lessandro Antonelli: CONTROLLO OTTIMALE DELLA PRESSIONE ARTERIOSA dal congresso di Foligno del Gruppo Ipertensione della SIN

1. Dr. A.Antonelli SIN GI
CONTROLLO OTTIMALE DELLA
PRESSIONE ARTERIOSA
Alessandro Antonelli
U.O Nefrologia
Ospedale Campo di Marte - Lucca
2° Corso Interattivo di Aggiornamento
sulla “Ipertensione Arteriosa”
IL DANNO D’ORGANO
Foligno, 23-24 Ottobre 2003
Dr. A.Antonelli SIN GI
Da oltre cento anni, da quando
l’ipertensione fu chiaramente distinta
dalla Malattia di Bright, si discute sul
livello di pressione arteriosa da
considerare patologico
• “ Non esiste
una vera demarcazione. Quanto più è elevata la
pressione, tanto peggiore è la prognosi “ Pickering 1972
• “L’ipertensione è il livello al quale i benefici dell’intervento
superano quelli dell’astensione “ Rose 1980
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2. Dr. A.Antonelli SIN GI
“ L’Ipertensione arteriosa è il
livello di pressione per il quale i
benefici (meno i rischi ed i costi )
dell’azione sono superiori ai rischi e
ai costi
( meno i benefici )
dell’astensione “
Kaplan 1998
Dr. A.Antonelli SIN GI
Prevalenza ipertensione %
Prevalenza di ipertensione arteriosa
in rapporto ad età e razza negli USA
Maschi
80
70
60
50
Neri
Bianchi
Ispanici
40
30
20
10
0
18-29
30-39
40-49
50-59
Età anni
60-69
70-79
> 80
NHANES III, Hypertension 1995
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3. Dr. A.Antonelli SIN GI
Prevalenza ipertensione %
Prevalenza di ipertensione arteriosa
in rapporto ad età e razza negli USA
Femmine
90
80
70
60
50
40
30
Neri
Bianchi
Ispanici
20
10
0
18-29
30-39
40-49
50-59
60-69
70-79
Età anni
> 80
NHANES III, Hypertension 1995
Dr. A.Antonelli SIN GI
50
Cardiopatia
ischemica
normotesi
N° eventi/2anni/1000 persone
ipertesi
40
30
20
Scompenso
cardiaco
Arteriopatie
periferiche
Ictus
10
0
OR
M
F
22.7-11.8
M
9.1-3.8
F
M
F
4.9-5.3
M
F
10.4-4.2
Kannel WB, JAMA 1996
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4. Dr. A.Antonelli SIN GI
Multiple Risk Factor Intervention Trial
Causes of death, RR
3,5
3,2
3
2,5
2,5
2
3,0
2,8
2,3
1,5
1
0,5
0
All
deaths
CHD
Stroke
Other
CVDs
All CV
deaths
Stamler J. et al., Diabetes Care, 1993
Dr. A.Antonelli SIN GI
Riduzione percentuale dei tassi di
mortalità corretti per l’età negli USA
%
1972
1975
1980
1985
1990
1995
10
0
-10
Malattie non CV
-20
-30
-40
-50
Ictus
Cardiopatia
Ischemica
-60
-70
National Center for Health Statistics, 1997
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5. Dr. A.Antonelli SIN GI
Trials exploring the
optimal drug
Trials comparing more
intensive and less
intensive blood
pressure lowering
strategies
Dr. A.Antonelli SIN GI
Prospectively designed overviews of randomised trials
Trials comparing more intensive and less intensive blood
pressure lowering strategies
ABCD-hypert
HOT
UKPDS-HDS
SBP
-6
-3
-10
DBP
-8
-3
-5
follow-up
5
4
8
Blood Pressure Lowering Treatment Trialist’ Collaboration, The Lancet, 356, 2000
5

6. Dr. A.Antonelli SIN GI
Prospectively designed overviews of randomised trials
Trials comparing more intensive and less intensive blood
pressure lowering strategies
Stroke
0.80 (0.65-0.98)
CHD
0.81 (0.67-0.98)
HF
0.78 (0.53-1.15)
Major CV events
0.85 (0.76-0.96)
CV deaths
0.90 (0.75-1.09)
Total mortality
0.97 (0.85-1.11)
0.5
1
Favours more
intensive
Relative risk
2
Favours less
intensive
Blood Pressure Lowering Treatment Trialist’ Collaboration, The Lancet, 356, 2000
Dr. A.Antonelli SIN GI
HOT Study: Significant Benefit from
Intensive Treatment in the Diabetic Subgroup
25
20
Major
cardiovascular 15
events/1,000
patient-years
10
p = 0.005 for trend
5
0
≤ 90
≤ 85
≤ 80
mmHg
Target Diastolic Blood Pressure
Hansson L et al. Lancet 1998;351:1755-1762.
