multiple risk factors. A total of 3 371 patients (3 516 PCIs) were treated and monitored for perioperative cardiac injury markers. The patients were divided into perioperative myocardial infarction group and non-perioperative myocardial infarction group according to the occurrence of perioperative myocardial infarction (PMI) defined by SCAI. The independent risk factors of perioperative myocardial infarction were identified by logistic multivariate regression analysis and the perioperative myocardial infarction risk model was established. The predictive power and effectiveness of the risk model and scoring system were further validated by the Bootstrap method (sample size n = 3516, sample number B = 1000). Results: Of the 3 371 patients who had successfully undergone percutaneous coronary intervention, 107 were enrolled. Perioperative myocardial infarction occurred in 108 PCI patients (3.1%). The independent risk factors for perioperative myocardial infarction were age (OR) 1.037,95% confidence interval (CI): 1.016-1.058; P 0.01), multi-vessel therapy (OR: 1.697,95% CI: 1.095-2.629; P = 0.02). Treatment of fork lesions (OR 1.869, 95% CI: 1.213-2.878; P 0.01), total length of target lesions (OR 1.016, 95% CI: 1.009-1.024; P 0.01). The area under the ROC curve of the PMI scoring system was 0.71 (95% CI: 0.66-0.76) and H-L P = 0.5. The average area under the ROC curve of the PMI risk scoring system was 0.707 and the median ROC curve was obtained by internal verification of Bootstrap method. According to the quartile of PMI score, the first three quartile Q1-Q3 was defined as non-PMI high-risk group (corresponding risk score 10 points), while the fourth quartile Q4 was defined as PMI high-risk group (corresponding risk score < 10 points), and the perioperative risk of myocardial infarction was significantly higher in PMI high-risk group than in non-PMI high-risk group (P 0.01). Independent risk factors affecting perioperative myocardial infarction were systematically screened: age, total length of target lesion, multi-vessel therapy, to
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541.4

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