王慧清，王琰娜，金耀來，鄧承慧

論著·臨床

血漿同型半胱氨酸與冠狀動(dòng)脈病變的關(guān)系探討

王慧清，王琰娜，金耀來，鄧承慧

目的探討冠心病患者血漿同型半胱氨酸(Hcy)與冠狀動(dòng)脈病變程度的關(guān)系。方法選擇行冠狀動(dòng)脈造影確診為冠心病患者178例為冠心病組，并根據(jù)病變支數(shù)分為1支病變亞組(48例)，2支病變亞組(57例)，≥3支病變亞組(73例)。選擇同期行冠狀動(dòng)脈造影檢查正常者48例為非冠心病組。檢測并比較2組患者血漿Hcy水平、總膽固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)，并測定冠心病組冠狀動(dòng)脈狹窄程度，記錄Gensini冠狀動(dòng)脈病變積分。結(jié)果冠心病組血漿Hcy水平、TC、TG均高于非冠心病組，HDL低于非冠心病組，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。冠心病患者隨著冠狀動(dòng)脈病變程度的加重，血漿Hcy水平和Gensini評(píng)分均逐漸增加，1支病變亞組<2支病變亞組<≥3支病變亞組，與非冠心病組比較差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。Hcy、TC、TG是冠心病的危險(xiǎn)因子，而HDL是冠心病的保護(hù)因子(P<0.05)。結(jié)論高Hcy是冠心病獨(dú)立危險(xiǎn)因素，隨著冠狀動(dòng)脈病變程度加重而升高，可通過檢測Hcy水平評(píng)價(jià)冠狀動(dòng)脈病變程度。

同型半胱氨酸; 冠狀動(dòng)脈病變; Gensini評(píng)分

隨著人們生活水平的提高，我國冠心病的發(fā)病率呈逐年上升的趨勢(shì)，相對(duì)于傳統(tǒng)危險(xiǎn)因素而言，非傳統(tǒng)危險(xiǎn)因素逐漸被大家所重視。大量實(shí)驗(yàn)和臨床研究均顯示同型半胱氨酸(Hcy)是冠心病的一個(gè)獨(dú)立危險(xiǎn)因素[1～3]?，F(xiàn)探討血漿Hcy與冠心病患者冠狀動(dòng)脈病變的關(guān)系。

1 資料與方法

1.1 臨床資料 2011年7月—2013年8月因胸痛在我院行冠狀動(dòng)脈造影診斷為冠心病患者178例為冠心病組，均符合第7版《內(nèi)科學(xué)》冠心病臨床診斷標(biāo)準(zhǔn)[4]，其中男120例，女58例；年齡41～78(62.2±9.2)歲；病程3周～40年；合并高血壓57例，糖尿病108例；其中穩(wěn)定型心絞痛46例，不穩(wěn)定型心絞痛64例，新發(fā)心肌梗死36例，陳舊心肌梗死32例。選擇同期行冠狀動(dòng)脈造影檢查冠狀動(dòng)脈正常者48例為非冠心病組，其中男20例，女28例；年齡34～81(58.4±11.6)歲；合并高血壓35例，糖尿病18例。2組均排除各種急慢性感染、嚴(yán)重肝腎功能障礙、惡性腫瘤，所有患者半年內(nèi)未服用過維生素B、葉酸、卡馬西平等影響同型半胱氨酸的藥物。2組患者性別、年齡比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)，具有可比性。

1.2 觀測方法

1.2.1 Hcy和血脂水平檢測： 受檢者冠狀動(dòng)脈造影術(shù)前空腹8～12 h抽取靜脈血3 ml置促凝試管中，待血液凝固后于3 000 r/min離心5 min后，使用美國雅培公司生產(chǎn)的自動(dòng)免疫發(fā)光分析儀，化學(xué)發(fā)光微粒子免疫檢測法檢測Hcy，參考值為4.44～13.56 μmol/L，該試劑盒購自雅培貿(mào)易(上海)有限公司；使用酶法測定TG和TC，直接法測定HDL。

