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Magnitude of the BurdenCauses of Death Magnitude of the BurdenCauses of Death in the United Statesin the United StatesDeaths in 1996(thousands)CVDCancerAccidentsHIV/AIDS959.2544.793.832.7American Heart Association.1999 Heart and Stroke Statistical Update.1998.Economic Direct and Indirect Cost of CVD in the Economic Direct and Indirect Cost of CVD in the United StatesUnited StatesHospital/nursing homePhysicians/other professionalsDrugsHome health/other medical durablesLost productivity/morbidityLost productivity/mortalityAmerican Heart Association.1999 Heart and Stroke Statistical Update.1998.Total direct andindirect costs:$286.5 billion5-Year Expected Total Cost per Case5-Year Expected Total Cost per CaseWittels EH et al.Am J Cardiol 1990;65:432440.Average Cost(1986$)CHD eventsAcute myocardial infarction51,211Angina pectoris24,980Unstable angina pectoris40,581Sudden death9,078ProceduresAngioplasty26,916Bypass surgery32,465Preventive Medicine CostsPreventive Medicine CostsnCost of preventive measuresTreatmentTestingComplications of preventive measuresnTreating cases that arise anywaynTreating diseases discoverednTreating other illnesses in population living longernPay“up-front”for benefit laternFalse positiveTreating those who will not develop diseaseCost-Effectiveness AnalysisCost-Effectiveness AnalysisnPurpose:Consider both the effectiveness and cost of an intervention Cost =Cost of medical intervention+cost of illnessEffectiveness=quality adjusted life year savedCE=Cost-effectiveness ratioCE2-1=Cost2 Cost1QALY2 QALY1Whose Costs Matter?Whose Costs Matter?Patient:The costs the patient bears directly(depends on co-payment)Insurance:Costs the insurance bears directlySocietal:Includes all costs and avoids double countingMeasuring CostsMeasuring CostsDirect Costs:Direct medical costs related to the diagnosis and treatment of the disease+disease-specific costs that may be induced or avertedIndirect Costs:Lost earningsOther Costs:Prolonged life increased cancer,nursing home patientsPremature events,disability payments,reduced productivityCost-Effectiveness:Cost-Effectiveness:Quality Adjusted Life YearsQuality Adjusted Life YearsMild hypertension male age 40$23,300Estrogen therapy postmenopausal Sx$32,900Neonatal intensive care$38,800School tuberculosis testing$53,300Hospital hemodialysis$65,900General Guidelines Incremental Cost-General Guidelines Incremental Cost-Effectiveness(QALY)Effectiveness(QALY)Goldman L et al.Circulation 1992;85:19601968.0$20,000 Very attractive$20,000$40,000 Currently funded Hemodialysis Rx mild hypertension$60,000$100,000 Currently accepted$100,000+UnattractiveCholesterol Lowering:Cholesterol Lowering:Cost-EffectivenessCost-EffectivenessGoldman L et al.JAMA 1991;265:11451151.TreatmentSexAgeCHDChol mg/dlCost/LifeYrLovastatinM35-54+2502503,500LovastatinM45-54-300110,000LovastatinW45-54-300320,000Cost Effectiveness of Simvastatin Cost Effectiveness of Simvastatin Treatment for 5 Years in 59-Year-Old Treatment for 5 Years in 59-Year-Old Patients with CHD and a Pretreatment Patients with CHD and a Pretreatment Total Cholesterol Level of 261 mg/dlTotal Cholesterol Level of 261 mg/dlDirect CostsDirect+Indirect CostsVariableMenWomenMenWomenCosts($)Intervention2,2422,4102,2422,410 Associated morbidity7187251,7831,601 Net1,5241,685459809Years of life gained0.280.160.280.16Cost per year($)5,40010,5001,6005,100Johannesson M et al.N Engl J Med 1997;336:332336.Copyright 1997 Massachusetts Medical Society.Cost Per Year of Life Gained in Patients Cost Per Year of Life Gained in Patients with CHD Who Received Simvastatin with CHD Who Received Simvastatin Treatment for 5 YearsTreatment for 5 YearsTC before treatment(mg/dl)Age 35Age 59Age 70MenWomenMenWomenMenWomenDirect costs 21311,40027,4007,00016,4006,20013,300 2618,80018,8005,50010,3004,7008,500 3096,70013,2004,2007,1003,8006,200Direct+indirect costs 213SavingsSavings2,1008,6006,20013,300 261SavingsSavings1,6004,9004,7008,500 309SavingsSavings1,2003,2003,8006,200Johannesson M et al.N Engl J Med 1997;336:332336.Copyright 1997 Massachusetts Medical Society.WOSCOPS Placebo Group 5-Year Total WOSCOPS Placebo Group 5-Year Total Event RatesEvent RatesWest of Scotland Coronary Prevention Group.Lancet 1996;348:13391342.Men 4554Men 5564Minor ECG11.921.2Smoking10.114.4HDL-C 40 mg/dl8.114.1HTN8.012.3Family CHD7.513.2High cholesterol3.55.3New Tests for Risk AssessmentNew Tests for Risk AssessmentI.Lipoprotein