控制糖尿病患者心血管危险的干预治疗策略-课件

控制糖尿病患者心血管危险

的干预治疗策略控制糖尿病患者心血管危险

的干预治疗策略糖尿病与心血管危险影响心血管危险的因素综合控制的理论与实践糖尿病与心血管危险CountriesWithHighestNumbersofEstimatedCasesofDiabetesfor2000and2030RankingCountryPeoplewithdiabetes(millions)CountryPeoplewithdiabetes(millions)200020301 India 31.7 India 79.42 China 20.8 China 42.33 U.S. 17.7 U.S. 30.34 Indonesia 8.4 Indonesia 21.35 Japan 6.8 Pakistan 13.96 Pakistan 5.2 Brazil 11.37 RussianFederation 4.6 Bangladesh 11.18 Brazil 4.6 Japan 8.99 Italy 4.3 Pinecones 7.810 Bangladesh 3.2 Egypt1 6.7Total:177million366MILLIONBY2030CountriesWithHighestNumbersType2diabetesandCHD

7-YearIncidenceofFatal/NonfatalMI(EastWestStudy)

IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI18.8HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)3.00.57.83.23.545.020.2Eventsper

100person-yr:P<0.001p<0.001Type2diabetesandCHD

7-YearType2diabetesandStroke

7-YearIncidenceofFatal/NonfatalStroke(EastWestStudy)IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI7.2HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)1.20.33.41.61.919.510.3Eventsper

100person-yr:P=0.01p<0.001Type2diabetesandStroke

7-YPrevalenceofCHDbytheMetabolicSyndromeandDiabetesintheNHANESPopulationAge50+AlexanderCetal.Diabetes2003;52:1210-121425%20%15%10%5%0%NoMS/NoDM8.7%13.9%7.5%19.2%MS/NoDMDM/NoMSDM/MS%ofpopulation= 54.2% 28.7% 2.3% 14.8%CHDPrevalencePrevalenceofCHDbytheMetab1.00.90.80.70.60.00246810Follow-up,years#atrisk174214099062828935NometabolicsyndromeMetabolicsyndromelog-rank=45.4p<0.001Event-freesurvivalSchillaciG.JACC.2004;43:1817-1822代谢综合征与心血管危险1.00.90.80.70.60.00246810FolloMlandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationMlMicrovascularandpointsMlMicrovascularandpoints50403020100806040200Adjustedincidenceper1000person-yr(%)110120130140150160170567891011UpdatedmeansystolicBP(mmHg)UpdatedmeanHbA1cconcentration(%)Adjustedincidenceper1000person-yr(%)AdlerAletal.BMJ2000;321:412-419StrationIMetal.BMJ2000;321:405-412MlandMicrovascularEndPointMetS和DM患者血脂异常特征游离脂肪酸TGHDL-C

VLDL-C

小而密LDL颗粒氧化LDL-C餐后高脂血症MetS和DM患者血脂异常特征游离脂肪酸MaleGender-adjustedFemaleReducedriskwithsmall,denseLDL0.1Relativeriskformyocardialinfarction110Increasedriskwithsmall,denseLDLSmall,denseLDLincreases

cardiovascularriskMaleGender-adjustedFemaleReducUKPDS

StepwiseSelectionofRiskFactors*inPatientswithType2Diabetes

VariableLDL-CHDL-CHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.UKPDS

StepwiseSelectionofRMangagingoverweightintype2diabeticsEffectiveweightmanagementisthefirststepintreatingtype2diabetesWeightloss(kg)infirst12monthsLeanMEJetal.,DiabetMed,1990;7:228-233Lifeexpectancy(years)95%confidenceinterval1816141210800481216Mangagingoverweightintype2Weightlossisdifficulttomaintainbydietandexercisealoneintype2diabetesUKPDS34.Lancet1998;352:354InsulinChlorpropamideGllbenclamideDietaloneMetforminWeightchange(kg)76543210-10246810YearsfromrandomisationWeightlossisdifficulttomaGoodglycemiccontrolisnotenoughUKPDSGOODGLYCEMICCONTROLMICROVASCULARCOMPLICATIONSSignificantreductionsMACROVASCULARCOMPLICATIONSNosignificanteffectGoodglycemiccontrolisnotePROACTIVEStudySept.2005,欧洲糖尿病会议

PioglitazonevsPlaceboPROACTIVEStudySept.2005,欧洲糖ACCORDStudyActiontoControlCardiovascularriskinDiabetesPrisantLM.JClinPharmacol2004;44(4):423-430HbA1c:≤6.0%vs7.0-7.9%ACCORDStudyPrisantLM.JClin

