降压治疗策略与目标回顾及进展

1、降压治疗策略与目标回顾及进展降压治疗策略研究的重点降压治疗策略研究的重点l 血压水平与心血管危险l 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 2002,360:1903Stroke mortality(floating absolute risk and 95%CI)2561286432168421120140160180Usual sysytolic bloodPressure (mmHg)Usual diastolic bloodPressure (mmHg)25612864321684217080

2、10011090Stroke mortality(floating absolute risk and 95%CI)A: Systolic blood pressureB: Diastolic blood pressureAge at rist:80-89Years70-79Yaes60-69years50-59YearsAge at rist:80-89Years70-79Yaes60-69years50-59YearsIHD mortality(floating absolute risk and 95%CI)2561286432168421120140160180Usual sysyto

3、lic bloodPressure (mmHg)Usual diastolic bloodPressure (mmHg)2561286432168421708010011090IHD mortality(floating absolute risk and 95%CI)A: Systolic blood pressureB: Diastolic blood pressureAge at rist:80-89Years70-79Yaes60-69years50-59Years40-49yearsAge at rist:80-89Years70-79Yaes60-69years50-59Years

4、40-49yearsLancet 2002,360:1903CauseAge atNumber ofOf deathrisk(years)deathsStroke40-494140.36 (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)IHD40-4913220.49 (0.45-0.53)50-5955940.50 (0.49-0.52)60-69104500.54 (0.53-0.55)70-79108520.60 (

5、0.58-0.61)80-8956490.67 (0.64-0.70)Other40-493860.43 (0.38-0.48)vascular50-5913770.50 (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)0.250.350.50.71.0A: usual systolic blood pressure ( 115 mmHg)Hazard ratio (95% CI) for 20 mmHgLower usual systolic blood pressur

6、eLancet 2002,360:1903CauseAge atNumber ofOf deathrisk(years)deathsStroke40-493480.35 (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)IHD40-4911140.47 (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)8

7、0-8950680.70 (0.65-0.74)Other40-493160.43 (0.37-0.50)vascular50-5911400.48 (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)0.250.350.50.71.0B: usual diastolic blood pressure ( 75 mmHg)Hazard ratio (95% CI) for 10 mmHgLower usual diastolic blood pressureLancet 20

8、02,360:1903脑卒中脑卒中 冠心病冠心病SBP 89% 93%DBP 83% 73%PP 37% 43%MAP 100% 97%Mid BP 100% 100%Lancet 2002,360:1903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）

9、 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. 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 分类收缩压(mmHg)舒张压(mmHg)理想血压 1

10、20 80正常血压 120 - 129 80 - 84正常高值 130 - 139 85 - 891级高血压(轻度) 140 - 159 90 - 992级高血压(中度) 160 - 179 100 - 1093级高血压(重度) 160 110单纯收缩期高血压 140 90110110119120129130139140149150159160+SBP, mm Hg% of men302520151050Adjusted relative risk5432107070747579808485899094100+DBP, mm Hg% of men302520151050Adjusted rel

11、ative risk32.521.510.509599MRFIT: 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%降压治疗临床试验荟萃分析结果降压治疗临床试验荟萃分析结果T = treatmentC = controlNon-fatal eventsFatal eventsTCTCTCTCNumbers individuals020040060080010001200% reductionin oddsStroke39%CHD16%Vascular deaths21%All other deaths2%0.080.06

12、0.040.020012345Years after randomizationIschemic StrokeHemorrhagic StrokePlacebo TreatmentActive TreatmentCumulative Stroke RateSHEP study: JAMA 2000; 284:2651.82.310.90.811.41.10.50.60.3600.511.522.5EWPHESTOPSHEPSyst-EurUKPDSPlaceboTherapyTrialNumber of end pointsTreat:ControlOdds rations andconfid

13、ence limitsSHEPSYST-EURSYST-CHINAALLHeterogeneity:P=0.38Reduction andSDTreatment betterTreatment worse0.51.01.5SHEPSYST-EURSYST-CHINAALLHeterogeneity:P=0.82All cardiovascular end points199:289137:18674:94410:56932%SD 52P=0.001Fatal and non-fatal stroke103:15944:7745:59195:29537%SD 62P=0.00125%SD 82P

14、=0.004SHEPSYST-EURSYST-CHINAALLHeterogeneity:P=0.96Fatal and non-fatal MI(including sudden death)90:11259:7733:44182:233Eur Heart J 1999:1(suppl):p3Eur Heart J 1999:1(suppl):p3TrialNumber of end pointsTreat:ControlOdds rations andconfidence limitsSHEPSYST-EURSYST-CHINAALLHeterogeneity:P=0.38Reductio

