摘要
目的：探讨血压昼夜节律、大动脉功能、左心室肥厚、ACE I／D多态性与高血压病中医证型相关性，以期为高血压病中医辨证提供更加客观的依据，为中西医结合预防和治疗高血压提供新途径、新方法，使高血压病的研究与治疗迈上一个新台阶。
研究方案：采用问卷调查方式，填写高血压患者登记表格及中医症候分级量化表，测量血压及心率，采空腹血，用于生化指标及基因检测。采用无创性携带式动态血压监测仪(美国Welch Allyn QuieTrakTM5100)，测量白昼(6am-10pm)与夜间(10pm-6am)两个阶段血压。采用澳大利亚桡动脉压力波分析仪(SphygmoCor，Sydney，Auatralia)记录桡动脉脉搏压力波形。采用GE Medical Systems公司生产的Cardiosoft version 4.2版本心电图仪同步记录常规十二导联ECG。采用HP5500超声心动图检查仪，测量升主动脉内径(LAD)、舒张末期左心室内径(LVID)、左心室收缩内径(LVESD)、室间隔厚度(ISV)和左室后壁厚度(PWT)。使用聚合酶链反应、琼脂糖电泳法进行ACE I／D基因分型。观察指标：研究对象的中医辨证分型、基本特征(包括近期服药史、高血压及其它心血管疾病史、家族史、糖尿病史、饮酒、吸烟，测量身高、体重等)；诊室血压及心率、24小时动态血压变化与高血压病中医证型的相关性；大动脉弹性指数(外周反射波增强指数、中心动收缩压、中心动脉脉压、中心动脉反射波增强指数)、Sokolow-lyon Index与高血压病中医证型的相关性；心脏超声指数(升主动脉内径、左室舒张内径、左室收缩内径、左室后壁厚度)与高血压病证型的相关性；ACE基因分型及等位基因与高血压病中医证型的相关性。
结果：原发性高血压患者中肝火亢盛证型患者明显高于其他证型。研究人群男女之间在年龄、收缩压、舒张压、以及高血压的治疗率等均无显著差别，但女性在吸烟、饮酒比例及体重、尿酸、尿肌酐等显著低于男性，总胆固醇明显高于男性，男性在糖尿病患病率明显高于女性。无症状组诊室血压的平均收缩压明显低于其它证型组，且有明显差异(P＜0.05)，痰湿壅盛证型组、阴虚阳亢组平均收缩压明显高于其它证型组，且有明显差异(P＜0.05)，肝火亢盛证型组、证型不明确组、阴阳两虚证型组之间平均收缩压无明显差异。24小时动态血压痰湿壅盛证型组、阴阳两虚证型组24小时平均收缩压明显高于其它组，(P＜0.05)，证型无法确定组24小时平均收缩压明显低于其它组别(P＜0.05)，各组之间24小时平均舒张压、平均心率无明显差别。大动脉弹性指数无症状组外周反射波增强指数(P_AI)、中心动脉收缩压(C_SP)明显低于肝火亢盛、阴虚阳亢、痰湿壅盛、阴阳两虚及证型不明确组别，且有明显统计学差异(P＜0.05)。阴阳两虚证型组外周反射波增强指数(P_AI)、中心动脉收缩压(C_SP)、中心动脉脉压(C_PH)、中心动脉反射波增强指数(C—AI)均明显高于无症状、肝火亢盛、阴虚阳亢、痰湿壅盛及证型不明确组别组别，且有明显统计学差异(P＜0.05)。心电图Sokolow-lyon指数测定阴阳两虚证型、痰湿壅盛证型组两Sokolow-lyon-Index明显高无症状组、肝火亢盛组、阴虚阳亢组、证型不明确组，且有统计学差异(P＜0.05)。心脏超声各证型心脏超声升主动脉内径、左室舒张内径(LVEDD)、左室收缩内径(LVESD)左室后壁厚度(PWT)无明显差别。ACEI／D多态性的基因型与中医症型之间的关系，得出各证型组在各基因型之间均未见显著差异。
结论：各证型组中阴阳两虚证型血压昼夜节律性较差、大动脉硬化程度明显大于其他组；痰湿壅盛、阴阳两虚证型左心室肥厚的发病率高于其他组别；ACEI／D多态性基因型与中医证型无相关性。
Aims: to investigate the correlation between blood pressure rhythm, aorta functionsand left ventricular hypertrophy, ACE I/D polymorphism and circardian varioussyndromes of hypertension. We hope to provide more objective data to supporttraditional Chinese medic, ine differentiation of hypertension. By doing this, we couldprovide new integrated methods to prevent and treat hypertension. As a result, theresearch and therapeutic methods of hypertension will arrive at a new level.
