利用生物標志物患者急性心血管疾病.ppt

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UseofBiomarkersinPatientswithAcuteCardiovascularDisease,AllanS.Jaffe,MD.*Consultant-Cardiology95:2053-2059,,Antman,19981.1(0.4-3.5)Benamer,199813.7(3.9-48.3)Brisisc,19988.0(0.9-65.1)Cin,199617.9(5.2-61.2)Galvani,19976.6(1.3-32.3)Hamm,199211.7(3.2-42.6)Luscher,19972.5(1.3-4.8)Ohman,19964.7(1.7-12.7)Olatidoye,1998156.1(17.4-1,402)Ottani,19976.6(2.0-22.1)Rebuzzi,199825.3(5.2-123.2)Solymoss,19972.4(0.7-8.1)Stubbs,19961.5(0.5-4.2)Wu,199531.5(6.7-144.9)Antman,19963.8(1.8-8.03),IndividualStudiesofPatientswith“UnstableAngina”WithoutSTSegmentElevation,PetoOR2.66-7.78,RapidTroponinIAssay,OutcomesinRelationtoTroponinValues:TheIssueofAssaySensitivity,CP1148152-9,IntJCardiol93:113,2004,%,Neg,,,Death,MI,DeathorMI,56,98,92,130,132,205,TroponinT(0.1?g/L),TroponinT(0.01?g/L),OR1.80;1.30-2.54,1.82;1.38-2.40,1.64;1.31-2.06,OR3.20;2.22-4.59,2.26;1.79-2.85,1.47;1.12-1.93,3.42;2.57-5.98,4.29;3.02-6.09,Pos,%,%,41,15,113,139,86,25,136,197,116,36,221,301,CorrespondenceBetweenCommercialAssaysandWesternBlotting,,,AssayPositiveWBDSANegativeWBDSATotal,Beckman10%CV+172037-11106117Roche10%CV+16824-12118130Beckman99th%+203858-88896Roche99th%+214465-78289,MyeloperoxidasePredictionsofEventsWhencTNT“Negative”,CP1131968-3,NEJM349:1600,2003,Oddsratio,Oddsratio,RevascularizationMyeloperoxidasequartile2Myeloperoxidasequartile3Myeloperoxidasequartile4MajoradversecardiaceventsMyeloperoxidasequartile2Myeloperoxidasequartile3Myeloperoxidasequartile4,30Days,6Months,PrognosticEffectsofMPOat72Hours,CP1132618-7,Death,MI(%),Circulation108:1443,2003,BeforePCI,,Adjustedhazardratio2.04(0.65-6.42),Adjustedhazardratio3.07(1.21-4.26),MPOhigh,MPOlow,AfterPCI,Hours,,cTnINegativeACS?,Circulation107:533,2003,CP1104508-19,,SensitivityofcTnI,CK-MB,andMyoglobinwithSensitiveContemporaryAssays,AHJ148:577,2004,,TnI(0.1g/L)CK-MB(3.5g/L)Myo(98/56g/L),,,CP1176222-2,0min,30min,60min,90minSensitivity,2hr,3hr,6hr,6hrSpecificity,,,TnI(0.4g/L)TnI(0.1g/L)TnI(0.07g/L),,,cTnTandAngiographicMeasures,CP1179389-5,TnT(<0.01),,,ProgCardiovascDis47(3),2004,P0.01),P=0.02,Thrombus(%),P=0.03,TFG0/1(%),P<0.001,TMPG0/1(%),,JACC36(3):970-1062,2000,MedicalandInterventionalResponsetoGPIIb/IIIaAgentsinTroponinPositivePatients,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,+24h,+48h,?,+24h,+48h,?,+72h,n=1,265,OR=0.37,P=0.032,CAPTURE,2.8%,1.3%,n=9,461,OR=0.72,P=0.003,PURSUIT,n=1,570,OR=0.45,P=0.016,PRISM-PLUS,n=12,296,OR=0.66,P=0.001,All,n=1,239,OR=0.46,P=0.009,n=1,228,OR=0.71,P=0.105,n=287,OR=0.35,P=0.062,n=2,754,OR=0.59,P=0.001,5.8%,2.8%,10.3%,7.6%,8.0%,2.9%,8.0%,4.9%,4.4%,3.2%,3.8%,1.8%,4.3%,3.9%,DeathorMI(%),StartGPIIb/IIIainhibitor/placebo,Percutaneouscoronaryintervention,CP956024-13,LMWHeparinvsVFHeparininTIMI11B,JAmCollCardiol36:1812,2000,CP1008642-5,TACTICS(TIMI18),CP1036852-9,ConservativeInvasiveNo.treatmenttreatmentPrimaryendpoint<0.1ng/mL7344.36.60.1-<0.418116.54.40.4-<1.521317.65.4?1.569315.68.8DeathorMI<0.1ng/mL7341.93.00.1-<0.418112.14.40.4-<1.521311.82.7?1.569310.05.9,CardiactroponinI,JAMA286:2405,2001,Favorsinvasivetreatment,FavorsConservativetreatment,,,,,Oddsratio,RelationBetweenCreatinineClearance,TroponinT,andOutcomes,,,,,,,,,,,CURERatesandRelativeRisksofFirstPrimaryOutcome,CP1019654-1,NEJM345:494,2001,CP1189452-4,4peptidesrelatedwitheachotherregardingbiochemistryandphysiologicalfunctionAtrialnatriureticpeptide(ANP)Brain(orBtype)natriureticpeptide(BNP)C-typenatriureticpeptide(CNP)Urodilatin,aslightlyextendedformofANP,NatriureticPeptideFamily,Common17-aminoacidringstructureRingstructurehighlyconserved11/17aminoacidsarehomologousRingstructureessentialforphysiologicalactivity,CP1189452-5,NatriureticPeptideFamilyBiochemistry,,,Cardiomyocyte,Blood,proBNP(108aa)BNP-32(proBNP77-108),,BNP-32Physiologicallyactiveform,NT-proBNP1-76,SecretionLVstretchWalltension,Pre-proBNP(134aa),,,Signalpeptide(26aa),proBNP,Serinprotease(Corin?),Mair:ScandJClinLabInvest,1999,CP1189452-10,,CP1189452-20,97.5%percentile(pg/mL),<3030-3940-4950-59?60,Agegroups,,Age-SpecificReferenceRangeforNT-proBNP,,,,,AHJ149(4),April2005,pg/mL,NT-proBNP,pg/mL,BNP,Weightcategories(BMI),Weightcategories(BMI),?25,25-29.9,?30,?25,25-29.9,?30,,,,,P<0.001,P<0.001,ValuesofBNPandNTproBNPbyWeight,,,CP1189452-21,384,,BNPconcentration(pg/mL),Diagnosis,n=139,1,076138,NoCHF,CP1189452-25,n=97,CHF,,LVdysfunctionNoacuteCHF,n=14,14131,,BNPLevelsofPatientsDiagnosedWithoutCHF,withBaselineLeftVentricularDysfunction,andwithCHF,BNPLevelsinHeartFailure,MedianBNPlevel(pg/mL),CP1189452-26,BNPLevelsinNormalSubjectsandInpatientswithHeartFailure,Normal,I,II,III,IV,Class,,CP1189452-27,EDProbabilityofCHFRecorded,P<0.0001fromclinicaljudgmenttocombined,McCulloughPAetal:Circulation106:416,2002,Diagnosticaccuracy(%),Clinicaljudgment,BNP,Combined,70727476788082,74.0,81.2,81.5,n=1,538,BNPStudyPrimaryEndPoint,,n=1,586;?50%CHF;56%male;6417yo;41%COPD;?30%HxCHF,CP1189452-28,BNP(pg/mL)SensSpecPPVNPV50976271951009076798915085838385,AUC=0.91,BreathingNotProper(BNP)MulticenterTrial,AJC95,April15,2005,Optimalcut-pointSensSpecPPVNPVAccuracy(%)(%)(%)(%)(%)(%)Rule-incutpointsAllpt(n=599)9009085769487<50yrold4509395679995n=144?50yrold9009180779285n=455Rule-outptAllpt(n=599)3009968629983,CP1189452-30,OptimalNT-proBNPCutpointsforAcuteCongestiveHeartFailure,,McCulloughPAetalfortheBNPMultinationalStudyInvestigators:JAmCollCardiol41:278A,2003,ApplicationofBNPTestinginCHF,“GreyZone”BNP,BNP(pg/mL),,,,“GreyZone”BNP100-500pg/mL,26.4%ofallcases,16.5%CHF,7.9%NoCHF,0,100,200,300,400,500,600,700,800,900,1,000,1,100,1,200,1,300,CP1189452-31,CP1189452-32,pg/mLCoronarypulmonale200-500Primarypulmonary300-500hypertensionAcutepulmonary150-500embolism,BNPElevationsRight-SidedCoronaryHeartFailure,CP1189452-33,AcuteorchronicsystolicordiastolicHFLVhypertrophyInflammatorycardiacdiseasesSystemicarterialhypertensionwithLVHPulmonaryhypertensionAcuteorchronicrenalfailureAsciticlivercirrhosisEndocrinedisorders(eg,hyper-aldosteronism,Cushing’ssyndrome),WhenCanNon-CHFPatientsPresentwithBNPElevations?,CP1189452-34,WellHFpatientsAcutemitralregurgitationPulmonaryedema<1houroldOthercases“up-stream”fromleftventricleMitralstenosisAtrialmyoxma,WhenWillCHFPresentWithoutBNPElevations?,P<0.0001,P=0.9,,BaselineBNP&ClinicalOutcomes,P<0.0001,P=0.9,Death,MI,N=1356,N=320,MorrowDAJACC2004,CP1173030-6,RelationshipofNT-proBNPandcTnT,*P<0.01vsNT-proBNP≤250ng/LCirculation110:3206,2004,*,*,Death/MIat6months,Testforinteraction:P=NS,%,BNPnegBNPcutpoint=80pg/mL,CP1189452-45,CONS,,INV,,BNPpos(19%BNPpos),n=681685156164,MorrowDA:JACC,2004,BaselineBNP:CONSvsINVStrategy,,Beta-BlockerTherapyandBNPLevels,LuchnerAetal:JACC32:1839,1998,pg/mL,pmol/mL,ANP?32%,BNP?89%,cGMP?18%,n=592,n=80,P<0.01,P<0.01,P<0.01,Nob-blocker(n=592)b-blocker(n=80),,,CP1189452-59,OutcomesbyNumberofPositiveOutcomesTACTICS-TIMI18,CP1143360-10,Circ109:584,2004,DeathorMI(%),P=NS,Positivemarkers(no.),P=NS,P=NS,2.9,4.4,6.2,6.5,12.1,13.3,DeathorMIbyMultimarkerApproach,OddsofPositiveMarkerTACTICS-TIMI18,CP1143360-7,Circ109:583,2004,T18TnlT11TnlCombinedT18TnTT11TnTCombinedT18BNPT16BNPCombinedT18CRPT11CRPCombined,Malemorelikely,Femalemorelikely,00.511.52,