ESH/ESC Guidelines: Definitions and Classification of BP Levels (mmHg)

ESH/ESC Guidelines: ESH/ESC Guidelines: Definitions and Classification of BP Levels (mmHg)Definitions and Classification of BP Levels (mmHg)

ESH/ESC Guidelines: ESH/ESC Guidelines: Definitions and Classification of BP Levels (mmHg)Definitions and Classification of BP Levels (mmHg)

6254 M6254 M

CategoryCategory

OptimalOptimalNormalNormalHigh normalHigh normalGrade 1 hypertension (mild)Grade 1 hypertension (mild)Grade 2 hypertension (moderate)Grade 2 hypertension (moderate)Grade 3 hypertension (severe)Grade 3 hypertension (severe)Isolated systolic hypertensionIsolated systolic hypertension

SystolicSystolic

< 120< 120120-129120-129130-139130-139140-159140-159160-179160-179

≥ ≥ 180180≥ ≥ 140140

DiastolicDiastolic

< 80< 8080-8480-8485-8985-8990-9990-99

100-109100-109≥ ≥ 110110 < 90< 90

When a patient’s SBP and DBP fall into different categories, the higher category should apply.When a patient’s SBP and DBP fall into different categories, the higher category should apply.Isolated systolic hypertension can also be graded (grades 1, 2, 3) according to SBP values in the Isolated systolic hypertension can also be graded (grades 1, 2, 3) according to SBP values in the ranges indicated, provided diastolic values are < 90ranges indicated, provided diastolic values are < 90

0.25

0.50

1.00

2.00

4.00

0.25

0.50

1.00

2.00

4.00

CHD and usual BPCHD and usual BP(in 5 categories defined by baseline (in 5 categories defined by baseline

DBP)DBP)9 prospective observational studies: 9 prospective observational studies:

4856 events4856 events

CHD and usual BPCHD and usual BP(in 5 categories defined by baseline (in 5 categories defined by baseline



Approximate mean usual BP(estimated from later remeasurements

in the Framingham Study)



BaselineDBP category

Usual SBPUsual DBP


Usual SBPUsual DBP

1 2 3 4 5

123 76123 76

136 84136 84

148 91148 91

162 99162 99

175105175105

0.25

0.50

1.00

2.00

4.00

0.25

0.50

1.00

2.00

4.00

1 2 3 4 5

123 76123 76

136 84136 84

148 91148 91

162 99162 99

175105175105

Stroke and usual BPStroke and usual BP(in 5 categories defined by baseline (in 5 categories defined by baseline



Stroke and usual BPStroke and usual BP(in 5 categories defined by baseline (in 5 categories defined by baseline







Relative Riskof Stroke



Usual SBPUsual DBP


Usual SBPUsual DBP

Collins R and McMahon S, British Medical Bulletin 1994Collins R and McMahon S, British Medical Bulletin 1994



35103510

JNC 7JNC 7

Individuals with Individuals with

SBP of 120-139 or DBP of 80-89 mmHg should SBP of 120-139 or DBP of 80-89 mmHg should be considered as prehypertensive be considered as prehypertensive

and and require health promoting require health promoting

lifestyle modifications to prevent CVDlifestyle modifications to prevent CVD

0

10

20

30

40

50

%

Optimum BP <120/80 mmHg

Normal BP120-129/80-84 mmHg

High normal BP130-139/85-89 mmHg

0

10

20

30

40

50

%

Optimum BP <120/80 mmHg

Normal BP120-129/80-84 mmHg

High normal BP130-139/85-89 mmHg

4-Year Frequency (%) of Progression to HT 4-Year Frequency (%) of Progression to HT according to BP Values within Normal Range * (n = 9845, Framingham)according to BP Values within Normal Range * (n = 9845, Framingham)

4-Year Frequency (%) of Progression to HT 4-Year Frequency (%) of Progression to HT according to BP Values within Normal Range * (n = 9845, Framingham)according to BP Values within Normal Range * (n = 9845, Framingham)

7395 M7395 M Vasan et al., Lancet 2001; 358: 1682Vasan et al., Lancet 2001; 358: 1682

* Data adjusted for sex, age, BMI, baseline examinations* Data adjusted for sex, age, BMI, baseline examinations

35-64 ys35-64 ys35-64 ys35-64 ys 65-94 ys65-94 ys65-94 ys65-94 ys

5.35.3

17.617.6

37.337.3

16.016.0

25.525.5

49.549.5

““Prehypertension” - CriticismPrehypertension” - Criticism““Prehypertension” - CriticismPrehypertension” - Criticism

8222 M 8222 M

Progression to HT less frequent in several studiesProgression to HT less frequent in several studies

““Hypertension” has an ominous significance by the laymanHypertension” has an ominous significance by the layman

Anxiety over the term may create need for medical visits / lab Anxiety over the term may create need for medical visits / lab examinationsexaminations

Several lifestyle changes must be preceded by / performed under Several lifestyle changes must be preceded by / performed under medical check / guidancemedical check / guidance

Lifestyle changesLifestyle changes-- Not invariably devoid of costNot invariably devoid of cost-- Reflection on subject’s QoL, freedom etc.Reflection on subject’s QoL, freedom etc.

ESH/ESC Guidelines: Stratification of Risk to Quantify PrognosisESH/ESC Guidelines: Stratification of Risk to Quantify PrognosisESH/ESC Guidelines: Stratification of Risk to Quantify PrognosisESH/ESC Guidelines: Stratification of Risk to Quantify Prognosis

7772 M7772 M

Very high Very high added riskadded risk



High High added riskadded risk





Moderate Moderate added riskadded risk



Low Low added riskadded risk

Blood Pressure (mmHg)Blood Pressure (mmHg)

Other Risk FactorsOther Risk Factorsand Disease Historyand Disease History

No other risk factorsNo other risk factors

1-2 risk factors1-2 risk factors

Associated ClinicalAssociated ClinicalConditionsConditions

Grade 1Grade 1SBP 140-159 SBP 140-159

or DBP 90-99or DBP 90-99


or DBP 100-109or DBP 100-109

Grade 3Grade 3SBP ≥ 180SBP ≥ 180

or DBP ≥ 110or DBP ≥ 110

3 or more risk factors3 or more risk factorsor TOD or diabetesor TOD or diabetes





Average Average riskrisk


LowLowadded riskadded risk


NormalNormalSBP 120-129SBP 120-129


High NormalHigh NormalSBP 130-139SBP 130-139


Low risk: < 15%; Medium risk: 15-20%; High risk: 20-30%; Very high risk: > 30%Low risk: < 15%; Medium risk: 15-20%; High risk: 20-30%; Very high risk: > 30%

ESH/ESC Guidelines: Factors Influencing PrognosisESH/ESC Guidelines: Factors Influencing PrognosisESH/ESC Guidelines: Factors Influencing PrognosisESH/ESC Guidelines: Factors Influencing Prognosis

6250 M6250 M

Risk factors for CV disease used Risk factors for CV disease used for stratificationfor stratification

Levels of SBP and DBPLevels of SBP and DBP

Men > 55 yearsMen > 55 years

Women > 65 yearsWomen > 65 years

SmokingSmoking

DyslipidaemiaDyslipidaemia(total chol. > 250 mg/dl, or LDL-(total chol. > 250 mg/dl, or LDL-chol. > 155 mg/dl, or HDL-chol. chol. > 155 mg/dl, or HDL-chol. M < 40, W < 48 mg/dlM < 40, W < 48 mg/dl

Family history of premature Family history of premature CV disease (at age < 55 years M, CV disease (at age < 55 years M, < 65 years W)< 65 years W)

Abdominal obesityAbdominal obesity(abdominal circumference (abdominal circumference >> 102 102 cm, W cm, W >> 88 cm) 88 cm)

C-reactive protein C-reactive protein >> 1 mg/dl 1 mg/dl

Target Organ Damage (TOD)Target Organ Damage (TOD)

Left ventricular hypertrophyLeft ventricular hypertrophy(electrocardiogram: (electrocardiogram: Sokolow-Lyons > 38 mm; Sokolow-Lyons > 38 mm; Cornell > 2440 mm*ms; Cornell > 2440 mm*ms; echocardiogram:echocardiogram:LVMI LVMI >> 125, W 125, W >> 110 g/m 110 g/m22))

Ultrasound evidence of arterial Ultrasound evidence of arterial wall thickening wall thickening (carotid IMT (carotid IMT >> 0.9 mm) or 0.9 mm) or atherosclerotic plaqueatherosclerotic plaque

Slight increase in serum Slight increase in serum creatininecreatinine(M 115-133, W 107-124 (M 115-133, W 107-124 mol/l; mol/l; M 1.3-1.5, W 1.2-1.4 mg/dl)M 1.3-1.5, W 1.2-1.4 mg/dl)

MicroalbuminuriaMicroalbuminuria(30-300 mg/24h; albumin-(30-300 mg/24h; albumin-creatinine ratio M creatinine ratio M >> 22, W 22, W >> 31 31 mg/g; M mg/g; M >> 2.5, W 2.5, W >> 3.5 3.5 mg/mmol)mg/mmol)

Diabetes MellitusDiabetes Mellitus

Fasting plasma glucose Fasting plasma glucose 7.0 mmol/l (126 mg/dl)7.0 mmol/l (126 mg/dl)

Postprandial plasma Postprandial plasma glucose > 1.0 mmol/l glucose > 1.0 mmol/l (198 mg/dl)(198 mg/dl)

Associated Clinical ConditionsAssociated Clinical Conditions(ACC)(ACC)

