MANAGEMENT OF ESSENTIAL

HYPERTENSION

Dr. Stella Palar, SpPD, K-GH

 MOZAIC OF HYPERTENSION PATHWAYS
genetic

metabolic hormonal

sodium
cardiovascular retention

autonomic
RAA system nervous system

endothelial dysfunction
Arterial Hypertension, Rosenthal, 1982)
 Definition of Hypertension (JNC VII)

 Blood pressure classification on people age > 18 y.o

 Adults on no antihypertensive medications & who are not
acutely ill.

Systolic Diastolic
Category (mm Hg) (mm Hg)

Normal <120 and <80

Prehipertension 120-139 or 80-89
Hipertension
Stage 1 140-159 or 90-99
Stage 2 > 160 or >100
 Hypertension is an important
public health challenge worldwide
Population (in millions) with
hypertension globally
In 2000,
> quarter of
global population
with hypertension

Kearney PM, et al. Lancet. 2005;365:217-223.

6
 Prevalence of Hypertension
Hypertension is often founded in practical clinic
70
prevalence of hypertension (%)

SBP > 140 mm Hg 64 65

60
DBP > 90 mm Hg
50 54
44
40

30
21
20
4 11
10
age (yrs) 18-29 30-39 40-49 50-59 60-69 70-79 80+
0

Franklin, S.S., J Hypertens 1999; 17 (suppl 5): S29-S36

 Cardiovascular Mortality Risk Doubles with Each 20/10
mmHg Increment in Systolic/Diastolic BP*

8x
8
7
6
5
4x
Cardiovascular

4
Mortality Risk

3
2x
2
1
0
115/75 135/85 155/95 175/105
Systolic/Diastolic Blood Pressure (mm Hg)
*Measurements taken in individuals aged 40–69 years, beginning with a blood
pressure of 115/75 mm Hg.
Lewington S, et al. Lancet. 2002;360:1903-1913; Chobanian AV, et al. JAMA. 2003;289:2560-2572.
RULE OF HALF
Hypertensive patients
Patients who are aware who are treated
but remain untreated but uncontrolled
and uncontrolled

25% 12.5%
12.5%

50%

Hypertensive patients Hypertensive patients

who are unaware who are treated
and controlled

Source : Joffres et al. (1997) Am. J. Hypertension 10: 1097-1102

 Hypertension Prevalence and Treatment:
North America and Europe

Patients on Therapy
US
55 Canada
100 Italy
50
90 Sweden
45 England
80 Spain
40
70 Finland
% 35 % Germany
60
30
50
25
40
20
30
15
20
10
10
5
0
0
Country Country
Wolf-Maier K et al. JAMA. 2003;289:2363-2369.
 The percentages of well controlled
hypertension patients
< 140/90 mmHg < 160/95 mmHg
USA Canada Finland Spain Australia
16 20.5 20 19
27

England France Germany Scotland India

6 9
24 22.5 17.5

> 65 years

USA: JNC VI. Arch Intern Med 1997 Marques-Vidal P et al. J Hum Hypertens 1997
Canada: Joffres et al. Am J Hypertens 1997
England: Colhoun et al. J Hypertens 1998
France: Chamontin et al. Am J Hypertens 1998
Adapted from G. Mancia / L. Ruilope
 Hypertension-We try hard but
it does not get much better
About 50% of hypertensive patients remain uncontrolled
100 (NHANES ≈ EUROSPIRE)

Failed to achieve BP control*

Percentage of population

75

**
50
**

25

0
1976– 1988– 1991– 1999– 2001– 2003– 2005– 2007–
1980 1991 1994 2000 2002 2004 2006 2008
Year
* BP control defined as BP < 140/90 mmHg; BP < 130/80 mmHg for patients with diabetes or CKD; includes
treated and untreated patients, except ** (only treated patients)
 Classification of European Society of
JNC VII -2003 Hypertension / ESH
 Blood pressure classification on people
Classification 2003
age > 18 y.o
 Adults on no antihypertensive Category Systolic Diastolic
medications and who are not acutely ill.

