64排CT測(cè)量心外膜脂肪組織體積與冠心病的相關(guān)性

黃少華 王 駿 孫育民 張 雁 曹 賓 陶文其 徐志強(qiáng) 羅心平 李 劍

(1上海市靜安區(qū)中心醫(yī)院心內(nèi)科 上海 200040; 2復(fù)旦大學(xué)附屬華山醫(yī)院心內(nèi)科 上海 200040)

64排CT測(cè)量心外膜脂肪組織體積與冠心病的相關(guān)性

黃少華1,2王 駿1孫育民1張 雁1曹 賓1陶文其1徐志強(qiáng)1羅心平2△李 劍2

(1上海市靜安區(qū)中心醫(yī)院心內(nèi)科 上海 200040;2復(fù)旦大學(xué)附屬華山醫(yī)院心內(nèi)科 上海 200040)

目的 評(píng)價(jià)心外膜脂肪組織(epicardial adipose tissue,EAT)體積與冠心病的存在及嚴(yán)重度的相關(guān)性。 方法 納入同期行64排CT (computed tomography,CT)冠狀動(dòng)脈成像及經(jīng)皮冠狀動(dòng)脈造影的疑似冠心病患者201例。通過(guò)CT測(cè)量EAT體積和冠狀動(dòng)脈鈣化積分(coronary artery calcium,CAC)。根據(jù)冠脈造影結(jié)果進(jìn)行CAGE≥20、CAGE≥50及Gensini評(píng)分,再根據(jù)評(píng)分確定冠心病的程度和嚴(yán)重性。通過(guò)統(tǒng)計(jì)學(xué)方法分析EAT體積值與冠心病的相關(guān)性。 結(jié)果 根據(jù)冠狀動(dòng)脈造影結(jié)果分為正常組(108例)及冠心病組(93例)。冠心病組EAT體積平均值明顯大于正常組[(135.36±45.36) cm3vs. (88.56±40.64)cm3],兩組相比差異有顯著統(tǒng)計(jì)學(xué)意義(P=0.004),而體質(zhì)量指數(shù)(BMI)及腰圍(WC)在兩組間無(wú)統(tǒng)計(jì)學(xué)差異。在多因素Logistic回歸分析中,在調(diào)整了年齡、性別、吸煙、飲酒以及BMI因素后,EAT體積與冠心病和CAC顯著相關(guān)(P=0.009)。在線性回歸分析中,EAT體積與CAGE≥20、CAGE≥50和Gensini評(píng)分顯著相關(guān)(P<0.05)。并且隨著EAT體積的增加,冠心病的嚴(yán)重程度隨之增加(P<0.05)。 結(jié)論 EAT體積與冠心病的存在和嚴(yán)重程度相關(guān)。EAT可以作為冠心病風(fēng)險(xiǎn)的預(yù)測(cè)因子。

心外膜脂肪組織; 冠心病; 多層螺旋CT

傳統(tǒng)觀念認(rèn)為心外膜脂肪組織(epicardial adipose tissue,EAT)僅為能量?jī)?chǔ)備器官和心臟保護(hù)支持結(jié)構(gòu),新近研究發(fā)現(xiàn)EAT與動(dòng)脈粥樣硬化的發(fā)生和發(fā)展密切相關(guān)[1-2]。鑒于EAT在冠心病發(fā)病機(jī)制中的基礎(chǔ)研究進(jìn)展,業(yè)界開(kāi)始關(guān)注EAT擴(kuò)增能否成為預(yù)測(cè)冠心病發(fā)生、發(fā)展的新標(biāo)志物。目前國(guó)內(nèi)外已有EAT與冠心病的相關(guān)性研究報(bào)道,但對(duì)于EAT與冠心病的嚴(yán)重程度或冠狀動(dòng)脈粥樣硬化的關(guān)系仍有爭(zhēng)論[3-6],部分是源于測(cè)量方法的限制[7]。近年來(lái)隨著醫(yī)學(xué)影像技術(shù)的進(jìn)展,使得CT可以準(zhǔn)確對(duì)EAT進(jìn)行定量分析[8]。本研究采用64排多層螺旋CT(multislice spiral CT,MSCT)測(cè)量EAT體積,評(píng)價(jià)其與冠心病的存在和嚴(yán)重程度的相關(guān)性。

