Integrating Aggressive CV Risk Management in Primary Care(英文版)(ppt 95页).ppt

1、Integrating Aggressive CV Risk Management in Primary Care,High prevalence of multiple CV risk factors in US adults,CDC. MMWR. 2005;54:113-40,Behavioral Risk Factor Surveillance System, 2003,2 of hypertension, hypercholesterolemia, diabetes, smoking, physical inactivity, obesity,40.0%46.2,36.0%39.9,3

2、3.0%35.9,27.0%32.9,INTERHEART: Exponential rise in CV disease with added risk factors,Odds ratio for1st MI* (99% CI,64,512,16,1,2,256,128,32,8,4,Smk(1,DM(2,HTN(3,ApoB/A1 ratio (4,1+2+3,All 4,All 4+ Obes,All 4+ Ps,All 9 riskfactors,2.9,2.4,1.9,3.3,13.0,42.3,68.5,182.9,333.7,Yusuf S et al. Lancet. 200

3、4;364:937-52,Smk = smoking; DM = diabetes; HTN = hypertension; Obes = obesity; Ps = psychosocial factors *Plotted on a doubling scale,INTERHEART: Any smoking increases CV risk,Teo KK et al. Lancet. 2006;368:647-58,vs never smoked,N = 27,098 from 52 countries,12,34,56,78,910,1112,1314,1516,1718,1920,

4、Odds ratio for first MI,Cigarettes smoked (n/day,Never,21,0.75,1,2,4,8,Lifetime CVD risk estimate and risk factor burden,70,60,50,40,30,20,10,0,50,60,70,80,90,69,50,46,36,5,60,50,40,30,20,10,0,Men(n = 3564,Women (n = 4362,Adjusted cumulative incidence of CVD(,50,60,70,80,90,2 Major RFs,1 Major RF,1

5、Elevated RF,1 Not optimal RF,All optimal RFs,70,50,39,27,8,Attained age (years,Lloyd-Jones DM et al. Circulation. 2006;113:791-8,2-fold in higher age group,Additive risk of age with hypertension + hypercholesterolemia,Wong ND et al. Am J Cardiol. 2006;98:204-8,NHANES 2001-2002; N = 2864,Clinical man

6、ifestations of obesity,Insulinresistance Glucotoxicity Lipotoxicity Adiponectin Leptin,Atherosclerosis,Courtesy of Selwyn AP, Weissman PN. 2006,Metabolic consequences of visceral obesity,Visceral/abdominal obesity Correlates more strongly with insulin resistance than lower body obesity Is associated

7、 with plasma levels of fatty acids and accompanying TG Insulin resistance Altered hepatic fat accumulation and metabolism Dyslipidemia Proinflammatory adipokines (insulin resistance, risk for CV disease) Visceral fat correlates more strongly with insulin resistance than subcutaneous fat,Grundy SM et

8、 al. Circulation. 2005;112:2735-52. Desprs J-P et al. BMJ. 2001;322:716-20,Visceral obesity in CV risk,CT scans from men matched for BMI and total body fat White = visceral fat area (VFA); black = subcutaneous fat,Desprs J-P. Eur Heart J Suppl. 2006;8(suppl B):B4-12,Subcutaneous obesity Fat mass: 19

9、.8 kg VFA: 96 cm2,Visceral obesity Fat mass: 19.8 kg VFA: 155 cm2,Visceral obesitydrives CV risk progression independent of BMI,Measurement of waist circumference may offer a more useful surrogate marker of visceral adiposity than waist-hip ratio,Optimal marker(s) for visceral adiposity,Desprs JP et

10、 al. BMJ. 2001;322:716-720,Measuring waist circumference,NHLBI. ,Iliac crest,CDC Projections 2005 to 2050: Diabetes focus,Narayan KMV et al. Diabetes Care. 2006;29:2114-6,Revised projection “appears more alarming than previously estimated,32.1 million new diabetes patients by 2050,1

