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1、稳定性冠心病的血压管理研究证据和临床意义,广东省人民医院心内科 广东省心血管病研究所 陈鲁原,高血压与冠心病,血压的升高促使动脉粥样硬化的发生与发展；冠心病的心血管事件、死亡与升高的收缩压/舒张压水平正相关；高血压患者冠心病的患病率是血压正常的3-4倍；全球60%-70%冠心病患者有高血压；49的心肌梗塞病例都是由高血压引起,Effect of Systolic BP and Diastolic BP on CHD Mortality:MRFIT Screenees(N=316,099)*,*Men aged 35 to 57 years followed up for a mean of 1
2、2 years.,Death rateper 10,000person-years,Diastolic BP(mm Hg),Systolic BP(mm Hg),Adapted from:Neaton et al.Arch Intern Med.1992;152:56-64.,稳定型冠心病临床试验基线血压水平,SBP(mmHg),HOPEEUROPAQUIETPEACECAMELOTACTION,139/79137/82123/74134/78129/78137/80,糖尿病、心脏病、肾脏病，有脑卒中史和血管病者130/80mmHg 根据：PROGRESS(127/75 rather than
3、 136/76mmHg)EUROPA（128/78 rather than 133/80 mmHg）CAMELOT（124/76 rather than 130/77 mmHg)上述冠心病和脑卒中后患者的受益，主要来自血压降低。是二级预防研究，还是降压试验呢？,ESH/ESC 2007年高血压指南,INVEST:International Verapamil SR-Trandolapril Study:,a prospective,randomized,open,blinded-endpoint(so-called PROBE)trial 22,576 patients aged/=50 ye
4、ars with hypertension and coexisting CAD.Patients were randomized to a regimen containing either verapamil SR or atenolol.a mean follow-up of 2.7 years primary outcome:first occurrence of all cause death,nonfatal MI,or nonfatal stroke.,INVEST 研究：舒张压与事件,事件发生率%,0,2,4,6,8,10,12,14,16,18,20,60,60-70,70-
5、80,80-90,90-100,100-110,110,卒中,DBP（mmHg）,INVEST,冠心病患者是一类更加特殊的群体,冠脉血流受血压的影响较大低血压时冠脉血流量降低，而高血压时心肌耗氧量增加总体来讲,冠脉血流与舒张压呈正相关，当舒张压低于60 mmHg时，冠脉血流明显降低因此，冠心病患者在抗高血压治疗的同时必须警惕降压过低的风险,高血压合并冠心病患者的降压靶标,冠心病合并心衰患者的降压靶标,卡维地洛前瞻性随机累积存活(COPERNICUS:The Carvedilol Prospective Randomized Cumulative Survival)试验提示较低的血压(SP 12
6、0 mm Hg)对有些患者是合乎需要的声明建议对于合并心衰患者，血压应 130/80 mm Hg,但尚应考虑血压甚至进一步降至低于120/80 mm Hg,Rosendorff C et al.Circulation.2007;115:2761-88,冠心病合并高血压治疗三个核心原则,对于高血压合并冠心病的患者,降压治疗应缓慢进行;舒张压(DBP)不应降得太低,不宜低于60 mm Hg;降压治疗的起始与目标血压在大多数这类患者为130/80 mm Hg 但AHA声明还指出：在未控制的严重高血压患者，服用抗血小扳药或抗凝药时，血压应即刻降低。,这些原则说明了高血压合并冠心病患者降压治疗的复杂性,
7、也决定了采用个体化的治疗原则,Rosendorff C et al.Circulation.2007;115:2761-88,对于脉压大的老年患者：降低收缩压往往容易引起舒张压过低(60 mm Hg).医生应该仔细观察病人是否出现不利的症状,各地城市会问得最多的问题之一：老年患者BP170/60 mmHg,是否应该降压？,VALUE:Analysis of Results Based on BP Control at 6 Months,Fatal/Non-fatal cardiac events,Fatal/Non-fatal stroke,All-cause death,Myocardial
8、 infarction,Heart failure hospitalisations,*SBP 140 mmHg at 6 months.,*P 0.01.,Patients Treated With Valsartan,Patients Treated With Amlodipine,Hazard Ratio 95%CI,0.4,0.6,0.8,1.0,1.2,Controlled patients*(n=5253),Non-controlled patients(n=2396),*,*,*,*,0.4,0.6,0.8,1.0,1.2,Controlled patients*(n=5502)