資 料 和 方 法

入選病例 2014年1月至2015年12月在復(fù)旦大學(xué)附屬華山醫(yī)院靜安分院就診的疑似心絞痛患者,同期行64排MSCT冠脈檢查及經(jīng)皮冠狀動(dòng)脈造影(coronary angiography,CAG)檢查。共納入201例患者,其中男性108例(年齡40～75歲,平均年齡60.4歲),女性93例(年齡43～78歲,平均年齡63.3歲)。

排除標(biāo)準(zhǔn) (1) 對(duì)造影劑過(guò)敏患者;(2) 肥胖患者(BMI>27);(3)拒絕接受CT血管造影(CT angiograph,CTA)或CAG檢查患者;(4)嚴(yán)重肝腎功能不全者;(5)既往曾行冠狀動(dòng)脈介入手術(shù)或冠脈搭橋手術(shù)者;(6)年齡>80歲;(7)甲狀腺功能疾病患者;(8)家族性高脂血癥患者;(9)心室率無(wú)法控制在75次/分以下及房顫患者。

心外膜脂肪體積及鈣化積分的測(cè)量方法 應(yīng)用64排多層螺旋CT(德國(guó)Simens SOTOMON)行回顧性心電門控掃描。經(jīng)上肢遠(yuǎn)端靜脈或肘正中靜脈用雙筒高壓注射器以5.0 mL/s流率注射碘普羅胺(370 mgI/100 mL),掃描范圍從胸廓入口至橫膈下10 mm。選擇左冠狀動(dòng)脈開(kāi)口層面作為監(jiān)測(cè)層面,使用團(tuán)注方法監(jiān)測(cè)主動(dòng)脈根部的時(shí)間密度變化,計(jì)算冠狀動(dòng)脈CTA掃描的延遲時(shí)間。掃描參數(shù):管電壓120 kV,管電流300～800 mA,掃描層厚5 mm,重建層厚0.625 mm。掃描后由兩位經(jīng)驗(yàn)豐富的影像學(xué)醫(yī)生采用半自動(dòng)離線工作站Volume Viewer專用程序(德國(guó)Simens公司)分別測(cè)量舒張期位相EAT體積值(圖1)。具體方法:使用-190～-30 HU窗寬值獲得脂肪組織,手動(dòng)選取從心包橫竇中點(diǎn)左肺動(dòng)脈起源處開(kāi)始至左心室心尖部下緣為止可辨認(rèn)的心臟纖維膜(即為心外膜邊界),通常以0.5～1 cm為間隔逐層選取。利用鈣化積分軟件計(jì)算鈣化積分(Agatston法)。

圖1 心外膜脂肪組織在心臟周圍分布的總體積(紅色區(qū)域)

經(jīng)皮冠狀動(dòng)脈造影方法及冠狀動(dòng)脈病變?cè)u(píng)價(jià)方法 采用荷蘭Phillips Allura Xper FD20數(shù)字減影血管造影機(jī)對(duì)研究對(duì)象進(jìn)行冠狀動(dòng)脈造影。冠狀動(dòng)脈狹窄程度根據(jù)美國(guó)心臟協(xié)會(huì)冠狀動(dòng)脈血管圖像評(píng)價(jià)標(biāo)準(zhǔn)。將任一冠狀動(dòng)脈主支或分支管腔狹窄程度<20%定義為正常冠狀動(dòng)脈,將管腔狹窄程度>20%定義為任何冠心病,將管腔狹窄程度大于>50%的定義為顯著冠心病。根據(jù)CAGE≥20、CAGE≥50積分來(lái)確定冠心病的嚴(yán)重程度,將冠狀動(dòng)脈狹窄程度≥50%的節(jié)段總數(shù)定義為CAGE≥50,將狹窄程度≥20%的節(jié)段總數(shù)定義為CAGE≥20[9]。通過(guò)Gensini積分系統(tǒng)[10]對(duì)冠狀動(dòng)脈病變程度進(jìn)行定量。