11、74,220,470,423,606% in blacks 75 yr,2050,2005,Individuals with diabetes (millions,Diabetes2005-2050 (,Multiple risk factors: Undertreated and poorly controlled,Wong ND et al. Am J Cardiol. 2006;98:204-8,NHANES 2001-2002; n = 638 with hypertension and hypercholesterolemia,Sudden cardiac death: Too of

12、ten the first sign of CV disease,Fox CS et al. Circulation. 2004;110:522-7,50% of sudden cardiac deaths occur in persons with no CV disease history,Call to action,Identify all risk factors,Base treatment on global risk assessment,Treat multiple risk factors aggressively,ABCs of multiple risk factor

13、management,Platelet activationand aggregation,Hypertension,Hyperglycemia/ Insulin resistance,Dyslipidemia,Adapted from Cohen JD. Lancet. 2001;357:972-3. Beckman JA et al. JAMA. 2002;287:2570-81,AHA diet and lifestyle recommendations,Healthy diet Fruits, vegetables, legumes, whole grains, non-fat/low

14、-fat dairy, fish, poultry, limited alcohol intake Physical activity 30 min on most days No smoking Avoid use of and exposure to tobacco products,Lichtenstein AH et al. Circulation. 2006;114:82-96,CV risk,Weight loss improves CV risk factors,Sjstrm L et al. N Engl J Med. 2004;351:2683-93,Conventional

15、 treatment (n = 1660,Gastric surgery (n = 1845,At 2 years,N = 4047 with obesity,3-Week diet + exercise regimen yields favorable metabolic changes,P 0.01 P 0.05,Roberts CK. et al. J Appl Physiol. 2006;100:1657-65,U/mL,N = 31 overweight/obese men; weight 8.4 lbs,Baseline,Follow-up,Physical activity re

16、duces CV and all-cause mortality,Fang J et al. Am J Hypertens. 2005;18:751-8,N = 9791; moderate physical activity vs little or no physical activity,0.75 (0.531.05,0.76 (0.391.49,0.79 (0.650.97,All-cause death,CV death,All-cause death,Prehypertension,CV death,Hypertension,Hazard ratio,1.5,1.0,0.5,Nor

17、mal BP,0,2.0,All-cause death,CV death,0.79 (0.581.09,0.88 (0.800.98,0.84 (0.730.97,Adjusted HR (95% CI,Favorsexercise,Favorsno exercise,NHANES 1 Epidemiological Follow-up Survey (19711992,Dietary programs can be effective yet difficult to maintain,Dansinger ML et al. JAMA. 2005;293:43-53,N = 160 ove

18、rweight or obese with 1 CV risk factor,Emerging strategies in weight control,Lifestyle interventions must include both diet and exercise Even moderate weight loss (5%10%) can: Decrease cardiometabolic risk factors Encourage continued health-promoting behaviors and adherence to medical therapy Novel

19、approaches to decreasing cardiometabolic risk factors are needed,Eckel RH et al. Circulation. 2006;113:2943-6. Gelfand EV, Cannon CP. J Am Coll Cardiol. 2006;47:1919-26,Goals for optimal health,AACE. Endocr Pract. 2002;8(suppl 1):40-82,Steno-2: Rationale for Target-Driven Behavior Modification and P

20、olypharmacy,Steno-2: Goals of intensive pharmacologic strategy,Gde P et al. N Engl J Med. 2003;348:383-93,Steno-2 results: Better control with intensive therapy,Gde P et al. N Engl J Med. 2003;348:383-93,Conventional therapy (n = 80,Intensive therapy (n = 80,Follow-up (years,Follow-up (years,0,1,2,3

21、,4,5,6,7,8,50,150,250,350,0,0,1,2,3,4,5,6,7,8,110,130,150,170,0,SBP(mm Hg,P 0.001,Total-C(mg/dL,P 0.001,0,1,2,3,4,5,6,7,8,50,150,250,350,0,AlC(,P 0.001,TG (mg/dL,P = 0.015,0,1,2,3,4,5,6,7,8,5,7,9,11,0,Steno-2: Multifactorial intervention improves macrovascular outcomes,Gde P et al. N Engl J Med. 200

