前言

高血压作为一种慢性非传染性疾病，也是我国患病率较高、致残率较高及疾病负担较重的慢性疾病。2016 年国家卫生计生委发布的数据显示：我国 18 岁及以上成人高血压患病率为 25.2%。尽管近些年我国人群的高血压知晓率、治疗率、控制率已有改善，但仍处于较低水平。全球疾病负担研究显示：中国人群因高血压造成的伤残调整寿命年（DALY）高达 3794 万人年，占总 DALY 的 12.0%，占心血管病总DALY的63.5%；其中伤残损失寿命年（YLD）为 3557 万人年，早逝损失寿命年（YLL）为 236.5 万人年，占心血管病 YLD 和 YLL 的 50.1% 和 64.5%，是心血管病负担的首位危险因素。全国每年因血压升高所致的过早死亡人数高达 200 余万，每年直接医疗费用达 366 亿。2016 年我国一项发表于 JAMA杂志的队列研究结果显示，我国治疗后的高血压患者的血压达标率为 29.6%。高血压作为心脑血管病最重要的危险因素，流行态势严重，其主要并发症如卒中、心肌梗死、心力衰竭及慢性肾脏病等的致残致死率高，严重消耗医疗和社会资源，给家庭和社会造成沉重负担，已成为我国一项重要的公共卫生问题。尽管近年来高血压的诊断和治疗取得了长足进展，高血压治疗药物也层出不穷，但高血压药物治疗亦存在诸多不合理之处，由此也影响了患者治疗的依从性、持续性及血压控制率。国家卫生计生委近年颁布了高血压分级诊疗策略，提出高血压治疗要规范，并下沉到基层医疗服务中心，这将使药物的合理应用提升至更高的位置，希望高血压治疗药物不仅在等级医院应用合理，在基层医院也能规范地合理应用。基于此，在第 1 版《高血压合理用药指南》颁布 2 年之后，顺应高血压治疗形势的改变，国家卫生计生委合理用药专家委员会和中国医师协会高血压专业委员会组织进行该指南的更新和再版。第 2 版指南增加了药物基因组学内容、正在研究的新药、药物的循证推荐，同时增加具有知识产权的国产创新降压药物章节，丰富了药物治疗的内容。我们希望此版《高血压合理用药指南》能够帮助医生认识规范使用降压药物的重要性，指导医生在不同血压水平、不同高血压并发症情况下恰当、合理地使用降压药物，提高自身的治疗水平，使高血压患者的治疗依从性和持续性有所改善，提高血压控制率，减少心脑血管事件。

孙宁玲：北京大学人民医院高血压研究室主任  国家卫生计生委合理用药专家委员会  心血管药物专业组副组长  中国医师协会高血压专业委员会名誉主任委员

循证医学相关方法说明

2016 年 10 月 13 日，由国家卫生计生委合理用药专家委员会和中国医师协会高血压专业委员会组成指南修订联合委员会，经 4 次联合会议讨论后最终确定了指南修订的总体原则及新指南拟回答的核心问题。指南工作组针对这些核心问题制定了具体的文献检索和评价策略，综合评价、筛选出相关文献。修订过程主要包括下列几项特点：

（1）    本指南是在尽可能全方位检索复习临床循证研究证据的基础上，由指南工作组有关专家及团队（循证医学、流行病学、心血管病学、高血压、内分泌代谢、肾脏病学、神经病学及药理学领域的专家）分工写作而成。草案完成后，经过多次修改，并经多方评审。

（2）    本指南的工作组由多专业学科的专家，特别是一直从事高血压研究的专家以及流行病学和药理学专家组成，他们是：曾哲淳、詹思延教授（循证医学专家），王丽敏、王增武、孙宁玲教授（第 1 章：高血压流行及治疗现状），蔡军、陈鲁原、刘蔚教授（第 2 章：高血压药物分类），孙宁玲、郭艺芳、陈源源、林金秀、陈晓平、冯颖青、王浩、初少莉、张宇清、卢新政教授（第 3 章：用药原则及规范），范利、张新军、吴海英、荆珊、袁洪、李建平、陈源源、陈鲁原教授（第 4 章：国产创新药物），林金秀、孙刚、陶军、李玉明、谢良地、王鸿懿、李勇、孙跃民教授（第 5 章：高血压特殊合并症的药物治疗原则），祝之明、姜一农、李玉明、牟建军、高平进、李南方、宋雷、尹新华教授（第 6 章：常见特殊类型高血压的治疗原则和药物选择），孙英贤教授（第 7 章：基层高血压患者的国家基本药物的应用原则），赵志刚教授（附录：常见降压药物列表）。完稿后由《中国医学前沿杂志（电子版）》编辑部负责统稿，最终由主编孙宁玲教授组织修订，并亲自逐字逐句地审稿最后定稿。

（3）    写作团队针对每个核心问题，确定文献检索策略，检索的数据库包括 PUBMED、EMBASE、 CBMDISC、CNKI、万方、维普及 CMCC 等数据库中 2006—2017 年发表的关于高血压药物治疗的相关文献，并对文献进行初步筛选。

（4）    文献筛选的纳入标准：①随机对照试验（RCT）：≥50 对、设计良好的随机对照临床研究。要注意结果的稳健性，最好有灵敏度分析。②观察性研究：自然人群为基础的代表性良好的生态学研究、代表性良好的横断面研究、队列研究、病例对照研究和注册研究，样本量应＞ 1000 例。③系统综述：综述中纳入的研究数量至少应≥3 个，应包含荟萃分析。同样的主题，选择包含的研究较多、时间较近、分析研究质量较高的系统综述。

（5）    针对筛选后的文献，写作团队根据文献全文对其进行证据质量的综合评级，再由工作组临床专家针对该核心问题提出各项推荐等级的建议，推荐等级是在系统评价证据质量及临床实践的基础上，由多学科专家反复讨论形成，当专家意见出现分歧时，在充分考虑不同意见的基础上接受多数专家的共识，并形成最终推荐等级。

（6）    写作过程中参考或引用了中国和国际上影响较大的几个最新版高血压防治相关指南的证据质量评级和推荐等级的结果。

（7）    本指南采用的证据质量评级和推荐等级参考了欧洲心脏病学会的标准，并进行适当修改。

（8）    指南的制定过程参考了国外及中华医学会临床指南制订的标准流程。

1 高血压流行及治疗现状

1.1 高血压流行现状 

随着社会经济的发展，城镇化和老龄化速度加快，居民行为和生活方式发生改变，慢性非传染性疾病（简称慢性病）已成为影响我国乃至全球居民健康的重大公共卫生问题 ^[1]，而高血压是患病率较高的慢性病之一，也是心脑血管病最重要的危险因素。据世界卫生组织（WHO）统计资料显示，2012 年全球心血管病死亡人数为 1700 万，占慢性病死亡人数的 46%，其中高血压并发症死亡人数为 940 万，占全部疾病负担的 7%

[1]      刘明波， 李镒冲， 刘世炜， 等．2010年中国人群高血压疾病负担[J]． 中华流行病学杂志，2014，35（6） ：680-683．

[2]     World Health Organization. GLOBAL STATUS REPORT on noncommunicable diseases 2014[EB/OL]. http://apps.who.int/iris/bitstream/10665/148114/1/9789241564854_eng.pdf

[3]      国家卫生计生委疾病预防控制局． 中国居民营养与慢性病状况报告2015[M]． 北京 ： 人民卫生出版社，2015．

[4]      世界银行创建健康和谐生活，遏制中国慢病流行[EB/OL]https://file1p.dxycdn.com/2017/0707/954/3219920661209740367-8.pdf?Expires ＝1501493921&OSSAccessKeyId＝LTAIVd8OrTwlQDJl&Signature＝   1eb8QCLVLOJJuc66u5UG9Mn%2BRVA%3D

[5]     国家心血管病中心． 中国心血管病报告2013[M]． 北京 ：中国大百科全书出版社，2015．

[6]      Li Yi, Yang L, Wang L, et al. Burden of hypertension in China: A nationally representative survey of 174, 621 adults[J]. Int J Cardiol, 2017, 227:516-523.