Cerebrovascular disease: Cerebrovascular disease: ischaemic stroke; ischaemic stroke; cerebral haemorrhage;cerebral haemorrhage;transient ischaemic attacktransient ischaemic attack

Heart disease:Heart disease:myocardial infarction;myocardial infarction;angina;angina;coronary revascularization;coronary revascularization;congestive heart failurecongestive heart failure

Renal disease:Renal disease:diabetic nephropathy;diabetic nephropathy;renal impairment (serum renal impairment (serum creatinine M > 1.5, W > 1.4 creatinine M > 1.5, W > 1.4 mg/dl)mg/dl)proteinuria (> 300 mg/24h)proteinuria (> 300 mg/24h)

Peripheral vascular diseasePeripheral vascular disease

Advanced retinopathy:Advanced retinopathy:haemorrhages or exudates, haemorrhages or exudates, papilloedemapapilloedema

8236 M8236 M PROGRESS, Lancet 2001PROGRESS, Lancet 2001

HTHTHTHT

NTNTNTNT

-32-32-29-29

Stroke recurrencyStroke recurrency CVDCVD

-40-40

-30-30

-20-20

-10-10

00

-29-29

-24-24

Stroke recurrencyStroke recurrency CVDCVD

-40-40

-30-30

-20-20

-10-10

00

159159149149

6060

8080

100100

120120

140140

160160

136136127127

6060

8080

100100

120120

140140

160160

94949090

7979 7575

BP

(m

mH

g)B

P (

mm

Hg)

BP

(m

mH

g)B

P (

mm

Hg)

RR

R (

%)

RR

R (

%)

RR

R (

%)

RR

R (

%)

8175 = 6397 alt. M 8175 = 6397 alt. M

StrokeStroke MoreMore vs lessvs less

CHDCHD MoreMore vs lessvs less

Heart failure Heart failure MoreMore vs lessvs less

Major CV events Major CV events MoreMore vs lessvs less

CV death CV death MoreMore vs lessvs less

Total mortality Total mortality MoreMore vs lessvs less

Mean BP Mean BP (mmHg)(mmHg)

-4 / -3-4 / -3

-4 / -3-4 / -3

-4 / -3-4 / -3

-4 / -3-4 / -3

-4 / -3-4 / -3

-4 / -3-4 / -3

Relative RiskRelative Risk(95% CI)(95% CI)

0.77 (0.63-0.95)0.77 (0.63-0.95)

0.86 (0.72-1.03)0.86 (0.72-1.03)

0.84 (0.59-1.18)0.84 (0.59-1.18)

0.86 (0.77-0.96)0.86 (0.77-0.96)

0.93 (0.77-1.11)0.93 (0.77-1.11)

0.96 (0.84-1.09)0.96 (0.84-1.09)

FavoursFavoursactiveactive

Favours Favours controlcontrol

0.50.5 1.01.0 2.02.0Relative riskRelative risk

RR of CVD with Low-Dose Aspirin (vs Placebo) in HOTRR of CVD with Low-Dose Aspirin (vs Placebo) in HOTRR of CVD with Low-Dose Aspirin (vs Placebo) in HOTRR of CVD with Low-Dose Aspirin (vs Placebo) in HOT

8247 M 8247 M Zanchetti et al., J Hypertens 2002; 20: 2309Zanchetti et al., J Hypertens 2002; 20: 2309

On-treatment BP (mmHg)On-treatment BP (mmHg)

Medium riskMedium risk

High / very high riskHigh / very high risk

~ 140/83~ 140/83

1.001.00

0.78 0.78 **

* statistically significant* statistically significant

On-Treatment BP and On-Treatment BP and Events with Atorvastatin (vs Placebo) Events with Atorvastatin (vs Placebo) in ASCOTin ASCOT

On-Treatment BP and On-Treatment BP and Events with Atorvastatin (vs Placebo) Events with Atorvastatin (vs Placebo) in ASCOTin ASCOT

8248 M 8248 M

All patients with ≥ 3 risk factorsAll patients with ≥ 3 risk factors

BP (mmHg)BP (mmHg) ~ 138/80~ 138/80

StrokeStroke -27%-27%

CHDCHD -29%-29%

CVDCVD -21%-21%

Total mortalityTotal mortality -13% (NS)-13% (NS)

Initiation of Antihypertensive TreatmentInitiation of Antihypertensive Treatment

Immediate drugImmediate drugtreatment and treatment and

lifestyle changeslifestyle changes











Drug treatmentDrug treatmentandand




Lifestyle changesLifestyle changesfor several monthsfor several months

Then Then drug treatmentdrug treatment






Then drug Then drug treatment if treatment if

preferred by thepreferred by the patient and patient and

resources availableresources available






Associated clinical Associated clinical conditionsconditions

Grade 1Grade 1

SBP 140-159 SBP 140-159


Grade 2Grade 2

SBP 160-179 SBP 160-179

or DBP 100-109or DBP 100-109

Grade 3Grade 3

SBP ≥ 180SBP ≥ 180








Lifestyle changesLifestyle changes

No BPNo BPinterventionintervention

LifestyleLifestylechangeschanges

LifestyleLifestylechangeschanges

No BPNo BPinterventionintervention

NormalNormal

SBP 120-129SBP 120-129


High NormalHigh Normal

SBP 130-139SBP 130-139


23132313

Association of Hypertension with Other CAD Risk Factors:Association of Hypertension with Other CAD Risk Factors:Framingham StudyFramingham Study

Kannel, Am J Hypertens 2000; 13: 3S-10SKannel, Am J Hypertens 2000; 13: 3S-10S

TwoTwo25%25%

OneOne26%26%

NoneNone19%19%

Four or moreFour or more8%8%

ThreeThree22%22%

TwoTwo24%24%

OneOne27%27%

NoneNone17%17%

Four or moreFour or more12%12%

ThreeThree20%20%

MenMenMenMen WomenWomenWomenWomen

1910 11 11

81

3551

60

5538

29

0

20

40

60

80

100

Routine After ECHO and US TSA After ECHO After US TSA

Low Medium High

Cuspidi et al, J Hypertens 2002

Echocardiography and US TSA in Low Risk HypertensivesAPROS STUDY RISK RE-CLASSIFICATION

7637 M7637 M

Risk Factors in Subjects of the SMOOTH Study with BP from Optimal to Untreated HTRisk Factors in Subjects of the SMOOTH Study with BP from Optimal to Untreated HTRisk Factors in Subjects of the SMOOTH Study with BP from Optimal to Untreated HTRisk Factors in Subjects of the SMOOTH Study with BP from Optimal to Untreated HT

00

55

1010

1515

%%

00

2020

4040

6060

%%

Optimal BP Optimal BP

Normal BP Normal BP

High normal BP High normal BP

Untreated HT Untreated HT

SmokingSmoking BMIBMI ChCh TGTG

HDL-ChHDL-Ch UAUA DMDM

* * P < 0.0001P < 0.0001 P < 0.0002P < 0.0002

** * * * *

NSNS * * * *

22.222.2

48.948.9

60.360.3

14.314.3

26.126.1

43.743.7

57.757.7

12.212.2

25.4

33.1

53.4

12.0

30.124.5

48.4

8.0

5.25.2 5.35.3

12.112.1

5.25.2

6.36.3

13.113.1

6.3

3.8

6.16.0

2.4

5.1

JNC VII: Classification and Management of Blood Pressure JNC VII: Classification and Management of Blood Pressure for Adults Agfed 18 years and Olderfor Adults Agfed 18 years and Older

JNC VII: Classification and Management of Blood Pressure JNC VII: Classification and Management of Blood Pressure for Adults Agfed 18 years and Olderfor Adults Agfed 18 years and Older

6273 M6273 M

Two-drug combination for mostTwo-drug combination for most†† (usually thiazide-type diuretic and (usually thiazide-type diuretic and ACEI or ARB or BB or CCB).ACEI or ARB or BB or CCB).

YesYes or or >>100100

>>160160 Stage 2 Stage 2 HypertensionHypertension

Drug(s) for the Drug(s) for the compelling compelling indications.indications.‡‡

Other Other antihypertensive antihypertensive drugs (diuretics, drugs (diuretics, ACEI, ARB, BB, ACEI, ARB, BB, CCB) as needed. CCB) as needed.

Thiazide-type diuretics for Thiazide-type diuretics for most. May consider ACEI, most. May consider ACEI, ARB, BB, CCB, or combination.ARB, BB, CCB, or combination.

YesYes or 90–or 90–9999

140–140–159159

Stage 1 Stage 1 HypertensionHypertension

Drug(s) for compelling Drug(s) for compelling indications. indications. ‡‡

No antihypertensive drug indicated.No antihypertensive drug indicated. YesYes or 80–89or 80–89 120–139120–139 PrehypertensionPrehypertension

EncourageEncourage and <80and <80 <120<120 NormalNormal

With compelling indicationsWith compelling indicationsWithout compelling indication Without compelling indication

Initial drug therapyInitial drug therapy

Lifestyle Lifestyle modificationmodification

DBP* DBP* mmHgmmHg

SBP* SBP* mmHgmmHg

BP BP classificationclassification

*Treatment determined by highest BP category.*Treatment determined by highest BP category.††Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg. Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.

