于　佳　溫志超　洪　晉　李　劍　施海明　范維琥　倪喚春　羅心平

200040 上海，復(fù)旦大學(xué)附屬華山醫(yī)院心內(nèi)科

?

·臨床研究·

綜合糖脂代謝指標(biāo)與冠狀動(dòng)脈病變嚴(yán)重程度的相關(guān)性研究

于佳溫志超洪晉李劍施海明范維琥倪喚春羅心平

200040 上海，復(fù)旦大學(xué)附屬華山醫(yī)院心內(nèi)科

【摘要】目的：探討綜合糖脂代謝指標(biāo)與冠狀動(dòng)脈(冠脈)病變程度的關(guān)系及其臨床意義。方法：入選2012年3月至2013年12月于我院接受冠脈造影的717例患者，根據(jù)造影結(jié)果分為冠脈造影陰性的對(duì)照組(n=385)和冠心病組(n=332)。檢測(cè)所有研究對(duì)象的血清糖化血紅蛋白(HbA1c)、總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C)、三酰甘油(TG)等，采用Gensini評(píng)分評(píng)估冠脈病變嚴(yán)重程度。采用Pearson相關(guān)系數(shù)分析連續(xù)性變量之間的相關(guān)性，Spearman相關(guān)系數(shù)檢測(cè)分類變量之間的相關(guān)性。線性回歸分析綜合糖脂代謝指標(biāo)HbA1c×LDL-C/HDL-C與Gensini積分的線性關(guān)系，非條件Logistic回歸分析HbA1c×LDL-C/HDL-C與冠脈病變支數(shù)的相關(guān)性，受試者工作特征(ROC)曲線評(píng)價(jià)HbA1c×LDL-C/HDL-C預(yù)測(cè)冠脈嚴(yán)重程度、冠脈多支病變的價(jià)值。結(jié)果：血清HbA1c、LDL-C水平、HbA1c×LDL-C/HDL-C與Gensini積分呈正相關(guān)，而HDL-C水平與Gensini積分呈負(fù)相關(guān)。線性回歸顯示HbA1c×LDL-C/HDL-C與Gensini積分呈線性相關(guān)，其判斷冠脈病變嚴(yán)重程度的ROC曲線下面積為0.724(P<0.01)。Logistic回歸分析顯示HbA1c×LDL-C/HDL-C與冠脈病變支數(shù)顯著相關(guān)，其判斷冠脈病變支數(shù)的ROC曲線下面積為0.638(P<0.01)。結(jié)論：綜合糖脂代謝指標(biāo)對(duì)冠脈粥樣硬化病變嚴(yán)重程度、病變支數(shù)有一定的預(yù)測(cè)價(jià)值。

【關(guān)鍵詞】冠狀動(dòng)脈粥樣硬化性心臟??；糖化血紅蛋白；低密度脂蛋白膽固醇；高密度脂蛋白膽固醇

冠狀動(dòng)脈粥樣硬化性心臟病(冠心病)存在多個(gè)危險(xiǎn)因素，其中低密度脂蛋白膽固醇(LDL-C)是目前公認(rèn)的危險(xiǎn)因素，與冠心病的發(fā)病率和死亡率密切相關(guān)[1-2]。高密度脂蛋白膽固醇(HDL-C)水平降低可增加冠心病發(fā)病風(fēng)險(xiǎn)[3]，糖化血紅蛋白(HbA1c)是心血管疾病發(fā)生和死亡的重要預(yù)測(cè)因子[4-5]。臨床上冠心病患者常合并血糖、血脂紊亂，單一指標(biāo)難以準(zhǔn)確、全面地反映冠心病風(fēng)險(xiǎn)。本研究將血清LDL-C、HDL-C和HbA1c水平合并作為綜合糖脂代謝指標(biāo)，探討其與冠狀動(dòng)脈(冠脈)粥樣硬化嚴(yán)重程度的關(guān)系。

