血脂领域重大循证研究汇总ppt课件

Gould AL et al. Circulation. 1998;97:946-952.,Clinical Benefits of Cholesterol Reduction,A recent meta-analysis of 38 trials demonstrated that for every 10% reduction in TC CHD mortality decreased by 15% (P0.001) total mortality decreased by 11% (P0.001) Decreases were similar for all treatment modalities Cholesterol reduction did not increase non-CHD mortality,PREMIER: Percentage of All Participants With Hypertension (6 mo)*,PREMIER Writing Group. JAMA. 2003;289:2083-2093.,*BP 140/90 mm Hg or on antihypertensive medication; comparison with baseline hypertension status to assess persistent vs incident hypertension DASH=Dietary Approaches to Stop Hypertension,Advice Only Established Established + DASH (n=257) (n=251) (n=253),%,P0.001,P=0.01,P=0.12,PREMIER: Percentage of All Participants With Optimal Blood Pressure (6 mo)*,PREMIER Writing Group. JAMA. 2003;289:2083-2093.,*BP 120/80 mm Hg; comparison with baseline hypertension status DASH=Dietary Approaches to Stop Hypertension,Advice Only Established Established + DASH (n=257) (n=251) (n=253),%,P0.001,P=0.005,P=0.24,Lp(a): An Independent CHD Risk Factor in Men of the Framingham Offspring Cohort,RR=relative risk; HT=hypertension; GI=glucose intolerance. Bostom AG et al. JAMA. 1996;276:544-548.,1.9,1.8,1.8,1.2,2.7,3.6,RR,0.1,1,10,2,5,0.2,0.5,Lp(a) TC HDL-C HT GI Smoking,AFCAPS/TexCAPS: RR of Acute Coronary EventsLDL-C and Homocysteine*,*Median LDL-C=149 mg/dL; median Hcy=11.27 mmol/L. Calculated on 5 patient-years at risk to prevent one event. RR=relative risk; Hcy=homocysteine; CI=confidence interval. Data from Ridker PM et al. Circulation. 2002;105:1776-1779.,RR with 95% CI,0.0 0.5 1.0 1.5,Lovastatin (L) better,Placebo (P) better,No. Needed to Treat 104 130 115 26,AFCAPS/TexCAPS: RR of Acute Coronary EventsTC:HDL-C Ratio and CRP Level*,*Median TC:HDL-C ratio=5.96; median CRP=0.16 mg/dL. Calculated on 5 patient-years at risk to prevent one event. RR=relative risk; CRP=C-reactive protein; CI=confidence interval. Adapted from Ridker PM et al. N Engl J Med. 2001;344:1959-1965.,RR with 95% CI,0.0 0.5 1.0 1.5 2.0 2.5,Lovastatin (L) better,Placebo (P) better,No. Needed to Treat 983 43 35 62,TM, 2001, Professional Postgraduate Services,,PRINCE: Change in CRP Levels at 24 Weeks,*12-week data used for 23% of patients in each arm. PRINCE=Pravastatin Inflammation/CRP Evaluation; CRP=C-reactive protein IQR=interquartile range. Adapted from Albert MA et al. JAMA. 2001;286:64-70.,TM, 2001, Professional Postgraduate Services,,LRC Follow-up Study: CVD Mortality by NonHDL-C and LDL-C in Men,LRC=Lipid Research Clinics; RR=relative risk; CI=confidence interval. Adapted from Cui Y et al. Arch Intern Med. 2001;161:1413-1419.,0 0.25 0.50 0.75 1.00 1.25 1.50 1.75 2.00 2.25 2.50 2.75 3.00,RR with 95% CI,TM, 2001, Professional Postgraduate Services,,LRC Follow-up Study: CVD Mortality by NonHDL-C and LDL-C in Women,LRC=Lipid Research Clinics; RR=relative risk; CI=confidence interval. Adapted from Cui Y et al. Arch Intern Med. 2001;161:1413-1419.,0 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00,RR with 95% CI,TM, 2001, Professional Postgraduate Services,,ACCESS: Change in LDL-C, NonHDL-C in All Patients at 54 Weeks,ACCESS=Atorvastatin Comparative Cholesterol Efficacy and Safety Study. Data from Ballantyne CM et al. Am J Cardiol. 