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Clinical Evaluation and Nonlipid Treatment of Coronary Artery Disease in the Diabetic PatientRichard Nesto,MDClinical Evaluation and NonlipPrevalence of Asymptomatic CAD in Diabetes MellitusKoistinen MJ.BMJ 1990;301:92-95.Type 2 Type 1 ControlsNaka M et al.Am Heart J 1992;123:46-53.Type 2 ControlsMiSAD Group.Am J Cardiol 1997;79:134-139.Type 2Rutter MK et al.Am J Cardiol 1999;83:27-31.Type 2 w microalb Type 2 w/o microalbLe A et al.Am J Kidney Dis 1994;24:65-71.Type 1 Renal TransplantHolley JL et al.Am J Med 1991;90:563-570.Type 1&2 Renal Transplant n=64 n=72 n=80 n=142 n=149 n=925 n=43 n=43 Positive Positive ETTETTPositive Positive AngiographyAngiography(thal201)36%24%9%31%30%12.1%65%40%58%55%9%11%9%12.1%5.3%6.4%35%43%Prevalence of Asymptomatic CADIndications for Cardiac Testing in Diabetic PatientsnTypical or atypical cardiac symptomsnResting ECG suggestive of ischemia or infarctionnPeripheral or carotid occlusive arterial diseasenSedentary lifestyle or plan to begin a vigorous exercise programnTwo or more of the risk factors listed below -Total cholesterol 240 mg/dL,LDL cholesterol 160 mg/dL,or HDL cholesterol 140/90 mmHg -Smoking -Family history of premature CAD -Positive micro/macroalbuminuriaIndications for Cardiac TestinFactors Limiting Accuracy of Noninvasive Stress Tests for CADnHypertensive CardiomyopathynDiabetic CardiomyopathynAutonomic CardiomyopathynRenal InsufficiencynMicrovascular DysfunctionFactors Limiting Accuracy of NBenefits of Early Detection of CADnImplement more aggressive CHD prevention regimennInitiate anti-ischemic medicationsnIdentify patients who would benefit from revascularizationnEducate patients to recognize coronary symptomsBenefits of Early Detection ofKannel WB et al.Am Heart J 1991;121:1268-1273.Blood Pressure and CVD:Blood Pressure and CVD:Framingham Heart StudyFramingham Heart StudyAge-adjusted CV Event Rate/1,000Systolic BP(mmHg)105135165195Systolic BP(mmHg)105135165195Age-adjusted CV Event Rate/1,00024503877591199017415312348367456113No Glucose IntoleranceGlucose IntoleranceNo Glucose IntoleranceGlucose IntoleranceMENMENWOMENWOMENKannel WB et al.Am Heart J 19UKPDS Group.Lancet 1998;352:837-853.Effect of Glycemic Control in the UK Prospective Diabetes Study(UKPDS)Any diabetes related*MIStrokePVDMicrovascular40.914.75.61.18.6 4617.4 51.611.40.0290.0520.520.150.0099111625(rate/1000 pt yrs)*Combined microvascular and macrovascular eventsIntensive%Decrease(rate/1000 pt yrs)PConventionalEndpointsUKPDS Group.Lancet 1998;352:8Reasons for Death in UKPDS Intensive Treatment Arm:10-Year Follow-upUKPDS Group.Lancet 1998;352:837-853.Fatal MI or SDCancerOtherFatal StrokeRenal DiseaseAccidentsPVDHypo-or Hyperglycemia231120744316521(8.4%)(4.4%)(2.9%)(1.6%)(0.6%)(0.2%)(0.07%)(0.04%)(%)N=272947%47%8.7%8.7%24%24%15%15%3.3%3.3%2.5%2.5%MI or SDMI or SDCancerCancerStrokeStrokeOtherOtherRenalRenalAccidents,PVD,Hypo-Accidents,PVD,Hypo-&Hyperglycemia&HyperglycemiaReasons for Death in UKPDS IntUKPDS Group.BMJ 1998;317:703-713.Effect