降压治疗的策略和目标课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,降压治疗策略与目标,回顾与进展,降压治疗策略研究的重点,血压水平与心血管危险,降压治疗与心血管危险控制,治疗益处及来源,(,why),治疗对象,(,who),治疗目标水平,(,what),治疗方案,(,which),Lancet 2002,360:1903,血压、年龄与脑卒中死亡率,(100,万人群资料分析,),Stroke mortality,(floating absolute risk and 95%CI),256,128,64,32,16,8,4,2,1,120,140,160,180,Usual sysytolic,blood,Pressure (mmHg),Usual diastolic blood,Pressure (mmHg),256,128,64,32,16,8,4,2,1,70,80,100,110,90,Stroke mortality,(floating absolute risk and 95%CI),A: Systolic blood pressure,B: Diastolic blood pressure,Age at rist,:,80-89,Years,70-79,Yaes,60-69,years,50-59,Years,Age at rist,:,80-89,Years,70-79,Yaes,60-69,years,50-59,Years,IHD mortality,(floating absolute risk and 95%CI),256,128,64,32,16,8,4,2,1,120,140,160,180,Usual sysytolic,blood,Pressure (mmHg),Usual diastolic blood,Pressure (mmHg),256,128,64,32,16,8,4,2,1,70,80,100,110,90,IHD mortality,(floating absolute risk and 95%CI),A: Systolic blood pressure,B: Diastolic blood pressure,Age at rist,:,80-89,Years,70-79,Yaes,60-69,years,50-59,Years,40-49,years,Age at rist,:,80-89,Years,70-79,Yaes,60-69,years,50-59,Years,40-49,years,Lancet 2002,360:1903,血压、年龄与冠心病死亡率,(100,万人群资料分析,),CauseAge atNumber of,Of deathrisk(years)deaths,Stroke,40-494140.36 (0.32-0.40),50-5913720.38 (0.35-0.40),60-6929390.43 (0.41-0.45),70-7943270.50 (0.48-0.52),80-8926360.67 (0.63-0.71),IHD,40-4913220.49 (0.45-0.53),50-5955940.50 (0.49-0.52),60-69104500.54 (0.53-0.55),70-79108520.60 (0.58-0.61),80-8956490.67 (0.64-0.70),Other,40-493860.43 (0.38-0.48),vascular,50-5913770.50 (0.47-0.54),60-6925490.53 (0.51-0.56),70-7932270.64 (0.61-0.67),80-8922510.70 (0.65-0.75),0.25,0.35,0.5,0.7,1.0,A: usual systolic blood pressure (,115 mmHg),Hazard ratio (95% CI) for 20 mmHg,Lower usual systolic blood pressure,Lancet 2002,360:1903,收缩压,20,mmHg,差值对心血管危险影响,CauseAge atNumber of,Of deathrisk(years)deaths,Stroke,40-493480.35 (0.30-0.40),50-5912430.34 (0.32-0.37),60-6926460.40 (0.38-0.42),70-7939150.48 (0.45-0.51),80-8923400.63 (0.58-0.69),IHD,40-4911140.47 (0.43-0.51),50-5949450.52 (0.50-0.55),60-6992890.56 (0.54-0.58),70-7997270.62 (0.60-0.64),80-8950680.70 (0.65-0.74),Other,40-493160.43 (0.37-0.50),vascular,50-5911400.48 (0.44-0.52),60-6922200.49 (0.46-0.53),70-7928530.61 (0.57-0.66),80-8919760.71 (0.64-0.79),0.25,0.35,0.5,0.7,1.0,B: usual diastolic blood pressure (,75 mmHg),Hazard ratio (95% CI) for 10 mmHg,Lower usual diastolic blood pressure,Lancet 2002,360:1903,舒张压,10,mmHg,差值对心血管危险影响,血压参数预测脑卒中和冠心病死亡率的相对能力,脑卒中 冠心病,SBP 89% 93%,DBP 83% 73%,PP 37% 43%,MAP 100% 97%,Mid BP 100% 100%,Lancet 2002,360:1903,ESRD,危险性随血压升高而增加,血压分级 患者,ESRD,数目 年龄校正后的 校正后的,RR,(n = 322554) (n = 814),每,10,万人年发生率,(95%,CI),理想,61089 51 5.3 1.0,正常,81621 86 6.6 1.2 (0.8-1.7),正常高值,73798 134 11.1 1.9 (1.4-2.7),高血压,1,级（轻度）,85684 275 21.0 3.1 (2.3-4.3),2,级（中度）,23459 158 43.6 6.0 (4.3-8.4),3,级（重度）,5464 73 96.1 11.2 (7.7-16.2),4,级（极重度）,1429 37 187.1 22.1 (14.2-34.3),Klag MJ, Whelton PK, Randali,BL et al, New Eng J Med. 1996;334:14-18.,血压水平的分类和定义,(,JNC-7),分类 收缩压,(mmHg),舒张压,(,mmHg),正常血压, 120,和, 80,高血压前期,120 - 139,或,80 - 89,高血压,1,级,140 - 159,或,90 - 99,高血压,2,级,160,或,100,血压水平的分类和定义,(,ESH/ESC 2003),分类,收缩压,(mmHg),舒张压,(mmHg),理想血压, 120 80,正常血压,120 - 129 80 - 84,正常高值,130 - 139 85 - 89,1,级高血压,(,轻度,) 140 - 159 90 - 99,2,级高血压,(,中度,) 160 - 179 100 - 109,3,级高血压,(,重度,) 160 110,单纯收缩期高血压, 140 90,110,110119,120129,130139,140149,150159,160+,SBP, mm Hg,% of men,30,25,20,15,10,5,0,Adjusted relative risk,5,4,3,2,1,0,70,7074,7579,8084,8589,9094,100+,DBP, mm Hg,% of men,30,25,20,15,10,5,0,Adjusted relative risk,3,2.5,2,1.5,1,0.5,0,9599,MRFIT: Arch Intern Med 1993; 153:598,正常血压者,临界血压者,正常血压者,临界血压者,90%,10%,47%,53%,临界高血压转归,(,Tecumsch,Study, 3,年随访,),降压治疗临床试验荟萃分析结果,T = treatment,C = control,Non-fatal events,Fatal events,T,C,T,C,T,C,T,C,Numbers individuals,0,200,400,600,800,1000,1200,%,reduction,in odds,Stroke,39%,CHD,16%,Vascular deaths,21%,All other deaths,2%,0.08,0.06,0.04,0.02,0,0,1,2,3,4,5,Years after randomization,Ischemic,Stroke,Hemorrhagic Stroke,Placebo Treatment,Active Treatment,Cumulative Stroke Rate,SHEP study: JAMA 2000; 284:265,Anti-hypertensive therapy & incidence of HF,n 840 1,627 4,736 4,695 1,148,F.U. (mths) 56 25 53 24 101,Reduction 17% 51% 54% 29% 56%,p, ns 0.01 0.001 ns 0.0043,%,per year,Trial,Number of end points,Treat:Control,Odds rations and,confidence limits,SHEP,SYST-EUR,SYST-CHINA,ALL,Heterogeneity:P=0.38,Reduction