新的CHD危险因素及评估方法

MagnitudeoftheBurden—CausesofDeathintheUnitedStatesDeathsin1996(thousands)CVDCancerAccidentsHIV/AIDS959.2544.793.832.7AmericanHeartAssociation.1999HeartandStrokeStatisticalUpdate.1998.EconomicDirectandIndirectCostofCVDintheUnitedStatesHospital/nursinghomePhysicians/otherprofessionalsDrugsHomehealth/othermedicaldurablesLostproductivity/morbidityLostproductivity/mortalityAmericanHeartAssociation.1999HeartandStrokeStatisticalUpdate.1998.Totaldirectandindirectcosts:$286.5billion5-YearExpectedTotalCostperCaseWittelsEHetal.AmJCardiol1990;65:432–440.AverageCost(1986$)CHDeventsAcutemyocardialinfarction51,211Anginapectoris24,980Unstableanginapectoris40,581Suddendeath9,078ProceduresAngioplasty26,916Bypasssurgery32,465PreventiveMedicineCostsCostofpreventivemeasuresTreatmentTestingComplicationsofpreventivemeasuresTreatingcasesthatariseanywayTreatingdiseasesdiscoveredTreatingotherillnessesinpopulationlivinglongerPay“up-front”forbenefitlaterFalsepositiveTreatingthosewhowillnotdevelopdiseaseCost-EffectivenessAnalysisPurpose: Considerboththeeffectivenessandcostofanintervention

Cost= Costofmedicalintervention+costofillness Effectiveness= qualityadjustedlifeyearsaved CE= Cost-effectivenessratioCE2-1=Cost2–Cost1QALY2–QALY1WhoseCostsMatter?

Patient: Thecoststhepatientbearsdirectly(dependsonco-payment)

Insurance: Coststheinsurancebearsdirectly

Societal: IncludesallcostsandavoidsdoublecountingMeasuringCostsDirectCosts: Directmedicalcostsrelatedtothe diagnosisandtreatmentofthedisease+ disease-specificcoststhatmaybe inducedoravertedIndirectCosts: LostearningsOtherCosts: Prolongedlifeincreasedcancer, nursinghomepatients Prematureevents,disabilitypayments, reducedproductivityCost-Effectiveness:

QualityAdjustedLifeYearsMildhypertensionmaleage40$23,300EstrogentherapypostmenopausalSx$32,900Neonatalintensivecare$38,800Schooltuberculosistesting$53,300Hospitalhemodialysis$65,900GeneralGuidelinesIncrementalCost-Effectiveness(QALY)GoldmanLetal.Circulation1992;85:1960–1968.0–$20,000Veryattractive$20,000–$40,000Currentlyfunded

–Hemodialysis

–Rxmildhypertension$60,000–$100,000>Currentlyaccepted$100,000+UnattractiveCholesterolLowering:

Cost-EffectivenessGoldmanLetal.JAMA1991;265:1145–1151.TreatmentSexAgeCHDCholmg/dlCost/LifeYrLovastatinM35-54+>250<0LovastatinW45-54+>2503,500LovastatinM45-54->300110,000LovastatinW45-54->300320,000CostEffectivenessofSimvastatinTreatmentfor5Yearsin59-Year-OldPatientswithCHDandaPretreatmentTotalCholesterolLevelof261mg/dlDirectCostsDirect+

IndirectCostsVariableMenWomenMenWomenCosts($)

Intervention2,2422,4102,2422,410

Associatedmorbidity–718–725–1,783–1,601

Net1,5241,685459809Yearsoflifegained0.280.160.280.16Costperyear($)5,40010,5001,6005,100JohannessonMetal.NEnglJMed1997;336:332–336.Copyright©1997MassachusettsMedicalSociety.CostPerYearofLifeGainedinPatientswithCHDWhoReceivedSimvastatinTreatmentfor5YearsTCbeforetreatment(mg/dl)Age35Age59Age70MenWomenMenWomenMenWomenDirectcosts