Methods: we used a questionnaire, hypertension patient's registration forms andTCM symptom severity index to record information. Blood pressure and heart ratewere also recorded. Serum chemistry and gene polymorphism were tested in thefast. Ambulatyory blood pressure monitoring devices (Welch Allyn Quie Trak TM5100) were used to measure blood pressure during the day (6am-10pm) and night(10pm-6pm). We also used Sphygmocor (Sydney, Australia) to record PulseWaveform of the radial artery. The Cardiosoft version4.2 (GE Medical Systems) wasused to simultaneously record 12channel electro cardiography with.Echocardiography of HP5500 was used to measure left atrium diameter (LAD), leftventricular internal diameter (LVID), left ventricular end-systolic diameter(LVESD), inter septal (ISV) and posterior wall thickness(PWT). The polymerasechain reaction and agarose gel electrophoresis were used to analyze ACE I/Dgenotype. Observations included TCM differentiation, basic characters (includingrecent drug intake, medical history of hypertension and other cardiovascular diseases,family history, diabetes history, drinking, smoking, height and body weight), clinicblood pressure, heart rate, and 24h ambulatous blood pressure in different syndromes.Large artery elasticity index in different syndromes, such as P-AI, C-SP, C-PH, C-AI,Sokolow -lyon Index (Sv1+Rv5 or Rv6) and echocardiography index, such as Aos,LVEDD, LVESD, PWT were also been studied. The genotype and alleles of ACEpolymorphism were recorded.
Results: In the primary hypertension patients, more patients suffered from theLiver fire flare than other types. Among the subjects of this study, there was nosignificant difference between male and female in age, systolic and diastolic pressure,use of medication. However, smoking, drinking, body weight, uric acid and uriccreatinine in women were lower than men(P＜0.05), while total cholesterol washigher than men. The incidence of diabetes in men was higher than women. Theaverage systolic pressure in asymptomatic group was significantly fower than othergroups. Systolic pressure in Phlegm dampness accumulation group and Yindeficiency Yang excess group were significantly higher than other groups (P＜0.05).There was no difference among the Liver fire flare group, group of patients who had symptoms without definite syndrome and Yin and Yang deficiency group. There wasno difference between these groups in regard to heart rate. In the 24h ambulatorsblood pressure measurement, average systolic pressure of Phlegm dampnessaccumulation group and Yin and Yang deficiency group were much higher than othergroups (P＜0.05). 24h arnbulators blood pressure in the group of patients who hadsymptoms without definite syndrome was much lower than other groups (P＜0.05).There was no significant difference between these groups with regard tothe average 24h diastolic: pressure and heart rate. Large artery elasticity indexes inthe asymptomatic group, such as P_AI, C_SP, were obviously lower than Liver fireflare group, Phlegm dampness accumulation group, Yin deficiency Yang excessgroup, Yin and Yang deficiency group and group without definite syndrome (P＜0.05). P_AI, and C_SP, C—AI in the Yin and Yang deficiency group weremuch higher than asymptomatic group, Liver fire flare group, Yin deficiency Yangexcess group, Phlegm dampness accumulation group and the group without definitesyndrome (P＜0.05). Sokolow-lyon Index of electrocardiography in Yin and Yangdeficiency and Phlegm dampness accumulation group were much higher than theasymptomatic group, Liver fire flare group, Yin deficiency Yang excess group andthe group without definite syndrome (P＜0.05) Echocardiography index, such asAos,LVEDD,LVESD, and PWT were not significant differentbetween there groups.The ACEI/D polymorphism genotype frequency in different syndrome group wasnot significanc different.