Clinical Outcomes (6 yr rate .100 persons) in ALLHATClinical Outcomes (6 yr rate .100 persons) in ALLHAT

* * P < 0.02P < 0.02 ** ** P < 0.01P < 0.01

CHDCHD

StrokeStroke

CHFCHF

ESRFESRF

AA

11.311.3

5.45.4

10.210.2****

2.12.1

LL

11.411.4

6.36.3**

8.78.7****

2.02.0

CC

11.511.5

5.65.6

7.77.7

1.81.8

4673 M4673 M

Comparison of ACEI-based therapy and calcium-antagonist-based therapy vs placebo

Comparison of ACEI-based therapy and calcium-antagonist-based therapy vs placebo

18161816

Stroke

CHD

CHF

CV events

CV death

Total mortality

Stroke

CHD

CHF

CV events

CV death

Total mortality

Favours ACEI

Favours ACEI

1.01.0 2.02.0

Favours placeboFavours placebo

0.70 (0.57-0.85)

0.80 (0.72-0.89)

0.84 (0.68-1.04)

0.79 (0.73-0.86)

0.74 (0.64-0.85)

0.84 (0.76-0.94)

0.70 (0.57-0.85)

0.80 (0.72-0.89)

0.84 (0.68-1.04)

0.79 (0.73-0.86)

0.74 (0.64-0.85)

0.84 (0.76-0.94)

Relative riskRelative risk

RR (95% CI)

RR (95% CI)

0.50.5

Favours CA

Favours CA

1.01.0 2.02.0

Favours placeboFavours placebo

0.61 (0.44-0.85)

0.79 (0.59-1.06)

0.72 (0.48-1.07)

0.72 (0.59-0.87)

0.72 (0.52-0.98)

0.87 (0.70-1.09)

0.61 (0.44-0.85)

0.79 (0.59-1.06)

0.72 (0.48-1.07)

0.72 (0.59-0.87)

0.72 (0.52-0.98)

0.87 (0.70-1.09)

Relative riskRelative risk

RR (95% CI)

RR (95% CI)

0.50.5

5487 M5487 M

Trials on “New” vs “Old” TreatmentsTrials on “New” vs “Old” TreatmentsPrimary Endpoints (RR Primary Endpoints (RR ++ 95% CI) 95% CI)

Mancia G. et al., 2003Mancia G. et al., 2003

CAPPP*CAPPP*

STOP2*STOP2*

ANBP2*ANBP2*

ALLHAT°ALLHAT°

STOP2*STOP2*

NORDIL*NORDIL*

INSIGHT*INSIGHT*

ALLHAT°ALLHAT°

INVEST*INVEST*

ALLHAT°ALLHAT°

SCOPE*SCOPE*

LIFE*LIFE*

ACE-IACE-I

ACE-IACE-I

ACE-IACE-I

ACE-IACE-I

CCBCCB

CCBCCB

CCBCCB

CCBCCB

CCBCCB

BB

ARBARB

ARBARB

n = 10985n = 10985

n = 4418n = 4418

n = 6083n = 6083

n = 9054n = 9054

n = 4209n = 4209

n = 10881n = 10881

n = 6321n = 6321

n = 9048n = 9048

n = 22599n = 22599

n = 24335n = 24335

n = 4506n = 4506

n = 9193n = 91930.50.5 1.01.0 2.02.0

New betterNew better Old betterOld better

1.05 (0.90-1.22)1.05 (0.90-1.22)

1.01 (0.84-1.22)1.01 (0.84-1.22)

0.89 (0.79-1.00)0.89 (0.79-1.00)

0.99 (0.91-1.08)0.99 (0.91-1.08)

0.97 (0.80-1.17)0.97 (0.80-1.17)

1.00 (0.87-1.15)1.00 (0.87-1.15)

1.10 (0.91-1.34)1.10 (0.91-1.34)

0.98 (0.90-1.07)0.98 (0.90-1.07)

0.98 (0.90-1.06)0.98 (0.90-1.06)

1.03 (0.90-1.17)1.03 (0.90-1.17)

0.89 (0.75-1.06)0.89 (0.75-1.06)

0.87 (0.77-0.98)0.87 (0.77-0.98)

* CVD; ° CHD* CVD; ° CHD

ANBP2: Primary End-Points among All, Male, and Female SubjectsANBP2: Primary End-Points among All, Male, and Female Subjects

5370 M5370 MWing et al., N Engl J Med 2003; 348: 583-92Wing et al., N Engl J Med 2003; 348: 583-92

All SubjectsAll Subjects

End PointEnd PointAll CV events or death from any causeAll CV events or death from any causeFirst CV event or death from any causeFirst CV event or death from any causeDeath from any causeDeath from any cause

Male SubjectsMale Subjects

End PointEnd PointAll CV events or death from any causeAll CV events or death from any causeFirst CV event or death from any causeFirst CV event or death from any causeDeath from any causeDeath from any cause

Female SubjectsFemale Subjects

End PointEnd Point All CV events or death from any causeAll CV events or death from any causeFirst CV event or death from any causeFirst CV event or death from any causeDeath from any causeDeath from any cause

Hazard Ratio (95% CI)Hazard Ratio (95% CI)0.89 (0.79-1.00)0.89 (0.79-1.00)0.89 (0.79-1.01)0.89 (0.79-1.01)0.90 (0.75-1.09)0.90 (0.75-1.09)



P ValueP Value0.050.050.060.060.270.27

P ValueP Value0.020.020.020.020.140.14

P ValueP Value0.980.980.980.980.940.94

ACE-I superiorACE-I superior Diuretics superiorDiuretics superior0.20.2 1.01.0 5.05.0



5563 M5563 M Staessen, J Hypertens 2003Staessen, J Hypertens 2003

TrialsTrials

MIDAS/NICS/VHASMIDAS/NICS/VHASSTOP2/CCBsSTOP2/CCBsNORDILNORDILINSIGHTINSIGHTALLHAT/AmlALLHAT/AmlELSAELSACCBs without CONVINCECCBs without CONVINCE Het. p = 0.78Het. p = 0.78

CONVINCECONVINCEAll CCBsAll CCBs Het. p = 0.86Het. p = 0.86

UKPDSUKPDSSTOP/ACEIsSTOP/ACEIsCAPPPCAPPPALLHAT/LisALLHAT/LisANBP2ANBP2All ACEIsAll ACEIs Het. p = 0.006Het. p = 0.006

LIFELIFESCOPESCOPEAll ARBsAll ARBs Het. p = 0.69Het. p = 0.69

ALLHAT/DoxALLHAT/Dox

All TrialsAll Trials Het. p < 0.0001Het. p < 0.0001

OldOld

37/ 135837/ 1358 637/ 2213637/ 2213 453/ 5471453/ 5471 397/ 3164397/ 31643941/152553941/15255 33/ 115733/ 11575498/286185498/28618

365/ 8297365/ 82975863/369155863/36915

78/ 35878/ 358 637/ 2213637/ 2213 401/ 5493401/ 54933941/152553941/15255 429/ 3039429/ 30395486/263585486/26358

588/ 4588588/ 4588 268/ 2460268/ 2460 856/ 7048856/ 7048

2245/152682245/15268

7627/532797627/53279

Number of events / patientsNumber of events / patientsNewNew

39/ 135339/ 1353 636/ 2196636/ 2196 466/ 5410466/ 5410 383/ 3157383/ 31572432/ 90482432/ 9048 27/ 117727/ 11773983/223413983/22341

364/ 8179364/ 81794347/305204347/30520

107/ 400107/ 400 586/ 2205586/ 2205 438/ 5492438/ 54922514/ 90542514/ 9054 394/ 3044394/ 30444039/201954039/20195

508/ 4605508/ 4605 242/ 2477242/ 2477 750/ 7082750/ 7082

1592/ 90671592/ 9067

10728/6729510728/67295

DifferenceDifference(SD)(SD)

3.6% (2.4) 2p = 0.143.6% (2.4) 2p = 0.14

3.4% (2.3) 2p = 0.153.4% (2.3) 2p = 0.15

2.6% (3.6) 2p = 0.592.6% (3.6) 2p = 0.59

-14.3% (5.5) 2p = 0.004-14.3% (5.5) 2p = 0.004

1.4% (4.8) 2p = 0.691.4% (4.8) 2p = 0.69

00 11 22 33New drugs betterNew drugs better Old drugs betterOld drugs better

All Cardiovascular EventsAll Cardiovascular EventsOdds ratiosOdds ratios(95% CIs)(95% CIs)

..

..

CVD and HTNCVD and HTN

Antihypertensive T reduces CVDAntihypertensive T reduces CVD

Benefit with a variety of drug classesBenefit with a variety of drug classes DD BBBB ACEIACEI CACA ARBARB

BP reduction BP reduction per seper se major factor major factor

4662 M4662 M

7939 = 6398 M mod.7939 = 6398 M mod.

