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,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,PPT课件,*,Klicka hr fr att ndra format,p bakgrundsrubriken,Klicka hr fr att ndra format p bakgrundstexten,Niv tv,Niv tre,Niv fyra,Niv fem,解读,ACC/AHA 2005,心衰指南,代文,在高血压及心衰治疗中地位,1,PPT课件,Heart Failure in the United States, 145%, 260%,1979n=35,051,1999,50,624,1979,377,000,1999,962,000,Deaths,HospitalizationDischarges,AHA Statistical Update 2002,2,PPT课件,慢性心衰发病率,绝对患者数 (,1,000,000,),比率 (每百万人群),西欧,5.3,14,000,东欧,1.3,13,000,前苏联,5.6,19,000,北美,5.2,18,000,日本,2.4,19,000,其他,2.8,11,000,WHO Statistics 1996,3,PPT课件,心衰预后,心衰患者死亡率高，平均寿命低于多种常见类型肿瘤,; (Ho et al. 1993),HF,高死亡率：,25%,新发患者在,1,年内死亡,(ESC 1999,1979,年至,1999,年间,心衰引起的,死亡增加,145%,(AHA 2005),HF,中位生存时间约为诊断后,1.7,3.2,年,(Kannel et al. 1988; Kannel,1991),心衰反复入院治疗很常见，,超过,50%,患者,半年内即再入院治疗,(Krumholz,et al. 1997, Vinson et al. 1990, Burns et al. 1997),4,PPT课件,The Cardiovascular Continuum:,Targeting Mechanisms and Mediators,Adapted from Dzau,V et al.,Am Heart J,. 1991.,Endothelial,Dysfunction,Target Organ,Damage,Risk Factors,Vascular,Dysfunction,Vascular Disease,Tissue Injury,(MI, Stroke),Pathological,Remodeling,Target Organ Dysfunction,(,CHF,Renal),End-stage,Organ Failure,Death,Angiotensin,II,5,PPT课件,Stages of Renal and CV Disease,ESRD,CRI (, GFR),Albuminuria,Proteinuria,Elderly, DM,HTN,Chronic RenalDisease,CVDisease,Elderly, DM,HTN,CAD,LVH,ASCVD Events,CHF,End-,stage,Progression,Initiation,“At-risk”,6,PPT课件,Natural History of CVD Progression,Elevated BP,Target Organ Damage,More Recent Paradigm,A Proposed Future Paradigm,Elevated BP,Target Organ Damage,Vascular Dysfunction,Elevated BP,Target Organ Damage,Vascular Dysfunction,EndothelialDysfunction,Early Paradigm,Angina Pectoris,Stroke,MI,Renal Damage,LVH,?,Hypertension: The Disease Continuum,7,PPT课件,CAD,Hyp,CM,Valv,LVD,重构,低,EF,死亡,非心脏因素,症状,CHF,心律失常,泵衰竭,激活,SNS,RAS,激活,SNS,RAS,激活,SNS,RAS,8,PPT课件,心血管事件链,“,心脏疾病是一系列疾病延时间发展而成的统一体。它以危险因子为开端，中间经过诸如急性心梗等独立的危险事件，这些事件或者引发猝死或者促进心功能衰竭，因此,我们必须停止将不同心血管疾病割裂开来对待,.,”,Mandeep,Mehra, M.D.,Head of Cardiology,University of Maryland Medical Center,“,心力衰竭,心脏病最后的大战场,”,E,Braunwald,ACC 2003,9,PPT课件,心衰危险因素,高血压,是 心衰最主要的危险因子,使,心衰危险增加,3,倍,(AHA 2005),75%,的心衰患者曾患,高血压,(AHA 2005),约,65%,的心衰由冠状动脉疾病引起,。