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7. Dr. A.Antonelli SIN GI
Trials exploring the
optimal drug
Trials comparing
active treatment and
placebo
Dr. A.Antonelli SIN GI
Prospectively designed overviews of randomised trials
ACE-inhibitor-based therapy vs placebo
HOPE
PART2
QUIET
SCAT
SBP
-3
-6
---4
DBP
-1
-4
---3
follow-up
5
4
2
5
Blood Pressure Lowering Treatment Trialist’ Collaboration, The Lancet, 356, 2000
7

8. Dr. A.Antonelli SIN GI
Prospectively designed overviews of randomised trials
ACE-inhibitor-based therapy vs placebo
Stroke
0.70 (0.57-0.85)
CHD
0.80 (0.72-0.89)
HF
0.84 (0.68-1.04)
Major CV events
0.79 (0.73-0.86)
CV deaths
0.74 (0.64-0.85)
Total mortality
0.84 (0.76-0.94)
0.5
1
Favours ACEs
Relative risk
2
Favours placebo
Blood Pressure Lowering Treatment Trialist’ Collaboration, The Lancet, 356, 2000
Dr. A.Antonelli SIN GI
Effects of ramipril on cardiovascular and microvascular
outcomes in people with diabetes mellitus: results of the
HOPE study and MICRO-HOPE substudy.
combined
primary
0
-5
myocardial stroke
cardio-
infarction
vascular mortality
outcome
25%
total
revascularization
death
22%
33%
37%
overt
nephro-
heart
failure
pathy
24%
17%
24%
20%
-10
-15
p=0.031
-20
-25
-30
-35
-40
%
p=0.019
p=0.01
p=0.004
p=0.000
4
p=0.0074
p=0.027
p=0.0001
HOPE Study Investigators, The Lancet, 2000
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9. Dr. A.Antonelli SIN GI
Prospectively designed overviews of randomised trials
Calcium-antagonist-based therapy vs placebo
PREVENT
SYST-EUR
SBP
-5
-10
DBP
-4
-5
follow-up
3
2
Blood Pressure Lowering Treatment Trialist’ Collaboration, The Lancet, 356, 2000
Dr. A.Antonelli SIN GI
Prospectively designed overviews of randomised trials
Calcium-antagonist-based therapy vs placebo
Stroke
0.61 (0.44-0.85)
CHD
0.79 (0.50-1.06)
HF
0.72 (0.48-1.07)
Major CV events
0.72 (0.59-0.87)
CV death
0.72 (0.52-0.98)
Total mortality
0.87 (0.70-1.09)
0.5
Favours CCBs
1
Relative risk
2
Favours placebo
Blood Pressure Lowering Treatment Trialist’ Collaboration, The Lancet, 356, 2000
9

10. Dr. A.Antonelli SIN GI
Prospectively designed overviews of randomised trials
ACE-inhibitors vs
Calcium antagonists:
a comparison “at
distance”
Stroke
CHD
HF
Major CV events
CV death
Total mortality
0.5
Favours ACEc/CCBs
1
Relative risk
2
Favours placebo
Blood Pressure Lowering Treatment Trialist’ Collaboration, The Lancet, 356, 2000
Dr. A.Antonelli SIN GI
Cause principali di nuovi casi di ESRD negli
USA (1997)
Glomerulonefriti
9%
Altre cause
Altre cause 10%
urologiche
2%
Cisti
2%
Diabete
43%
Cause non
note
9%
Ipertensione
25%
USRDS 1999
Renal Data Report
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11. Dr. A.Antonelli SIN GI
Ruolo dell’ipertensione arteriosa nel
determinare il danno renale
Ipertensione arteriosa
(stadio III)
Ipertensione arteriosa
(stadio I- II)
Fino a 10 anni fa
prevaleva l’idea che
fosse una situazione
innocua per il rene
Ben documentato
Dr. A.Antonelli SIN GI
<100
80
100-110
60
%
>110
40
0
2
4
Time, years
6
8
MAP, mmHg
Probability of survival
100
10
Renal survival probability in 423 patients with non diabetic renal
disease and chronic renal failure
Oldrizzi L, Am J Kidney Dis 1993
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12. Dr. A.Antonelli SIN GI
% Ipertesi in Trattamento
% Ipertesi Controllati
Controllati
24%
47%
53%
29%
Non controllati
Non trattati
Trattati
Burt et al; Hypertension 95
Dr. A.Antonelli SIN GI
Qual’ è la prevalenza del controllo
ottimale dell’ipertensione arteriosa in
Italia ?
