高血壓心血管事件的臨床研究課件

1、The Relationship of Systolic and Diastolic Blood Pressure to Cardiovascular Disease Risk: Observational DataPrevalence of Hypertension in the USPercent hypertensive18-29Based on NHANES III (phase 1 and 2)Hypertension defined as blood pressure 140/90 mmHg or treatment30-3940-4950-5960-6970-7980+Age3

2、%9 %18 %38 %51 %66 %72 %JNC-VI. Arch Intern Med. 1997;157:2413-2446.Risk of hypertension (%)Residual lifetime risk of developing hypertension among people with blood pressure 140/90 mmHgYearsLifetime Risk of Developing Hypertension Beginning at Age 65MenWomenVasan RS, et al. JAMA. 2002; 287:1003-101

3、0.Copyright 2002, American Medical Association.Mortality According to Blood Pressure in Men Age 50 to 69Society of Actuaries. Blood Pressure Study, 1939.Ratio (%) of actual to expected mortalitySystolic blood pressure (mmHg)Diastolic blood pressure (mmHg)Age-adjusted annualincidence of CHD per 1000B

4、ased on 30 year follow-up of Framingham Heart Study subjects free of coronary heart disease (CHD) at baselineSystolic blood pressure (mmHg)Blood Pressure and Risk for Coronary Heart Disease in MenDiastolic blood pressure (mmHg)Age 65-94Age 35-64Age 65-94Age 35-64Framingham Heart Study, 30-year Follo

5、w-up. NHLBI, 1987.Relative risk of CHD mortality He J, et at. Am Heart J. 1999;138:211-219.Copyright 1999, Mosby Inc.11215198(lowest 10%)(highest 10%)SBP (mmHg)DBP (mmHg)Systolic blood pressure (SBP)Diastolic blood pressure (DBP)CHD=coronary heart diseaseRelative risk of stroke death 11215198(lowest

6、 10%)(highest 10%)SBP (mmHg)DBP (mmHg)Systolic blood pressure (SBP)Diastolic blood pressure (DBP)He J, et at. Am Heart J. 1999;138:211-219.Copyright 1999, Mosby Inc.Age-adjusted annual CVD event rate per 1000Wilking SV et al. JAMA. 1988;260:3451-3455.MenWomenIsolated Systolic Hypertension and CVD Ri

7、sk in FraminghamISH BP 160/95 mmHgBP 140/95 mmHg8243332.4182.5CVD=cardiovascular disease ISH=isolated systolic hypertensionP0.001 for difference between both men and women with ISH and blood pressure (BP) 140/95 mmHgThe Relationship of Hypertension Treatment to CVD Risk Reduction:IntroductionInciden

8、ce of cardiovascular disease120Hypertension Treatment Effect Mirrors Observational Data140160180200220Observational DataTreatment EffectSystolic blood pressure (mmHg)Landmark Clinical TrialsHypertension Treatment and Cardiovascular Disease Outcomes1967 VA Cooperative Study on DBP 115-1291970 VA Coop

9、erative Study on DBP 90-1141979 HDFP1980 Australian Trial, Oslo Trial1985 MRC I, EWPHE1991 SHEP, STOP-Hypertension 1992 MRC II in the elderly1997 Syst-Eur 2002 LIFE2002 ALLHATVeterans Administration, 1967Veterans Administration, 1970Hypertension Stroke Study, 1974USPHS Study, 1977EWPHE Study, 1985Co

10、ope and Warrender, 1986SHEP Study, 1991STOP-Hypertension Study, 1991MRC Study, 1992Syst-Eur Study, 1997TotalRelative Risk for Coronary Heart DiseaseOdds ratios and95% confidence intervals00.511.520.79(0.69 to 0.90)He J, et al. Am Heart J. 1999; 138:211-219.Copyright 1999, Mosby, Inc.Active treatment

11、 better than placeboActive treatment worse than placeboVeterans Administration, 1967Veterans Administration, 1970Hypertension Stroke Study, 1974USPHS Study, 1977EWPHE Study, 1985Coope and Warrender, 1986SHEP Study, 1991STOP-Hypertension Study, 1991MRC Study, 1992Syst-Eur Study, 1997TotalRelative Ris

12、k for Stroke 00.511.520.63(0.55 to 0.72)Odds ratios and95% confidence intervalsActive treatment better than placeboActive treatment worse than placeboHe J, et al. Am Heart J. 1999; 138:211-219.Copyright 1999, Mosby, Inc.The Veterans Administration Cooperative Study on Antihypertensive AgentsThe VA C

13、ooperative Study, 1967Cohort143 menMean age51 yearsEligibilityDiastolic BP 115-129 mmHgDesignDouble blind; placebo controlTherapyHCTZ, reserpine, hydralazineDuration1.5 yearsBP change-43/30 mmHgVA Cooperative Study Group. JAMA. 1967;202:1028-1034.HCTZ=hydrochlorothiazide -1212The VA Cooperative Stud

