1、學(xué)士論文胱抑素C對(duì)急性冠脈綜合征PCI術(shù)預(yù)后的判斷    【摘要】目的 探討血漿胱抑素C（cystatin C，CysC）水平對(duì)急性冠脈綜合征（acute coronary syndromes，ACS）患者經(jīng)皮冠狀動(dòng)脈介入（percutanceous coronary intervention，PCI）術(shù)后預(yù)后的判斷價(jià)值。策略 連續(xù)選取2009年9月至2010年6月于鄭州大學(xué)第一附屬醫(yī)院心內(nèi)科住院的ACS患者660例為探討對(duì)象。入選標(biāo)準(zhǔn)：冠脈造影顯示至少一支血管狹窄程度為75%以上，成功接受PCI手術(shù)治療，且腎功能正常或有著輕度腎功能不建全腎小球?yàn)V過率（

2、GFR）>60 ml/（min?1.73 m2）。排除標(biāo)準(zhǔn)：嚴(yán)重肝腎功能損傷或患有腫瘤、心臟瓣膜病。記錄患者入院24 h內(nèi)血漿CysC濃度（乳膠增強(qiáng)免疫比濁法）及其他臨床資料。于2011年3月至7月進(jìn)行門診和電話隨訪，記錄心臟不良事件的發(fā)生情況。根據(jù)CysC四分位數(shù)將患者分為4組：Q1（CysC【關(guān)鍵詞】急性冠脈綜合征；血管成形術(shù)；經(jīng)皮冠狀動(dòng)脈介入；胱抑素C；心臟不良事件The predictive value of cystatin C in patients with acute coronary syndrome after percutaneous coronary interv

3、ention SUN Tong-wen, XU Qing-yan, YAO Hai-mu, ZHANG Xiao-juan, WU Qiong, YAO Rui,ZHANG Jin-ying，LI Ling,GUAN Fang-xia,KAN Quan-cheng.Department of Integrated ICU, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaCorresponding author:KAN Quan-cheng,Email:suntongwen【Abstract】O

4、bjective To investigate the predictive value of plasma cystatin C (CysC) in patients with acute coronary syndrome(ACS) after percutaneous coronary intervention (PCI) . Methods A total of 660 patients with ACS admitted to cardiovascular department were enrolled in this study from January 2009 to June

5、 2010. The enrollment criteria were: (1) the stenosis degree was above 75% in at least one coronary artery checked by coronary angiography and successful PCI; (2) normal renal function or mild dysfunction with glomerular filtration rate (GFR) >60 ml/（min?1.73 m2）. Exclusion criteria were severe l

6、iver and renal insufficiency, malignancies and valvular heart diseases. The plasma CysC levels were examined by the latex enhanced immune turbidity method within 24 hours after admission. The relevant clinical data were recorded. The patients were followed up by out-patient interview or telephone fr

7、om March to June 2011 and adverse cardiovascular events were recorded. The patients were divided into four groups according to CysC level: Q1 (CysC< 1.35 mg/L) and Q4 (CysC1.35 mg/L). Univariate and multivariate Cox hazards regressions were established to analyze the factors related to prognosis.

8、 The proportion differences between four groups were tested by 2. The survival ratio was estimated using the Kaplan-Meier method. Statistical significance was established at a P value of less than 0.05.Results A total of 606 (91.7%) patients successfully accepted follow-up. Mean follow-up time was （

9、14.3±1.7） months. Of them, 95 patients were subjected to adverse cardiovascular events (15.7%). The incidences of adverse cardiovascular events in Q2, Q3, Q4 were significantly higher than those in Q1 (P以是否發(fā)生心臟不良事件為因變量，以性別、年齡、糖尿病、高血壓病、CysC、WBC計(jì)數(shù)、肌酐、GFR、LVEF、既往行PCI術(shù)、NYHA分組、病變血管支數(shù)、置入支架數(shù)作為協(xié)變量（各變量的

