全勇俊，朱 航，蘇小俊，王昊天，何 凱，張子云，孫金燕

青年冠心病危險因素的探討

全勇俊1，朱 航2，蘇小俊1，王昊天3，何 凱4，張子云5，孫金燕1

目的探討青年冠心病的危險因素。方法選擇2008-06至2013-03在解放軍總醫(yī)院門診及住院期間收治的青年(年齡≤40歲)疑似冠心病患者855例，其中確診為青年冠心病455例(冠心病組)和非冠心病400例(對照組)。詳細(xì)采集病史，用高效液相色譜法檢測血清同型半胱氨酸(homocysteine，Hcy)水平。采用單因素與多因素非條件Logistic 回歸分析青年冠心病患者病因及危險因素。結(jié)果冠心病組和對照組在冠心病家族史、HDL-C、APOA1、血Hcy指標(biāo)的差異均有統(tǒng)計學(xué)意義(P<0.01 或P<0.05)。多因素非條件Logistic 回歸分析顯示：冠心病家族史(OR=3.556，P=0.002)、Hcy(OR=1.380，P=0.001)是青年冠心病患者的獨立危險因素。結(jié)論血漿Hcy水平和冠心病家族史是青年冠心病患者的危險因素。

冠心病；同型半胱氨酸；青年；危險因素

冠心病是脂代謝紊亂而引起的冠狀動脈粥樣硬化性病變，具有高發(fā)病率和高病死率，且發(fā)病趨勢越來越年輕化。青年冠心病預(yù)后評估取決于對危險因素的干預(yù)和對病情的診斷。多項研究證實，同型半胱氨酸(homocysteine，Hcy)是心肺血管疾病的獨立危險因素[1,2]。血漿Hcy水平與青年冠心病的關(guān)系，尚缺乏充分的研究。本研究將通過對大量青年冠心病患者有效指標(biāo)的評估，旨在探討Hcy及其他傳統(tǒng)冠心病危險因素與青年冠心病的關(guān)系，為中國人群中青年冠心病的危險因素的評估及早期診斷提供依據(jù)。

1 對象與方法

1.1 對象 選擇2011-06至2013-03在解放軍總醫(yī)院門診及住院期間收治的，年齡≤40歲的疑似冠心病患者855例，排除不符合WHO缺血性心臟病標(biāo)準(zhǔn)或臨床資料不完整的患者，排除患有腦梗死病史，嚴(yán)重的肝腎疾病、惡性腫瘤、自身免疫性疾病、應(yīng)用葉酸或利尿藥等影響Hcy水平藥物的疾病者。其中，根據(jù)冠狀動脈造影、心電圖及血壓等診斷為青年冠心病455例(青年冠心病組)，非冠心病400例(對照組)。

1.2 病史采集 通過臨床資料及問診調(diào)查患者性別、年齡、高血壓、糖尿病和冠心病病史及家族史、2型糖尿病病史等。

1.3 血漿標(biāo)本收集方法 入選者采用Judkins法行冠狀動脈造影后,Seldinger法穿刺抽取靜脈血，加入抗凝藥后, 于3000 r/min，離心10 min, 取血清于-80 ℃冰箱中保存待測。

1.4 血漿Hcy含量測定 血漿Hcy水平用高效液相色譜法(日本Shimadzu公司)進(jìn)行檢測。

1.5 相關(guān)觀察指標(biāo) 所有患者于入院后取隔夜空腹12 h 靜脈血，按中華醫(yī)學(xué)會檢驗學(xué)會推薦的方法測定總膽固醇(TC)、三酰甘油(TG)、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇(LDL-C)等指標(biāo)。

2 結(jié) 果

2.1 單因素分析 青年冠心病組和對照組在性別、年齡、高血壓病史、收縮壓、2型糖尿病病史、TG、TC、LDL-C、APOB值等方面比較，差異均無統(tǒng)計學(xué)意義，但在冠心病家族史、HDL-C、APOA1、Hcy上比較，差異均有統(tǒng)計學(xué)意義(P<0.05，表1、2)。

2.2 多因素分析 多因素非條件Logistic 回歸分析結(jié)果顯示，冠心病家族史、Hcy是青年冠心病患者的獨立危險因素(表3)。

表1 青年冠心病組和對照組患者的計數(shù)資料比較 (n；%)

比較指標(biāo)青年CHD組(n=455)對照組(n=400)tP年齡(歲)36．5±0．334．6±3．6 0．2010．841收縮壓(mmHg)94±592±7 0．1320．895TG(mmol/L)2．09±1．521．63±0．690．0430．482TC(mmol/L)4．93±1．214．82±2．061．3250．185LDL?C(mmol/L)2．72±1．232．55±1．311．8450．065HDL?C(mmol/L)0．90±0．241．21±1．472．3010．022APOA1(mmol/L)1．04±0．521．24±0．812．0000．045APOB(mmol/L)217±98 220±1071．1150．265Hcy(μmol/L)19．23±8．43 15．72±6．32 5．2840．000