14、y, 1967: Change in Systolic and Diastolic Blood PressureChange in Systolic BP (mmHg)Percent of patientsPercent of patientsChange in Diastolic BP (mmHg)-76-60-44-28028Decrease (-)(+) IncreaseActive drugsPlaceboActive drugsPlaceboVA Cooperative Study Group. JAMA. 1967;202:1028-1034.Copyright 1967, Ame

15、rican Medical Association.-1212-76-60-44-28028Decrease (-)(+) IncreaseThe VA Cooperative Study, 1967:Assessable Morbid/Fatal EventsPlacebon=70Active Rx*n=73 Accelerated hypertension120Stroke41Coronary event20CHF20Renal damage20Deaths40VA Cooperative Study Group. JAMA. 1967;202:1028-1034.*P0.001 acti

16、ve drug therapy vs placebo The VA Cooperative Study, 1967:ConclusionsThe actively treated group experienced a reduction in multiple hypertension-related endpoints21 morbid/fatal events on placebo1 morbid/fatal event on active therapyVA Cooperative Study Group. JAMA. 1967;202:1028-1034.The VA Coopera

17、tive Study, 1970Cohort380 menMean age50 yearsEligibilityDiastolic BP 90-114 mmHgDesignDouble blind; placebo controlTherapyHCTZ, reserpine, hydralazineDuration5.5 years (mean=3.8 yrs)BP changeDiastolic BP -19 mmHgVA Cooperative Study Group. JAMA. 1970;213:1143-1152.Placebon=194Active Rx*n=186 Acceler

18、ated hypertension40Stroke205Total coronary event1311Fatal coronary event116Congestive heart failure110Renal damage30Deaths198The VA Cooperative Study, 1970:Assessable Morbid/Fatal EventsVA Cooperative Study Group. JAMA. 1970;213:1143-1152.*P 60 yrs old; mean 72 yrs oldEligibilitySystolic BP 150239 m

19、mHg; diastolic BP 90119 mmHgDesignDouble blind; placebo controlTherapyHCTZ, triamtereneDuration4.7 yearsBP change-21/10 mmHg at 5 yearsAmery A, et al. Lancet. 1985;1:1349-1354. Survival free of event (%)Year of follow-upEWPHE Cardiovascular Mortality On-Treatment AnalysisActive (n=416)Placebo (n=424

20、)P=0.02301362457Amery A, et al. Lancet. 1985;1:1349-1354.Reprinted with permission from Elsevier Science. EWPHE=European Working Party on High Blood Pressure in the Elderly EWPHEConclusionsActive treatment reduced cardiovascular (CV) mortality, largely due to a reduction in cardiac mortalityOlder pa

21、tients (60 yrs old) with combined systolic and diastolic hypertension who received active therapy experienced 29 fewer CV events and 14 fewer CV deaths per 1,000 patient-years of treatmentAmery A, et al. Lancet. 1985;1:1349-1354. EWPHE=European Working Party on High Blood Pressure in the Elderly The

22、 Hypertension Detection and Follow-up Program, 1979The Hypertension Detection and Follow-up Program, 1979Cohort10,940; 54% men; 44% blackAge3069 yrs old; mean 50.8 yrs oldEligibilityDiastolic BP 90 mmHgDesignStepped Care vs Referred CareTherapyChlorthalidone (reserpine, methyldopa)Duration5 yearsBP

23、change5 mmHg (Stepped Care vs Referred Care)HDFP Cooperative Group. JAMA. 1979;242:2562-2571. Cumulative mortality (%)0136Year of follow-upHDFP Mortality RatesEntire Cohort245Referred CareStepped CareHDFP=Hypertension Detection and Follow-up Program *P0.01 HDFP Cooperative Group. JAMA. 1979;242:2562

24、-2571. (n=5,456) (n=5,485) *0136245Cumulative mortality (%)HDFP Mortality RatesDiastolic BP 90104 mmHgReferred CareStepped CareHDFP=Hypertension Detection and Follow-up Program Year of follow-up*P0.01 HDFP Cooperative Group. JAMA. 1979;242:2562-2571. (n=3,822) (n=3,903) *BP=blood pressureHDFPConclus

25、ionsOverall, stepped care (SC) compared to referred care (RC) reduced total mortality by 17% (6.4 vs. 7.7%; P0.01)In patients with baseline diastolic blood pressure 90104 mmHg (n=7,725), mortality was reduced by 20% with SC vs. RC (5.9% vs. 7.4%; P0.01)Aggressive treatment of SC patients with the lo

26、west baseline diastolic blood pressures (9094 and 9599 mmHg) reduced mortalityHDFP=Hypertension Detection and Follow-up Program HDFP Cooperative Group. JAMA. 1979;242:2562-2571. The Systolic Hypertension in the Elderly Program, 1991The Systolic Hypertension in the Elderly Program, 1991SHEP Research

27、Group. JAMA. 1991;265:3255-3264.Cohort4,736; 43% menAge 60 yrs old; mean 71.6 yrs oldEligibilitySystolic BP 160219 mmHg and Diastolic BP 90 mmHgDesignDouble blind; placebo controlTherapyChlorthalidone (atenolol as step 2)Duration4.5 yearsBP changeSystolic BP 12 mmHgBP=blood pressureChange in BP (mmH