結(jié) 果

臨床基線特征 在相同相位窗不同影像學(xué)醫(yī)生所測(cè)得EAT體積值具有良好的可重復(fù)性,所測(cè)95%一致性界限為(-5.245,6.824)。臨床基線特征見(jiàn)表1。根據(jù)CAG檢查結(jié)果,按冠狀動(dòng)脈狹窄程度將201例患者分為冠心病組(狹窄程度>20%)和正常組,其中正常組108例,冠心病組93例。冠心病組平均EAT體積明顯大于正常組[(135.36 ± 45.36)cm3vs.(88.56 ± 40.64)cm3,P=0.004]。同時(shí),年齡、吸煙、糖尿病、高血壓、代謝綜合征、低密度脂蛋白膽固醇(LDLcholesterolLDL-C)、C反應(yīng)蛋白(c-reactiveprotein,CRP)、冠脈鈣化積分(coronaryarterycalcium,CAC)兩組間亦有顯著差異;性別、總膽固醇、三酰甘油、BMI或腰圍(waistcircumference,WC)兩組間無(wú)統(tǒng)計(jì)學(xué)差異。

表1 研究對(duì)象基線特征Tab 1 General characteristics of the subjects (n=201)

WC:Waist circumference;BMI:Body mass index;CRP:C-reactive protein;EAT:Epicardial adipose tissue.

EAT體積與冠心病、冠脈鈣化積分的關(guān)系 通過(guò)多因素Logistic回歸分析對(duì)EAT體積與冠心病及鈣化積分關(guān)系進(jìn)行評(píng)估(表2),結(jié)果發(fā)現(xiàn)EAT體積與冠心病呈顯著正相關(guān)。在調(diào)整了年齡和性別因素后(模型1),EAT體積與冠心病仍顯著相關(guān)。在進(jìn)一步調(diào)整了吸煙、飲酒因素后,其相關(guān)性仍然存在(模型2)。而在調(diào)整了年齡、性別、吸煙、飲酒以及BMI因素后(模型3),則發(fā)現(xiàn)EAT體積仍是冠心病(OR=1.76,95%CI:1.21～2.38,P=0.005)、鈣化積分(OR=1.82,95%CI:1.18～3.27,P=0.009)的獨(dú)立危險(xiǎn)因素。

表2 EAT體積與冠心病及CAC的多因素Logistic回歸分析Tab 2 Multivariate Logistic regression analysis for EAT volume with CAD and CAC

EAT:Epicardial adipose tissue.

根據(jù)EAT體積高低比較冠心病的嚴(yán)重性 根據(jù)EAT體積值從低到高將病例均分為3組(每組67例),取平均值。發(fā)現(xiàn)EAT體積的高低與冠心病的嚴(yán)重程度呈顯著相關(guān)(表3)。冠心病的嚴(yán)重程度隨著EAT體積的增加呈線性增加。3組間的平均Gensini積分、CAGE≥20、CAGE≥50的平均積分隨著EAT體積的增加而增加,且組間有顯著統(tǒng)計(jì)學(xué)差異(P<0.05)。此外,鈣化積分(CAC)也隨著EAT體積的增加而增加(P<0.05)。

EAT體積與冠心病嚴(yán)重性的相關(guān)性 冠心病的多種危險(xiǎn)因素與冠心病嚴(yán)重程度的多元線性回歸分析見(jiàn)表4。本研究發(fā)現(xiàn),在調(diào)整了年齡、性別、吸煙和飲酒等危險(xiǎn)因素后進(jìn)行線性回歸分析,EAT體積分別與Gensini評(píng)分、CAGE≥20和CAGE≥50評(píng)分呈顯著相關(guān)。其中WC、收縮壓、舒張壓、LDL-c和葡萄糖與CAGE評(píng)分呈顯著正相關(guān)。此外,LDL-c和葡萄糖等因素也被發(fā)現(xiàn)與Gensini評(píng)分呈顯著相關(guān)。

表3 EAT體積值高中低分組與冠心病嚴(yán)重程度的關(guān)系Tab 3 The relationship between the EAT volume and the severity of CAD ±s)

CAC:Coronary artery calcium.

表4 冠心病嚴(yán)重程度的多元線性回歸分析Tab 4 Multivariatelinear regression analysis for the extent of CAD

EAT:Epicardial adipose tissue;WC:Waist circumference;LDL:Low-density lipoprotein;SBP:Systolic blood pressure;DBP:Diastolic blood pressure.

