冠心病危险因素新视点课件.ppt

1、1874 Waters D Slide#115th Great Wall International Congressof CardiologyBeijing,ChinaDavid D.Waters,MDOctober 18,20041874 Waters D Slide#2FernandoBoteroLady with aGreen Parrot1874 Waters D Slide#31874 Waters D Slide#41874 Waters D Slide#51874 Waters D Slide#660,000,000 obese adults in China7.1%of th

2、e populationthis number has doubled in 10 yrsHealth Ministry report(Oct 13,2004)Guan Chen,age 24,191 Kg1874 Waters D Slide#7the prevalence of type 2 diabetes and obesity are increasing dramatically in most of the worldLDL-cholesterol can now be readily controlled with statinsnew risk factors such as

3、 hs-CRP and CAC score by EBCT are entering clinical usetreatments proven to reduce risk are being greatly underutilizedworldwide,aggressive marketing of tobacco and the availability of cheap atherogenic foods will lead to an epidemic of coronary disease1874 Waters D Slide#8cross-sectional survey in

4、a nationally representative sample of 15,540 Chinese adults age 35 to 74,conducted in 2000-0124%had borderline high total cholesterol(200-240 mg/dl)and 9%had high cholesterol(240 mg/dl)17%had LDL-C between 130-159 mg/dl,5%had LDL-C between 160-189 mg/dl,and 2.7%had an LDL-C 190 mg/dl19%had low HDL-c

5、holesterol(40 mg/dl)only 8.8%of men and 7.5%of women were aware of their condition;only 3.5%were treatedHe J,et al,Circulation 2004;110:4051874 Waters D Slide#9validated model using MONICA and Sino-MONICA databetween 1984 and 1989,CHD mortality rates increased by 50%in men and 27%in women aged 35-74

6、 yearstotal cholesterol increased from 166 to 206 mg/dlsmoking prevalence increased from 49%to 57%in men and decreased in women from 16%to 9%prevalence of diabetes increased from3%to 9%BMI increased from 23.9 to 24.9 kg/m2Critchley J,et al,Circulation 2004;110:12361874 Waters D Slide#10changes in ri

7、sk factors together produced a best estimate of 1,822 more CHD deaths in 1999 compared to 1984cholesterol77%diabetes19%BMI 4%smoking 1%improved treatments prevented or postponed an estimated 642 deathstreatment of MI41%treatment of hypertension24%secondary prevention11%heart failure10%CABG and PTCA

8、2%Critchley J,et al,Circulation 2004;110:12361874 Waters D Slide#11Law MR and Wald NJ.BMJ 2002;324:1570-1576.Diastolic BP320.5Relative riskRelativerisk708090100110Usual DBP(mm Hg)Serum Cholesterol4567mmol/LBody Mass IndexRelativeriskkg/m2 3210.52530354010.253211.50.751874 Waters D Slide#121874 Water

9、s D Slide#135%1.20.6%decline/yr in BMD in postmenopausal women10%2722BMI,age 601%230 mg/dL120 mg/dLSerum cholesterol,age 605%80 mm Hg70 mm HgDiastolic BP,age 601%145 mm Hg110 mm HgSystolic BP,age 60Current Western Pop 90th PercentileAssociated DisorderPhysiologic Variable1874 Waters D Slide#15Reduci

10、ng the risk factor reduces the risk of an event by a constant proportion of the existing risk,irrespective of the starting level of the risk factor or of the riskWhether a risk factor should be treated thus depends on the level of risk,not the level of the risk factorAll reversible risk factors shou

11、ld be treated in a patient at high riskTerms like hypertension and hypercholesterolemia that focus on the tails of the distribution of physiologic variables are misleading and thus best avoidedLaw MR and Wald NJ.BMJ.2002;324:1570-1576.1874 Waters D Slide#1620,536 patients in the U.K.at increased ris

12、k of CHD death due to:MI or other coronary heart diseaseocclusive disease of noncoronary arteriesdiabetes mellitus or treated hypertensionAge 40-80 yrTotal cholesterol 3.5 mmol/L(135 mg/dL)Randomized to simvastatin 40 mg/day or placebo and followed for 5 years1874 Waters D Slide#17VascularEventTotal

13、 CHDTotal strokeRevascularizationANY OF ABOVEStatinPlacebo(10,269)(10,267)9141234 456 613 926118520422606(19.9%)(25.4%)Risk Ratio and 95%Cl Statin better Statin worse0.40.60.81.01.21.424%SE 2.6reduction(2p0.00001)No.Events1874 Waters D Slide#18BaselineFeatureLDL(mg/dL)100(2.6 mmol/L)100 130130(3.4 m