1.2.2 冠狀動(dòng)脈造影： 應(yīng)用德國西門子血管造影機(jī)(ArTISGEE)，采用Judkin法，經(jīng)橈動(dòng)脈或股動(dòng)脈途徑穿刺，每支血管選擇多體位、不同角度分別行左右冠狀動(dòng)脈造影，造影結(jié)果由2名以上有經(jīng)驗(yàn)的心內(nèi)科介入醫(yī)師判定，并以國際通用的直徑法評(píng)估冠狀動(dòng)脈情況，經(jīng)冠狀動(dòng)脈造影測量至少1支主要冠狀動(dòng)脈狹窄≥50%為有意義的狹窄，診斷為冠心病。根據(jù)冠狀動(dòng)脈造影結(jié)果，采用Gensini評(píng)分系統(tǒng)確定冠狀動(dòng)脈病變嚴(yán)重程度：狹窄程度<25%計(jì)1分，26%～50%計(jì)2分，51%～75%計(jì)4分，76%～90%計(jì)8分，91%～99%計(jì)16分，100%計(jì)32分。不同節(jié)段再乘以相應(yīng)系數(shù)：左主干×5，左前降支近段×2.5，中段×1.5，遠(yuǎn)段×1，第一對(duì)角支×1，第二對(duì)角支×0.5，左回旋支×2.5，遠(yuǎn)段和后降支鈍緣支均×1，后側(cè)支×0.5，右冠中遠(yuǎn)段和后降支均×1,總積分為各節(jié)段積分之和。根據(jù)受累主要冠狀動(dòng)脈支數(shù)為病變支數(shù)，分為1支病變，2支病變和≥3支病變，左主干受累以同時(shí)累及左前降支和左回旋支計(jì)算。

1.3 統(tǒng)計(jì)學(xué)方法 采用SPSS 17.0軟件進(jìn)行統(tǒng)計(jì)分析。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差表示，2組間比較采用t檢驗(yàn),多組間比較采用F檢驗(yàn)；計(jì)數(shù)資料采用χ2檢驗(yàn),各變量與冠狀動(dòng)脈病變的關(guān)系采用Logistic多元逐步回歸分析。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié) 果

2.1 生化指標(biāo)比較 冠心病組血漿Hcy水平、TC、TG均高于非冠心病組，HDL低于非冠心病組，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)，見表1。

表1 冠心病組和非冠心病組生化指標(biāo)比較

2.2 血漿Hcy水平與Gensini評(píng)分 冠心病患者隨著冠狀動(dòng)脈病變程度的加重，血漿Hcy水平和Gensini評(píng)分均逐漸增加，與非冠心病組比較差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)，見表2。

表2 冠心病組冠狀動(dòng)脈病變不同程度血漿Hcy與Gensini評(píng)分

注：與冠心病1支病變比較,aP<0.05;與冠心病2支病變比較,bP<0.05

2.3 Logistic回歸分析 以冠狀動(dòng)脈病變?yōu)橐蜃兞?，Hcy、TC、TG、HDL為自變量，進(jìn)行多因素Logistic回歸分析，結(jié)果顯示：Hcy、TC、TG是冠心病的危險(xiǎn)因子，HDL是冠心病的保護(hù)因子，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，見表3。

表3 冠心病危險(xiǎn)因素與冠狀動(dòng)脈病變的多因素Logistic回歸分析

3 討 論

血漿Hcy一直是醫(yī)學(xué)領(lǐng)域的研究熱點(diǎn)，很多研究認(rèn)為高Hcy血癥是動(dòng)脈硬化的獨(dú)立危險(xiǎn)因素[5]，與冠心病的發(fā)病密切相關(guān)。在冠心病的發(fā)病危險(xiǎn)因素中，高Hcy是僅次于傳統(tǒng)危險(xiǎn)因素的最主要的非傳統(tǒng)危險(xiǎn)因素，與傳統(tǒng)危險(xiǎn)因素血脂一起促進(jìn)了冠心病的發(fā)生發(fā)展[6]，在學(xué)術(shù)界引起了廣泛的關(guān)注。有學(xué)者分析了有關(guān)Hcy水平與血管疾病相關(guān)的研究，得出輕中度高Hcy血癥是動(dòng)脈粥樣硬化性疾病的一個(gè)獨(dú)立的且有劑量效應(yīng)關(guān)系的危險(xiǎn)因素[7]。血漿Hcy水平每升高5 μmol/L，發(fā)生冠心病的OR值在男性為1.6，女性為1.8，效果與0.5 mmol/L的總膽固醇相當(dāng)[8]。并且鹿慶華等[9]研究提示，血漿Hcy每升高1 μmol/L，Gensini積分增加5分，即血漿Hcy水平升高，患冠心病的危險(xiǎn)性增加，冠狀動(dòng)脈病變程度越嚴(yán)重。在本研究中，冠心病組血漿Hcy水平明顯高于非冠心病組，隨著冠狀動(dòng)脈病變積分的增加，血漿Hcy濃度增加，總膽固醇和三酰甘油也明顯升高，冠狀動(dòng)脈病變程度加重，與既往研究相符。

