高血压英文ppt精品课件clinicaltrials of antihypertensive medication for mci and

ClinicalTrialsofAnti HypertensiveMedicationforMCIanddementia IngmarSkoog M D Ph D InstituteofNeuroscienceandPhysiologyUnitofNeuropsychiatricEpidemiologySahlgrenskaAcademyatG teborgUniversityG teborg Sweden DISCLOSURES Consultant AstraZenecafortheSCOPEtrialSpeakersBureau Esai JansenCilag AstraZeneca Shire Pfizer Novartis Background PrevalenceofhypertensionincreaseswithageMorethan50 ofelderlypopulationshavehypertensionwithcurrentcriteria 140 90 Anemergingprobleminthedevelopingworld End organdamage ThearterialtreeHeartKidneyBrainEyes SystolicBloodPressure 140 CardiovascularRisk HYPERTENSIONINRELATIONTOCOGNITION HypertensionStrokeWhiteMatterLesionsCognitiveimpairment AB rjessonHanson2001 Hypertensionandthebrain CerebralautoregulationBloodbrainbarrierdysfunctionDecreasedcerebralbloodfloowStroke hemorrhagic ischemic WhitematterlesionsDementiaandAlzheimer sdisease RISKOFDEMENTIAINRELATIONTOSTROKE70 G teborg Lind n SkoogetalNeuroepidemiology2004 Cognitiveimpairmentinnon dementedstrokepatients70 G teborg Lind n SkoogetalNeuroepidemiology2004 SILENTINFARCTS ThefrequencyofsilentinfarctsonMRIincreaseswithage Vermeeretal Stroke2003 Increasestheincidenceofdementia HR2 3 95 CI1 1 4 7 during3 6yearsfollow upRelatedtoworseperformanceonpsychometrictestingatbaselineIncreasesriskofclinicalstrokeonfollow up Vermeeretal NEnglJMed2003 RISKOFDEMENTIAINRELATIONTOINFARCTSONCTANDHISTORYOFSTROKEATAGE85H 70STUDY G TEBORG SWEDEN Liebetrau Skoog Stroke2004 Hypertensionandthebrain CerebralautoregulationBloodbrainbarrierdysfunctionDecreasedcerebralbloodfloowStroke hemorrhagic ischemic WhitematterlesionsDementiaandAlzheimer sdisease WHITEMATTERLESIONSINRELATIONTODEMENTIAIN85 YEAR OLDS Nodementia34Alzheimer sdisease64 Vasculardementia70 Otherdementias80 SkoogetalJGeriatrPsychiatryNeurol1994 Cognitivefunctioninnon demented85 year oldsinrelationtowhitematterlesions Skoogetal ActaNeurolScand1996 Hypertensionandthebrain CerebralautoregulationBloodbrainbarrierdysfunctionDecreasedcerebralbloodfloowStroke hemorrhagic ischemic WhitematterlesionsAlzheimer sdisease LONGITUDINALSTUDIESONBLOODPRESSUREANDALZHEIMER SDISEASE Previoushighbloodpressure5 15yearsAlzheimer sdiseaseinlatelife TheH70 studyinGothenburgSkoogetal Lancet1996TheHonolulu AsiaAgingStudyLauneretal NeurobiolAging2000TheRotterdamStudyRuitenbergetal Dissertation2000KaiserPermanente USAWhitmeretal Neurology2005 Kuopio FinlandKivipeltoetal BMJ2001KungsholmenStudyQiuetalArchNeurol2003ChineseStudyWuetalLifeScience2003 RelationtoADpathology HONOLULU ASIAAGINGSTUDY HighmidlifesystolicbloodpressureNeuriticplaque inoldage Petrovitchetal NeurobiologyofAging2000 Possiblepathogeneticmechanisms Ischemiaincreasesproductionofbeta amyloidBlood brainbarrierdysfunctionRenin angiotensinsystem A15 yearfollow upofbloodpressureanddementia Skoogetal Lancet1996 BLOODPRESSUREINALZHEIMER SDISEASE IncreasedbeforeonsetLowerjustbeforeorafteronset HypertensionandriskofMCI Reitzetal ArchNeurol 2007 64 1734 40 Bloodpressureandcognitivefunction Midlife HighbloodpressurerelatedtolowercognitivefunctionOldage Lowbloodpressurerelatedtolowercognitivefunction TreatmentofhypertensionandMCI dementia Alzheimerdisease ANTIHYPERTENSIVEDRUGS