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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 80-89 80-89高血压高血压 140 140 或或 90 90 1 1级级 140-159 140-159 或或 90-99 90-99 2 2级级 160-179 160-179 或或 100-109 100-109 3
2、3级级 180 180 或或 110 110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36.148.443.038.634.030.415.612.313.75.85.15.42.52.42.4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 1991 1991年年 2002 2002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.StrokeStrokeCHDCHD2562561281286464323216168 84
4、 42 21 1120120140140160160180180Usual SBP(mmHg)Usual SBP(mmHg)Stroke mortalityStroke mortality(floating absolute risk and 95%CI)(floating absolute risk and 95%CI)Age Age at riskat risk(y):(y):80-8980-8970-7970-7960-6960-6950-5950-5980-8980-8970-7970-7960-6960-6950-5950-59Age Age at riskat risk(y):(y
5、):2562561281286464323216168 84 42 21 1120120140140160160180180Usual SBP(mmHg)Usual SBP(mmHg)40-4940-49 Stroke and CHD Mortality Rate in Each Decade of Age versus Stroke and CHD Mortality Rate in Each Decade of Age versus Usual Systolic Blood Pressure at the Start of That DecadeUsual Systolic Blood P
6、ressure at the Start of That Decade100%80%60%40%20%0%4040-4950-5960-6970-7980+17%16%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 ov
7、erall percentage distribution of untreated hypertension in that age group.,ISH(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;17:955-9
8、62IDH,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(2005)(2005)心血管危险水平分层心血管危险水平分层 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 160N
9、ormoalbuminuria2.5(1.2-5.3)5.3(2.2-13.0)3.3(1.6-6.9)2.2(1.3-3.7)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 1.51ClP:0.0001 0.0001 0.0001 0.0001 0.0001Majorcardiovas
10、culareventsAll myocardialinfarctionAll strokeCardiovascularmortalityTotalmortalityRisk:MediumHighVery High20151050Events per 1000 patient years中国高血压防治疗指南中国高血压防治疗指南(2010)(2010)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
11、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)降压治疗的实施过程降压治疗的实施过程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
12、No ofRelative riskRelative 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 stroke135670.7
13、9(0.62 to 1.00)1315930.66(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
14、 clinical trials 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 CVD1086420-2-405101530Absolut
15、e 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 Events141210
16、86420010203040506070Absolute 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 Risk RR(95%CI)RR(95%CI)BP DifferenceB
17、P Difference(mm Hg)(mm Hg)FavorsFavorsFirst ListedFirst ListedFavorsFavorsSecond ListedSecond ListedMajor CV eventsMajor CV eventsCV mortalityCV mortalityTotal mortalityTotal mortality 1.02(0.98,1.07)1.02(0.98,1.07)2/02/0 ACEI vs D/BB ACEI vs D/BB 1.03(0.95,1.11)1.03(0.95,1.11)2/02/0 ACEI vs D/BB AC
18、EI vs D/BB 1.00(0.95,1.05)1.00(0.95,1.05)2/02/0 ACEI vs D/BB ACEI vs D/BB 1.04(0.99,1.08)1.04(0.99,1.08)1/01/0 CA vs D/BB CA vs D/BB 1.05(0.97,1.13)1.05(0.97,1.13)1/01/0 CA vs D/BB CA vs D/BB 0.99(0.95,1.04)0.99(0.95,1.04)1/01/0 CA vs D/BB CA vs D/BB 0.97(0.92,1.03)0.97(0.92,1.03)1/11/1 ACEI vs CA A
19、CEI vs CA 1.03(0.94,1.13)1.03(0.94,1.13)1/11/1 ACEI vs CA ACEI vs CA 1.04(0.98,1.10)1.04(0.98,1.10)1/11/1 ACEI vs CA ACEI vs CABlood Pressure Lowering Treatment Trialists Collaboration.Blood Pressure Lowering Treatment Trialists Collaboration.LancetLancet.2003;362:1527-1535.2003;362:1527-1535.BP-Low
20、ering Treatment 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/
21、01/01/10.50.711.42Specified 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)1013700.
