高血压与降压治疗策略中国高血压防治南解读

1、高血压与降压治疗策略高血压与降压治疗策略中国高血压防治指南解读中国高血压防治指南解读中国高血压防治指南中国高血压防治指南(2005)(2005)血压水平分类和定义血压水平分类和定义 分类分类 收缩压收缩压(mmhg) (mmhg) 舒张压舒张压(mmhg)(mmhg)正常血压正常血压 120 120 和和 80 80正常高值正常高值 120-139 120-139 或或 80-8980-89高血压高血压 140 140 或或 9090 1 1级级 140-159 140-159 或或 90-9990-99 2 2级级 160-179 160-179 或或 100-109100-109 3 3级

2、级 180 180 或或 110110单纯收缩期高血压单纯收缩期高血压 140 140 和和 90 90男性男性女性女性合计合计604530150构成比例构成比例 (%)正常血压正常血压正常高值正常高值高血压高血压i级级高血压高血压ii级级高血压高血压iii级级36.148.443.038.634.030.415.612.32.4中国大陆成年人群血压水平分类中国大陆成年人群血压水平分类(2002)(2002)卫生部心血管病防治研究中心，中国心血管病报告 2007中国大陆人群血压正常高值检出率中国大陆人群血压正常高值检出率(%)(%)1991(29.0%)

3、1991(29.0%) 2002(34.0%)2002(34.0%)18-24 25.4 28.525-34 26.0 30.935-44 30.2 36.745-54 32.9 38.055-64 32.7 34.965-74 31.2 30.375 28.7 28.1年龄组年龄组 19911991年年 20022002年年卫生部心血管病防治研究中心，中国心血管病报告 2007prospective studies collaboration. lancet. 2002;360:1903-1913.100%80%60%40%20%0%4040-4950-5960-6970-7980+17%1

4、6%16%20%20%11%age (y)frequency of hypertensionsubtypes in all untreatedsubjects (%)frequency distribution of untreated hypertensive individuals by age and hypertension subtype. numbers at the tops of bars represent the overall percentage distribution of untreated hypertension in that age group. , is

5、h (sbp140 mm hg and dbp90 mm hg); , sdh (sbp140 mm hg and dbp90 mm hg); , idh (sbp140 mm hg and dbp90 mm hg).idh, sdh and ish subtypes in american patients franklin ss. hypertension 2001;37:869huang j, et al. j hypertens 2004;17:955-962idh, sdh and ish subtypes in chinese patients 中国高血压防治指南中国高血压防治指南

6、(2005)(2005)心心血管危险水平分层血管危险水平分层 血压(mmhg)1级2级3级sbp 140159或 sbp 160179或 sbp180或dbp 9099 dbp 100109 dbp110i无其它危险因素低危中危高危ii12个危险因素中危中危很高危iii3个危险因素高危高危很高危或靶器官损害或糖尿病iv并存临床情况很高危很高危很高危其它危险因素和病史microalbuminuria6543210relative risk of ihdsbp 160normoalbuminuria2.5 (1.2-5.3)5.3 (2.2-13.0)3.3 (1.6-6.9)2.2 (1.3-3

7、.7)1.01.5 (0.9-2.7)收缩压、微量蛋白尿与心血管危险收缩压、微量蛋白尿与心血管危险borch-johnsen k, et al. arteioscler thromb vasc biol 1999; 19:1992hothot：心血管危险分层与：心血管危险分层与cvdcvd事件事件bmj 2002, 324:71rr： 1.58 1.38 1.60 1.79 1.51cl: 1.45-1.72 1.18-1.61 1.41-1.82 1.56-2.05 1.38-1.66p:0.0001 0.0001 0.0001 0.0001 0.0001majorcardiovascula

8、reventsall myocardialinfarctionall strokecardiovascularmortalitytotalmortalityrisk:mediumhighvery high20151050events per 1000 patient years心血管高危患者心血管高危患者建议建议 收缩压180mmhg 和/或 舒张压110mmhg 糖尿病 3 个心血管危险因素 伴1个或多个亚临床器官损害: 心电图(尤其是心肌劳损)或超声心动图(尤其是向心性)左心室肥厚 超声检查显示颈动脉壁增厚或斑块 动脉硬度增加 血清肌酐轻度升高 估测的肾小球滤过率或肌酐清除率下降 微量白蛋