28、g)YearsSHEPChange in Blood PressurePlacebo (n=2,371)Active Rx (n=2,365)Years012345012345Systolic BPDiastolic BPSHEP Research Group. JAMA. 1991;265:3255-3264.Copyright 1991, American Medical Association.BP=blood pressureSHEP=Systolic Hypertension in the Elderly Program Placebo (n=2,371)Active Rx (n=2

29、,365)Blood pressure (mmHg)0123660Months of follow-upSHEPAverage Blood Pressure During Follow-up24480SHEP=Systolic Hypertension in the Elderly Program SHEP Research Group. JAMA. 1991;265:3255-3264.Copyright 1991, American Medical Association.Cumulative stroke rate per 100 persons0123660Months of foll

30、ow-upSHEPCumulative Stroke Rate244872P=0.0003Placebo(n=2,371)Active Rx (n=2,365)SHEP=Systolic Hypertension in the Elderly Program SHEP Research Group. JAMA. 1991;265:3255-3264.Copyright 1991, American Medical Association.Relative risk (95% CI)StrokeCHDActive Therapy vs. PlaceboCHFDeath0.630.460.680.

31、87CVD0.75SHEPCardiovascular Disease EndpointsSHEP Research Group. JAMA. 1991;265:3255-3264.SHEP=Systolic Hypertension in the Elderly Program CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease SHEPConclusionsSHEP was the first clinical trial to demonstrate that reduc

32、tion of blood pressure in patients with isolated systolic hypertension reduced cardiovascular (CV) mortalityThe relative risk of stroke was reduced by 36% with therapy compared to placebo (P=0.0003)The 5-year absolute benefits were a reduction in 30 strokes and 55 major CV disease events per 1,000 p

33、ersonsSHEP Research Group. JAMA. 1991;265:3255-3264.SHEP=Systolic Hypertension in the Elderly Program The Systolic Hypertension in Europe (Syst-Eur) Trial, 1997The Systolic Hypertension in Europe Trial, 1997Cohort4,695; 67% womenAge 60 yrs oldEligibilitySystolic BP 160219 mmHg and diastolic BP 95 mm

34、HgDesignDouble blind; placebo controlTherapyNitrendipine (enalapril, HCTZ as Step 2)DurationMedian 2 yrs (1-97 months)BP difference-10/5 mmHgStaessen JA, et al. Lancet. 1997;350:757-764.Systolic BP (mmHg)Syst-Eur Mean Sitting Systolic Blood Pressure0Placebo (n=2,297)Active treatment (n=2,398) 1234Ye

35、ars since randomizationStaessen JA, et al. Lancet. 1997;350:757-764.Reprinted with permission from Elsevier Science.Syst-Eur=Systolic Hypertension in Europe Trial P0.001Syst-Eur Mean Sitting Diastolic Blood Pressure01234Diastolic BP (mmHg)Placebo (n=2,297)Active treatment (n=2,398) P0.001Years since

36、 randomizationStaessen JA, et al. Lancet. 1997;350:757-764.Reprinted with permission from Elsevier Science.Syst-Eur=Systolic Hypertension in Europe Trial Events per 100 patientsSyst-Eur Primary EndpointFatal and Nonfatal StrokePlacebo (n=2,297)Active treatment (n=2,398) 01342P=0.003Years since rando

37、mizationStaessen JA, et al. Lancet. 1997;350:757-764.Reprinted with permission from Elsevier Science.Syst-Eur=Systolic Hypertension in Europe Trial Percentage relative risk reduction (95% CI)StrokeMIActive therapy vs. placeboCHFDeath42%P=0.00329%31%P0.00114%All CVD30%Syst-EurCardiovascular Disease E

38、ndpointsStaessen JA, et al. Lancet. 1997;350:757-764.MI=myocardial infarction; CHF=congestive heart failure; CVD=cardiovascular disease Syst-Eur=Systolic Hypertension in Europe Trial Syst-Eur ConclusionsOlder men and women with isolated systolic hypertension who received active treatment with a dihy

39、dropyridine calcium channel blocker experienced fewer strokes and cardiovascular disease (CVD) events than those receiving placebo.Treatment of 1,000 patients for 5 years with this type of regimen could prevent 29 strokes or 53 major CVD endpoints.Staessen JA, et al. Lancet. 1997;350:757-764.Syst-Eu

40、r=Systolic Hypertension in Europe Trial The Australian National Blood Pressure (ANBP) Study, 1980The Australian National Blood Pressure Study, 1980The Australian Study Committee. Lancet. 1980;1:1261-1267.Cohort3,427; 80% menAge3069 yrs oldEligibilityDiastolic BP 95109 mmHgDesignSingle blind; placebo controlTherapyChlorothiazide (methyldopa, beta blocker)Duration4 yrsBP difference-6 mmHgThe Australian Study Mean Diastolic Blood PressureDiastolic blood pressure (mmHg)The Australian Study Committee. Lancet. 1980;1:1261-1267.The Australian Study Incidence of Trial Endpoints (TEP)*Intention-to-tr