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ATPIII:NewApproachesinIdentifyingandTreatingHigh-RiskPatientsStevenHaffner,MD0.01.02.03.04.05.06.0HospitalizationforMIHasN

otDeclinedHospitalizationforMI(per1,000)**Age-adjusted19871989199019921988199319941991RosamondWDetal.NEnglJMed1998;339:861-867.©199

8MassachusettsMedicalSociety.Allrightsreserved.MenWomenCriteriaforAcceptingCardiovascularRiskFactorManagementasSimilarinCHDEqu

ivalentsasinCHDPatients1.TheriskofvasculardiseaseissimilarinCHDequivalentsandinpatientswithCHD.2.LipidinterventionstoreduceCHDcanbeequall

yeffectiveinCHDequivalentandCHDpatients.3.Indiabeticpatients,glycemiaalonewillnotcompletelyeliminatetheexcessCHDri

sk.NewCHDRiskEquivalents◼>20%10-yearriskofCHD(Framinghamprojections)◼Diabetes◼Otherformsofclinicalatheroscleroticdis

ease:–Peripheralarterialdisease–Abdominalaorticaneurysm–CarotidarterydiseaseExpertPanelonDetection,E

valuation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.NoncoronaryAtherosclerosis:Overview◼Atheroscle

roticdiseaseinoneregionofthearterialtreeisassociatedwithandpredictsdiseaseinotherarterialregions–Pathobiologyandpredisposingriskfactorsaresimi

larforatherosclerosisincoronary,peripheral,andcarotidarteries◼Thus,clinicalatheroscleroticdiseaseinno

ncoronaryarteriesisapowerfulpredictorofCHDPeripheralArterialDisease(PAD)◼StudiesofpatientswithatheroscleroticPADsupporttheconce

ptthatPAD,regardlessofdiagnosisbyABI,lowerlimbbloodflowstudies,orclinicalsymptoms,isaCHDriskequivalentEdinburghArteryS

tudy◼Ankle/brachialbloodpressureindex(ABI)inrandomlyselectedpopulation,5-yearfollow-up◼1592menandwomen,614withCHD,aged55–74◼137fatalandnonfatalCHDeve

ntsduringfollow-up>1.11.1–1.011.0–0.910.9–0.71<0.7ABICHDEventOutcomesperYear(%)LengGCetal.BMJ1996;313:1440-1444.1

.4%3.8%01234AbdominalAorticAneurysm(AAA)◼Studypopulation:300menand43women(aged45–89)operatedonforAAA,separatedinto4groupsbasedonpreoperati

veCHDhistoryandECG◼Follow-up:6–11years◼Results:annualCHDmortality–1.9%inpersonswithnosymptoms,nopriorhistoryofCHD,a

ndnormalECG(31%)–2.0%inpersonswithnosymptoms,butpreviousMIbyECG(33%)–3.9%inpersonswithangina/priorMI(30%)◼BecausetherateofCHDeventsisatleasttw

icethatofCHDmortality,patientswithnoprevioushistoryofCHDeventswouldfallintotheCHDriskequivalentcategoryHertzerNR.Ann

Surg1980;192:667-673.CarotidArteryDisease:Symptomatic◼NorthAmericanSymptomaticCarotidEndarterectomyTrial(NASCET)

–Symptomaticpatientsundergoingcarotidendarterectomyhadanaverage10-yearCHDmortalityof19%◼EuropeanCarot

idSurgeryTrial(ECST)–Symptomaticpatientshadveryhighdeathratesfromnonstrokevasculardiseaseregardlessofthepercentofcarotidarterystenosis

attheonset–72%ofdeathswereduetononstrokevasculardiseaseandthus10-yearCHDdeathisestimatedat30%FergusonGGe

tal.Stroke1999;30:1751-1758.|BarnettHJetal.NEnglJMed1998;339:1415-1425.|ECSTCollaborativeGroup.Lancet1998;351:1379-