21311,40027,4007,00016,4006,20013,300

2618,80018,8005,50010,3004,7008,500

3096,70013,2004,2007,1003,8006,200Direct+indirectcosts

213SavingsSavings2,1008,6006,20013,300

261SavingsSavings1,6004,9004,7008,500

309SavingsSavings1,2003,2003,8006,200JohannessonMetal.NEnglJMed1997;336:332–336.Copyright©1997MassachusettsMedicalSociety.WOSCOPSPlaceboGroup5-YearTotalEventRatesWestofScotlandCoronaryPreventionGroup.

Lancet1996;348:1339–1342.Men45–54Men55–64MinorECG11.921.2Smoking10.114.4HDL-C<40mg/dl8.114.1HTN8.012.3FamilyCHD7.513.2Highcholesterol3.55.3NewTestsforRiskAssessmentI. Lipoproteinassessment Lipoprotein(a)*

Apoproteins:apoB-100,*A-I,CIII-B

LDLparticlesize

ApoEgenotype*FrequentlyusedatBaylorLipidMetabolismandAtherosclerosisClinicLp(a)inAtherogenesis:AnotherCulprit?IdenticaltoLDLparticleexceptforadditionofapo(a)Plasmaconcentrationpredictiveofatheroscleroticdiseaseinmany,althoughnotall,epidemiologicstudiesAccumulatesinatheroscleroticplaqueBindsapoB–containinglipoproteinsandproteoglycansTakenupbyfoamcellprecursorsMayinterferewiththrombolysisMaherVMGetal.JAMA1995;274:1771-1774.SteinJHetal.ArchInternMed1997;157:1170-1176.EffectsofLipid-ModulatingDrugsonLp(a)NiacinandestrogenreduceLp(a)levelsApheresisreducesLp(a)levelsNobenefitfromstatinsNoconsistentbenefitwithfibrates,althoughstudiesarevariableApoEGenotypeApoEmediatesthemetabolismofchylomicrons,chylomicronremnants,VLDL,IDL,andasubclassofHDLparticles.1The3allelesoftheapoEgeneareassociatedwithvariationsinLDL-Clevel,whichishigherwith4andlowerwith2comparedwith3.2LDL-Cresponsetodietisreportedlygreaterinpatientswith4,3responsetostatinsgreaterwith2or3.1MahleyRW.Science1988;240:622-630.2DavignonJetal.Arteriosclerosis1988;8:1-21.3MänttäriMetal.Metabolism1991;40:217-221.Intensityoflipid-loweringtherapy

isdependentupontheabsoluteriskforCHDeventsNCEPRiskFactorsinPrimaryPreventionPositiveRiskFactorsAgeMale45yearsFemale55yearsorprematuremenopausewithoutERTFamilyhistoryofprematureCHDCurrentcigarettesmokingHypertension(140/90mmHgoronantihypertensivemedication)LowHDL-C(<35mg/dl)DiabetesmellitusNegativeRiskFactorHighHDL-C(60mg/dl)NationalCholesterolEducationProgram.

Circulation1994;89:1329-445.NewTestsforRiskAssessmentNonlipidriskfactors Homocysteine*

Fibrinogen

Plasminogenactivatorinhibitor

C-reactiveprotein

Celladhesionmolecules*FrequentlyusedatBaylorLipidMetabolismandAtherosclerosisClinicHomocysteineasaCVDRiskFactorHighplasmahomocysteinemaybedirectlyrelatedtoatherosclerosisdevelopment.HighplasmahomocysteinemayberelatedtoCVDriskbyEnhancinginflammatoryprocessesIncreasingriskforthrombosisDecreasedfolicacidorB12andB6maybetheprimarycauseofincreasedCVDrisk.TheremaybenocausalassociationbetweenelevatedhomocysteineandCVDrisk.KullerLHetal.Circulation1998;98:196-199.PlasmaHomocysteine

andMortalityinCHDPatientsProspectiveevaluationof587CHDpatients,followedupfor4.6yearsFastingplasmahomocysteinemeasuredatbaselineStrong,gradedrelationshipbetweenhomocysteinelevelsandall-causemortalityNygardOetal.NEnglJMed1997;337:230–236.NygardOetal.NEnglJMed1997;337:230–236.PlasmaHomocysteine

andMortalityinCHDPatientsHomocysteineLevel(µmol/L)MortalityRatio9–14.91.915–19.92.8