9、白尿或蛋白尿 临床心、脑血管病或慢性肾脏疾病 中国高血压防治指南中国高血压防治指南(2005)降降压治疗的实施过程压治疗的实施过程q对高血压患者临床评价后，进行心血管危险水平分层(低危、中危、高危、很高危)q所有患者都应采用非药物治疗措施q制定降压治疗计划，确定血压控制目标值l很高危、高危患者：立即开始药物治疗l中危：随访观测数周，然后决定是否开始药物治疗l低危：随访观测数月，然后决定是否开始药物治疗q治疗随访，调整治疗方案chd events strokesno ofno ofrelative riskrelative riskno of no ofrelative riskrelative

10、 riskblood pressure difference trialstrials events(95% ci)(95% ci)trials events(95% ci)(95% ci)no history of vascular disease2634290.79 (0.72 to 0.86)2528430.54 (0.45 to 0.65)history of coronary heart disease3758150.76 (0.68 to 0.86)129840.65 (0.53 to 0.80)history of stroke135670.79 (0.62 to 1.00)13

11、15930.66 (0.56 to 0.79)all trials7198110.78 (0.73 to 0.83)4554200.59 (0.52 to 0.67)cohort studies61104500.75 (0.73 to 0.77)6129390.64 (0.62 to 0.66)0.50.711.420.50.711.420.50.711.42treatmentbetterplacebobetterplacebobettertreatmentbetterrelative risk estimates of chd events and stroke in clinical tr

12、ials and in epidemiological cohort studiesmeta-analysis of 147 randomised trialslaw mr, et al. online from bmj.com on 24 may, 2009for reduction of 10mmhg sbp and/or 5mmhg dbp在中国大陆的降压治疗临床试验在中国大陆的降压治疗临床试验 stone 57% 41% cnit 50% 44% syst-china 38% 37% fever 28% 28% stroke cvd1086420-2-405101530absolute

13、 risk of chd event(per 1000 patients of follow-up)chd events saved(per 1000patient-years of treatment)stop-1europaprogesstestpatscoope & warrendersyst-eursyst-chinashepewphedutch tiamrc-1hopeidntscopehdfp2040anbp-1diabhycarmrc-equietpeacepart2renaal2535心血管危险程度与降压治疗绝对获益心血管危险程度与降压治疗绝对获益chd events1

14、4121086420010203040506070absolute risk of stroke(per 1000 patients of follow-up)strokes saved(per 1000patient-years of treatment)stop-1patsprogesshscsgstonecoope & warrendersyst-eursyst-chinashepewphemrc-emrc-1hdfp心血管危险程度与降压治疗绝对获益心血管危险程度与降压治疗绝对获益stroke0.51.02.0relative riskbp-lowering treatment

15、trialistscomparisons of different active treatmentsbpltt: strokecomparisons of different active treatments2003 rr (95% ci) favours first listed favours second listed0.51.02.0relative riskbp difference(mm hg) 1.09 (1.00,1.18) acei vs. d/bb 0.93 (0.86,1.01) ca vs. d/bb 1.12 (1.01,1.25) acei vs. ca2/01

16、/01/10.50.711.42specified drug better0.50.711.42placebobetterspecified drug betterplacebobettercoronary heart disease eventsstrokeno ofno ofrelative riskrelative riskno of no ofrelative riskrelative risktrials events(95% ci)(95% ci)trials events(95% ci)(95% ci)thiazides1117100.86 (0.75 to 0.98)10137

17、00.62 (0.53 to 0.72)b blockers68510.89 (0.78 to 1.02)76900.83 (0.70 to 0.99)anglotensin converting enzyme inhibitors2140830.83 (0.78 to 0.89)1312200.78 (0.66 to 0.92)angiotensin receptor blockers43780.86 (0.53 to 1.40)00calcium channel blockers2220090.85 (0.78 to 0.92)99760.66 (0.58 to 0.75)drug cho

18、ice open58710.89 (0.78 to 1.01)47630.96 (0.75 to 1.23)all classes of drug6494170.85 (0.81 to 0.89)3847120.73 (0.66 to 0.80)relative risk estimates of chd events and stroke according to class of druglaw mr, et al. online from bmj.com on 24 may, 2009excluding chd events in trials of blockers in people

