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1、高血压合并多重危险因素及靶器官损害患者的治疗指南,葛世俊 宁波市李惠利医院心内科,BMJ 2003;326:1419 A strategy to reduce cardiovascular disease by more than 80% 减少心血管疾病80%以上的策略 polypill策略: 同时针对四种危险因素: low density lipoprotein cholesterol blood pressure serum homocysteine platelet function),方法:meta-analyses of randomised trials and cohort st
2、udies and a meta-analysis of 15 trials of low dose (50-125 mg/day) aspirin,结果: Polypill组成: 1. a statin (for example, atorvastatin (daily dose 10 mg) or simvastatin (40 mg); 2. three blood pressure lowering drugs (for example, a thiazide, a blocker, and an angiotensin converting enzyme inhibitor), ea
3、ch at half standard dose; 3. folic acid (0.8 mg); 4. aspirin (75 mg).,估计: Polypill减少缺血性心脏病88%(84% to 91%) .减少中风80% (71% to 87%). 三分之一55岁或以上人群能得益.平均延长无缺血性心脏病和中风寿命11年.,降压抗动脉粥样硬化：降低心血管病超过80%,BMJ. 2003;326:1419,风险降低(%),缺血性心脏病,46%,降压药,他汀,阿司匹林,叶酸,总计,卒中,降压药,他汀,阿司匹林,叶酸,总计,61%,32%,16%,88%,63%,17%,16%,24%,80%
4、,风险降低(%),该论文意义在于提出了多重危险因素干预的概念(multifactorial interventions ) 多重危险因素干预的理由主要有: 1、心血管疾病的主要敌人是动脉粥样硬化 2、心血管危险因素有聚集性 3、干预单一危险因素效果并不理想,Most Patients Have Overlapping CV Risk Factors,Of all Hypertensives 65% have dyslipidemia 16% have type 2 diabetes 45% are overweight / obese,Of all Dyslipidemics 48% have
5、 hypertension 14% have type 2 diabetes 35% are overweight / obese,Of all Type 2 Diabetics 60% have hypertension 60% have dyslipidemia 90% are overweight / obese,Hypertension,Type 2 Diabetes,Dyslipidemia,Multiple comorbidities increases risk 400-700%,1 Based on Framingham risk,高血压人群中，动脉粥样硬化的发生率更高,Pre
6、vention and Control (2005) 1, 315,PDAY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,The Burden of Cardiovascular Disease in West Virginia,BRFSS(1996)： 69.6%高血压
7、患者合并其它危险因素,非HTN 72.6%,HTN 27.4%,只有HTN 30.4%,合并危险因素的HTN 患者69.6%,REACH注册研究： 90.3%的高血压患者合并超过3个危险因素,Vascular Health and Risk Management 2007;3(5):587-603,44个国家、67,888名年龄45岁的患者,危险因素包括：接受治疗的糖尿病、糖尿病肾病、无症状的颈动脉狭窄70%、收缩压150mmHg、接受治疗的高胆固醇血症、吸烟、男性55岁、女性70岁,81.8% 高血压,90.3%3个危险因素,LDL-C ,BP ,糖尿病,吸烟,肥胖,多种危险因素共同存在，加
8、速动脉粥样硬化,可干预的危险因素,不可干预的危险因素,年龄,男性,早发家族史,氧化应激,内皮功能受损，炎症反应,高血压患者中， 随危险因素增多，心血管风险增加,Hypertension. 2001;37:1256-1261.,男性高血压患者(N=60343) vs. 男性非高血压对照者（N=29640),年龄55岁,年龄55岁,随访时间（年）,随访时间（年）,存活率（）,存活率（）,无HTN,HTN0RF,HTN1-2RF,HTN3RF,无HTN,HTN0RF,HTN1-2RF,HTN3RF,Log-rank=P0.001,Log-rank=P0.001,21 2,1,20 1,0,多种危险因