204.5HomocysteineinRiskAssessment

andRiskReductionMechanismsofatherogenesisfromhomocysteinearenotknown,butendothelialinjuryand/orpotentiationoflipoproteinoxidationarepossible.LaboratorytestingofhomocysteinelevelsneedstobebetterstandardizedTreatmentwithhigh-dosefolicacid(1–2mg/d)and/orpyridoxine(250mg/d)canlowerhomocysteinelevels;empiricB12frequentlyaddedElevatedPlasmaFibrinogen

AMajorandIndependentRiskFactorEpidemiologicalstudiesCross-sectionalanalysesClinicalcohortstudies Thereisasizeablebodyofevidenceidentifyingfibrinogenasamajor,independentriskfactorErnstE,etal.EurHeartJ.1995;16(supplA):47-53.FibrinogenandAtherosclerosisPresenceorAbsenceofPlaqueLevensonJ,etal.ArteriosclerThrombVascBiol.1995;15:1263-1268.n=652menEffectsofLipid-Lowering

AgentsonFibrinogenNoconsistentbenefitseenwithstatinsFibrateshaveshownbenefitinmoststudiesLevelsreducedwithapheresisNicotinicacidhasshownamodestreductioninsomebutnotallstudiesCirculatingAdhesionMoleculesintheAtherosclerosisRiskinCommunities(ARIC)StudyBiracialpopulationof15,792adults,aged45–64,in4U.S.communitiesIncidentCHD:fatalornonfatalMI,surgicalrevascularization(n=204)Carotidarteryatherosclerosis:B-modeultrasoundassessmentoffarwallIMT>1.0mm(n=272)Controls:IMT<0.68mm(n=312)stratifiedbygenderandageHwangS-Jetal.Circulation1997;96:4219–4225.CirculatingAdhesionMoleculesintheAtherosclerosisRiskinCommunities(ARIC)Study*Adjustedforrace,age,gender,BMI,HTN,DM,TC,HDL-C,TG,cigarettes,VWF,fibrinogen,andWBCHwangS-Jetal.Circulation1997;96:4219–4225.QuartileOddsratio*95%CI2nd1.370.69–2.733rd1.460.75–2.844th5.532.51–12.21 RelativeRisksforFirstMIforBaselinesICAM-1>260ng/dl01230–11–24–82–4YearsofStudyFollow-UpRelativeRiskRidkerPMetal.Lancet1998;351:88-92.ReprintedwithpermissionfromElsevierScience.NewTestsforRiskAssessmentNoninvasiveimagingofearlyatherosclerosis Carotidultrasound—IMT UltrafastCT—calciumscore MagneticresonanceimagingNoninvasiveassessmentofendothelialfunction BrachialforearmflowreservePredictiveValueofCACScoreCACscoreSensitivitySpecificityPPVNPVOR1000.890.770.0550.99825.81600.890.820.0710.99835.46800.500.950.1400.99220.0AradYetal.Circulation1996;93:1951–1953.LimitedPredictivityofCoronaryCalciumScoreforCoronaryEvents:ROCCurveAreasDetranoRCetal.Circulation1999;99:2633-2638.MIor

coronarydeathP*MI,coronarydeath,orrevascularizationP*Calciumscore0.640.05.070.650.04.06Framinghammodel0.690.05.200.670.04.10Data-derivedmodel0.680.05.090.690.04.06Data-derivedmodel