討 論

本研究通過(guò)MSCT測(cè)量EAT體積來(lái)評(píng)估其對(duì)冠心病及冠脈CAC的影響,結(jié)果發(fā)現(xiàn)EAT體積測(cè)量結(jié)果具有良好的可重復(fù)性。EAT體積在冠心病組明顯高于正常冠脈組,且與冠脈病變的嚴(yán)重程度相關(guān),多因素Logistic回歸分析顯示EAT體積與冠心病呈顯著正相關(guān)。此外,EAT體積和冠心病的嚴(yán)重度相關(guān),與冠脈CAC嚴(yán)重度亦呈顯著正相關(guān)。

早先的研究發(fā)現(xiàn)EAT厚度與冠心病之間的關(guān)系在不同研究人群中不盡一致。在非肥胖受試者中,EAT厚度與冠心病或冠脈CAC呈顯著正相關(guān)[11]。但在另一些納入肥胖(BMI>27 kg/m2)受試者的研究中則并無(wú)這種相關(guān)性[12]。這些相互矛盾的研究結(jié)果或許可以歸因于測(cè)量方式的局限性。既往研究多采用超聲心動(dòng)圖的方法來(lái)測(cè)量EAT厚度,而超聲并不能充分獲取心臟各節(jié)段的窗口,并且重復(fù)性較差[7]。此外,對(duì)于肥胖患者,超聲心動(dòng)圖往往因?yàn)楂@取圖像質(zhì)量不良而無(wú)法取得滿意數(shù)據(jù)。

與此相反,與超聲心動(dòng)圖相比,MSCT由于其高分辨率從而能對(duì)心外膜脂肪進(jìn)行精確定量。通過(guò)心臟CT來(lái)測(cè)量EAT體積被認(rèn)為是獲取EAT質(zhì)量指數(shù)的一個(gè)有效方法。已經(jīng)有許多研究證明,通過(guò)CT測(cè)量的EAT體積與傳統(tǒng)心血管危險(xiǎn)因素、冠狀動(dòng)脈CAC及冠心病顯著相關(guān)[13-15]。在本研究中,我們通過(guò)CT測(cè)量發(fā)現(xiàn)EAT體積與冠心病和冠狀動(dòng)脈CAC顯著相關(guān),與既往研究結(jié)果一致[15-17]。

另有既往研究報(bào)道,EAT體積還與冠心病嚴(yán)重程度存在關(guān)聯(lián)。Bettencourt等[18]報(bào)道了通過(guò)CT測(cè)量的EAT體積與的冠狀動(dòng)脈的斑塊負(fù)荷呈正相關(guān)。Eroglu等[19]則報(bào)告,通過(guò)超聲心動(dòng)圖測(cè)量的EAT厚度與冠心病的嚴(yán)重程度相關(guān)。本研究進(jìn)一步證實(shí)了通過(guò)CT測(cè)量的EAT體積與冠心病嚴(yán)重性相關(guān)。相比一些其他已知的危險(xiǎn)因素,包括WC、血壓、空腹血糖和LDL-c,EAT體積和冠心病的嚴(yán)重程度呈顯著相關(guān);通過(guò)線性回歸分析顯示,在調(diào)整了吸煙、飲酒、性別和年齡因素后,CAGE≥20、CAGE≥50以及Gensini積分仍與EAT體積呈顯著關(guān)聯(lián),CAGE≥20,CAGE≥50和Gensini積分隨著EAT體積的增加而線性增加。上述結(jié)果表明EAT體積是冠心病存在和嚴(yán)重程度的獨(dú)立危險(xiǎn)因素。