1對(duì)象和方法

1.1研究對(duì)象

入選2012年3月至2013年12月在復(fù)旦大學(xué)附屬華山醫(yī)院心內(nèi)科住院并接受冠脈造影的擬診冠心病患者717例。根據(jù)造影結(jié)果分為2組：冠脈造影陰性的對(duì)照組(n=332)和冠心病組(n=332)。冠心病診斷標(biāo)準(zhǔn)：冠脈造影示左主干、左前降支、回旋支、右冠脈或其主要分支的血管直徑狹窄≥50%。高血壓病診斷標(biāo)準(zhǔn)：收縮壓≥140 mmHg和(或)舒張壓≥90 mmHg，或正在服用降壓藥物治療。糖尿病診斷采用美國(guó)糖尿病協(xié)會(huì)標(biāo)準(zhǔn)：空腹血糖≥7.0 mmol/L，或葡萄糖耐量試驗(yàn)2 h血糖≥11.1 mmol/L，或正在服用降糖藥物治療。排除標(biāo)準(zhǔn)：臨床資料或冠脈造影資料不全；嚴(yán)重肝、腎功能不全；惡性腫瘤。本研究經(jīng)過(guò)華山醫(yī)院醫(yī)學(xué)倫理委員會(huì)同意，所有入選者簽署知情同意書。

1.2研究方法

所有患者入院8 h內(nèi)采集病史，進(jìn)行全身體格檢查，24 h內(nèi)采集空腹肘靜脈血，進(jìn)行血脂、血糖、HbA1c、肝功能、腎功能等生化檢查。

所有入選對(duì)象在完善常規(guī)生化檢查、排除造影禁忌后，進(jìn)行冠脈造影。采用Judkins法體位投照，血管入路首選經(jīng)皮穿刺橈動(dòng)脈，經(jīng)橈動(dòng)脈入路困難時(shí)采用經(jīng)皮穿刺股動(dòng)脈。

冠脈病變支數(shù)的判斷以管徑狹窄≥50%為病變陽(yáng)性。冠脈多支病變指2支及以上的冠脈在造影中存在≥50%的狹窄和(或)左主干病變。

Gensini評(píng)分由兩位有經(jīng)驗(yàn)的心內(nèi)科醫(yī)生在盲法下獨(dú)立進(jìn)行。Gensini積分計(jì)算方法如下：(1)冠脈狹窄程度≤25%為1分，25%～49%為2分，50%～74%為4分，75%～89%為8分，90%～98%為16分，99%～100%為32分；(2)病變部位系數(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，回旋支：近段×2.5、中段×1、鈍緣支×1、后降支×1、后側(cè)支×0.5，右冠脈：近段×1、遠(yuǎn)段×1、后降支×1；(3)相應(yīng)積分?jǐn)?shù)與系數(shù)相乘后求和為Gensini積分[6]。

1.3統(tǒng)計(jì)學(xué)分析

采用SPSS19統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)處理。計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差表示，計(jì)數(shù)資料用例數(shù)和百分?jǐn)?shù)表示。計(jì)量資料組間比較使用t檢驗(yàn)；計(jì)數(shù)資料組間比較采用方差分析。Pearson相關(guān)系數(shù)檢測(cè)連續(xù)性變量之間的相關(guān)性，Spearman相關(guān)系數(shù)檢驗(yàn)分類變量之間的相關(guān)性。線性回歸分析HbA1c×LDL-C/HDL-C與Gensini積分的線性關(guān)系，非條件Logistic回歸分析HbA1c×LDL-C/HDL-C與冠脈病變支數(shù)的相關(guān)性，ROC曲線評(píng)價(jià)HbA1c×LDL-C/HDL-C預(yù)測(cè)冠脈病變嚴(yán)重程度、多支病變的價(jià)值。以P<0.05為有統(tǒng)計(jì)學(xué)差異。