10、取值方式見表3），進(jìn)行多因素Cox回歸淺析，結(jié)果顯示與心臟不良事件的發(fā)生有關(guān)的危險(xiǎn)因子是CysC和LVEF。與Q1組比較，CysC較高的Q3、Q4組發(fā)生心臟不良事件RR值分別為3.930（95% CI 1.30611.829，P=0.015）和6.38（95% CI 2.17118.751，P=0.001），而輕度升高Q2組的RR值分別為1.272（95% CI 0.3404.758，P=0.72）。與LVEF50%組比較，40%LVEF<50%組和LVEF<0.01）（見表4）。2.5 Kaplan-Meier存活曲線淺析結(jié)果對(duì)CysC四組患者進(jìn)行Kaplan-Meier存活曲線

11、淺析，log-rank檢驗(yàn)結(jié)果顯示： Q2、Q3、Q4組患者無心臟不良事件存活率較Q1組顯著降低， P<0.01，見圖1。3 討論既往探討表明，輕微的或亞臨床期腎功能不建全是預(yù)測(cè)冠心病患者死亡和心臟不良事件發(fā)生的獨(dú)立危險(xiǎn)因素4，本探討結(jié)果顯示肌酐是預(yù)后不良的危險(xiǎn)因素，但GFR與預(yù)后不相關(guān)（P=0.057），考慮是計(jì)算歷程中的誤差或抽樣誤差或樣本含量少所致。評(píng)估腎功能的傳統(tǒng)指標(biāo)有肌酐和肌酐清除率等，但是這些指標(biāo)在檢測(cè)輕度腎功能不建全方面有一定局限性，肌酐一般在GFR< 60 ml/ (min ? 1.73 m2)以下時(shí)才會(huì)顯著升高，并且易受年齡、性別、肌肉活動(dòng)、飲食等因素的影響，肌酐

12、清除率檢測(cè)歷程較復(fù)雜，臨床很少運(yùn)用；然而CysC在體內(nèi)含量穩(wěn)定，不受年齡、性別、肌肉活動(dòng)等因素影響，敏感反映GFR轉(zhuǎn)變，在腎功能輕度下降時(shí)即可升高，對(duì)于心血管患者早期檢測(cè)腎功能不建全具有重要的作用，以而可盡早干預(yù)，改善預(yù)后。近年來， CysC在粥樣硬化及心血管疾病發(fā)生、進(jìn)展方面的重要作用越來越受到關(guān)注5-6，國外一些探討顯示CysC水平與心血管疾病患者預(yù)后密切相關(guān)。Taglieri等7發(fā)現(xiàn)顯示CysC0.93 mg/L 的ACS患者隨訪1年后出現(xiàn)心源性死亡、心梗和不穩(wěn)定心絞痛事件的比率較大，并且質(zhì)量濃度越高，比率越大。Keller等8以腎功能正常或輕度下降的ACS患者為探討對(duì)象，結(jié)果顯示Cys

13、C濃度與心臟死亡事件的發(fā)生密切相關(guān)，引入 C反應(yīng)蛋白（C-reactive protein，CRP）、氨基末端腦鈉肽后，這種相關(guān)性仍較強(qiáng)。Koenig等9探討表明高水平CysC與再次發(fā)生心梗、腦卒中有關(guān)。但是關(guān)于CysC在ACS患者PCI術(shù)后的預(yù)測(cè)作用報(bào)道相對(duì)較少。雖然Eiji等10 關(guān)于ST段抬高型ACS患者PCI術(shù)后探討顯示高水平CysC組患者由于心力衰竭再入院機(jī)率較大，但納入標(biāo)準(zhǔn)不嚴(yán)格，考慮預(yù)后不良與嚴(yán)重腎功能不建全有關(guān)。而本探討選取腎功能正常或輕度腎功能不建全的ACS并成功實(shí)施PCI治療的患者為探討對(duì)象，單因素和多因素淺析結(jié)果均顯示，隨著血漿CysC水平的升高，心臟不良事件的發(fā)生率逐漸

