Integrating Aggressive CV Risk Management in Primary Care英文版).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

2、%,33.0%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. L

3、ancet. 2004;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,12,34,56,78,910,1112,1314,15

4、16,1718,1920,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 Maj

5、or RFs,1 Major RF,1 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

6、; N = 2864,Clinical manifestations 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 bo

7、dy obesity Is associated 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 subcu

8、taneous fat,Grundy SM et 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.,Subcuta

9、neous obesity Fat mass: 19.8 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 visce

10、ral adiposity,Desprs JP et al. BMJ. 2001;322:716-720.,Measuring waist circumference,NHLBI. .gov.,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

11、patients by 2050*,174%,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,S

12、udden cardiac death: Too often 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,A

13、BCs of multiple risk factor 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, legum

14、es, whole grains, non-fat/low-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.

15、 2004;351:2683-93.,Conventional 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,Bas

16、eline,Follow-up,Physical activity reduces 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,H

17、ypertension,Hazard ratio,1.5,1.0,0.5,Normal 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,Dansing

18、er ML et al. JAMA. 2005;293:43-53.,N = 160 overweight 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 beh

19、aviors and adherence to medical therapy Novel 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: Rationa

20、le for Target-Driven Behavior Modification and Polypharmacy,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 therap

21、y (n = 80),Follow-up (years),Follow-up (years),0,1,2,3,4,5,6,7,8,50,150,250,350,0,0,1,2,3,4,5,6,7,8,110,130,150,170,0,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 imp

22、roves macrovascular outcomes,Gde P et al. N Engl J Med. 2003;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

23、 = 20%,N = 160 with type 2 diabetes and microalbuminuria,Steno-2: 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

24、 complications after 4 years was maintained at 8 years,Relative risk,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

25、,180,Usual SBP (mm Hg),Usual DBP (mm Hg),70,90,100,110,80,Systolic BP,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: Compar

26、ison of more- vs less-intensive BP lowering,Blood Pressure Lowering Treatment 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 mar

27、kedly increase CV disease severity Standard BP-lowering therapies (diuretics 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

28、 more CV events,BPLTTC. Arch Intern Med. 2005;165:1410-9.Dahlf B et al. Lancet. 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 (treat

29、ed)+ 3 other risk factors N = 19,257,Amlodipine 510 mg perindopril 48 mg,Atenolol 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

30、. 2001;19:1139-47. Sever PS et al. Lancet. 2003;361:1149-58.,Patients with risk factor (%),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 P

31、eripheral vascular disease,ASCOT-BPLA: BP reductions over time,Blood pressure(mm Hg),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 =

32、 1.9, P 0.0001,60,100,0,80,120,140,160,180,Mean difference = 2.7, P 0.0001,Diastolic BP,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 bendroflumethiazi

33、de 1.252.5 mg/potassium,Amlodipine 510 mg perindopril 48 mg,Dahlf B et al. Lancet. 2005;366:895-906.,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

34、 Total coronary endpoint14.6 16.8 Total CV events and procedures 27.4 32.8 All-cause mortality13.9 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,Amlodip

35、ine-based(n = 9639),Atenolol-based (n = 9618),Amlodipine-based better,Atenolol-based better,0.50,0.70,1.00,1.45,2.00,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 Amlo

36、dipine 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,Time (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 an

37、d hemodynamics with amlodipine perindopril vs atenolol bendroflumethiazide, despite similar brachial 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. Cir

38、culation. 2006;113:1213-25.,Beyond BP Reduction: Integrating RAAS Modulation in Vascular Protection,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 f

39、actor LVEF = left ventricular ejection fraction,HOPE Study Investigators. N Engl J Med. 2000. EUROPA 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 Investigator

40、s. Lancet. 2003. PEACE Trial Investigators. N Engl J Med. 2004.,HOPE, EUROPA, PEACE: Primary outcomes,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,

41、Placebo,Perindopril 8 mg,8,6,2,5,2,20% RR P = 0.0003,RR = risk reduction,HOPE, EUROPA, PEACE: Reduction 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

42、Dagenais GR et al. Lancet. 2006;368:581-8.,1.1,1.0,0.5,0.9,Odds ratio (95% CI),AntiplateletsNo antiplatelets 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,PInterac

43、tion,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 better,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 reducti

44、on (%),25,10,0,CV death,* nonfatal MI or stroke,ACEI worse,ACEI better,*Or total mortality in AIRE, TRACE, SOLVD, 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.

45、,CHD = MI and CV death,Blood Pressure Lowering Treatment Trialists Collaboration meta-analysisN = 137,356; 21 randomized 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,

46、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 in patients with vascular disease with/without LVSD or HF Benefit in addition to antiplatelet agents, -blockers, and lipid-lowering agents Combining ACEIs with these agen

47、ts provides greatest benefit Benefit in patients across a broad range of risk for CV events Annual rate in placebo groups of 1.4%22.6%,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 to

48、lerability Use doses proven in clinical trials,Integrating Statinsin CV Risk Reduction,Statins reduce all-cause death,CTT Collaborators. 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,A

49、ny 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:,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,Rela

50、tive risk,Treatment(n = 45,054),Control(n = 45,002),Meta-analysis of 14 trials,HPS: Assessing statin benefit in high-risk patients,HPS Collaborative 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)

51、N = 20,536,Simvastatin 40 mg,Follow-up: 5 years,Primary outcomes:Mortality (overall analysis) Fatal/nonfatal vascular events (subcategory analysis),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

52、%),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,HPS Collaborative Group. .,24% reduction 2P 0.00001,Rate ratio (95% CI),Patients with multiple risk factors may develop CV disease at LDL-

53、C levels 100 mg/dL,N = 20,536; Fatal/nonfatal vascular events,ASCOT-LLA: Rationale,Premise High prevalence of dyslipidemia in hypertensive patients Most CV disease events occur in patients with BP and lipid concentrations deemed normal Hypothesis Lipid lowering will benefit hypertensive patients not

54、 conventionally deemed dyslipidemic,Sever PS et al. Lancet. 2003;361:1149-58.,Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm,ASCOT-LLA: Design,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

55、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 250 mg/dLn = 10,305,Atorvastatin 10 mg,Placebo,RandomizedDouble-blind,ASCOT-LLA: Statin reduces primary outcome in hypertension,Sever PS et al. Lan

56、cet. 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,Follow-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*,Atorvasta

57、tin,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,Placebobetter,Sever PS et al. Am J Cardiol. 2005;96(suppl):39F-44F.,ASCOT-LLA post hoc analysis: Time to benefit,n = 10,305,ASCOT: Integrati

58、on of antihypertensive regimens with statin,Courtesy of Appel G, 2006.Adapted from Dahlf B et al. .,Cumulativeincidence(%),4.0,3.0,0,2.0,1.0,0,1.0,2.0,3.0,3.5,4.0,3.0,0,2.0,1.0,0,1.0,2.0,3.0,3.5,Placebo,Atorvastatin,Primary endpoint: Nonfatal MI and fatal CHD,Years,HR 0.47 (0.320.69)P = 0.001,HR 0.8

59、4 (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,Courtesy 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