of Blood Pressure Control in the UKPDSEffect of Blood Pressure Control in the UKPDSTight vs.Less Tight ControlTight vs.Less Tight ControlAny diabetes-related endpointDiabetes-related deathsHeart failureStrokeMyocardial infarctionMicrovascular diseaseTight Controln1,148 Type 2 patientsnAverage BP lowered to 144/82 mmHg(controls:154/87);9-year follow-up243256442137Risk Reduction(%)P value0.00460.0190.00430.013 NS0.0092UKPDS Group.BMJ 1998;317:703-UKPDS:ACE Inhibitor vs.Beta-blocker for HTNUKPDS:ACE Inhibitor vs.Beta-blocker for HTNAggregate Clinical Endpoints0.50.51 12 2Relative Risk&95%CIRelative Risk&95%CIAny diabetes-related endpointDiabetes-related deathsAll-cause mortalityMyocardial infarctionStrokeMicrovascular1.101.271.141.201.121.290.430.280.440.350.740.30p pRRRRUKPDS Group.BMJ 1998;317:713-720.FavorsFavorsACE inhibitorACE inhibitorFavorsFavorsBeta blockerBeta blockerUKPDS:ACE Inhibitor vs.Beta-PlaceboEvents/1000 Pt-YearsSystolic Hypertension in Europe(Syst-Eur)Trial:Systolic Hypertension in Europe(Syst-Eur)Trial:Effect of Systolic BP Control on All Cardiovascular Events Effect of Systolic BP Control on All Cardiovascular Events at 2 Yearsat 2 YearsTuomilehto J et al.NEJM 1999;340:677-684.N=492;N=492;P P=0.002=0.002Active Rx57.657.622.022.062%RiskRiskReductionReductionN=4,203;N=4,203;P P=0.02=0.0231.431.423.523.5PlaceboActive Rx25%RiskRiskReductionReductionDiabetic PatientsNondiabetic PatientsPlaceboEvents/1000 Pt-YearsSMajor CV EventsMIEvents/1000 Pt-YearsMajor Outcomes of the Hypertension Optimal Major Outcomes of the Hypertension Optimal Treatment(HOT)Trial:Treatment(HOT)Trial:Diabetes SubgroupDiabetes SubgroupHansson L et al.Lancet 1998;351:1755-1762.CV Mortality90 mmHg(N=501)85 mmHg(N=501)80 mmHg(N=499)Diastolic Targetp0.045p0.016p0.005Major CV EventsMIEvents/100090Events/1000 Pt-YearsHOT Trial:Cardiovascular Events in Diabetics and HOT Trial:Cardiovascular Events in Diabetics and NondiabeticsNondiabeticsEffect of Diastolic Target at 4 YearsEffect of Diastolic Target at 4 YearsHansson L et al.Lancet 1998;351:1755-1762.DiabeticDiabetic Patients Patientsn=1,501;p=0.016n=1,501;p=0.0168580908580NondiabeticNondiabetic Patients Patientsn=18,790;p=NSn=18,790;p=NS24.424.418.618.611.911.99.99.910.010.09.39.348%RiskRiskReductionReduction90Events/1000 Pt-YearsHOT TCompleted Clinical Trials with Antihypertensive Agents in DiabetesSHEP=Systolic Hypertension in the Elderly Program;GISSI=Grupo Italiano per lo Studio della Sopravvivenza nellInfarto Miocardico;Syst-Eur=Systolic Hypertension in Europe;HOT=Hypertension Optimal Treatment;CAPPP=Captopril Prevention ProjectCurb JD et al.JAMA 1996;276:1886-1892;Zuanetti G et al.Circulation 1997;96:4239-4245;Staessen JA et al.Am J Cardiol 1998;82:20R-22R;Hansson L et al.Lancet 1998;351:1755-1762;UK Prospective Diabetes Study Group.BMJ 1998;317:703-713;Hansson L et al.Lancet 1999;353:611-616.SHEPGISSI-3Syst-EurHOTUKPDSCAPPPResults on CVDResults on CVDDiabetic/TotalDiabetic/TotalTrialTrial583/47362790/18,131492/46951501/18,7901148572/10,985BeneficialBeneficialBeneficialBeneficialBeneficialBeneficialCompleted