控制糖尿病患者心血管危險(xiǎn)

的干預(yù)治療策略控制糖尿病患者心血管危險(xiǎn)

的干預(yù)治療策略糖尿病與心血管危險(xiǎn)影響心血管危險(xiǎn)的因素綜合控制的理論與實(shí)踐糖尿病與心血管危險(xiǎn)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代謝綜合征與心血管危險(xiǎn)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患者血脂異常特征游離脂肪酸TGHDL-C

VLDL-C

小而密LDL顆粒氧化LDL-C餐后高脂血癥MetS和DM患者血脂異常特征游離脂肪酸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,歐洲糖尿病會(huì)議

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

糖尿病患者降壓治療臨床試驗(yàn)SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDS

糖尿病患者降壓治療臨床試驗(yàn)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;Py?r?l?Ketal.DiabetesCare1997;20:614-620;TheLong-TermInterventionwithPravastatininIschaemicDisease(LIPID)StudyGroup.NEnglJMed1998;339:1349-1357;HaffnerSMetal.ArchInternMed1999;159:2661-2667.CHDPreventionTrialswithStaCARDS:主要終點(diǎn)年安慰劑組事件數(shù)127立普妥?組事件數(shù)83累積危險(xiǎn)(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.

37％CARDS:主要終點(diǎn)年安慰劑組事件數(shù)127立普妥?組事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險(xiǎn)因素的控制目標(biāo)★減輕體重★降糖:HbA1c≤7.0%★降壓:130/80★調(diào)脂:LDL-C1.81mmol/L糖尿病患者心血管危險(xiǎn)因素的控制目標(biāo)★減輕體重Steno-2StudyMultifactorialInterventionandCardiovascularDiseaseinPatientswithType2DiabetesGradeP,etal.NENGLJMED2003;348:383-393Steno-2StudyGradeP,etal.Steno-2:IntensiveTherapyNEJM2000;342:905-912BasicIntervention脂肪攝入30%飽和脂肪酸攝入10%運(yùn)動(dòng)30’35次/wACEIorARB多種維生素AspirinPharmacologyIntervention降糖

metformingliclazide

metformin+gliclazide降壓

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小結(jié)T2DM患者有多重心血管危險(xiǎn)因素集聚，是心血管高危人群。T2DM治療的主要目標(biāo)應(yīng)該轉(zhuǎn)移到預(yù)防或延緩心血管病事件。在改善生活行為的同時(shí)，積極有效地實(shí)施降壓、降脂和降糖綜合措施，是控制糖尿病患者心血管危險(xiǎn)的主要治療策略。小結(jié)T2DM患者有多重心血管危險(xiǎn)因素集聚控制糖尿病患者心血管危險(xiǎn)

的干預(yù)治療策略控制糖尿病患者心血管危險(xiǎn)

的干預(yù)治療策略糖尿病與心血管危險(xiǎn)影響心血管危險(xiǎn)的因素綜合控制的理論與實(shí)踐糖尿病與心血管危險(xiǎn)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代謝綜合征與心血管危險(xiǎn)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患者血脂異常特征游離脂肪酸TGHDL-C

VLDL-C

小而密LDL顆粒氧化LDL-C餐后高脂血癥MetS和DM患者血脂異常特征游離脂肪酸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,歐洲糖尿病會(huì)議

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

糖尿病患者降壓治療臨床試驗(yàn)SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDS

糖尿病患者降壓治療臨床試驗(yàn)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;Py?r?l?Ketal.DiabetesCare1997;20:614-620;TheLong-TermInterventionwithPravastatininIschaemicDisease(LIPID)StudyGroup.NEnglJMed1998;339:1349-1357;HaffnerSMetal.ArchInternMed1999;159:2661-2667.CHDPreventionTrialswithStaCARDS:主要終點(diǎn)年安慰劑組事件數(shù)127立普妥?組事件數(shù)83累積危險(xiǎn)(%)051015012344.75P=0.001ColhounHM,BetteridgeDJ,DurringtonPN,etal.Lancet.2004;364:685-696.

37％CARDS:主要終點(diǎn)年安慰劑組事件數(shù)127立普妥?組事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險(xiǎn)因素的控制目標(biāo)★減輕體重★降糖:HbA1c≤7.0%★降壓:130/80★調(diào)脂:LDL-C1.81mmol/L糖尿病患者心血管危險(xiǎn)因素的控制目標(biāo)★減輕體重Steno-2StudyMultifactorialInterventionandCardiovascularDiseaseinPatientswithType2DiabetesGradeP,etal.NENGLJMED2003;348:383-393Steno-2StudyGradeP,etal.Steno-2:IntensiveTherapyNEJM2000;342:905-912BasicIntervention脂肪攝入30%飽和脂肪酸攝入10%運(yùn)動(dòng)30’35次/wACEIorARB多種維生素AspirinPharmacologyIntervention降糖

metformingliclazide

metformin+gliclazide降壓

thiazideACEIorARB+CCB

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