高血压心血管事件的临床研究（PPT 51页）

TheRelationshipofSystolicandDiastolicBloodPressuretoCardiovascularDiseaseRisk:ObservationalDataPrevalenceofHypertensionintheUSPercenthypertensive18-29BasedonNHANESIII(phase1and2)Hypertensiondefinedasbloodpressure140/90mmHgortreatment30-3940-4950-5960-6970-7980+Age3%9%18%38%51%66%72%JNC-VI.ArchInternMed.1997;157:2413-2446.Riskofhypertension(%)Residuallifetimeriskofdevelopinghypertensionamongpeoplewithbloodpressure<140/90mmHgYearsLifetimeRiskofDevelopingHypertensionBeginningatAge65MenWomenVasanRS,etal.JAMA.2002;287:1003-1010.Copyright2002,AmericanMedicalAssociation.MortalityAccordingtoBloodPressureinMenAge50to69SocietyofActuaries.BloodPressureStudy,1939.Ratio(%)ofactualtoexpectedmortalitySystolicbloodpressure(mmHg)Diastolicbloodpressure(mmHg)Age-adjustedannualincidenceofCHDper1000Basedon30yearfollow-upofFraminghamHeartStudysubjectsfreeofcoronaryheartdisease(CHD)atbaselineSystolicbloodpressure(mmHg)BloodPressureandRiskforCoronaryHeartDiseaseinMenDiastolicbloodpressure(mmHg)Age65-94Age35-64Age65-94Age35-64FraminghamHeartStudy,30-yearFollow-up.NHLBI,1987.RelativeriskofCHDmortalityHeJ,etat.AmHeartJ.1999;138:211-219.Copyright1999,MosbyInc.<112<71RiskofCHDDeathAccordingtoSBPandDBPinMRFIT12345678910Decile112-71-118-76-121-79-125-81-129-84-132-86-137-89-142-92->151>98(lowest10%)(highest10%)SBP(mmHg)DBP(mmHg)Systolicbloodpressure(SBP)Diastolicbloodpressure(DBP)CHD=coronaryheartdiseaseRelativeriskofstrokedeath<112<71RiskofStrokeDeathAccordingtoSBPandDBPinMRFIT12345678910Decile112-71-118-76-121-79-125-81-129-84-132-86-137-89-142-92->151>98(lowest10%)(highest10%)SBP(mmHg)DBP(mmHg)Systolicbloodpressure(SBP)Diastolicbloodpressure(DBP)HeJ,etat.AmHeartJ.1999;138:211-219.Copyright1999,MosbyInc.Age-adjustedannualCVDeventrateper1000WilkingSVetal.JAMA.1988;260:3451-3455.MenWomenIsolatedSystolicHypertensionandCVDRiskinFraminghamISHBP160/<95mmHgBP<140/95mmHg8243332.4182.5CVD=cardiovasculardiseaseISH=isolatedsystolichypertensionP<0.001fordifferencebetweenbothmenandwomenwithISHandbloodpressure(BP)<140/95mmHgTheRelationshipofHypertensionTreatmenttoCVDRiskReduction:IntroductionIncidenceofcardiovasculardisease120HypertensionTreatmentEffectMirrorsObservationalData140160180200220ObservationalDataTreatmentEffectSystolicbloodpressure(mmHg)LandmarkClinicalTrialsHypertensionTreatmentandCardiovascularDiseaseOutcomes1967–VACooperativeStudyonDBP115-1291970–VACooperativeStudyonDBP90-1141979–HDFP1980–AustralianTrial,OsloTrial1985–MRCI,EWPHE1991–SHEP,STOP-Hypertension1992–MRCIIintheelderly1997–Syst-Eur2002–LIFE2002–ALLHAT更多内容欢迎莅临天马行空官方博客：http://t.qq.com/tmxk_docinCoopeandWarrender,1986EWPHEStudy,1985SHEPStudy,1991STOP-HypertensionStudy,1991MRCStudy,1992Syst-EurStudy,1997TotalUSPHSStudy,1977HypertensionStrokeStudy,1974VeteransAdministration,1970VeteransAdministration,1967RelativeRiskforCoronaryHeartDiseaseOddsratiosand95%confidenceintervals00.511.520.79(0.69to0.90)HeJ,etal.AmHeartJ.1999;138:211-219.Copyright1999,Mosby,Inc.ActivetreatmentbetterthanplaceboActivetreatmentworsethanplaceboCoopeandWarrender,1986EWPHEStudy,1985SHEPStudy,1991STOP-HypertensionStudy,1991MRCStudy,1992Syst-EurStudy,1997TotalUSPHSStudy,1977HypertensionStrokeStudy,1974VeteransAdministration,1970VeteransAdministration,1967RelativeRiskforStroke00.511.520.63(0.55to0.72)Oddsratiosand95%confidenceintervalsActivetreatmentbetterthanplaceboActivetreatmentworsethanplaceboHeJ,etal.AmHeartJ.1999;138:211-219.Copyright1999,Mosby,Inc.TheVeteransAdministrationCooperativeStudyonAntihypertensiveAgentsTheVACooperativeStudy,1967-43/30mmHgBPchange1.5yearsDurationHCTZ,reserpine,hydralazineTherapyDoubleblind;placebocontrolDesignDiastolicBP115-129mmHgEligibility51yearsMeanage143menCohortVACooperativeStudyGroup.JAMA.1967;202:1028-1034.HCTZ=hydrochlorothiazide-1212TheVACooperativeStudy,1967:ChangeinSystolicandDiastolicBloodPressureChangeinSystolicBP(mmHg)PercentofpatientsPercentofpatientsChangeinDiastolicBP(mmHg)-76-60-44-28028Decrease(-)(+)IncreaseActivedrugsPlaceboActivedrugsPlaceboVACooperativeStudyGroup.JAMA.1967;202:1028-1034.Copyright©1967,AmericanMedicalAssociation.-1212-76-60-44-28028Decrease(-)(+)IncreaseTheVACooperativeStudy,1967:AssessableMorbid/FatalEvents02Coronaryevent14Stroke02CHF04Deaths02Renaldamage012AcceleratedhypertensionActiveRx*n=73Placebon=70VACooperativeStudyGroup.JAMA.1967;202:1028-1034.*P<0.001activedrugtherapyvsplaceboTheVACooperativeStudy,1967:ConclusionsTheactivelytreatedgroupexperiencedareductioninmultiplehypertension-relatedendpoints21morbid/fataleventsonplacebo1morbid/fataleventonactivetherapyVACooperativeStudyGroup.JAMA.1967;202:1028-1034.TheVACooperativeStudy,1970DiastolicBP-19mmHgBPchange5.5years(mean=3.8yrs)DurationHCTZ,reserpine,hydralazineTherapyDoubleblind;placebocontrolDesignDiastolicBP90-114mmHgEligibility50yearsMeanage380menCohortVACooperativeStudyGroup.JAMA.1970;213:1143-1152.611Fatalcoronaryevent1113Totalcoronaryevent520Stroke011Congestiveheartfailure819Deaths03Renaldamage04AcceleratedhypertensionActiveRx*n=186Placebon=194TheVACooperativeStudy,1970:AssessableMorbid/FatalEventsVACooperativeStudyGroup.JAMA.1970;213:1143-1152.*P<0.001activedrugtherapyvsplaceboTheVACooperativeStudy,1970:ConclusionsActivetreatmentreducedfatalandnonfatalendpointsAsubsequentanalysisrevealedthatbenefitswerestatisticallysignificantonlyforthosewithbaselinediastolicbloodpressure105-114mmHgVACooperativeStudyGroup.Circulation.1972;45(5):991-1004.VACooperativeStudyGroup.JAMA.1970;213:1143-1152.TheEuropeanWorkingPartyonHighBloodPressureintheElderly,1985TheEuropeanWorkingPartyonHighBloodPressureintheElderly,1985-21/10mmHgat5yearsBPchange4.7yearsDurationHCTZ,triamtereneTherapyDoubleblind;placebocontrolDesignSystolicBP150239mmHg;diastolicBP90119mmHgEligibility>60yrsold;mean72yrsoldAge840;30%menCohortAmeryA,etal.Lancet.1985;1:1349-1354.Survivalfreeofevent(%)Yearoffollow-upEWPHECardiovascularMortalityOn-TreatmentAnalysisActive(n=416)Placebo(n=424)P=0.02301362457AmeryA,etal.Lancet.1985;1:1349-1354.ReprintedwithpermissionfromElsevierScience.EWPHE=EuropeanWorkingPartyonHighBloodPressureintheElderlyEWPHEConclusionsActivetreatmentreducedcardiovascular(CV)mortality,largelyduetoareductionincardiacmortalityOlderpatients(>60yrsold)withcombinedsystolicanddiastolichypertensionwhoreceivedactivetherapyexperienced29fewerCVeventsand14fewerCVdeathsper1,000patient-yearsoftreatmentAmeryA,etal.Lancet.1985;1:1349-1354.EWPHE=EuropeanWorkingPartyonHighBloodPressureintheElderlyTheHypertensionDetectionandFollow-upProgram,1979TheHypertensionDetectionandFollow-upProgram,19795mmHg(SteppedCarevsReferredCare)BPchange5yearsDurationChlorthalidone(reserpine,methyldopa)TherapySteppedCarevsReferredCareDesignDiastolicBP90mmHgEligibility3069yrsold;mean50.8yrsoldAge10,940;54%men;44%blackCohortHDFPCooperativeGroup.JAMA.1979;242:2562-2571.Cumulativemortality(%)0136Yearoffollow-upHDFPMortalityRatesEntireCohort245ReferredCareSteppedCareHDFP=HypertensionDetectionandFollow-upProgram*P<0.01HDFPCooperativeGroup.JAMA.1979;242:2562-2571.