1、降壓治療策略與目標的回顧及進展降壓治療策略與目標的回顧及進展降壓治療策略研究的重點 血壓水平與心血管危險 降壓治療與心血管危險控制 治療益處及來源(why) 治療對象(who) 治療目標水平(what) 治療方案(which)2降壓治療策略與目標的回顧及進展降壓治療策略研究的重點 血壓水平與心血管危險2降壓治療策略與Lancet 2002,360:1903血壓、年齡與腦卒中死亡率(100萬人群資料分析)Stroke mortality(floating absolute risk and 95%CI)2561286432168421120140160180Usual sysytolic blo

2、odPressure (mmHg)Usual diastolic bloodPressure (mmHg)2561286432168421708010011090Stroke mortality(floating absolute risk and 95%CI)A: Systolic blood pressureB: Diastolic blood pressureAge at rist:80-89Years70-79Yaes60-69years50-59YearsAge at rist:80-89Years70-79Yaes60-69years50-59Years3降壓治療策略與目標的回顧及

3、進展Lancet 2002,360:1903血壓、年齡與腦卒中死IHD mortality(floating absolute risk and 95%CI)2561286432168421120140160180Usual sysytolic bloodPressure (mmHg)Usual diastolic bloodPressure (mmHg)2561286432168421708010011090IHD mortality(floating absolute risk and 95%CI)A: Systolic blood pressureB: Diastolic blood p

4、ressureAge at rist:80-89Years70-79Yaes60-69years50-59Years40-49yearsAge at rist:80-89Years70-79Yaes60-69years50-59Years40-49yearsLancet 2002,360:1903血壓、年齡與冠心病死亡率(100萬人群資料分析)4降壓治療策略與目標的回顧及進展IHD mortality25612864321684211CauseAge atNumber ofOf deathrisk(years)deathsStroke40-494140.36 (0.32-0.40)50-591

5、3720.38 (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 (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

6、(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 pressureLancet 2002,360:1903收縮壓 20 mmHg 差值對心血管危險影響5降壓治療策略與目標的回顧及進展CauseAge atNumber of0.250.35CauseAge atNumber ofOf de

7、athrisk(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)80-8950680.70 (0.65-0.74)Other40-493160.43 (0.3

8、7-0.50)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 2002,360:1903舒張壓 10 mmHg 差值對心血管危險影響6降壓治療策略與目標的回顧及

9、進展CauseAge atNumber of0.250.35血壓參數預測腦卒中和冠心病死亡率的相對能力 腦卒中 冠心病 SBP 89% 93%DBP 83% 73%PP 37% 43%MAP 100% 97%Mid BP 100% 100%Lancet 2002,360:19037降壓治療策略與目標的回顧及進展血壓參數預測腦卒中和冠心病死亡率的相對能力 ESRD危險性隨血壓升高而增加血壓分級 患者 ESRD數目 年齡校正后的 校正后的RR (n = 322554) (n = 814) 每10萬人年發生率 (95%CI)理想 61089 51 5.3 1.0正常 81621 86 6.6 1.2

10、 (0.8-1.7)正常高值 73798 134 11.1 1.9 (1.4-2.7)高血壓 1級（輕度） 85684 275 21.0 3.1 (2.3-4.3) 2級（中度） 23459 158 43.6 6.0 (4.3-8.4) 3級（重度） 5464 73 96.1 11.2 (7.7-16.2) 4級（極重度）1429 37 187.1 22.1 (14.2-34.3)Klag MJ, Whelton PK, Randali BL et al, New Eng J Med. 1996;334:14-18.8降壓治療策略與目標的回顧及進展ESRD危險性隨血壓升高而增加血壓分級 血壓水

11、平的分類和定義(JNC-7) 分類 收縮壓(mmHg) 舒張壓(mmHg)正常血壓 120 和 80高血壓前期 120 - 139 或 80 - 89高血壓1級 140 - 159 或 90 - 99高血壓2級 160 或 100 9降壓治療策略與目標的回顧及進展血壓水平的分類和定義(JNC-7) 分類 血壓水平的分類和定義(ESH/ESC 2003)分類收縮壓(mmHg)舒張壓(mmHg)理想血壓 120 80正常血壓 120 - 129 80 - 84正常高值 130 - 139 85 - 891級高血壓(輕度) 140 - 159 90 - 992級高血壓(中度) 160 - 179 1