雖然在大多數(shù)的研究報(bào)道中揭示了EAT體積與冠心病之間存在相關(guān)性。但是它與冠心病嚴(yán)重程度的關(guān)聯(lián)仍有爭(zhēng)議[3,5,12,20]。在這些研究中,冠心病的嚴(yán)重程度與EAT缺乏關(guān)聯(lián)可以從以下幾個(gè)方面解釋:首先,在這些未發(fā)現(xiàn)EAT體積與冠心病嚴(yán)重程度存在相關(guān)性的研究中,并沒(méi)有納入正常受試者。而本研究中納入了正常受試者以及一些輕度狹窄的患者。結(jié)果發(fā)現(xiàn),EAT體積與冠心病的嚴(yán)重性呈線性增加,這表明EAT體積可以反映早期冠心病的最小變化。其次,以前多數(shù)的研究中所采用的是冠心病的狹義定義,導(dǎo)致沒(méi)有納入冠心病的整個(gè)譜系[3-4,6,21]。在這些研究中,冠心病定義為狹窄程度在50%以上,反之,則認(rèn)為是正常冠狀動(dòng)脈。與此相比,本研究通過(guò)使用CAGE≥20,CAGE≥50和Gensini評(píng)分來(lái)更詳細(xì)的定義冠心病的嚴(yán)重性,結(jié)果提示EAT體積與冠心病的嚴(yán)重性相關(guān)。因此,本研究結(jié)果提供了更多強(qiáng)有力的證據(jù)來(lái)支持使用EAT體積來(lái)評(píng)估冠心病的嚴(yán)重度。

本項(xiàng)試驗(yàn)的局限性:首先,參加該研究的人群數(shù)量相對(duì)較少,研究結(jié)果可能不適用于一般人群。其次,研究只是橫斷面研究,因此,尚無(wú)法確定EAT和冠心病之間的因果關(guān)系。本研究表明,CT測(cè)量的EAT體積與冠心病的存在及嚴(yán)重性相關(guān)聯(lián);EAT體積是一個(gè)獨(dú)立于肥胖的導(dǎo)致冠心病的危險(xiǎn)因素;此外,EAT體積反映了冠心病的早期變化。這些結(jié)果表明,EAT為冠心病風(fēng)險(xiǎn)評(píng)估提供了重要的信息,并且可以作為冠心病風(fēng)險(xiǎn)的預(yù)測(cè)因子。

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Associations of epicardial adipose tissue volume measured by 64-slice CT with coronary artery disease

HUANG Shao-hua1,2, WANG Jun1, SUN Yu-min1, ZHANG Yan1, CAO Bin1, TAO Wen-qi1, XU Zhi-qiang1, LUO Xin-ping2△, LI Jian2

(1DepartmentofCardiology,Jing’anDistrictCentreHospitalofShanghai,Shanghai200040,China;2DepartmentofCardiology,HuashanHospital,FudanUniversity,Shanghai200040,China)

Objective To evaluate the epicardial adipose tissue (EAT) volume associated with the presence and the severity of coronary artery disease(CAD). Methods A total of 201 suspected coronary heart disease patients who underwent 64-slice CT and percutaneous coronary angiography were included for this study.We measured the EAT volume and coronary artery calcium (CAC) by CT.CAGE≥20,CAGE≥50 and Gensini index according to the results of coronary angiography were used to define the extent and severity of CAD.The correlation between EAT volume and CAD were analyzed by statistical methods. Results The subjects were divided into normal and CAD groups based on the results of diagnostic coronary angiography (108 normal subjects and 93 patients with CAD).While there was no significant difference in body mass index (BMI) and waist circumference (WC) between the two groups,the mean EAT volume was higher in the CAD group than in the normal subjects [(135.36±45.36) cm3versus (88.56±40.64) cm3,P=0.004].In multivariate logistic regression models,EAT volume was significantly associated with the presence of CAD and CAC in age,gender,smoking,alcohol uptake,and BMI adjusted models (P=0.009).Similarly,EAT was significantly associated with CAGE≥20,CAGE≥50 and Gensini score by linear regression analyses (P<0.05).The severity of CAD increased linearly with each increase in EAT volume(P<0.05).Conclusions EAT volume is associated with the presence and severity of CAD.EAT may be used as a predictor of CAD risk.

epicardial adipose tissue ; coronary artery disease; MSCT

R541.4

A

10.3969/j.issn.1672-8467.2017.01.016

2016-05-24;編輯:張秀峰)

上海市科學(xué)技術(shù)委員會(huì)科研計(jì)劃項(xiàng)目(134119b3300);上海市衛(wèi)計(jì)委重點(diǎn)學(xué)科建設(shè)項(xiàng)目(ZK2015B13)

△Corresponding author E-mail:lucashua@163.com

*This work was supported by the Scientific Research Program of Science and Technology Commission of Shanghai Municipality (134119b3300) and the Foundation for Key Discipline Construction of Shanghai Municipal Commission of Health and Family Planning (ZK2015B13).