冠心病危险因素新视点ppt课件

A New Look at Coronary Risk Factors,15th Great Wall International Congress of Cardiology Beijing, China David D. Waters, MD October 18, 2004,UCSF,Fernando Botero,Lady with a Green Parrot,Leonardo 16th Century Botero 20th Century,Obesity in China,60,000,000 obese adults in China 7.1% of the population this number has doubled in 10 yrs Health Ministry report (Oct 13, 2004),Guan Chen, age 24, 191 Kg,A New Look at Coronary Risk Factors,the prevalence of type 2 diabetes and obesity are increasing dramatically in most of the world LDL-cholesterol can now be readily controlled with statins new risk factors such as hs-CRP and CAC score by EBCT are entering clinical use treatments proven to reduce risk are being greatly underutilized worldwide, aggressive marketing of tobacco and the availability of cheap atherogenic foods will lead to an epidemic of coronary disease,Cardiovascular Disease Has Become the Leading Cause of Death in China,cross-sectional survey in a nationally representative sample of 15,540 Chinese adults age 35 to 74, conducted in 2000-01 24% 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/dl 19% had low HDL-cholesterol (40 mg/dl) only 8.8% of men and 7.5% of women were aware of their condition; only 3.5% were treated He J, et al, Circulation 2004;110:405,Explaining the Increase in Coronary Heart Disease Mortality in Beijing Between 1984 and 1999,validated model using MONICA and Sino-MONICA data between 1984 and 1989, CHD mortality rates increased by 50% in men and 27% in women aged 35-74 years total cholesterol increased from 166 to 206 mg/dl smoking 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/m2 Critchley J, et al, Circulation 2004;110:1236,Explaining the Increase in Coronary Heart Disease Mortality in Beijing Between 1984 and 1999,changes in risk factors together produced a best estimate of 1,822 more CHD deaths in 1999 compared to 1984 cholesterol 77% diabetes 19% BMI 4% smoking 1% improved treatments prevented or postponed an estimated 642 deaths treatment of MI 41% treatment of hypertension 24% secondary prevention 11% heart failure 10% CABG and PTCA 2% Critchley J, et al, Circulation 2004;110:1236,Relation Between Risk Factors and the Incidence of Coronary Disease in Cohort Studies,Law MR and Wald NJ. BMJ 2002;324:1570-1576.,Diastolic BP,3,2,0.5,Relative risk,Relative risk,70,80,90,100,110,Usual DBP (mm Hg),Serum Cholesterol,4,5,6,7,mmol/L,Body Mass Index,Relative risk,kg/m2,3,2,1,0.5,25,30,35,40,1,0.25,3,2,1,1.5,0.75,What Is Normal? Physiologic Variables in Prehistoric Communities and in Current Western Societies,5%,1.2,0.6,% decline/yr in BMD in postmenopausal women,10%,27,22,BMI, age 60,1%,230 mg/dL,120 mg/dL,Serum cholesterol, age 60,5%,80 mm Hg,70 mm Hg,Diastolic BP, age 60,1%,145 mm Hg,110 mm Hg,Systolic BP, age 60,Current Western Pop Prehistoric Average,Current Western Societies,Prehistoric Communities,Physiologic Variable,Law MR and Wald NJ. BMJ 2002;324:1570-1576.,Extent to Which Disease Is Concentrated in the Population With Extreme Physiologic Values,22%,Hip fracture,BMD,23%,Diabetes,BMI,22%,Coronary disease,BMI,21%,Coronary disease,Serum cholesterol,21%,Coronary disease,Systolic BP,28%,Stroke,Systolic BP,Cases in Subjects With Values 90th Percentile,Associated Disorder,Physiologic Variable,Implications,Reducing 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 risk Whether a risk factor should be treated thus depends on the level of risk, not the level of the risk