19、 with a history of chdblood pressure lowering treatment trialists collaboration. lancet. 2003;362:1527-1535.bplttc (who/ish, 2003)中国高血压防治指南中国高血压防治指南(2005)(2005)血血压控制目标值压控制目标值q中青年高血压患者 140/90 mmhgq老年高血压患者 150/90 mmhg q糖尿病或肾病患者130/80 mmhginvestinvest血压控制达标与终点事件发生的关系血压控制达标与终点事件发生的关系15.05.72.4

20、161412108642025% 25%至50% 50%至75% 75% 随诊时血压达标百分比（140/90 mmhg）患者总数（n） 3838 3757 6664 8316一级终点心肌梗死（致死非致死性）脑卒中（致死非致死性）发生临床终点事件百分比p 值均小于0.001value：bp control and outcomesproportion of time with bp hr(95% ci)reduced riskincreased riskcontrol ( 140; 90mmhg)primary endpoint 25%1.79(1.357-2

21、.363) 25% to 50%1.30(1.035-1.625) 50% to 75%1.06(0.875-1.277) 75%1.00cv morbidity or mortality 25%1.76(1.382-2.243) 25% to 50%1.24(1.009-1.513) 50% to 75%1.14(0.893-1.250) 75%1.00mi (fatal and non fatal) 25%1.64(1.073-2.509) 25% to 50%1.24(0.079-1.757) 50% to 75%1.14(0.859-1.512) 75%1.00stroke (fata

22、l and non fatal) 25%2.04(1.270-3.265) 25% to 50%1.14(0.761-1.697) 50% to 75%1.11(0.822-1.535) 75%1.00hospitalization for chf 25%1.74(1.157-2.630) 25% to 50%1.16(0.831-1.630) 50% to 75%0.99(0.746-1.314) 75%1.0003.5321hr (95% cl)exponential time-to-event model adjusted for covariates age. bmi

23、 history of chd. stroke. lvh. type 2 diabetes. smoking.high total cholesterol and proteinuria. additional adjustment for 5th order polynomials of msdbp and mssbp. major cardiovascular events (per 100 patients-years) in all treated hypertensive and in hypertensive patients with diabetes in relation t

24、o target blood pressures of 90. 85, and 80 mm hg. 302520151050 80 85 90 90 85 80p=0.50 for trendp=0.005 for trendall hypertensive patients(n=18790)hypertensive with diabetes(n=1501)target blood pressure groupsmajor cardiovascular events/1000 patients-yearshot: hot: 糖尿病患者血压控制与糖尿病患者血压控制与cvcv事件发生率事件发生率

25、10987654100110120130140150160170achieved systolic blood pressure (mmhg)annual patient event rate (%)median systolic bloodpressure (mmhg)106116125135144154168no. of person-years14314266897411983913849423470advance: achieved bp levels and all renal eventsde galan be, et al. j am soc nephrol. 2009; feb

26、.18, onlinesbps achieved by treatment in placebo-controlled trials in elderly hypertensivesewphe 840 72 182 150 172 coope and warrender 884 68 196 162 180 shep 4376 72 170 143 155 stop-1 1627 76 195 167 186 mrc elderly 4396 70 185 156 165 syst-eur 4695 70 174 151 161 syst-china 2394 67 171 151 160sc

27、ope 4964 76 166 145 148 hyvet 3845 83 173 144 159jatos 4418 74 171 138 147zanchetti a, et al. j hypertens. 2009;27: n age(years) baseline sbpachieved sbpactive control中国高血压防治指南中国高血压防治指南(2005)(2005)长长期治疗随访实施过程期治疗随访实施过程l继续治疗l血压控制1年以上可减少剂量治疗3个月后，达到降压目标值治疗3个月后，未达到降压目标值有明显副作用l增加剂量l改用另一类降压药l联合治疗l改用另一类降压药l

28、减少剂量 降压治疗后血压下降幅度主要取决于：降压治疗后血压下降幅度主要取决于： 血压水平和药物平均剂量血压水平和药物平均剂量 sbp= 9.1+0.1(p-154) dbp= 5.5+0.11(p-97) law mr, et al. bmj. 2003;326:1427-1431.降压药物联合治疗的依据降压药物联合治疗的依据(一一) 150/90时，一种药物在标准剂量下，血压平均时，一种药物在标准剂量下，血压平均 降低仅降低仅8.7/4.7 mmhg；一种、两种、三种药物；一种、两种、三种药物 在在1/2标准剂量下，血压分别平均降低标准剂量下，血压分别平均降低6.7/3.7、 13.3/7.