,35%,由非缺血性疾病如瓣膜疾病、心脏毒性药物、心肌炎或原发性心肌病引起,(Chobanian et al. 2003),年龄和冠心病是心衰的主要决定因素，其他预测因子包括,高血压、糖尿病,、吸烟和肥胖,10,PPT课件,ACC/AHA Practice Guidelines,Pyramid Approach to HF Stages,High Risk for Developing HF,Hypertension,CAD,Diabetes mellitus,Family history of cardiomyopathy,Asymptomatic HF,Previous MI,LV systolic dysfunction,Asymptomatic valvular disease,Symptomatic HF,Known structural heart disease,Shortness of breath and fatigue,Reduced exercise tolerance,Refractory End-Stage HF,Marked symptoms at restdespite maximal medical therapy,A,B,C,D,Hunt SA et al.,J Am Coll Cardiol,.,2001;38:2101-2113.,11,PPT课件,心衰的,A,阶段,对血压,血脂及代谢异常的干预,高血压阶段的,主要组织结构的病变特点,12,PPT课件,Evolution of Cardiovascular Events: ACC/AHA Stage A Heart Failure,Adapted from HFSA.,Pharmacotherapy.,2000;20:495.,SNS-RAS,SNS-RAS,Metabolic,Syndrome(Insulin resistance, diabetes),HTN,MI,Cardio-myopathy,HF,Does effective therapy of HTN prevent CVD & HF?,13,PPT课件,Average Percent Reduction,Stroke incidence 35-40%,Myocardial infarction 20-25%,Heart failure50%,JNC VII: Benefits of Lowering BP,14,PPT课件,Not at Goal Blood Pressure (140/90 mm Hg) (,160 or DBP,100 m,m Hg) 2-drug combination for most (usually thiazide,-type diuretic and ACEI, or,ARB,or BB, or CCB),Stage 1 Hypertension,(SBP 140,-159 or DBP 90-99 mm Hg) Thiazide,-type diuretics for most. May consider ACEI,ARB, BB, CCB, or combination.,Without Compelling Indications,Not at Goal Blood Pressure,Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist.,JNC 7,高血压治疗流程,15,PPT课件,大量临床试验证明了,ARB,卓越的治疗作用,ARB,不仅在应用,ACEI,发生咳嗽时推荐使用,无咳嗽时仍可以使用,确立了,ARB,在高血压伴有某些特殊疾病时的治疗地位,对,ARB,治疗地位的肯定,2004,年高血压治疗指南,16,PPT课件,ARB,在特殊疾病时的,治疗地位,糖尿病高血压,要求将血压降至,130/80mmHg,以下，,常须联合用药,ARB,对,2,型糖尿病防止肾损害有益,慢性肾病,ACEI,、,ARB,有利于防止肾病进展,，重度病人须合用袢利尿剂,心力衰竭,在,症状多的将,ACEI,、,阻滞剂、,ARB,和醛固酮拮抗剂与袢利尿剂合用,2004,年高血压治疗指南,17,PPT课件,代文降压疗效与氨氯地平相同,4,周时血压平均下降值,(mmHg),Palatini,et al.,J,Hypertens,2001; 19: 1-6,舒张压,收缩压,-9.1,-10.3,代文,80mg,氨氯地平,5mg,代文,80mg,氨氯地平,5mg,-19.5,-20.2,P=NS,P=NS,18,PPT课件,双倍剂量代文降压疗效,优于双倍剂量依那普利,Fogari,et al.,Eur,J,Clin,Pharmacol,2004; 59: 863-868,-13.7,-18.6,-10.9,-15.6,P0.01,P0.01,16,周时血压较基线值的改变,(mmHg),舒张压,收缩压,代文,160mg,依那普利,20mg,代文,160mg,依那普利,20mg,19,PPT课件,不同,ARB,治疗后的血压下降值,(mmHg),舒张压,-9.8,-6.9,收缩压,-14.1,-9.9,代文,80mg,氯沙坦,50mg,厄贝沙坦,150mg,代文,80mg,氯沙坦,50mg,厄贝沙坦,150mg,-13.8,-9.9,-7.9,-10.8,坎地沙坦,8mg,坎地沙坦,8mg,拉丁方试验证实,ARB,降压的疗效有了充分体现,Fogari,et