1 - 50%
2 - 32%
3 - 24%
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13. USA
Canada
27 %
Italia
24 %
Germania
Dr. A.Antonelli SIN GI
Australia
16 %
Inghilterra
India
9 %
Finlandia
22.5 %
19 %
9 %
Spagna
20.5 %
20 %
Marques Am J Hypertens 2000
Dr. A.Antonelli SIN GI
Stratification of Risk to Quantify Prognosis
1999 WHO-ISH Guidelines for the Managenent of Hypertension
Other Risk Factors &
Disease History
Grade 1
(mild)
Grade 2
(moderate)
Grade 3
(severe)
SBP 140-159 or
DBP 90-99
SBP 160-179 or
DBP 100-109
SBP >180 or
DBP >110
I.
no other risk factors
LOW RISK
MED RISK
HIGH RISK
II.
1-2 risk factors
MED RISK
MED RISK
V HIGH RISK
HIGH RISK
HIGH RISK
V HIGH RISK
V HIGH RISK
V HIGH RISK
V HIGH RISK
III. 3 or more risk factors
or TOD or diabetes
IV.
ACC
TOD - Target Organ Damage
ACC - Associated Clinical Conditions, including clinical CVD or renal disease
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14. Dr. A.Antonelli SIN GI
Stratification of Risk to Quantify Prognosis
1999 WHO-ISH Guidelines for the Managenent of Hypertension
Other Risk Factors &
Disease History
Grade 1
(mild)
Grade 2
(moderate)
SBP 140-159 or SBP 160-179 or
DBP 90-99
DBP 100-109
Grade 3
(severe)
SBP >180 or
DBP >110
I.
no other risk factors
Lifestyle 12
Drug therapy
Drug therapy
II.
1-2 risk factors
Lifestyle 6
Drug therapy
Drug therapy
III. 3 or more risk factors
or TOD or diabetes
Drug therapy
Drug therapy
Drug therapy
IV.
Drug therapy
Drug therapy
Drug therapy
ACC
TOD - Target Organ Damage
ACC - Associated Clinical Conditions, including clinical CVD or renal disease
Dr. A.Antonelli SIN GI
Stratification of Risk to Quantify Prognosis
1999 WHO-ISH Guidelines for the Managenent of Hypertension
Other Risk Factors &
Disease History
HighNormal
Grade 1
(mild)
Grade 2
(moderate)
Grade 3
(severe)
Drug therapy
SBP 130-139 SBP 140-159 or SBP 160-179 or SBP >180 or
DBP 85-89
DBP 90-99
DBP 100-109
DBP >110
I.
no other risk factors
Lifestyle
Lifestyle 12
Drug therapy
II.
1-2 risk factors
Lifestyle
Lifestyle 6
Drug therapy Drug therapy
III. 3 or more risk factors
or TOD or diabetes
Drug therapy
Drug therapy
Drug therapy Drug therapy
IV.
Drug therapy
Drug therapy
Drug therapy Drug therapy
ACC
TOD - Target Organ Damage
ACC - Associated Clinical Conditions, including clinical CVD or renal disease
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15. Dr. A.Antonelli SIN GI
Stratification of Risk to Quantify Prognosis
European Society of Hypertension Guidelines 2003
Altri fattori di rischio
e anamnesi
I.no other risk factors
Normale
Normale alta
Grado 1
Grado 2
PAS 120-129 PAS 130-139 PAS 140-159 PAS 160-179
o PAD 80-84
RANGE RISK
o PAD 85-89
RANGE RISK
LOW RISK
MED RISK
LOW RISK
MED RISK
MED RISK
II.1-2 risk factors
LOW RISK
III.3 or more risk factors
or TOD or diabetes
MED RISK
HIGH RISK
IV ACC
HIGH RISK
V HIGH RISK
Grado 3
PAS >180
o PAD 90-99 o PAD 100-109 DBP >110
HIGH RISK
V HIGH RISK
HIGH RISK
V HIGH RISK
HIGH RISK
V HIGH RISK
V HIGH RISK
V HIGH RISK
TOD - Target Organ Damage
ACC - Associated Clinical Conditions, including clinical CVD or renal disease
Dr. A.Antonelli SIN GI
Soglia di
intervento
Obiettivi del
trattamento
PAS
PAD
PAS
PAD
National Joint Committee VI
1997
In presenza di proteinuria>1g/24h
130
85
<130
<125
<85
<75
Italian Hypertension Guidelines
140
90
<130
<85
140
90
140
90
<130
<130
<125
<135
<125
<85
<80
<75
<85
<75
140
90
<130
<80
1999
World Health Organization &
International Society of Hypertens 1999
In presenza di proteinuria<1g/24h
In presenza di proteinuria>1g/24h
German Hypertension Guidelines
In presenza di proteinuria>1g/24h 2002
American Diabetes Association
2002
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16. Dr. A.Antonelli SIN GI
Quali sono i valori ottimali della
pressione arteriosa secondo i
criteri del JNC VII ?