Conclusion: In the primary hypertension patients, more patients suffered fromthe Liver fire flare. The ACEI/D genotype in different syndrome group was notsignificantly different. Among these groups, blood pressure rhythm in the Yin andYang deficiency group was worse than the others and its sclerosis degree of largearteries was also more obvious than others. The incidence of left ventricularhypertrophy in the Phlegm dampness accumulation group and Yin and Yangdeficiency groups was higher than other the groups. The ACE I/D polymorphismwas not correlated to TCM syndromes.
引文
1．李立明，饶克勤，孔灵芝等．中国居民2002年营养与健康状况调查．中华流行病学杂志 2005：26(7)：478-484．
2. Wang JG, Staessen JA. Conventional therapy and newer drug classes for cardiovascular protection in hypertension. J Am Soc Nephrol 2002; 13(suppl 3): S208-S215.
1．候延丽。123例高血压病血液流变学变化与中医辨证分型的关系。陕西中医。2002，23(8)：703
2．王晓光，陈宝田。84例老年性高血压病的中医辨证分析及治疗规律探讨。实用中西医结合杂志。1995，8(7)：410
3．侯建民。辨证分型治疗高血压病205例。河北中医。1989，11(5)：
4．章凤杰，吴悦。高血压病经颅多普勒检测结果与辨证分型关系探讨。江苏中医。1997，18(8)：41
5．魏丽华。中药治疗轻中度高血压400例观察。实用中医药杂志。2001，11，17(11)：
6．王少阳，秦萌。高血压病辨治体会。中国民间疗法。2000，8(11)：7
7．王兆禹等 高血压病中医不同证型患者糖代谢脂代谢指标差异比较。安徽中医临床杂志2000，10，12(5)：364
8．王学美，富宏，刘庚信。高血压中医辨证分型与T琳巴细胞亚群及NK细胞相关性的研究。中国中西医结合急救杂志。2000，5，7(3)：174
9．黄炎明，邓水明，潘腊梅。高血压病中医辨证分型与血液流变学关系的探讨。辽宁中医杂志。1989，(3)：17
10．高喜源，包桂英，张雪峰等。高血压病中医辨证心钠素肾素血管紧张素醛圃酮系统的测定。实用中西医结合杂志。1998，11(12)：1059
11．张三林，马峰。高血压病人中医辨证分性与甲襞微循环变化的关系。微循环杂志。1994，5(1)：39
12．蔡光先，朱克俭，韩育明。高血压病常见症候临床流行病学观察。中医杂志。1999，40(8)492
13．徐贵成，徐承秋，张士荣．平肝益肾法治疗Ⅱ期高血压的临床研究．北京中医杂志．t991，(6)：12．
14．陈金水等．高血压病辨证分型与实验室检查心电图、眼底和夜尿量关系及预后观察．中西医结合急救杂志，1999，10(10)：448-449．
15．张发荣．高血压病气虚血瘀型特征探析．江苏中医，1997，18(9)：238．
16．郑新，刘卫红．高血压病辨证分型的血压变化及胸主动脉CT改变的研究．中国中西医结合杂志．1997，(12)：733．
17．夏亦嗣，陈可冀．高血压病患者血压昼夜节律与阴阳证型关系研究．中医杂志 1998，39(5)：300-302．
18．王裕颐．高血压病人24小时动态血压与中医证型关系的观察．中国医学学报 2001，(3)：28．
19．张世亮，门雪琳．高血压病不同中医证型与24h动态血压关系的研究．山东中医药大学学报，2003，27(2)：115-116
20．李洪波，庞军，李成林，等．原发性高血压病患者血压昼夜节律变异与中医辨证分型的关系．新中医，2001，33(9)：35．
21．杨海燕，金艳蓉，杨红．原发性高血压病辨证分型与24h动态血压关系．中国中医药信息杂志，2004，11(1)：23
22．侯延丽．123例高血压病血液流变学变化与中医辨证分型的关系．陕西中医2002，23(8)：703．