表3 青年冠心病危險因素的非條件Logistic 回歸分析

3 討 論

近期研究表明，青年冠心病患者由于其特殊人群、不同的生活及飲食習(xí)慣，在臨床表現(xiàn)及冠脈病變上有著自身特點[3-5]。因此，不能僅依據(jù)傳統(tǒng)冠心病的危險因素及指標(biāo)來評估青年冠心病，需要更加精確的符合青年冠心病特點的評估手段。本次研究目的是通過采集大量青年冠心病患者，在大樣本(>400例)的情況下探討青年冠心病患者與血漿Hcy水平及其他危險因素的關(guān)系，更加準(zhǔn)確地評估青年冠心病危險因素。

本研究發(fā)現(xiàn)，青年冠心病組與對照組的比較中，冠心病家族史、HDL-C、APOA1、HCY差異均具有統(tǒng)計學(xué)意義(P<0.05)。進(jìn)一步對青年冠心病危險因素進(jìn)行多因素非條件Logistic 回歸分析發(fā)現(xiàn)，冠心病家族史、Hcy又是青年冠心病患者的獨立危險因素。

青年冠心病患者血漿Hcy水平可能與青年患者的遺傳因素有關(guān)[7,8]，基因多態(tài)性主要是參與Hcy代謝的酶的突變或缺陷，主要包括3種：亞甲基四氫葉酸還原酶(MTHFR)基因多態(tài)性[9-13]、蛋氨酸合成酶基因多態(tài)性[14,15]，以及CBS基因多態(tài)性[16,17]。另外，隨著生活水平的提高，青年人的生活習(xí)慣也影響著血Hcy水平。研究表明，長期嗜酒可引起肝細(xì)胞的蛋氨酸合成酶活性下降，造成高Hcy血癥[18]。吸煙、飲食中攝入過多蛋氨酸、飲用高糖咖啡飲品等，均可導(dǎo)致血漿Hcy濃度升高，而且?guī)追N因素聯(lián)合作用明顯大于各因素的單獨作用[19，21]。研究發(fā)現(xiàn)，不受冠心病已知危險因素的影響，Hcy水平每增加5 μmol/L，發(fā)生冠心病的危險性將增高約20%[22]。高Hcy血癥可通過血管內(nèi)皮及平滑肌細(xì)胞、炎性作用、凝血因子及血小板等多因素共同作用，在短期內(nèi)發(fā)展成動脈粥樣硬化。

本研究結(jié)果示，Hcy是青年冠心病獨立的危險因素，可作為青年冠心病發(fā)病的預(yù)測分子。根據(jù)青年的血漿Hcy水平及對遺傳因素對冠心病早期發(fā)病風(fēng)險進(jìn)行分層，有助于對青年冠心病的早期干預(yù)。隨著生活條件的提升，高脂飲食，長期吸煙嗜酒等常見的不良習(xí)慣也影響著青年冠心病的發(fā)病率。通過預(yù)防這些不良因素可有效控制青年冠心病發(fā)病率。

[1] Wan J, Deng Y, Guo J,etal. Hyperhomocysteinemia inhibited cardiac stem cell homing into the peri-infarcted area post myocardial infarction in rats [J]. Exp Mol Pathol, 2011, 91(1): 411-418.

[2] 朱 航，薛 浩，王廣義，等. 血清同型半胱氨酸水平與急性肺栓塞患者早期死亡的相關(guān)性[J]. 中華心血管病雜志，2013, 41(9): 756-760.

[3] Che J, Li G, Shao Y,etal. An analysis of the risk factors for premature coronary artery disease in young and middle-age Chinese patients with hypertension [J]. Exp Clin Cardiol, 2013, 18 (2): 89-92.

[4] Cameron S J, Block R C, Richeson J F. Severe coronary disease in an adult considered at low cardiovascular disease risk with a healthy lifestyle [J]. J Clin Lipidol, 2013, 7(5): 526-530.

[5] Huang Y, Hu Y, Mai W,etal. Plasma oxidized low-density lipoprotein is an independent risk factor in young patients with coronary artery disease [J]. Dis Markers, 2011, 31 (5): 295-301.

[6] Forges T, Monnier-Barbarino P, Alberto J M,etal. Impact of folate and homocysteine metabolism on human reproductive health [J]. Hum Reprod Update, 2007, 13 (3): 225-238.

[7] Zidan H E, Rezk N A, Mohammed D. MTHFR C677T and A1298C gene polymorphisms and their relation to homocysteine level in Egyptian children with congenital heart diseases [J]. Gene, 2013, 529 (1): 119-124.

[8] Gupta S K, Kotwal J, Kotwal A,etal. Role of homocysteine & MTHFR C677T gene polymorphism as risk factors for coronary artery disease in young Indians [J]. Indian J Med Res, 2012, 135(4): 506-512.

[9] Arai H, Yamamoto A, Matsuzawa Y,etal. Polymorphisms of apolipoproteine and methylenetetrahydrofolate reductase in the Japanese population [J]. J Atheroscler Thromb, 2007, 14 (4): 167-171.