and,SD,Treatment better,Treatment worse,0.51.01.5,SHEP,SYST-EUR,SYST-CHINA,ALL,Heterogeneity:P=0.82,All cardiovascular end points,199:289,137:186,74:94,410:569,32%,SD 5,2P=0.001,Fatal and,non-fatal stroke,103:159,44:77,45:59,195:295,37%,SD 6,2P=0.001,25%,SD 8,2P=0.004,SHEP,SYST-EUR,SYST-CHINA,ALL,Heterogeneity:P=0.96,Fatal and non-fatal MI,(including sudden death),90:112,59:77,33:44,182:233,Eur Heart J 1999:1(suppl,):p3,Eur Heart J 1999:1(suppl,):p3,Trial,Number of end points,Treat:Control,Odds rations and,confidence limits,SHEP,SYST-EUR,SYST-CHINA,ALL,Heterogeneity:P=0.38,Reduction and,SD,Treatment better,Treatment worse,0.51.01.5,SHEP,SYST-EUR,SYST-CHINA,ALL,Heterogeneity:P=0.82,Total mortality,213:242,133:137,61:82,397:461,17%,SD 6,2P=0.008,Cardiovascular mortality,90:112,59:77,33:44,182:233,25%,SD 8,2P=0.005,PROGRESS:,预防脑卒中再发,随访时间（年）,发生事件患者的比例,安慰剂组,治疗组,危险下降,28%,(95%,的可信限,17-38%),P0.0001,Lancet,2001; 358: 1033-41,0.20,0.15,0.10,0.05,0.00,1,2,3,4,降压治疗的益处,平均下降,脑卒中,3540%,心肌梗死,2025%,心力衰竭,50%,TrialsNumber ofOdds ratios Diferece,vents/paitients(95% Cls,)(SD),OldNew,MIDAS/NICS/VHAS15/135815/1353,STOP2/CCBs,369/2213362/2196,NORDIL228/5471153/3157,INSIGHT152/3164153/3157,ALLHAT/Aml,2203/152551256/9048,ELSA 17/115713/1177,CCBs,without CONVINCE2984/286182030/22341-3.1% (3.2) 2,P,=0.31,Heterogeneity,P,=0.95,CONVINCE319/8297337/8179,All CCBs,3303/369152367/30520-2.3% (2.9) 2,P,=0.42 Heterogeneity,P,=0.95,UKPDS59/35875/400,STOP2/ACEIs,369/2213380/2205,CAPPP190/5493184/5492,ALLHA/Lis,2203/152551314/3044,ANBP2210/3039195/3044,HYVET/AD30/42627/431,All ACEIs,3061/267842175/20626-0.4% (3.1) 2,P,=0.89,Heterogeneity,P,=0.90,LIFE 431/4588383/4605,SCOPE266/2460259/2477,All ARBs,697/7048642/7082-9.2% (5.9) 2,P,=0.09,Heterogeneity,P,=0.42,ALLHAT/Dox,851/15268514/9067,All trias,4489/532795698/67295-1.8% (2.1) 2,P,=0.38,Heterogeneity,P,=0.96,降压治疗临床试验汇萃分析：总死亡率,（,CCB,、,ACEI,、,ARB vs,利尿剂,/,b,阻滞剂）,New drugs better,Old drugs better,0,1,2,3,Total mortality,Staessen JA. J Hypertens,2003,21:1055,TrialsNumber ofOdds ratios Diferece,vents/paitients(95% Cls,)(SD),OldNew,MIDAS/NICS/VHAS7/135810/1353,STOP2/CCBs,221/2213212/2196,NORDIL115/5471131/5410,INSIGHT52/316460/3157,ALLHAT/Aml,992/15255592/9048,ELSA 