HYPERTENSION

SYAIFUL AZMI
Subdivision of Nephrology, Faculty of Medicine
Andalas University
Padang

Buku pegangan.
HARRISON

: INTERNAL MEDICINE

SUPARTONDO : ILMU OENYAKIT DALAM

NORMAN KAPLAN : CLINICAL
HYPERTENSION

Bahaya HIPERTENSI
(bila tdk dikendalikan)

Kerusakan pada Organ Target

LVH
Gagal
Jantung
PJK
Retinopati
(buta)

Stroke
Penyakit Ginjal
khronik
Gagal Ginjal
Terminal

Each mmHg BP reduction

lowers the cardiovascular risk
Meta-analysis of 61 prospective studies
1 million patients
12.7 million patient years
7%
2 mmHg
BP
reduction
(systolic)

Lewington S, et al. Lancet 2002;360:190313

risk reduction
CHD mortality

10%
risk reduction
stroke mortality

Implications of small reductions in DBP

for primary prevention
DBP reduction

7.5 mmHg

5-6 mmHg

-6

-10
Risk reduction (%)

2 mmHg

-15

-16

-20
-21
-30
-40
-50

-38

CHD
Stroke

-46

DBP, diastolic blood pressure; CHD, coronary heart

disease

Cook NR, et al. Arch Intern Med 1995;155:701-709

Section 1: Definition and Classification

of Hypertension

Definition and classification of

hypertension: ESH/ESC 2003
Hypertension is defined as blood pressure 140/90 mmHg
Category

Systolic

Diastolic

Optimal

(mmHg)
<120

(mmHg)
<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

When a patients systolic and diastolic blood pressures fall into different
categories, the higher category should apply

ESH/ESC Guidelines 2003

J Hypertens 2003;21:1011-1053

Definition and classification of

hypertension: JNC VII
Hypertension is defined as blood pressure 140/90 mmHg
Category

Systolic

Diastolic

(mmHg)

(mmHg)

<120

and <80

Pre hypertension

120-139

or 80-89

Stage 1 hypertension

140-159

or 90-99

Stage 2 hypertension

160

or 100

Normal

JNC VII. JAMA 2003;289:2560-2572

Definition and classification of

hypertension: WHO/ISH 1999/2003
Hypertension is defined as blood pressure 140/90 mmHg
Category

Systolic

Diastolic

(mmHg)

(mmHg)

Optimal

<120

<80

Normal

<130

<85

High-normal

130-139

85-89

Grade 1 hypertension (mild)

140-159

or 90-99

140-149

90-94

160-179

or 100-109

Grade 3 hypertension (severe)

180

or 110

Isolated systolic hypertension

140

<90

140-149

<90

Subgroup: borderline
Grade 2 hypertension (moderate)

Subgroup: borderline
When a patients systolic and diastolic blood pressures fall
into different categories, the higher category should apply

2003 WHO/ISH Statement on Hypertension.

J Hypertens 2003;21:1983-1992; 1999 WHO/ISH Guidelines for the
Management of Hypertension. J Hypertens 1999;17:151-183

Section 2: Prevalence of Hypertension

Prevalence of hypertension*:
North America and Europe
80
Prevalence (%)

70
60

Men
Women
Total

50
40
30
20
10
an
y

G
er
m

nd
nl
a
Fi

in
Sp
a

Sw
ed
en
En
gl
an
d

Ita
ly

Eu
ro
pe

ad
a
C
an

U
ni

te
d

St
at
es

* BP 140/90 mmHg or treatment with antihypertensive medication

Wolf-Maier K, et al. JAMA 2003;289:2363-2369

Men
Women
Total

20
Ta
01
iw
)
an
H
(1
on
99
g
4)
Ko
ng
Si
(1
ng
99
ap
7)
or
e
(1
M
99
al
8)
ay
si
a
(1
Th
99
ai
6)
la
nd
Ph
(1
il ip
99
pi
1)
ne
s
(1
In
99
do
9)
ne
In
s
ia
di
a
(1
(M
99
um
4)
ba
i,
Ja
19
pa
99
n
)
(1
99
295
)

80
70
60
50
40
30
20
10
0

hi

na

(2
0

00
/

Prevalence (%)

Prevalence of hypertension: Asia

Gu DF, et al. Hypertension 2002;40:920-927; Singh RB, et al. J Hum Hypertens 2000;14:749-763; Janus ED. Clin Exp Pharmacol Physiol
1997;24:987-988; National Health Survey 1998, Singapore. Epidemiology and Disease Department, Ministry of Health, Singapore.; Lim TO, et al.
Singapore Med J 2004;45:20-27; Tatsanavivat P, et al. Int J Epidemiol 1998;27:405-409; Muhilal H. Asia Pacific J Clin Nutr 1996;5:132-134;
Gupta R. J Hum Hypertens 2004;18:73-78; Asai Y, et al. Nippon Koshu Eisei Zasshi 2001;48:827-836 [in Japanese]