23．白春锦等．不同中医证型高血压患者的心血管危险因素分层、高血压分期、分级及血脂等指标变化特征．中国临床康复，2005，9(23)：146-147
24．朱国强．高血压病的中医证型与血液流变学关系的临床研究．南京中医药大学学报，1997，13(3)：143-144．
25．张玉金．高血压病证分型和血液动力流变学的关系．辽宁中医杂志1998，25(11)：507．
26．王彤，张崇．原发性高血压病脉图血流动力学与中医辨证关系研究．江西中医药2002，28(7)：17．
27．李泓，张济颖，胡宪蕴．肾素-血管紧张素-醛固酮、血浆心钠素水平在原发性高血压中医分型的研究．天津中医，1989，(3)12-15，17．
28．唐树德，王宪衍，王谷亮．高血压患者辨证分型与肾素-血管紧张素-醛固酮系统的关系．辽宁中医杂志，1985，(12)：4-6．
29．王爱珍，蔡治宾，吴罗杰．原发性高血压病中医辨证分型与肾素、血管紧张素Ⅱ初探．中国现代医学杂志，1998，8(5)：43．
30．张玲端，刘淑蕴，白智峰．原发性、肾性高血压中医症候衍变规律与RAS、ANP的关系．天津中医，1993，(1)：21．
31．李恩，赵玉庸，谢惠芳，等．肾性高血压中医分型与血浆前列腺素、肾素、血管紧张素、环核苷酸变化的观察．中西医结合杂志，1983，3(3)：165-167．
32．黎杏群，李学文，朱崇学．中西医结合治疗高血压病的研究．中西医结合杂 志，1991，11(11)647-650．
33．严冬，陈晓虎．高血压病中医辨证分型的实质研究进展．内蒙古中医药，2000，19(2)：41
34．胡随瑜，金益强，张翔，等．肝阳上亢证实验诊断指标研究．中医杂志，1998，39(11)：680．
35．高国仗．胰岛素抵抗及其检测方法．中华心血管病杂志，1996，24(1)：3．
36．沈毅，张继东．原发性高血压病中医辨证分型与胰岛素抵抗的相关性研究．山东大学学报(医学版)，2005，43(2)：143-144
37．高志扬，钱少平，易向明等．2型糖尿病中医分型与B细胞功能、胰岛素敏感性的关系．中西医结合心脑血管病杂志，2003，1(1)：85
38．吴启锋，熊尚全，温茂详等．高血压病中医证型与盐敏感性及胰岛素抵抗关系临床研究．福建中医药，2002，33(3)：3
39．袁丽萍，方若平．66例高血压中医辨证与超声心动图改变对比分析．云南中医中药杂志，1998，19(4)：11．
40．段开骏，刘沽．不同中医辨证分型的高血压患者左心结构和功能指标变化．中国临床康复2006，10(3)：51-54
41．张凤杰，吴悦．高血压病经颅多普勒检测结果与辨证分型关系探讨．江苏中医，1997，18(8)：41．
42．雷燕，胡锡衷．高血压病虚实辨证与性激素及β_2-MG关系的探讨．中国中西医结合杂志，1994，14(11)：675-676
43．顾仁樾，周端，吕洁，等．高血压病中医辨证分型与血清β_2微球蛋白含量关系的探讨．中国中西医结合杂志，1989，13(6)：25—26．
1. Guideline subcommittee.1999 world health organization/international society of hypertension guidelines for the management of hypertension. J Hypertens, 1999,17:151-183
2. Franklin SS, Gustin W, Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham HeartStudy[J]. Circulation,1997,Jul 1,96(1):308-15.
3. Tulis DA,Unthank IL,Prewitt RT, et al. Flow induced arterial remodeling in rat mesenteric vasculature[J].AM J Physiol,1998,274(43):H874-H882.
4. London GM,Guerin AP, Pannier B,et al.Large artery structure and function in hypertension and end-stage renal disease[J].J Hypertens, 1998,16(12pt2):1931—1938.
5. Gosse P, Guillo p, Ascher G, et al. Assessment of arterial distensibility by monitoring the timing of Korotkoff sounds [J]. Am-J-Hypertens, 1994,7(3):228-33.