Clinical Trials withHeart Outcomes Prevention Evaluation(HOPE)StudyHeart Outcomes Prevention Evaluation(HOPE)StudyEffect of Ramipril on Cardiovascular Events(Myocardial Effect of Ramipril on Cardiovascular Events(Myocardial Infarction,Stroke,or CVD Death)4.5 Yrs Infarction,Stroke,or CVD Death)4.5 Yrs Hope Study Investigators.NEJM 2000;342:145-153.Placebo%of PatientsRamipril19.819.815.015.024%RiskRiskReductionReduction16.416.413.013.0PlaceboRamipril21%RiskRiskReductionReductionDiabetic PatientsNondiabetic PatientsN=3,578,N=3,578,P P=0.001=0.001N=5,719,N=5,719,P P=0.001=0.001Heart Outcomes Prevention EvalDiabetes Increases Risk of Coronary PlaqueDisruption and Thrombosis Cause of Myocardial InfarctionPlaquePlaqueFormationFormationF VIIF VIIF VIIIF VIIICoronary ArteryCoronary ArterySympathetic ToneSympathetic TonePAI-1PAI-1TPATPAPGIPGI2 2Platelet AggregationPlatelet AggregationFibrinogenFibrinogenvWFvWFThrombusThrombusPlaquePlaqueDisruptionDisruptionDiabetes Increases Risk of CorImpact of Serum Fibrinogen and Total Cholesterol Impact of Serum Fibrinogen and Total Cholesterol Levels on Risk of Coronary Events in ECATLevels on Risk of Coronary Events in ECATThompson SG.N Engl J Med 1995;332:635-641.FibrinogenLowerMiddleHigherHigherMiddleLowerTotal CholesterolRisk of Coronary Events(%)4/3069/26110/2825/3113/24710/28111/26616/30421/305Impact of Serum Fibrinogen andEffect of Aspirin on Mortality in Type 2 Patients with Effect of Aspirin on Mortality in Type 2 Patients with CHD:CHD:Bezafibrate Infarction Prevention StudyBezafibrate Infarction Prevention StudyHarpaz D et al.Am J Med 1998;105:494-499.Survival(%)NodiabetesType 2diabetesTime(Years)0123456No aspirinAspirinOR=0.8(0.7-0.9)OR=0.7(0.6-0.8)Effect of Aspirin on MortalityAntiplatelet Agents Reduce CVD Events in Patients with Diabetes:Antiplatelet Trialists CollaborationAntiplatelet Trialists Collaboration.BMJ 1994;308:81-106.CVD Events(%)DiabetesAntiplatelet TherapyControlNo DiabetesP0.002P0.00001Antiplatelet Agents Reduce CVDDiabetes Mellitus Insulin Glucose Infusion in Acute Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction(DIGAMI):Myocardial Infarction(DIGAMI):Benefit of Tight Glycemic Benefit of Tight Glycemic Control in No Insulin Low Risk CohortControl in No Insulin Low Risk CohortMalmberg K et al.BMJ 1997;314:1512-1515.0.70.60.50.40.30.20.100.70.60.50.40.30.20.10MortalityMortalityTotal CohortNo Insulin Low RiskYears in StudyYears in StudyControlInsulin-glucoseInfusion012345012345Insulin-glucoseInfusionControlp=.0111p=.004n=133n=139n=314n=306Diabetes Mellitus Insulin GlucEffect of Trandolapril on Post-MI CHF Progression:Effect of Trandolapril on Post-MI CHF Progression:Trandolapril Cardiac Evaluation(TRACE)Trandolapril Cardiac Evaluation(TRACE)YearsGustafsson I et al.J Am Coll Cardiol 1999;34:83-89.Diabetics(n=237)Diabetics(n=237)01234Event RateYearsNondiabetics(n=1512)Nondiabetics(n=1512)01234Event RateRelative risk,0.38P0.001Relative