1 - < 129/84 mmHg
2 - < 120/80 mmHg
3 - < 140/90 mmHg
Dr. A.Antonelli SIN GI
The Seventh report of the Joint National Committee
on Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure
Classification and Management of Blood Pressure
Normal
With
compelling
indications
Stage 1
Hypertension
Stage 2
hypertension
SBP <120
DBP <80
Lifestyle
modification
Prehypertension
SBP 120-139
DBP 80-89
SBP 140-159
DBP 90-99
SBP >159
DBP >99
Encourage
Yes
Yes
Yes
Drug(s) for the
compelling
indications
Drug(s) for the
compelling
indications
Drug(s) for the
compelling
indications
The JNC 7 Report, JAMA 289: 2560-2572, 2003
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17. Dr. A.Antonelli SIN GI
The Seventh report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure
Compelling Indications for Individual Drug Classes
High-Risk
Conditions with
compelling
indications
Diuretic
ß-Blocker
ACE
inhibitor
ARB
CCB
Aldosterone
antagonist
Heart failure
Post-myocardial
infarction
High coronary
disease risk
DIABETES
Chronic kidney
disease
Recurrent
stroke
prevention
The JNC 7 Report, JAMA 289: 2560-2572, 2003
Dr. A.Antonelli SIN GI
Quali dei seguenti sono fattori
utilizzati per la stratificazione del
rischio cardiovascolare ?
1
2
3
4
5
6
- Dislipidemia
- Abitudine al fumo
- Microalbuminuria
- Obesità addominale
- Nefropatia Diabetica
- Proteina C Reattiva
17

18. Dr. A.Antonelli SIN GI
Factors influencing prognosis
Risk factors for cardiovascular disease used for
stratification
• Levels of systolic and diastolic BP
• Men >55 years
• Women > 65 years
• Smoking
• Dyslipidaemia
(total cholesterol >6.5 mmol/l, >250 mg/dl,
or LDL-cholesterol > 4.0 mmol/l, >155 mg/dl,
or HDL-cholesterol M < 1.0,W < 1.2 mmol/l,
M < 40,W < 45 mg/dl)
• Family history of premature cardiovascular disease
(at age < 55 years M, < 65 years W)
• Abdominal obesity
(abdominal circumference M > 102 cm, W> 88 cm)
• C-reactive protein >1 mg/dl
TARGET ORGAN DAMAGE
Dr. A.Antonelli SIN GI
• Left ventricular hypertrophy
(electrocardiogram:
Sokolow–Lyons .38 mm; Cornell .2440 mm_ms;
echocardiogram:
LVMI M > 125, W> 110 g/m2)
• Ultrasound evidence of arterial wall thickening
(carotid IMT > 0.9 mm) or atherosclerotic
plaque
• Slight increase in serum creatinine
(M 115–133,W 107– 124 _mol/l;
M 1.3–1.5,W1.2–1.4 mg/dl)
• Microalbuminuria
(30–300 mg/24 h; albumin–creatinine
ratio M > 22,W >31 mg/g;
M > 2.5,W > 3.5 mg/mmol)
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19. Clinical Conditions Associated
Dr. A.Antonelli SIN GI
• Cerebrovascular disease:
ischaemic stroke;
cerebral haemorrhage;
transient ischaemic attack
• Heart disease:
myocardial infarction;
angina;
coronary revascularization;
congestive heart failure
• Renal disease:
diabetic nephropathy;
renal impairment
(serum creatinine M >133, W>124 umol/l;M
>1.5,W>1.4 mg/dl)
proteinuria (>300 mg/24 h)
• Peripheral vascular disease
• Advanced retinopathy:
haemorrhages or exudates,
papilloedema
CONCLUSIONI
Hypertension:
Dr. A.Antonelli SIN GI
“test of vascular health”
“important target in the prevention of
cardiovascular disease”
T.D. Giles New York ASH 15/5/2003
• Le nostre conoscenze sull’ipertensione arteriosa sono
notevolmente aumentate negli anni ed è il momento di
valorizzarle trasformandole in comportamenti di buona
pratica clinica.
• Le linee guida diagnostiche terapeutiche delle diverse
comunità scientifiche rappresentano una ulteriore risorsa
per raggiungere il controllo ottimale della pressione
arteriosa.
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