[7]     中国疾病预防控制中心慢性非传染性疾病预防控制中心．中国慢性病及其危险因素监测报告2013[M]． 北京 ： 军事医学科学出版社，2016．

[8]     Li Y, Feng X, Zhang M, et al. Clustering of cardiovascular behavioral risk factors and blood pressure among people diagnosed with hypertension: a nationally representative survey in China[J]. Sci Rep, 2016, 6:27627.

[9]     刘月玲， 朱焕池， 朱秋玲， 等．150例住院患者抗高血压药物利用分析[J]． 今日药学，2010，20（12） ：54-57．

[10]   刘立新， 刘立敏， 武云涛， 等． 美国JNC8高血压指南简介[J]．中国循证心血管医学杂志，2014，6（4） ：379-381．

[11]   陈凌，钱月晟，朱鼎良，等．上海莘庄社区 2007-2011 年抗高血压药物的应用情况分析 [J]．中国全科医学，2014，17（1）：101-104．

[12]   闫鹏丽．不同级别医院门诊抗高血压药物调查分析 [D]．天津：天津医科大学，2014 ：16-23．

[13]   王轶瓯．对社区卫生服务中心抗高血压药物使用情况的调查分析 [J]．当代医药论丛，2015，13（3）：155-156．

[14]   李旭，纪雨辰．上海嘉定社区医院门诊抗高血压药物处方分析 [J]．世界临床医药，2014，35（10）：611-616．

[15]   李维维．社区高血压治疗药物的合理应用 [J]．内蒙古中医药，2016，35（3）：75-76．

[16]   王晓明．高血压病社区药物治疗方法分析 [J]．医学信息，2016，29（19）：200．

[17]   Kramoh EK, N'Goran YN, Ake-Traboulsi E, et al. Hypertension management in an outpatient clinic at the Institute of Cardiology of Abidjan (Ivory Coast)[J]. Arch Cardiovasc Dis, 2011, 104 (11):558-564.

[18]   Wang Z, Wang X, Chen Z, et al. Hypertension Control in Community Health Centers Across China: Analysis of Antihypertensive Drug Treatment Patterns[J]. Am J Hypertens, 2014, 27(2):525-259.

[19]   何江江，杨燕，吴文辉，等．上海市慢性病门诊用药现状调查：以高血压、糖尿病为例 [J]．中国卫生资源，2016，19（3）：167-171．

[20]   董婷，刘素珍，李继平．社区高血压管理病人药物降压治疗管理及血压达标的影响因素分析 [J]．护理研究，2016，30（4）：1445-1448．

[21]   黄立，文春颖，郑春英，等．社区原发性高血压患者抗高血压药使用调查 [J]．北方药学，2016，13（8）：176-177．

[22]   崔宇超，李雄方．基层社区利用健康档案对辖区内高血压患者用药情况的统计与点评 [J]．今日药学，2015，25（4）：303-305．

[23]   王敬丽，许祥贵，王静珍，等．上海某社区高血压人群抗高血压药物的应用分析 [J]．中华全科医师杂志，2010，（9 9）：603-606．

[24]   刘秀云，邓灿亮．社区新发高血压患者初始药物治疗的依从性及相关影响因素分析 [J]．临床医学工程，2016，23（7）：987-988．

[25]   喻珏砚，范群，连燕舒，等．江苏城市社区高血压控制率及相关因素调查 [J]．江苏预防医学，2012，23（3）：46-47．

[26]   王洁，张烨雄，郭芳玲．256 例高血压病社区管理分析 [J]．内蒙古中医药，2012，31（15）：93-94．

[27]   Bremer T, Man A, Kask K, et al. CACNA1C polymorphisms are associated with the efficacy of calcium channel blockers in the treatment of hypertension[J]. Pharmacogenomics, 2006, 7(3):271-279.

[28]   Yasar U, Forslund-Bergengren C, Tybring G, et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype[J]. Clin Pharmacol Ther, 2002, 71(1):89-98.

[29]   Yasar U, Tybring G, Hidestrand M, et al. Role of CYP2C9 polymorphism in losartan oxidation[J]. Drug Metab Dispos, 2001, 29(7):1051-1056.

[30]   Rigat B, Hubert C, Alhenc-Gelas F, et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels[J]. J Clin Invest, 1990, 86(4):1343-1346.

[31]   Thorn GF, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for angiotensinconverting enzyme[J]. Pharmacogenet Genomics, 2010, 20(2):143-146.

[32]   Parvez B, Chopra N, Rowan S, et al. A common beta1-adrenergic receptor polymorphism predicts favorable response to rate-control therapy in atrial fibrillation[J]. J Am Coll Cardiol, 2012, 59(1):49-56.

[33]   周宏灏，陈小平，张伟，等．国家卫生计生委医政医管局关于印发《药物代谢酶和药物作用靶点基因检测技术指南（试行）》和《肿瘤个体化治疗检测技术指南（试行）》的通知 [EB/OL]．http://www.nhfpc.gov.cn/yzygj/s3593/201507/fc a7d0216fed429cac797cdafa2ba466.shtml

[34]   陈修．心血管药理学 [M]．3 版．北京：人民卫生出版社，1989．

[35]   Spruce AE, Standen NB, Stanfield PR. Voltage-dependent ATPsensitive potassium channels of skeletal muscle membrane[J]. Nature, 1985, 316(6030):736-738.

[36]   tanden NB, Quayle JM, Davies NW, et al. Hyperpolarizing vasodilators activate ATP-sensitive K⁺ channels in arterial smooth muscle[J]. Science, 1989, 245(4914):177-180.

[37]   Cook DL, Hales CN. Intracellular ATP directly blocks K⁺ channels in pancreatic B-cells[J]. Nature, 1984, 311(5983):271-273.

[38]   Ashford ML, Sturgess NC, Trout NJ, et al. Adenosine-5'-triphosphate-sensitive ion channels in neonatal rat cultured central neurones[J]. Pflügers Arch, 1988, 412(3):297-304.

[39]   Bernardi H, De Weille JR, Epelbaum J, et al. ATP-modulated K⁺ channels sensitive to antidiabetic sulfonylureas are present in adenohypophysis and are involved in growth hormone release[J]. Proc Natl Acad Sci U S A, 1993, 90(4):1340-1344.

[40]   Tsuchiya K, Wang W, Giebisch G, et al. ATP is a coupling mod u lator of parallel Na, K-ATPase-K-channel activity in the renal proximal tubule[J]. Proc Natl Acad Sci U S A, 1992, 89(14): 6418-6422.

[41]   Inoue I, Nagase H, Kishi K, et al. ATP-sensitive K⁺ channel in the mitochondrial inner membrane[J]. Nature, 1991, 352 (6332):244-247.