8/11574/1177,CCBs,without CONVINCE1438/309471039/246852.0% (4.4) 2,P,=0.64,Heterogeneity,P,=0.59,CONVINCE143/8297152/8179,All CCBs,1581/392441191/328642.7% (4.1) 2,P,=0.51 Heterogeneity,P,=0.68,UKPDS32/35848/400,STOP2/ACEIs,221/2213226/2205,CAPPP95/549376/5492,ALLHA/Lis,992/15255609/9054,ANBP282/303984/3044,HYVET/AD23/42622/431,All ACEIs,1539/231461365/191262.2% (4.3) 2,P,=0.61,Heterogeneity,P,=0.50,LIFE 234/4588204/4605,SCOPE152/2460145/2477,All ARBs,386/7048349/7082-10.6% (8.1) 2,P,=0.15,Heterogeneity,P,=0.59,All trias,2104/501152349/560230.5% (3.1) 2,P,=0.87,Heterogeneity,P,=0.53,降压治疗临床试验汇萃分析：心血管病死亡率,（,CCB,、,ACEI,、,ARB vs,利尿剂,/,b,阻滞剂）,New drugs better,Old drugs better,0,1,2,3,Total mortality,TrialsNumber ofOdds ratios Diferece,vents/paitients(95% Cls,)(SD),OldNew,MIDAS/NICS/VHAS37/135839/1353,STOP2/CCBs,637/2213636/2196,NORDIL453/5471466/5410,INSIGHT397/3164383/3157,ALLHAT/Aml,3941/152552432/9048,ELSA 33/115727/1177,CCBs,without CONVINCE5498/286183983/223413.6% (2.4) 2,P,=0.14,Heterogeneity,P,=0.78,CONVINCE365/8297364/8179,All CCBs,5863/369154347/305203.4% (2.3) 2,P,=0.15 Heterogeneity,P,=0.86,UKPDS78/358107/400,STOP2/ACEIs,637/2213586/2205,CAPPP401/5493438/5492,ALLHA/Lis,3941/152552514/9054,ANBP2429/3039394/3044,All ACEIs,*5486/263584039/201952.6% (3.6) 2,P,=0.59,Heterogeneity,P,=0.006,LIFE 588/4588508/4605,SCOPE268/2460242/2477,All ARBs,856/7048750/7082-14.3% (5.5) 2,P,=0.004,Heterogeneity,P,=0.69,ALLHAT/Dox,2245/152681592/9067,All trias,*7627/5285310728/66864-1.4% (4.8) 2,P,=0.69,Heterogeneity,P,0.0001,降压治疗临床试验汇萃分析：,CVD,发生率,（,CCB,、,ACEI,、,ARB vs,利尿剂,/,b,阻滞剂）,New drugs better,Old drugs better,0,1,2,3,Total mortality,Staessen JA. J Hypertens,2003,21:1055,收缩压下降与,CVD,危险汇萃相关分析,Staessen JA. J Hypertens,2003,21:1055,All cardiovascular events,Difference (referecne,minus experimental in systolic pressure (mmHg),0,5,10,15,20,25,-5,1.50,1.25,1.00,0.75,0.50,0.25,Odd ratio (experimental/reference),p 0.0001,STONE,UKPDS L vs,H,PART2/SCAT,HOPE,PATS,SHEP,PROGRESS/Com,STOP1,RCT70-80,HEP,EWPHE,MRC2,MRC1,ATMH,Syst-Eur,Syst,-China,RENAAL,PROGRESS/Per,STOP2/ACEIS,HOT L vs,H,INSIGMT,HOT M