6. Stamler J, stamler R, Neaton J, et al. Blood pressure, systolic and diastolic pressure,cardiovascular risk:US population data[J]. Arch intern med,1993, 153:598-615.
7. Marchais S J, Guerin AP, pannier B, et al. arterial complince and blood pressure[J]. Drugs, 1993,46:282-7.
8. Safar ME,LaurentS.Behavior of conduit arter hypertension[J].Clin-Exp,Hypertens, 1993,15(6): 1033-45
9．吴桂贤，吴兆苏，刘静等．人群脉压分布特征的研究[[J]．中华心血管杂志，2001，29：436—430．
10．英俊岐，王歆月，濮蓉晖，等．高血压左室肥厚形成及其逆转研究进展[J]．医学综述，2003，9(12)：738-740．
11. Franz H,Messerli, Reinhandlkettlhut. Left ventricular hypertrophy: A pressure-independlent cardiovascular risk factor[J].J Cardiovase: Pharmacol, 1993, 22(Suppl 1):S7-S13.
12. FrancisG. Mare A.Left ventricular hypertrophy in hypertension[J].N Engl Med,1999, 340(16):1221-1227.
13．陈志君．高血压左心室肥厚研究的进展[J]．同济大学学报，2001，22(1)：81-83．
14．张维忠．高血压与大动脉功能[J]．中华内科杂志，2000，39(5)：355-356．
15．谈志强，庞振摇，陈平，等．药物干预高血压昼夜节律对左室肥厚的影响[J]．广西医科大学学报，1997，14(4)：45-47．
16．刘力生，龚兰生．中国医药导刊，2000，2(1)：3-25．
17．占成业，陶秀良，田橙，等．细胞间黏附分子1在高血压左室肥厚发病中的作用及丹参酮A对其表达的影响[J]．中国中西医结合急救杂志，2004，11(4)：208-210．
18. Staessen JA, Wang JG. Bianchi G. Essential Hypertension. Lancet 2003; 361(9369): 1629-1641.
19. Williams SM, Addy JH, Phillips JA Ⅲ, et al. Combinations of variations in multiple genes are associated with hypertension. Hypertension 2000; 36(1):2-6.
20. Dominiczak AF, Negrin DC, Clark JS, et al. Genes and hypertension. Hypertension 2000; 35 (1 Pt 2): 164-172.
21. Gambaro G, Anglani F, D'Angeio A. Association studies of genetic polymorphisms and complex disease. Lancet 2000; 355 (9200):308-31.
22．朱鼎良．我国高血压基因研究十年回顾和几点建议．中华心血管病杂志，2005：33(7)：585-587．
23. Wang JG, Staessen JA. Genetic polymorphisms in the rennin-angiotensin system: relevance for susceptibility to cardiovascular disease. Eur J Pharmacol 2000; 410 (2-3):289-302.
24. Corvol P, Persu A, Gimenez-Roqueplo AP, et al. Seven lessons from two candidate genes in human essential hypertension. Hypertension 1999; 33(6): 1324-1331.
25. Weatherall D. From genotype to phenotype: genetics and medical practice in the new millennium. Philos Trans R Soc Lond B Biol Sci 1999; 354 (1392):1995-2010.
