抗高血压治疗我们能做得更.ppt

抗高血压治疗：我们能做得更好,李 勇 复旦大学附属华山医院心脏科 上海 200040 ,单纯收缩期高血压,(%),(%),脑卒中,冠心病,总死亡,心血管 死亡,非心血管 死亡,致死和致残事件,死亡率,收缩压和舒张压均升高的高血压,脑卒中,冠心病,总死亡,心血管 死亡,非心血管 死亡,致死和致残事件,死亡率,降压治疗的临床获益,ESH-ESC Hypertension Guidelines. J Hypertens. 2003.,0.01,0.01,0.001,NS,0.001,0.001,0.02,0.01,NS,0.001,SBP降低10-12mmHg,降压治疗的主要获益来源于血压降低本身 至少将血压降至 SBP 140mmHg 和 DBP 90mmHg 对糖尿病患者 SBP 130mmHg 和 DBP 80mmHg 对老年人SBP 150mmHg和 DBP 90mmHg 仍然强调严格控制血压,降压治疗的目标,中国高血压指南2005,CV=cardiovascular. Neal B et al. Lancet. 2000;356:19551964.,Current Antihypertensive Therapy Reduces CV Events,Average Reduction in Events, %,Major CV Events,20%30%,Stroke,30%40%,CV Death,30%40%,60,40,20,0,100,80,联合降压药物治疗为基本策略,Approximately 70% of Patients* Do Not Reach Blood Pressure Goal,Wolf-Maier et al. Hypertension 2004;43:1017,*Treated for hypertension BP goal is 140/90 mmHg,Patients (%),England,Sweden,Germany,Spain,Italy,China,中国居民营养与健康现状. 卫生部、科技部、统计局, 2004年10月12日,USA,达标血压：糖尿病或肾病患者血压130/80mmHg，其他患者140/90mmHg,* 单因素Logistic 回归分析结果，P0.05与1级高血压患者相比,我国三甲医院门诊高血压总达标率仅为31.1%,0%,5%,10%,15%,20%,25%,30%,35%,40%,总达标率,1级高血压,2级高血压,3级高血压,31.1%,37.3%,32.6%,26.5%,中國降压药物治疗现状：联合治疗比例偏低,43.9%的患者单药降压治疗,21%起始联合降压或复方制剂,Target BP (mm Hg),Number of antihypertensive agents,1,Trial,2,3,4,Multiple Antihypertensive Agents Are Needed to Achieve Target BP,DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure. Bakris GL et al. Am J Kidney Dis. 2000;36:646-661. Lewis EJ et al. N Engl J Med. 2001;345:851-860. Cushman WC et al. J Clin Hypertens. 2002;4:393-405.,2007 ESH-ESC 高血压诊治指南 2007-06-12,利尿剂, 受体阻断剂, 受体阻断剂,ACE抑制剂,钙拮抗剂,血管紧张素受体阻断剂(ARBs),ASCOT trial：CV death + MI + Stroke,0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,0.0,2.0,4.0,6.0,8.0,10.0,氨氯地平 培哚普利 (No. of events = 796),阿替洛尔 苄氟噻嗪 (No. of events = 937),HR = 0.840 (0.760.92) p 0.0003,Number at risk 氨氯地平 培哚普利 9639 9415 9228 9007 8778 7655 阿替洛尔 苄氟噻嗪 9618 9400 9152 8891 8629 7500,%,危险降低 16%,ACCOMPLISH研究：主要终点,累积事件率,HR (95% CI): 0.80 (0.72, 0.90),20%,第一个CV事件/死亡出现的时间 (天),p = 0.0002,650,526,2008年3月初步结果,ASH Position Article Combination Therapy in Hypertension,J Am Soc Hypertens 2010; 4(1) : 4250,Recommendations,B = 阻滞剂；C = 二氢吡啶类钙拮抗剂；non-DHP C = 非二氢吡啶钙拮抗剂；D = 利尿剂；,积极控制血压 血压越低越好,BP Differences of 10 mmHg Are Associated With Up to a 40% Effect on CV Risk,Meta-analysis of 61 prospective, observational studies 1 million adults 12.7 million person-years,Lewington S et al. Lancet. 2002;360:19031913.,10 mmHg decrease in mean SBP,40% reduction in risk of stroke mortality,30% reduction in risk of IHD mortality,Staessen JA, et al. Lancet. 2001;358:1305-15.,Difference in SBP (mm Hg),Odds Ratio,P = 0.003,0,5,10,15,20,25,- 5,1.50,1.25,1.00,0.75,0.50,0.25,SBP Reduction and CV Mortality,90,Events / 1000 Pt-Years,HOT Trial: CV Events in Diabetics and Nondiabetics Effect of Diastolic Target at 4 Years,Hansson L et al. Lancet 1998;351: 1755-1762.,Diabetic Patients n=1,501; p=0.016,85,80,90,85,80,Nondiabetic Patients n=18,790; p=NS,24.4,18.6,11.9,9.9,10.0,9.3,RRR=51%,降压治疗血压水平越低越好？ UKPDS 、 ADVANCE 和 ACCORD的启示,BMJ. 2000; 321,BP: 133.5 Standard vs. 119.3 Intensive, Delta = 14.2,Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3,ACCORD trial：SBP reductions,Primary Outcome Nonfatal MI, Nonfatal Stroke or CVD Death,Total Mortality,HR = 0.88 95% CI (0.73-1.06),HR = 1.07 95% CI (0.85-1.35),ACCORD trial：Outcomes,优质降压，降低血压变异性,ASCOT： BP Changes,Blood pressure (mmHg),60,80,100,120,140,160,180,Follow-up (years),Baseline,0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,5.5,amlodipine perindopril atenolol bendroflumethiazide,137.7,136.1,79.2,77.4,Mean difference 1.9,Last visit,Mean difference 2.7,SBP,DBP,163.9,164.1,94.8,94.5,ASCOT-BPLA: summary of all endpoints,The area of the blue square is proportional to the amount of statistical information,Amlodipine perindopril better,Atenolol thiazide better,0.50,0.70,1.00,1.45,Primary Non-fatal MI (incl. silent) + fatal CHD Secondary Non-fatal MI (excl. silent) + fatal CHD Total coronary endpoint Total CV events and procedures All-cause mortality Cardiovascular mortality Fatal and non-fatal stroke Fatal and non-fatal heart failure Tertiary Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment Post hoc Primary endpoint + coronary revasc procs CV death + MI + stroke,2.00,Unadjusted hazard ratio (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05) 1.27 (0.80-2.00) 0.68 (0.51-0.92) 0.98 (0.81-1.19) 0.65 (0.52-0.81) 1.07 (0.62-1.85) 0.70 (0.63-0.78) 0.85 (0.75-0.97) 0.86 (0.77-0.96) 0.84 (0.76-0.92),Dahlf B et al. Lancet 2005:366;895-906 (Online Sept 4, 2005),不同降压治疗方案的临床获益差异,血压差异并不足以解释 显著的心脑获益 是否有血压之外的其他原因 ？,单次随访和24h动态血压(ABPM)变异性都能够预测心血管结局；而5年的随房间血压变异性则为最强的心血管结局预测因素 -Prof.Peter Sever,标准差SD,变异系数CV,收缩压均值,独立于均值的变异性VIM,脑卒中风险,冠脉事件风险,血压变异性 较平均血压增加更强预测心血管事件,Peter M Rothwell, et al.Lancet 2010; 375: 895905,风险比(95%CI),风险比(95%CI),风险比(95%CI),风险比(95%CI),氨氯地平,阿替洛尔,ASCOT-BPLA中氨氯地平组和阿替洛尔组的随诊间血压变异性参数的升高均与卒中和CHD风险增加相关,随访时间,基线,3个月,1年,2年,3年,4年,5年,6年,个体间SBP标准差,p110 20,Peter M Rothwell et al.Lancet Neurol 2010; 9: 46980,所有患者,氨氯地平显著降低个体间血压变异性,阿替洛尔组,氨氯地平组,氨氯地平 组的血压 变异性 持续降低,血压变异是卒中风险的强预测因素,P值,氨氯地平组显著降低卒中风险,0.5,1,1.5,氨氯地平组更优,阿替洛尔组更优,校正平均血压后，两组的卒中风险仍有显著差别,说明平均血压的差别不能解释两组卒中风险差异,SD：标准差；WVSD：同次随诊血压变异性；mean：平均血压 VIM ：独立于平均血压外的血压变异性,卒中风险比(95%CI),Peter M Rothwell et al.Lancet Neurol 2010; 9: 46980,进一步校正随诊间 后，两组卒中风险的差异消失,证明血压变异性能很好的解释氨氯地平组中卒中事件发生率低的原因,说明随诊间血压变异性可以部分解释两者卒中风险的差别,进一步校正随诊内和随诊间血压变异性后，两组卒中风险差异消失,RAS抑制不可或缺,RAAS活性增强导致心血管危险增加 与血压水平无关,Events per 1000 patient years,18,16,14,12,10,8,6,4,2,0,低,低,高,高,正常,正常,0,1.8,7.8,5.5,8.2,17.5,RAAS 活性,无危险因素,1 危险因素,Alderman M et al. N Eng J Med 1991;324:10981104,即使患者的血压已经获得良好控制，随着RAAS活性增强，高血压患者发生心肌梗死的危险性仍显著增加,Candido, R. et al. Circulation 2004;109:1536-1542,Diabetes-associated Atherosclerosis Is Ameliorated by RAS inhibitor than CCB,-SMA immunostaining in sections of aorta,吳,Parving HH, et al. N Engl J Med. 2001 Sep 20;345(12):870-8,随访时间(月),糖尿病肾病发生率(%),P0.001,70%,IRMA-2研究 厄贝沙坦显著降低糖尿病肾病发生率,安慰剂,厄贝沙坦 150mg,厄贝沙坦 300mg,随访时间(月),主要终点事件发生率(%),Lewis EJ, et al. N Engl J Med. 2001; 345(12):851-860,vs 氨氯地平P=0.006,IDNT研究 厄贝沙坦降低肾脏终点事件显著优于CC