12、00 - 1093級高血壓(重度) 160 110單純收縮期高血壓 140 9010降壓治療策略與目標的回顧及進展血壓水平的分類和定義(ESH/ESC 2003)分類收縮110110119120129130139140149150159160+SBP, mm Hg% of men302520151050Adjusted relative risk5432107070747579808485899094100+DBP, mm Hg% of men302520151050Adjusted relative risk32.521.510.509599MRFIT: Arch Intern Med 19

13、93; 153:59811降壓治療策略與目標的回顧及進展1101101191201291301391401正常血壓者臨界血壓者正常血壓者臨界血壓者90%10%47%53%臨界高血壓轉歸(Tecumsch Study, 3年隨訪)12降壓治療策略與目標的回顧及進展正常血壓者臨界血壓者正常血壓者臨界血壓者90%10%47%5降壓治療臨床試驗薈萃分析結果T = treatmentC = controlNon-fatal eventsFatal eventsTCTCTCTCNumbers individuals020040060080010001200% reductionin oddsStroke3

14、9%CHD16%Vascular deaths21%All other deaths2%13降壓治療策略與目標的回顧及進展降壓治療臨床試驗薈萃分析結果T = treatmentC =0.080.060.040.020012345Years after randomizationIschemic StrokeHemorrhagic StrokePlacebo TreatmentActive TreatmentCumulative Stroke RateSHEP study: JAMA 2000; 284:26514降壓治療策略與目標的回顧及進展0.080.060.040.020012345Yea

15、rs aAnti-hypertensive therapy & incidence of HFn 840 1,627 4,736 4,695 1,148F.U. (mths) 56 25 53 24 101 Reduction 17% 51% 54% 29% 56%p ns 0.01 0.001 ns 0.0043% per year15降壓治療策略與目標的回顧及進展Anti-hypertensive therapy & inTrialNumber of end pointsTreat:ControlOdds rations andconfidence limitsSHEPSYST-EURSY

16、ST-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=0.004SHEPSYST-EURSYST-CH

17、INAALLHeterogeneity:P=0.96Fatal and non-fatal MI(including sudden death)90:11259:7733:44182:233Eur Heart J 1999:1(suppl):p316降壓治療策略與目標的回顧及進展TrialNumber of end pointsOdds Eur Heart J 1999:1(suppl):p3TrialNumber of end pointsTreat:ControlOdds rations andconfidence limitsSHEPSYST-EURSYST-CHINAALLHetero

18、geneity:P=0.38Reduction 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=0.00517降壓治療策略與目標的回顧及進展Eur Heart J 1999:1(suppl):p3TrPROGRESS: 預防腦卒中再發隨訪時間

19、（年）發生事件患者的比例安慰劑組 治療組危險下降28% (95%的可信限 17-38%)P0.0001Lancet 2001; 358: 1033-410.200.150.100.050.00123418降壓治療策略與目標的回顧及進展PROGRESS: 預防腦卒中再發隨訪時間（年）發生事件患降壓治療的益處 平均下降 腦卒中 3540% 心肌梗死 2025% 心力衰竭 50% 19降壓治療策略與目標的回顧及進展降壓治療的益處 TrialsNumber ofOdds ratios Diferecevents/paitients(95% Cls)(SD)OldNewMIDAS/NICS/VHAS15

20、/135815/1353STOP2/CCBs369/2213362/2196NORDIL228/5471153/3157INSIGHT152/3164153/3157ALLHAT/Aml 2203/152551256/9048ELSA 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=

21、0.95UKPDS59/35875/400STOP2/ACEIs369/2213380/2205CAPPP190/5493184/5492ALLHA/Lis2203/152551314/3044ANBP2210/3039195/3044HYVET/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=0.09Heterogen

22、eity P=0.42ALLHAT/Dox851/15268514/9067All trias 4489/532795698/67295-1.8% (2.1) 2P=0.38Heterogeneity P=0.96 降壓治療臨床試驗匯萃分析：總死亡率（CCB、ACEI、ARB vs 利尿劑/b阻滯劑）New drugs betterOld drugs better0123Total mortalityStaessen JA. J Hypertens 2003,21:105520降壓治療策略與目標的回顧及進展TrialsNumber ofOdds ratiosTrialsNumber ofOdd