14、增高。多因素Cox回歸淺析結(jié)果顯示CysC是ACS患者PCI術(shù)后出現(xiàn)心臟不良事件的獨(dú)立危險(xiǎn)因素，CysC 1.17 mg /L和CysC 1.35 mg /L 時(shí)患者出現(xiàn)心臟不良事件的風(fēng)險(xiǎn)增加3.93倍和6.38倍。進(jìn)一步淺析顯示，CysC與死亡、心肌梗死或血運(yùn)重建、心力衰竭事件發(fā)生密切相關(guān)，而與腦卒中、心絞痛再發(fā)沒有顯示出統(tǒng)計(jì)學(xué)作用。筆者認(rèn)為，這表明CysC與疾病的嚴(yán)重程度有關(guān)，可以預(yù)測(cè)死亡、心肌梗死、心力衰竭的發(fā)生。而腦卒中、心絞痛再發(fā)病情相對(duì)較輕，且例數(shù)較少，故未顯示出統(tǒng)計(jì)學(xué)作用。本探討結(jié)果未顯示肌酐、GFR與預(yù)后相關(guān)，推測(cè)CysC還可以通過非腎臟作用影響預(yù)后。CysC可以抑制組織蛋白酶

15、和一些激素前體的活性，參與炎癥歷程，影響細(xì)胞外基質(zhì)降解以而影響動(dòng)脈粥樣硬化的進(jìn)程。有動(dòng)物實(shí)驗(yàn)直接證實(shí)了CysC可以減少血管壁外細(xì)胞質(zhì)基質(zhì)降解，延緩血管壁重構(gòu)進(jìn)程11。粥樣硬化病變及血管損傷的內(nèi)皮增生部位的組織蛋白酶和CysC均升高12，組織蛋白酶推動(dòng)彈性纖維和膠原分解， 而CysC能強(qiáng)烈抑制組織蛋白酶活性，但增高程度沒有前者大，兩者之間不平衡影響細(xì)胞外基質(zhì)的動(dòng)態(tài)平衡，最后導(dǎo)致血管狹窄形成。CysC可以影響中性粒細(xì)胞的遷移，與CRP、白介素-6（interleukin，IL-6）和腫瘤壞死因子-（tumor necrosis factor-，TNF-）等炎癥因子有關(guān)，可以反映炎癥增強(qiáng)及病變程度。

16、另外CysC與動(dòng)脈粥樣斑塊的消退及穩(wěn)定性密切相關(guān)13，本探討選取ACS接受PCI治療的患者為探討對(duì)象，發(fā)現(xiàn)CysC可以預(yù)測(cè)死亡、心梗或血運(yùn)重建和心力衰竭的發(fā)生，表明CysC與冠狀動(dòng)脈粥樣硬化的進(jìn)展和斑塊的不穩(wěn)定有關(guān)。既往探討表明，高血壓、糖尿病、高血脂、吸煙以及血管病變程度、多支病變、支架長度等因素，是再狹窄發(fā)生的預(yù)測(cè)因素14-15。而本探討顯示CysC、肌酐、年齡、LVEF、既往PCI史、NYHA分級(jí)3級(jí)是發(fā)生心臟不良事件的危險(xiǎn)因素，也與再狹窄有關(guān)。年齡較大、心功能較差、既往PCI術(shù)史的患者則可能血管病變較嚴(yán)重或者有著多支病變，CysC和肌酐升高，腎功能不建全會(huì)導(dǎo)致脂質(zhì)代謝異常，與以上探討結(jié)

17、果相似。張良等16探討發(fā)現(xiàn) ， CysC水平較高的患者，PCI術(shù)后6個(gè)月支架內(nèi)再狹窄和靶血管新生病變的發(fā)生率顯著增高，表明CysC與再狹窄相關(guān)。PCI術(shù)后再狹窄的發(fā)生還與血管平滑肌細(xì)胞增生過度、凋亡不足、血栓形成、內(nèi)皮細(xì)胞損傷及炎癥等有關(guān)。本探討顯示CysC水平高的患者，心梗和再次血運(yùn)重建的發(fā)生率較高，也間接表明CysC與再狹窄的發(fā)生有關(guān)。另外，本探討顯示病變血管數(shù)、植入支架數(shù)與預(yù)后的聯(lián)系沒有顯示出統(tǒng)計(jì)學(xué)作用，考慮為單中心樣本，抽樣誤差有關(guān)。本探討未記錄冠狀動(dòng)脈病變的狹窄程度、置入支架的長度、直徑等，未記錄CRP、腦鈉肽等可能預(yù)測(cè)預(yù)后的指標(biāo)，無法對(duì)CysC與這些因素的聯(lián)系進(jìn)行探討；未能記錄患者

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