2結(jié)果

2.1基線資料比較

兩組間年齡、性別構(gòu)成、體質(zhì)量指數(shù)(BMI)、收縮壓、舒張壓、三酰甘油(TG)水平無(wú)顯著差異(P均>0.05)。與對(duì)照組相比，冠心病組中吸煙率、高血壓和糖尿病患病率、血清HbA1c、總膽固醇(TC)和LDL-C水平明顯較高(P<0.05)，而HDL-C和左室射血分?jǐn)?shù)(LVEF)明顯低于對(duì)照組(P<0.05)。

表1　兩組患者的臨床基線資料

2.2糖脂代謝指標(biāo)與Gensini積分

冠心病風(fēng)險(xiǎn)因素與Gensini積分的相關(guān)性分析顯示，HbA1c、LDL-C水平與Gensini積分呈正相關(guān)，HDL-C水平與Gensini積分呈負(fù)相關(guān)，HbA1c×LDL-C/HDL-C與Gensini積分的正相關(guān)性更顯著，見(jiàn)表2。

線性回歸分析顯示，HbA1c×LDL-C/HDL-C與Gensini積分具有顯著線性關(guān)系，方程為y=1.07x+38.69，y=Gensini積分，x=HbA1c×LDL-C/HDL-C，r2=0.038，P<0.01。

表2　冠心病組風(fēng)險(xiǎn)因素與Gensini積分的相關(guān)性分析

根據(jù)Gensini積分結(jié)果將患者分為低Gensini積分組(<40分)和高Gensini積分組(≥40分)[7]。將HbA1c×LDL-C/HDL-C劃分為若干臨界點(diǎn)，以每個(gè)臨界點(diǎn)對(duì)應(yīng)的靈敏度為縱坐標(biāo)，1-特異度為橫坐標(biāo)，作圖得到ROC曲線(見(jiàn)圖1)，曲線下面積為0.724(0.679～0.768)，P<0.01。約登指數(shù)最大值為0.385，此時(shí)對(duì)應(yīng)的HbA1c×LDL-C/HDL-C值為15.46。

圖1　綜合糖脂代謝指標(biāo)判斷冠脈病變的ROC曲線

2.3糖脂代謝指標(biāo)與冠脈病變支數(shù)

以冠脈多支病變?yōu)橐蜃兞?，Logistic回歸分析HbA1c×LDL-C/HDL-C與冠脈多支病變的關(guān)系，結(jié)果顯示高HbA1c×LDL-C/HDL-C是發(fā)生冠狀動(dòng)脈多支病變的危險(xiǎn)因素(OR=1.053，95%CI：1.021～1.086，P=0.001)。

根據(jù)冠脈造影結(jié)果將冠心病患者分為單支病變組和多支病變組，將HbA1c×LDL-C/HDL-C劃分為若干臨界點(diǎn)，作ROC曲線(見(jiàn)圖2)得到曲線下面積為0.638(0.576～0.699)，P<0.01。約登指數(shù)最大值為0. 251，此時(shí)對(duì)應(yīng)的HbA1c×LDL-C/HDL-C值為15.11。

圖2　綜合糖脂代謝指標(biāo)判斷冠脈多支病變的ROC曲線

3討論

血脂異常，特別是高水平LDL-C和低水平HDL-C已被確定為冠心病的危險(xiǎn)因素[8-9]。薈萃分析顯示，LDL-C水平每下降1 mmol/L，冠脈事件可減少23%[10]。當(dāng)HDL-C<40 mg/dL時(shí),冠心病風(fēng)險(xiǎn)增加明顯[11]，HDL-C水平每降低1 mg/dL，冠心病風(fēng)險(xiǎn)上升2%～3%[12]。Quebec心血管研究顯示，HDL-C水平每下降10%，冠心病風(fēng)險(xiǎn)增加13%[13]。研究發(fā)現(xiàn)，LDL-C/HDL-C比單一的LDL-C、HDL-C更能預(yù)測(cè)冠心病風(fēng)險(xiǎn)，LDL-C/HDL-C與冠脈病變嚴(yán)重程度具有顯著相關(guān)性[14]。TC/HDL-C、LDL-C/HDL-C、TG/HDL-C與冠脈病變支數(shù)密切相關(guān)[15]。HbA1c是血紅蛋白與葡萄糖發(fā)生緩慢非酶促反應(yīng)形成的復(fù)合物，反映近2個(gè)月的平均血糖水平。多項(xiàng)研究顯示高HbA1c水平增加冠心病發(fā)生率[16-17]。HbA1c水平每上升1%，心血管事件和全因死亡率增加20%～30%，并且這種相關(guān)性不受糖尿病的影響[18]。