[10] Terruzzi I, Senesi P, Montesano A,etal. Genetic polymorphisms of the enzymes involved in DNA methylation and synthesis in elite athletes [J]. Physiol Genomics, 2011, 43(16): 965-973.

[11] Bahadir A, Eroz R, Dikici S. Investigation of MTHFR C677T gene polymorphism, biochemical and clinical parameters in Turkish migraine patients: association with allodynia and fatigue [J]. Cell Mol Neurobiol, 2013, 33(8): 1055-1063.

[12] Ubeda N, Reyes L, González-Medina A,etal. Physiologic changes in homocysteine metabolism in pregnancy: a longitudinal study in Spain [J]. Nutrition, 2011, 27(9): 925-930.

[13] Lefaucheur R, Triquenot-Bagan A, Quillard M,etal. Stroke and iridodonesis revealing a homocystinuria caused by a compound heterozygous mutation of cystathionine beta-synthase [J]. Rev Neurol, 2008, 164 (8-9): 728-732.

[14] Hosseini M. Role of polymorphism of methyltetrahydrofolate-homocysteine methyltransferase (MTR) A2756G and breast cancer risk [J]. Pol J Pathol, 2013, 64 (3):191-195.

[15] Belkahla R, Omezzine A, Kchok K,etal. Effect of polymorphisms on key enzymes in homocysteine metabolism, on plasma homocysteine level and on coronary artery-disease risk in a Tunisian population [J]. Ann Cardiol Angeiol, 2008, 57 (4): 219-224.

[16] Nienaber-Rousseau C, Ellis S M, Moss S J,etal. Gene-environment and gene-gene interactions of specific MTHFR, MTR and CBS gene variants in relation to homocysteine in black South Africans [J]. Gene, 2013, 530 (1): 113-118.

[17] Van Meurs J B, Pare G, Schwartz S M,etal. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease [J]. Am J Clin Nutr, 2013, 98 (3): 668-676.

[18] Franco Brochado M J, Domenici F A, Candolo Martinelli A D,etal. Methylenetetrahydrofolate reductase gene polymorphism and serum homocysteine levels in nonalcoholic fatty liver disease [J]. Ann Nutr Metab, 2013, 63 (3): 193-199.

[19] Chuang C H, Lee Y Y, Sheu B F,etal. Homocysteine and C-reactive protein as useful surrogate markers for evaluating CKD risk in adults [J]. Kidney Blood Press Res, 2013, 37 (4-5): 402-413.

[20] Bigio R S, Verly E Jr, de Castro M A,etal. Are plasma homocysteine concentrations in Brazilian adolescents influenced by the intake of the main food sources of natural folate ? [J]. Ann Nutr Metab, 2013, 62 (4): 331-338.

[22] Linda L, Rongwei F, Kevin R,etal. Homocysteine level and coronary heart disease incidence [J]. Mayo Clin Proc, 2008, 83 (11): 1203-1212.

(2013-12-24收稿 2014-03-25修回)

(責(zé)任編輯 武建虎)

Astudyonriskfactorsinyoungpatientswithcoronaryheartdisease

QUAN Yongjun1, ZHU Hang2, SU Xiaojun1, WANG Haotian3, HE kai4, ZHANG Ziyun5, and SUN Jinyan1.

1. Medical College of Nankai University, Tianjin 300071, China; 2. Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China; 3. Medical Center of Tsinghua University, Beijing 100084, China; 4. Department of Cardiology, People’s Hospital of Chongqing Municipality,Chongqing 400053, China; 5. Department of Cardiology, Henan Honli Hospital, Changyuan 453400, China

ObjectiveTo study the risk factors in young patients with coronary heart disease.MethodsA total of 855 patients (age≤40 years) hospitalized in this department between June 2011 and March 2013 were included in this study. Patients with definite diagnosis were as young coronary heart disease group (n=455) and other patients were as control group (n=400). Their serum homocysteine was measured by high performance liquid chromatography. The single factor analysis and multivariate logistic regression analysis were used for risk factors of young coronary heart disease.ResultsThe serum Hcy, family history of coronary heart disease in young coronary heart disease group were all higher than those in control group(P<0.01 orP<0.05). The logistic regression analysis demonstrated that Hcy(OR=1.380，P=0.001)and history of coronary heart disease(OR=3.556，P=0.002)were all independent risk factors for young coronary heart disease patients.ConclusionsHigh serum homocysteine and family history of CHD are independent risk factors for young CHD patients.

coronary heart disease; homocystein; young; risk factors

全勇俊，碩士研究生，E-mail:qyongjun@yeah.net

1.300071天津，南開大學(xué)醫(yī)學(xué)院；2. 100853北京，解放軍總醫(yī)院心內(nèi)科；3. 100084北京，清華大學(xué)醫(yī)學(xué)中心；4.400053，重慶市第十三人民醫(yī)院心內(nèi)科；5.453400長垣，河南宏力醫(yī)院心血管內(nèi)科

朱 航，E-mail: zhuhang301@126.com

R541.4