Systolic Diastolic Optimal  120 and  80

Category
(mm Hg) (mm Hg)
Normal 120-129 and/or 80-84
Normal < 120 and <80
High Normal 130-139 and/or 85-89
Pre
Hypertension 120-139 80-89
or
Grade 1 Hypertension 140-159 and/or 90-99

Hypertension
Grade 2 Hypertension 160-179 and/or 100-109
Stage 1 140-159 And/or 90-99
Grade 3 Hypertension ≥ 180 and/or ≥110
Stage 2 > 160 or ≥100

Isolated Systolic
≥ 140 and  90
Hypertension
 Classification of JNC
Des
2013
JNC
JNC 88
Lifestyle modification
JNC 7 Continue throughout management

General population Diabetes or CKD present

Category Systolic Diastolic (no diabetes or CKD)
(mm Hg) (mm Hg) All ages All ages
Diabetes present CKD present with/
≥60 years <60 years No CKD without diabetes
Normal < 120 and <80
BP goal BP goal
Pre BP goal BP goal <140/90 <140/90
Hypertension 120-139 80-89
or <150/90 <140/90

nonblack black

Hypertension Initiate thiazide-type Initiate thiazide-type Initiate ACEI or ARB,

diuretic diuretic alone or in
or ACEI or CCB, or CCB, alone or in combination with
Stage 1 140-159 And/or 90-99 alone or in combination other drug class
combination

Stage 2 > 160 or ≥100 Select a drug treatment titration strategy

A. Maximize 1st medication before adding 2nd or
B. Add 2nd med before reaching max. dose of 1st med or
C. Start with 2 med classes separately or as fixed-dose combination
 Etiology
• Primer (essential)
• No specific causes that can be
identified
• 95% of all hypertension cases Hypertension
• Secondary
• Causes can be identified
• 5% of all hypertension cases.
• Kidney disease is the main cause Secondary
(90%) of all secondary hypertension: Essential
1. Renal parenchymal disease: Causes
• acute nephritis,
• chronic glomerulonephritis, etc.
2. Renovascular disease:
• renal artery stenosis,
• atherosclerosis,
• fibroplasia, etc.
3. Endocrine causes Non-Endocrine Endocrine
Hypertension Hypertension
 Complications of Hypertension:
End-Organ Damage

Hypertension

Hemorrhage, LVH, CHD, CHF

Stroke

Peripheral
Vascular
Disease Renal Failure,
Retinopathy
Proteinuria
CHD = coronary heart disease
CHF = congestive heart failure
LVH = left ventricular hypertrophy Slide Source
Hypertension Online
Chobanian AV, et al. JAMA. 2003;289:2560-2572. www.hypertensiononline.org
 Hypertension complication

Eyes Brain Target Organ damage!!

retinopathy stroke

Heart
ischaemic heart disease
Kidneys left ventricular hypertrophy
renal failure heart failure Damages depend on:
• How high of the blood
pressures

Peripheral arterial disease • How long the uncontrolled

and untreated high blood
presure
EARLY TREATMENT MAKES A DIFFERENCE

Brenner, et al., 2001

 Target of
Anti Hypertensive Therapy

1. BLOOD PRESSURE
LOWERING

Myocardial Infarction
(20-25%)

Stroke
(35-40%)
2. TARGET ORGAN
Heart Failure
PROTECTION & (>50%)
IMPROVEMENT
 Treatment Goals

• Reduce morbidity & mortality

• Select drug therapy based on evidence
demonstrating risk reduction

Patient Population Target BP

Most patients < 140/90 mmHg
DM/CKD < 140/90 mmHg
Elderly < 150/90 mmHg

20
 2014 Hypertension Guideline
Management Algorithm (JNC 8)