vs,H,MIDAS/NICS/VHAS,NORDIL,CAPPI,STOP2/CCBs,UKPDS C vs,A,ALLHAT,0,5,10,15,20,25,-5,1.50,1.25,1.00,0.75,0.50,0.25,Odd ratio (experimental/reference),ALLHAT/Lis bLACKS,ALLHAT/Lis,65 y,ALLHAT/Lis,ALLHAT/Aml,CONVINCE,ABCD/NT L vs,H,DIABHYCAR,ANBP2,IDNT2,LIFE/ALL,SCOPE,PREVENT,ELSA,AASK L vs,H,NICOLE,LIFE/DM,LIFE:,收缩压差值的意义,Odds Ratio(95% CI),观察值 预期值,p,All patients (1 mmHg),CVD,死亡率,0.87(0.72-1.05) 0.90(0.78-1.05)0.75,CVD,事件,0.85(0.76-0.96) 0.93(0.85-1.02),0.24,Stroke 0.74(0.63-0.88) 0.87(0.79-0.95)0.11,MI 1.05(0.86-1.28) 0.93(0.85-1.02)0.28,Diabetic patients (3 mmHg),CVD,死亡率,0.62(0.41-0.92) 0.86(0.76-0.99)0.12,CVD,事件,0.73(0.57-0.95) 0.84(0.77-0.91),0.34,Stroke 0.78(0.54-1.13) 0.78(0.71-0.85)0.99,MI 0.81(0.54-1.22) 0.85(0.78-0.93)0.82,Staessen: Eur,Heart J 2003;24:504,ALLHAT Collaborative Research Group.,JAMA,. 2002;288:2981-2997.,相对危险,(95%,CI),氯噻酮更好,氨氯地平,0.98 (0.90-1.07),0.7,1.3,赖诺普利,0.99 (0.91-1.08),氨氯地平更好赖诺普利更好,1,ALLHAT,主要终点：,CHD,死亡和非致死性心肌梗死,WHO/ISH,Blood Pressure Lowering,Trialists, Collaboration,(BPLT,临床试验协作研究,),BPLT,协作研究第二轮分析新入选的临床试验,AASK ANBP2,ASCOT,ALLHAT BENEDICT CONVINCE DIAB-HYCAR ELSA,HYVET,LIFE PHYLLIS,PRIME PROGRESS RENAAL SCOPE SHELL,BPLT,协作研究第二轮分析结果,(,二,),RR 95% CI,ACEI vs,利尿剂,/,阻滞剂,1.09 1.00-1.18,CCB vs,利尿剂,/,阻滞剂,0.93 0.86-1.21,ACEI vs,CCB 1.12 1.01-1.25,脑卒中,r=.93,p.001,SYST-EUR,STOP,Coope,SHEP,EWPHE,MRC-E,MRC,-I,05101520253035,14,12,10,8,6,4,2,0,Stroke Rate in Placebo Group (per 1000 pt-yr),Stroke Prevented (per 1000 pt-yr),Lever AF. J Hypertens,1995;13(6):571,BPLT,协作研究第一轮分析结果,(,二,),积极降压的,RR,总死亡率,0.97(0.85-1.11),CVD,死亡率,0.90(0.75-1.09),CVD,事件,0.85(0.76-0.96),Stroke0.80(0.65-0.98),CHD0.81(0.67-0.98),CHF0.78(0.53-1.15),0,5,10,15,20,25,Major CV events/,1000 patient years,Target DBP mm Hg,p=0.005 for trend,90,85,80,HOT:,目标血压与,CVD,事件,高血压合并糖尿病患者,降压治疗与心血管危险控制,基本观点,临床试验证实长期有效降压治疗能减少,30%-50%,心脑血管病发生率。,降压治疗的益处主要来自血压降低。,益处大小受患者心血管危险程度、血压控制目标,水平、治疗方案降压以外有利作用或不利作用的,影响。