al.,Curr,Ther,Res,2000; 61 (10): 669-679,P0.05,P=NS,P0.05,P=NS,20,PPT课件,心肌缺血发生的时间与分钟,缺血,(,分钟,),01:00 05:00 09:00 13:00 17:00 21:00,时间,300,250,200,150,100,50,0,0-2 3-5 6-8 9-11 12-14 15-17 18-20 21:-2,4,n=11816,180,160,140,120,100,80,60,40,20,0,脑梗死发作的时间及,%,ARB,降压的长效与平稳可以减少心脑血管事件发生,21,PPT课件,Time-Dependent Effects of Valsartan on ABP: Double-Digit 24-h BP Reductions With Morning or Evening Dosing,*,P,0.001 vs baseline.Hermida RC et al.,Hypertension,. 2003;42:283-290.,Systolic,Diastolic,17.0*,11.3*,20,15,10,5,0,24-h Mean,in BP,(mm Hg),14.6*,11.4*,Valsartan 160 mg at awakening,(n = 46),Valsartan,160 mg atbedtime,(n = 44),Treatment With Valsartan Reduces Percent of Nocturnal Non-dippers,Hermida RC et al.,Hypertension,. 2003;42:283-290.,Percent of Nocturnal Non-dippers,0,20,40,60,80,100,52.2,45.7,59.1,15.9,Before treatment,After treatment, valsartan 160 mg,Awakening,Bedtime,RRR = 73.1%,RRR = 12.5%,Relative r,isk reduction of,73.1%,with bedtime administration,心衰,A,期的组织结构的,的主要变化,ARB,在心衰,A,期的干预作用,24,PPT课件,血管主要的结构病变特性,25,PPT课件,Vascular Remodeling:,Clinical Implications,Myocardial Infarction,Renal Failure,Hypertension,Stroke,Tissue Ischemia,26,PPT课件,Coronary reserve in hypertension and LVH,0 20 40 60 80 100 120 140 160,100,200,300,400,500,Flow (ml/min),Coronary Flow,Reserve,Maximal,Vasodilation,NT,HT,LVH,Arterial Pressure (mmHg),27,PPT课件,LV,功能不全,RAAS,激活,阻力,LV,重构,28,PPT课件,Ang II and Vascular Remodeling,Ang,II,Vascular Hypertrophy,Vascular Compliance,Afterload,M/L Ratio,Vascular Fibrosis,M,L,M,L,29,PPT课件,Influence of Angiotensin II on the Blood Vessel,Weir MR, Dzau,VJ.,Am J Hypertens,. 1999;12:205S213S.,Induction of Angiotensin II Pathways at the Tissue Level, Local Angiotensin II production,Vascular remodeling,Blood Pressure,Vascular Injury,30,PPT课件,6%,Media-lumenratio,ACEI,ARB,CCB,Hypertensive,8.5%*, 7%,8.5%*,Atenolol,No change,Improve,Normotensive,*,p, 0.01,vs,normotensive,p, 0.05,vs,hypertensive and atenolol,31,PPT课件,32,PPT课件,*,*P, 0.05 vs baseline.,250,0,50,100,150,200,Valsartan,Baseline,Week 8,300,350,% Change in F,orearm Blood Flow in Response to ACh,Valsartan Improves Endothelial Function,Tzemos N et al.,Am J Hypertens,. 