23、s ratios Diferecevents/paitients(95% Cls)(SD)OldNewMIDAS/NICS/VHAS7/135810/1353STOP2/CCBs221/2213212/2196NORDIL115/5471131/5410INSIGHT52/316460/3157ALLHAT/Aml 992/15255592/9048ELSA 8/11574/1177CCBs without CONVINCE1438/309471039/246852.0% (4.4) 2P=0.64Heterogeneity P=0.59CONVINCE143/8297152/8179All

24、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/AD23/42622/431All ACEIs1539/231461365/191262.2% (4.3) 2P=0.61Heterogeneity P=0.50LIFE 234/4588204/4605SCOPE152/2460145/2477

25、All 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 降壓治療臨床試驗匯萃分析：心血管病死亡率（CCB、ACEI、ARB vs 利尿劑/b阻滯劑）New drugs betterOld drugs better0123Total mortality21降壓治療策略與目標的回顧及進展TrialsNumber ofOdds ratiosTrialsNumber ofOdds ratios

26、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=0.78CONVINCE365/8297364/8179All CC

27、Bs5863/369154347/305203.4% (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 588/4588508/4605SCOPE268/2460242/2477All ARBs856/7

28、048750/7082-14.3% (5.5) 2P=0.004Heterogeneity P=0.69ALLHAT/Dox2245/152681592/9067All trias*7627/5285310728/66864-1.4% (4.8) 2P=0.69Heterogeneity P0.0001 降壓治療臨床試驗匯萃分析：CVD發生率（CCB、ACEI、ARB vs 利尿劑/b阻滯劑）New drugs betterOld drugs better0123Total mortalityStaessen JA. J Hypertens 2003,21:105522降壓治療策略與目標的回顧

29、及進展TrialsNumber ofOdds ratios收縮壓下降與CVD危險匯萃相關分析Staessen 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/SCATHOPEPATSSHEPPROGRES

30、S/ComSTOP1RCT70-80HEPEWPHEMRC2MRC1ATMHSyst-EurSyst-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

31、/NT L vs HDIABHYCARANBP2IDNT2LIFE/ALLSCOPEPREVENTELSAAASK L vs HNICOLELIFE/DM23降壓治療策略與目標的回顧及進展收縮壓下降與CVD危險匯萃相關分析Staessen JA. LIFE:收縮壓差值的意義 Odds Ratio(95% CI) 觀察值 預期值 pAll 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

32、(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)0.82Staessen: Eur Heart J 2003;24:50424降壓治療策略與目標的回顧及進展LIF

33、E:收縮壓差值的意義 ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997.相對危險 (95% CI)氯噻酮更好氨氯地平 0.98 (0.90-1.07)0.71.3 賴諾普利 0.99 (0.91-1.08)氨氯地平更好賴諾普利更好1ALLHAT主要終點：CHD死亡和非致死性心肌梗死25降壓治療策略與目標的回顧及進展ALLHAT Collaborative Research WHO/ISHBlood Pressure LoweringTrialists Collaboration(BPLT臨床試驗協作研究)26降壓治療策略

34、與目標的回顧及進展WHO/ISH26降壓治療策略與目標的回顧及進展BPLT協作研究第二輪分析新入選的臨床試驗AASK ANBP2 ASCOT ALLHAT BENEDICT CONVINCE DIAB-HYCAR ELSA HYVET LIFE PHYLLIS PRIME PROGRESS RENAAL SCOPE SHELL27降壓治療策略與目標的回顧及進展BPLT協作研究第二輪分析新入選的臨床試驗AASK ABPLT協作研究第二輪分析結果(二) RR 95% CIACEI vs 利尿劑/ 阻滯劑 1.09 1.00-1.18CCB vs 利尿劑/ 阻滯劑 0.93 0.86-1.21ACE

35、I vs CCB 1.12 1.01-1.25腦卒中28降壓治療策略與目標的回顧及進展BPLT協作研究第二輪分析結果(二)腦卒中28降壓治療策r=.93,p.001SYST-EURSTOPCoopeSHEPEWPHEMRC-EMRC-I0510152025303514121086420Stroke Rate in Placebo Group (per 1000 pt-yr)Stroke Prevented (per 1000 pt-yr)Lever AF. J Hypertens 1995;13(6):57129降壓治療策略與目標的回顧及進展r=.93,p.001SYST-EURSTOPCoo