SBP difference between randomized groups (mmHg)SBP difference between randomized groups (mmHg)

Relative risk of outcome eventRelative risk of outcome event1.501.50

1.251.25

1.001.00

0.750.75

0.500.50

0.250.25

1.501.50

1.251.25

1.001.00

0.750.75

0.500.50

0.250.25

1.501.50

1.251.25

1.001.00

0.750.75

0.500.50

0.250.25

1.501.50

1.251.25

1.001.00

0.750.75

0.500.50

0.250.25

1.501.50

1.251.25

1.001.00

0.750.75

0.500.50

0.250.25

StrokeStroke Major CVDMajor CVD CHDCHD

CVD deathCVD death Total mortalityTotal mortality

-10-10 -8-8 -6-6 -4-4 -2-2 00 22 44 -10-10 -8-8 -6-6 -4-4 -2-2 00 22 44 -10-10 -8-8 -6-6 -4-4 -2-2 00 22 44

-10-10 -8-8 -6-6 -4-4 -2-2 00 22 44 -10-10 -8-8 -6-6 -4-4 -2-2 00 22 44

Risk of CVD according to SBP Control by TreatmentRisk of CVD according to SBP Control by TreatmentRisk of CVD according to SBP Control by TreatmentRisk of CVD according to SBP Control by Treatment

8273 M 8273 M Pepine, Koney, Kupfer, Benetos, Mancia et al., 2004Pepine, Koney, Kupfer, Benetos, Mancia et al., 2004

00

1010

2020

3030

4040 CHFCHFCHFCHF Prior MIPrior MIPrior MIPrior MI DiabetesDiabetesDiabetesDiabetes Prior Prior Stroke / TIAStroke / TIA

Prior Prior Stroke / TIAStroke / TIA

RenalRenalImpairmentImpairment

RenalRenalImpairmentImpairment

AgeAgeAgeAge

NoNo YesYes NoNo YesYes NoNo YesYes NoNo YesYes NoNo YesYes ≤ ≤ 7070 > 70> 70

13.513.5

7.47.4

30.230.2

21.021.0

12.412.4

6.46.4

18.718.7

11.911.9 12.412.4

6.76.7

18.918.9

11.911.913.613.6

7.47.4

24.124.1

17.417.4

14.014.0

7.97.9

29.829.8

24.624.6

10.810.8

5.15.1

20.320.3

14.814.8

< 140 mmHg< 140 mmHg≥ ≥ 140 mmHg140 mmHg

* P < 0.001; * P < 0.001; P = 0.03; † P = 0.04 P = 0.03; † P = 0.04

**

**

**

**

††

††

UKPDS=United Kingdom Prospective Diabetes Study; MDRD=Modification of Diet in Renal Disease; UKPDS=United Kingdom Prospective Diabetes Study; MDRD=Modification of Diet in Renal Disease; HOT=Hypertension Optimal Treatment; AASK=African American Study of Kidney Disease; RENAAL=Reduction of Endpoints in HOT=Hypertension Optimal Treatment; AASK=African American Study of Kidney Disease; RENAAL=Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan; IDNT=Irbesartan Diabetic Nephropathy Trial; MAP=mean arterial pressure.NIDDM with the Angiotensin II Antagonist Losartan; IDNT=Irbesartan Diabetic Nephropathy Trial; MAP=mean arterial pressure.

Hypertension in High-Risk Patients: Number Hypertension in High-Risk Patients: Number of Agents Required to Achieve BP Goal of Agents Required to Achieve BP Goal

Number of BP MedicationsNumber of BP Medications

UKPDS (<85 mm Hg, diastolic)UKPDS (<85 mm Hg, diastolic)

4433 2211

MDRD (92 mm Hg, MAP)MDRD (92 mm Hg, MAP)

HOT (<80 mm Hg, diastolic)HOT (<80 mm Hg, diastolic)

AASK (<92 mm Hg, MAP)AASK (<92 mm Hg, MAP)

RENAAL (<140/90 mm Hg)RENAAL (<140/90 mm Hg)

IDNT (IDNT (135/85 mm Hg)135/85 mm Hg)

Bakris et al. Am J Kidney Dis. 2000;36:646-661; Brenner et al. N Engl J Med. 2001;345:861-869;Bakris et al. Am J Kidney Dis. 2000;36:646-661; Brenner et al. N Engl J Med. 2001;345:861-869;Lewis et al. N Engl J Med. 2001;345:851-860Lewis et al. N Engl J Med. 2001;345:851-8605129 M5129 M

DiureticsDiuretics

ACE inhibitorsACE inhibitors

Calcium Calcium antagonistsantagonists

ATAT11-receptor -receptor

blockersblockersß-blockersß-blockers

11-blockers-blockers

6220 M6220 M

2003 ESH/ESC Guidelines2003 ESH/ESC Guidelines

6219 M6219 M

2003 ESH/ESC Guidelines2003 ESH/ESC GuidelinesConsider:Consider:

Untreated BP levelUntreated BP levelAbsence or presence of TOD and risk Absence or presence of TOD and risk

factorsfactors

Choose betweenChoose between

If goal BP not achievedIf goal BP not achieved

If goal BP not achievedIf goal BP not achieved

Single agentSingle agentat low doseat low dose

Two-drug combinationTwo-drug combinationat low doseat low dose

Two-three drug combination Two-three drug combination at effective dosesat effective doses

Previous agentPrevious agentat full doseat full dose

Switch to differentSwitch to differentagent at low doseagent at low dose

Previous combinationPrevious combinationat full doseat full dose

Add a third drug Add a third drug at low doseat low dose

Two-three drug Two-three drug combinationcombination

Full doseFull dosemonotherapymonotherapy

ESH/ESC GuidelinesESH/ESC GuidelinesESH/ESC GuidelinesESH/ESC Guidelines

Particular attention should be given to adverse Particular attention should be given to adverse events, even primarily subjective disturbances, events, even primarily subjective disturbances, because they may be an important cause of non-because they may be an important cause of non-compliancecompliance

Pts should always be asked about adverse effects and Pts should always be asked about adverse effects and doses or drugs changed accordinglydoses or drugs changed accordingly

6375 M6375 M

ESH/ESC Guidelines - Specific Indications for Drug ClassesESH/ESC Guidelines - Specific Indications for Drug ClassesESH/ESC Guidelines - Specific Indications for Drug ClassesESH/ESC Guidelines - Specific Indications for Drug Classes

ThiazidesThiazides

Loop diureticsLoop diuretics

Antialdosterone DAntialdosterone D

BB

CCB (DHP)CCB (DHP)

CCB (non-DHP)CCB (non-DHP)

ACEIACEI

ARBARB

BB

6372 M6372 M

CHF / Elderly / ISH / BlacksCHF / Elderly / ISH / Blacks

Renal insufficiency / CHFRenal insufficiency / CHF

CHF / Post-MICHF / Post-MI

Angina / Post-MI / CHF / Pregnancy / TachyarrhythmiasAngina / Post-MI / CHF / Pregnancy / Tachyarrhythmias

Elderly / ISH / Angina / PVD / Ca atherosclerosis / PregnancyElderly / ISH / Angina / PVD / Ca atherosclerosis / Pregnancy

Angina / Ca atherosclerosis / Suprav. tachycardiaAngina / Ca atherosclerosis / Suprav. tachycardia

CHF / LV dysfunction / Post-MI / Non-DN / Type I DN / ProteinuriaCHF / LV dysfunction / Post-MI / Non-DN / Type I DN / Proteinuria

Type 2 DN / Diabetic microalbuminuria / Proteinuria / LVH / ACEI-coughType 2 DN / Diabetic microalbuminuria / Proteinuria / LVH / ACEI-cough

BPH / HyperlipidaemiaBPH / Hyperlipidaemia

1993 ESH/ESC Guidelines: 1993 ESH/ESC Guidelines: Antihypertensive Treatment in DMAntihypertensive Treatment in DM

1993 ESH/ESC Guidelines: 1993 ESH/ESC Guidelines: Antihypertensive Treatment in DMAntihypertensive Treatment in DM

6262 M6262 M

Non-pharmacological measures (particularly weight loss and Non-pharmacological measures (particularly weight loss and Na intake) Na intake) in all patientsin all patients

BP goal a 130/80 mmHgBP goal a 130/80 mmHg

Combination T required most oftenCombination T required most often

Use of all effective / well tolerated agents recommendedUse of all effective / well tolerated agents recommended

Renoprotection benefits from regular inclusion in combination T of Renoprotection benefits from regular inclusion in combination T of -- ACEI in type I DMACEI in type I DM-- ARB in type II DMARB in type II DM

In type II DM with normal BP use first a RAS blockerIn type II DM with normal BP use first a RAS blocker

Microalbuminuria (type I/II DM) is an indication for T, especially with Microalbuminuria (type I/II DM) is an indication for T, especially with RAS blocker, irrespective of BP valuesRAS blocker, irrespective of BP values

7997 M7997 M

RiskRiskFactorsFactors

RiskRiskFactorsFactors

SubclinicalSubclinicalOrganOrgan

DamageDamage

SubclinicalSubclinicalOrganOrgan

DamageDamageEventsEventsEventsEvents

Not surrogateNot surrogatebut but

““intermediate”intermediate” end-point end-point

-20

-15

-10

-5

0

-20

-15

-10

-5

0

LVH Regression by Different Classes of Antihypertensive DrugsLVH Regression by Different Classes of Antihypertensive DrugsLVH Regression by Different Classes of Antihypertensive DrugsLVH Regression by Different Classes of Antihypertensive Drugs

6362 M6362 MKlingbeil A, Schmieder RE, Curr Cardiol Report 2003Klingbeil A, Schmieder RE, Curr Cardiol Report 2003

Red

uct

ion

of

LV

M (

%)

Red

uct

ion

of

LV

M (

%)

DiureticsDiuretics -Blockers-BlockersCalciumCalcium

antagonistsantagonists ACE-IACE-IAg II-Ag II-

BlockersBlockers

p < 0.01p < 0.01

p < 0.01p < 0.01

p < 0.05p < 0.05

5811 M5811 M

HOPE:HOPE:Reduction in Primary Outcome with Regression/Prevention of Reduction in Primary Outcome with Regression/Prevention of

LVHLVH

Mathew J et al., Circulation 2001; 104: 1615-1621

20002000150015001000100050050000

Days of follow-upDays of follow-up

0.000.00

0.050.05

0.100.10

0.150.15

0.200.20Proportion ofProportion ofall patientsall patients

with primary outcomewith primary outcome(CV death, MI, (CV death, MI,

stroke)stroke) Development / PersistenceDevelopment / Persistence

Regression / PreventionRegression / Prevention

P = 0.0061P = 0.0061

* whether or not hospitalized* whether or not hospitalized

-50-50

-40-40

-30-30

-20-20

-10-10

00

New DM in Antihypertensive Drugs TrialsNew DM in Antihypertensive Drugs TrialsNew DM in Antihypertensive Drugs TrialsNew DM in Antihypertensive Drugs Trials