2001;14:66A67A. Abstract P-111.,The clinical significance of these effects is unknown.,33,PPT课件,Valsartan,Improves Vessel Elasticity*,inAugmentationIndex,*BP reductions similar for valsartan and HCTZ.,P,0.01,vs HCTZ and vs placebo.,Adapted with permission from,Klingbeil AU et al.,J Hypertens,. 2002;20:2423-2428.,40,30,20,10,0,Valsartan,Placebo,HCTZ,Valsartan improves arterial compliance in patients with hypertension.,Effects are independent of BP reduction.,-21.7,(n = 20),-3.2,(n = 20),-0.3,(n = 20),34,PPT课件,*,P,0.005 vs placebo.Adapted with permission from Peters S et al.,J Invasive Cardiol.,2001;13:93-97.,Val-PREST: In-Stent Restenosis and,Reintervention Rates at 6 Months,PatientsWithRestenosis,%,Valsartan 80 mg,(n = 99),Placebo,(n = 101),50% reduction,with valsartan vs placebo,*,0,10,20,30,40,50,Restenosis,Reintervention,*,58% reduction,with valsartan vs placebo,35,PPT课件,心衰,-,心血管事件链的最后阶段,危险因素,糖尿病,高血压,动脉粥样硬化,左室肥厚,心肌梗死,左室重构,心室扩张,终末期心脏病死亡,充血性,心力衰竭,心血管事件链是一系列以病生理为主线，,将心血管危险因子和临床疾病连接而成的链条,36,PPT课件,Sympathetic Nervous System,CNS sympathetic outflow,Cardiac sympathetic activity,Renal sympathetic activity,Sodium retention,Myocyte hypertrophy,Myocyte injury,Increased arrhythmias,Disease progression,1,b,1,b,1,b,2,1,Vascular sympathetic activity,Vasoconstriction,1,Activation,of RAS,37,PPT课件,异常的血管收缩,激活,S,NS,血管加压素,肌细胞增生,血管,平滑肌增生,胶原,心肌,血管重构,PAI-1/,血栓形成,血小板聚集,超氧化产物,内皮素,Ang II,血管紧张素,II,的在心肌及血管重构的有害作用,Adapted from,Burnier,M, Brunner HR.,Lancet,. 2000;355:637645.,Brown NJ, Vaughan DE.,Adv Intern Med,. 2000;45:419429.,醛固酮,38,PPT课件,Pathophysiologic Effects of Ang II,Adapted from Burnier,M et al.,Lancet,. 2000;355:637645.,Abnormal,Vasoconstriction,Activate,SNS,Aldosterone,Vasopressin,Collagen,Contractility,PAI-1/,Thrombosis,Platelet Aggregation,Superoxide,Production,Endothelin,Vascular Smooth Muscle Growth,Myocyte Growth,Ang II,39,PPT课件,Sympathetic Fibers,Angiotensinogen,NE,b,Renin,receptors(kidney,heart,vessels),PresynapticAngiotensin I,AT,1,receptor ACE,Angiotensin II,+,Sun Ning,ling,40,PPT课件,Levels,Adapted from Cohn JN.,Cardiology.,1997;88:26.,血浆,去甲肾上腺素,(pg/,mL,),NL,HF,血浆,肾素激活,(,ng,/,mL,/h),15,12,9,6,3,0,NL,HF,精氨酸,血管加压素,(pg/,mL,),12,6,4,2,0,NL,HF,心房钠尿肽,(pg/,mL,),300,250,200,150,100,50,0,NL,HF,内皮素,-1,(pg/,mL,),8,6,4,2,0,NL,HF,600,500,400,300,200,100,0,心衰神经激素激活,41,PPT课件,BNP,(pg/ml),238,BNP,随机化后时间,(,月,),生存率,20,10,30,0,40,0.5,0.6,0.7,0.8,1.0,0.9,9.7,14.3,