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CountriesWithHighestNumbersofEstimatedCasesofDiabetesfor2000and2030RankingCountryPeoplewithdiabetes(millions)CountryPeoplewithdiabetes(millions)200020301India31.7India79.42China20.8China42.33U.S.17.7U.S.30.34Indonesia8.4Indonesia21.35Japan6.8Pakistan13.96Pakistan5.2Brazil11.37RussianFederation4.6Bangladesh11.18Brazil4.6Japan8.99Italy4.3Pinecones7.810Bangladesh3.2Egypt16.7Total:177million366MILLIONBY2030Type2diabetesandCHD7-YearIncidenceofFatal/NonfatalMI(EastWestStudy)01020304050IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI18.8HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)3.00.57.83.23.545.020.2Eventsper100person-yr:P0.001p0.001Type2diabetesandStroke7-YearIncidenceofFatal/NonfatalStroke(EastWestStudy)0510152025IncidenceDuringFollow-up(%)(n=69)NondiabeticswithpriorMINondiabeticswithnopriorMIDiabeticswithpriorMIDiabeticswithnopriorMI7.2HaffnerSMetal.NEnglJMed1998;339:229-234.(n=1304)(n=169)(n=890)1.20.33.41.61.919.510.3Eventsper100person-yr:P=0.01p0.001PrevalenceofCHDbytheMetabolicSyndromeandDiabetesintheNHANESPopulationAge50+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%CHDPrevalence1.00.90.80.70.60.00246810Follow-up,years#atrisk174214099062828935NometabolicsyndromeMetabolicsyndromelog-rank=45.4p0.001Event-freesurvivalSchillaciG.JACC.2004;43:1817-1822代谢综合征与心血管危险MlandMicrovascularEndPoints:IncidencebyMeanSystolicBPandHbA1cConcentrationMlMicrovascularandpointsMlMicrovascularandpoints50403020100806040200Adjustedincidenceper1000person-yr(%)110120130140150160170567891011UpdatedmeansystolicBP(mmHg)UpdatedmeanHbA1cconcentration(%)Adjustedincidenceper1000person-yr(%)AdlerAletal.BMJ2000;321:412-419StrationIMetal.BMJ2000;321:405-412MetS和DM患者血脂异常特征•游离脂肪酸•TG•HDL-C•VLDL-C•小而密LDL颗粒•氧化LDL-C•餐后高脂血症MaleGender-adjustedFemaleReducedriskwithsmall,denseLDL0.1Relativeriskformyocardialinfarction110Increasedriskwithsmall,denseLDLSmall,denseLDLincreasescardiovascularriskUKPDSStepwiseSelectionofRiskFactors*inPatientswithType2DiabetesVariableLDL-CHDL-CHemoglobinA1cSystolicBloodPressureSmokingPValue0.00010.00010.00220.00650.056CoronaryArteryDisease(n=280)PositioninModelFirstSecondThirdFourthFifth*Adjustedforageandsex.TurnerRCetal.BMJ1998;316:823-828.Mangagingoverweightintype2diabeticsEffectiveweightmanagementisthefirststepintreatingtype2diabetesWeightloss(kg)infirst12monthsLeanMEJetal.,DiabetMed,1990;7:228-233Lifeexpectancy(years)95%confidenceinterval1816141210800481216Weightlossisdifficulttomaintainbydietandexercisealoneintype2diabetesUKPDS34.Lancet1998;352:354InsulinChlorpropamideGllbenclamideDietaloneMetforminWeightchange(kg)76543210-10246810YearsfromrandomisationGoodglycemiccontrolisnotenoughUKPDSGOODGLYCEMICCONTROLMICROVASCULARCOMPLICATIONSSignificantreductionsMACROVASCULARCOMPLICATIONSNosignificanteffectPROACTIVEStudySept.2005,欧洲糖尿病会议PioglitazonevsPlaceboACCORDStudyActiontoControlCardiovascularriskinDiabetesPrisantLM.JClinPharmacol2004;44(4):423-430HbA1c:≤6.0%vs7.0-7.9%糖尿病患者降压治疗临床试验SHEPALLHATSYST-EURHOPECAPPPHOTNORDILRENAALSTOP-2PRIMEINSIGHTLIFEUKPDSMajorcardiovascularevents(per100patients-years)inalltreatedhypertensiveandinhypertensivepatientswithdiabetesinrelationtotargetbloodpressuresof90.85,and80mmHg.302520151050808590908580P=0.50fortrendP=0.005fortrendAllhypertensivepatients(n=18790)Hypertensivewithdiabetes(n=1501)TargetbloodpressuregroupsMajorcardiovascularevents/1000patients-yearsHOTStudy:ResultsinPatientswithDMEffectofIntensivevsModerateAntihypertensiveTreatmentonStrokeIncidenceinDiabeticNormotensivesIntensiveModerateAchievedBP(mmHg)128/75137/81Stroke(%)1.75.4P=0.03Schrieretal.,KidneyInt2002;61:1086CHDPreventionTrialswithStatinsinDiabeticSubjectsSubgroupAnalysesPrimaryPreventionAFCAPS/TexCAPSSecondaryPreventionCARE4SLIPID4S-ExtendedCHDRiskReduction(overall)DrugNo.LovastatinPravastatinSimvastatinPravastatinSimvastatin43%25%(p=0.05)55%(p=0.002)19%42%(p=0.001)37%23%32%25%32%239586202782483CHDRiskReduction(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.CARDS: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％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;angiostudyFIELD