[42]   IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial[J]. Lancet, 2002, 359(9314):1269-1275.

[43]   Ambrosio G, Komajda M, Mugelli A, et al. Management of stable angina: A commentary on the European Society of Cardiology guidelines[J]. Eur J Prev Cardiol, 2016, 23(13): 1401-1412.

[44]   Wang SY, Cui WY, Wang H. The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels[J]. Acta Pharmacol Sin, 2015, 36(12):1444-1450.

[45]   Rosenthal N, Meininger G, Ways K, et al. Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus[J]. Ann N Y Acad Sci, 2015, 1358(1): 28-43.

[46]   Oliva RV, Bakris GL. Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors[J]. J Am Soc Hypertens, 2014, 8(5):330-339.

[47]   Baker WL, Smyth LR, Riche DM, et al. Effects of sodiumglucose co-transporter 2 (SGLT2) inhibitors on blood pressure: a systematic review and meta-analysis[J]. J Am Soc Hypertens, 2014, 8(4):262-275.

[48]   Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older[J]. N Engl J Med, 2008, 358(18):1887-1898.

[49]   Okin PM, Oikarinen L, Viitasalo M, et al. Prognostic value of changes in the electrocardiographic strain pattern during antihypertensive treatment: the Losartan Intervention for EndPoint Reduction in Hypertension Study (LIFE)[J]. Circulation, 2009, 119(14):1883-1891.

[50]   Parving HH, Lehnert H, Bröchner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes[J]. N Engl J Med, 2001, 345(12): 870-878.

[51]   Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes[J]. N Engl J Med, 2001, 345(12):851-860.

[52]   宗文漪，杨文英，向红丁，等．厄贝沙坦治疗 2 型糖尿病伴白蛋白尿患者有效性和安全性多中心随机双盲对照研究 [J]．中华内分泌代谢杂志，2008，24（1）：55-58．

[53]   Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial[J]. Lancet, 2004, 363(9426):2049-2051.

[54]   Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT)[J]. Lancet, 2000, 356 (9227):366-372.

[55]   Liu L, Zhang Y, Liu G, et al. for the FEVER Study Group. The Felodipine Event Reduction (FEVER) Study: arandomized longterm placebo-controlled trial in Chinese hypertensive patients[J]. J Hypertens, 2005, 23(12):2157-2172.

[56]   Kario K, Saito I, Kushiro T, et al. Home blood pressure and cardiovascular outcomes in patients during antihypertensive therapy: primary results of HONEST, a large-scale prospective, real-world observational study[J]. Hypertension, 2014, 64(5): 989-996.

[57]   中华医学会心血管病学分会高血压血组．清晨血压临床管理的中国专家指导建议 [J]．中华心血管病杂志，2014，42（9）：721-725．

[58]   Feldman RD, Zou GY, Vandervoort MK, et al. A Simplified Approach to the Treatment of Uncomplicated Hypertension. A Cluster Randomized, Controlled Trial[J]. Hypertension, 2009, 53(4):646-653.

[59]   Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis[J]. Hypertension, 2010, 55(2):399-407.

[60]   Brown MJ, Williams B, Morant SV, et al. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial[J]. Lancet Diabetes Endocrinol, 2016, 4(2):136-147.

[61]   Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial[J]. Lancet, 2005, 366(9489):895-906.

[62]   SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systo lic hypertension. Final results of the Systolic Hyperte nsion in the Elderly Program (SHEP)[J]. JAMA, 1991, 265(24): 3255-3264.

[63]   ALLHAT officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in highrisk hypertensive patients randomized to angiot ensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)[J]. JAMA, 2002, 288(23):2981-2997.

[64]   PATS Collaborating Group. Post-stroke antihypertensive treatment study. A preliminary result[J]. Chin Med J (Engl), 1995, 108(9):710-717.

[65]   Williams B, MacDonald TM, Morant S, et al. Spiron olactone versus placebo, bisoprolol, and doxazosin to deter mine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial[J]. Lancet, 2015, 386(10008):2059-2068.

[66]   Psaty BM, Lumley T, Furberg CD, et al. Health outcomes assoc iated with various antihypertensive therapies used as first line agents: a network meta-analysis[J]. JAMA, 2003, 289 (19):2534-2544.

[67]   Wright JM, Musini VM. First-line drugs for hypertension[J]. Cochrane Database Syst Rev, 2009, (3):CD001841.

[68]   Wing LM, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-convertingenzyme inhibitors and diuretics for hypertension in the elderly[J]. NEJM, 2003, 348(7):583-592.

[69]   MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results [J]. BMJ, 1992, 304(6824):405-412.

[70]   PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack[J]. Lancet, 2001, 358(9287):1033-1041.

[71]   Patel A, ADVANCE Collaborative Group, MacMahon S, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial[J]. Lancet, 2007, 370(9590):829-840.

[72]   Jamerson KA. Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypert ension Trial. The first hypertension trial comparing the effects of two fixeddose combination therapy regimens on combination therapy in patients living with systolic hypertension (ACCOMPLITH)[J]. J Clin Hypertens (Greenwich), 2003, 5(4 Suppl 3):29-35.

[73]   Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Opti mal Treatment (HOT) randomised trial[J]. Lancet, 1998, 351(9118):1755-1762.

[74]   Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Soc iety of Cardiology (ESC)[J]. Eur Heart J, 2013, 34(28):2159-2219.

[75]   中国高血压防治指南修订委员会．中国高血压防治指南2010[J]．中国医学前沿杂志（电子版），2011，3（5）：42-93．

[76]   Liu L, Wang JG, Gong L, et al. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension: Systolic Hypertension in China (Syst-China) Collaborative Group[J]. J Hypertens, 1998, 16(12 Pt 1):1823-1829.

[77]   Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators[J]. Lancet, 1997, 350 (9080):757-764.

[78]   Zanchetti A, Bond MG, Hennig M, et al. Calcium antagonist lacidipine slows down progression of asymptomatic carotid athero sclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, longterm trial[J]. Circulation, 2002, 106(19):2422-2427.

[79]   Poole-Wilson PA, Lubsen J, Kirwan BA, et al. Effect of longacting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): Randomised controlled trial[J]. Lancet, 2004, 364(9437):849-857.

[80]   Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calci um antagonist vs a non-calcium antagonist hypertension treat ment strategy for patients with coronary heart disease. The International Verapamil-Trandolapril Study (INVEST): a rand omized controlled trial[J]. JAMA, 2003, 290(21):2805-2816.

[81]   Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a rando mized controlled trial[J]. JAMA, 2004, 292(18):2217-2225.

[82]   Mancia G, Paratia G, Biloa G, et al. Blood pressure control by the nifedipine GITS-telmisartan combination in patients a high cardiovascular risk: the TALENT study[J]. J Hypertens, 2011, 29(3):600-609.

[83]   Fagard RH, Celis H, Thijs L, et al. Regression of left ventricular mass by antihypertensive treatment: a meta-analysis of ran domized comparative studies[J]. Hypertension, 2009, 54(5): 1084-1091.

[84]   Byington RP, Miller ME, Herrington D, et al. Rationale, design, and baseline characteristics of the Prospective Rand-omized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT)[J]. Am J Cardiol, 1997, 80(8):1087-1090.

[85]   Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from pros pective epidemiological studies[J]. BMJ, 2009, 338:b1665.