14、mol/L)ALL PATIENTSStatinPlacebo(10,269)(10,267)285 360 670 8811087136520422606(19.9%)(25.4%)0.40.60.81.01.21.424%SE 2.6reduction(2p6.5 mmol/L(250 mg/dL)4000 TC 6.5 mmol/L(250 mg/dL)5000 TC 6.5 mmol/L(250 mg/dL)R500 open lipid lowering45002250 statin2250 placebo2250 placebo2250 statinR4500500 open li

15、pid lowering+8000 open lipid lowering18,000 hypertensivesR=Randomized1874 Waters D Slide#22 To compare the effects of atorvastatin 10 mg and placebo on cardiac death+nonfatal MI in hypertensive patients with total cholesterol levels of 6.5 mmol/L(250 mg/dL)Sever PS,et al,Lancet 2003;361:1149Eligibil

16、ity criteriaSBP 160 mm Hg and/or DBP 100 mm Hg(untreated)or SBP 140 mm Hg and/or DBP 90 mm Hg(treated)TC 6.5 mmol/L(250 mg/dL)and TGs 4.5 mmol/L(400 mg/dL)40-79 years of age3+CVD risk factorsNo history of CHDSever PS,et al,Lancet 2003;361:11491874 Waters D Slide#242460123Atorvastatin 10 mgPlacebo123

17、4012320015015075125100100(mg/dL)(mg/dL)Total cholesterol(mmol/L)LDL cholesterol(mmol/L)Years50 mg/dL42 mg/dL46 mg/dL39 mg/dLSever PS et al,Lancet 2003;361:11491874 Waters D Slide#25012340.00.51.01.52.02.53.03.5YearsCumulative Incidence(%)36%reductionHR=0.64(0.50-0.83)Atorvastatin 10 mgNumber of even

18、ts100PlaceboNumber of events 154p=0.0005Sever PS,et al,Lancet 2003;361:11491874 Waters D Slide#2627%reductionHR=0.73(0.56-0.96)p=0.0235Atorvastatin 10 mgNumber of events 89PlaceboNumber of events12101230.00.51.01.52.02.53.03.5YearsCumulative Incidence(%)Sever PS,et al,Lancet 2003;361:11491874 Waters

19、 D Slide#27Percentage with CHD eventPrimary preventionPravastatinLovastatinAtorvastatin105.4(210)2.3(90)2.8(110)3.4(130)3.9(150)4.4(170)4.9(190)WOSCOPS-SWOSCOPS-P05AFCAPS-SAFCAPS-P98764321ASCOT-PASCOT-SLDL-C,mmol/L(mg/dL)S=statin treated;P=placebo treated1874 Waters D Slide#281874 Waters D Slide#29I

20、n 1986 Ella underwent quintuple coronary bypass surgery,and was diagnosed as having diabetes,which accounted for her failing vision.By 1991 she had recorded over 200 albums and gave her 26th and final concert at Carnegie Hall.She developed severe circulatory problems due to her diabetes,requiring be

21、low the knee amputations of both legs.She never fully recovered,and died at age 79 in 1996.1874 Waters D Slide#30BaselineFeaturePrevious MIOther CHD(not MI)No prior CHD CVD PVD DiabetesALL PATIENTS Statin Placebo (10,269)(10,267)10071255 452 597 182 215 332 427 279 36920422606(19.9%)(25.4%)Risk Rati

22、o and 95%Cl Statin better Statin worse0.40.60.81.01.21.424%SE 2.6reduction(2p0.00001)No.Events1874 Waters D Slide#31Aim:To evaluate the effectiveness and safety of atorvastatin 10 mg daily versus placebo in the primary prevention of cardiovascular disease(CAD and stroke)in patients with type 2 diabe

23、tes without raised cholesterol levels1874 Waters D Slide#32CARDS Eligibility CriteriaType 2 diabetes 40-75 years of ageNo clinical history of coronary,cerebrovascular or severe peripheral vascular diseaseLDL-C 4.14 mmol/L(160 mg/dL)TG 6.78 mmol/L(600 mg/dL)One of:Hypertension defined as receiving an

24、tihypertensive treatment or SBP 140 mm Hg or DBP 90 mm HgRetinopathyMicroalbuminuria or macroalbuminuriaCurrent smoking1874 Waters D Slide#33132 Centres in UK and Ireland4053 patients screened2838(70%)randomized1874 Waters D Slide#34PlaceboAtorvastatinAge(years)61.861.5Women32%32%Hypertension84%84%C