8092 M = 4850 new8092 M = 4850 new

-14

-4

-34

-2 -2

-23-25*

-25

-20

-40*

-30**

CAPPPCAPPP

ACEIACEIvsvs

ConvConv

STOP-2STOP-2

ACEIACEIvsvs

ConvConv

ALLHATALLHAT

ACEIACEIvsvsDD

HOPEHOPE

ACEIACEIvsvsPLPL

STOP-2STOP-2

CACAvsvs

ConvConv

INSIGHTINSIGHT

CACAvsvsDD

ALLHATALLHAT

CACAvsvsDD

STOP-2STOP-2

ACEIACEIvsvs

CACA

LIFELIFE

ARBARBvsvsBBBB

SCOPESCOPE

ARBARBvsvs

ConvConv

* T, 2 yrs; ** T, 4 yrs* T, 2 yrs; ** T, 4 yrs* T, 2 yrs; ** T, 4 yrs* T, 2 yrs; ** T, 4 yrs

-21

CHARMCHARM

ARBARBvsvsPLPL

INVESTINVEST

CACAvsvs

ConvConv

-16**

-16

Rate of Metabolic Syndrome and New Onset Diabetes Rate of Metabolic Syndrome and New Onset Diabetes in ALPINE after 1 Year Tin ALPINE after 1 Year T

Rate of Metabolic Syndrome and New Onset Diabetes Rate of Metabolic Syndrome and New Onset Diabetes in ALPINE after 1 Year Tin ALPINE after 1 Year T

8270 M 8270 M Lindholm et al., J Hypertens 2003; 21: 1563Lindholm et al., J Hypertens 2003; 21: 1563

CandesartanCandesartan

HCTZHCTZ

BB

13 (6.6%)13 (6.6%)

12 (6.1%)12 (6.1%)

TT

5 (2.6%)5 (2.6%)

18 (9.2%)18 (9.2%)

DiabetesDiabetes

1 (0.5%)1 (0.5%)

8 (4.1%)8 (4.1%)

Metabolic SyndromeMetabolic Syndrome

Importance (Hazard Ratio) of Importance (Hazard Ratio) of Blood Glucose at Age 50 to 60 Blood Glucose at Age 50 to 60 on Risk of MI after 60on Risk of MI after 60

Importance (Hazard Ratio) of Importance (Hazard Ratio) of Blood Glucose at Age 50 to 60 Blood Glucose at Age 50 to 60 on Risk of MI after 60on Risk of MI after 60

6232 M6232 M

GlucoseGlucoseGlucoseGlucose BMIBMIBMIBMI SBPSBPSBPSBP DBPDBPDBPDBP

YesYes(n = 291)(n = 291)

1.371.37**1.041.040.880.880.110.110.960.960.990.990.850.850.920.92

NoNo(n = 1358)(n = 1358)

1.141.141.161.160.980.98

1.191.19°°1.251.25

1.271.27††1.011.01

1.26 1.26 °°

Antihypertensive T (mainly D/BB)Antihypertensive T (mainly D/BB)

** P = 0.0004; P = 0.0004; °° P = 0.02; P = 0.02; †† P = 0.01 P = 0.01 Dunder et al., BMJ 2003, 326Dunder et al., BMJ 2003, 326

Association of Systolic BP and Cardiovascular Death in Type 2 Diabetes

< 120 120-139 140-159 160-179 180-199 200Systolic blood pressure (mmHg)

0

50

100

150

200

250

Nondiabetic

Diabetic

Stamler J et al. Diabetes Care 1993; 16: 434-444

Association of Systolic BP and Cardiovascular Death in Type 2 Diabetes

Cardiovascularmortality

rate/10,000person-yr

16251625

JNC 7 - Stage I HypertensionJNC 7 - Stage I HypertensionJNC 7 - Stage I HypertensionJNC 7 - Stage I Hypertension

6701 M6701 M

As it isAs it is

ImprovedImproved

Further Further improvementimprovement

IdealIdeal

Thiazide diuretics for mostThiazide diuretics for mostMay consider ACEI / ARB / CCB or combinationMay consider ACEI / ARB / CCB or combination

Thiazide diureticsThiazide diureticsFor most may consider ACEI / ARB / CCB or combinationFor most may consider ACEI / ARB / CCB or combination

Thiazide diureticsThiazide diureticsFor most may consider ACEI / ARB / CCB / BB or,For most may consider ACEI / ARB / CCB / BB or,more frequently, combination Tmore frequently, combination T

ESH/ESC GuidelinesESH/ESC Guidelines

Percent of Italian Hypertensives with BP Control (<140/90 mmHg)Percent of Italian Hypertensives with BP Control (<140/90 mmHg)after Year 2000after Year 2000

Percent of Italian Hypertensives with BP Control (<140/90 mmHg)Percent of Italian Hypertensives with BP Control (<140/90 mmHg)after Year 2000after Year 2000

8234 M8234 M

Forlife Forlife

(n = 12792)(n = 12792)SMOOTHSMOOTH

(n = 2144 *)(n = 2144 *)Mancia et al. Mancia et al.

J Hypertension 2004, 2J Hypertension 2004, 2(n = 3812)(n = 3812)

Hypertensives enrolled by physicians across Italian territoryHypertensives enrolled by physicians across Italian territory** Population survey in San Marino - n refers to hypertensive fractionPopulation survey in San Marino - n refers to hypertensive fraction

PractitionersPractitioners PractitionersPractitioners SpecialistsSpecialists

12.212.212.212.2 21.721.721.721.7 14.014.014.014.0

ACE ACE InhibitorsInhibitors

Calcium Calcium ChannelChannelBlockersBlockers

-blockers-blockers ControlControl

ProteinuriaProteinuriaAlbuminuriaAlbuminuria

-0.6-0.6

-0.4-0.4

-0.2-0.2

-0.0-0.0

0.20.2

Log

ch

ange

fro

m b

asel

ine

Log

ch

ange

fro

m b

asel

ine

Kasiske et al Ann Intern Med 1993Kasiske et al Ann Intern Med 1993

** **

** p < 0.05 vs controlp < 0.05 vs control

Effects of antihypertensive agents on changes in proteinuria and albuminuria Effects of antihypertensive agents on changes in proteinuria and albuminuria in patients with type 1 and 2 diabetes mellitusin patients with type 1 and 2 diabetes mellitus

(meta-regression analysis, 100 studies, 2494 patients)(meta-regression analysis, 100 studies, 2494 patients)

5993 M5993 M

8290 M8290 M

ITT PP 1 PP 2 Compl.0

0.01

0.02

0.03

0.04

0.05

0.06Mean Change

(mm)

Atenolol

Lacidipine

CBMCBMmaxmax: Final Scan versus Baseline Scan: Final Scan versus Baseline Scan

Ratios of Mean Changes and 95% CIRatios of Mean Changes and 95% CIITTITT

PP 1PP 1

PP 2 PP 2

Compl.Compl.

0.20.2 0.40.4 0.60.6 0.80.8 11 1.21.2 1.41.4Lacidipine betterLacidipine better Atenolol betterAtenolol better

ESH/ESC vs JNC 7 - Major AgreementsESH/ESC vs JNC 7 - Major AgreementsESH/ESC vs JNC 7 - Major AgreementsESH/ESC vs JNC 7 - Major Agreements

6705 M6705 M

Benefits of antihypertensive TBenefits of antihypertensive T

Avoidance of complex lab examinationsAvoidance of complex lab examinations

BP measurement procedureBP measurement procedure

Use / value of ABPM / home BPUse / value of ABPM / home BP

Use of antiplatelet / lipid lowering drugsUse of antiplatelet / lipid lowering drugs

BP targets (and thresholds?)BP targets (and thresholds?)

Follow-up strategiesFollow-up strategies

Value of fixed / long-acting / low dose combinationsValue of fixed / long-acting / low dose combinations

Compelling drug indications (Compelling drug indications ( more of format than of substance) more of format than of substance)

Combination T (as above)Combination T (as above)

Treatment of most specific conditionsTreatment of most specific conditions

Progression of non-diabetic renal diseaseProgression of non-diabetic renal disease

Jafar TH, Ann Int Med 2001;135:73-87.