Prevalence of hypertension:
Other countries
80

Men
Women
Total

60
50
40
30
20
10

)
99
6
Is
ra

el

(1

(2
bi
a
C
ol
om

ad

or
(

20
0

00
2

0)

Ec
u

Prevalence (%)

70

Ordunez P, et al. Pan Am J Public Health 2001;10:226-231;

Cubillos-Garzon LA, et al. Am Heart J 2004;147:412-417; Amad S, et al. J Hum Hypertens 1996;10:S31-S33

TABEL 4 Prevalensi Hipertensi Pada Populasi,

Obese, TGT dan DM di SumBar 2005
N
O

KOTA

POPULASI
(%)

OBESE

TGT

DM

1 P.Panjang

22.3

(%)

22.4

(%)

26.3

(%)

33.3

2 Bt.Sangkar

23.4

23.4

32.5

42.2

3 Solok

26.1

24.6

33.3

41.2

4 Pariaman

22.9

22.2

35.6

40.0

5 Payakumbuh

19.1

17.6

326.6

18.4

6 Painan

16.0

17.7

36.4

29.4

7 Bukittinggi

26.6

37.6

38.2

28.6

8 Padang
RERATA

11.8
21.1

12.0
22.2

25.3
30.4

23.1
30.0

Section 3 : Classification of
hypertension

CLASSIFICATION
PRIMARY ( 90 % )
SECUNDARY ( 10 % )
renovascular hypertension
renal parenchymal hypertension
hypertension with pregnancy
pheochromocytoma
primary aldosteronemia
drug induced or related causes
JNC 7 2003, Caplan, clinical hypertension 2002

Section 4 : Risk factors of

Hypertension

Table Cardiovaskuler risk factors

Major Risk Factors
Hypertension*
Cigarette* (body mass index 30 kg/m2)
Physical inactivity
Dislipidemia*
Diabetes mellitus*
Microalbuminuria or estimated GFR < 60 mL/min
Age (older than 55 for men, 65 for women)
Family history of premature cardiovascular disease (men under age 55 or women under age 65)

Target Organ Damage

Heart
Left ventricular hypertrophy

Angina or prior myocardial infarction

Prior coronary revascularization

Heart failure

Brain
Stroke or transient ischemic attack

Chronic kidney disease

Peripheral arterial disease
Retinopathy
GFR, glomerular filtration rate
* Components of the metabolic syndrome

JNC VII 2003

Risk factors
Gender
Race
Age
Family history
Cigarette smoking
Obesity ( BMI 30 Kg/m2 )*
Physical activity
Dyslipidemia*
Diabetes Mellitus*
Microalbuminuria

componen of metabolic syndrome

JNC 7 2003

Section 5 : Pathophysiology and

Pathogenesis of Hypertension

PATHOPHYSIOLOGY OF HYPERTENSION
Several hypothesis exists of the original pathogenesis
of hypertension
- Excess Na intake
- Renal Na retention
- RAS
- Stress & sympathetic activity
- Peripheral resistance
- Endothelial dysfunction
- Obesity
- Insulin resistance

Pathogenesis hipertensi
( Kaplan N, 2002 )

Renin-angiotensin-aldosterone system
(-)

Angiotensinogen
Renin
Angiotensin I

Angiotensinconverting
enzyme

Angiotensin II

BP

BP, blood pressure

AT1

Vasoconstriction
Aldosterone secretion
Catecholamine release
Proliferation
Hypertrophy

Bradykinin

Inactive kinins

AT2

Vasodilation
Inhibition of cell growth
Cell differentiation
Injury response
Apoptosis
Ellis ML, et al. Pharmacotherapy 1996;16:849-860;
Carey RM, et al. Hypertension 2000;35:155-163

Section 6 : Diagnosis of Hypertension

SYMPTOMS
Headache
Nocturia
Palpitation
Dizziness
Tinitus
Epistaxis

Kaplan N , 2002

PHYSICAL EXAMINATION

27

TABLE. IMPORTANT ASPECTS OF THE PHYSICAL

EXAMINATION
ACCURATE MEASUREMENT OF BLOOD PRESSURE
GENERAL APPEARANCE : DISTRIBUTION OF BODY FAT,
SKIN LESSION,MUSCLESTRENGTH.

FUNDUSCOPY.
NECK : PALPATION AND AUSCULTATION OF CAROTIDS, THYROID.
HEART : SOUND, RHYTHM, SIZE.
LUNG : RALES.
ABDOMEN : RENAL MASSES, BRUIT OVER AORTA OR RENAL
ARTERIES, FEMORAL PULSES, WAIST CIRCUMFERENCE.

EXTREMITIES : PERIPHERAL PULSES, EDEMA.