risk,0.81P=0.1PlaceboTrandolaprilPlaceboTrandolaprilEffect of Trandolapril on PostCardiovascular deathSudden deathReinfarctionProgression in CHFDiabeticsDiabeticsRR(95%CI)PRR(95%CI)PEnd PointEnd PointEffect of Trandolapril on Secondary Endpoints in TRACE0.56(0.37-0.85)0.46(0.25-0.85)0.55(0.29-1.07)0.38(0.21-0.67)0.79(0.66-0.96)0.84(0.63-1.12)0.93(0.69-1.26)0.81(0.63-1.04)0.170.090.150.03NondiabeticsNondiabeticsRR(95%CI)PRR(95%CI)PInteractionInteractionP PCI=confidence interval;RR=relative risk.Gustafsson I et al.J Am Coll Cardiol 1999;34:83-89.0.010.010.080.0010.020.230.650.10Cardiovascular deathDiabeticsEWoodfield SL et al.J Am Coll Cardiol 1996;28:1661-1669.Effect of Diabetes on 30-Day Mortality:Effect of Diabetes on 30-Day Mortality:Global Utilization of Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries(GUSTO-I)Coronary Arteries(GUSTO-I)2.72.12.42.0012345Odds Ratio for 30-Day MortalityDiabetes vs no diabetes(unadjusted)Adjusted for clinical variablesAdjusted for angiographicvariablesAdjusted for clinical&angiographic variablesWoodfield SL et al.J Am Coll Overall 5-Year Mortality in the Bypass Angioplasty Overall 5-Year Mortality in the Bypass Angioplasty Revascularization Investigation(BARI-1)Revascularization Investigation(BARI-1)Detre KM et al.N Engl J Med 2000;342:989-997.0MortalityDM-PTCADM-CABGNon DM-CABGNon DM-PTCAFollow-up(years)0.250.180.080.0712345Overall 5-Year Mortality in thImpact of PTCA vs.CABG on Mortality in BARI-1MortalityFollow-up(years)Years after Q-MIDM-PTCADM-CABGNon DM-CABGNon DM-PTCAMortalityMortality in PatientsMortality in Patientswithout Q-MIwithout Q-MIMortality in PatientsMortality in PatientsAfter Q-MIAfter Q-MI0123450123450.220.220.160.160.070.070.060.060.790.790.290.290.270.270.170.17Detre KM et al.N Engl J Med 2000;342:989-997.Impact of PTCA vs.CABG on MorImpact of Diabetes on 7-year Survival in BARIImpact of Diabetes on 7-year Survival in BARIBARI Investigators.J Am Coll Cardiol 2000;35:1122-1129.%Survival01345726YearsPatients without Treated DiabetesPatients without Treated Diabetes%Survival01345726All PatientsAll Patients%Survival01345726Patients with Treated DiabetesPatients with Treated Diabetesp=0.0425p=0.7155p=0.0011CABG(n=914)PTCA(n=915)CABG(n=180)PTCA(n=173)CABG(n=734)PTCA(n=742)84.480.976.455.786.886.4Impact of Diabetes on 7-year SEight-Year Mortality in Emory Angioplasty vs Surgery Eight-Year Mortality in Emory Angioplasty vs Surgery Trial(EAST)Trial(EAST)King SB III et al.J Am Coll Cardiol 2000;35:1116-1121.%SurvivalYears after RandomizationPatients without DiabetesPatients without Diabetes%SurvivalAll EAST PatientsAll EAST Patients%SurvivalTreated Diabetic PatientsTreated Diabetic Patientsp=0.40p=0.71p=0.23CABG(n=194)PTCA(n=198)CABG(n=30)PTCA(n=29)CABG(n=164)PTCA(n=169)01345827601345827601345827682.779.3Eight-Year Mortality in Emory 6-Month Angiographic Outcome after PTCA in Diabetes(377 Patients with 476 Lesions)Van Belle E et al.J Am Coll Cardiol 1999;34:476-485.Lesions(%)Angiographic FU=6 months62%PTCA Site(s)1 Site2 Sites3 SitesOverall Restenosis RateOverall