James P et al. JAMA. 2013;289: E1-E14

 Reasons for inadequate
BP control

PATIENTS PHYSICIANS
• Knowledge deficit •Poor physician-patients
• Medication not taken by communication
patient

MEDICATIONS
•Medication cost
•Side effects
•Complicated regimens
 Lifestyle Modifications
Approximate Systolic
Modification Recommendation
BP Reduction (mm Hg)
Maintain normal body weight 5–20 per 10-kg
2
Weight loss (BMI 18.5–24.9 kg/m ) weight loss

Consume a diet rich in fruits,

DASH-type vegetables, and low-fat dairy products 8–14
diet with a reduced content of fat
Reduce dietary Na intake to no more
Reduced salt than 100 mmol per day 2–8
intake (2.4 g Na or 6 g NaCl)
Regular aerobic physical activity (at
Physical least 30 min/d, most days of the week) 4–9
activity
Limit consumption to 2 drinks/d in men
Moderation of and 1 drink/d in women & lighter- 2–4
alcohol intake weight persons

DASH, Dietary Approaches to Stop Hypertension 23

 History of antihypertensive drugs

Effectiveness and general tolerability

1940’s 1950 1957 1960’s 1970’s 1980’s 1990’s 2000 2007

Direct Alpha- ACE ARBs DRI

vasodilators blockers inhibitors
Peripheral Thiazide
sympatholytics diuretics
Central 2
Ganglion
agonists Calcium
blockers
Calcium antagonists-
Veratrum
antagonists- DHPs
alkaloids
non-DHPs
Beta-blockers

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

EFFECTIVE in reducing systolic & diastolic

hypertension

Economical daily cost

Minimum side effect and protect the target organ

(brain, heart & kidney damage )

Practical with once daily dose

Int’l Forum on Angiotensin Receptor Antagonist, Monte Carlo, 19999

 First line classes of
antihypertensive drugs
• Diuretics
– Inhibit the reabsorption of salts and water from kidney tubules into the
bloodstream
• 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
• Calcium-channel Blocker
– Inhibit influx of calcium into cardiac and smooth muscle
• Beta-blockers
– Inhibit stimulation of beta-adrenergic receptors
 Diuretics
• Cara Kerja : Efek Samping :
Menghambat 1. Hipokalemia
reabsorbsi Na & Cl  2. Hipomagnesimia
Volume sel plasma & 3. Hiponatremia
ekstraseluler ↓  ↓ 4. Hiperuricemia
CO ↓ Jumlah cairan 5. Resistensi Insulin &
tubuh  Resisten ↑ glukosa darah
perifer ↓ 6. ↑ kadar lemak darah
7. Disfungsi Ereksi
Diuretics
 Thiazide Diuretics
Veins
•Mekanisme : menghambat
pompa Na/K di tubulus distal
•Contoh:
• Hydrocholorthiazide 12.5-
25 mg/d
• Chlorthalidone 12.5-50
mg/d
•Efekif sebagai lini pertama
•Jika digunakan tunggal, lebih
efektif pada GFR >30 ml/min
Loop Diuretics
Veins
•Mekanisme: menghambat
Na/K/Cl ATPase pada ansa
henle ascending
•Contoh: Furosemide
• Menguntungkan pada pasien
dengan HPT resisten & adanya
overload cairan; efektif jika CrCl
<30 ml/min
•Diberikan pagi dan siang untuk
menghindari nocturia
 Aldosterone Receptor Antagonists
Veins

Thiazides •Mekanisme: menghambat reseptor

Loops aldosterone  ↓ retensi Na & air
Aldosterone Ant. •Spironolactone 25 mg daily
•Dapat ↓ TD s/d 25 mmHg, sebagai
obat pilihan dari 4 regimen obat HPT
resisten
•Monitor Creatinin & K

Am J Hypertension. 2003; 16:925-930.