36、peSBPLT協作研究第一輪分析結果(二)積極降壓的RR總死亡率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)30降壓治療策略與目標的回顧及進展BPLT協作研究第一輪分析結果(二)積極降壓的RR30降壓0510152025Major CV events/1000 patient yearsTarget DBP mm Hgp=0.005 for trend 90 85 80HOT:目標血壓與CVD事件高血壓合并糖尿病患

37、者31降壓治療策略與目標的回顧及進展0510152025Major CV events/Targ 降壓治療與心血管危險控制基本觀點 臨床試驗證實長期有效降壓治療能減少30%-50% 心腦血管病發生率。 降壓治療的益處主要來自血壓降低。 益處大小受患者心血管危險程度、血壓控制目標 水平、治療方案降壓以外有利作用或不利作用的 影響。32降壓治療策略與目標的回顧及進展 降壓治療與心血管危險控制 臨床試驗證實長期有效降壓治療能血壓控制目標值(JNC-7)高血壓患者： 140/90 mmHg糖尿病和慢性腎臟疾病患者：130/80 mmHg33降壓治療策略與目標的回顧及進展血壓控制目標值(JNC-7)高血

38、壓患者：33降壓治療策略與血壓控制目標值(ESH/ESC 2003)高血壓患者140/90 mmHg糖尿病患者130/80 mmHg34降壓治療策略與目標的回顧及進展血壓控制目標值(ESH/ESC 2003)高血壓患者14JNC-7：降壓治療流程生活方式改變血壓未達到控制目標值 ( 140/90), 糖尿病和慢性腎臟病 ( 180 orDBP 110No other riskfactors12 risk factors3 or more riskfactors or TODor diabetesACCV HIGH RISKV HIGH RISKV HIGH RISK V HIGH RISKHI

39、GH RISKHIGH RISKHIGH RISK MEDIUM RISK MEDIUM RISKMEDIUM RISKLOW RISKSBP 120129 orDBP 8084SBP 130139 orDBP 8589 V HIGH RISKV HIGH RISKAVERAGE RISKLOW RISK LOW RISKAVERAGE RISK心血管危險分層標準(ESH/ESC 2003)MEDIUM RISK HIGH RISK HIGH RISK 38降壓治療策略與目標的回顧及進展BLOOD PRESSURE (mm Hg)SBP 140降壓治療策略與目標的回顧及進展培訓課件靶器官損害(

40、ESH/ESC 2003) 左心室肥厚 (心電圖: Sokolow-Lyons 38 mm, Cornell 2440 mmmms 超聲心動圖: LVMI男 125, 女 110 g/m2) 超聲有動脈壁增厚 (頸動脈IMT 0.9 mm)或粥樣斑塊證據 血肌酐輕度升高 (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)40降壓治療策略與目標的回顧及進展靶器官損害(ESH/ESC 2003) 左心室肥厚40糖尿病(ESH/ESC 2003)空腹血糖 7.0 mmol/L餐后血糖 11.0 mmol/L4

41、1降壓治療策略與目標的回顧及進展糖尿病(ESH/ESC 2003)空腹血糖 7.0 mm并存的臨床情況(ESH/ESC 2003)腦血管病缺血性卒中腦出血短暫性腦缺血發作心臟疾病心肌梗死心絞痛冠狀動脈血運重建充血性心力衰竭腎臟疾病糖尿病腎病腎臟損害(血肌酐男133, 女124 mol/L)蛋白尿(300 mg/24h)周圍血管疾病重度視網膜病變出血或滲出視乳頭水腫42降壓治療策略與目標的回顧及進展并存的臨床情況(ESH/ESC 2003)腦血管病心臟疾病腎降壓治療指征(B)1級和2級高血壓:Very High RiskHigh RiskMedium RiskLow Risk43降壓治療策略與目標的回顧及進展降壓治療指征(B)1級和2級高血壓:Very High Ri降壓治療指征(B)Stratify riskMediumMonitor BP & otherrisk factors for at least 3 monthsSBP 140or DBP 90Begin drugtreatmentSBP 140and DBP 140or DBP 90Consider drugtreatmentSBP 140and DBP 90Continueto monitor44降壓治療策略與目標的回顧及進展降壓治療指征(B