2001;88:265-269.,-42,-29,-36,-28,-36,-38,-26,-32,-26,-32,-50,-40,-30,-20,-10,0,10,20,LDL-C,NonHDL-C,% D,Atorvastatin Fluvastatin Lovastatin Pravastatin Simvastatin (n=1,888) (n=474) (n=472) (n=461) (n=462),TM, 2001, Professional Postgraduate Services,,PDAY: Percentage of Right Coronary Artery Intimal Surface Affected With Early Atherosclerosis,PDAY= Pathobiological Determinants of Atherosclerosis in Youth. Strong JP, et al. JAMA. 1999;281:727-735.,Fatty streaks,Raised lesions,White,15-19,20-24,25-29,30-34,0,10,20,30,Women,0,10,20,30,15-19,20-24,25-29,30-34,Black,Age (y),0,10,20,30,White,15-19,20-24,25-29,30-34,Men,Black,Intimal surface (%),PDAY: Prevalence of Lesions in LAD,McGill HC Jr, et al. Circulation. 2000;102:374-379.,20,0,40,60,80,100,15-19,Age (y) Prevalence (%),30-34,25-29,60,60,40,40,20,20,0,0,0,1,2,3,4,5,0,20,40,60,20-24,0,1,2,3,4,5,AHA lesion grade,AHA lesion grade,Women,Men,Error bar=SE.,PDAY: Prevalence of Risk Factors,*NonHDL-C=TC minus HDL-C; IGT=impaired glucose tolerance. McGill HC Jr, et al. Circulation. 2000;102:374-379.,High nonHDL-C*,Low HDL-C,Smoking,Hypertension,Obesity,IGT,%,PDAY: Prevalence of Lesions by Smoking and NonHDL-C Status,McGill HC Jr, et al. Circulation. 2000;102:374-379.,40,50,30,20,10,0,15-19,20-24,25-29,30-34,40,50,30,20,10,0,15-19,20-24,25-29,30-34,40,50,30,20,10,0,15-19,20-24,25-29,30-34,40,50,30,20,10,0,15-19,20-24,25-29,30-34,Smoking (%),Non HDL-C (%),Normal nonHDL-C,High nonHDL-C,Grade 2-3 lesions,Grade 4-5 lesions,Age (y),Age (y),SHEEP: Risk Factors for Nonfatal MI in Men and Women,SHEEP=Stockholm Heart Epidemiology Program. Reuterwall C et al. J Intern Med. 1999;246:161-174.,Risk Factor Diabetes High TC (6.5 mmol/L) High TG (6.3 mmol/L) HTN (170/95 mm Hg) Overweight (BMI 30 kg/m) WHR (0.85) Physical inactivity Smoking Job strain,Men,Women,Odds Ratio,Elevated TC Effects on Risk of CHD Death in Younger Men: A Meta-analysis,*The difference in absolute risk with high baseline TC vs risk with favorable levels (200 mg/dL). As compared with men with TC 160 mg/dL. MRFIT=Multiple Risk Factor Intervention Trial; CHA=Chicago Heart Association Detection Project in Industry; PG=Peoples Gas Company. Stamler J, et al. JAMA. 2000;19:311-318.,MRFIT CHA PG (37-53 y) (30-55 y) (32-66 y) Absolute risk 15.5 54.2 154.0 (per 1,000) TC 240 mg/dL Absolute excess risk* 12.1 43.6 81.4 (per 1,000) TC 240 mg/dL Relative risk 8.09 11.93 8.06 TC 280 mg/dL,NHANES I Epidemiologic Follow-up Study: CHD Incidence and Survival in African-American Men and Women,Study cohort: 11,406 white and African-American persons aged 25 to 74 with no history of CHD Age-adjusted risk for CHD higher in African-American women aged 25 to 54 than in white women (RR: 1.76) No significant differences in survival,Gillum RF et al. Ann Intern Med. 1997;127:111-118.,LDL-C target levels (mg/dL) 2 RF: 130 CHD: 100 National Center for Health Statistics. National Health and Nutrition Examination Survey (III); 1994. (Data collected 1991-1994.) Pearson TA et al. Arch Intern Med. 2000;160:459-467.,% not at LDL-C targets,2 RF CHD Risk profile,63,82,82.5,54.6,0,20,40,60,80,100,NHANES III,L-TAP,Adult Population Not Reaching LDL-C Targets,18,9.9,13,14.4,11.2,9.4,7.9,16.6,0,5,10,15,20,25,% of patients,100 101- 111- 121- 131- 141- 151- 160 110 120 130 140 150 160,LDL-C (mg/dL) on-treatment,n = 1,460,L-TAP: Majority of Patients With CHD Do Not Reach NCEP LDL-C Targets,Pearson TA et al. Arch Intern Med. 2000;160:459-467. Other