[86]   Hou FF, Xie D, Zhang X, et al. Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insuffic iency[J]. J Am Soc Nephrol, 2007, 18(6):1889-1898.

[87]   Julius S, Nesbitt S, Egan B, et al. Trial of Preventing Hypertension:Design and 2-Year Progress Report[J]. Hypertension, 2004, 44(2):146-151.

[88]   Saito I, Kario K, Kushiro T, et al. Rationale, study design, baseline characteristics and blood pressure at 16 weeks in the HONEST Study[J]. Hypertens Res, 2013, 36(2):177-182.

[89]   Schrader J, Lüders S, Kulschewski A, et al. The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors[J]. Stroke, 2003, 34(7):1699-1703.

[90]   Stumpe KO, Agabiti-Rosei E, Zielinski T, et al. Carotid intimamedia thickness and plaque volume changes following 2-year angiotensin Ⅱ -receptor blockade. The Multicentre Olmesartan atherosclerosis Regression Evaluation (MORE) study[J]. Ther Adv Cardiovasc Dis, 2007, 1(2):97-106.

[91]   Schrader J, Lüders S, Kulschewski A, et al. Morbidity And Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES)[J]. Stroke, 2005, 36(6): 1218-1226.

[92]   Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol[J]. Lancet, 2002, 359(9311):995-1003.

[93]   Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascularrisk treated with regimens based on valsartan or amlodipine: the VALUE randomized trial[J]. Lancet, 2004, 363(9426):2022-2031.

[94]   Hasford J, Mimran A, Simons WR. A population-based european cohort study of persistence in newly diagnosed hypertensive patients[J]. J Hum Hypertens, 2002, 16(8):569-575.

[95]   Ogihara T, Nakao K, Fukui T, et al. Effects of candesartan compared with amlodipine in hypertensive patients with high cardiovascular risks: candesartan antihypertensive survival evaluationin Japan trial[J]. Hypertension, 2008, 51(2):393-398.

[96]   Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial[J]. J Hypertens, 2003, 21(5):875-886.

[97]   Jiao Y, Ke Y, Sun N, et al. Reduction of the morning blood pressure surge treated with olmesartan in Chinese patients with mild to moderate essential hypertension--a multicenter, openlabel, single treatment group clinical study[J]. Eur Rev Med Pharmacol Sci, 2012, 16(5):653-659.

[98]   Ogawa H, Kim-Mitsuyama S, Jinnouchi T, et al. Rationale, design and patient baseline characteristics of OlmeSartan and calcium antagonists randomized (OSCAR) study: a study comparing the incidence of cardiovascular events between high-dose angiotensin Ⅱ receptor blocker (ARB) monotherapy and combination therapy of ARB with calcium channel blocker in Japanese elderly high-risk hypertensive patients[J]. Hypertension Res, 2009, 32(7):575-580.

[99]   荆珊，孙宁玲，张抒扬，等．阿利沙坦酯治疗轻中度原发性高血压的有效性和安全性 [J]．中国临床药理学杂志，2013，29（10）：728-731．

[100] Kjeldsen SE, Stålhammar J, Hasvold P, et al. Effects of losartan vs candesartan in reducing cardiovascular events in the primary treatment of hypertension[J]. J Hum Hypertens, 2010, 24(4): 263-273.

[101] Konstam MA, Neaton JD, Dickstein K, et al. Effects of highdose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial[J]. Lancet, 2009, 374(9704):1840-1848.

[102] Cohn JN, Tognoni G. Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure[J]. N Engl J Med, 2001, 345(23):1667-1675.

[103] Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme[J]. Lancet, 2003, 362(9386):759-766.

[104] ACTIVE I Investigators, Yusuf S, Healey JS, et al. Irbesartan in patients with atrial fibrillation[J]. N Engl J Med, 2011, 364 (10):928-938.

[105] ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events[J]. N Engl J Med, 2008, 358(15):1547-1559.

[106] Hirohata A, Yamamoto K, Miyoshi T, et al. Impact of olmesartan on progression of coronary atherosclerosis a serial volumetric intravascular ultrasound analysis from the OLIVUS (impact of OLmesarten on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) trial[J]. J Am Coll Cardiol, 2010, 55(10):976-982.

[107] Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on Renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy[J]. N Engl J Med, 2001, 345(12):861-869.

[108] Viberti G, Wheeldon NM, Microalbuminuria Reduction With VALsartan (MARVAL) Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect[J]. Circulation, 2002, 106(6):672-678.

[109] Hollenberg NK, Parving HH, Viberti, et al. Albuminuria response to very high-dose valsartan in type 2 diabetes mellitus[J]. J Hypertens, 2007, 25(9):1921-1926.

[110] Parving HH, Lewis JB, Ravid M, et al. Prevalence and risk factors for microalbuminuria in a referred cohort of type Ⅱ diab e tic patients: a global perspective[J]. Kidney Int, 2006, 69 (11):2057-2063.

[111] Haller H, Viberti GC, Mimran A, et al. Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study[J]. J Hypertens, 2006, 24(2): 403-408.

[112] Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, doubleblind, controlled trial[J]. Lancet, 2008, 372(9638):547-553.

[113] Turnbull F, Neal B, Algert C, et al. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials[J]. Arch Intern Med, 2005, 165(12):1410-1419.

[114] Schmieder RE, Hilgers KF, Schlaich MP, et al. Renin-angiotensin system and cardiovascular risk[J]. Lancet, 2007, 369 (9568):1208-1219.

[115] Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms and cardiovascular risk factors[J]. Hypertension, 2005, 46(4):667-675.

[116] Kunz R, Friedrich C, Wolbers M, et al. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease[J]. Ann Intern Med, 2008, 148(1):30-48.

[117] Rutten FH, Zuithoff NP, Halk E, et al. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease[J]. Arch Intern Med, 2010, 170 (10):880-887.

[118] Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes[J]. N Engl J Med, 2012, 367(23):2204-2213.

[119] James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)[J]. JAMA, 2014, 311(5):507-520.

[120] Shimamoto K, Ando K, Fujita T, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2014)[J]. Hypertens Res, 2014, 37(4):253-390.

[121] Leung AA, Nerenberg K, Daskalopoulou SS, et al. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagn osis, Assessment of Risk, Prevention, and Treatment of Hype rtension[J]. Can J Cardiol, 2016, 32(5):569-588.

[122] Palatini P, Rosei EA, Casiglia E, et al. Management of the hypertensive patient with elevated heart rate: Statement of the Second Consensus Conference endorsed by the European Society of Hypertension[J]. J Hypertens, 2016, 34(5):813-821.

[123] Black HR., Elliott WJ, Grandits G, et al. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial[J]. JAMA, 2003, 289(16):2073-2082.

[124] Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group[J]. BMJ, 1998, 317 (7160): 703-713.

[125] Wikstrand J, Warnold I, Olsson G, et al. Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study[J]. JAMA, 1988, 259(13):1976-1982.

[126] Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study[J]. Lancet, 1999, 354(9192):1751-1756.

[127] Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial[J]. Lancet, 1999, 353(9153):611-616.

[128] King DE, Everett CJ, Mainous AG 3rd, et al. Long-term prognostic value of resting heart rate in subjects with prehypertension[J]. Am J Hypertens, 2006, 19(8):796-800.