1387.◼MayoAsymptomaticCarotidAtherosclerosisStudy–Subjects—158patients,40%withhistoryofCAD,15%diabetic–Diseaseseverity—Asymptomat

icstenosis50%—TrialstoppedbecauseofhighMIandTIAeventrateinsurgicalarmsecondarytocessationofmedicaltherapy(aspirin)–CHDevents—After2.5-yearfollow-

up:12CHDevents—Estimated10-yearCHDeventrate=30%ExecutiveCommitteefortheAsymptomaticCarotidAtheroscleros

isStudy.JAMA1995;273:1421-1428.CarotidArteryDisease:AsymptomaticHeartProtectionStudy:VascularEventsbyBaselineDiseaseBaselinefeatureSimvastatin(

n=10,269)Placebo(n=10,267)PreviousMI10071255OtherCHD(notMI)9141234NopriorCHDCVD182215PVD332427Diabetes279369Allpatie

nts2042(19.9%)2606(25.4%)CollinsR.PresentedatAHA,Anaheim,California,13November2001.Riskratioand95%CIStatinbetterStatinworse24±2.6%(

2P<0.00001)0.40.60.81.01.21.4-50-40-30-20-1001020*InnationalsampleofadultsinNHANESI(1971–75)andNHANESII(19

82–84).GuKetal.JAMA1999;281:1291-1297.ChangesinCHDMortalityRatesinPatientswithandwithoutDiabetes*%ChangeinMortality

–16.610.7–43.8–20.4NondiabeticsDiabeticsP=0.46P=0.76P=0.001P=0.12MenWomenMenWomenCVDDeathRate/10,000PersonYears(Age-Adjusted

)StamlerJetal.DiabetesCare1993;16:434-444.MRFIT:DiabetesAmplifiesRiskfromOtherRiskFactorsNo.ofAdditiona

lRFs*NoDiabetesDiabetes01236311259229147125*TC>200mg/dLSBP>120mmHgCurrentsmoker020406080100120%MortalityMenMiet

tinenHetal.DiabetesCare1998;21:69-75.1-YearMortalityinDiabeticandNondiabeticSubjectsafteraFirstMIWomenDiabetesNoDiabetesDiabetesNoDiabetes01020304

050Hospitalization–28d28d–1yOutofhospital28.611.05.522.17.53.010.920.07.611.97.92.201020304050Haffne

rSMetal.NEnglJMed1998;339:229-234.IncidenceofMIduringa7-YearFollow-upinaFinnishPopulationFatalorNonfatalMI(%)PriorMI18.83.545.020.2P<0.001P<0.001Pr

iorMINopriorMINopriorMINondiabeticsubjectsDiabeticsubjects(n=1373)(n=1059)0.000.050.100.150.200.25OASIS

Study:TotalMortalityEventRateMonths69153182112RR=2.88(2.37–3.49)MalmbergKetal.Circulation2000;102:1014-1019.©2000Lip

pincottWilliams&Wilkins.24RR=1.99(1.52–2.60)RR=1.71(1.44–2.04)RR=1.00Diabetes/CVD(n=1148)NoDiabetes/CVD(n=3503)Diabetes/No

CVD(n=569)NoDiabetes/NoCVD(n=2796)StudyDrugNo.BaselineLDL-C,mg/dl(mmol/L)LDL-CLoweringPrimaryPreventionAFCAPS/TexCAPSLovastatin155150(3.

9)25%HPSSimvastatin3985127(3.3)30%SecondaryPreventionCAREPravastatin586136(3.6)28%4SSimvastatin202186(4.8)36%LIPID*Pravastatin78

2150(3.9)25%HPSSimvastatin1978127(3.3)30%CHDPreventionTrialswithStatinsinDiabeticSubjects:SubgroupAnalyses*

LDL-CvaluesforoverallgroupDownsJRetal.JAMA1998;279:1615-1622.|HPSInvestigators.PresentedatAHA,2001.|GoldbergRBetal.Circul

ation1998;98:2513-2519.|PyoralaKetal.DiabetesCare1997;20:614-620.|HaffnerSMetal.ArchInternMed1999;159:2661-266

7.|LIPIDStudyGroup.NEnglJMed1998;339:1349-1357.StudyDrugNo.CHDRiskReduction(overall)CHDRiskReduction(diab

etics)PrimaryPreventionAFCAPS/TexCAPSLovastatin15537%43%(NS)HPSSimvastatin398524%26%(p<.00001)SecondaryPreventionCAREPravastatin58623%25%(

p=.05)4SSimvastatin20232%55%(p=.002)LIPIDPravastatin78225%19%4SReanalysisSimvastatin48332%42%(p=.001)HPSSimvastatin197824%unreportedCHDPreventi

onTrialswithStatinsinDiabeticSubjects:SubgroupAnalyses(cont’d)DownsJRetal.JAMA1998;279:1615-1622.|HPSInvestigators.PresentedatAHA,2001.|Gold

