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ESH/ESC Guidelines: Definitions and Classification of BP Levels (mmHg). Category Optimal Normal High normal Grade 1 hypertension (mild) Grade 2 hypertension (moderate) Grade 3 hypertension (severe) Isolated systolic hypertension. Systolic < 120 120-129 130-139 140-159 160-179 - PowerPoint PPT Presentation
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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
DBP)DBP)9 prospective observational studies: 9 prospective observational studies:
4856 events4856 events
Approximate mean usual BP(estimated from later remeasurements
in the Framingham Study)
Approximate mean usual BP(estimated from later remeasurements
in the Framingham Study)
BaselineDBP category
Usual SBPUsual DBP
BaselineDBP category
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
DBP)DBP)7 prospective observational studies: 7 prospective observational studies:
843 events843 events
Stroke and usual BPStroke and usual BP(in 5 categories defined by baseline (in 5 categories defined by baseline
DBP)DBP)7 prospective observational studies: 7 prospective observational studies:
843 events843 events
Approximate mean usual BP(estimated from later remeasurements
in the Framingham Study)
Approximate mean usual BP(estimated from later remeasurements
in the Framingham Study)
Relative Riskof Stroke
Relative Riskof Stroke
BaselineDBP category
Usual SBPUsual DBP
BaselineDBP category
Usual SBPUsual DBP
Collins R and McMahon S, British Medical Bulletin 1994Collins R and McMahon S, British Medical Bulletin 1994
Relative Riskof Stroke
Relative Riskof Stroke
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
Very high Very high added riskadded risk
Very high Very high added riskadded risk
High High added riskadded risk
Very high Very high added riskadded risk
Very high Very high added riskadded risk
High High added riskadded risk
High High added riskadded risk
Moderate Moderate added riskadded risk
Moderate Moderate 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
Grade 2Grade 2SBP 160-179 SBP 160-179
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
Very high Very high added riskadded risk
High High added riskadded risk
High High added riskadded risk
Moderate Moderate added riskadded risk
Average Average riskrisk
Low Low added riskadded risk
LowLowadded riskadded risk
Average Average riskrisk
NormalNormalSBP 120-129SBP 120-129
or DBP 80-84or DBP 80-84
High NormalHigh NormalSBP 130-139SBP 130-139
or DBP 85-89or DBP 85-89
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
Immediate drugImmediate drugtreatment and treatment and
lifestyle changeslifestyle changes
Immediate drugImmediate drugtreatment and treatment and
lifestyle changeslifestyle changes
Immediate drugImmediate drugtreatment and treatment and
lifestyle changeslifestyle changes
Immediate drugImmediate drugtreatment and treatment and
lifestyle changeslifestyle changes
Immediate drugImmediate drugtreatment and treatment and
lifestyle changeslifestyle changes
Drug treatmentDrug treatmentandand
lifestyle changeslifestyle changes
Drug treatmentDrug treatmentandand
lifestyle changeslifestyle changes
Lifestyle changesLifestyle changesfor several monthsfor several months
Then Then drug treatmentdrug treatment
Lifestyle changesLifestyle changesfor several monthsfor several months
Then Then drug treatmentdrug treatment
Lifestyle changesLifestyle changesfor several monthsfor several months
Then Then drug treatmentdrug treatment
Lifestyle changesLifestyle changesfor several monthsfor several months
Then drug Then drug treatment if treatment if
preferred by thepreferred by the patient and patient and
resources availableresources available
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
3 or more risk factors3 or more risk factorsor TOD or diabetesor TOD or diabetes
Associated clinical Associated clinical conditionsconditions
Grade 1Grade 1
SBP 140-159 SBP 140-159
or DBP 90-99or DBP 90-99
Grade 2Grade 2
SBP 160-179 SBP 160-179
or DBP 100-109or DBP 100-109
Grade 3Grade 3
SBP ≥ 180SBP ≥ 180
or DBP ≥ 110or DBP ≥ 110
Immediate drugImmediate drugtreatment and treatment and
lifestyle changeslifestyle changes
Drug treatmentDrug treatmentandand
lifestyle changeslifestyle changes
Drug treatmentDrug treatmentandand
lifestyle changeslifestyle changes
Lifestyle changesLifestyle changes
No BPNo BPinterventionintervention
LifestyleLifestylechangeschanges
LifestyleLifestylechangeschanges
No BPNo BPinterventionintervention
NormalNormal
SBP 120-129SBP 120-129
or DBP 80-84or DBP 80-84
High NormalHigh Normal
SBP 130-139SBP 130-139
or DBP 85-89or DBP 85-89
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)
Hazard Ratio (95% CI)Hazard Ratio (95% CI)0.83 (0.71-0.97)0.83 (0.71-0.97)0.83 (0.71-0.97)0.83 (0.71-0.97)0.83 (0.66-1.06)0.83 (0.66-1.06)
Hazard Ratio (95% CI)Hazard Ratio (95% CI)1.00 (0.83-1.21)1.00 (0.83-1.21)1.00 (0.83-1.20)1.00 (0.83-1.20)1.01 (0.76-1.35)1.01 (0.76-1.35)
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
ACE-I superiorACE-I superior Diuretics superiorDiuretics superior0.20.2 1.01.0 5.05.0
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
Very high Very high added riskadded risk
Very high Very high added riskadded risk
Very high Very high added riskadded risk
High High added riskadded risk
Very high Very high added riskadded risk
Very high Very high added riskadded risk
High High added riskadded risk
High High added riskadded risk
Moderate Moderate added riskadded risk
Moderate Moderate 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
ACCACC
Grade 1Grade 1SBP 140-159 SBP 140-159
or DBP 90-99or DBP 90-99
Grade 2Grade 2SBP 160-179 SBP 160-179
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
Very high Very high added riskadded risk
High High added riskadded risk
High High added riskadded risk
Moderate Moderate added riskadded risk
Average Average riskrisk
Low Low added riskadded risk
LowLowadded riskadded risk
Average Average riskrisk
NormalNormalSBP 120-129SBP 120-129
or DBP 80-84or DBP 80-84
High NormalHigh NormalSBP 130-139SBP 130-139
or DBP 85-89or DBP 85-89
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
Recommended