1. WIIO/ISII. Guidelines for the mananement of hypertention. J Hypertens 1999; 17:151.
2．郑筱萸主编．中药新药临床研究指导原则．北京：中国医药科技出版社，2002：73-77．
3．任常陵．血压的日内变动和降压药的使用方法[]．日本医学介院绍，2005，2(1)：27-28．
4. GuoYF Skin PK Circadian rhythm in the cardiovuscular svstem: chronocurdiology [J],Am Heart J 2003, 145 779-786
5．张维忠，龚兰生，邱慧丽，等．动态血压与高血压性左室肥厚的关系[J]．中华心血管病杂志．1993，21(3)：
6．张维忠，杨忠奇，戚文航，等．氨地平对异常血压昼夜节律的逆转作用[J]．中国高血压杂志．1997，5(增刊)：1-3．
7．龚兰生，刘力生．血压昼夜节律变异及临床意义．中华心血管杂志，1994，22：323-324．
8. Mancia G, ParaLi G, Castiglioni P eL al.Daily life blood pressure changes are steeper in hypertensive than in nomotensive subjects Hypertension, 2003, 42: 277-282
9．夏亦嗣，陈可冀，苗阳，等．高血压患者血压昼夜节律与阴阳证型关系研究[J]．中医杂志．1998，39(5)：300-302
10．张黎明，王涤松．血压昼夜节律[J]．心血管病进展，1997．18(5)：261
1. Cohn LN.Vascular wall function as a risk [J].Hyperteng 1999, 41-44
2. Cohn LN.Arterial compliance to stratify cardiovascular risk more precision in therapeutic decision making[J].Hypertens 2001,14:258—263
3. Benetos A, Safar M, Rudnichi A, et al.Pulse pressure a predictor of long-term cardiovascular mortality in a french male population.Hypertension, 1997, 30:1410—1415.
4. Sagawa K, Lie RK, Schaefer J. Translation of Otto Frank's paper"Die Grundform des Arteriellen Pulses"Zeus Christ fur Biologic 37:483-526(1899), J Mol Cell Cardiol, 1990, 22:253—277.
5．杨鹏麟，徐定修，张素勤。脉压指数评价血管硬化的可行性探讨。中华心血管病杂志，2002．30：334—337
6. Jams MA. Watt PAC,Potter JF, et al.Pulse pressure and resistance artery structure in the elderly.Hypertension 1995;26:301-6
7. Kelly R, Haywood C, Avolio A, et al.Noninvasive determination of age-related changes yn the human arterial pulse. Circulation i 989;80:1652-9
8. Cameron R, Benetos A, Topouchian J, et al.Assesssment of arterial distensibility by automate pulse wave velocity measrrement.Validation and clinical application studies, Hypertension 1995;26:485-90
9. Chen CH, Nevo E, Fetics B, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure:validation of generalized transfer function [J].Cireulation, 1997, 95: 1827-1836.
10. Ronrke MF. Wave travel and reflection in the arterial system [J],J Hypertens, 1999, 17(Suppl 5):S45-47
11. Madhavan S OoiWL,Cohen H, et al Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction[J]. Hypertension 1994, 23 (3): 395-401.
12．周北凡，刘小清，武阳丰，等．我国中年人群脉压对于心血管病事件发病的预测价值[J]． 中华心血管病杂志，2002，30(11)]：687—691．
13. Cohn J, Finkelstein S,Mc Veigh G. Noenva sive pulse wave analysis for the early detection of the vascular disease [J]. Hypertension, 1993,26(3):503-508
14. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine[J].Nature 1980,288.(5789)373-376
15．张维忠．高血压研究新视点：脉压与动脉弹性功能[J]．高血压杂志，2003，11(6)：506—507．
16．张维忠．降压治疗新视点：中心动脉压[J]．中华心血管病杂志，2006，34(5)：471—473．
17. Rrman MJ,K izerJR,Ali,T, et al Central blood pressure betterpredicts cardiovascularevents than does peripheral blood prssure the Strong Heart Study [J] Circulation,2005,112 SupplⅡ:Ⅱ—778
18. Boutouyrie P, Tropeano Al, Asmar R, et al. Aortic stiffness is an independent predictor of primary coronary event in hypertensive batients. a longitudinalstudy. Hvbertension。2002. 39: 10-15
1. Casale PN,Devereux RB,Alonso DR,et al.lmproved sex-specifice criteria of eft ventricular hypertrophy for clinical and computer interpretation of electro cardiograms:validation with autopsy findings.Circulation, 1987,75:565)572.
2. Verdecchia P, Schillaci G, Borgioni C,et al.Prognostic significance of Seri alchanges in left ventricular mass in essential hypertension.Circulation, 1998,97:48)54.
