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1、高血压抗动脉粥样硬化治疗策略,江苏省人民医院 黄峻,高血压从 “无需治疗”时代穿越,“The treatment of hypertension itself is a difficult and almost hopeless task in the present state of knowledge, and in fact for aught we know . the hypertension may be an important compensation mechanism which should not be tampered with, even were it certa
2、in that we could control it.“,高血压可能是一种重要的代偿机制，我们不应该干预它 Paul Dudley White, 1937年,Paul Dudley White (1886-1973)：近代著名的世界级心脏病学家，AHA创始人之一，预激综合征的最早发现者之一，世界最早的专著的作者,罗斯福总统最后一个任期时的文件詳細记载了他的健康Franklin D. Roosevelt （FDR） was referred to Dr. Howard Bruenn, a cardiologist at Bethesda Naval Hospital who, on March
3、 27, 1944 found him cyanotic, breathless, with an enlarged left ventricle and a blood pressure of 186/108. Bruenn diagnosed hypertensive heart disease and wanted to give digitalis, but was prohibited by Dr. Ross McIntire, the presidents personal physician and then surgeon-general of the U.S. Navy. T
4、he next day, FDR developed moist rales at the base of the right lung. During a press conference that day, FDR was asked about his physical condition and answered, “I got bronchitis.“ By March 30 crackles were present at the base of both lungs. Bruenn diagnosed congestive heart failure, but it was no
5、t until the next day, after FDR was examined by civilian consultants, that digitalis was begun. FDR would continue the digitalis for the rest of his life. By April 3, FDR was better. His color was better, he could lie flat without dyspnea, and the crackles disappeared from both lungs. His blood pres
6、sure, however, was 210/110. The nation was stunned when FDR died unexpectedly on April 12, 1945 - less than six months after being elected to a fourth term in office. The death was unexpected because the presidents personal physician, VADM Ross McIntire, whenever asked, had proclaimed that FDRs heal
7、th was excellent.1944年3月27日：血压186/1081944年4月3日：血压210/110总统的医生宣称：罗斯福总统健康状况很好！1945年4月12日，罗斯福总统死於脑溢血。,“Franklin D. Roosevelts health was excellent”！？ 1944年,高血压治疗发展史（20世纪初中期）,The American Journal of Medicine (1972),一些基本问题有待回答：什么是高血压？血压高于多少诊断为高血压？如何评估预后和治疗效果？,血压诊断标准不断修正：,百年高血压治疗史：成绩斐然,www.sma.org; Ann In
8、tern Med 1970;72:579-591; Mourad et al. Journal of hypertension 2004,22:2379-2385; Journal of Hypertension 2007, 25:11051187; Sever PS et al. European Heart Journal 2006;27:2982-2988,不治疗,限盐治疗,序贯治疗,阶梯治疗,联合治疗,优化联合治疗,脑卒中,冠心病,下降% / DBP降低6 mm Hg,流行病学资料,随机试验,流行病学资料,随机试验,0 10 20 30 40 50,但是， 降压治疗降低冠心病事件的幅度