NEUROLOGIC ASSESSMENT, INCLUDING COCNITIVE
FUNCTION.

LABORATORY TEST
ROUTINE LAB WORK UP
RISK FACTORS : BLOOD SUGAR, LIPID

PROFILE, ELECTROLYTES.

LAB OF TARGET ORGAN DEMAGE

PLASMA INSULIN, PLASMA RENIN
ACTIVITY

FUNDUSCOPY EXAMINATION :
RETINOPATHY
CARDIAC ASSESSMENT : LVH, ARYTHMIA
CEREBRAL ASSESSMENT :
ENCEPHALOPATHY
RENAL ASSESSMENT

Section 7 : Treatment Guidelines

Table Lifestyle modifications to manage hypertension *

Modification

Recommendation

Approximate SBP
Reduction (range)

Weight reduction
Adopt DASH eating plan

Maintain normal body weight (body mass

index 18.5-24.9 kg/m2)

5-20 mmHg/10 kg weight

loss23-24

Consume a diet rich in fruits, vegetables, 8-14 mmHg25-26

and lowfat dairy products with a reduced
content of saturated and total fat
Dietary sodium reduction
Reduce dietary sodium intake to no more 2-8 mmHg25-27
than 100 mmol per day (2.4 g sodium or
6 g sodium chloride)
Physical activity
Engage in regular aerobic physical
4-9 mmHg26-27
activity such as brisk walking (at least 30
min per day, most days of the week0
Moderation of alcohol
Limit consumption to no more than 2
2-4 mmHg30
consumption
drinks ( 1 oz or 30 mL ethanol; e.g., 24
oz beer, 10 oz wine, or 3 oz 80-proof
whiskey) per day in most men and to no
more than 1 drink per day in women and
DASH, Dietary Approaches to Stop Hypertension.
*
For overall cardiovascular risk reduction, stop smoking.
lighterareweight

The effects of implementing these modifications

dose and persons
time dependent, and could be greater for some individuals
JNC VII 2003

THE IDEAL ANTIHYPERTENSIVE AGENT

- Effectively reduces BP
- Maintains BP control over 24 hours with oncea-day dosing
- Effective in all hypertensive patients
- No adverse effects
- No negative metabolic side effects

History of antihypertensive drugs

Effectiveness and general tolerability

1940s

1950

1957

1960s

Alphablockers

Direct
vasodilators
Peripheral
sympatholytics
Ganglion
blockers
Veratrum
alkaloids

1970s

Thiazide
diuretics

Central 2
agonists

Calcium
antagonistsnon-DHPs
Betablockers

1980s

ARBs
ACE
inhibitors

Calcium
antagonistsDHPs

DHP, dihydropyridine;
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker

1990s

2000

Multiple antihypertensive agents

are needed to achieve target BP
Trial

Number of antihypertensive agents

Target BP (mmHg) 1
2
3
4

UKPDS

DBP <85

ABCD

DBP <75

MDRD

MAP <92

HOT

DBP <80

AASK

MAP <92

IDNT

SBP <135/DBP <85

ALLHAT SBP <140/DBP <90

DBP, diastolic blood pressure; MAP, mean arterial pressure;

SBP, systolic blood pressure

Bakris GL, et al. Am J Kidney Dis 2000;36:646-661;

Lewis EJ, et al. N Engl J Med 2001;345:851-860;
Cushman WC, et al. J Clin Hypertens 2002;4:393-404

Main classes of antihypertensive drugs

Diuretics
Inhibit the re absorption of salts and water from kidney
tubules into the bloodstream

Calcium-channel antagonists
Inhibit influx of calcium into cardiac and smooth muscle

Beta-blockers

Inhibit stimulation of beta-adrenergic receptors

Angiotensin-converting enzyme (ACE) inhibitors

Inhibit formation of angiotensin II

Angiotensin II receptor blockers (ARBs)

Inhibit binding of angiotensin II to type 1 angiotensin II
receptors

Clinical trial and guideline basis for compelling indications for individual drug
classes
COMPELLING INDICATION
Heart failure

RECOMMENDED DRUGS+
DIURETIC

Postmyocardial infarction

BB

ACEI

ARB

High coronary disease risk

Diabetes

Chronic Kidney disease

Recurrent stroke prevention

CCB

ALDO ANT

CLINICAL TRIAL BASIS+

ACC/AHA Heart Failure Guideline,40 MERIT-HF, 41 COPERNICUS,42 CIBIS,43 SOLVD,44 AIRE,45

TRACE,44 ValHEFT,47 RALES48

ACC/AHA post-MI Guideline,49

BHAT,50 SAVE,51 Capricorn,52
EPHESUS,53

ALLHAT,33 HOPE,34 ANBP2,36

LIFE,32 CONVINCE31

NKF-ADA Guideline,31,32 UKPDS,34

ALLHAT33
NKF Guideline,22 captopril Trial,55
RENALL,56 IDNT,57 REIN,58 AASK59
PROGRESS35

JNC VII , 2003

Compeling indications for antihypertensive drugs are based on benefits from outcome studies or existing
clinical guidelines; the compelling indications is managed in parallel with the BP
+ Drug abbreviations; ACEI, angiotensin converting enzyme inhibitor; ARB,angiotensin receptor blicker;
Aldo ANT, aldosterone antagonist; BB, beta-blocker; CCB, calcium channel blocker
Conditions for which trials demonstrate benefit of specific classes of antihypertensive drugs.