3．吴华堂，范金茹．从肝治心法逆转自发性高血压大鼠左室肥厚的实验研究[J]．中医药学刊，2003，21(1)：81．
4．杨传华，韩玉水，刘政．中医药逆转高血压左心室肥厚的理论探讨[J]．河北中医，1994，16(5)：1-2．
5．翁伟强．探索中西医结合治疗高血压病的最佳结合点[J]．中国中医基础医学杂志，1995，1(3)：34-35．
6．严灿．心肌康对高血压病左室肥厚逆转的临床作用观察及机理探讨[J]．中国中医药科技，1995，2(5)：17-18．
7．刘劲松，张榴修，周宜轩．高血压左室肥厚的中医病机学说[J]．中国中医基础医学杂志，2004，10(2)：72．
8．杨传华，郭伟星．高心病临床证治体会[J]．山东中医药大学学报，1997，21(3)：193
9. Hong SJ,Park CG, Seo HS,et al.Association among plasma adiponeetin,hypertension,left ventrovular diastolic function and left centricular mass index .Blood Press2004; 13(4):236-42
10．于俊生，痰瘀相关学说与临床[M]，北京：科学技术文献出版社，1995：4
11．张金枝，高血压病与心肌肥厚[J]．临床心血管病杂志，1997；7(3)：187
1. Erdos EG, Skidgel RA. Structure and function of Human angiotensin converting en-zyme (kininase Ⅱ).Biochem Soc Transact, 1985, 13:42
2. Lieberman J, Sastre A .Angiotensin converting enzyme activity in postmorterm human tissues. Lab Invest, 1983,48:711
3. Gordon Mc Znnes. Angzotensin Ⅱ Antagonists. London:Science Press Ltd, 1998.1
4. Alhenc GF, Richard J, Courbon D, et al.Distribution of plasma argiotensin l-converting enzyme levels in healthy men relationship to environmental and hormonal parameters. J Lab Clin Med, 1991, 117:33
5. Tiret L, Rigat B, Visvikis A, et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin Ⅰ-converting enzyme＜ACE) gene controts plasma ACE levels. Am J Hum Genet, 1992, 51:197
6. Hubert C. Houot AM Corvol P, et al. Structure of the angiotensin Ⅰ converting en-zyme gene. J Bio chem, 1991,266(23): 15377
7. Foy CA, Rice Gl, Ossei-Gerning N, et al. Angiotensin converting enzyme (ACE) gene polymorphisms in patients characterised by coronary angiography. Hum Genet, 1997, 100:420
8．谈红，张国元，黄超，等．国人ACE基因插人／缺失多态性分析及与血清ACE水平的相关性．第二军医大学学报，1997，18(4)：337
9. RigatB,HubertC,Algende-GalasF, etal.Aninsertion/deletionpolymorphism in the angiotensin Ⅰ-converting enzyme gene accounting for half the variance of serum enzyme levels. J Chin Invest, 1990, 86:1343
10. Guyton AC. Blood pressure, control-special role of the kidneys and body fluids. Science 1991; 252(5014):1813-1816.
11. Hilbert P, Lindpaintner K, Beckmann JS, et al. Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature 1991; 353(6344):521-529.
12. Jacob HJ, Lindpaintner K, Lincoln SE, et al. Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 1991; 67(1):213-224.
13. Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359(6396):641-644.
14. Staessen JA, Wang JG, Ginocchio G, et al. The deletion/insertion polymorphism of the converting-enzyme and cardiovascular-renal risk. J Hypertens 1997; 15 (12 Pt 2): 1579-1592.
15.Kunz R, Bork JP, Fritsche L, et al. Association betweenthe angiotensin-converting enzyme insertion/deletion polymorphism anddiabetic nephropathy: a methodologic appraisal and systematic review. J Am Soc Nephrol 1998; 9(9): 1653-1.663.
16. Kuznetsova T, Staessen JA, Wang JG, et al. Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a metaanalysis. J Hum Hypertens 2000; 14(7):447-454.
17. O'Donnell C J, Lindpaintner K, Larson MG. et al. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation. 1998; 97 (18):1766-72.
18. Higaki J, Baba S, Katsuya T. et al. Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men: the Suita Study. Circulation. 2000; 101(17):2060-5.