糖尿病患者降压治疗临床试验SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDS

糖尿病患者降压治疗临床试验SHEPMajorcardiovascularevents(per100patients-years)inalltreatedhypertensiveandinhypertensivepatientswithdiabetesinrelationtotargetbloodpressuresof90.85,and80mmHg.302520151050808590908580P=0.50fortrendP=0.005fortrendAllhypertensivepatients(n=18790)Hypertensivewithdiabetes(n=1501)TargetbloodpressuregroupsMajorcardiovascularevents/1000patients-yearsHOTStudy:ResultsinPatientswithDMMajorcardiovascularevents(pEffectofIntensivevsModerateAntihypertensiveTreatmentonStrokeIncidenceinDiabeticNormotensives Intensive ModerateAchievedBP(mmHg) 128/75 137/81Stroke(%) 1.7 5.4P=0.03Schrieretal.,KidneyInt2002;61:1086EffectofIntensivevsModeratCHDPreventionTrialswithStatinsinDiabeticSubjects

SubgroupAnalyses

PrimaryPreventionAFCAPS/TexCAPSSecondaryPreventionCARE4SLIPID4S-ExtendedCHDRisk

Reduction

(overall)DrugNo.LovastatinPravastatinSimvastatinPravastatinSimvastatin43%25%(p=0.05)55%(p=0.002)19%42%(p=0.001)37%23%32%25%32%239586202782483CHDRisk

Reduction

(diabetes)StudyAdaptedfromDownsJRetal.JAMA1998;279:1615-1622;GoldbergRBetal.Circulation1998;98:2513-2519;PyöräläKetal.DiabetesCare1997;20:614-620;TheLong-TermInterventionwithPravastatininIschaemicDisease(LIPID)StudyGroup.NEnglJMed1998;339:1349-1357;HaffnerSMetal.ArchInternMed1999;159:2661-2667.CHDPreventionTrialswithStaCARDS:主要终点年安慰剂组事件数127立普妥®组事件数83累积危险(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.

37％CARDS:主要终点年安慰剂组事件数127立普妥®组事TrialswithFibratesinPatientswithDiabetesStudyEffectp-valueCommentHelsinkiHeartStudy(gemfibrozil)75%eventsnsPrimaryprevention;

post-hocsubgroupanalysisSENDCAP(bezafibrate)65%events0.01SpecificallyconductedinType2diabetes;post-hocanalysisforIHDVA-HIT(gemfibrozil)24%events0.05Secondaryintervention;pre-plannedsubgroupanalysisDAIS(fenofibrate)40-42%focalangiochanges0.02SpecificallyconductedinType2diabetes;mixedprimaryandsecondaryintervention;angiostudyTrialswithFibratesinPatienFIELDStudyFenofibrateInterventionandEventLoweringinDiabetesMazzoneT.AmJCardiol2004;93:27C-31CFIELDStudyMazzoneT.AmJCa糖尿病患者心血管危险因素的控制目标★减轻体重★降糖:HbA1c≤7.0%★降压:130/80★调脂:LDL-C1.81mmol/L糖尿病患者心血管危险因素的控制目标★减轻体重Steno-2StudyMultifactorialInterventionandCardiovascularDiseaseinPatientswithType2DiabetesGradeP,etal.NENGLJMED2003;348:383-393Steno-2StudyGradeP,etal.Steno-2:IntensiveTherapyNEJM2000;342:905-912BasicIntervention脂肪摄入30%饱和脂肪酸摄入10%运动30’35次/wACEIorARB多种维生素AspirinPharmacologyIntervention降糖

metformingliclazide

metformin+gliclazide降压

thiazideACEIorARB+CCB

-blocker降脂statinsSteno-2:IntensiveTherapyNEJMSteno-2:TreatmentGoalsVariable ConventionalIntensive Therapy TherapySBP(mmHg) 140130

DBP(mmHg) 8580

Hba1c(%)6.56.5TC(mg/dl)190175

TG(mg/dl)

150150Steno-2:TreatmentGoalsVariabSteno-2ChangeinClinicalVariablesattheEndoftheStudyVariableConventionalIntensivepTherapy TherapySBP(mmHg) -33-1420.001DBP(mmHg)-82-1220.006

Carbohydrates(%)4.80.99.30.9

0.001FPG(mg/dl)-1811-5280.001HbA1c(%)0.20.3-0.50.20.001

TC(mg/dl)-37-5040.001LDL-C(mg/dl)-136-4750.001

TG(mg/dl)