22、3;348:383-93,CV death, MI, stroke, revascularization, amputation, PAD surgery; Unadjusted,Primary composite outcome* (,Follow-up (months,60,50,40,30,20,10,0,Conventional,Intensive,0,12,24,36,48,60,72,84,96,NNT = 5Absolute risk reduction = 20,N = 160 with type 2 diabetes and microalbuminuria,Steno-2:

23、 Intensive intervention improves vascular and neuropathic outcomes,Gde P et al. N Engl J Med. 2003;348:383-93,0.0,1.0,2.0,Variable,RR,P,Intensivebetter,Conventionalbetter,0.39,0.42,0.37,1.09,0.003,0.02,0.002,0.66,Risk of microvascular complications after 4 years was maintained at 8 years,Relative ri

24、sk,3.0,Integrating Antihypertensive Agents in CV Risk Reduction,Relation of BP to CV disease is continuous,Meta-analysis of 61 observational studies; N = 958,074,Prospective Studies Collaboration. Lancet. 2002;360:1903-13,120,140,160,180,Usual SBP (mm Hg,Usual DBP (mm Hg,70,90,100,110,80,Systolic BP

25、,Diastolic BP,Age at risk (y,8089,7079,6069,5059,4049,Age at risk (y,8089,7079,6069,5059,4049,256,128,64,32,16,8,4,2,1,0,256,128,64,32,16,8,4,2,1,0,IHDmortality(floatingabsoluterisk,Plotted on a doubling scale,BPLTTC: Comparison of more- vs less-intensive BP lowering,Blood Pressure Lowering Treatmen

26、t Trialists Collaboration. Lancet. 2003;362:1527-35,Meta-analysis of 4 trials; 1998-2002; N=162,341,0.6,1.0,1.4,Relative risk,Favorsmore intensive,Favorsless intensive,ASCOT-BPLA: Rationale,Premise Multiple risk factors markedly increase CV disease severity Standard BP-lowering therapies (diuretics

27、and -blockers) have not been proven to prevent CHD events ASCOT-BPLA compared newer vs older antihypertensive regimens in patients with 3 risk factors Hypothesis Newer, aggressive combination BP-lowering agents will prevent more CV events,BPLTTC. Arch Intern Med. 2005;165:1410-9.Dahlf B et al. Lance

28、t. 2005;366:895-906,Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm,ASCOT-BPLA: Comparison of older vs newer therapy,Plus K supplement if needed,BP 160/100 mm Hg (untreated) or BP 140/90 mm Hg (treated)+ 3 other risk factors N = 19,257,Amlodipine 510 mg perindopril 48 mg,Atenol

29、ol 50100 mg bendroflumethiazide 1.252.5 mg,Primary outcome: Nonfatal MI and fatal CHD,Follow-up: 5.5 years,RandomizedDouble-blind,Dahlf B et al. Lancet. 2005;366:895-906,ASCOT patient profile,Sever PS et al. J Hypertens. 2001;19:1139-47. Sever PS et al. Lancet. 2003;361:1149-58,Patients with risk fa

30、ctor (,0,10,20,30,40,50,60,70,80,90,100,Hypertension Aged 55 years Male Microalbuminuria/proteinuria Smoker Family history of CHD Plasma TC:HDL-C 6 Type 2 diabetes ECG abnormalities LVH Prior cerebrovascular events Peripheral vascular disease,ASCOT-BPLA: BP reductions over time,Blood pressure(mm Hg,

31、Atenolol 50100 mg bendroflumethiazide 1.252.5 mg/potassium,Amlodipine 510 mg perindopril 48 mg,Dahlf B et al. Lancet. 2005;366:895-906,Time (years,1.0,2.0,3.0,4.0,5.0,0,0.5,1.5,2.5,3.5,4.5,5.5,BP,Mean difference = 1.9, P 0.0001,60,100,0,80,120,140,160,180,Mean difference = 2.7, P 0.0001,Diastolic BP