19. Staessen JA, Wang JG, Brand E. et al. Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population. J Hypertens. 2001; 19(8): 1349-1358.
20. Wang JG, Liu LF, Zagato L. et al. Blood pressure in relation to three candidate genes in a Chinese population. J hypertens. 2004; 22(5):937-944.
21.Strazzullo P, Iacone R, Iacopino L, et al. Genetic variation in the renin-angiotensin system and abdominal adiposityin men: the Olivetti Prospective Heart Study. Ann Intern Med 2003; 138(1):17-23.
22. Lee YJ, Tsai JCR. ACE gene insertion/deletion polymorphism associatedwith 1998 World Health Organization definition of metabolic syndrome inChinese type 2 diabetic patients. Diabet Care 2002; 25(6): 1002-1008.
23. Bengtsson K, Orho-Melander M, Lindblad U, et al. Polymorphism in the angiotensin converting enzyme butnot in the angiotensinogen gene is associated with hypertension and type2 diabetes: the Skaraborg Hypertension and Diabetes Project. J Hypertens 1999; 17(11):1569—1575.
24.Wang JG, He X, Wang GL, et al. Family-based associations between the angiotensin- converting enzyme insertion/deletion polymorphism and multiple cardiovascular risk factors in Chinese. J Hypertens 2004; 22(3):487-491.
25. Martinez E, Puras A, Escribano J. et al. Angiotensin-converting enzyme (ACE) gene polymorphisms, serum ACE activity and blood pressure in a Spanish-Mediterranean population. J Hum Hypertens 2000; 14(2): 131-135.
26. Uemura K, Nakura J, Kohara K, et al. Association of ACE I/D polymorphism with cardiovascular risk factors. Hum Genet 2000; 107(3):239-242.
27. Urn JY, Mun KS, An NH, et al. Polymorphism of angiotensin-converting enzyme gene and BMI in obese Korean women. Clin Chim Acta 2003; 328(1-2): 173-178.
28. Engeli S, Negrel R, Sharma AM. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 2000; 35(6):1270-1277.
29. Saint-Marc P, Kozak LP, Ailhaud G, et al. Angiotensin II as a trophic factor of white adipose tissue: stimulation of adipose cell formation. Endocrinology 2001; 142(1):487-492.
30.Cooper R, McFarlane-Anderson N, Bennett FI, et al. ACE, angiotensinogen and obesity: a potential pathway leading to hypertension. J Hum Hypertens 1997; 11(2):107-111.
31. Montgomery HE, Marshall R, Hemingway H, et al. Human gene for physical performance. Nature 1998; 393(6682):221-222.
32.Staessen JA, Wang JG Bianchi G. Essential Hypertension. Lancet 2003; 361(9369): 1629-1641.
33.Williams SM, Addy JH, Phillips JA III, et al. Combinations of variations in multiple genes are associated with hypertension. Hypertension 2000; 36(1):2-6.
34.Province MA, Kardia SL, Ranade K, et al. A meta-analysis of genome-wide linkage scans for hypertension: the National Heart, Lung and Blood Institute Family Blood Pressure Program. Am J Hypertens 2003; 16(2):144-147.
35.Caulfield M, Munroe P, Pembroke J, et al. Genome-wide mapping of human loci for essential hypertension. Lancet 2003; 361(9375):2118-2123.
36.Zhu DL, Wang HY, Xiong MM, etc. Linkage of hypertension to chromosome 2ql4-q23 in Chinese families. J Hypertens 2001; 19(1):55-61.
37.Wang JG, Staessen JA. Genetic polymorphisms in the rennin-angiotensin system: relevance for susceptibility to cardiovascular disease. Eur J Pharmacol 2000; 410 (2-3):289-302.
38. Corvol P, Persu A, Gimenez-Roqueplo AP, et al. Seven lessons from two candidate genes in human essential hypertension. Hypertension 1999; 33(6): 1324-1331.
39.Weatherall D. From genotype to phenotype: genetics and medical practice in the new millennium. Philos Trans R Soc Lond B Biol Sci 1999; 354 (1392):1995-2010.