29、3、19.9/10.7 mmhg。law mr, et al. bmj. 2003;326:1427-1431.sbp= r+n0.078 (p-150)dbp= r+n0.088 (p-90)0.20thiazidebeta blockerace inhibitorcalcium channelblockerall classes1.04(0.88-1.20)1.00(0.76-1.24)1.16(0.93-1.39)1.01(0.90-1.12)adding a drug from another class(on average standard do

30、ses)doubling dose of same drug(from standard dose to twice standard)incremental systolic blood pressure reductionratio of observed to expected additive effects 0.89(0.69-1.09)0.19(0.08-0.30)0.23(0.12-0.34)0.2(0.14-0.28)0.37(0.29-0.45)0.22(0.19-0.25)降压药物联合治疗的依据降压药物联合治疗的依据(二二)combination therapy versu

31、s monotherapymeta-analysis from 42 trialswald ds, et al. am j med. 2009;122:290-300. 通过不同的药理作用，中和或对抗相通过不同的药理作用，中和或对抗相互的不良反应。互的不良反应。 通过降低剂量减少和减轻不良反应。通过降低剂量减少和减轻不良反应。降压药物联合治疗的依据降压药物联合治疗的依据( (三三) )不良反应不良反应(a+b) 不良反应不良反应(a) + 不良反应不良反应(b)不良反应不良反应(a+b) 不良反应不良反应(2a) 或或 不良反应不良反应(2b)优化降压联合治疗方案优化降压联合治疗方案dhp-c

32、cb + acei/arb (ascot, accomplish)dhp-ccb + blocker (hot, insight, allhat)acei/arb + diuretics (life, value, accomplish)dhp-ccb + diuretics (value, fever)acei/arb + blocker (allhat) blocker + diuretics (life, ascot, insight) acei + arb (ontarget)insight：糖尿病患者：糖尿病患者终点事件终点事件患者百分数(%)0.04.08.0co-amilozid

33、e12.0p = 0.03nifedipine gits16.020.0mancia g, et al. hypertension 2003;41:4316.所有主要终点所有主要终点, ,非心脑血管性死亡非心脑血管性死亡,esrd,esrd,心绞痛和短暂性脑缺血心绞痛和短暂性脑缺血co-amilozidenifedipine gitsinsight serious and metabolic adverse eventsserious adverse events0%5%10%15%20%25%30%0%2%4%6%8%10%nifedipine gitsco-amilozidehypokal

34、aemiap=0.02p0.0001hyponatraemiahyperlipidaemiahyperglycaemiaimpaired renal functionhyperuricaemiap0.0001p0.0001p=0.001p0.0001p0.0001brown m, et al. lancet 2000;356:36672.176 (5.6%)insight: 对新发糖尿病的影响对新发糖尿病的影响 nifedipine gits020406080100120140160180co-amilozide136 (4.3%)p=0.023patients with newly diag

35、nosed diabetes mellitus (n)mancia g, et al. hypertension 2003;41:4316.（氨氯地平（氨氯地平+/-培哚普利培哚普利 vs. 阿替洛尔阿替洛尔+/-苄氟噻嗪）苄氟噻嗪）*p0.05降低百分比(%)-35-30-25-20-15-10-50*非致死心梗和冠心病死亡心血管死亡总死亡总冠脉事件致死/非致死性卒中总心血管事件和介入新发糖尿病肾损害dahlof b, sever p, et al. lancet. 2005;366:895-906. ascot-bpla:ascot-bpla:终点事件发生率终点事件发生率cumulativ

36、e event rate hr (95% ci) 0.80 (0.72, 0.90)20% risk reductiontime to 1st cv morbidity/mortality (days)p = 0acei / hctzccb / acei650526.0002accomplish: 主要终点主要终点中国中国高血压高血压人群的临床特点人群的临床特点l最主要的心血管危险是脑卒中l高血压发生和血压水平与摄盐量或饮食钠/钾比值较高密切有关l老年人占的比例很高l约定1/10男性患者有嗜酒行为脑卒中与心肌梗死的比值脑卒中与心肌梗死的比值不同临床试验比较不同临床试验比较stone8.0syst-china8.7nics-eh4.0shep1.2mrc ii0.8stop-h1.2syst-eur1.7action: events in patients