20.7,32.4,%,死亡率,NE,572,274,274394,395572,NE,(pg/,mL,),0.5,0.6,0.7,0.8,1.0,0.9,24.2,%,死亡率,13.8,16.5,23.0,Val-HeFT,:,BNP,和,NE,基线四分法全因死亡率亚组分析,20,10,30,0,40,Anand,IS.,Circulation.,2003;107:12781283.,随机化后时间,(,月,),42,PPT课件,降低进程,I,LV,重构,神经激素,机械因素,机械因素,灌注,/,代谢,细胞死亡,(,坏死,/,凋亡,),延缓进程,II,神经激素因素,SNS,RAAS,醛固酮,内皮素,血管加压素,激酶,一氧化氮,(,保护作用,),延缓进程,III,机械性因素,血管壁压力,内皮下灌注,非同步收缩,43,PPT课件,传统的心衰常规治疗,-,强心、利尿、扩血管,已被以神经内分泌拮抗剂为主的新的,“,常规治疗,”,或,“,标准治疗,”,所取代：,ACEI/ARB,、,受体阻滞剂、利尿剂、有时加用地高辛,44,PPT课件,2001 ACC/AHA Practice Guidelines,Pyramid Approach to HF Therapy,Treat HTN, lipids; smoking cessation, exercise, limit alcohol,ACE-I in appropriate populations,All measures under “A” and ACE-I,-Blockersin the appropriate,populations,All under “A” and ACE-I,-blockers, diuretics, digoxin,CRT, dietary salt restriction,All under “A,B,C,”+ inotropes,transplant, VAD, hospice,A,B,C,D,Hunt SA et al.,J Am Coll Cardiol,.,2001;38:2101-2113.,High Risk for Developing HF,Asymptomatic HF,Symptomatic HF,End-Stage,HF,A,B,C,D,45,PPT课件,Neurohormonal Activation,in Heart Failure,Hypertrophy, apoptosis, ischemia,arrhythmias, remodeling, fibrosis,Angiotensin II,Norepinephrine,Morbidity and Mortality,ACE-I,46,PPT课件,CONSENSUS*,NYHA Class IV,SOLVD Treatment,NYHA Class II,III,*,危险降低,40% (,P,= 0.003),危险降低,16% (,P,= 0.0036),安慰剂,(n = 126),依那普利,(n = 1285),60,80,40,20,0,安慰剂,(n = 1284),死亡率,(%),12,6,18,30,36,42,0,24,48,Months,Swedberg,K et al.,Circulation,. 1990;82:17301736.,The SOLVD Investigators.,N Engl,J Med,. 1991;325:293302.,ACEI,在,CONSENSUS,和,SOLVD,试验中,对,CHF,的作用,依那普利,(n = 126),47,PPT课件,Beta-blocker Therapy in Heart Failure,Potential Beneficial Effects,Protection from,Catecholamine,Toxicity,Renin,- Angiotensin System,Reversal of Remodeling,Up-regulation,of,b,-,adrenergic,Receptors,Ancillary,Factors,48,PPT课件,2P = 0.0002,LVES,容积,mL/m,4,0, 4, 8,12, 12,8,2P = 0.0042,LVED,容积,mL/m,4,0, 4, 8,12, 12,8,ANZ,卡维地洛试验,Doughty RN et al.,J Am Coll Cardiol,. 1997;29:106066.,P = 0.019,LVES,容积,mL,6,个月,基线,12,个月,4,个月,基线,12,个月,4,0, 4, 8,12, 12,8,P = 0.025,LVED,容积,mL,4,0, 4, 8,12, 12,8,SOLVD,试验,Greenberg B et al.,Circulation.,1995;91:257381.,安慰剂,依那普利,安慰剂,依那普利,l,安慰剂,卡维地洛,安慰剂,卡维地洛,ACEI,和,受体阻滞剂对心室重构的作用,49,PPT课件,Neurohormonal Activation,in Heart Failure,Hypertrophy, apoptosis, ischemia,arrhythmias, remodeling, fibrosis,Angiotensin