,血压控制目标值,(,JNC-7),高血压患者：,140/90 mmHg,糖尿病和慢性肾脏疾病患者：,130/80,mmHg,血压控制目标值,(,ESH/ESC 2003),高血压患者,140/90 mmHg,糖尿病患者,130/80,mmHg,JNC-7,：降压治疗流程,生活方式改变,血压未达到控制目标值,( 140/90),糖尿病和慢性肾脏病,(,180 or,DBP,110,No other risk,factors,12,risk factors,3,or more risk,factors or TOD,or diabetes,ACC,V HIGH RISK,V HIGH RISK,V HIGH RISK,V HIGH RISK,HIGH RISK,HIGH RISK,HIGH RISK,MEDIUM RISK,MEDIUM RISK,MEDIUM,RISK,LOW RISK,SBP 120129 or,DBP 8084,SBP 130139 or,DBP 8589,V HIGH RISK,V HIGH RISK,AVERAGE,RISK,LOW RISK LOW RISK,AVERAGE,RISK,心血管危险分层标准,(,ESH/ESC 2003),MEDIUM RISK,HIGH RISK,HIGH RISK,用于危险性分层的危险因素,(,ESH/ESC 2003),收缩压和舒张压水平,(13,级,),男性, 55,岁,女性, 65,岁,吸烟,血脂异常,(,TC 6.5 mmol,/L,或,LDL-C4.0 mmol,/L,或,HDL-C,男,1.0,女,1.2,mmol,/L,),早发心血管病家族史,(,发病年龄男, 55,岁，女, 38 mm,Cornell 2440 mm,mms,超声心动图,: LVMI,男, 125,女, 110,g/m,2,),超声有,动脉壁增厚,(,颈动脉,IMT, 0.9 mm,),或粥样斑块证据,血肌酐轻度升高,(,男,115 133,女,107 124,mmol,/L,),尿微量白蛋白,(30 300 mg/24h;,白蛋白,/,肌酐男, 22,女,31,mg/g,),糖尿病,(,ESH/ESC 2003),空腹血糖, 7.0,mmol,/L,餐后血糖, 11.0 mmol,/L,并存的临床情况,(,ESH/ESC 2003),脑血管病,缺血性卒中,脑出血,短暂性脑缺血发作,心脏疾病,心肌梗死,心绞痛,冠状动脉血运重建,充血性心力衰竭,肾脏疾病,糖尿病肾病,肾脏损害,(,血肌酐,男,133,女,124,mol/L,),蛋白尿,(300,mg/24h),周围血管,疾病,重度视网膜,病变,出血或渗出,视乳头水肿,降压治疗指征,(,B),1,级和,2,级高血压,:,Very High Risk,High Risk,Medium Risk,Low Risk,降压治疗指征,(,B),Stratify risk,Medium,Monitor BP & other,risk factors for at least 3 months,SBP,140,or DBP,90,Begin drug,treatment,SBP 140,and DBP ,140,or DBP,90,Consider drug,treatment,SBP 140,and DBP 90,Continue,to monitor,各类降压药物治疗高血压的地位,从,JNC-6,到,JNC-7,利尿剂,b,-,阻滞剂,ACEI,CCB ARB,-,阻滞剂,用于起动和持续治疗的合适降压药物,(,ESH/ESC),利,尿剂,b,-,阻滞剂,钙拮抗剂,ACE,抑制剂,血管紧张素,II,受体拮抗剂,影响降压药物选择的主要因素,患者对某类药物的降压疗效和不良反应,药品价格,患者心血管危险因素状况,存在,TOD,、心脑血管病、肾脏病和糖尿病,存在有益或限制某类降压药使用的合并症,与其它药物相互作用的可能性,更合理的,降压治疗,合理的血压目标水平,适宜的降压药物,最佳的联合治疗方案？,恰当的费用,/,效益比值,Diuretics,b,-blockers,AT,1,-receptor,blockers,a,-blockers,Calcium,antagonists,ACE inhibitors,合理的降压联合治疗方案,容量,-RAS,两极学说与降压药联合,利尿剂,b,-,阻滞剂,ACEI,CCB ARB,HOT,与,ALLHAT：,降压治疗方案,不同点,HOT ALLHAT,起始药物,CCB,利尿剂,联合药物,阻滞剂或,ACEI,交感抑制剂或,阻滞剂,剂量递增 先联合後递增 先递增後联合,ALPINE:,不同降压治疗方案对代谢的影响,血胰岛素,(,mIU,/L) 9.65 11.00 9.25,8.96 0.01,空腹血糖,(,mmol,/L) 5.29 5.42 5.17 5.10 0.001,血甘油三酯,(,mmol,/L) 1.52 1.95 1.58,1.66 0.001,HDL-C(mmol,/L) 1.39 1.31 1.36,1.35 0.001,HCT/,blocker ARB/CCB,前 后 前 后,p,建立在硬终点事件,临床试验基础上的,循证医学，对临床实践具有重要的指导意义。然而，临床试验,显示的是治疗药物或治疗方案在特定人群中的平均效果，其结论是一种总体评价。临床医师面临的是生物个体多样化的具体患者，不可能采用同一种治疗模式，需要多种降压治疗模式。,HOT,治疗方案为我们提供了有重要示范意义的治疗模式。,多种降压治疗模式的,临床意义,结 论,长期有效抗高血压治疗能显著降低心血管危险。,降压治疗的益处主要来自血压降低，益处大小受患者心血管危险程度、血压控制目标水平、治疗方案降压以外有利作用或不利作用的影响。,抗高血压治疗尚需进一步提高治疗益处和扩展治疗群体。,