9、,Non-controlled patients(n=2094),Hazard Ratio 95%CI,*,*,*,*,0.76(0.660.88),0.60(0.480.74),0.79(0.690.91),0.83(0.661.03),0.62(0.500.77),Odds Ratio,0.73(0.630.85),0.50(0.390.64),0.79(0.690.92),0.91(0.711.17),0.64(0.520.79),Odds Ratio,Weber MA et al.Lancet.2004;363:204749.,VALUE:Analysis of Results Bas
10、ed on Immediate Response*,Fatal/Non-fatal cardiac events,Fatal/Non-fatal stroke,All-cause death,Myocardial infarction,Heart failure hospitalisations,0.4,0.6,0.8,1.0,1.2,1.4,Immediate responders*(n=9336),Non-immediate responders(n=5663),Odds Ratio 95%CI,*Those not on previous tx:SBP 10 mmHg at one mo
11、nth;those on previous tx:SBP baseline at one month.*P 0.05;P 0.01.,*,*,0.88(0.790.97),0.83(0.710.98),0.90(0.810.99),0.89(0.761.04),0.87(0.751.01),Odds Ratio,Weber MA et al.Lancet.2004;363:204749.,at one month,兴奋,抑制,降压过快危害一：导致心率增加,心率过快是心血管死亡的独立危险因素和预测因素,姚泰主编，生理学，人民卫生出版社，2001,降压过快危害二：引起冠脉血供不足,冠心病及高血压患
12、者,冠脉粥样硬化,冠脉自我调节力降低,冠脉血供不足,回心血量减少,冠心病,高血压,“大多数慢性高血压病人应该在 几周内逐渐降低血压至目标水平，这样对远期事件的减低有益。”,2005中国高血压防治指南,2007ACC/AHA 冠心病降压治疗建议,“in patients with an elevated DBP and occlusive CAD with evidence of myocardial ischemia,the BP should be lowered slowly”,指南、建议对降压速度的描述,那么冠心病患者呢？,日本高血压指南对降压速度的建议,老年人肝脏、肾脏功能减退，药物代
13、谢缓慢。起始应采用半量，四周后加量，使血压在2-3个月或更长时间内达标,Toshio OGIHARA,et al.Hypertens Res 2003;26:136,高血压合并冠心病的5个阶段,高血压合并高冠心病风险;高血压合并慢性稳定性心绞痛;高血压合并急性冠脉综合征或NSTEMI高血压合并STEMI;高血压合并缺血性心脏病所导致的心力衰竭,AHA/ACC关于缺血性心脏病降压治疗的声明,药物的选择，需分类而行,Rosendorff C et al.Circulation.2007;115:2761-88,0.2,1.8,2.0,15,10,5,-5,Odds ratio for CHD,AC
14、E Is,Systolic BP difference between groups(mmHg),Verdecchia et al 2005,0,Relationship Between Odds Ratio for CHD and Achieved BP Differences,Prevention of CVD,ACEIs?HOPE、ONTARGET ARBs?ONTARGET and TRANSCEND?Combination of ACEIs and ARBs?ONTARGET x,ACEI outcome trials in chronic stable CAD patients w
15、ithout HF:Totality of trial evidence,MI,Stroke,All-cause death,Event rate(%),Favors ACEI,ACEI,Revascularization,Favors placebo,Placebo,7.5,6.4,2.1,15.5,8.9,7.7,2.7,16.3,0.86,0.86,0.77,0.93,0.0004,0.0004,0.0004,0.025,0.5,0.75,1.25,1,Odds ratio,P,Pepine CJ,Probstfield JL.Vasc Bio Clin Pract.CME Monogr
16、aph;UF College of Medicine.2004;6(3).,HOPE,EUROPA,PEACE,QUIET,亚组：在阻滞剂、他汀和抗血小板的基础上应用ACEI治疗稳定性冠心病患者,ACERTIL 8 mg,高血压合并冠心病的降压治疗,不论血压是否增高，EUROPA、PROGRESS、ADVANCE研究结果高度一致,总人群,高血压人群,非高血压人群,PROGRESS Collaborative Group.Lancet 2001;358:1033-41.EUROPA Investigators.Lancet 2003;362:782-88.ADVANCE Collaborativ
