高血压治疗研究进展

优化治疗策略

张维忠

Lancet 2002; 360: 1903-1913

StrokeStrokeStrokeStroke CHDCHDCHDCHD

256

128

64

32

16

8

4

2

1

120 140 160 180Usual SBP (mmHg)

Stro

ke m

orta

lity

(flo

atin

g ab

solu

te r

isk

and

95%

CI)

Age at risk

(y):

80-89

70-79

60-69

50-59

80-89

70-7970-79

60-6960-69

50-59

Age at risk

(y):

256

128

64

32

16

8

4

2

1

120 140 160 180Usual SBP (mmHg)

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40-49

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Stroke and CHD Mortality Rate in Each Decade of Age versus Usual Systolic Blood Pressure at the Start of That Decade

Systolic Blood Pressure(ROC) curve

150 mmHg

160 mmHg

140 mmHg

130 mmHg120 mmHg

100

80

60

40

20

0

0 20 40 60 80 100

False-positive error rate (%)

Se

ns

itiv

ity

HOT Study: Risk of a major cardiovascular event reduced by 30%

0

5

10

15

20

25

30

105 100 95 90 85 80Achieved DBP

mm Hg

% risk reduction

83mmHgOptimal DBPreduction

Hansson, et al 1998

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 1.4Controlled patients*

(n = 10755)Non-controlled patients

(n = 4490)

Hazard Ratio 95% CI*SBP < 140 mmHg at 6 months.

（ 6 个月时）**

**

**

**

**P < 0.01.

0.75 (0.67–0.83)

0.55 (0.46–0.64)

0.79 (0.71–0.88)

0.86 (0.73–1.01)

0.64 (0.55–0.74)

Odds Ratio

Weber MA et al. Lancet. 2004;363:2047–49.

VALUE: 收缩压控制目标与终点事件

降压治疗更大程度获益 ,

应该关注或重视怎样的干预策略？

( 一 ) 强调早期干预控制心血管风险PREVENTRETARD

REGRESS

Target organ damageAsymptomatic

CKDNew risk factors

Atherosclerosis

Risk factors ESRD Death

Target organDamage

Symptomatic

Trial ACC CAM PEA EU INV JM ALL LIFE ACT CNT TR HOP VAL PROG TIA PROF PATS MOS

Age (y) 68 57 64 60 66 65 67 67 64 64 67 66 67 64 65 66 60 66DM (%) 60 18 17 - 28 2 36 13 15 37 36 38 32 13 5 28 - 37MI (%) 23 38 55 65 32 42 16* 52 49 46 52 46 16 6 - - 8Stroke (%) 13 4 7 3 5 - 8 - 21 22 11 20 100 100 100 100 100Any CVD (%) - 100 100 100 100 100 52 25 100 91 91 88 60 100 100 100 100 100LVH (%) 13 - - - 22 - 16.5 100 - 13.6 13 8.5 15 - 11 15.5 -LLT (%) 68 86 70 57 37 28 25 - 88 62 95 28 46 7 - 47 - 31APT (%) 65 94 90 92 57 55 36 - 86 81 79 76 73 60 49 100 - 78AHT (%) 0 139 109 102 0 0 0 0 37 118 131 101 0 50 0 103 0 0SBP (mmHg) 132 124 129 128 131 136 135 144 130 133 136 135 139 132 150 136 143 136

30

20

0

40.0

34.3

27.026.925.4

16.817.815.8

14.112.5

14.013.0

8.0

16.1

19.2

25.6 25.4

10

12.112.411.011.211.7

10.53.5

8.310.5 10.6 11.0

11.5 11.4 12.213.9 13.9 14.0

8.512.0

11.7

40

5043.5

Incidence of Major CV Events in Trials on High CV Risk Patients

Zanchetti A. J Hypertens. 2009; 27:1509-1520.

FEVER: Fatal and non-fatal stroke in groups with or without previous history of CVD

Placebo betterPlacebo betterFelodipine betterFelodipine better

0.40.4 0.60.6 0.80.8 1.01.0 1.51.5 2.02.0

HR 95% CIHR 95% CI ppHRHRPatient groupsPatient groups No.No.