[129] Thomas F, Bean K, Provost JC, et al. Combined effects of heart rate and pulse pressure on cardiovascular mortality according to age[J]. J Hypertens, 2001, 19(5):863-869.

[130] Palatini P, Thijs L, Staessen JA, et al. Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension[J]. Arch Intern Med, 2002, 162(20):2313-2321.

[131] Paul L, Hastie CE, Li WS, et al. Resting heart rate pattern during follow-up and mortality in hypertensive patients[J]. Hypertension, 2010, 55(2):567-574.

[132] Okin PM, Kjeldsen SE, Julius S, et al. All-cause and cardiovascular mortality in relation to changing heart rate during treat ment of hypertensive patients with electrocardiographic left ventricular hypertrophy[J]. Eur Heart J, 2010, 31(18):2271-2279.

[133] Saxena A, Minton D, Lee DC, et al. Protective role of resting heart rate on all-cause and cardiovascular disease mortality[J]. Mayo Clin Proc, 2013, 88(12):1420-1426.

[134] 中华医学会心血管病学分会，中华心血管病杂志编辑委员会．非 ST 段抬高急性冠状动脉综合征诊断和治疗指南 [J]．中华心血管病杂志，2012，40（5）：353-367．

[135] 中华医学会心血管病学分会，中华心血管病杂志编辑委员会．急性 ST 段抬高型心肌梗死诊断和治疗指南 [J]．中华心血管病杂志，2015，43（5）：380-393．

[136] Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)[J]. Lancet, 1999, 353(9169):2001-2007.

[137] The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial[J]. Lancet, 1999, 353(9146):9-13.

[138] Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure[J]. N Engl J Med, 2001, 344(22):1651-1658.

[139] Kotecha D, Manzano L, Krum H, et al. Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis[J]. BMJ, 2016, 353:i1855.

[140] Roberts R, Rogers WJ, Muellers HS, et al. Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) Ⅱ -B Study[J]. Circulation, 1991, 83(2):422-437.

[141] Van de Werf F, Janssens L, Brzostek T, et al. Short-term effects of early intravenous treatment with a beta-adrenergic blocking agent or a specific bradycardiac agent in patients with acute myocardial infarction receiving thrombolytic therapy[J]. J Am Coll Cardiol, 1993, 22(2):407-416.

[142] Kotecha D, Holmes J, Krum H, et al. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individualpatient data meta-analysis[J]. Lancet, 2014, 384(9961):2235-2243.

[143] Scheuermeyer FX, Grafstein E, Stenstrom R, et al. Safety and efficiency of calcium channel blockers versus beta-blockers for rate control in patients with atrial fibrillation and no acute underlying medical illness[J]. Acad Emerg Med, 2013, 20(3):222-230.

[144] Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure[J]. N Engl J Med, 2008, 358:2667-2677.

[145] Dabrowski R, Borowiec A, Smolis-Bak E, et al. Effect of combined spironolactone-β-blocker±enalapril treatment on occurrence of symptomatic atrial fibrillation episodes in patients with a history of paroxysmal atrial fibrillation (SPIR-AF study)[J]. Am J Cardiol, 2010, 106(11):1609-1614.

[146] Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/ AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons[J]. J Am Coll Cardiol, 2012, 60(24):e44-e164.

[147] Chapman N, Chang CL, Dahlof B, et al. Effect of doxazosin gastrointestinal therapeutic system as third-line antihypertensive therapy on blood pressure and lipids in the Anglo-Scandinavian Cardiac Outcomes Trial[J]. Circulation, 2008, 118(1):42-48.

[148] Black HR, Keck M, Meredith P, et al. Controlled-release doxazosin as combination therapy in hypertension: the GATES study[J]. J Clin Hypertens (Greenwich), 2006, 8(3):159-166.

[149] ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)[J]. JAMA, 2000, 283(15):1967-1975.

[150] Denolle T, Chamontin B, Doll G, et al. Management of resistant hypertension: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology[J]. J Hum Hypertens, 2016, 30(11):657-663.

[151] Ceral J, Solar M. Doxazosin: safety and efficacy in the treatment of resistant arterial hypertension[J]. Blood Press, 2009, 18(1-2):74-77.

[152] 孙宁玲，霍勇，王继光，等．难治性高血压诊断治疗中国专家共识 [J]．中国医学前沿杂志（电子版），2013，5（6）：5-12．

[153] National Clinical Guideline Centre (UK). Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34[EB/OL]. (201102) [2017-04-26]. https://www.nice.org.uk/guidance/cg127/ documents/hypertension-update-draft-full-guideline2

[154] Homma Y, Gotoh M, Yokoyama O, et al. Outline of JUA clinical guidelines for benign prostatic hyperplasia[J]. Int J Urol, 2011, 18(11):741-756.

[155] Chung BH, Hong SJ. Long-term follow-up study to evaluate the efficacy and safety of the doxazosin gastrointestinal therapeutic system in patients with benign prostatic hyperplasia with or without concomitant hypertension[J]. BJU Int, 2006, 97(1): 90-95.

[156] Pessina AC, Ciccariello L, Perrone F, et al. Clinical efficacy and tolerability of alpha-blocker doxazosin as add-on therapy in patients with hypertension and impaired glucose metabolism[J]. Nutr Metab Cardiovasc Dis, 2006, 16(2):137-147.

[157] Dell'Omo G, Penno G, Del Prato S, et al. Doxazosin in metabolically complicated hypertension[J]. Expert Rev Cardiovasc Ther, 2007, 5(6):1027-1035.

[158] KDIGO. Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease[EB/OL]. (2012-12) [2017-04-26]. http://kdigo.org/clinical_practice_guidelines/pdf/KDIGO_BP_GL.pdf

[159] 中国医师协会肾脏内科医师分会，中国中西医结合学会肾脏疾病专业委员会．中国肾性高血压管理指南 2016（简版）[J]．中华医学杂志，2017，97（20）：1547-1555．

[160] 中华医学会内分泌学分会肾上腺学组．嗜铬细胞瘤和副神经节瘤诊断治疗的专家共识 [J]．中华内分泌代谢杂志，2016，32（3）：181-187．

[161] Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline[J]. J Clin Endocrinol Metab, 2014, 99(6):1915-1942.

[162] Mulatero P, Rabbia F, Milan A, et al. Drug effects on aldosterone/plasma renin activity ratio in primary aldoster onism[J]. Hypertension, 2002, 40(6):897-902.

[163] 《单片复方制剂降压治疗中国专家共识》专家组，中华医学会心血管病学分会，中国老年学学会心脑血管病专业委员会．单片复方制剂降压治疗中国专家共识 [J]．中华高血压杂志，2012，20（7）：624-628．

[164] NUSSBAUM HE, LEFF WA, MATTIA VD JR, et al. Fixed com bination of chlorothiazide-reserpine in hypertension[J]. Am J Med Sci, 1958, 236(6):786-789.