AngiotensinConvertingEnzymeInhibitorsorAngiotensinIItype1 AT1 receptorblockerBeta blockersCalcium channelblockersDiuretics Treatmenttargetsinrelationtodementia MCI Dementia ADLSocialabiliy MildCognitiveImpairment Normal Observationalstudies BLOODPRESSUREANDDEMENTIA ISITDANGEROUSTOTREATHYPERTENSIONINTHEELDERLY A15 yearfollow upofbloodpressureandAlzheimer sdisease Skoogetal Lancet1996 BLOODPRESSUREINRELATIONTODEMENTIAIN85 YEAR OLDS BloodpressuremmHgmmHgmmHgSystolic162148 151 Diastolic797876 NoAlzheimer sVascularDementiadiseasedementia Skoogetal Hypertension1998 LOWBLOODPRESSUREANDALZHEIMER SDISEASE AriskfactorforAlzheimer sdisease AconsequenceofAlzheimer sdisease BloodpressuredecreasesduringthecourseofAlzheimer sdiseaseLowerbloodpressureisrelatedtobrainatrophyandnumberofneuronsincertainareasofthebrain HONOLULU ASIAAGINGSTUDY HighmidlifebloodpressureinmennottreatedforhypertensionAlzheimer sdiseaseinoldageVasculardementiainoldage Launeretal NeurobiologyofAging2000 ProspectivePopulationStudyofWomeninGothenburg HighmidlifebloodpressureinwomennottreatedforhypertensionDementiainoldage Skoogetal2008 ANTIHYPERTENSIVEDRUGSANDRISKOFDEMENTIA Indianapolis prevalence ORDementia0 67Alzheimer sDisease0 59 Richardsetal JAmGeriatrSoc2000 48 1035 41Kungsholmen incidence RR 95 CI Dementia0 7 0 6 1 0 Guoetal ArchNeurol1999 56 991 996Rotterdam incidence RR 95 CI Dementia0 76 0 52 1 12 Vasculardementia0 30 0 11 0 99 In tVeldetal NeurobiolAging 2001 22 407 412CasheCountyStudy incidence RR 95 CI Alzheimer sdisease0 64 0 41 0 98 Khachaturianetal ArchNeurol2006 63 686 92 HonoluluAsiaStudy Foreachadditionalyearofantihypertensivetreatmenttherewasareductionintheriskofincidentdementia hazardratio HR 0 94 95 CI 0 89to0 99 SameresultforincidentAlzheimer sdiseaseThus thelongertimeontreatment thelowerriskofdementia Peilaetal Stroke2006 RISKFACTORSDEMENTIA SBU Strong moderateevidence Age ApoEe4FamilyaggregationMidlifebloodpressureDiabetesmellitusAntihypertensivedrugs protective LoweducationLeisureactivity protective Fratiglionietal PREVIOUSDATAAREBASEDONOBSERVATIONALSTUDIESRANDOMISEDCONTROLLEDTRIALSMORERELIABLETHANOBSERVATIONALSTUDIES WHATHAVEWELEARNEDFROMRANDOMISEDCONTROLLEDPREVENTIONTRIALS LARGEHYPERTENSIONTRIALS SystolicHypertensionintheElderlyProgram SHEP N 4736 Chlorthalidon D MedicalResearchCouncil s MRC TreatmentTrialofhypertension N 4396 Atenolol B Hydrochlorthiazide D TheSystolicHypertensioninEuropeStudy Syst Eur N 2418 Nitrendipine C TheStudyonCognitionandPrognosisintheElderly SCOPE N 4937 Candersatan A PerindoprilProtectionagainstRecurrentStrokeStudy PROGRESS N 6105 Perindopril A TheHypertensionintheVeryElderlyTrial HYVET N 3336 Indapamide D perindopril A LARGEHYPERTENSIONTRIALS SystolicHypertensionintheElderlyProgram SHEP N 4736 ChlorthalidonMedicalResearchCouncil s MRC TreatmentTrialofhypertension N 4396 Atenolol HydrochlorthiazideTheSystolicHypertensioninEuropeStudy Syst Eur N 2418 NitrendipineTheStudyonCognitionandPrognosisintheElderly SCOPE N 4937 CandersatanPerindoprilProtectionagainstRecurrentStrokeStudy PROGRESS N 6105 PerindoprilTheHypertensionintheVeryElderlyTrial HYVET N 3336 Indapamide perindopril NEnglJMed2008 LancetNeurol2008 SAMPLES SHEP160 219 90MRC160 209 115Syst Eur160 219 95Nodementia PROGRESSPriorstrokeorTIAMeanage64SCOPE160 