L-TAP data courtesy of TA Pearson.,% of patients,L-TAP: Majority of High-Risk Patients Without CHD Do Not Reach NCEP LDL-C Targets,Pearson TA et al. Arch Intern Med. 2000;160:459-467. Other L-TAP data courtesy of TA Pearson.,n = 2,285,130,130- 140,141- 150,151- 160,161- 170,171- 180,181- 190,191- 200,200,LDL-C (mg/dL) on-treatment,L-TAP: Patient Success in Achieving Target LDL-C Levels,Pearson TA et al. Arch Intern Med. 2000;160:459-467.,Nondrug therapy,282,361,108,751,861,1,924,1,352,4,137,Drug therapy,No.,% patient success,Low risk (P=0.001),High risk (P0.001),CHD (P=0.004),All patients,Note: P values based on univariate analysis comparing success rates among patients who did, and patients who did not, receive lipid-lowering therapy.,Adjusted* Relative Risk for First Cardiovascular Event Based on CRP, LDL-C,Data from Ridker PM et al. N Engl J Med. 2002;347:1557-1565.,*Adjusted for age, smoking status, diabetes, blood pressure, and HRT.,RR, 2003 Thomson Professional Postgraduate Services,,0.0,0.5,1.0,1.5,2.0,2.5,RR,P0.001,P0.001,0.49 0.49 1.08 2.09 4.19 -1.08 -2.09 -4.19,97.6 97.6 115.4 132.2 153.9 -115.4 -132.2 -153.9,Quintiles of CRP (mg/L),Quintiles of LDL-C (mg/dL),Event-Free Survival With CRP, LDL-C Levels Above or Below the Median*,Ridker PM et al. N Engl J Med. 2002;347:1557-1565.,*Median values: CRP=1.52 mg/L, LDL-C=123.7 mg/dL., 2003 Thomson Professional Postgraduate Services,,1.00 0.99 0.98 0.97 0.96 0.00,0 2 4 6 8,Years,Probability,N=27,939,Low CRPlow LDL-C,Low CRPhigh LDL-C,High CRPlow LDL-C,High CRPhigh LDL-C,Effects of Three Treatments on CRP,*P0.02 vs respective baseline values. CEE=conjugated equine estrogen. Note: Brackets with significance figures indicate post hoc comparisons between treatment periods after demonstration of significance among periods by ANOVA (P0.001).,Koh KK et al. Circulation. 2002;105:1531-1533.,0.00,0.20,0.40,0.60,0.80,Baseline,Treatment,Baseline,Treatment,Baseline,Treatment,CRP (mg/dL),CEE,Statin,CEE + Statin,P0.05,P0.001,*,*,*, 2003 Thomson Professional Postgraduate Services,,0,5,10,15,20,25,30,(2.60),(3.25),(3.90),(4.50),(5.15),(5.80),(6.45),(7.10),(7.75),(8.40),(9.05),Cholesterol and CHD: Seven Countries Study,TC mg/dL (mmol/L),CHD mortality rates (%),Verschuren WMM et al. JAMA. 1995;274:131-136.,100,125,150,175,200,225,250,275,300,325,350,Northern Europe United States Southern Europe, Inland Southern Europe, Mediterranean Siberia Japan,Lyon Diet Heart Study: Cumulative Survival Without Cardiac Death and Nonfatal MI,de Lorgeril M et al. Circulation. 1999;99:779-785.,1,2,3,4,5,70,80,90,100,Year,Experimental,Control,% without event,P=0.0001,Wine Consumption and CHD,CHD = -4.99W + 652.4 r = -0.580,Hegsted DM, Ausman LM. J Nutr. 1988;118:1184-1189.,Effect of Lifestyle Changes on Angiographic CAD,Study,N,Patient type,Therapy,Duration,(yr),% (Control-Treatment),Progression,Regression,Lifestyle,28,CAD,Diet,exercise,meditation,1,35,-40,STARS,90,CAD, high,TC,Diet (including,fiber),3.2,35,-38,Heidelberg,113,CAD,Diet + exercise,1,25,-15,-9,-47,-9,-20,-14,-23,-8.5,-19,-11,-34,-50,-45,-40,-35,-30,-25,-20,-15,-10,-5,0,%+,Adapted from Levine GN et al. N Engl J Med. 1995;332:512-521.,* Net difference between treatment and control groups (P values are for events).,TC *,CHD events *,N=number enrolled.,Early Primary-Prevention Trials: Overview,WHO: Clofibrate N=15,745, P0.05,Oslo: Diet/smoking cessation