(n=5,456)(n=5,485)*0136245Cumulativemortality(%)HDFPMortalityRatesDiastolicBP90104mmHgReferredCareSteppedCareHDFP=HypertensionDetectionandFollow-upProgramYearoffollow-up*P<0.01HDFPCooperativeGroup.JAMA.1979;242:2562-2571.(n=3,822)(n=3,903)*BP=bloodpressureHDFPConclusionsOverall,steppedcare(SC)comparedtoreferredcare(RC)reducedtotalmortalityby17%(6.4vs.7.7%;P<0.01)Inpatientswithbaselinediastolicbloodpressure90104mmHg(n=7,725),mortalitywasreducedby20%withSCvs.RC(5.9%vs.7.4%;P<0.01)AggressivetreatmentofSCpatientswiththelowestbaselinediastolicbloodpressures(9094and9599mmHg)reducedmortalityHDFP=HypertensionDetectionandFollow-upProgramHDFPCooperativeGroup.JAMA.1979;242:2562-2571.TheSystolicHypertensionintheElderlyProgram,1991TheSystolicHypertensionintheElderlyProgram,1991SHEPResearchGroup.JAMA.1991;265:3255-3264.SystolicBP–12mmHgBPchange4.5yearsDurationChlorthalidone(atenololasstep2)TherapyDoubleblind;placebocontrolDesignSystolicBP160219mmHgandDiastolicBP<90mmHgEligibility60yrsold;mean71.6yrsoldAge4,736;43%menCohortBP=bloodpressureChangeinBP(mmHg)YearsSHEPChangeinBloodPressurePlacebo(n=2,371)ActiveRx(n=2,365)Years012345012345SystolicBPDiastolicBPSHEPResearchGroup.JAMA.1991;265:3255-3264.Copyright©1991,AmericanMedicalAssociation.BP=bloodpressureSHEP=SystolicHypertensionintheElderlyProgramPlacebo(n=2,371)ActiveRx(n=2,365)Bloodpressure(mmHg)0123660Monthsoffollow-upSHEPAverageBloodPressureDuringFollow-up24480SHEP=SystolicHypertensionintheElderlyProgramSHEPResearchGroup.JAMA.1991;265:3255-3264.Copyright©1991,AmericanMedicalAssociation.Cumulativestrokerateper100persons0123660Monthsoffollow-upSHEPCumulativeStrokeRate244872P=0.0003Placebo(n=2,371)ActiveRx(n=2,365)SHEP=SystolicHypertensionintheElderlyProgramSHEPResearchGroup.JAMA.1991;265:3255-3264.Copyright©1991,AmericanMedicalAssociation.Relativerisk(95%CI)StrokeCHDActiveTherapyvs.PlaceboCHFDeath0.630.460.680.87CVD0.75SHEPCardiovascularDiseaseEndpointsSHEPResearchGroup.JAMA.1991;265:3255-3264.SHEP=SystolicHypertensionintheElderlyProgramCHD=coronaryheartdisease;CHF=congestiveheartfailure;CVD=cardiovasculardiseaseSHEPConclusionsSHEPwasthefirstclinicaltrialtodemonstratethatreductionofbloodpressureinpatientswithisolatedsystolichypertensionreducedcardiovascular(CV)mortalityTherelativeriskofstrokewasreducedby36%withtherapycomparedtoplacebo(P=0.0003)The5-yearabsolutebenefitswereareductionin30strokesand55majorCVdiseaseeventsper1,000personsSHEPResearchGroup.JAMA.1991;265:3255-3264.SHEP=SystolicHypertensionintheElderlyProgramTheSystolicHypertensioninEurope(Syst-Eur)Trial,1997TheSystolicHypertensioninEuropeTrial,1997-10/5mmHgBPdifferenceMedian2yrs(1-97months)DurationNitrendipine(enalapril,HCTZasStep2)TherapyDoubleblind;placebocontrolDesignSystolicBP160–219mmHganddiastolicBP<95mmHgEligibility60yrsoldAge4,695;67%womenCohortStaessenJA,etal.Lancet.1997;350:757-764.SystolicBP(mmHg)Syst-EurMeanSittingSystolicBloodPressure0Placebo(n=2,297)Activetreatment(n=2,398)1234YearssincerandomizationStaessenJA,etal.Lancet.1997;350:757-764.ReprintedwithpermissionfromElsevierScience.Syst-Eur=SystolicHypertensioninEuropeTrialP<0.001Syst-EurMeanSittingDiastolicBloodPressure01234DiastolicBP(mmHg)Placebo(n=2,297)Activetreatment(n=2,398)P<0.001YearssincerandomizationStaessenJA,etal.Lancet.1997;350:757-764.ReprintedwithpermissionfromElsevierScience.Syst-Eur=SystolicHypertensioninEuropeTrialEventsper100patientsSyst-EurPrimaryEndpointFatalandNonfatalStrokePlacebo(n=2,297)Activetreatment(n=2,398)01342P=0.003YearssincerandomizationStaessenJA,etal.Lancet.1997;350:757-764.ReprintedwithpermissionfromElsevierScience.Syst-Eur=SystolicHypertensioninEuropeTrialPercentagerelativeriskreduction(95%CI)StrokeMIActivetherapyvs.placeboCHFDeath42%P=0.00329%31%P<0.00114%AllCVD30%Syst-EurCardiovascularDiseaseEndpointsStaessenJA,etal.Lancet.1997;350:757-764.MI=myocardialinfarction;CHF=congestiveheartfailure;CVD=cardiovasculardiseaseSyst-Eur=SystolicHypertensioninEuropeTrialSyst-EurConclusionsOldermenandwomenwithisolatedsystolichypertensionwhoreceivedactivetreatmentwithadihydropyridinecalciumchannelblockerexperiencedfewerstrokesandcardiovasculardisease(CVD)eventsthanthosereceivingplacebo.Treatmentof1,000patientsfor5yearswiththistypeofregimencouldprevent29strokesor53majorCVDendpoints.StaessenJA,etal.Lancet.1997;350:757-764.Syst-Eur=SystolicHypertensioninEuropeTrialTheAustralianNationalBloodPressure(ANBP)Study,1980TheAustralianNationalBloodPressureStudy,1980TheAustralianStudyCommittee.Lancet.1980;1:1261-1267.-6mmHgBPdifference4yrsDurationChlorothiazide(methyldopa,betablocker)TherapySingleblind;placebocontrolDesignDiastolicBP95–109mmHgEligibility30–69yrsoldAge3,427;80%menCohortTheAustralianStudyMeanDiastolicBloodPressureDiastolicbloodpressure(mmHg)TheAustralianStudyCommittee.Lancet.1980;1:1261-1267.TheAustralianStudyIncidenceofTrialEndpoints(TEP)*3.6255.1Intention-to-treatActive(n=1,721)Placebo(n=1,706)24.519.42.52.6Rate138113178No.1.1‡18Cardiovascular19.7†168AllTEP16.2133Non-fatalTEP2.417Non-cardiovascular35TotalFatalTEPRateNo.*Ratesper1,000person-yearsexposuretorisk.†P<0.05‡P<0.025TheAustralianStudyCommittee.Lancet.1980;1:1261-1267.TheAustralianStudyIntention-to-TreatTrialEndpoints617410365285Activen=1,721Placebon=1,70616Hemorrhageorthrombosis10Othernonfatal18Otherfatal9TransientcerebralischemicattacksCerebrovascularevents22Nonfatalmyocardialinfarction11Fatal676No.ofeventsNonfatalFatalNonfatalotherIschemicheartdiseaseTheAustralianStudyCommittee.Lancet.1980;1:1261-1267.TheAustralianStudyOn-TreatmentTrialEndpoints(TEP)NumberoftrialendpointsDaysintrial200016001200600400AllTEPP<0.01AllFatalTEPP<0.05Active(n=1,721)Placebo(n=1,706)TheAustralianStudyCommittee.Lancet.1980;1:1261-1267.ReprintedwithpermissionfromElsevierScience.TheAustralianStudyConclusionsTheactivelytreatedcomparedtoplacebogroupexperienced30fewertrialendpointsendpoints(P<0.05)Therewasasignificantreductioninmortalityintheactivelytreatedgroup,mostlyduetoareductionindeathfromcardiovasculardisease(P<0.025)TheAustralianStudyCommittee.Lancet.1980;1:1261-1267.