本研究將以上3個(gè)冠心病的重要危險(xiǎn)因素合并為一個(gè)綜合指標(biāo)HbA1c×LDL-C/HDL-C，評(píng)價(jià)其對(duì)冠脈病變嚴(yán)重程度和病變支數(shù)的預(yù)測(cè)作用。結(jié)果顯示，HbA1c、LDL-C、HbA1c×LDL-C/HDL-C水平均與Gensini積分呈正相關(guān)，HDL-C水平與Gensini積分呈負(fù)相關(guān)，與已有研究結(jié)果一致[19-21]。線性回歸分析顯示，HbA1c×LDL-C/HDL-C與Gensini積分具有顯著的線性關(guān)系，其判斷冠脈病變嚴(yán)重程度的ROC曲線下面積為0.724，診斷臨界值為15.46。Logistic回歸分析顯示HbA1c×LDL-C/HDL-C與冠脈多支病變的風(fēng)險(xiǎn)顯著相關(guān)，ROC曲線下面積為0.638，臨界診斷值為15.11。該綜合糖脂代謝指標(biāo)對(duì)冠脈病變嚴(yán)重程度、多支病變具有一定的預(yù)測(cè)意義。

本研究中HbA1c×LDL-C/HDL-C判斷冠脈病變嚴(yán)重程度、多支病變的ROC曲線下面積均不大。此外，本研究樣本量偏小，該綜合糖脂代謝指標(biāo)對(duì)于冠脈病變嚴(yán)重程度的相關(guān)性需增加樣本量進(jìn)一步明確。

參考文獻(xiàn)

[1]Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010[J]. Lancet,2012,380(9859):2095-2128.

[2]Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins[J]. Lancet,2005,366(9493):1267-1278.

[3]Boekholdt SM, Arsenault BJ, Hovingh GK, et al. Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis[J]. Circulation,2013,128(14):1504-1512.

[4]van't Riet E, Rijkelijkhuizen JM, Alssema M, et al. HbA1c is an independent predictor of non-fatal cardiovascular disease in a Caucasian population without diabetes: a 10-year follow-up of the Hoorn Study[J]. Eur J Prev Cardiol,2012,19(1):23-31.

[5]Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults[J]. N Engl J Med,2010,362(9):800-811.

[6]Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease[J]. Am J Cardiol,1983,51(3):606.

[7]Wang Y, Zheng A, Yan Y, et al. Association between HMW adiponectin, HMW-total adiponectin ratio and early-onset coronary artery disease in Chinese population[J]. Atherosclerosis,2014,235(2):392-397.

[8]National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel Ⅲ) final report[J]. Circulation,2002,106(25):3143-3421.

[9]Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel Ⅲ)[J]. JAMA,2001,285(19):2486-2497.

[10]Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials[J]. Lancet,2010,376(9753):1670-1681.

[11]Castelli WP, Anderson K, Wilson PW, et al. Lipids and risk of coronary heart disease. The Framingham Study[J]. Ann Epidemiol,1992,2(1-2):23-28.

[12]Gotto AM, Jr. High-density lipoprotein cholesterol and triglycerides as therapeutic targets for preventing and treating coronary artery disease[J]. Am Heart J,2002,144(6 Suppl):S33-S42.

[13]Despres JP, Lemieux I, Dagenais GR, et al. HDL-cholesterol as a marker of coronary heart disease risk: the Quebec cardiovascular study[J]. Atherosclerosis,2000,153(2):263-272.