17、e Group.Lancet 2007;370:829-40.,卒中后患者,卒中再发,-20,-10,0,-30,RRR(%),-32%,-27%,-28%,心血管死亡、心肌梗死和可复苏的心脏骤停,-15,-10,-5,0,-20,RRR(%),-20%,-18%,-20%,稳定性冠心病患者,血管事件,-5,0,-10,RRR(%),-9%,-10%,-9%,糖尿病患者,雅施达保护心脑血管作用显著（1）,The consistency of the treatment effect of an angiotensin-converting enzyme-inhibitor-based trea
18、tment regimen in patients with vascular disease or high risk of vascular disease:a combined analysis of individual data of ADVANCE,EUROPA,and PROGRESS trials in 29 463 patients,J.J.Brugts,T.Ninomiya,E.Boersma,W.Remme,M.Bertrand,R.Ferrari,K.Fox,S.MacMahon,J.Chalmers,and M.L.Simoons.Eur Heart J;accept
19、ed Feb 2009:,Mortality and CV events reduction in 29 463 patients receiving Coversyl-based therapy(ADVANCE,EUROPA,PROGRESS analysis,2009),11%,15%,18%,18%,All-cause mortality,Cardiovascular mortality,Cardiovascular mortality,myocardial infarction,Cardiovascular mortality,myocardial infarction,stroke,
20、18%,Fatal and non-fatal stroke,Non-fatal myocardial infarction,20%,Hospital admission for heart fail,16%,(P=0.006),(P=0.004),(P0.001),(P0.001),(P=0.002),(P0.001),(P=0.015),1.J.J.Brugts,T.et al.Eur Heart J;accepted Feb 2009:,RRR,%,阻滞剂治疗急性心梗患者减少死亡、再梗死和室颤的发生,死亡,再梗死,室颤和心跳骤停,26个小随机试验、MIAMI、ISIS-1、COMMIT低
21、风险亚组的荟萃分析,COMMIT collaborative group.Early intravenous then oral metoprolol in 45 852 patients with acute myocardial infarction:randomized placebo controlled trial.Lancet 2005;366:162232,P=0.0006,P=0.002,P=0.0002,发生率变化（%）,-22%,-15%,-13%,-25,-20,-15,-10,-5,0,在常规治疗基础上阻滞剂显著降低心衰患者死亡率,1.MERIT-HF Study Gr
22、oup.Lancet.1999;253:20012007.2.CIBIS-II Investigators.Lancet.1999;353:913.3.Packer M et al.N Engl J Med.2001;344:16511658.,死亡率降低（%）,CIBIS,MERIT-HF,COPERNICUS,P0.0001,P=0.0062,P=0.00013,-35%,-34%,-34%,-50,-40,-30,-20,-10,0,比索洛尔（n=2647）,美托洛尔控释片（n=3991）,卡维地洛（n=2289）,AHA/ACC高血压合并冠心病降压治疗建议各类降压药物的异质性,AHA/
23、ACC关于高血压合并冠心病降压治疗的声明,在高血压合并各种冠心病的患者中,受体阻滞剂与血管紧张素转化酶抑制剂(ACEI)具有不可替代的作用。但因患者目标治疗血压较低,多数患者需要联合使用钙离子拮抗剂,才能有效控制血压,控制心绞痛症状。,Rosendorff C,et al.Circulation.2007;115:2761-88,稳定性冠心病降压治疗ACEI联合DHP-CCB,作用特点 同时扩张动、静脉 抗心绞痛作用 抑制反射性交感激活 抗动脉粥样硬化作用 改善胰岛素敏感性 与他汀类有协同作用 优势人群 左心室功能减退 心绞痛和心肌缺血 糖尿病 血压较高,ACEI DHP-CCB,结论,高血压合并冠心病患者的降压治疗，应坚持个体化原则，缓慢降到安全而又获益的水平阻滞剂和ACEI可改善冠心病患者预后,同时可有效降压,因此在合并冠心病的高血压治疗中备受重视稳定性冠心病患者联合应用ACEI和钙拮抗剂可进一步降低心血管事件的风险,Thank you,