943-41140.015

Steno-2VariableSteno-2Study:CompositeEndPointGradePetal.NEnglJMed2003;348:383-393Primarycompositeendpoint(%)605040302010001224364860728496Monthsoffollow-upHazardratio=0.47(95%Cl0.24,0.73)

P=0.008ConventionalTherapyIntensivetherapySteno-2Study:CompositeEndP小结T2DM患者有多重心血管危险因素集聚，是心血管高危人群。T2DM治疗的主要目标应该转移到预防或延缓心血管病事件。在改善生活行为的同时，积极有效地实施降压、降脂和降糖综合措施，是控制糖尿病患者心血管危险的主要治疗策略。小结T2DM患者有多重心血管危险因素集聚控制糖尿病患者心血管危险

的干预治疗策略控制糖尿病患者心血管危险

的干预治疗策略糖尿病与心血管危险影响心血管危险的因素综合控制的理论与实践糖尿病与心血管危险CountriesWithHighestNumbersofEstimatedCasesofDiabetesfor2000and2030RankingCountryPeoplewithdiabetes(millions)CountryPeoplewithdiabetes(millions)200020301 India 31.7 India 79.42 China 20.8 China 42.33 U.S. 17.7 U.S. 30.34 Indonesia 8.4 Indonesia 21.35 Japan 6.8 Pakistan 13.96 Pakistan 5.2 Brazil 11.37 RussianFederation 4.6 Bangladesh 11.18 Brazil 4.6 Japan 8.99 Italy 4.3 Pinecones 7.810 Bangladesh 3.2 Egypt1 6.7Total:177million366MILLIONBY2030CountriesWithHighestNumbersType2diabetesandCHD

7-YearIncidenceofFatal/NonfatalMI(EastWestStudy)

IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI18.8HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)3.00.57.83.23.545.020.2Eventsper

100person-yr:P<0.001p<0.001Type2diabetesandCHD

7-YearType2diabetesandStroke

7-YearIncidenceofFatal/NonfatalStroke(EastWestStudy)IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI7.2HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)1.20.33.41.61.919.510.3Eventsper

100person-yr:P=0.01p<0.001Type2diabetesandStroke

7-YPrevalenceofCHDbytheMetabolicSyndromeandDiabetesintheNHANESPopulationAge50+AlexanderCetal.Diabetes2003;52:1210-121425%20%15%10%5%0%NoMS/NoDM8.7%13.9%7.5%19.2%MS/NoDMDM/NoMSDM/MS%ofpopulation= 54.2% 28.7% 2.3% 14.8%CHDPrevalencePrevalenceofCHDbytheMetab1.00.90.80.70.60.00246810Follow-up,years#atrisk174214099062828935NometabolicsyndromeMetabolicsyndromelog-rank=45.4p<0.001Event-freesurvivalSchillaciG.JACC.2004;43:1817-1822代谢综合征与心血管危险1.00.90.80.70.60.00246810FolloMlandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationMlMicrovascularandpointsMlMicrovascularandpoints50403020100806040200Adjustedincidenceper1000person-yr(%)110120130140150160170567891011UpdatedmeansystolicBP(mmHg)UpdatedmeanHbA1cconcentration(%)Adjustedincidenceper1000person-yr(%)AdlerAletal.BMJ2000;321:412-419StrationIMetal.BMJ2000;321:405-412MlandMicrovascularEndPointMetS和DM患者血脂异常特征游离脂肪酸TGHDL-C

VLDL-C

小而密LDL颗粒氧化LDL-C餐后高脂血症MetS和DM患者血脂异常特征游离脂肪酸MaleGender-adjustedFemaleReducedriskwithsmall,denseLDL0.1Relativeriskformyocardialinfarction110Increasedriskwithsmall,denseLDLSmall,denseLDLincreases

cardiovascularriskMaleGender-adjustedFemaleReducUKPDS

StepwiseSelectionofRiskFactors*inPatientswithType2Diabetes

VariableLDL-CHDL-CHemoglobinA1cSystolicBloodPressureSmokingPValue<0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.UKPDS

StepwiseSelectionofRMangagingoverweightintype2diabeticsEffectiveweightmanagementisthefirststepintreatingtype2diabetesWeightloss(kg)infirst12monthsLeanMEJetal.,DiabetMed,1990;7:228-233Lifeexpectancy(years)95%confidenceinterval1816141210800481216Mangagingoverweightintype2Weightlossisdifficulttomaintainbydietandexercisealoneintype2diabetesUKPDS34.Lancet1998;352:354InsulinChlorpropamideGllbenclamideDietaloneMetforminWeightchange(kg)76543210-10246810YearsfromrandomisationWeightlossisdifficulttomaGoodglycemiccontrolisnotenoughUKPDSGOODGLYCEMICCONTROLMICROVASCULARCOMPLICATIONSSignificantreductionsMACROVASCULARCOMPLICATIONSNosignificanteffectGoodglycemiccontrolisnotePROACTIVEStudySept.2005,欧洲糖尿病会议