179 90 99MMSE24 30NodementiaHYVETSBPabove160Ageabove80 COGNITIVEEND POINTS Dementia SHEP Syst Eur SCOPE PROGRESS HYVET SignificantCognitiveDecline PROGRESS SCOPE COGNITIVEEND POINTS MeanchangeincognitivefunctionSyst Eur Progress SCOPEMiniMentalStateExamination MMSE MRC Pairedassociatelearning TrailMakingTest MAINRESULTSCardiovascularendpoints AntihypertensivetreatmentreducedriskofmostcardiovascularendpointsinclstrokeAlsoinHYVET whichonlyincludedpersonsaboveage80 NEnglJMed2008 MAINRESULTSDEMENTIA Decreasedincidenceofdementia Syst Eur Nodifference SHEP SCOPE Progress HYVET Nohypertensiontrialshowincreasedriskfordementiaorcognitivedecline MAINRESULTSMEANCOGNITIVECHANGE Nodifference MRC SHEP SCOPE Syst Eur Lessdeclineinactivetreatmentgroup PROGRESS WHYSONEGATIVERESULTS Methodologicalissues AgeHealthyvolunteereffectSelectiveattrition missingdataTimeoffollow upTimeinrelationtodementiaDiagnosisanddetectionofdementiaTestingCeilingeffectLearningeffectSensitivitytochangeSubgroups Riskgroups TypeofdrugEffectotherthanbloodpressure SAMPLES SHEPAboveage60MRCAge65 74Syst EurAboveage60 mean70 NodementiaHYVETAgeabove80 PROGRESSPriorstrokeorTIAMeanage64SCOPEAge70 89 mean76 MMSE24 30Nodementia Methodologicalissues AgeHealthyvolunteereffectSelectiveattrition missingdataTimeoffollow upTimeinrelationtodementiaDiagnosisanddetectionofdementiaTestingCeilingeffectLearningeffectSensitivitytochangeSubgroups Riskgroups TypeofdrugEffectotherthanbloodpressure Meantestscoreatbaseline SYST EUR 28 5 max30 inMMSESCOPE 28 5inMMSE Methodologicalissues AgeHealthyvolunteereffectSelectiveattrition missingdataTimeoffollow upTimeinrelationtodementiaDiagnosisanddetectionofdementiaTestingCeilingeffectLearningeffectSensitivitytochangeSubgroups Riskgroups TypeofdrugEffectotherthanbloodpressure Effectofdifferentialdrop outinSHEP PlacebogrouphadmoremissedassessmentsCaVaeventspredictedmissedassessments20 30 ofmissedassessmentswereassumedtobecognitivelyimpairedThenactivetreatmentreducedtheriskofcognitiveimpairment DiBarietal AmJEpidemiol2001 Methodologicalissues AgeHealthyvolunteereffectSelectiveattrition missingdataTimeoffollow upTimeinrelationtodementiaDiagnosisanddetectionofdementiaTestingCeilingeffectLearningeffectSensitivitytochangeSubgroups Riskgroups TypeofdrugEffectotherthanbloodpressure Timeoffollow up SHEP5yearsMRC4 5yearsSyst EurMedian2 0yearsPROGRESSMean3 9yearsSCOPEMean3 7yearsHYVETMean2 2years LONGITUDINALSTUDIESONBLOODPRESSUREANDALZHEIMER SDISEASE Previoushighbloodpressure5 15yearsAlzheimer sdiseaseinlatelife TheH70 studyinGothenburgSkoogetal Lancet1996TheHonolulu AsiaAgingStudyLauneretal NeurobiolAging2000TheRotterdamStudyRuitenbergetal Dissertation2000 Kuopio FinlandKivipeltoetal BMJ2001KungsholmenStudyQiuetalArchNeurol2003ChineseStudyWuetalLifeScience2003USAWhittmeretal Neurology2005 Tooshortfollow uptoevaluateaneffectondementia Decliningbloodpressurebeforedementiaonset A15 yearfollow upofbloodpressureanddementia Skoogetal Lancet1996 SAMPLES SHEP160 219 90MRC160 209 115Syst Eur160 219 95Nodementia PROGRESSPriorstrokeorTIAMeanage64SCOPE160 179 90 99MMSE24 30NodementiaHYVETSBP 160 Ifloweredbloodpressureisamarkerofpreclinicaldementia thoseincludedinhypertensiontrialsmaybeatlowshort termriskfordementia