bergRBetal.Circulation1998;98:2513-2519.|PyoralaKetal.DiabetesCare1997;20:614-620.|LIPIDStudyGroup.NEnglJMed1998;339:1349-1357.|Haffne

rSMetal.ArchInternMed1999;159:2661-2667.StudyDrug(dose)No.BaselineLDL-C,mg/dl(mmol/L)LDL-CLoweringCHDReductionPrimaryPreventionHelsinkiHea

rtStudyGemfibrozil(1200mg/d)135203(5.2)6%68%NSSecondaryPreventionVA-HITGemfibrozil(1200mg/d)627112*(2.9*)–24%P=.05DAISFenofibrate(200mg/d)4181

306%23%NSCHDPreventionTrialswithFibratesinDiabeticSubjects:SubgroupAnalyses*MedianvalueKoskinenPetal.DiabetesCare1992;15:820-825.|Ru

binsHBetal.NEnglJMed1999;341:410-418.|DAISInvestigators.Lancet2001;357:905-910.AdlerAIetal.BMJ2000;321:412-419.|StrattonIMetal.BMJ2000;321:405

-412.ReprintedwithpermissionfromtheBMJPublishingGroup.Adjustedincidenceper1000person-years(%)UpdatedmeanHbA1cconcentration(%)Upda

tedmeansystolicBP(mmHg)02040608001020304050Adjustedincidenceper1000person-years(%)567891011110120130140150160170MIMicrovascularendpointsMicrovascu

larendpointsMIMIandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationinUKPDSSummary:DiabetesasaCHDRiskEquivalent◼Impliesthat

enhancedbenefitwillbeachievedfromaggressiveLDL-loweringtherapy◼Post-hocanalysisofallstatintrialsshowedatrendforbenefitofLDLloweringinpersonswithdiab

etesATPIII:ManagementofDiabeticDyslipidemia◼Primarytargetoftherapy:LDL-C◼Diabetes:CHDriskequivalent◼Therefore,goalforpersonswithdiabetes:<100mg/dL◼Th

erapeuticoptions:–LDL-C100–129mg/dL:increaseintensityofTLC;adddrugtomodifyatherogenicdyslipidemia(fibr

ateornicotinicacid);intensifystatintherapy–LDL-C130mg/dL:simultaneouslyinitiateTLCandLDL-C–loweringdrugs◼AfterLDL-Cg

oalismet,ifTG200mg/dL:non–HDL-C(<130mg/dl)becomessecondarytargetExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JA

MA2001;285:2486-2497.TheMetabolicSyndrome◼MetabolicsyndromeisasecondarytargetoftherapyinATPIII.◼Primaryinterventionsarebehavioral,wi

thpharmacologicalagentssuggestedtotreatcomponentssuchashypertensionanddyslipidemia.◼Componentsofthemetabolicsyndromehavebeenshowntobestronglyp

redictiveofcardiovasculardisease.1◼Althoughinsulinconcentrationsstronglypredictthedevelopmentofmultiplemetabolicdi

sorders2andcardiovasculardisease,3insulinresistanceispresentinonlyoneortwocomponentsintheFraminghamStudy.4,51IsomaaBeta

l.DiabetesCare2001;24:683-689.2HaffnerSMetal.Diabetes1992;41:715-722.3PyoralaMetal.Circulation1998;98:398-404.4MeigsJB.AmJEpidemio

l2000;152:908-911.5MeigsJBetal.Diabetes1997;46:1594-1600.ATPIII:TheMetabolicSyndromeDiagnosisisestablishedwhen3oftheseriskfactorsarepresent.Expert

PanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.RiskFactorDefiningLevelAbdominal

obesity(Waistcircumference)MenWomen>102cm(>40in)>88cm(>35in)TG150mg/dLHDL-CMenWomen<40mg/dL<50mg/dLBloodpressure130/85mmHgFastingglucose110mg