Treatment strategy: WHO/ISH 2003

Compelling indication

Preferred drug

Elderly with isolated systolic

hypertension
Renal disease

Diuretic, DHPCCB

Diabetic nephropathy type 1

ACE-I

Diabetic nephropathy type 2

ARB

Non-diabetic nephropathy

ACE-I

Cardiac disease
Post-myocardial infarction

ACE-I, beta-blocker

Left ventricular dysfunction

ACE-I

Congestive heart failure (diuretics

almost always included)
Left ventricular hypertrophy

Beta-blocker,
spironolactone
ARB

Cerebrovascular disease

ACE-I + diuretic, diuretic

DHPCCB, dihydropyridine calcium-channel blocker;

ACE-I, angiotensin-converting enzyme inhibitor;
ARB, angiotensin II receptor blocker; CCB, calcium-channel blocker

2003 WHO/ISH Statement on Hypertension.

J Hypertens 2003;21:1983-1992

Treatment initiation: JNC VII

Lifestyle
modification

Normal

Prehypertension

Stage 1
hypertension

Stage 2
hypertension

Encourage

Yes

Yes

Yes

Initial drug therapy

Without
compelling
indication

No antihypertensive drug
indicated

With
compelling
indications

Drug(s) for compelling

indications

ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II

receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker

Thiazide-type
diuretics for most;
may consider
ACE-I, ARB, BB,
CCB, or
combination

Two-drug
combination for
most (usually
thiazide-type
diuretic and
ACE-I or ARB
or BB
or CCB)
Drug(s) for compelling
indications;
other antihypertensive drugs
(diuretics, ACE-I, ARB, BB, CCB)
as needed
JNC VII. JAMA 2003;289:2560-2572

Goals of treatment: JNC VII

The SBP and DBP targets are
<140/90 mmHg
The primary focus should be on achieving the
SBP goal
In patients with hypertension and diabetes or
renal disease, the BP goal is <130/80 mmHg

SBP, systolic blood pressure; DBP, diastolic blood pressure;

BP, blood pressure

JNC VII. JAMA 2003;289:2560-2572

Hypertension treatment strategy: JNC VII

Lifestyle modifications
Not at goal blood pressure (<140/90 mmHg)
(<130/80 mmHg for patients with diabetes or chronic kidney disease)
Initial drug choices
Without compelling
indications
Stage 1 hypertension
(SBP 140-159 or DBP
90-99 mmHg)
Thiazide-type diuretics
for most. May consider
ACE-I, ARB, BB, CCB
or combination

Stage 2 hypertension
(SBP 160 or DBP 100 mmHg)
Two-drug combination for
most (usually thiazide-type
diuretic and ACE-I or
ARB, or BB, or CCB)

With compelling
indications
Drug(s) for the
compelling indications
Other antihypertensive
Drugs (diuretics, ACE-I,
ARB, BB, CCB) as needed

Not at blood pressure goal

Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
SBP, systolic blood pressure; DBP, diastolic blood pressure; ACE-I,
angiotensin-converting enzyme inhibitor; ARB, angiotensin II
receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker

JNC VII. JAMA 2003;289:2560-2572

Circumstances in which ACE Inhibitors and ARBs Should Not Be

Used
Do Not Use
ACE Inhibitor

Pregnancy(A)
History of angioedema (A)
Cough due to ACE inhitors (A)
Allergy to ACE or ARB (A)

ARB

Allergy to ACE inhibitor or ARB (A)

Pregnancy (C)
Cough dua to ARB (C)

Use with Caution

Women not practicing contraception (A)
Bilateral renal artery stenosis*
Drugs causing hyperkalemia (A)

Bilateral renal artery stenosis*

Drugs causing hyperkalemia (A)
Women not practicing contraception (C)
Angioedema due to ACE inhibitors (C)
K-DOQI AJKD, 2004

* Including renal artery stenosis in the kidney transplant or in a solitary kidney.

Letters in parentheses denote strength of recommendations.

Diuretik : Hati hati pada :

- gangguan elektrolit
- dislipidemia
Beta bloker hati hati pada :
- Asma bronkhial / spasme bronkhus
- Diabetes melitus

nokomen