factor All reversible risk factors should be treated in a patient at high risk Terms like hypertension and hypercholesterolemia that focus on the tails of the distribution of physiologic variables are misleading and thus best avoided,Law MR and Wald NJ. BMJ. 2002;324:1570-1576.,Heart Protection Study,20,536 patients in the U.K. at increased risk of CHD death due to: MI or other coronary heart disease occlusive disease of noncoronary arteries diabetes mellitus or treated hypertension Age 40-80 yr Total cholesterol 3.5 mmol/L (135 mg/dL) Randomized to simvastatin 40 mg/day or placebo and followed for 5 years,Vascular Event Total CHD Total stroke Revascularization ANY OF ABOVE,Statin Placebo (10,269) (10,267) 914 1234 456 613 926 1185 2042 2606 (19.9%) (25.4%),Risk Ratio and 95% Cl Statin better Statin worse,0.4,0.6,0.8,1.0,1.2,1.4,24% SE 2.6 reduction (2p0.00001),Simvastatin: Major Vascular Events,No. Events,Baseline Feature LDL (mg/dL) 100 (2.6 mmol/L) 100 130 130 (3.4 mmol/L) ALL PATIENTS,Statin Placebo (10,269) (10,267) 285 360 670 881 1087 1365 2042 2606 (19.9%) (25.4%),0.4,0.6,0.8,1.0,1.2,1.4,24% SE 2.6 reduction (2p0.00001),Simvastatin: Vascular Events by Baseline LDL-C,Het =0.8,Risk Ratio and 95% Cl Statin better Statin worse,No. Events,P Sever (Co-chair), B Dahlf (Co-chair), N Poulter (Secretary), H Wedel (Statistician), G Beevers, M Caulfield, R Collins, SE Kjeldsen, A Kristinsson, J Mehlsen, G McInnes, M Nieminen, E OBrien, J stergren On behalf of the ASCOT Investigators,ASCOT Study Design,Sever PS, et al, J Hypertens. 2001;19:1139-1147,18,000 hypertensives,R = Randomized,Lipid-Lowering Arm (LLA) Primary Objective,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;361:1149,Patient Population: LLA,Eligibility criteria SBP 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 age 3+ CVD risk factors No history of CHD,Sever PS, et al, Lancet 2003;361:1149,Reductions in Total and LDL Cholesterol,50 mg/dL,42 mg/dL,46 mg/dL,39 mg/dL,Sever PS et al, Lancet 2003;361:1149,36% reduction,Primary End Point: Nonfatal MI and Fatal CHD,HR = 0.64 (0.50-0.83),Atorvastatin 10 mg Number of events 100 Placebo Number of events 154,p=0.0005,Sever PS, et al, Lancet 2003;361:1149,Secondary End Point: Fatal and Nonfatal Stroke,27% reduction,HR = 0.73 (0.56-0.96),p=0.0235,Atorvastatin 10 mg Number of events 89 Placebo Number of events 121,Sever PS, et al, Lancet 2003;361:1149,Primary Prevention Statin Trials: LDL-C Levels vs Events,Percentage with CHD event,Primary prevention,Pravastatin,Lovastatin,Atorvastatin,10,5.4 (210),2.3 (90),2.8 (110),3.4 (130),3.9 (150),4.4 (170),4.9 (190),WOSCOPS-S,WOSCOPS-P,0,5,AFCAPS-S,AFCAPS-P,9,8,7,6,4,3,2,1,ASCOT-P,ASCOT-S,LDL-C, mmol/L (mg/dL),S = statin treated; P = placebo treated,“It isnt where you come from, its where youre going that counts” Ella Fitzgerald,In 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 below the knee amputations of both legs. She never fully recovered, and died at age 79 in 1996.,Baseline Feature Previous MI Other CHD (not MI) No prior CHD CVD PVD Diabetes ALL PATIENTS,Statin Placebo (10,269) (10,267) 1007 1255 452 597 182 215 332 427 279 369 2042 2606 (19.9%) (25.4%),Risk Ratio and 95% Cl Statin better Statin worse,0.4,0.6,0.8,1.0,1.2,1.4,24% SE 2.6 reduction (2p0.00001),Simvastatin: Vascular Events by Prior Disease,No. Events,Collaborative Atorvastatin Diabetes Study (CARDS),Aim: 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 diabetes without raised cholesterol