[14]Momiyama Y, Ohmori R, Fayad ZA, et al. The LDL-cholesterol to HDL-cholesterol ratio and the severity of coronary and aortic atherosclerosis[J]. Atherosclerosis,2012,222(2):577-580.

[15]吳燕丹. TC/HDL-C、LDL-C/HDL-C、TG/HDL-C與冠心病不同程度相關(guān)性[J]. 臨床誤診誤治,2014,(6):64-67.

[16]Ueda H, Mitsusada N, Harimoto K, et al. Glycosylated hemoglobin is a predictor of major adverse cardiac events after drug-eluting stent implantation in patients with diabetes mellitus[J]. Cardiology,2010,116(1):51-57.

[17]Kataoka Y, Shao M, Wolski K, et al. Multiple risk factor intervention and progression of coronary atherosclerosis in patients with type 2 diabetes mellitus[J]. Eur J Prev Cardiol,2013,20(2):209-217.

[18]Khaw KT, Wareham N, Luben R, et al. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk)[J]. BMJ,2001,322(7277):15-18.

[19]Ashraf H, Boroumand MA, Amirzadegan A, et al. Hemoglobin A1C in non-diabetic patients: an independent predictor of coronary artery disease and its severity[J]. Diabetes Res Clin Pract,2013,102(3):225-232.

[20]Xu RX, Li S, Li XL, et al. High-density lipoprotein subfractions in relation with the severity of coronary artery disease: A Gensini score assessment[J]. J Clin Lipidol,2015,9(1):26-34.

[21]Niccoli G, Baca M, De Spirito M, et al. Impact of electronegative low-density lipoprotein on angiographic coronary atherosclerotic burden[J]. Atherosclerosis,2012,223(1):166-170.

(收稿：2015-08-10修回：2016-02-16)

(本文編輯：梁英超)

Correlation between glycolipid metabolism index and the severity of coronary artery disease

YUJia，WENZhichao,HONGJin,LIJian,SHIHaiming,FANWeihu,NIHuanchun,LUOXinping.

DepartmentofCardiology,HuashanHospital,FudanUniversity,Shanghai200040,China

【Abstract】Objective： To investigate the relation between comprehensive glycolipid metabolism index and the severity of coronary artery disease.Methods： From March 2012 to December 2013, a total of 385 patients were enrolled into the control group, and 332 patients were enrolled into the case group according to the result of coronary angiography. Levels of serum HbA1c, total cholesterol (TC),low-density lipoproteincholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were detected. The severity of coronary artery disease was assessed by Gensini score.Pearson correlation analysis was used to detect the relationship between continuous variables, and Spearman correlation analysis was used to detect the relationship between categorical variables.Linear regression was used to analyze the linear relation between glycolipid metabolism index and the Gensini score. Non-conditional logistic regression was used to identify the correlation between HbA1c×LDL-C/HDL-C and the number of coronary artery lesion vessels. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HbA1c×LDL-C/HDL-C for the severity of coronary artery disease and the number of coronary artery lesion vessels.Results： Correlation analysis showed that there were positive correlation between levels of HbA1c, LDL-C, HbA1c×LDL-C/HDL-C and the Gensini score, and there was a negative correlation between level of HDL-C and the Gensini score.Linear regression analysis revealed a strong correlation between HbA1c×LDL-C/HDL-C and the Gensini score, and the area under the ROC curve was 0.724(P<0.01).Logistic regression analysis showed that HbA1c×LDL-C/HDL-C was closely related with the number of lesion branches, and the area under the ROC curve was 0.638 (P<0.01).Conclusion： Glycolipid metabolism index has certain predictive value of the severity of coronary artery disease and number of coronary artery lesion vessels.

【Key words】Coronary artery disease； Hemoglobin A1c；Low-density lipoprotein cholesterol； High-density lipoprotein cholesterol

doi:10.3969/j.issn.1673-6583.2016.02.014

通信作者：倪喚春, Email：docnhc@126.com

基金項(xiàng)目：上海市衛(wèi)生局科研項(xiàng)目(20134312)