Syst

olic

BP

(mm

Hg

)

Follow-up (mo)

80

150

130

140

Blood Pressure

1.0

2.0

1.6

p<0.001

1.4

1.8

Urinary protein excretion

Surv

ival w

ithout

ES

RD

0.0

1.0

0.6

0.2

0.8

0.0

1.0

0.4

p<0.001

0.2

0.8

p<0.003

0.6

0.4

A meta-analysis of data on 1860 pts on antihypertensive regimens

A meta-analysis of data on 1860 pts on antihypertensive regimens

95

90

85

Dia

stolic

BP

(mm

Hg

)

1.2

139/85 vs 144/87p<0.001

0 12 24 36 48 0 12 24 36 48

Surv

ival w

ithout

doub

ling

of

base

line s

eru

m

Cre

ati

nin

e c

once

ntr

ati

on

of

ES

RD

Not including ACE-inhibitorsIncluding ACE-inhibitors

Uri

nary

pro

tein

excr

eti

on

g/d

919 752 632 404 63941 770 657 450 56

ControlACEI

Patient, n

Survival without end-stage renal diseaseDoubling of baseline serum creatinineconcentration or ESD

Follow-up (mo)

22832283

Results of IDNT: Primary ObjectiveResults of IDNT: Primary Objective

ASH 2001ASH 2001

Blood PressureBlood Pressure

IrbesartanIrbesartan 140/77140/77AmlodipineAmlodipine 141/77141/77PlaceboPlacebo 144/80144/80

irbesartan vs placeboirbesartan vs placeboamlodipine vs placeboamlodipine vs placeboirbesartan vs amlodipineirbesartan vs amlodipine

RRRR

0.770.771.071.070.710.71

p-valuep-value

0.0110.011nsns

0.0010.001

32

41 39

Irbesartan Amlodipine Placebo0

10

20

30

40

50

% doubling of serum creatinine, ESRD, death

32

41 39

Irbesartan Amlodipine Placebo0

10

20

30

40

50

% doubling of serum creatinine, ESRD, death

4826 M4826 M

Effect of Antihypertensive Treatment (n = 10)Effect of Antihypertensive Treatment (n = 10)

Parving et al., Lancet 1983Parving et al., Lancet 1983

95

105

115

125

65

75

85

95

105

-30 -24 -18 -12 -6 0 6 12 18 24 30 36 Months250

750

1250

95

105

115

125

65

75

85

95

105

-30 -24 -18 -12 -6 0 6 12 18 24 30 36 Months250

750

1250

MAPMAP(mmHg)(mmHg)

GFRGFR(ml/min/1.73 m(ml/min/1.73 m22))

AlbuminuriaAlbuminuria((g/min)g/min)

Start of treatmentStart of treatment

StrokeStroke ACEI ACEI vs D/BBvs D/BBCA CA vs D/BBvs D/BBACEI ACEI vs CAvs CA

CHDCHD ACEI ACEI vs D/BBvs D/BBCA CA vs D/BBvs D/BBACEI ACEI vs CAvs CA

Heart failure Heart failure ACEI ACEI vs D/BBvs D/BBCA CA vs D/BBvs D/BBACEI ACEI vs CAvs CA

Major CV events Major CV events ACEI ACEI vs D/BBvs D/BBCA CA vs D/BBvs D/BBACEI ACEI vs CAvs CA

CV death CV death ACEI ACEI vs D/BBvs D/BBCA CA vs D/BBvs D/BBACEI ACEI vs CAvs CA

Total mortality Total mortality ACEI ACEI vs D/BBvs D/BBCA CA vs D/BBvs D/BBACEI ACEI vs CAvs CA

6396 M6396 M

Mean BP Mean BP (mmHg)(mmHg)

+2 / 0+2 / 0 0 / 00 / 0+1 / +1+1 / +1

+2 / 0+2 / 0 0 / 00 / 0+1 / +1+1 / +1

+2 / 0+2 / 0 0 / 00 / 0+1 / +1+1 / +1

+2 / 0+2 / 0 0 / 00 / 0+1 / +1+1 / +1

+2 / 0+2 / 0 0 / 00 / 0+1 / +1+1 / +1

+2 / 0+2 / 0 0 / 00 / 0+1 / +1+1 / +1

Relative RiskRelative Risk(95% CI)(95% CI)

1.09 (1.00-1.18)1.09 (1.00-1.18)0.93 (0.86-1.01)0.93 (0.86-1.01)1.12 (1.01-1.25)1.12 (1.01-1.25)

0.98 (0.91-1.05)0.98 (0.91-1.05)1.01 (0.94-1.08)1.01 (0.94-1.08)0.96 (0.88-1.05)0.96 (0.88-1.05)

1.07 (0.96-1.19)1.07 (0.96-1.19)1.34 (1.22-1.47)1.34 (1.22-1.47)0.82 (0.73-0.92)0.82 (0.73-0.92)

1.02 (0.98-1.07)1.02 (0.98-1.07)1.04 (0.99-1.08)1.04 (0.99-1.08)0.97 (0.92-1.03)0.97 (0.92-1.03)

1.03 (0.95-1.11)1.03 (0.95-1.11)1.04 (0.97-1.12)1.04 (0.97-1.12)1.03 (0.94-1.13)1.03 (0.94-1.13)

1.00 (0.95-1.05)1.00 (0.95-1.05)0.99 (0.94-1.04)0.99 (0.94-1.04)1.04 (0.98-1.10)1.04 (0.98-1.10)

Favours first Favours first listedlisted

Favours second Favours second listedlisted

0.50.5 1.01.0 2.02.0Relative riskRelative risk

% < 3.5mmol/L% < 3.5mmol/L

PP<.001<.0010.80.8LisinoprilLisinopril

PP<.001<.0011.91.9AmlodipineAmlodipine

8.58.5ChlorthalidoneChlorthalidone

PP<.001<.0014.54.5LisinoprilLisinopril

PP<.001<.0014.44.4AmlodipineAmlodipine

4.14.1ChlorthalidoneChlorthalidone

Potassium - mmol/LPotassium - mmol/L

Intermediate Outcomes: Biochemical Changes at 4 years

5209 M5209 M

8081 M8081 M

ALLHAT - K+ Supplementation AnalysisALLHAT - K+ Supplementation AnalysisALLHAT - K+ Supplementation AnalysisALLHAT - K+ Supplementation Analysis

CC

8%8%

AA

4%4%

LL

2%2%

Diuretic-Induced HypokalemiaDiuretic-Induced HypokalemiaDiuretic-Induced HypokalemiaDiuretic-Induced Hypokalemia

8097 M 8097 M

CommonCommon

More lab examinations?More lab examinations?

Sudden death?Sudden death?

Protection by antihypertensive treatment?Protection by antihypertensive treatment?

48514851

Hazard Ratio of CVD According to Serum KHazard Ratio of CVD According to Serum K++ of Treated Patients of Treated Patients at 1 Year in SHEPat 1 Year in SHEP

CVDCVD

CHDCHD

StrokeStroke

0.10.1 0.50.5 11 22 55 1010

Placebo betterPlacebo betterTreatment betterTreatment better

KK++ < 3.5 mEq/l < 3.5 mEq/lKK++ ≥ 3.5 mEq/l ≥ 3.5 mEq/lKK++ < 3.5 mEq/l < 3.5 mEq/lKK++ ≥ 3.5 mEq/l ≥ 3.5 mEq/l

1.18 (0.73-1.76)1.18 (0.73-1.76)

0.61 (0.50-0.75)0.61 (0.50-0.75)

0.75 (0.56-1.01)0.75 (0.56-1.01)

0.51 (0.36-0,71)0.51 (0.36-0,71)

1.46 (0.79-2.67)1.46 (0.79-2.67)

1.43 (0.74-2.74)1.43 (0.74-2.74)

ESH/ESC Guidelines - Choice of Antihypertensive DrugsESH/ESC Guidelines - Choice of Antihypertensive DrugsESH/ESC Guidelines - Choice of Antihypertensive DrugsESH/ESC Guidelines - Choice of Antihypertensive Drugs

6407 M6407 M

Choice influenced byChoice influenced by-- Previous patient’s experiencePrevious patient’s experience-- Cost (to individual / health provider) *Cost (to individual / health provider) *-- Risk profile / TODRisk profile / TOD-- CVD / Renal diseaseCVD / Renal disease-- DiabetesDiabetes-- Coexisting disorders / Drugs interactionsCoexisting disorders / Drugs interactions-- Patient’s preferencePatient’s preference

Emphasis on 1st choice drugs outdated (predominance of Emphasis on 1st choice drugs outdated (predominance of combination T)combination T)

Cost consideration should not predominate over efficacy / tolerability in Cost consideration should not predominate over efficacy / tolerability in any individual patientsany individual patients

Dysmetabolic Effect of Diuretics (± BB)Dysmetabolic Effect of Diuretics (± BB)Dysmetabolic Effect of Diuretics (± BB)Dysmetabolic Effect of Diuretics (± BB)

8096 M 8096 M

CVD / Nephropathy / ESRFCVD / Nephropathy / ESRF

More med. visits / lab examinationsMore med. visits / lab examinations

More patients under antidiabetic drugsMore patients under antidiabetic drugs

More antihypertensive drugs (lower BP targets)More antihypertensive drugs (lower BP targets)

More antihypertensive drugs in diabeticsMore antihypertensive drugs in diabetics

Changes in OGT Test (2h) after 12 Months Antihypertensive TChanges in OGT Test (2h) after 12 Months Antihypertensive Tin ALPINE (n = 49)in ALPINE (n = 49)

Changes in OGT Test (2h) after 12 Months Antihypertensive TChanges in OGT Test (2h) after 12 Months Antihypertensive Tin ALPINE (n = 49)in ALPINE (n = 49)

8272 M 8272 M Lindholm et al., J Hypertens 2003; 21: 1563Lindholm et al., J Hypertens 2003; 21: 1563

S-InsulinS-InsulinS-InsulinS-Insulin P-glucoseP-glucoseP-glucoseP-glucose S-Ins / P-GlucS-Ins / P-GlucS-Ins / P-GlucS-Ins / P-Gluc

Candesartan, 16 mgCandesartan, 16 mg

HCTZ, 25 mgHCTZ, 25 mg

° ° p < 0.001p < 0.001†† p = 0.006p = 0.006

-10-10

00

1010

2020

3030

4040

5050

-10-10

47.7

-6.3-6.3

13.113.1

-1-1

3.53.5

%%°°

°°††

Biochemical Results – Fasting Glucose (mg/dL)

100.5 (19.5)*100.5 (19.5)*103.1 (27.7)103.1 (27.7)104.4 (28.5)104.4 (28.5)4 Years4 Years

Diabetes Incidence (follow-up fasting glucose Diabetes Incidence (follow-up fasting glucose 126 mg/dL) 126 mg/dL)