II,Norepinephrine,Morbidity and Mortality,ACE-I,-,阻滞剂,50,PPT课件,ACEI (yes) BB (yes),15.5,1.1,7.2,Ang,II,(,fmol,/,mL,),(n = 11),ACEI (yes) BB (no),(n = 11),101,5,10,20,15,100,95,Ang,I,(,fmol,/,mL,),5,10,20,15,100,95,血管紧张素,II,血管紧张素,I,105,105,ACEI + BB,在心衰患者中显著降低,Ang,II,水平,0,0,Campbell DJ et al.,Lancet.,2001;358:16091610.,51,PPT课件,Aldosterones Role,in Cardiovascular Disease,McMahon EG.,Current Opinion Pharmacol,. 2001;1:190-196.,Prothrombotic,effects,Potassium and,magnesium loss,Vascular,inflammation,and injury,Myocardial,fibrosis,Central,hypertensive,effects,Endothelial,dysfunction,Ventricular,arrhythmias,Sodium,retention,Catecholamine,potentiation,Cardiovascular disease,Deleterious effects,of aldosterone,52,PPT课件,Aldosterone Blockade,in Heart Failure,RALES: Randomized Aldactone Evaluation Study,1663 pts NYHA II, III, and IV, average age 65 and LVEF,0.35, on ACEI, loop diuretic,digoxin randomized to spironolactone 25 mg PO qd vs placebo.,Pitt B et al.,N Engl,J Med.,1999;341:709-717.,Spironolactone,Placebo,Follow-up (months),100,80,60,40,20,0,0,10,20,30,36,RR 0.70 (0.60-0.82),P,0.001,Probability of Survival (%),53,PPT课件,心肌梗死,ACE-I,醛固酮受体拮抗剂,左室重构,危险因素,高脂血症,高血压,糖尿病,吸烟,肥胖,胰岛素抵抗,动脉粥样硬化,左室肥厚,血管内皮功能不全,微小血管病,冠状动脉疾病,心力衰竭,死亡,终末期微小血管,肾病,SAVE,TRACE,AIRE,EPHESUS,CONSENSUS,SOLVD,RALES,HOPE,HOPE,HOPE,ACE-I,及醛固酮拮抗剂在心血管事件链中的作用,54,PPT课件,ACEI,长期治疗后的血管紧张素,II,逃逸现象,*,p,0.001 versus placebo.,Biollaz,J, et al.,J Cardiovasc Pharmacol,. 1982;4:966-972.,*,*,*,*,*,*,*,*,*,100,80,60,40,20,0,100,20,10,0,血浆,ACE,(nmol/mL/min,),血浆血管紧张素,(pg/mL,),安慰剂,4 h,24 h,1,2,3,4,5,6,月,住院,55,PPT课件,ARBs Prevent Angiotensin II Escape,Angiotensinogen,Angiotensin I,Angiotensin II,ACE-I,X,Angiotensin Receptor,Blocker,X,Degradation,Products,Renin,AT,1,Receptor,AT,2,Receptor,X,Non ACE-dependent,pathways to ANG II,production,Bradykinin,56,PPT课件,Chymase-Dependent vs ACE-Dependent A II Formation in Hearts of Various Species,Reprinted with permission from,Balcells E et al.,Am J Physiol.,1997;273:H1769-H1774.,A II Formation (%),Mouse,Rabbit,Rat,Dog,Human,0,40,60,80,100,20,ACE-dependent,Chymase-dependent,57,PPT课件,A II Formation in,Normal and Dysfunctional Vessels,A II Formed,(nmol/min/mg protein),Others (non-ACE, non-chymase dependent),ACE-dependent,Chymase-dependent,Normal aorta (n = 