15、n andSDTreatment betterTreatment worse0.51.01.5SHEPSYST-EURSYST-CHINAALLHeterogeneity:P=0.82Total mortality213:242133:13761:82397:46117%SD 62P=0.008Cardiovascular mortality90:11259:7733:44182:23325%SD 82P=0.005PROGRESS: PROGRESS: 预防脑卒中再发预防脑卒中再发随访时间（年）随访时间（年）发生事件患者的比例发生事件患者的比例安慰剂组安慰剂组 治疗组治疗组危险下降危险下降2

16、8% (95%的可信限的可信限 17-38%)P0.0001Lancet 2001; 358: 1033-410.200.150.100.050.001234 平均下降 脑卒中 3540% 心肌梗死 2025% 心力衰竭 50% TrialsNumber ofOdds ratios Diferecevents/paitients(95% Cls)(SD)OldNewMIDAS/NICS/VHAS15/135815/1353STOP2/CCBs369/2213362/2196NORDIL228/5471153/3157INSIGHT152/3164153/3157ALLHAT/Aml 2203/

17、152551256/9048ELSA 17/115713/1177CCBs without CONVINCE2984/286182030/22341-3.1% (3.2) 2P=0.31Heterogeneity P=0.95CONVINCE319/8297337/8179All CCBs3303/369152367/30520-2.3% (2.9) 2P=0.42 Heterogeneity P=0.95UKPDS59/35875/400STOP2/ACEIs369/2213380/2205CAPPP190/5493184/5492ALLHA/Lis2203/152551314/3044AN

18、BP2210/3039195/3044HYVET/AD30/42627/431All ACEIs3061/267842175/20626-0.4% (3.1) 2P=0.89Heterogeneity P=0.90LIFE 431/4588383/4605SCOPE266/2460259/2477All ARBs697/7048642/7082-9.2% (5.9) 2P=0.09Heterogeneity P=0.42ALLHAT/Dox851/15268514/9067All trias 4489/532795698/67295-1.8% (2.1) 2P=0.38Heterogeneit

19、y P=0.96 New drugs betterOld drugs better0123Total mortalityStaessen JA. J Hypertens 2003,21:1055TrialsNumber ofOdds ratios Diferecevents/paitients(95% Cls)(SD)OldNewMIDAS/NICS/VHAS7/135810/1353STOP2/CCBs221/2213212/2196NORDIL115/5471131/5410INSIGHT52/316460/3157ALLHAT/Aml 992/15255592/9048ELSA 8/11

20、574/1177CCBs without CONVINCE1438/309471039/246852.0% (4.4) 2P=0.64Heterogeneity P=0.59CONVINCE143/8297152/8179All CCBs1581/392441191/328642.7% (4.1) 2P=0.51 Heterogeneity P=0.68UKPDS32/35848/400STOP2/ACEIs221/2213226/2205CAPPP95/549376/5492ALLHA/Lis992/15255609/9054ANBP282/303984/3044HYVET/AD23/426

21、22/431All ACEIs1539/231461365/191262.2% (4.3) 2P=0.61Heterogeneity P=0.50LIFE 234/4588204/4605SCOPE152/2460145/2477All ARBs386/7048349/7082-10.6% (8.1) 2P=0.15Heterogeneity P=0.59All trias 2104/501152349/560230.5% (3.1) 2P=0.87Heterogeneity P=0.53 New drugs betterOld drugs better0123Total mortalityT

22、rialsNumber ofOdds ratios Diferecevents/paitients(95% Cls)(SD)OldNewMIDAS/NICS/VHAS37/135839/1353STOP2/CCBs637/2213636/2196NORDIL453/5471466/5410INSIGHT397/3164383/3157ALLHAT/Aml 3941/152552432/9048ELSA 33/115727/1177CCBs without CONVINCE5498/286183983/223413.6% (2.4) 2P=0.14Heterogeneity P=0.78CONV

23、INCE365/8297364/8179All CCBs5863/369154347/305203.4% (2.3) 2P=0.15 Heterogeneity P=0.86UKPDS78/358107/400STOP2/ACEIs637/2213586/2205CAPPP401/5493438/5492ALLHA/Lis3941/152552514/9054ANBP2429/3039394/3044All ACEIs*5486/263584039/201952.6% (3.6) 2P=0.59Heterogeneity P=0.006LIFE 588/4588508/4605SCOPE268