assessmentLipoprotein(a)*Apoproteins:apo B-100,*A-I,CIII-BLDL particle size Apo E genotype*Frequently used at Baylor Lipid Metabolism and Atherosclerosis ClinicLp(a)in Atherogenesis:Another Culprit?Lp(a)in Atherogenesis:Another Culprit?nIdentical to LDL particle except for addition of apo(a)nPlasma concentration predictive of atherosclerotic disease in many,although not all,epidemiologic studiesnAccumulates in atherosclerotic plaquenBinds apo Bcontaining lipoproteins and proteoglycansnTaken up by foam cell precursorsnMay interfere with thrombolysisMaher VMG et al.JAMA 1995;274:1771-1774.Stein JH et al.Arch Intern Med 1997;157:1170-1176.Effects of Lipid-Modulating Drugs on Lp(a)Effects of Lipid-Modulating Drugs on Lp(a)nNiacin and estrogen reduce Lp(a)levelsnApheresis reduces Lp(a)levelsnNo benefit from statinsnNo consistent benefit with fibrates,although studies are variableApo E GenotypeApo E GenotypenApo E mediates the metabolism of chylomicrons,chylomicron remnants,VLDL,IDL,and a subclass of HDL particles.1nThe 3 alleles of the apo E gene are associated with variations in LDL-C level,which is higher with 4 and lower with 2 compared with 3.2nLDL-C response to diet is reportedly greater in patients with 4,3 response to statins greater with 2 or 3.1Mahley RW.Science 1988;240:622-630.2Davignon J et al.Arteriosclerosis 1988;8:1-21.3Mnttri M et al.Metabolism 1991;40:217-221.Intensity Intensity of lipid-lowering therapy of lipid-lowering therapy is dependent upon theis dependent upon the absolute risk absolute risk for CHD eventsfor CHD eventsNCEP Risk Factors in Primary PreventionNCEP Risk Factors in Primary PreventionnPositive Risk FactorsnAgeMale 45 yearsFemale 55 years or premature menopause without ERTnFamily history of premature CHDnCurrent cigarette smokingnHypertension(140/90 mm Hg or on antihypertensive medication)nLow HDL-C(1.0 mm(n=272)nControls:IMT 260 ng/dlsICAM-1 260 ng/dl012301124824Years of Study Follow-UpRelative RiskRidker PM et al.Lancet 1998;351:88-92.Reprinted with permission from Elsevier Science.New Tests for Risk AssessmentNew Tests for Risk AssessmentIII.Noninvasive imaging of early atherosclerosisIV.Carotid ultrasoundIMTV.Ultrafast CTcalcium scoreVI.Magnetic resonance imagingIV.Noninvasive assessment of endothelial functionV.Brachial forearm flow reservePredictive Value of CAC ScorePredictive Value of CAC ScoreCAC scoreSensitivitySpecificityPPVNPVOR1000.890.770.0550.99825.81600.890.820.0710.99835.46800.500.950.1400.99220.0Arad Y et al.Circulation 1996;93:19511953.Limited Predictivity of Coronary Calcium Limited Predictivity of Coronary Calcium Score for Coronary Events:ROC Curve AreasScore for Coronary Events:ROC Curve AreasDetrano RC et al.Circulation 1999;99:2633-2638.MI or coronary deathP*MI,coronary death,or revascularizationP*Calcium score0.640.05.070.650.04.06Framingham model0.690.05.200.670.04.10Data-derived model0.680.05.090.690.04.06Data-derived model plus calcium score0.710.040.720.03*Comparison with highest area in preceding column.CT Monitoring of Effect of Therapy on CT Monitoring of Effect of Therapy on Plaque VolumePlaque VolumeNo Statin RxStatin Rx;LDL-C 120 mg/dlStatin Rx;LDL-C 120 mg/dlCalcium-Volume Scorep0.001p=0.005p=NSCallister TQ et al.N Engl J Med 1998;339:1972-1978.Copyright 1998 Massachusetts Medical Society.New Tools to Improve CHD Risk New Tools to Improve CHD Risk Stratification in Primary Prevention:Stratification in Primary Prevention:Framingham CHD Prediction EquationFramingham CHD Prediction EquationnIncorporates the following risk factors into a summary CHD risk score:nAge,sex,LDL-C,HTN,smoking,diabetesnCalculates 10-year absolute CHD risknAllows targeting of high-risk primary-prevention patientsWilson PWF et al.Circulation 1998;97:18371847.Improving Cost-Effectiveness of Lipid-Improving Cost-Effectiveness of Lipid-Lowering TreatmentLowering TreatmentIncrease treatment effectiveness:nImprove compliancenConsider agents(e.g.,niacin,estrogen)that improve HDL-C,Lp(a),or dense LDLnMore aggressive LDL-cholesterol reductions Improving Cost-Effectiveness of Lipid-Improving Cost-Effectiveness of Lipid-Lowering TreatmentLowering TreatmentReduce cost of therapy:nMaximize diet,exercise,smoking cessationnUse less expensive drugsnPill cutters演讲完毕，谢谢观看！Thank you for reading!In order to facilitate learning and use,the content of this document can be modified,adjusted and printed at will after downloading.Welcome to download!汇报人：XXX汇报日期：20XX年10月10日
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