9),0,1,2,3,4,5,6,Atherosclerotic lesions(n = 8),Aneurysm (n = 6),*,*,*,P,0.01 vs normal aorta.,P,0.01 vs chymase-dependent A II-forming activity in the normal aorta.,Reprinted with permission from Ihara M et al.,Hypertension.,1999;33:1399-1405.,58,PPT课件,药物对肾素血管紧张素系统的作用,血管紧张素原,肾素,Ang,I,AT,1,受体,Ang,II,ACEI,ARB,BB,59,PPT课件,Renin-Angiotensin-Aldosterone,System,Angiotensinogen,Angiotensin I,Angiotensin II,Bradykinin,Inactive,Fragments,ACE,AT,2,AT,1,B2, NO,Renin,Vasodilation,Antiproliferation,(kinins),Non-ACE Pathways,(tonin, chymase, CAGE),Vasoconstriction,Cell growth,Na/H,2,0 retention,Sympathetic activation,Aldosterone,cough,vasodilation,platelet agg,ischemia,+ inotropic,NE,BB,60,PPT课件,ARB,在心衰,A,B,C,期的干预作用,61,PPT课件,“,心脏重构可定义为基因表达，分子、细胞以及间质性的显著改变，在临床上表现为心脏受损后心脏大小、形状和功能的改变。,”,Cohn JN et al.,J Am Coll Cardiol,.,2000;35:569582.,心脏重构,“,Cardiac remodeling may be defined as genome expression, molecular, cellular and interstitial changes that are manifested clinically as changes in size, shape and function of the heart after cardiac injury.,”,62,PPT课件,SV 100,EF 60,SV 100,EF 40,SV 100,EF 25,左室重构,63,PPT课件,月,1.0,0.9,0.8,0.7,0.6,0,4,8,12,16,20,24,28,32,Q1,Q2,Q3,Q4,LVIDd,EF,生存概率,月,0,4,8,12,16,20,24,28,32,1.0,0.9,0.8,0.7,0.6,Q1,Q2,Q3,Q4,Val-HeFT,: Kaplan-Meier,死亡率曲线,LVIDd,和,EF,四分法与基线,Wong M et al.,J Am Coll Cardiol,. 2002,;40:970,975,.,P, 0.00001,P, 0.00001,64,PPT课件,Clinical Significance of,AT,1,Receptor Blockade,A II,AT,2,BP,Atherosclerosis,Endothelial,Function,Neuroendocrine,LVH,Cardioprotection,Vasculoprotection,Renoprotection,AT,1,receptor,blockade,A II,binding at the AT,2,receptor,ARB,LVH=left ventricular hypertrophy.,AT,1,65,PPT课件,ARB,对血管紧张素,II,和缓激肽的作用,ARB,血管紧张素转换酶,血管舒张,缓激肽,血管紧张素转换酶,血管紧张素原,血管紧张素,II,无活性缓激肽,NO,无咳嗽,无肾性水肿,血管收缩,;,血管舒张,AT1; AT,2,血管紧张素,I,肾素,No,生长,66,PPT课件,ARBs,在心血管事件链中的作用,心肌梗死,左室重构,危险因素,高脂血症,高血压,糖尿病,吸烟,肥胖,胰岛素抵抗,动脉粥样硬化,左室肥厚,血管内皮功能不全,微小血管病,冠状动脉疾病,心力衰竭,死亡,终末期微血管,心肾疾病,OPTIMAAL,VALIANT,RENAAL,IDNT,IRMA-2,MARVAL,Elite II,Val-HeFT,CHARM,NAVIGATOR,ONTARGET,TRANSCEND,LIFE,Value,卒中,67,PPT课件,Beta Blocker,ACE inhibitor,or,ARB ?,or,ACE inhibitor and,ARB?,Aldosterone,Receptor,Antagonist,+,+,CIBIS-2,MERIT-HF,COPERNICUS,CONSENSUS,SOLVD-T,ELITE-2,Val-,HeFT,CHARM,RALES,CAPRICORN,SAVEAIRE,TRACE,OPTIMAAL,VALIANT,VALIANT,EPHESUS,CHRONIC HEART FAILURE,AMI