32、,137.7 136.1,79.2 77.4,Systolic BP,ASCOT-BPLA: Reduction in primary outcome,Proportionof events (,6,2,4,0,1,2,3,4,8,10,5,6,0,Time (years,10% RRR HR 0.90 (0.791.02) P = 0.1052,Atenolol 50100 mg bendroflumethiazide 1.252.5 mg/potassium,Amlodipine 510 mg perindopril 48 mg,Dahlf B et al. Lancet. 2005;36

33、6:895-906,Nonfatal MI and fatal CHD,ASCOT-BPLA: Additional reductions with amlodipine-based regimen,Dahlf B et al. Lancet. 2005;366:895-906,Secondary endpoints Nonfatal MI (excluding silent)7.4 8.5+ fatal CHD Total coronary endpoint14.6 16.8 Total CV events and procedures 27.4 32.8 All-cause mortali

34、ty13.9 15.5 CV mortality4.9 6.5 Fatal/nonfatal stroke6.2 8.1 Fatal/nonfatal HF2.5 3.0 Tertiary endpoints Development of diabetes11.0 15.9 Development of renal impairment7.7 9.1,Rate/1000 patient-years,Amlodipine-based(n = 9639,Atenolol-based (n = 9618,Amlodipine-based better,Atenolol-based better,0.

35、50,0.70,1.00,1.45,2.00,Unadjusted hazard ratio,P 0.05 0.01 0.0001 0.05 0.001 0.001 NS 0.0001 0.05,CAFE: Lower central aortic BP with newer vs older antihypertensive regimen,Atenolol bendroflumethiazide Amlodipine perindopril,140,135,130,125,120,0,0,0.5,1.0,1.5,2.0,2.5,3.0,3.5,4.0,4.5,5.0,5.5,6.0,Tim

36、e (years,mm Hg,Brachial SBP,Central aortic SBP,CAFE Investigators. Circulation. 2006;113:1213-25,Similar effects on brachial BP,CAFE: Summary,Substantial and consistent differences in central aortic BP and hemodynamics with amlodipine perindopril vs atenolol bendroflumethiazide, despite similar brac

37、hial systolic BP effects Central aortic systolic BP and pulse pressure differences may explain ASCOT-BPLA outcomes Central aortic pulse pressure may be a determinant of CV outcomes,CAFE Investigators. Circulation. 2006;113:1213-25,Beyond BP Reduction: Integrating RAAS Modulation in Vascular Protecti

38、on,HOPE Study Investigators. N Engl J Med. 2000. EUROPA Investigators. Lancet. 2003. PEACE Trial Investigators. N Engl J Med. 2004,Vascular protection: Focus on ACE inhibition,or diabetes + 1 CV risk factor LVEF = left ventricular ejection fraction,HOPE Study Investigators. N Engl J Med. 2000. EUROP

39、A Investigators. Lancet. 2003. PEACE Trial Investigators. N Engl J Med. 2004,HOPE, EUROPA, PEACE: Concomitant CV therapies at baseline,HOPE Study Investigators. N Engl J Med. 2000. EUROPA Investigators. Lancet. 2003. PEACE Trial Investigators. N Engl J Med. 2004,HOPE, EUROPA, PEACE: Primary outcomes

40、,HOPE,Patients (,Placebo,22% RR P 0.001,15,5,10,0,20,0,Ramipril 10 mg,2,4,1,3,Time (years,PEACE,Placebo,Trandolapril 4 mg,30,20,10,15,5,1,2,3,4,5,25,0,6,4% RR P = 0.43,EUROPA,12,4,10,0,1,3,4,14,0,Placebo,Perindopril 8 mg,8,6,2,5,2,20% RR P = 0.0003,RR = risk reduction,HOPE, EUROPA, PEACE: Reduction

41、in all-cause mortality,Favors ACEI,Favors placebo,Odds ratio (95% CI,Dagenais GR et al. Lancet. 2006;368:581-8,0.6,1.0,1.4,HOPE, EUROPA: Benefit consistent across ancillary therapy,Adapted from Dagenais GR et al. Lancet. 2006;368:581-8,1.1,1.0,0.5,0.9,Odds ratio (95% CI,AntiplateletsNo antiplatelets

