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
Stroke
PJK

Retinopati Penyakit Ginjal

khronik
(buta)
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%
risk reduction
CHD mortality
2 mmHg
BP
reduction 10%
(systolic) risk reduction
stroke mortality

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

 Implications of small reductions in DBP
for primary prevention
DBP reduction

7.5 mmHg 5-6 mmHg 2 mmHg

0

-10 -6
Risk reduction (%)

-16 -15
-20
-21

-30

-40 CHD
-38
Stroke

-50 -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
(mmHg) (mmHg)
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

When a patients systolic and diastolic blood pressures fall into different ESH/ESC Guidelines 2003
categories, the higher category should apply 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)
Normal <120 and <80

Pre hypertension 120-139 or 80-89

Stage 1 hypertension 140-159 or 90-99

Stage 2 hypertension 160 or 100

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
Subgroup: borderline 140-149 90-94
Grade 2 hypertension (moderate) 160-179 or 100-109
Grade 3 hypertension (severe) 180 or 110
Isolated systolic hypertension 140 <90
Subgroup: borderline 140-149 <90

2003 WHO/ISH Statement on Hypertension.

When a patients systolic and diastolic blood pressures fall J Hypertens 2003;21:1983-1992; 1999 WHO/ISH Guidelines for the
into different categories, the higher category should apply Management of Hypertension. J Hypertens 1999;17:151-183
Section 2: Prevalence of Hypertension
 Prevalence of hypertension*:
North America and Europe
80
Men
70 Women
Prevalence (%)

60 Total
50
40
30
20
10
0

* BP 140/90 mmHg or treatment with antihypertensive medication Wolf-Maier K, et al. JAMA 2003;289:2363-2369
 Prevalence of hypertension: Asia

80
Men
70
Prevalence (%)

Women
60
Total
50
40
30
20
10
0

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
70 Women
Prevalence (%)

60 Total
50
40
30
20
10
0

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 KOTA POPULASI OBESE TGT DM

O (%) (%) (%) (%)
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 11.8 12.0 25.3 23.1

RERATA 21.1 22.2 30.4 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 Bradykinin
Angiotensin-
converting
enzyme
Angiotensin II Inactive kinins

BP AT1 AT2
Vasoconstriction Vasodilation
Aldosterone secretion Inhibition of cell growth
Catecholamine release Cell differentiation
Proliferation Injury response
Hypertrophy Apoptosis
Ellis ML, et al. Pharmacotherapy 1996;16:849-860;
BP, blood pressure 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 Maintain normal body weight (body mass 5-20 mmHg/10 kg weight
index 18.5-24.9 kg/m2) loss23-24

Adopt DASH eating plan
Dietary sodium reduction
Physical activity
Moderation of alcohol
consumption
Consume a diet rich in fruits, vegetables, 8-14 mmHg25-26
and lowfat dairy products with a reduced
content of saturated and total fat
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)
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
Limit consumption to no more than 2 2-4 mmHg30
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
lighter weight persons

DASH, Dietary Approaches to Stop Hypertension.

* For overall cardiovascular risk reduction, stop smoking.
The effects of implementing these modifications are dose and 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
once-a-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 1970s 1980s 1990s 2000

Direct Alpha- ACE ARBs

vasodilators blockers inhibitors
Peripheral Thiazide
sympatholytics diuretics
Central 2
Ganglion agonists Calcium
blockers antagonists-
Calcium
Veratrum antagonists- DHPs
alkaloids non-DHPs
Beta-
blockers
DHP, dihydropyridine;
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker
 Multiple antihypertensive agents
are needed to achieve target BP
Number of antihypertensive agents
Trial 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

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

DBP, diastolic blood pressure; MAP, mean arterial pressure; Lewis EJ, et al. N Engl J Med 2001;345:851-860;
SBP, systolic blood pressure 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
RECOMMENDED DRUGS+
COMPELLING INDICATION CLINICAL TRIAL BASIS+
DIURETIC BB ACEI ARB CCB ALDO ANT

Heart failure ACC/AHA Heart Failure Guide-

line,40 MERIT-HF, 41 COPERNI-
CUS,42 CIBIS,43 SOLVD,44 AIRE,45
TRACE,44 ValHEFT,47 RALES48

Postmyocardial infarction ACC/AHA post-MI Guideline,49

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

High coronary disease risk ALLHAT,33 HOPE,34 ANBP2,36

LIFE,32 CONVINCE31

Diabetes NKF-ADA Guideline,31,32 UKPDS,34

ALLHAT33

Chronic Kidney disease NKF Guideline,22 captopril Trial,55

RENALL,56 IDNT,57 REIN,58 AASK59

Recurrent stroke prevention 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 Diuretic, DHPCCB
hypertension
Renal disease
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 Beta-blocker,
almost always included) spironolactone
Left ventricular hypertrophy ARB
Cerebrovascular disease ACE-I + diuretic, diuretic
DHPCCB, dihydropyridine calcium-channel blocker;
ACE-I, angiotensin-converting enzyme inhibitor;
2003 WHO/ISH Statement on Hypertension.
ARB, angiotensin II receptor blocker; CCB, calcium-channel blocker J Hypertens 2003;21:1983-1992
 Treatment initiation: JNC VII
Normal Pre- Stage 1 Stage 2
hypertension hypertension hypertension

Lifestyle Encourage Yes Yes Yes

modification

Initial drug therapy

Without No antihypertensive drug Thiazide-type Two-drug
compelling indicated diuretics for most; combination for
indication may consider most (usually
ACE-I, ARB, BB, thiazide-type
CCB, or diuretic and
combination ACE-I or ARB
or BB or CCB)
With Drug(s) for compelling Drug(s) for compelling indications;
compelling indications other antihypertensive drugs
indications (diuretics, ACE-I, ARB, BB, CCB)
as needed
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
 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 With compelling
indications indications

Stage 1 hypertension Stage 2 hypertension

(SBP 140-159 or DBP (SBP 160 or DBP 100 mmHg) Drug(s) for the
90-99 mmHg) Two-drug combination for compelling indications
Thiazide-type diuretics most (usually thiazide-type
for most. May consider diuretic and ACE-I or Other antihypertensive
ACE-I, ARB, BB, CCB ARB, or BB, or CCB) Drugs (diuretics, ACE-I,
or combination 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 JNC VII. JAMA 2003;289:2560-2572
receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker
 Circumstances in which ACE Inhibitors and ARBs Should Not Be
Used

Do Not Use Use with Caution

ACE Inhibitor Pregnancy(A) Women not practicing contraception (A)

History of angioedema (A) Bilateral renal artery stenosis*
Cough due to ACE inhitors (A) Drugs causing hyperkalemia (A)
Allergy to ACE or ARB (A)

ARB Allergy to ACE inhibitor or ARB (A) Bilateral renal artery stenosis*
Pregnancy (C) Drugs causing hyperkalemia (A)
Cough dua to ARB (C) 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