Methodologicalissues HealthyvolunteereffectSelectiveattrition missingdataTimeoffollow upDiagnosisanddetectionofdementiaTestingCeilingeffectLearningeffectSensitivitytochangeSubgroups Riskgroups TypeofdrugEffectotherthanbloodpressure CHANGEINMMSESCORE Ceilingeffectinthosewith29 30Learningeffect testevery6months Lesspossibilityforincreaseinthosewith29 30 MMSE30 MMSE30 CHANGEINCOGNITIVEFUNCTION MMSE24 CHANGEINMMSESCORE Ceilingeffectinthosewith29 30Learningeffect testevery6months Lesspossibilityforincreaseinthosewith29 30 Increaseintestscores MRCtrialinhypertensionSyst EurSCOPE CHANGEINMMSESCORE Ceilingeffectinthosewith29 30Learningeffect testevery6months Lesspossibilityforincreaseinthosewith29 30 CHANGEINMMSESCOREFROMBASELINE SCOPE Methodologicalissues HealthyvolunteereffectSelectiveattrition missingdataTimeoffollow upDiagnosisanddetectionofdementiaTestingCeilingeffectLearningeffectSensitivitytochangeSubgroups Riskgroups TypeofdrugEffectotherthanbloodpressure SCOPE NewcastlesubstudyChangeintestscores Saxbyetal Neurology2008 70 1858 66 Treatmentofhypertensioninmildcognitiveimpairment MCI Treatmenttargetsinrelationtodementia Dementia ADLSocialabiliy MildCognitiveImpairment Normal MMSE24 28ATBASELINE SCOPE Morepreviousstroke 5 2 vs3 0 Morediabetesmellitus 14 vs10 Lessmyocardialinfarction 4 3vs4 7 Older 77 3vs75 8 SkoogetalAmJHypertension2005 MajorCardiovasculareventsinSCOPE per1000person years Cardiovascularmortality stroke myocardialinfarction SkoogetalAmJHypertension2005 Non fatalstroke per1000person years inSCOPE SkoogetalAmJHypertension2005 Dementia cumulativeincidence inSCOPE SkoogetalAmJHypertension2005 ChangeinMMSEScore ITT 0 8 0 7 0 6 0 5 0 4 0 3 0 2 0 1 0 ChangeinMMSEScore adjusted Candn 1419 Contn 1399 BaselineMMSE29 30 Candn 998 Contn 1010 BaselineMMSE24 28 p 0 20 p 0 04 Candn 2417 Contn 2409 Allpatients p 0 20 SkoogetalAmJHypertension2005 Treatmentofhypertensionindemented Treatmenttargetsinrelationtodementia Dementia ADLSocialabiliy MildCognitiveImpairment Normal NotmanystudiesonantihypertensivetreatmentindementedindividualsandnoRCT Prevalenceofhypertension bloodpressureabove160 90 in85 year olds HypertensionacceleratescognitivedeclineinAlzheimer sdisease HypertensionatbaselinewasassociatedwithsteepercognitivedeclineinAlzheimerpatientsbelowtheageof65 Noeffectofantihypertensivetreatment Bellewetal2004 SystolichypertensionatbaselinewasrelatedtosteepercognitivedeclineinAlzheimerpatientsfromtheCasheCountyStudy Mainlyamongtheelderly Antihypertensivetreatmentwasrelatedtoaslowerdecline Mielkeetal2007 AcetylcholinesteraseinhibitorsinAlzheimerpatientswithhypertension Betterlong termeffectofRivastigmineinAlzheimerpatientswithhypertension Erkinjunttietal2003 BettereffectofDonepezilinAlzheimerpatientswithhypertension Fukuietal2005 AntihypertensivetreatmentslowsprogressionofAlzheimerdisease TreatedhypertensiveswithAlzheimerdisease vasculardementia mildcognitiveimpairmenthadbettercognitivefunction Hajjaretal2005 Hanonetal2006 InAlzheimerpatientsonacetylcholinesteraseinhibitors thoseonantihypertensivetreatmentperformedbetteronMMSEafter40weeksoftreatment Rozzinietal2005 Treatmentofhypertensionmayhaveaneffectoncerebrovasculardiseaseinindividualswithcognitiveimpairment PROGRESSMRISubstudy Whitematterhyperintensitie