LVSD/HF,68,PPT课件,ELITE II:,Pitt B, et al.,Lancet.,2000;355:1582-1587.,全因死亡,存活概率,全因死亡或住院治疗,存活概率,猝死或心跳骤停复苏,存活概率,0,100,200,400,300,500,600,700,Follow-up (days),p,=0.16,p,=0.08,p,=0.18,卡托普利,氯沙,坦,1.0,0.8,0.6,0.4,0.2,0.0,1.0,0.8,0.6,0.4,0.2,0,1.0,0.8,0.6,0.4,0.2,0,氯沙坦在降低总死亡率或心源性,猝死方面的疗效,并不优于,卡托普利,69,PPT课件,VAL,SARTAN,HE,ART,F,AILURE,T,RIAL,缬沙坦治疗心力衰竭试验,心衰治疗的里程碑,70,PPT课件,0,1,2,3,4,5,Years,Val-,HeFT,65,岁健康白人男性,V-,HeFT,I,生存率,(%),0,50,60,70,80,90,100,SOLVD-T,V-,HeFT,II,MERIT-HF,在主要心衰试验中生存率最高,National Vital Statistics Report. 1999; Cohn et al. NEJM 2001;345:1667; SOLVD Investigators. NEJM 1991;325:293; Cohn et al. NEJM 1986;12; Packer M, et al. NEJM 1996; Consensus Study Group NEJM 1987; Packer M, et al. NEJM 1991;325:1468,71,PPT课件,研究回顾,5010,例患者,18,岁,; EF 40%; NYHA II,IV,利尿剂,(85%),地高辛,(67%),-,阻滞剂,(35%),ACE,抑制剂,( 93%),缬沙坦,40 mg bid,调整至,160 mg bid,随机分组,接受基础治疗,安慰剂,72,PPT课件,代文,降低所有原因病死率与病残率联合终点,13.2%,Cohn JN.,Circulation,. 2000;102:2672-2676.,0,65,70,75,80,85,90,95,0,3,6,9,12,15,18,21,24,27,缬沙坦,安慰剂,100,* p,=0.009,月,无事件概率,(%),13.2%,危险降低,*,73,PPT课件,代文,降低心力衰竭住院,*,27.5%,0,65,70,75,80,85,90,95,0,3,6,9,12,15,18,21,24,27,100,* p,0.00001,月,无事件概率,*First hospitalization.,Cohn JN.,Circulation,. 2000;102:2672-2676.,缬沙坦,安慰剂,27.5%,危险降低,*,74,PPT课件,代文,降低所有原因病死率和病残率联合终点,44%,未接受,ACEI,基础治疗亚组,0,3,6,9,12,15,18,21,24,27,0.40,0.49,0.57,0.66,0.74,0.83,0.91,1.00,* p,0.00002,月,无事件生存率,Maggioni AP, Anand,IS et al.,JACC,2002),缬沙坦,n = 185,安慰剂,n = 181,44%,危险降低,*,75,PPT课件,50,100,0,3,6,9,12,15,18,21,24,27,30,生存率,(%),60,70,80,90,随机分组后,(,月,),* P,= 0.017,代文,降低,所有原因死亡率,33%,Maggioni AP, Anand,IS et al.,JACC,2002),缬沙坦,n = 185,安慰剂,n = 181,未接受,ACEI,基础治疗亚组,33%,危险降低,*,76,PPT课件,Val-HeFT,:,左室功能的超声心动指标,缬沙坦,安慰剂,LVIDd,/BSA,变化,(cm/m,2,),EF,变化,(%),2.0,3.0,4.0,5.0,0.12,0.08,0.04,0.00,4 Months,12 Months,18 Months,24 Months,P, 0.0001,P, 0.001,P, 0.0001,P,= 0.031,P, 0.001,P, 0.0001,P, 0.0001,P,= 0.033,Wong M et al.,J Am Coll Cardiol,. 2002;40:970975.,77,PPT课件,0.5,0.6,0.7,0.8,0.9,1.0,1.1,1.2,1.3,1.4,Hazard ratio,患者,数,死亡率,Decrease ,+0.094 1135,首次事件发生时间,Decrease ,+0.094 1095,Val-HeFT: 4,个月时,LVIDd,/BSA,、死亡率危险度、首次事件发生与基线相比变化,78,PPT课件,时间,(,月,),安慰剂,基线,= 472,缬沙坦,基线,= 456,*Mean,SEM.,n = 1894,n = 1713,n = 840,n = 1855,n = 1635,n = 816,0,4,12,24,10,0,10,20,30,
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