25、urrent smoking23%22%BMI28.828.7Diabetes duration(years)7.87.9 oral treatment only65%65%insulin only15%15%diet only16%15%HbA1C(%)7.87.9 retinopathy30%30%1874 Waters D Slide#35Lipid Levels by TreatmentTotal cholesterol(mmol/L)LDL cholesterol(mmol/L)023414.523414.5Years of StudyYears of Study0012340246

26、PlaceboAtorvastatinAverage difference 26%1.4 mmol/L(54 mg/dL)p0.0001Average difference 40%1.2 mmol/L(46 mg/dL)p0.00011874 Waters D Slide#36Cumulative Hazard for Primary EndpointRelative Risk Reduction 37%(95%CI:17-52)Years328305694651107410221361130613921351AtorvaPlacebo14281410Placebo127 eventsAtor

27、vastatin83 eventsCumulative Hazard(%)051015012344.75P=0.001Subgroup*Placebo*Atorva*Hazard Ratio Risk Reduction(CI)LDL-C 3.06(120)66(9.5)44(6.1)38%(9-58)LDL-C 3.06(120)61(8.5)39(5.6)37%(6-58)p=0.96HDL-C 1.35(54)62(8.4)36(5.2)41%(11-61)HDL-C 1.35(54)65(9.6)47(6.4)35%(5-55)p=0.71Trig.1.7(150)67(9.6)40(

28、5.5)44%(18-62)Trig.20%stenosis)from 34 sitesrandomized to 18 months of treatment with atorvastatin 80 mg/day or pravastatin 40 mg/dayintracoronary ultrasound of 30 mm segment at baseline and end of studyprimary endpoint measure is percent change in total plaque volume for all slices of anatomically

29、comparable segments of the target coronary arteryNissen SE et al,JAMA 2004;291:10711874 Waters D Slide#440510152025303540455005101520253035404550-3-2-10123PravaAtorva25%46%LDL ReductionCRP ReductionPravaAtorva5%36%p0.0001p0.0001PravaAtorvaChange in Athero Volume2.7%-0.4%p=0.02Nissen SE et al,JAMA 20

30、04;291:10711874 Waters D Slide#45Mean change using linear regression analysis.95%confidence limits for mean values.Nissen et al.JAMA 2004;291:1071.%Change in low-density lipoprotein cholesterolPravastatin group(N=249)Atorvastatin group(N=253)520151005101580 70 60 50 40 30 20 100102080 70 60 50 40 30

31、 20 10010205201510051015Change in atheroma volume,mm31874 Waters D Slide#464,162 pts hospitalized with ACS within 10 daystotal cholesterol 240 mg/dl(30 days after ACS event)study designed to establish the“non-inferiority”of prava compared to atorva with respect to time to an endpoint eventCannon CP

32、et al,NEJM 2004;350.1874 Waters D Slide#47PROVE-IT:Changes in LDL-CholesterolNote:Changes in LDL-C may differ from prior trials:25%of patients on statins prior to ACS event ACS response lowers LDL-C from true baselineLDL-C(mg/dL)20406080100120Rand.30 Days 4 Mos.8 Mos.16 Mos.FinalPravastatin 40mg Ato

33、rvastatin 80mgP0.00130 dUA Hosp0.751.25Atorva 80 mg betterPrava 40 mg betterCHD DeathStrokeCannon CP,et al NEJM 2004;350:1495PROVE-IT:Event Reduction in SubgroupsAll pinteraction=NS except as notedAge 65Age 65MaleFemale0.50.751.01.251.5DiabetesNo Diabetes 2 Year Event Rates Atorva 80 Prava 4023.0%26

34、.2%20.3%27.0%28.8%34.6%21.0%24.6%28.1%29.5%20.1%25.0%27.5%28.9%20.6%25.5%21.7%26.7%23.1%26.0%20.1%28.2%23.5%25.6%Prior StatinNo Prior StatinAtorvastatin 80 mg BetterPravastatin 40 mg Better LDL-C 125pi=0.02HDL-C 40%of Pts7822188230 7025 75 44 56 27 731874 Waters D Slide#51in patients at high risk fo

35、r vascular events,all traditional risk factors should be treated,even when levels of the individual risk factors are not elevatedsome risk factors(LDL-C and hypertension)are easy to treat,others are difficult(diabetes and smoking),and some cannot be treated(age and family history);make sure you get the easy onespatients at high risk remain grossly undertreatedincreasing evidence suggests that more aggressive cholesterol-lowering produces more event reduction