[165] 刘力生，王文，姚崇华，等．中国高血压防治指南（2009 年基层版）[J]．中华高血压杂志，2010，18（1）：11-30．

[166] 吴彦，孙宁玲，洪昭光，等．北京降压 0 号治疗轻中度原发性高血压的长期疗效观察 [J]．中华心血管病杂志，2003，31（6）：408-412．

[167] 孙宁玲，吴彦，洪昭光，等．北京降压 0 号与氨氯地平治疗原发性高血压的临床对比试验 [J]．中国临床药理学杂志，2002，18（3）：171-173．

[168] 张奕，秦雪英，武轶群，等．降压 0 号治疗原发性高血压短期疗效和安全性分析 [J]．中华疾病控制杂志，2010，14（1）：5-7．

[169] 张奕，武轶群，秦雪英，等．降压 0 号治疗原发性高血压长期疗效和安全性评价 [J]．中国社区医师，2008，24（13）：19-21．

[170] 李振华，王丽华，张纪荣，等．长期服用复方降压片治疗1 或 2 级原发性高血压的疗效观察 [J]．中华全科医师杂志，2005，4（2）：86-88．

[171] 金智敏．珍菊降压片与其他一线降压药治疗原发性高血压临床研究 [J]．中成药，2001，23（12）：882-884．

[172] 李振华，王立华，张纪荣，等．长期服用复方降压片对轻、中度高血压病降压效果及血清糖、胰岛素、尿酸、血脂的影响 [J]．中国心血管病研究杂志，2004，2（1）：44-46．

[173] 章建梁，秦永文，郑兴，等．不同糖耐量状态对高血压患者抗高血压药物治疗后代谢变化的影响 [J]．中国全科医学，2005，8（4）：270-272，275．

[174] 章建梁，秦永文，郑兴，等．三种抗高血压药物联合应用方案对高血压患者胰岛素抵抗和代谢的影响 [J]．心肺血管病杂志，2004，23（3）：153-157．

[175] 王馨，段雪英，王增武，等．社区复方制剂抗高血压治疗研究：2 年干预效果分析 [J]．中国循环杂志，2015，30（5）：449-454．

[176] 朱国琴，王文健，何燕，等．珍菊降压片联合长效降压药物治疗高血压的临床研究 [J]．中国药师，2015，18（8）：1349-1352．

[177] 孟琼，黄昊，林锦培，等．珍菊降压片联合缬沙坦治疗原发性高血压（肝阳上亢证）患者的疗效观察 [J]．中国临床医学，2014，21（3）：348-350．

[178] Wang W, Ma L, Zhang Y, et al. The combination of amlodipine and angiotensin receptor blocker or diuretics in high-risk hypert ensive patients: rationale, design and baseline chara cteristics[J]. J Hum Hypertens, 2011, 25(4):271-277.

[179] Chrysant SG, Weber MA, Wang AC, et al. Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide[J]. Am J Hypertens, 2004, 17(3):252-259.

[180] Bakris GL, Serafidis PA, Weir MR, et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of randomised controlled trial[J]. Lancet, 2010, 375(9721):1173-1181.

[181] ADVANCE Collaborative Group. Effects of a fixed combin ation of perindopriland indapamide on macrovascular and micro vascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial[J]. Lancet, 2007, 370(9590):829-840.

[182] Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older[J]. N Engl J Med, 2008, 358(18):1887-1898.

[183] Dalhof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindoprilas required vs. atenolol adding bendroflumethiazide as required in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOTBPLA) a multicentre randomised controlled trial[J]. Lancet, 2005, 366 (9489):895-906.

[184] Huo Y, Li J, Qin X, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial[J]. JAMA, 2015, 313(13):1325-1335.

[185] Bousquet P, Feldman J, Schwartz J. Central cardiovascular effects of alpha-adrenergic drugs: differences between catecholamines and imidazolines[J]. J Pharmacol Exp Ther, 1984, 230(1):232-236.

[186] Nikolic K, Agbaba D. Imidazoline antihypertensive drugs, selective I1-Imdazoline receptor activation[J]. Cardiovascular Theraputics, 2012, 30(4):209-216.

[187] Denolle T, Chamontin B, Doll G, et al. Management of resistant hypertension: expert consensus statement from the French society of hypertension, an affiliate of the French Society of Cariology[J]. J Human Hypertens, 2016, 30(11):657-663.

[188] Magee LA, von Dadelszen P, Singer J, et al. The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregn ancy Study): Is Severe Hypertension Just an Elevated Blood Pressure?[J]. Hypertension, 2016, 68(5):1153-1159.

[189] Hoeltzenbein M, Beck E, Fietz AK, et al. Pregnancy Outcome After First Trimester Use of Methyldopa: A Prospective Cohort Study[J]. Hypertension, 2017, 70(1):201-208.

[190] Trimarco B, Rossielo G, Sarno D, et al. Effects of one-year treatment with rilmenidine on systemic hypertension induced left ventricular hypertrophy in hypertensive patients[J]. Am J Cardiol, 1994, 74(13):36A-42A.

[191] 中国老年医学学会高血压分会，中国医师协会高血压专业委员会．复方利血平氨苯蝶啶片临床应用中国专家共识 [J]．中国心血管杂志，2016，21（5）：339-343．

[192] 中华医学会心血管病学分会高血压学组．利尿剂治疗高血压的中国专家共识 [J]．中华高血压杂志，2011，19（3）：214-222．

[193] 范雯怡，武轶群，曹洋，等．降压 0 号治疗老年单纯收缩期高血压的疗效和安全性评价 [J]．现代预防医学，2012，39（4）：1008-1010，1021．

[194] 武轶群，何柳，宋岩，等．降压 0 号治疗原发性高血压有效性和安全性的系统评价 [J]．中华疾病控制杂志，2009，13（3）：225-231．

[195] 荆珊，王鸿懿，孙宁玲，等．复方利血平氨苯蝶啶片联合其他抗高血压药物治疗非杓型原发性高血压患者的血压达标情况及其安全性 [J]．中国慢性病预防与控制，2013，21（1）：45-47．

[196] 谭静，华琦，刘荣坤，等．动态血压监测比较北京降压 0 号和氢氯噻嗪的降压疗效 [J]．首都医科大学学报，2006，27（2）：222-225．

[197] 荆珊，王鸿懿，孙宁玲．不同时间服用复方利血平氨苯蝶啶片对非杓型原发性高血压患者血压节律和 24 小时动态血压的影响研究 [J]．中国全科医学，2013，16（2）：133-135，139．

[198] Franse LV, Pahor M, Di Bari M, et al. Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP)[J]. J Hypertens, 2000, 18(8):1149-1154.

[199] 黄高忠，汤晔华，顾兴建，等．复方尼群洛尔片治疗原发性高血压的随机双盲平行对照多中心临床试验 [J]．中国临床药理学杂志，2009，25（5）：391-394．

[200] 陈祚，王增武，王馨，等．尼群洛尔治疗社区轻中度原发性高血压的疗效和安全性 [J]．中华高血压杂志，2014，22 （5）：445-450．

[201] Li Y, Li XH, Huang ZJ, et al. A randomized, double blind, placebo-controlled, multicenter phaseⅡ trial of Allisartan Isoproxil in essential hypertensive population at low-medium risk[J]. PLoS One, 2015, 10(2):e0117560.

[202] 李建平，卢新政，霍勇，等．H型高血压诊断与治疗专家共识[J]．中国医学前沿杂志（电子版），2016，8（5）：23-28．

[203] Qin X, Li Y, Sun N, et al. Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin Converting Enzyme Inhibitors in Hypertensive Patients[J]. Arterioscler Thromb Vasc Biol, 2017, 37(1):166-172.

[204] Li J, Jiang S, Zhang Y, et al. H-type hypertension and risk of stroke in Chinese adults: A prospective, nested case-control study[J]. J Transl Intern Med, 2015, 3(4):171-178.