On-treatment SBP/DBP (mmHg) On-treatment SBP/DBP (mmHg)

FelodipineFelodipine PlaceboPlacebo

CVD-YesCVD-Yes 41114111 137.9/82.4137.9/82.4 142.2/84.4142.2/84.4 0.840.84 0.22170.2217

CVD-No 5600 138.1/82.8 142.2/85 0.64 0.0015

BP Variability BP

Levels

CV Diseases

age, ethnicity, male sex, obesity, genetic factors, low socioeconomic

status, low birth weight

( 二 )关注治疗过程的血压控制质量

Intra-individual SBP Variability during Treatment

High Low

mmHg mmHg

160 160

Months Months

Treatment Treatment

B 6 12 18 24 30 36 42 48 B 6 12 18 24 30 36 42 48

SBP <140 mmHg DBP < 90 mmHg SBP <140 mmHgand DBP < 90 mmHg

Clinic BP

Year

100

80

60

40

20

1 2 3 4 All years

%

0

Year

100

80

60

40

20

1 2 3 4 All years0

Year

100

80

60

40

20

1 2 3 4 All years0

% %

SBP <125 mmHgand DBP < 80 mmHg

DBP < 80 mmHgSBP <125 mmHg

24 h

100

80

60

40

20

1 2 3 40

All years

Year

%100

80

60

40

20

1 2 3 40

All years

Year

%100

80

60

40

20

1 2 3 40

All years

Year

%

ELSA: Clinic and ambulatory BP control

Zanchetti A, et al. J Hypertens 2007;25:2463

% of visits withBP < 140/90 mmHg HR (95% CI), MI Reduced Risk Increased Risk

<25% (n=3838) 1.0025 to <50% (n=3757) 0.70 (0.57-0.86)

50 to < 75% (n=6664) 0.68 (0.56-0.81)

≥ 75% (n=8316) 0.58 (0.48-0.69)

HR (95 CI), Stroke

< 25% (n=3838) 1.00

25 to <50% (n=3757) 0.89 (0.67-1.19)

50 to < 75% (n=6664) 0.70 (0.52-0.92)

≥ 75% (n=8316) 0.50 (0.37-0.68)

0.40 0.60 0.80 1.00 1.20HR (95% CI)

INVEST: Blood pressure and CV outcomesAccording to the percentage of visits with BP <140/90 mmHg

Mancia G, et al. Hypertens 2007;50:299

VALUE: Quality of BP Control and Outcomes

Clinical outcome by proportion of visits with BP control

Proportion of Visits with BP Control (%)

Primary endpoint

CV morbidity/mortality

MI(F+NF)

Stroke(F+NF)%

25

20

15

10

5

0<25% ≥25%

to<50%

≥50%to

<75%

≥75%

%25

20

15

10

5

0<25% ≥25%

to<50%

≥50%to

<75%

≥75%

%10

8

6

4

2

0<25% ≥25%

to<50%

≥50%to

<75%

≥75%

%10

8

6

4

2

0<25% ≥25%

to<50%

≥50%to

<75%

≥75%

AgingSmoking

BPLDL/HDLDiabetes

Oxidative StressBP

LDL/HDLInflammation

Small ArteryElasticity

Genetics EndothelialDysfunction

Atherosclerosis CVEvents

Pulse Pressure

PWV

Large Artery Elasticity

( 三 ) 重视心血管风险标记指导治疗

Devereux R, et al. JAMA. 2004;292:2350-2356

Hazard Ratio: 0.58 (0.38-0.86) p< .008

LIFE-ECHO substudyImpact on LVH regression on outcomes

ONTARGET and TRANSCED: Reduction in albuminuria translates to reduc

tion in CV events

Adjusted to age, sex, BMI, aicobet, eGFR, Plasma glucose, SBP, DBP, HR, diabetes, smoking and eGFR changes at 2 yrs

Patients with vascular disease, n=23,480, 32 months FUAll cause mortality

CV deaths

CompositeCV endpoint

Combinedrenal endpoint

Risk ratio 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0

decrease > 50% vs minor change

Minor change

increase > 100% vs minor change

decrease > 50% vs minor change

Minor change

increase > 100% vs minor change

decrease > 50% vs minor change

Minor change

increase > 100% vs minor change

decrease > 50% vs minor change

Minor change

increase > 100% vs minor change

0.026

0.140

0.032

0.015

<0.0001

<0.0001

<0.0001

0.005

Schmieder et al. JASN 2011

◆ 以长期高质量血压控制和预防或逆转靶器官损害为目标的优化治疗，更有利于指导降压治疗，并可能获得更大程度的益处。

降压治疗策略的新理念降压治疗策略的新理念

不同治疗方案影响终点事件的临床试验

● LIFE (2001)

● IDNT (2001)

● ASCOT-BPLA (2005)

● ACCOMPLISH (2008)

● COPE (2011)

◆ 优化治疗策略需要优化降压治疗的基本 元素、剂量，以及联合治疗方案与路径， Preferred drugs ， Preferred combinations 。

优化治疗策略的意义优化治疗策略的意义

◆ RAS 阻滞剂 ± 钙拮抗剂 ± 噻嗪类利尿剂 联合成为临床上主要的优化治疗方案。◆ 新观念和新思路将开拓高血压治疗的新 靶点，推动新药与新制剂研发。