高血压合并多重危险因素及靶器官损害患者的治疗指南

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BMJ2003;326:1419A 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 studies and a meta-ana

2、lysis of 15 trials of low dose (50-125 mg/day) aspirin 结果:Polypill组成:1. a statin (for exle, atorvastatin (daily dose 10 mg) or simvastatin (40 mg); 2. three blood pressure lowering drugs (for exle, a thiazide, a blocker, and an angiotensin converting enzyme inhibitor), each at half standard dose;3.

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;326:14190%20%40%60%80%100%0%20%40%60%80%100%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%风险降低(%)该论文意义在于提出了多

4、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 dyslipidemia16% have type 2 diabetes 45% are overweight / obeseOf all Dyslipidemics 48% have hypertension14% have ty

5、pe 2 diabetes35% are overweight / obese Of all Type 2 Diabetics 60% have hypertension60% have dyslipidemia90% are overweight / obese Hypertension Type 2Diabetes Dyslipidemia Multiple comorbidities increases risk 400-700% 1Based on Framingham risk 高血压人群中，动脉粥样硬化的发生率更高Prevention and Control (2005) 1, 3

6、15PDAY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）P0.001P0.001P0.0010102030405060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%高血压患者合并其它危险因素非HTN72.6%HTN27.4%只有HTN 30.4%合并危险因素的HTN 患

7、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):587-60344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

8、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) 1357911131517190.880.920.9611357911131517190.940.960.981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HTNHTN0RFHTN1-2RFHTN3RF无HTNHTN0RFHTN1-2RFHTN3RFLog-rank=P0.001Log-rank=P0.00121212010多种危险因素共同存在，加剧AS，导致CV事件倍增100806040200234522423824162

9、532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(%)36251428647586720102030405060708090100SHEP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

10、，获益远远不够Treating a Single Risk Factor is Not Enough: CV Risk Remains Even After Statin TherapyRisk of Primary Event (%)Kastelein JJP. Eur Heart J. 2005;7:F27-F33.Please see prescribing information at the end of this slide presentation.Multiple CV Risk Management Results in Dramatic Reductions in CVD1

11、0% Reductionin BP10% Reductionin TC+45% Reductionin CVD=“Attention should be moved from knowing ones BP and cholesterol concentrations to knowing ones absolute CV risk and its determinants.” J. Emberson et aland Jackson et alEmberson J et al. Eur Heart J. 2004;25:484-491. Jackson R et al. Lancet. 20

12、05;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012340.00.51.01.52.02.53.03.5随访年数累积事件发生率（） 阿托伐他汀 10 mg安慰剂p=0.000536% 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;361:1149-58ASCOT-LLA：降压基础上，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 (%)0102030405060708090100高血压年龄 55岁

13、男性微量白蛋白尿/蛋白尿吸烟家族CHD史血清TC:HDL-C 62型糖尿病确认ECG异常LVH先前发生脑血管事件外周血管病847761302724241413116ASCOT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 ArterialHypertension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

14、for the Management of ArterialHypertension、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 115 mmol/l (1.3 mg/dl) Therefore, treatments witha 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