[205] Casas JP, Bautista LE, Smeeth L, et al. Homocysteine and stroke: evidence on a causal link from mendelian randomiz ation[J]. Lancet, 2005, 365(9455):224-232.

[206] Xu X, Li J, Sheng W, et al. Meta-analysis of genetic studies from journals published in China of ischemic stroke in the Han Chinese population[J]. Cerebrovasc Dis, 2008, 26(1):48-62.

[207] Qin X, Shen L, Zhang R, et al. Effect of folic acid supplementation on cancer risk among adults with hypertension in China: A randomized clinical trial[J]. Int J Cancer, 2017, 141(4):837-847.

[208] Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis[J]. Lancet, 2007, 369(9576):1876-1882.

[209] Huo Y, Qin X, Wang J, et al. Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis[J]. Int J Clin Pract, 2012, 66(6):544-551.

[210] Zhao M, Wu G, Li Y, et al. Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers[J]. Neuro logy, 2017, 88(19):1830-1838.

[211] Li Y, Huang T, Zheng Y, et al. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials[J]. J Am Heart Assoc, 2016, 5(8). pii:e003768.

[212] Albert CM, Cook NR, Gaziano JM, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial[J]. JAMA, 2008, 299(17):2027-2036.

[213] 李建平，霍勇，刘平，等．马来酸依那普利叶酸片降压、降同型半胱氨酸的疗效和安全性 [J]．北京大学学报（医学版），2007，39（6）：614-618．

[214] 孙宁玲，秦献辉，李建平，等．依那普利叶酸片固定复方与依那普利和叶酸自由联合在 H 型高血压人群中降低同型半胱氨酸的疗效比较 [J]．中国新药杂志，2009，18（7）：1635-1640．

[215] Qin X, Li J, Spence JD, et al. Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients[J]. Stroke, 2016, 47(11):2805-2812.

[216] Xu RB, Kong X, Xu BP, et al. Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention[J]. Am J Clin Nutr, 2017, 105(3):564-570.

[217] Xu X, Qin X, Li Y, et al. Efficacy of Folic Acid Therapy on the Progr ession of Chronic Kidney Disease: The Renal Substudy of the China Stroke Primary Prevention Trial[J]. JAMA Intern Med, 2016, 176(10):1443-1450.

[218] Li Y, Qin X, Luo L, et al. Folic acid therapy reduces the risk of mortality associated with heavy proteinuria among hypertensive patients[J]. J Hypertens, 2017, 35(6):1302-1309.

[219] Li Y, Liang M, Wang G, et al. Effects of Folic Acid Therapy on the New-onset Proteinuria in Chinese Hypertensive Patients: A Post-hoc Analysis of the Renal Sub-study of China Stroke Primary Prevention Trial[J]. Hypertension, 2017. [Epub ahead of print]

[220] Qin X, Li Y, He M, et al. Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Prim ary Prevention Trial (CSPPT)[J]. Am J Clin Nutr, 2017, 105(4):882-889.

[221] Qin X, Li J, Cui Y, et al. MTHFR C677T and MTR A2756G polym or phisms and the homocysteine lowering efficacy of differ ent doses of folic acid in hypertensive Chinese adults[J]. Nutr J, 2012, 11:2.

[222] Zhao M, Wang X, He M, et al. Homocysteine and stroke risk: modifying effect of methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention[J]. Stroke, 2017, 48(5):1183-1190.

[223] Xu B, Kong X, Xu R, et al. Homocysteine and all-cause mortality in hypertensive adults without pre-existing cardiovascular conditions: Effect modification by MTHFR C677T polymorphism[J]. Medicine (Baltimore), 2017, 96(8):e5862.

[224] 中国医师协会心血管内科医师分会，中国老年学学会心脑血管病专业委员会．苯磺酸左旋氨氯地平临床应用专家共识 [J]．中华内科杂志，2010，49（11）：987-989．

[225] 方志高．左旋氨氯地平治疗高血压及逆转左心室肥厚 140 例 [J]．中国新药杂志，2002，11（12）：958-960．

[226] 庞志华，赵伟．马来酸左旋氨氯地平对原发性高血压患者血压变异及左心室肥厚的影响 [J]．实用心脑肺血管病杂志，2013，21（1）：13-14，17．

[227] 马丽媛，王文，邓卿，等．马来酸左旋氨氯地平治疗对高血压患者动态血压和左心室质量的影响 [J]．中华高血压杂志，2013，21（9）：880-883．

[228] 陈海生，刘卓敏．左旋氨氯地平与厄贝沙坦对原发性高血压早期肾小球滤过率和微量白蛋白的影响 [J]．中国心血管杂志，2006，11（5）：372-374．

[229] 陈源源，马志毅，孙宁玲．左旋氨氯地平对血压控制不良患者微量白蛋白尿逆转作用的研究 [J]．中华老年心脑血管病杂志，2012，14（7）：675-678．

[230] 高兆录，常娟．依那普利联合左旋氨氯地平治疗 2 型糖尿病肾病临床观察 [J]．医学理论与实践，2006，19（1）：12-14．

[231] 于欢，陈忻，翟所迪．左旋氨氯地平对原发性高血压患者肾功能保护作用的 Meta 分析 [J]．中国药房，2011，22（36）：3433-3437．

[232] 张荷，刘坤申，高仁果，等．左旋氨氯地平和氨氯地平对高血压病人内皮功能及血清胆固醇影响 [J]．中国新药与临床杂志，2003，22（6）：337-340．

[233] 李宁榕，黄琦，洪雪云，等．左旋氨氯地平对颈动脉内膜 - 中膜厚度及血管内皮功能的影响 [J]．国际医药卫生导报，2008， 14（5）：63-65．

[234] 高俊岭，丁永明，付华．社区高血压患者苯磺酸左旋氨氯地平服药依从性的观察 [J]．中华高血压杂志，2017，25（1）：79-82．

[235] 邱蓉，付妍，赵兴山，等．左旋氨氯地平与氨氯地平、硝苯地平、非洛地平所致不良反应的对比研究 [J]．药物不良反应杂志，2009，11（5）：315-320．

[236] 胡大一，赵秀丽，孙宁玲，等．苯磺酸左旋氨氯地平与苯磺酸氨氯地平治疗原发性轻中度高血压的随机、双盲平行研究 [J]．中国医刊，2002，37（5）：46-47．

[237] 易洪刚，黄高忠，刘关键．苯磺酸左旋氨氯地平治疗原发性高血压有效性和安全性的系统评价 [J]．中国循证医学杂志，2008，8（7）：543-550．

[238] 贾坦，张李军，战义强，等．苯磺酸左旋氨氯地平治疗轻中度原发性高血压的疗效和安全性 [J]．中华心血管病杂志，2013，41（4）：301-303．

[239] 于华．苯磺酸左旋氨氯地平联用卡托普利治疗老年高血压病70 例疗效观察 [J]．中国现代药物应用，2009，3（5）：88-89．

[240] 刘娅，廖礼强．左旋氨氯地平对中青年高血压患者血压和血压变异性的影响 [J]．中国新药与临床杂志，2014，33（3）：196-200．

[241] 孙宁玲，喜杨，荆珊，等．左旋氨氯地平的时间药理学对纠正老年非杓型高血压的作用 [J]．中华高血压杂志，2007，15（1）：26-29．

[242] 张慧敏，黄建凤，吴海英，等．马来酸左旋氨氯地平与苯磺酸氨氯地平治疗轻中度原发性高血压 [J]．中华高血压杂志，2010，18（7）：648-652．

[243] 柴文静，耿雪，崔炜，等．马来酸左旋氨氯地平治疗原发性高血压有效性及安全性的 Meta 分析 [J]．临床荟萃，2015，30（11）：1240-1250．