/dLComparisonofATPIIIRiskFactorCountingandtheMetabolicSyndromeRiskFactorRiskFactorCountingMetabolicSyndromeAbdomin

alobesityMenWomenNotincluded>102cm>88cmTGNotincluded*150mg/dLHDL-CMenWomen<40mg/dL<40mg/dL<40mg/dL<50mg/dLBloodp

ressure140/90mmHg130/85mmHgFastingglucoseNotincluded†110mg/dL‡*TG200mg/dLpartofcriteriatodetermi

newhethernon-HDL-Cshouldbetargeted.†DiabetesisaCHDriskequivalent.‡DiabetesplusIFG.ExpertPanelonDetectio

n,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.ComparisonofATPIIIRiskFactorCountingandtheMetabolicSyndrome(cont'

d)RiskFactorRiskFactorCountingMetabolicSyndromeCigarettesmokingIncludedNotincludedFamilyhistoryofCHDIncludedNotincludedAgeMen(45)Women(55)In

cludedIncludedNotincludedNotincludedNegativeriskfactorHDL60mg/dLIncludedNotincludedExpertPanelonDetection,Evaluation,andTre

atmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.BaselineInsulinDisorderLow(%)High(%)RelativeRiskPValueHypertension5

.511.42.040.21Hypertriglyceridemia2.68.93.46<.001LowHDL-C16.226.31.630.012HighLDL-C16.420.11.230.223Type2diabetes2.212.35.62<.0

01RelationshipofFastingInsulinLevelstoRelativeRiskforMultipleMetabolicDisorders:SanAntonioHeartStudyHaffnerSMetal.Dia

betes1992;41:715-722.RiskofMajorCHDEventAssociatedwithInsulinQuintilesinNondiabeticSubjects:HelsinkiPolicemenStudy0.700.

750.800.850.900.951.00Years5102001525PyoralaMetal.Circulation1998;98:398-404.©1998LippincottWilliams&Wilkins.Logrank:OverallP=.001Q5vs.Q1P<.001Q1Q2

Q3Q4Q5ProportionwithoutMajorCHDEvent0ClinicalManagementofMetabolicSyndrome◼Managementofunderlyingcauses–Weightcontr

olenhancesLDLloweringandreducesallriskfactors–PhysicalactivityreducesVLDLandLDLandincreasesHDL◼Treatlipidandnonlipi

driskfactors–Hypertension–AspirininCHDpatients–Elevatedtriglycerides–LowHDLExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdul

ts.JAMA2001;285:2486-2497.MultipleRiskFactors:AdditiveRiskThetotalseverityofmultiplelow-levelriskfactorsoftenexc

eedsthatofasingleseverelyelevatedriskfactor.8%GrundySMetal.JAmCollCardiol1999;34:1348-1359.BP165/95mmHgBP165

/95mmHgAge56yearsBP165/95mmHgAge56yearsLDL-C155mg/dLBP165/95mmHgAge56yearsLDL-C155mg/dLSmoker13%19%27%051015202530MeanAbso

luteRisk(%)CHDRiskEquivalentSummary◼PatientswithestablishedCHDhaveariskforrecurrentMIandCHDdeaththatexceeds20%per10years

.Clinicallyevidentnoncoronaryatherosclerosis,aswellastype2diabetesmellitus,imposeanapproximatelyequalriskfordevelopingCHDinpatientswith

outclinicalCHD.◼CHDriskequivalents:–Multipleriskfactors(>20%10-yearCHDrisk)–Type2diabetesmellitus–Peri

pheralarterialdisease–Abdominalaorticaneurysm–CarotidarterydiseaseExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholest

erolinAdults.JAMA2001;285:2486-2497.ClassificationofSerumTriglyceridesTriglycerideCategoryATPIILevelsATPIIILevelsNormal<200mg/dL<150mg/dLBord

erline-high200–399mg/dL150–199mg/dLHigh400–1000mg/dL200–499mg/dLVeryhigh>1000mg/dL500mg/dLExpertPanelonDetection,Evaluat

ion,andTreatmentofHighBloodCholesterolinAdults.JAMA1993;269:3015-3023.|ExpertPanelonDetection,Evaluation,andTrea

tmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.RationaleforChangeintheCategorizationofTriglycerideLevels

inATPIII◼ATPIIIgivesadditionalemphasistomoderateelevationsoftriglycerides(150–200mg/dL)forthefollowingreasons:–Newmeta-analysissugg

eststhatraisedtriglyceridelevelsmaybeanindependentriskfactorforCHD.1–2–Elevatedtriglyceridesareassociatedwithcomp

onentsofthemetabolicsyndromesuchasglucoseintolerance,lowHDL,inflammation,andprothromboticstate.3–Subjectswithmodestlyelevatedtriglyceridelev

elshaveatherogenicremnantlipoproteins.3◼IncreasedtriglyceridesarenotaspecifictargetforinterventioninATPIIIbutenterintothedeterminationofwhet

hertotargetnon-HDL-C.1AustinMA.CanJCardiol1998;14:14B-17B.2AssmannGetal.EurHeartJ1998;19:M8-M14.3Gru

ndySM.AmJCardiol1998;81:18B-25B.ClassificationofSerumHDL-CLevelsHDL-CCategoryATPIILevelsATPIIILevelsLowHDL-C<35

mg/dL<40mg/dLHighHDL-C60mg/dL60mg/dLExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA1993;

269:3015-3023.|ExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.RationaleforChan

geintheLowHDL-CCategoryintheATPIIIGuidelines◼TheinverseassociationbetweenHDL-CconcentrationsandCHDriskiscontinuous;

nothresholdrelationshiphasbeenidentified.Clearly,lowHDL-ClevelspredictCHDatlevelsabove35mg/dL.1◼WomentypicallyhavehigherHDL-Clevelsthanmen,andacutp

ointof<40mg/dLwillidentifymorementhanwomenwithlowHDL-C,i.e.,approximatelyone-thirdofmenandone-fifthofwomeninthegeneralpopulation.1WilsonP

Wetal.Circulation1998;97:1837-1847.AtherogenicParticlesApolipoproteinBNon-HDL-CMEASUREMENTS:TG-richlipoproteinsVLDLVLDLRIDL

LDLSmall,denseLDLAtherogenicLipoproteins◼Non-HDL-C=TC–HDL-C◼Canbeaccuratelymeasuredinnonfastingstate◼ApoBconcentr

ationrepresentstotalnumberoflipoproteinparticles(LDL+IDL+VLDL)◼Thismaybecalled“non-HDL”cholesterolor“atherogeniccholesterol”GrundySM.Ci

rculation1997;95:1-4.CuiYetal.ArchInternMed2001;161:1413-1419.LRCFollow-upStudy:CVDMortalitybyNon-HDL-CandLDL-CinMenLRC=LipidResearchC

linics;RR=Relativerisk;CI=confidenceinterval.00.250.500.751.001.251.501.752.002.252.502.753.00RRwith95%CINon-HDL-C(mg/dL)Rate/10,00

0<16038.0160to<19043.0190to<22053.922080.6LDL-C(mg/dL)<13040.2130to<16048.2160to<19054.919071.3Cui

Yetal.ArchInternMed2001;161:1413-1419.LRCFollow-upStudy:CVDMortalitybyNon-HDL-CandLDL-CinWomenLRC=LipidResearchClinics;RR=Relativerisk;CI=co

nfidenceinterval.00.501.001.502.002.503.003.504.00RRwith95%CINon-HDL-C(mg/dL)Rate/10,000<16017.6160to<19026.5190to<220

29.222051.3LDL-C(mg/dL)<13025.4130to<16022.8160to<19027.719040.1CorrelationCoefficientsbetweenApoBandLDL-CorNon-HDL-CatWeek54:AC

CESSBallantyneCMetal.AmJCardiol2001;88:265–269.©2001,ReprintedwithpermissionfromExcerptaMedicaInc.Non-HDL-CandapoBLDL-Candap

oBAllpatients0.9380.849BaselineTGstratumTG<150mg/dLTG150–250mg/dLTG>250mg/dL0.9460.9440.9000.9220.885

0.805ATPIIriskcategory<2RFwithoutCHD2RFwithoutCHDCHD0.9080.9360.9290.8550.8350.810Allpvalues<0.0001.Non-HDL-CGoalsinPati

entswithTG200mg/dLRiskcategoryNon-HDL-Cgoal(mg/dL)CHDorCHDriskequivalents(10-yrrisk>20%)<1302+riskfactor

s(10-yrrisk20%)<1600–1riskfactor<190ExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.Summary:Id

entifyingandTreatingHigh-RiskIndividuals◼Increasednumberofpatientswith"CHDequivalent"withLDL-Cgoal<100mg/dL◼NewcriteriaforHDL-C,TG,andthemetabol

icsyndrome◼Newtargetsfornon-HDL-CinpatientswithTG200mg/dL谢谢您的聆听与观看THANKYOUFORYOURGUIDANCE.感谢阅读！为了方便学习和使用，本文档的内容可以在下载后随意修改，调整和打印。

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