22、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 choice open587
23、10.89(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 with a history of
24、 CHDSBP difference between randomized groups(mmHg)SBP difference between randomized groups(mmHg)Relative risk of outcome eventRelative risk of outcome event1.501.501.251.251.001.000.750.750.500.500.250.251.501.501.251.251.001.000.750.750.500.500.250.251.501.501.251.251.001.000.750.750.500.500.250.25
25、1.501.501.251.251.001.000.750.750.500.500.250.251.501.501.251.251.001.000.750.750.500.500.250.25StrokeStrokeMajor CVDMajor CVDCHDCHDCVD deathCVD deathTotal mortalityTotal mortality-10-10-8-8-6-6-4-4-2-20 02 24 4-10-10-8-8-6-6-4-4-2-20 02 24 4-10-10-8-8-6-6-4-4-2-20 02 24 4-10-10-8-8-6-6-4-4-2-20 02
26、24 4-10-10-8-8-6-6-4-4-2-20 02 24 4Blood 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)血压控制目标值血压控制目标值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15.05.72.41
27、0.84.32.39.23.81.68.13.11.1161412108642025%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 OutcomesClinical outcomes by proportion of time with BP ControlClinical outcomes by proportion of time with BP Control(co
28、variate adjusted)(covariate adjusted)proportion of time with BP HR(95%CI)Reduced RiskIncreased RiskControl(140;90mmHg)Primary Endpoint 25%1.79(1.357-2.363)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(
29、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(Fatal 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%
30、to 75%0.99(0.746-1.314)75%1.0000.51.52.53.5321HR(95%CL)Exponential time-to-event model adjusted for covariates age.BMI 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 even
31、ts(per 100 patients-years)in all treated hypertensive and in hypertensive patients with diabetes in relation to 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
32、 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10987654100110120130140150160170Achieved systolic blood pressure(mmHg)Annual patient event rate(%)Median systolic bloodPressure(mmHg)106116125135144154168No.of person-Years14314266897411983913849
33、423470ADVANCE:Achieved BP levels and all renal eventsDe Galan BE,et al.J Am Soc Nephrol.2009;Feb.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 18
34、6 MRC elderly 4396 70 185 156 165 Syst-Eur 4695 70 174 151 161 Syst-China 2394 67 171 151 160SCOPE 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)长期治疗随访实施过程长期治
35、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
36、/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、13.3/7.3、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)1.41.21.00.80.60.40.20ThiazideBeta blockerACE InhibitorCalcium channelblockerAll Classes1.04(0.88-1.20)1.00(0.76-1.24)1.16(0.93-1.
37、39)1.01(0.90-1.12)Adding a drug from another class(on average standard doses)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(0.2
38、9-0.45)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 Versus 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
39、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-CCB+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
40、点事件终点事件患者百分数(%)0.04.08.0Co-amilozide12.0p=0.0314.214.2Nifedipine GITS16.020.018.718.7Mancia 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%
41、2%4%6%8%10%Nifedipine GITSCo-amilozideHypokalaemiap=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-amilozide
42、136(4.3%)p=0.023Patients with newly diagnosed 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:ASC
43、OT-BPLA:终点事件发生率终点事件发生率Cumulative 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
44、临床试验比较STONE8.0Syst-China8.7NICS-EH4.0SHEP1.2MRC II0.8STOP-H1.2Syst-Eur1.7ACTION:Events in Patients with Hypertension vs ISH Primary Endpoint EfficacyPrimary Endpoint safetyAny CV EventDeath,any CV Event orRevascularisationAny Vascular Event orRevascularisation0.6511.3HR(95%CI)Elliott&Meredith,2009Fa
45、vours Nifedipine GITSFavours Nifedipine GITSFavours PlaceboFavours PlaceboAll patientsHypertensivesISH patientsInitial therapy with a low dose DHP-CCB or DHP-CCB/RAS blocker or DHP-CCB/-blocker combinationContinue withcurrent therapyUp-titration ofcombination therapysuccessively to thehighest doseDH
46、P-CCB/RAS blocker/diuretic or DHP-CCB/-blocker/diuretic combinationand up-titrationContinue withCurrent therapyContinue withcurrent therapyAdd an a a-blocker,Or spironolactoneContinue withcurrent therapyIS BLOOD PRESSURE CONTROLLED?IS BLOOD PRESSURE CONTROLLED?YesNoNoYesYesNo降压治疗方案推荐流程降压治疗方案推荐流程New
47、recommendationReinforcement of previous recommendationDifferent interpretations of results/potential for confusing messages to clinical practice欧洲高血压治疗指南修改背景欧洲高血压治疗指南修改背景(ESC/ESH,2009)(ESC/ESH,2009)欧洲高血压治疗指南修改要点欧洲高血压治疗指南修改要点(ESC/ESH,2009)(ESC/ESH,2009)重申心血管危险分层重申心血管危险分层 推荐推荐80岁以上高龄高血压患者实施降压治疗岁以上高龄高血压患者实施降压治疗 解释启动降压治疗血压水平和血压控制目标解释启动降压治疗血压水平和血压控制目标 一般人群：一般人群：140/90，140/90 高危以上人群：高危以上人群：130/85，130/80 建议在心血管高危患者建议在心血管高危患者血压控制不低于血压控制不低于120/70120/70。淡化一线降压药物概念，强调首选联合治疗，淡化一线降压药物概念，强调首选联合治疗，重视重视ACEIACEI、ARBARB和和CCBCCB的治疗地位。的治疗地位。