Hcy為蛋氨酸的中間代謝產(chǎn)物，其值升高與葉酸、維生素B12缺乏、MTHFRC677T基因突變有關(guān)[10～12]。高Hcy血癥致動(dòng)脈硬化機(jī)制，可能與損傷內(nèi)皮細(xì)胞，形成氧自由基、減少內(nèi)皮細(xì)胞產(chǎn)生一氧化氮、促進(jìn)低密度脂蛋白的氧化；或激活血小板，增加血小板黏附，促進(jìn)血小板釋放血小板衍生的生長因子，激活因子V、X、XII，抑制蛋白C激活，以及抑制細(xì)胞表面血栓調(diào)節(jié)素和降低組織型纖溶酶原激活劑的活性，促進(jìn)血栓形成，降低一氧化氮的利用度[8]，及促進(jìn)脂蛋白a的釋放，使氧化型低密度脂蛋白增加有關(guān)[13]，其中內(nèi)皮功能失調(diào)可能是Hcy致冠狀動(dòng)脈病變的重要機(jī)制[14]。

綜上所述，高Hcy是冠心病的獨(dú)立危險(xiǎn)因素，隨著Hcy濃度的增加，冠狀動(dòng)脈病變程度加重，臨床監(jiān)測血漿Hcy水平是比較經(jīng)濟(jì)有用的非侵入性評(píng)價(jià)冠狀動(dòng)脈病變程度的有效手段，值得臨床推廣應(yīng)用。

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Studyontherelationshipbetweenplasmahomocysteineandcoronaryarterylesions

WANGHuiqing*,WANGYanna,JINYaolai,DENGChenghui.

*DepartmentofCardiology,AffiliatedZhongshanHospitalofDalianUniversity,Dalian116011,China

ObjectiveTo investigate the correlation between plasma homocysteine in patients with coronary artery disease (Hcy) associated with the severity of coronary artery lesion.Methods178 patients with coronary angiography confirmed coronary heart disease were enrolled as CHD group, and according to the number of diseased arteries, they were divided into 1 vessel disease subgroup (48 cases), 2-vessel disease subgroup (57 cases), 3-vessel disease subgroup (73 cases). The same period 48 cases of normal patients were selected non-CHD group. Levels of plasma Hcy, total cholesterol (TC), three triacylglycerol (TG), high density lipoprotein (HDL) were detected and compared between the 2 groups, and to determine the extent of coronary artery stenosis, record the Gensini coronary artery score.ResultsThe levels of plasma Hcy, TC, TG of coronary heart disease group were higher than that in non CHD group, HDL was lower than that in non CHD group, the differences were statistically significant (P<0.05). Coronary heart disease patients along with the severity of coronary artery disease, plasma Hcy level and Gensini score were increased, 1 vessel disease subgroup <2 vessel disease subgroup < 3 vessel disease subgroup, and differences between former and non CHD group were statistically significant (P<0.05). Logistic regression analysis revealed that Hcy, TC, TG were risk factors of coronary artery lesions,while HDL was protective factor of coronary artery lesions; the differences were statistically significant (P<0.05).ConclusionHigh Hcy is an independent risk factor of coronary heart disease, and increased with the severity of coronary artery lesions, according to detect Hcy level, the severity of coronary artery disease can be assessed.

Homocysteine;Coronary artery lesion; Gensini score

116011 大連大學(xué)附屬中山醫(yī)院循環(huán)內(nèi)科(王慧清、王琰娜)，腎內(nèi)科(鄧承慧)； 大連市西崗區(qū)香爐礁社區(qū)衛(wèi)生 服務(wù)中心(金耀來)

10.3969 / j.issn.1671-6450.2014.09.003

2014-06-16)