高血壓合并多重危險因素及靶器官損害患者的治療指南

1、高血壓合并多重危險因素及靶器官損害患者的治療指南BMJ2003;326:1419A strategy to reduce cardiovascular disease by more than 80% 減少心血管疾病80%以上的策略polypill策略: 同時針對四種危險因素: 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 結(jié)果:Polypill組成: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). 估計: Polypill減少缺血性心臟病88%(84% to 91%) .減少中風(fēng)80% (71% to 87%). 三分之一55歲或以上人群能得益.平均延長無缺血性心臟病和中風(fēng)壽命11年.降壓抗動脈粥樣硬化：降低心血管病超過80%BMJ. 2003;326:14190%20%40%60%80%100%0%20%40%60%80%100%風(fēng)險降低(%)缺血性心臟病46%降壓藥他汀阿司匹林葉酸總計卒中降壓藥他汀阿司匹林葉酸總計61%32%16%88%63%17%16%24%80%風(fēng)險降低(%)該論文意義在于提出了多

4、重危險因素干預(yù)的概念(multifactorial interventions )多重危險因素干預(yù)的理由主要有: 1、心血管疾病的主要敵人是動脈粥樣硬化 2、心血管危險因素有聚集性 3、干預(yù)單一危險因素效果并不理想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 高血壓人群中，動脈粥樣硬化的發(fā)生率更高Prevention and Control (2005) 1, 3

6、15PDAY研究 (Pathobiological Determinants of Atherosclerosis in Youth Study) 全球15個國家的18個臨床中心 1277名因外傷死亡的人群（年齡15-34歲）P0.001P0.001P0.0010102030405060胸主動脈腹主動脈右冠狀動脈高血壓血壓正常發(fā)生動脈粥樣硬化的百分比The Burden of Cardiovascular Disease in West Virginia BRFSS(1996)：69.6%高血壓患者合并其它危險因素非HTN72.6%HTN27.4%只有HTN 30.4%合并危險因素的HTN 患

7、者69.6%REACH注冊研究：90.3%的高血壓患者合并超過3個危險因素Vascular Health and Risk Management 2007;3(5):587-60344個國家、67,888名年齡45歲的患者危險因素包括：接受治療的糖尿病、糖尿病腎病、無癥狀的頸動脈狹窄70%、收縮壓150mmHg、接受治療的高膽固醇血癥、吸煙、男性55歲、女性70歲81.8% 高血壓90.3%3個危險因素LDL-C BP 糖尿病吸煙肥胖多種危險因素共同存在，加速動脈粥樣硬化可干預(yù)的危險因素不可干預(yù)的危險因素年齡男性早發(fā)家族史氧化應(yīng)激內(nèi)皮功能受損，炎癥反應(yīng)高血壓患者中，隨危險因素增多，心血管風(fēng)險增

8、加Hypertension. 2001;37:1256-1261.男性高血壓患者(N=60343) vs. 男性非高血壓對照者（N=29640) 1357911131517190.880.920.9611357911131517190.940.960.981年齡55歲年齡55歲隨訪時間（年）隨訪時間（年）存活率（）存活率（）無HTNHTN0RFHTN1-2RFHTN3RF無HTNHTN0RFHTN1-2RFHTN3RFLog-rank=P0.001Log-rank=P0.00121212010多種危險因素共同存在，加劇AS，導(dǎo)致CV事件倍增100806040200234522423824162

9、532相對風(fēng)險絕對風(fēng)險(/1,000病例/6年)危險數(shù)（糖尿病、高血壓、吸煙、CHD家族史、低HDL-C）一級預(yù)防JAMA. 1991;265:3255-3264; BMJ. 1992;304:405-412; Lancet. 1997;350:757-764; Lancet. 2001;358:1033-1041.原發(fā)事件的風(fēng)險(%)36251428647586720102030405060708090100SHEP氯噻酮+/-阿替洛爾MRC-O HCTZ+阿替洛爾Syst-Eur尼群地平, 依拉普利, HCTZ PROGRESS培哚普利+/-利尿劑風(fēng)險降低(%)沒有消除的事件(%)單純降壓

10、，獲益遠遠不夠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.高血壓的主要治療目標：最大程度降低心血管疾病總體風(fēng)險主要終點：非致死性心梗和致死性冠心病012340.00.51.01.52.02.53.03.5隨訪年數(shù)累積事件發(fā)生率（） 阿托伐他汀 10 mg安慰劑p=0.000536% 3.3年由于主要終點在很早就出現(xiàn)了非常顯著的差異，調(diào)脂部分比計劃提前近2年結(jié)束Sever PS, et al, Lancet. 2003;361:1149-58ASCOT-LLA：降壓基礎(chǔ)上，他汀治療獲益顯著ASCOT所有病人有高血壓伴 3個CHD危險因素病人伴危險因素比例 (%)0102030405060708090100高血壓年齡 55歲

13、男性微量白蛋白尿/蛋白尿吸煙家族CHD史血清TC:HDL-C 62型糖尿病確認ECG異常LVH先前發(fā)生腦血管事件外周血管病847761302724241413116ASCOT研究的病人的危險程度100多重危險因素干預(yù)：1、治療性生活方式改變2、藥物： A 他汀 B 阿司匹林2007 Guidelines for the Management of ArterialHypertension關(guān)于他汀治療、對高血壓伴心血管疾病或糖尿病患者應(yīng)給予他汀治療。目標：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、對高血壓無明顯心血管疾病但高危患者(20% risk of events in 10 years)，即使基線TC和LDL-C水平并不增高，也應(yīng)給予他汀治療。目標：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