Among baseline nondiabetics with baseline <126 mg/dLAmong baseline nondiabetics with baseline <126 mg/dL

TotalTotal

4 Years4 Years

BaselineBaseline

4 Years4 Years

BaselineBaseline

8.1%*8.1%*9.8%*9.8%*11.6%11.6%

93.3 (11.8)93.3 (11.8)93.0 (11.4)93.0 (11.4)93.1 (11.7)93.1 (11.7)

121.5 (51.3)*121.5 (51.3)*123.7 (52.0)123.7 (52.0)126.3 (55.6)126.3 (55.6)

122.9 (56.1)122.9 (56.1)123.1 (57.0)123.1 (57.0)123.5 (58.3)123.5 (58.3)

LisinoprilLisinoprilAmlodipineAmlodipineChlorthalidoneChlorthalidone

*p<.05 compared to chlorthalidone*p<.05 compared to chlorthalidone

ALLHATALLHAT

5246 M5246 M

130130

140140

150150

160160

170170

180180

190190

200200mmHgmmHg mmHgmmHg

FACETFACET

Micro HOPEMicro HOPE

CAPPPCAPPP

INSIGHTINSIGHT

HOTHOT

VALUEVALUE

STOP-2STOP-2

UKPDSUKPDS

LIFELIFE

RENAALRENAAL

IDNTIDNT

IRMAIRMA

ABCDABCD

120120Mancia G., Grassi G., J Hypertension 2002Mancia G., Grassi G., J Hypertension 2002

7070

8080

9090

100100

110110

120120

6060

SBPSBPSBPSBP DBPDBPDBPDBP

1186 G1186 G

Systolic vs Diastolic BP Control in Trials on Diabetic HypertensivesSystolic vs Diastolic BP Control in Trials on Diabetic Hypertensives

BB TT BB TT

Cumulative Yearly Rates of Development of Sight-Threatening Cumulative Yearly Rates of Development of Sight-Threatening Diabetic Retinopathy in 4770 Patients with Type 2 DiabetesDiabetic Retinopathy in 4770 Patients with Type 2 Diabetes

Cumulative Yearly Rates of Development of Sight-Threatening Cumulative Yearly Rates of Development of Sight-Threatening Diabetic Retinopathy in 4770 Patients with Type 2 DiabetesDiabetic Retinopathy in 4770 Patients with Type 2 Diabetes

7148 M7148 M Younis N et al., Lancet 2003; 361: 195Younis N et al., Lancet 2003; 361: 195

CumulativeCumulativeincidenceincidence

(%)(%)

Patients at riskPatients at riskLevel 30Level 30Level 20Level 20Level 10Level 10

0 1 2 3 4 5 6

Observation period (years)

0

10

20

30

40

50

60

70

80Level 30

Level 20

Level 10

0 1 2 3 4 5 6

Observation period (years)

0

10

20

30

40

50

60

70

80Level 30

Level 20

Level 10

217217810810

37433743

217217810810

37433743

175175732732

35683568

116116531531

25582558

6969355355

15841584

3333218218943943

1818149149630630

p = 0.0012 (for trend)

Prevalence (%) of Different Stages of Nephropathy Prevalence (%) of Different Stages of Nephropathy with Increasing Duration of Diabeteswith Increasing Duration of Diabetes

Prevalence (%) of Different Stages of Nephropathy Prevalence (%) of Different Stages of Nephropathy with Increasing Duration of Diabeteswith Increasing Duration of Diabetes

7156 M7156 M Adler et al. - UKPDS, Kidney Int 2003; 63: 225Adler et al. - UKPDS, Kidney Int 2003; 63: 225

Time Time (years)(years)

00

55

1010

1515

2020

MicroalbuminuriaMicroalbuminuriaor worseor worse

7.37.3

17.317.3

24.924.9

28.028.0

34.3 (model)34.3 (model)

MacroalbuminuriaMacroalbuminuriaor worseor worse

0.70.7

2.82.8

5.15.1

7.67.6

10.0 (model)10.0 (model)

SCr /SCr /renal replacementrenal replacement

0.00.0

0.40.4

0.80.8

2.32.3

RR of New Onset Diabetes in CAS (vs NCAS) Patients RR of New Onset Diabetes in CAS (vs NCAS) Patients in INVESTin INVEST

RR of New Onset Diabetes in CAS (vs NCAS) Patients RR of New Onset Diabetes in CAS (vs NCAS) Patients in INVESTin INVEST

7542 M7542 M

00

11

22

RRRR

TrandolaprilTrandolapril HCTZHCTZ

No Yes(25)

Yes(50.0)

No Yes(2)

Yes(4)

0.950.950.950.95

0.860.860.860.860.770.770.770.77

0.950.950.950.95

1.171.171.171.17

1.361.361.361.36

8010 M8010 M

Cardiovascular Events in Hypertensive Subjects with Regression Cardiovascular Events in Hypertensive Subjects with Regression versus Persistence or New Development of Left Ventricular Hypertrophy*versus Persistence or New Development of Left Ventricular Hypertrophy*

Cardiovascular Events in Hypertensive Subjects with Regression Cardiovascular Events in Hypertensive Subjects with Regression versus Persistence or New Development of Left Ventricular Hypertrophy*versus Persistence or New Development of Left Ventricular Hypertrophy*

Verdecchia P et al., Am J Hypertens 2003; 16: 895Verdecchia P et al., Am J Hypertens 2003; 16: 895* LVH detected by echocardiography* LVH detected by echocardiography

n = 1064n = 1064FU 2.8-10.0 ysFU 2.8-10.0 ysLVH at B 22%LVH at B 22%

n = 1064n = 1064FU 2.8-10.0 ysFU 2.8-10.0 ysLVH at B 22%LVH at B 22%

StudyStudy

Muiesan (1995)Muiesan (1995)

Verdecchia (1998)Verdecchia (1998)

Cipriano (2001)Cipriano (2001)

Koren (2002)Koren (2002)

TotalTotal

Heterogeneity: Heterogeneity: 22 = 2.50; df = 3; p = 0.48 = 2.50; df = 3; p = 0.48Z = -2.71 p = 0.0068Z = -2.71 p = 0.0068

LVHLVHregressionregression

4/ 324/ 32

3/ 523/ 52

5/ 525/ 52

1/ 161/ 16

13/15213/152

LVHLVHpersistence/newpersistence/new

15/ 4115/ 41

13/10013/100

17/13417/134

12/ 4212/ 42

57/31757/317

Odds RatioOdds Ratio(95% CI)(95% CI)

0.24 (0.07-0.84)0.24 (0.07-0.84)

0.41 (0.11-1.51)0.41 (0.11-1.51)

0.73 (0.25-2.10)0.73 (0.25-2.10)

0.17 (0.02-1.40)0.17 (0.02-1.40)

0.41 (0.21-0.78)0.41 (0.21-0.78)

Odds RatioOdds Ratio(95% CI)(95% CI)

0.10.1 0.20.2 0.50.5 11 22 55

FavoursFavoursLVH regressionLVH regression

FavoursFavoursLVH persistence/newLVH persistence/new

Low-Dose Diuretics as 1st Choice -Low-Dose Diuretics as 1st Choice -1993 WHO/ISH Statement1993 WHO/ISH Statement

Low-Dose Diuretics as 1st Choice -Low-Dose Diuretics as 1st Choice -1993 WHO/ISH Statement1993 WHO/ISH Statement

8094 M 8094 M

It is contradictory to emphasize the need for treatment It is contradictory to emphasize the need for treatment

to address “global” CV risk and recommend as 1st to address “global” CV risk and recommend as 1st

choice treatments that may increase it.choice treatments that may increase it.

7998 M7998 M

Goal(s) of TreatmentGoal(s) of TreatmentGoal(s) of TreatmentGoal(s) of Treatment

In young / middle age / not high risk patients In young / middle age / not high risk patients

treatment goal is treatment goal is notnot to prevent an (unlikely) event to prevent an (unlikely) event

in few years in few years butbut to prevent progression (or achieve to prevent progression (or achieve

regression) of silent organ damage that will cause regression) of silent organ damage that will cause

an event many years later.an event many years later.

Superior Effect of New vs Conventional Drugs on Markers of TOD Superior Effect of New vs Conventional Drugs on Markers of TOD (Intermediate End-Points)(Intermediate End-Points)

Superior Effect of New vs Conventional Drugs on Markers of TOD Superior Effect of New vs Conventional Drugs on Markers of TOD (Intermediate End-Points)(Intermediate End-Points)

6073 M6073 M

LV hypertrophyLV hypertrophy

Carotid artery IMT / AtherosclerosisCarotid artery IMT / Atherosclerosis

Arteriolar remodellingArteriolar remodelling

Urinary protein excretionUrinary protein excretion

Endothelial dysfunctionEndothelial dysfunction

Arterial stiffeningArterial stiffening

Mild renal damageMild renal damage

CA coronary contentCA coronary content

ACEI / CA / ARBACEI / CA / ARB

CA / ACEICA / ACEI

ACEI / ARB / CAACEI / ARB / CA

ACEI / ARBACEI / ARB

CA / ACEI (?) / ARB (?)CA / ACEI (?) / ARB (?)

??