9、未达预期,Collins and Peto, 1994,-52%,-38%,-21%,-16%,卒中,心衰,CVD死亡,CHD事件,收缩压降低10-12mmHg或舒张压降低5-6mmHg,风险降低 (%),Collins and Peto, 1994,荟萃分析： 单纯降压治疗的冠心病获益存在瓶颈,治疗的高血压患者,即使控制血压， 高血压患者的冠心病风险仍显著高于常人,Andersson OK. Br Med J. 1998;317:167-171.,686名高血压患者和6810名血压正常人群，平均随访22-23年,冠心病生存,185/114145/89mmHg,146/93mmHg,1.0,0
10、.9,0.8,0.7,0 2 4 6 8 10 12 14 16 18 20 22,无高血压患者,P=0.0001,高血压患者的冠心病风险,Andersson OK. Br Med J. 1998;317:167-171.,多变量Coxs回归分析：评价危险因素与冠心病风险增加间的关系,胆固醇水平是唯一与冠心病风险增加显著相关的危险因素作者认为，一些高血压患者在研究入选时可能已经存在进展性的动脉粥样硬化病变,Libby P. Circulation. 2001;104:365-372; Ross R. N Engl J Med. 1999;340:115-126.,单核细胞,LDL-C,黏附分子
11、,巨噬细胞,泡沫细胞,氧化的 LDL-C,斑块破裂,CRP,动脉粥样硬化的病理机制,内皮功能受损是启动因子LDL-C是罪魁祸首炎症反应贯穿全程,高血压患者的冠心病风险,高血压(+),高血压加剧动脉粥样硬化发生,单核细胞,LDL穿透性,巨噬细胞,内皮依赖的血管舒张性,内皮通透性,oxLDL,脂蛋白与血管壁的接触时间,武阳丰等，中华流行病学杂志 2004年10月第25卷第10期,高血压患者动脉粥样硬化发生率更高,北京石景山区1198名农村居民（43-73岁）：横断面调查和颈动脉超声,理想血压,1期高血压,2期高血压,3期高血压,OR值,1,1.7,2.3,2.1,1,1.6,1.7,3.9,不同血
12、压类型人群检出斑块的危险性比较,即使年轻高血压患者，AS发生率已高达约50%,Prevention and Control (2005) 1:315,PBDAY研究 (Pathobiological Determinants of Atherosclerosis in Youth Study)全球15个国家的18个临床中心1277名因外伤死亡的人群（年龄15-34岁）,P0.001,P0.001,P0.001,0,10,20,30,40,50,60,胸主动脉,腹主动脉,右冠状动脉,高血压,血压正常,发生动脉粥样硬化的百分比,39,49,54,荟萃分析： 降压抗AS能实现更多心血管保护,BMJ.
13、 2003;326:1419,降压药,他汀,阿司匹林,叶酸,总计,缺血性心脏病风险降低(%),46%,61%,32%,16%,88%,其中他汀的获益最显著！,降压他汀进一步显著获益 ASCOT给了充分的回答,所有病人有高血压伴 3个CHD危险因素 但无临床诊断冠心病,病人伴危险因素(%),0,10,20,30,40,50,60,70,80,90,100,高血压 年龄 55岁 男性 微量白蛋白尿/蛋白尿 吸烟 家族CHD史 血清TC:HDL-C 6 2型糖尿病 确认ECG异常 LVH 先前发生脑血管事件 外周血管病,84,77,61,30,27,24,24,14,13,11,6,100,Seve
14、r PS, et al, Lancet. 2003;361:1149-58,主要终点：非致死性心肌梗死和致死性冠心病,0,1,2,3,4,0.5,1.0,1.5,2.0,2.5,3.0,3.5(年),主要终点事件发生率 (%),P=0.0005,降压药阿托伐他汀，LDL-C 133 90mg/dL,降压药安慰剂，LDL-C 133126mg/dL,36%,ASCOT-LLA：降压基础上联合阿托伐他汀， 进一步显著降低冠心病事件36%,在单纯降压降低冠心病事件10%的基础上，加用阿托伐他汀10mg，进一步显著降低冠心病事件36%，突破了冠心病的获益不足的瓶颈。,Sever PS, et al,
15、Lancet. 2003;361:1149-58,在单纯降压降低脑卒中事件23%的基础上，加用阿托伐他汀10mg，还进一步显著降低脑卒中事件27%,ASCOT-LLA：降压基础上联合阿托伐他汀， 脑卒中也进一步显著下降27%,0,0.5,1.0,1.5,2.0,2.5,3.0,3.5(年),卒中事件累计发生率(%),1,2,3,P=0.0236,27%,降压药阿托伐他汀，LDL-C 133 90mg/dL,降压药安慰剂，LDL-C 133126mg/dL,ASCOT研究之后：各种指南迅速作出反应,Guidelines Committee. J Hypertension. 2003;21:1011-1053. De Backer. Eur Heart J. 2003;24:1601-1610. Joint British Society 2. Heart. 2005;91:v1-v52. The National Collaborating Centre for Chronic Conditions. NICE Clinical Guidelines 18. 2006.,