levels,CARDS Eligibility Criteria,Type 2 diabetes 40-75 years of age No clinical history of coronary, cerebrovascular or severe peripheral vascular disease LDL-C 4.14 mmol/L (160 mg/dL) TG 6.78 mmol/L (600 mg/dL) One of : Hypertension defined as receiving antihypertensive treatment or SBP 140 mm Hg or DBP 90 mm Hg Retinopathy Microalbuminuria or macroalbuminuria Current smoking,132 Centres in UK and Ireland,4053 patients screened 2838 (70%) randomized,CARDS: Baseline Clinical Features,Lipid Levels by Treatment,Total cholesterol (mmol/L),LDL cholesterol (mmol/L),0,2,3,4,1,4.5,2,3,4,1,4.5,Years of Study,Years of Study,0,0,1,2,3,4,0,2,4,6,Placebo,Atorvastatin,Average difference 26% 1.4 mmol/L (54 mg/dL) p0.0001,Average difference 40% 1.2 mmol/L (46 mg/dL) p0.0001,Cumulative Hazard for Primary Endpoint,Relative Risk Reduction 37% (95% CI: 17-52),Years,328,305,694,651,1074,1022,1361,1306,1392,1351,Atorva,Placebo,1428,1410,Placebo 127 events,Atorvastatin 83 events,Cumulative Hazard (%),P=0.001,* units in mmol/L (mg/dL) * N (% of randomised),Treatment Effect on the Primary Endpoint by Subgroup,.2,.4,.6,.8,1,1.2,Favours Atorvastatin Favours Placebo,Big Statins Are Better Than Little Statins,hypertension: ASCOT versus ALLHAT elderly: HPS versus PROSPER surrogate endpoints: ASAP, ARBITER, REVERSAL ACS: MIRACL versus PACT and FLORIDA head-to-head: PROVE-IT, (TNT, SEARCH, IDEAL),Comparative Statin Trials in Hypertension,Images courtesy of Steven E. Nissen MD, Intravascular Ultrasound Laboratory, Cleveland Clinic,Intracoronary Ultrasound Reveals Lesions That Are Not Visible By Coronary Angiography,Distal Fiduciary Site,Proximal Fiduciary Site,Proximal Fiduciary Site,IVUS Computation of Atheroma Volume,Distal Fiduciary Site,Nissen SE et al. JAMA 2004;291:1071-1080,Lumen Area,EEM Area,Atheroma Area,Ultrasound Measurement of Atheroma Area,Precise Manual Planimetry of EEM and Lumen Borders,Reversal of Atherosclerosis with Lipitor (REVERSAL) Study,654 patients with angiographic CAD (20% stenosis) from 34 sites randomized to 18 months of treatment with atorvastatin 80 mg/day or pravastatin 40 mg/day intracoronary ultrasound of 30 mm segment at baseline and end of study primary endpoint measure is percent change in total plaque volume for all slices of anatomically comparable segments of the target coronary artery Nissen SE et al, JAMA 2004;291:1071,REVERSAL,Prava,Atorva,25%,46%,LDL Reduction,CRP Reduction,Prava,Atorva,5%,36%,p0.0001,p0.0001,Prava,Atorva,Change in Athero Volume,2.7%,-0.4%,p=0.02,Nissen SE et al, JAMA 2004;291:1071,Low-Density Lipoprotein Cholesterol Reduction and Change in Atheroma Volume,Mean change using linear regression analysis. 95% confidence limits for mean values. Nissen et al. JAMA 2004;291:1071.,% Change in low-density lipoprotein cholesterol,Pravastatin group (N=249),Atorvastatin group (N=253),Change in atheroma volume, mm3,PROVE IT: PRavastatin Or AtorVastatin Evaluation and Infection Therapy (TIMI 22),4,162 pts hospitalized with ACS within 10 days total cholesterol 30 days after ACS event) study designed to establish the “non-inferiority” of prava compared to atorva with respect to time to an endpoint event Cannon CP et al, NEJM 2004;350.,PROVE-IT: Changes in LDL-Cholesterol,Note: 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 baseline,Cannon CP et al NEJM 2004; 350:1495,PROVE-IT: Primary Endpoint,Cannon CP, et al NEJM 2004;350:1495,PROVE-IT: Major Cardiovascular Endpoints,2 Year Event Rates RRR Atorva 80 Pra