N=1,232, P=0.02,Upjohn: Colestipol N=2,278, P0.02,LRC-CPPT: Cholestyramine N=3,806, P0.05,HHS: Gemfibrozil N=4,081, P0.02,Early Secondary-Prevention Trials: Overview,Adapted from Levine GN et al. N Engl J Med. 1995;332:512-521.,* Net difference between treatment and control groups (P values are for events).,N=number enrolled; ns=not significant.,TC *,CHD events *,CDP: Niacin (n=1,119) N=8,341, P=ns,CDP: Clofibrate (n=1,103) N=8,341, P=ns,Stockholm: Clofibrate + niacin N=555, P=ns,POSCH: Partial ileal bypass N=838, P0.001,%+,-20,-26,5,-31,-33,-22,-25,-35,8,-34,-42,-30,-20,-28,5,-24,-20,-9,-45,-40,-35,-30,-25,-20,-15,-10,-5,0,5,10,WOSCOPS (N=6,595),4S (N=4,444),CARE (N=4,159),N=number enrolled.,TC,LDL-C,HDL-C,1o prevention,2o prevention,2o prevention,Summary of Effects of Lipid Lowering on Lipids and Clinical Events in Recent Statin Trials,Nonfatal MI/CHD death,CHD death,All-cause mortality,%+,-20,-26,5,-33,-22,-31*,-35,-30,-25,-20,-15,-10,-5,0,5,10,Shepherd J et al. N Engl J Med. 1995;333:1301-1307.,* P0.0005. P=0.042. P=0.051.,Subjects: 6,595 men Age range: 45-64 yr Mean baseline TC: 272 mg/dL Mean baseline LDL-C: 192 mg/dL Duration: 5 yr Intervention: Pravastatin 40 mg/day,TC,LDL-C,HDL-C,Nonfatal MI/CHD death,CHD death,All-cause mortality,WOSCOPS: Effects of Lipid Lowering on Coronary Events in Primary Prevention Trial in Men,%+,5-year event rate (per 100),WOSCOPS Group. Circulation. 1998;97:1440-1445.,WOSCOPS: Relation of Baseline LDL-C to Event Rate,WOSCOPS: Relation of Baseline HDL-C to Event Rate,WOSCOPS Group. Circulation. 1998;97:1440-1445.,5-year event rate (per 100),WOSCOPS: Relation Between Quintiles of LDL-C Reduction and CHD Events,% LDL-C,4.4-yr event rate,WOSCOPS Group. Circulation. 1998;97:1440-1445.,4S Group. Lancet. 1994;344:1383-1389.,*P0.00001. 95% CI: -27 to -54. P=0.003.,4S: Effect of LDL-C Lowering on Coronary Events in Secondary Prevention Trial in Men and Women,-25,-35,8,-42 ,-30 ,-34,-45,-40,-35,-30,-25,-20,-15,-10,-5,0,5,10,Subjects: 4,444 (81% men, 19% women) Age range: 35-70 yr Mean baseline TC: 261 mg/dL Mean baseline LDL-C: 188 mg/dL Duration: 5 yr Intervention: Simvastatin 20-40 mg/day,TC,LDL-C,HDL-C,Nonfatal MI/CHD death,CHD death,All-cause mortality,%+,*,4S: Effects of Cholesterol Lowering on Noncoronary Ischemic Symptoms and Angina,Pedersen TR et al. Am J Cardiol. 1998;81:333-335.,Fraction of patients,Fraction of patients,Fraction of patients,Fraction of patients,Months,Months,Months,Months,Simvastatin Placebo,Intermittent Claudication,Carotid Bruit,Angina,Cerebrovascular Events,4S: Findings From a Post Hoc Analysis,The thinner curves define the 95% CI. Pedersen TR. Circulation. 1998;97:1453-1460.,% reduction in coronary events after 1 year,% reduction in LDL-C at 1 year,Total mortality,Coronary mortality,Revascularization,Percent of patients,P=0.009,P=0.003,P=0.003,Miettinen TA et al. Circulation. 1997;96:4211-4218.,4S: Lipid Lowering Reduces CHD Event Rates in 65-Year-Old Subjects,4S: Impact of Drug Therapy on Lipids and Lipoproteins in Older Adults With Hypercholesterolemia,Data from Miettinen TA et al. Circulation. 1997;96:4211-4218.,-25.1,-34.2,6.9,-16.4,-25.8,-35.9,7.1,-13.6,-40,-35,-30,-25,-20,-15,-10,-5,0,5,10,TC,LDL-C,TG,HDL-C,% D,65 yr,65 yr,4S: Reduction in Coronary Events and Revascularizations in Older Adults With Established CHD,Data from Miettinen TA et al. Circulation. 