42、 Lipid-lowering agentsNo lipid-lowering agents -blockersNo -blockers RevascularizationNo revascularization,Subgroup,Patients (n,4-year rates in placebo groups,0.003 0.651 0.139 0.078,PInteraction,0.6,0.7,0.8,18,3313184 948912,026 11,32310,192 10,39411,123,13.217.9 10.616.4 13.414.3 11.516.0,ACEI bet

43、ter,ACEI worse,CV death, nonfatal MI, or stroke,HOPE, EUROPA, PEACE: Benefit of ACEIs across broad spectrum of risk,Dagenais GR et al. Lancet. 2006;368:581-8,5,20,40,5,30,15,35,Odds reduction (,25,10,0,CV death,* nonfatal MI or stroke,ACEI worse,ACEI better,Or total mortality in AIRE, TRACE, SOLVD,

44、SAVE trials,ACEIs vs ARBs: Comparative effect on stroke, HF, and CHD,Turnbull F. 15th European Meeting on Hypertension. 2005.Adapted by Strauss MH, Hall AS. Circulation. 2006;114:838-54,CHD = MI and CV death,Blood Pressure Lowering Treatment Trialists Collaboration meta-analysisN = 137,356; 21 rando

45、mized clinical trials,ACEI,ARB,Stroke,1% (9% to -10,HF,10% (10% to 0,CHD,9% (14% to 3,Stroke,2% (33% to -3,HF,16% (36% to -5,CHD,7% (7% to -24,30,0,30,Decrease,Increase,StrokeP = 0.6,HF P = 0.4,CHD P = 0.001,Risk,RRR,ACEIs in vascular disease: Conclusions,ACEIs reduce mortality, MI, HF, and stroke i

46、n patients with vascular disease with/without LVSD or HF Benefit in addition to antiplatelet agents, -blockers, and lipid-lowering agents Combining ACEIs with these agents provides greatest benefit Benefit in patients across a broad range of risk for CV events Annual rate in placebo groups of 1.4%22

47、.6,Dagenais GR et al. Lancet. 2006;368:581-8. Fox K et al. Eur Heart J. 2006;27:2154-7,Consider ACEIs in all patients with vascular disease Assess risk/benefits and tolerability Use doses proven in clinical trials,Integrating Statinsin CV Risk Reduction,Statins reduce all-cause death,CTT Collaborato

48、rs. Lancet. 2005;366:1267-78,Cholesterol Treatment Trialists Collaboration; N = 90,056,Cause of death,3.4,0.81,0.91,0.95,0.93,Vascular causes,Stroke,Other vascular,Any vascular,Any non-CHD vascular,0.6,0.6,1.2,4.7,2.4,0.2,0.1,1.1,3.8,8.5,9.7,4.0,1.2,0.1,0.3,2.4,5.7,1.3,0.7,0.6,4.4,Nonvascular causes

49、,Cancer,Respiratory,0.83,1.01,0.82,0.89,0.87,0.95,0.88,Trauma,Other/unknown,Any nonvascular,Any death,Events (,Treatment better,Controlbetter,1.5,1.0,0.5,CHD,Relative risk,Treatment(n = 45,054,Control(n = 45,002,Meta-analysis of 14 trials,HPS: Assessing statin benefit in high-risk patients,HPS Colla

50、borative Group. Lancet. 2002;360:7-22,Heart Protection Study,Total-C 135 mg/dL and diabetes, CAD, stroke, PAD, or treated hypertension (if male, aged 65 years)N = 20,536,Simvastatin 40 mg,Follow-up: 5 years,Primary outcomes:Mortality (overall analysis) Fatal/nonfatal vascular events (subcategory ana