[244] 李军伟，杨海燕，赵勇军．马来酸左旋氨氯地平治疗晨峰高血压的疗效观察 [J]．求医问药，2012，10（7）：548-549．

[245] 张惠娟，张凤萍．4 种常用钙通道阻滞剂治疗高血压的药物经济学分析 [J]．中西医结合心脑血管病杂志，2014，12（6）：695-696．

[246] 戚国庆，杜文涛，韩巍，等．硝苯地平缓释片（Ⅱ）与左旋氨氯地平治疗稳定型冠心病伴高血压 186 例 [J]．临床荟萃，2008，23（14）：1041-1042．

[247] 杨彦玲，陈庆华．左旋氨氯地平对高血压疾病中靶器官保护作用的研究进展 [J]．中国药房，2011，22（41）：3912-3914．

[248] 张雪羽，陈兰英，张秀丽．苯磺酸左旋氨氯地平联用脑复康治疗血管性痴呆的临床研究 [J]．中国药房，2008，19（8）：607-608．

[249] 毛翔．马来酸左旋氨氯地平对缺血性脑卒中合并高血压干预效果的临床研究 [J]．中国医疗前沿，2010，5（20）：57-58．

[250] 丁树珊，刘培良．左旋氨氯地平对高血压病病人胰岛素抵抗的影响 [J]．中西医结合心脑血管病杂志，2006，4（3）：274-275．

[251] Tamargo J, Duarte J, Ruilope LM. New antihypertensive drugs under development[J]. Curr Med Chem, 2015, 22(3):305-342.

[252] Kostis JB, Packer M, Black HR, et al. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial[J]. Am J Hypertens, 2004, 17(2):103-111.

[253] Supasyndh O, Sun N, Kario K, et al. Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension[J]. Hypertens Res, 2016, 40(5):472-476.

[254] Chen X, Qiu Z, Yang S, et al. Effectiveness and safety of a therapeutic vaccine against angiotensin Ⅱ receptor type 1 in hypertensive animals[J]. Hypertension, 2013, 61(2):408-416.

[255] Taddei S. Fixed-dose combination therapy in hypertension: pros[J]. High Blood Press Cardiovasc Prev, 2012, 19(2):55-57.

[256] Oparil S, Schmieder RE. New approaches in the treatment of hypertension[J]. Circ Res, 2015, 116(6):1074-1095.

[257] Laurent S, Schlaich M, Esler M. New drugs, procedures, and devices for hypertension[J]. Lancet, 2012, 380(9841):591-600.

[258] 中华医学会糖尿病学分会．中国 2 型糖尿病防治指南（2013 年版）[J]．中国医学前沿杂志（电子版），2015，7（3）：26-89．

[259] American Diabetes Association. Standards of Medical Care in Diabetes-2017[J]. Diabetes Care, 2017, 40(Suppl 1):S1-S135.

[260] Weber MA, Schiffrin EL, White WB, et al. Clinical practice guide lines for the management of hypertension in the community: a statement by the American Society of Hyperte nsion and the International Society of Hypertension[J]. J Clin Hypertens (Greenwich), 2014, 16(1):14-26.

[261] Task Force for the management of arterial hypertension of the European Society of Hypertension, Task Force for the management of arterial hypertension of the European Society of Card iology. 2013 ESH/ESC Guidelines for the management of arterial hypertension[J]. Blood Pressure, 2013, 22(4):193-278.

[262] Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outc omes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy[J]. Lancet, 2000, 355 (9200):253-259.

[263] Lindholm LH, Ibsen H, Dahlöf B, et al. Cardiovascular morbi dity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol[J]. Lancet, 2002, 359(9311): 1004-1010.

[264] Evans M, Bain SC, Hogan S, et al. Irbesartan delays progre ssion of nephropathy as measured by estimated glomerular filtration rate: post hoc analysis of the Irbesartan Diabetic Neph ro pathy Trial[J]. Nephrol Dial Transplant, 2012, 27(6): 2255-2263.

[265] Barnett A. Preventing renal complications in type 2 diabetes: results of the diabetics exposed to telmisartan and enalapril trial[J]. J Am Soc Nephrol, 2006, 17(4 Suppl 2):S132-S135.

[266] Rossing K, Schjoedt KJ, Jensen BR, et al. Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria[J]. Kidney Int, 2005, 68(3):1190-1198.

[267] Os I, Franco V, Kjeldsen SE, et al. Effects of losartan in women with hypertension and left ventricular hypertrophy: results from the Losartan Intervention for Endpoint Reduction in Hypertension Study[J]. Hypertension, 2008, 51(4):1103-1108.

[268] DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators, Gerstein HC, Yusuf S, et al. Effect of rosiglitazone on the frequency of diab-etes in patients with impaired glucose tolerance or impaired fas t ing glucose: a randomised controlled trial[J]. Lancet, 2006, 368(9541):1096-1105.

[269] Lam SK, Owen A. Incident diabetes in clinical trials of antihypertensive drugs[J]. Lancet, 2007, 369(9572):1513-1514.

[270] Julius S, Weber MA, Kjeldsen SE, et al. The Valsartan Ant ihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy[J]. Hypertension, 2006, 48(3):385-391.

[271] Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis[J]. Lan cet, 2015, 385(9982):2047-2056.

[272] Weber MA, Bakris GL, Jamerson K, et al. Cardiovascular events during differing hypertension therapies in patients with diabetes[J]. J Am Coll Cardiol, 2010, 56(1):77-85.

[273] Bakris GL, Weir MR, DeQuattro V, et al. Effects of an ACE inhibitor/calcium antagonist combination on proteinuria in diabetic nephropathy[J]. Kidney Int, 1998, 54(4):1283-1289.

[274] Glanz M, Garber AJ, Mancia G, et al. Meta-analysis of studies using selective alpha1-blockers in patients with hypertension and type 2 diabetes[J]. Int J Clin Pract, 2001, 55(10):694-701.

[275] Pollare T, Lithell H, Selinus I, et al. Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension[J]. Diabetologia, 1988, 31(7):415-420.

[276] Giorda C, Appendino M. Effects of doxazosin, a selective alpha 1-inhibitor, on plasma insulin and blood glucose response to a glucose tolerance test in essential hypertension[J]. Metabolism, 1993, 42(11):1440-1442.

[277] Feher MD. Doxazosin therapy in the treatment of diabetic hypertension[J]. Am Heart J, 1991, 121(4 Pt 2):1294-1301.

[278] Huupponen R, Lehtonen A, Vähätalo M. Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients[J]. Eur J Clin Pharmacol, 1992, 43(4):365-368.

[279] Feher MD, Henderson AD, Wadsworth J, et al. Alpha-blocker therapy; a possible advance in the treatment of diabetic hypertension--results of a cross-over study of doxazosin and atenolol monotherapy in hypertensive non-insulin dependent diabetic subjects[J]. J Hum Hypertens, 1990, 4(5):571-577.

[280] Khoury AF, Kaplan NM. Alpha-blocker therapy of hypert ension. An unfulfilled promise[