24、/2460242/2477All ARBs856/7048750/7082-14.3% (5.5) 2P=0.004Heterogeneity P=0.69ALLHAT/Dox2245/152681592/9067All trias*7627/5285310728/66864-1.4% (4.8) 2P=0.69Heterogeneity P0.0001 New drugs betterOld drugs better0123Total mortalityStaessen JA. J Hypertens 2003,21:1055收缩压下降与收缩压下降与CVD危险汇萃相关分析危险汇萃相关分析St

25、aessen JA. J Hypertens 2003,21:1055All cardiovascular eventsDifference (referecne minus experimental in systolic pressure (mmHg)0510152025-51.501.251.000.750.500.25Odd ratio (experimental/reference)p 0.0001STONEUKPDS L vs HPART2/SCATHOPEPATSSHEPPROGRESS/ComSTOP1RCT70-80HEPEWPHEMRC2MRC1ATMHSyst-EurSy

26、st-ChinaRENAALPROGRESS/PerSTOP2/ACEISHOT L vs HINSIGMTHOT M vs HMIDAS/NICS/VHASNORDILCAPPISTOP2/CCBsUKPDS C vs AALLHAT0510152025-51.501.251.000.750.500.25Odd ratio (experimental/reference)ALLHAT/Lis bLACKSALLHAT/Lis 65 yALLHAT/LisALLHAT/AmlCONVINCEABCD/NT L vs HDIABHYCARANBP2IDNT2LIFE/ALLSCOPEPREVEN

27、TELSAAASK L vs HNICOLELIFE/DMLIFE:LIFE:收缩压差值的意义收缩压差值的意义 CVD事件 0.85(0.76-0.96) 0.93(0.85-1.02) 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)0.28Diabetic patients (3 mmHg) CVD事件 0.73(0.57-0.95) 0.84(0.77-0.91) Stroke 0.78(0.54-1.13) 0.78(0.71-0.85)0.99 MI 0.81(0.54-1.22

28、) 0.85(0.78-0.93)0.82Staessen: Eur Heart J 2003;24:504AASK ANBP2 ASCOT ALLHAT BENEDICT CONVINCE DIAB-HYCAR ELSA HYVET LIFE PHYLLIS PRIME PROGRESS RENAAL SCOPE SHELL0510152025303514121086420Stroke Rate in Placebo Group (per 1000 pt-yr)Stroke Prevented (per 1000 pt-yr)Lever AF. J Hypertens 1995;13(6):

29、571Stroke0.80(0.65-0.98)CHD0.81(0.67-0.98)CHF0.78(0.53-1.15)0510152025Major CV events/1000 patient yearsTarget DBP mm Hgp=0.005 for trend 90 85 80 降压治疗与心血管危险控制降压治疗与心血管危险控制基本观点基本观点l 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。l 降压治疗的益处主要来自血压降低。l 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。q高血压患者： 140/90 mmH

30、gq糖尿病和慢性肾脏疾病患者：130/80 mmHgq高血压患者140/90 mmHgq糖尿病患者130/80 mmHgJNC-7JNC-7：降压治疗流程：降压治疗流程生活方式改变生活方式改变血压未达到控制目标值血压未达到控制目标值 ( 140/90), 糖尿病和慢性肾脏病糖尿病和慢性肾脏病 ( 180 orDBP 110No other riskfactors12 risk factors3 or more riskfactors or TODor diabetesACCV HIGH RISKV HIGH RISKV HIGH RISK V HIGH RISKHIGH RISKHIGH RI

31、SKHIGH RISK MEDIUM RISK MEDIUM RISKMEDIUM RISKLOW RISKSBP 120129 orDBP 8084SBP 130139 orDBP 8589 V HIGH RISKV HIGH RISKAVERAGE RISKLOW RISK LOW RISKAVERAGE RISKMEDIUM RISK HIGH RISK HIGH RISK q收缩压和舒张压水平(13级)q男性 55岁q女性 65岁q吸烟q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)q早发心血管病家族史(发病年龄男 55岁，女 38 mm, Cornell 2440 mmmms 超声心动图: LVMI男 125, 女 110 g/m2) 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31mg/g)q空腹血糖 7.0 mmol/Lq餐后血糖 11.0 mmol/Lq缺血性卒中q脑出血q短暂性脑缺血发作q心肌梗死q心绞痛q冠状动