1997;96:4211-4218.,-34,-42,-33,-28,-35,-34,-43,-33,-34,-41,-45,-40,-35,-30,-25,-20,-15,-10,-5,0,Major coronary events,*P0.001; P=0.003; P=0.004; P=0.007; |P=0.009. All P values represent within-group differences (treatment vs placebo). RR=relative risk.,RR (%),CHD mortality,Nonfatal MI,All-cause mortality,Revascular-izations,*,*,*,*,|,*,65 yr (n=3,423),65 yr (n=1,021),4S: Survival of Major Coronary Events in Older Adults,Miettinen TA et al. Circulation. 1997;96:4211-4218.,0,1,2,3,4,5,6,0,1,2,3,4,5,6,0.60,0,0.65,0.70,0.75,0.80,0.85,0.90,0.95,1.00,0.60,0,0.65,0.70,0.75,0.80,0.85,0.90,0.95,1.00,65 yr,65 yr,Log rank P0.00001,Log rank P0.001,Years after randomization,Years after randomization,Proportion without major CHD event,Simvastatin Placebo,-35,-34,-34,-31,-88,-100,-80,-60,-40,-20,0,Pedersen TR et al. Circulation. 1996;93:1796-1802.,Cost of simvastatin therapy,LDL-C,Hospital days,Major CHD events,Hospital costs,*P0.0001. Translates to savings of $3,872/patient. Translates to cost of $0.28/day.,*,LDL-C,CHD events,Admissions,Net cost of therapy,4S: Clinical and Economic Benefits of Treatment Over 5-Yr Period,%+,LIPID: Effect of Lipid Lowering on Lipid Values and Coronary Events in CHD Patients With Average Cholesterol,LIPID Study Group. N Engl J Med. 1998;339:1349-1357.,Subjects: 9,014 (83% men, 17% women) Age range: 55-67 yr Median baseline TC: 218 mg/dL Median baseline LDL-C: 150 mg/dL Duration: 6 yr Intervention: Pravastatin (40 mg/day),TC,LDL-C,Nonfatal MI/CHD death,CHD death,All-cause mortality,HDL-C,-18,-25,-24*,-24*,-22*,5,*P0.001,%,LIPID: Reduction in Nonfatal MI and CHD Death Risk Stratified by Prerandomization Age,-32,-20,-28,-15,40,30,20,10,0,Age,55 55-64 65-69 70,LIPID Study Group. N Engl J Med. 1998;339:1349-1357.,%,LIPID: Reduction in Nonfatal MI and CHD Death Risk Stratified by Sex,-26,-11,30,25,20,15,10,5,0,Male Female (n=7,498) (n=1,516),LIPID Study Group. N Engl J Med. 1998;339:1349-1357.,%,LIPID: Reduction in Nonfatal MI and CHD Death Risk Stratified by Diabetic Status,-19,-25,30,25,20,15,10,5,0,With diabetes Without diabetes (n=782) (n=8,232),LIPID Study Group. N Engl J Med. 1998;339:1349-1357.,%,LIPID Trial Follow-up: Cardiovascular Events Over 8 Years,The LIPID Study Group. Lancet. 2002;359:1379-1387.,*P0.0001. P=0.015. RR=relative risk; CI=confidence interval; LIPID=Long-term Intervention with Pravastatin in Ischemic Disease.,Total stroke,MI,CHD death or nonfatal MI,CHD death,Outcome,Placebo (n=4,502),Pravastatin (n=4,512),RR reduction (95% CI),911 (20.2%),570 (12.7%),272 (6.0%),224 (5.0%),20% (433),435 (9.6%),26% (1635)*,734 (16.3%),22% (1429)*,510 (11.3%),395 (8.8%),24% (1434)*,LIPID Trial Follow-up: Serious Adverse Events* Over 8 Years,*Not all SAEs are listed here; Excluding nonmelanomatous skin cancer; One case of nonfatal rhabdomyolysis in placebo group; RR=relative risk; CI=confidence interval; LIPID=Long-term Intervention with Pravastatin in Ischemic Disease.,Hepatic or biliary,Any new cancer,Melanoma or sarcoma,Bladder or kidney cancer,Prostate or testis cancer,Event,The LIPID Study Group. Lancet. 2002;359:1379-1387.,Placebo (n=4,502),Pravastatin (n=4,512),RR (95% CI),Myositis or myalgia,Respiratory,0.83 (0.59-1.17),756 (16.8%),1.04 (0.87-1.25),1.08 (0.98-1.20),499 (11.1%),0.91 (0.81-1.03),38 (0.8%),39 (0.9%),1.08 (0.69-1.70),50 (1.1%),60 (1.3%),1.04 (0.71-1.52),145 (3.2%),148 (3.3%),1.0 (0.80-1.26),526 (11.7%),234 (5.2%),60