51、lysis,Placebo,RandomizedOpen-label Blinded outcome,HPS: Statins confer benefit independent of baseline LDL-C,358 (21.0,282 (16.4,100,871 (24.7,668 (18.9,100 to 130,2585 (25.2,2033 (19.8,All patients,1356 (26.9,1083 (21.6,130,Placebo n (,Statin n (,Baseline LDL-C (mg/dL,Statin better,Placebo better,H

52、PS Collaborative Group. ,24% reduction 2P 0.00001,Rate ratio (95% CI,Patients with multiple risk factors may develop CV disease at LDL-C levels 100 mg/dL,N = 20,536; Fatal/nonfatal vascular events,ASCOT-LLA: Rationale,Premise High prevalence of dyslipidemia in hypertensive patients Mo

53、st CV disease events occur in patients with BP and lipid concentrations deemed normal Hypothesis Lipid lowering will benefit hypertensive patients not conventionally deemed dyslipidemic,Sever PS et al. Lancet. 2003;361:1149-58,Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm,ASCOT-LLA: D

54、esign,Dahlf B et al. Lancet. 2005;366:895-906.Sever PS et al. Lancet. 2003;361:1149-58,Plus K supplement if needed,BP 160/100 mm Hg (untreated) or BP 140/90 mm Hg (treated)+ 3 other risk factors N = 19,257,Amlodipine 510 mg perindopril 48 mg,Atenolol 50100 mg bendroflumethiazide 1.252.5 mg,Total-C 2

55、50 mg/dLn = 10,305,Atorvastatin 10 mg,Placebo,RandomizedDouble-blind,ASCOT-LLA: Statin reduces primary outcome in hypertension,Sever PS et al. Lancet. 2003;361:1149-58,Mean baseline LDL-C 133 mg/dL Nonfatal MI and fatal CHD,Patients (,Placebo,0,0,1,2,3,4,Atorvastatin,1.0,1.5,3.0,3.5,2.0,2.5,0.5,Foll

56、ow-up (years,36% RRRHR 0.64 (0.500.83) P = 0.0005,n = 10,305,Per 1000 patient-years,Censoring time,Hazard ratio,RRR (,Event rate,Atorvastatin,Placebo,30 days 90 days 180 days 1 year 2 years End of study,832.414.2 675.516.6 487.514.3 456.612.0 385.99.5 366.09.4,0,0.5,1.0,1.5,2.0,Atorvastatinbetter,Pl

57、acebobetter,Sever PS et al. Am J Cardiol. 2005;96(suppl):39F-44F,ASCOT-LLA post hoc analysis: Time to benefit,n = 10,305,ASCOT: Integration of antihypertensive regimens with statin,Courtesy of Appel G, 2006.Adapted from Dahlf B et al. ,Cumulativeincidence(,4.0,3.0,0,2.0,1.0,0,1.0,2

58、.0,3.0,3.5,4.0,3.0,0,2.0,1.0,0,1.0,2.0,3.0,3.5,Placebo,Atorvastatin,Primary endpoint: Nonfatal MI and fatal CHD,Years,HR 0.47 (0.320.69)P = 0.001,HR 0.84 (0.601.17)P = 0.30,Amlodipine 510 mg perindopril 48 mg,Atenolol 50100 mg bendroflumethiazide 1.252.5 mg/K,ASCOT: Total CV events and procedures,Co

59、urtesy of Appel G, 2006.Adapted from Dahlf B et al. ,12.0,10.0,0,8.0,4.0,0,1.0,2.0,3.0,3.5,0,1.0,2.0,3.0,3.5,2.0,6.0,12.0,10.0,0,8.0,4.0,2.0,6.0,HR 0.73 (0.600.88) P = 0.001,HR 0.85 (0.711.02) P = 0.08,Cumulativeincidence(,Placebo,Atorvastatin,Years,Amlodipine 510 mg perindopril 48

60、 mg,Atenolol 50100 mg bendroflumethiazide 1.252.5 mg/K,HPS, ASCOT: Summary and implications,Statins reduced CV events in moderate- to high-risk patients with “normal” LDL-C Global CV risk, not absolute LDL-C level, determines need for statin therapy Occlusive vascular disease Hypertension plus 3 oth