PioglitazonevsPlaceboPROACTIVEStudySept.2005,欧洲糖ACCORDStudyActiontoControlCardiovascularriskinDiabetesPrisantLM.JClinPharmacol2004;44(4):423-430HbA1c:≤6.0%vs7.0-7.9%ACCORDStudyPrisantLM.JClin

糖尿病患者降压治疗临床试验SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDS

糖尿病患者降压治疗临床试验SHEPMajorcardiovascularevents(per100patients-years)inalltreatedhypertensiveandinhypertensivepatientswithdiabetesinrelationtotargetbloodpressuresof90.85,and80mmHg.302520151050808590908580P=0.50fortrendP=0.005fortrendAllhypertensivepatients(n=18790)Hypertensivewithdiabetes(n=1501)TargetbloodpressuregroupsMajorcardiovascularevents/1000patients-yearsHOTStudy:ResultsinPatientswithDMMajorcardiovascularevents(pEffectofIntensivevsModerateAntihypertensiveTreatmentonStrokeIncidenceinDiabeticNormotensives Intensive ModerateAchievedBP(mmHg) 128/75 137/81Stroke(%) 1.7 5.4P=0.03Schrieretal.,KidneyInt2002;61:1086EffectofIntensivevsModeratCHDPreventionTrialswithStatinsinDiabeticSubjects

SubgroupAnalyses

PrimaryPreventionAFCAPS/TexCAPSSecondaryPreventionCARE4SLIPID4S-ExtendedCHDRisk

Reduction

(overall)DrugNo.LovastatinPravastatinSimvastatinPravastatinSimvastatin43%25%(p=0.05)55%(p=0.002)19%42%(p=0.001)37%23%32%25%32%239586202782483CHDRisk

Reduction

(diabetes)StudyAdaptedfromDownsJRetal.JAMA1998;279:1615-1622;GoldbergRBetal.Circulation1998;98:2513-2519;PyöräläKetal.DiabetesCare1997;20:614-620;TheLong-TermInterventionwithPravastatininIschaemicDisease(LIPID)StudyGroup.NEnglJMed1998;339:1349-1357;HaffnerSMetal.ArchInternMed1999;159:2661-2667.CHDPreventionTrialswithStaCARDS:主要终点年安慰剂组事件数127立普妥®组事件数83累积危险(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.

37％CARDS:主要终点年安慰剂组事件数127立普妥®组事TrialswithFibratesinPatientswithDiabetesStudyEffectp-valueCommentHelsinkiHeartStudy(gemfibrozil)75%eventsnsPrimaryprevention;

post-hocsubgroupanalysisSENDCAP(bezafibrate)65%events0.01SpecificallyconductedinType2diabetes;post-hocanalysisforIHDVA-HIT(gemfibrozil)24%events0.05Secondaryintervention;pre-plannedsubgroupanalysisDAIS(fenofibrate)40-42%focalangiochanges0.02SpecificallyconductedinType2diabetes;mixedprimaryandsecondaryintervention;angiostudyTrialswithFibratesinPatienFIELDStudyFenofibrateInterventionandEventLoweringinDiabetesMazzoneT.AmJCardiol2004;93:27C-31CFIELDStudyMazzoneT.AmJCa糖尿病患者心血管危险因素的控制目标★减轻体重★降糖:HbA1c≤7.0%★降压:130/80★调脂:LDL-C1.81mmol/L糖尿病患者心血管危险因素的控制目标★减轻体重Steno-2StudyMultifactorialInterventionandCardiovascularDiseaseinPatientswithType2DiabetesGradeP,etal.NENGLJMED2003;348:383-393Steno-2StudyGradeP,etal.Steno-2:IntensiveTherapyNEJM2000;342:905-912BasicIntervention脂肪摄入30%饱和脂肪酸摄入10%运动30’35次/wACEIorARB多种维生素AspirinPharmacologyIntervention降糖

metformingliclazide

metformin+gliclazide降压

thiazideACEIorARB+CCB

-blocker降脂statinsSteno-2:IntensiveTherapyNEJMSteno-2:TreatmentGoalsVariable Conventional