9、素共同存在，加剧AS， 导致CV事件倍增,100,80,60,40,20,0,2,3,4,5,22 4,23 8,24 16,25 32,相对风险,绝对风险 (/1,000病例/6年),危险数 （糖尿病、高血压、吸烟、CHD家族史、低HDL-C）,一级预防,JAMA. 1991;265:3255-3264; BMJ. 1992;304:405-412; Lancet. 1997;350:757-764; Lancet. 2001;358:1033-1041.,原发事件的风险(%),36,25,14,28,64,75,86,72,0,10,20,30,40,50,60,70,80,90,100,
10、SHEP 氯噻酮+/-阿替洛尔,MRC-O HCTZ+阿替洛尔,Syst-Eur 尼群地平, 依拉普利, HCTZ,PROGRESS 培哚普利+/-利尿剂,风险降低(%),没有消除的事件(%),单纯降压，获益远远不够,Treating a Single Risk Factor is Not Enough: CV Risk Remains Even After Statin Therapy,Risk of Primary Event (%),Kastelein JJP. Eur Heart J. 2005;7:F27-F33. Please see prescribing information
11、 at the end of this slide presentation.,Multiple CV Risk Management Results in Dramatic Reductions in CVD,“Attention should be moved from knowing ones BP and cholesterol concentrations to knowing ones absolute CV risk and its determinants.” J. Emberson et al and Jackson et al,Emberson J et al. Eur H
12、eart J. 2004;25:484-491. Jackson R et al. Lancet. 2005;365:434-441.,高血压的主要治疗目标： 最大程度降低心血管疾病总体风险,主要终点：非致死性心梗和致死性冠心病,0,1,2,3,4,0.0,0.5,1.0,1.5,2.0,2.5,3.0,3.5,随访年数,累积事件发生率（）,阿托伐他汀 10 mg 安慰剂,p=0.0005,36%,3.3年,由于主要终点在很早就出现了非常显著的差异， 调脂部分比计划提前近2年结束,Sever PS, et al, Lancet. 2003;361:1149-58,ASCOT-LLA： 降压基础
13、上，他汀治疗获益显著,ASCOT所有病人有高血压伴 3个CHD危险因素,病人伴危险因素比例 (%),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,ASCOT研究的病人的危险程度,100,多重危险因素干预： 1、治疗性生活方式改变 2、药物： A 他汀 B 阿司匹林,2007 Guidelines for the Management of Arter
14、ial Hypertension,关于他汀治疗 、对高血压伴心血管疾病或糖尿病患者应给予他汀治疗。 目标：TC 4.5 mmol/l (175 mg/dl) LDL-C 2.5 mmol/l (100 mg/dl),2007 Guidelines for the Management of Arterial Hypertension,、对高血压无明显心血管疾病但高危患者(20% risk of events in 10 years)，即使基线TC和LDL-C水平并不增高，也应给予他汀治疗。 目标：TC 5 mmol/l (190 mg/dl) LDL-C 3 mmol/l (115 mg/dl
15、),2007 Guidelines for the Management of Arterial Hypertension,关于抗血小板治疗 、高血压伴曾发生心血管事件的患者，如无过多出血危险，应给予抗血小板治疗，特别是小剂量阿司匹林,2007 Guidelines for the Management of Arterial Hypertension,、对高血压无心血管疾病史患者，如年龄大于50岁，伴血清肌酐中度升高或有高心血管危险应考虑小剂量阿司匹林治疗 (serum creatinine 115 mmol/l (1.3 mg/dl) Therefore, treatments witha
16、 low-dose aspirin have favourable benefit/risk ratios only if given to patients above a certain threshold of total cardiovascular risk (1520% in 10 years).,To minimize the risk of haemorrhagic stroke, antiplatelet treatment should be started after achievement of BP control.,2007 Guidelines for the Management of Arterial Hypertension,Subclinical organ damage 、LVH ACEI, CA, ARB 、Asympt.atherosclerosis CA, ACEI 、Microalbuminuria ACEI, ARB 、Renal dysfunction ACEI, ARB,谢谢,