CACA

CACA

JNC7 vs ESH-ESC GLsJNC7 vs ESH-ESC GLsMajor DifferencesMajor Differences

• Total CV risk assesmentTotal CV risk assesment• Term “pre-hypertension” avoided / no therapeutic reccomendations Term “pre-hypertension” avoided / no therapeutic reccomendations

if risk not highif risk not high• Drug administration in grade I hypertension more flexibleDrug administration in grade I hypertension more flexible• 5 drug classes (not only D) for T initiation / maintenance5 drug classes (not only D) for T initiation / maintenance• Intermediate end-points considered for risk assessment / treatment Intermediate end-points considered for risk assessment / treatment

goalsgoals• All trial (not only ALLHAT) consideredAll trial (not only ALLHAT) considered• Combination T as first choiceCombination T as first choice• Mention of Mention of -blockers / central agents-blockers / central agents• Wider disclosure of conflict of interestWider disclosure of conflict of interest

ESH/ESC 2003

Definitions and classification of blood pressure levels

Definitions and classification of blood pressure levels

Optimal <120 <80

Normal 120-129 80-84

High normal 130-139 85-89

Grade 1 hypertension (mild) 140-159 90-99

Grade 2 hypertension (moderate) 160-179 100-109

Grade 3 hypertension (severe) 180 110

Isolated systolic hypertension 140 <90

Systolic (mmHg)

Diastolic (mmHg)Category

“Due to the importance of target organ damage in determining the overall cardiovascular risk of the hypertensive patient, evidence of organ involvement should be sought carefully…”

“…the importance of organ damage, not only in diagnosing cardiovascular risk but also in the follow-up of patients, as well as in using additional enpoints for assessing treatment outcomes…”

Journal of Hypertension 2003

2003 European Society of Hypertension–European 2003 European Society of Hypertension–European Society of Cardiology guidelines for the Society of Cardiology guidelines for the management of arterial hypertensionmanagement of arterial hypertension

48564856

Unplanned Cross-Over Treatment in ALLHATUnplanned Cross-Over Treatment in ALLHAT

CC

13.2%13.2%

9.0%9.0%

22.2%22.2%

AA

16.6%16.6%

6.9%6.9%

23.5%23.5%

LL

15.7%15.7%

8.5%8.5%

24.2%24.2%

Addition of Addition of comparison drug(s)*comparison drug(s)*

Only taking Only taking comparison drug(s)*comparison drug(s)*

TotalTotal

* drug(s) classes* drug(s) classes

RR of New Onset Diabetes in NCAS (vs CAS) Patients in INVESTRR of New Onset Diabetes in NCAS (vs CAS) Patients in INVESTRR of New Onset Diabetes in NCAS (vs CAS) Patients in INVESTRR of New Onset Diabetes in NCAS (vs CAS) Patients in INVEST

7543 M7543 M

00

11

22

RRRR

HCTZHCTZ TrandolaprilTrandolapril

No Yes(2)

Yes(4)

No Yes(25)

Yes(50)

1.111.111.111.111.281.281.281.28

1.001.001.001.00 0.990.990.990.99 0.980.980.980.981.001.001.001.00

7479 M7479 MLindholm et al., J Hypertension 2003; 21: 1563Lindholm et al., J Hypertension 2003; 21: 1563

In ALPINE study risk of developing In ALPINE study risk of developing

metabolic syndrome metabolic syndrome 13 times greater13 times greater

with HCTZ (and BB) than with ARB with HCTZ (and BB) than with ARB

(and CA)(and CA)

BP Range Termed Hypertension is Clinically HeterogeneousBP Range Termed Hypertension is Clinically HeterogeneousBP Range Termed Hypertension is Clinically HeterogeneousBP Range Termed Hypertension is Clinically Heterogeneous

7390 M7390 M

Very high CV riskVery high CV risk

High CV riskHigh CV risk

Moderate CV riskModerate CV risk

Low CV riskLow CV risk

Drug treatmentDrug treatment

Drug treatment if BP “high normal”Drug treatment if BP “high normal”

Life style changes advisableLife style changes advisable

No intervention necessary No intervention necessary (particularly if BP “normal”)(particularly if BP “normal”)

10 Year Risk of Fatal CVD in 10 Year Risk of Fatal CVD in High RiskHigh Risk Regions of Europe Regions of Europe by Gender, Age, SBP, Total Cholesterol and Smoking Statusby Gender, Age, SBP, Total Cholesterol and Smoking Status10 Year Risk of Fatal CVD in 10 Year Risk of Fatal CVD in High RiskHigh Risk Regions of Europe Regions of Europe by Gender, Age, SBP, Total Cholesterol and Smoking Statusby Gender, Age, SBP, Total Cholesterol and Smoking Status

6614 M6614 M

7622 M7622 M

Are JNC-7 Recommendations Less Costly than ESH/ESC Recommendations?Are JNC-7 Recommendations Less Costly than ESH/ESC Recommendations?

ESH/ESCESH/ESC

More liberal recommendations, but those More liberal recommendations, but those patients in whom careful search has excluded patients in whom careful search has excluded TOD more likely to have deferred treatmentTOD more likely to have deferred treatment

In individuals with BP 120-139 or In individuals with BP 120-139 or 80-89 mmHg 80-89 mmHg onlyonly if other risk factors or TOD if other risk factors or TOD are presentare present

In individuals with BP In individuals with BP >> 140 or 90 mmHg 140 or 90 mmHg and no additional risk factor and no additional risk factor only only after up after up to 1 year of lifestyle measures, and to 1 year of lifestyle measures, and onlyonly if if preferred by the patients and resources preferred by the patients and resources availableavailable

All major classes of agents, but many patients All major classes of agents, but many patients with grade I hypertension and low additional with grade I hypertension and low additional risk will not necessarily receive drug treatmentrisk will not necessarily receive drug treatment

JNC-7JNC-7

Very simple, with poor characterization Very simple, with poor characterization of TODof TOD

InIn all all individuals with BP 120-139 or individuals with BP 120-139 or 80-89 mmHg 80-89 mmHg independently independently of of other risk factors and TODother risk factors and TOD

In In allall individuals with BP individuals with BP >> 140 or 90 140 or 90 mmHgmmHg

Thiazide diuretics for all individuals Thiazide diuretics for all individuals with BP with BP >> 140 or 90 mmHg without 140 or 90 mmHg without compelling indicationscompelling indications

DiagnosticDiagnosticProceduresProcedures

Life-styleLife-styleMeasuresMeasures

Initiation ofInitiation ofDrug Drug TreatmentTreatment

DrugsDrugs

7391 M7391 M

Death is in all living creatures’ futureDeath is in all living creatures’ future

Should they be called “predeath”?Should they be called “predeath”?

29362936

Relationship of CV Events and Organ DamageRelationship of CV Events and Organ Damage

Events do not take place on the background Events do not take place on the background of a healthy cardiovascular system but of a healthy cardiovascular system but on the top of subclinical organ damageon the top of subclinical organ damage

High / Very High Risk PatientsHigh / Very High Risk PatientsHigh / Very High Risk PatientsHigh / Very High Risk Patients

6707 M6707 M

BP BP >> 180/110 mmHg 180/110 mmHg

BP BP >> 130/ 85 mmHg if: 130/ 85 mmHg if:-- Risk factors Risk factors >> 3 3-- DiabetesDiabetes-- Associated CVDAssociated CVD-- TODTOD

LVHLVHCA thickeningCA thickeningMicroalbuminuriaMicroalbuminuriaMild renal damageMild renal damage

Arterial remodelling?Arterial remodelling?Endothelial dysfunction?Endothelial dysfunction?Arterial stiffening?Arterial stiffening?Calcium deposition?Calcium deposition?

Arguments Opposing Diuretics (D) as Sole 1Arguments Opposing Diuretics (D) as Sole 1stst Choice in HT Choice in HTArguments Opposing Diuretics (D) as Sole 1Arguments Opposing Diuretics (D) as Sole 1stst Choice in HT Choice in HT

6447 M6447 M

No evidence that D more protective than other drug classesNo evidence that D more protective than other drug classes

No evidence from trials on D at low doseNo evidence from trials on D at low dose

BP lowering effect limited with D at low dosesBP lowering effect limited with D at low doses

Diabetogenic / dismetabolic effects of D substantialDiabetogenic / dismetabolic effects of D substantial

Hypokalemic effect of D substantialHypokalemic effect of D substantial

7775 M7775 M

CA vs D or BB (n = 11685)CA vs D or BB (n = 11685)CA vs D or BB (n = 11685)CA vs D or BB (n = 11685)

Coll Group, Lancet 2003Coll Group, Lancet 2003

-20-20

-15-15

-10-10

-5-5

00

55

1010

1515

2020

RRRR

CVDCVD

+1%+1%+4%+4%

-14%-14%

+12%+12%+14%+14%

+1%+1%

n eventsn events 10781078 409409 454454 561561 274274 776776

**

°°

* * statistically significantstatistically significant°° borderline significantborderline significant

* * statistically significantstatistically significant°° borderline significantborderline significant

CVCVdeathdeath

StrokeStroke CHDCHD CHFCHF TotalTotalmortalitymortality

ESH/ESC Guidelines: Stratification of Risk to Quantify PrognosisESH/ESC Guidelines: Stratification of Risk to Quantify PrognosisESH/ESC Guidelines: Stratification of Risk to Quantify PrognosisESH/ESC Guidelines: Stratification of Risk to Quantify Prognosis

6252 M6252 M

















ACCACC




or DBP 100-109or DBP 100-109

Grade 3Grade 3SBP ≥ 180SBP ≥ 180









LowLowadded riskadded risk


NormalNormalSBP 120-129SBP 120-129


High NormalHigh NormalSBP 130-139SBP 130-139


ACC: associated clinical conditions; TOD: target organ damage; SBP: systolic blood pressure; DBP: diastolic blood pressure ACC: associated clinical conditions; TOD: target organ damage; SBP: systolic blood pressure; DBP: diastolic blood pressure

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ESH/ESC Guidelines: Definitions and Classification of BP Levels (mmHg)

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