Restenosis RateTotal OcclusionTotal Occlusion49%49%13%13%Restenosis(n=237)Total Occlusion(n=60)Patients(%)11%25%37%6-Month Angiographic Outcome aImpact of Restenosis and Total Occlusion on LV Function in DiabetesVan Belle E et al.J Am Coll Cardiol 1999;34:476-485.in EF(%)p=nsp=nsp=0.0001(n=297)(n=237)(n=60)Restenosis()Total Occlusion()Restenosis(+)Total Occlusion()Total Occlusion(+)-1.5+9.5+0.5+9.9-6.2+9.9Impact of Restenosis and TotalEffect of Stents on Target Vessel Effect of Stents on Target Vessel Revascularization(TVR)after PTCA in DiabetesRevascularization(TVR)after PTCA in Diabetes1.000.950.900.850.800.750.700Proportion Free of TVRp=0.021df=3,Log-rank TestRankin JM et al.Circulation 1998;98:I-79.Months Post PTCA024681012Year19941995199619971997199619951994N305425480288%Stent17.424.941.055.5Effect of Stents on Target VesEvaluation of Platelet IIb/IIIa Inhibitor for Stenting Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial(EPISTENT):Trial(EPISTENT):Benefit of Abciximab and Stenting in Benefit of Abciximab and Stenting in Diabetes on Reducing TVRDiabetes on Reducing TVRLincoff AM et al.N Engl J Med 1999;341:319-327.Days after RandomizationStent+PlaceboStent+AbciximabAngioplasty+AbciximabPatients with DiabetesPatients with Diabetes(n=491)(n=491)0309012018060150Incidence of repeated TVR at 6 mos.(%)Days after RandomizationPatients without DiabetesPatients without Diabetes(n=1908)(n=1908)0309012018060150Incidence of repeated TVR at 6 mos.(%)18.4%16.6%8.1%14.6%Stent+PlaceboStent+AbciximabAngioplasty+Abciximab9.0%8.8%Evaluation of Platelet IIb/III%of PatientsDaysEPISTENT:Optimization of PTCA/Stent Outcomes with Platelet IIb/IIIa InhibitionMarso SP et al.Circulation 1999;100:2477-2484.12.7%7.8%6.2%03090120180601506-Month Death,MI for Diabetics6-Month Death,MI for DiabeticsStent+PlaceboStent+AbciximabPTCA+Abciximabp=0.029%of PatientsDaysEPISTENT:OptConclusionsnidentify diabetic patients with particularly high risk for CAD and perform appropriate screening naggressively identify and modify coronary risk factorsnexplore and implement treatment to protect the left ventricle from ischemic injurynmaintain tight but judicious glycemic control in acute coronary syndromesnuse medications proven to dramatically improve outcomes in acute MI(beta blockers,ACE inhibitors,aspirin,IIb/IIIa platelet inhibitors,statins)In patients with diabetes mellitus,there are numerous opportunities In patients with diabetes mellitus,there are numerous opportunities to reduce morbidity and mortality from CAD:to reduce morbidity and mortality from CAD:Conclusionsidentify diabetic pFuture DirectionsnAdditional clinical trials are needed to evaluate cardiovascular therapeutic interventions in diabetic patients,because certain therapies may produce different results in the presence of diabetesFuture DirectionsAdditional cl谢谢您的聆听与观看THANK YOU FOR YOUR GUIDANCE.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。欢迎下载！汇报人：XXX日期：20XX年XX月XX日谢谢您的聆听与观看THANK YOU FOR YOUR GU
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