 Angiotensin Converting Enzyme
Inhibitor (ACE-I)
Cara Kerja :
ACE-I ↓ jumlah Angiotensin II
dalam plasma sehingga ↓ efek
vasokonstriksi dari peptida ini.

Efek Samping :
1.Batuk & Spasme pada Bronkus
2.Hiperkalemia
3.Hipoglikemi
4.Gangguan pada Eritropoietin
5.Angioedema
 ACE Inhibitors
Veins

Arteries

•Contoh:
ACEI •ACEI: Captopril 12.5 -50 BID, Enalapril
2.5-40 mg daily –BID, Lisinopril 5 – 40 mg
daily, Imidapril 5-10 QD, Perindopril 4-8
mg QD, Ramipril 2.5-20 mg
•Monitor: Creatinin dan Kalium
Angiotensin II Receptor Bloacker (ARB)

• Cara Kerja :
ARB menghambat
Angiotensin II dari semua
reseptor AT1 yang mana
menghasilkan efek yang
berlawanan dari simulasi
Angiotenin II terhadap
reseptor AT 1 sehingga
mengkibatkan ↓ TD
 ARB
Veins

Arteries

ARB •Contoh:
•ARB: Irbesartan 150-300 mg QD,
Losartan 25-100 mg BID,
Olmesartan 20-40 mg, Telmisartan
20-80 mg, Valsartan 90-160 mgQD
•Monitor: Creatinin & Kalium
 Calcium Channel Blocker
• Cara Kerja : Efek Samping :
Menghambat pengambilan ion Postural Hipotensi
calcium++ pada otot polos dan Palpitasi
otot jantung Takikardi
↓ Edema
Dilatasi pada arterior Perifer Dizziness
↓ Konstipasi
↓ resistensi pembuluh darah Sedasi
perifer
A-V Block
↓
Pusing
↓ Afterload
Rasa Cepat Lelah
↓
↓ Tekanan Darah
 CCB Non-Dihydropyridine:
Diltiazem and Verapamil
Heart

Arteries

Diltiazem •Contoh:
Verapamil •Diltiazem Long acting; CD 100 -400 mg
•Verapamil 60-480 mg, long acting SR
•Monitor: HR
•Verapamil  konstipasi
•Kontraindikasi relatif pada gagal jantung
 CCB: Dihydropyridine

Arteries

Dihydropyridine •Contoh:
CCBs •Amlodipine 2.5-10 mg PO daily
•Felodipine 2.5-10 mg PO daily
• OROS/GITS. Jangan gunakan nifedipine
kerja cepat
•Monitor: edema perifer, HR ( takikardi)
 β-Blocker
Cara Kerja : • Efek Samping :
Kompetitif menghambat 1. Kelelahan
ikatan katekolamin terhadap 2.↑ berat badan
reseptor β– adrenergic
3. ↓ sensitivitas insulin
1. ↓ Cardiac output
4. ↑ serum trigliserida
2. ↓ Jumlah renin yang
5. ↑ malformasi janin
dilepaskan
3. ↓ Jumlah blokade
presinaps yang
menghambat pelepasan
katekolamin
 β-Blocker
Heart

Beta Blockers •Atenolol 25-100 mg QD, Metoprolol 25 -

100 mg BID, Bisoprolol 2.5 – 10 mg QD,
Carvedilol 6.25-50 mg (alfa+Beta) BID
•Monitor: HR, Gula darah pada pasien DM
•Tidak di kontraindikasikan pada pasien
asma / PPOK namun gunakan dengan
hati-hati
 α-Blocker

Cara Kerja :
Penghambatan aktivitas
saraf simpatis
↓
Menghambat pelepasan
noradernalin
↓
↓ Vasokonstriksi
↓
↓ Tekanan Darah
 α-Blocker
Arteries

•Contoh:
•Terazosin 1 – 20 mg daily
Alpha1 Blockers •Doxazosin 1 – 16 mg daily
•Dapat menyebabkan hipotensi
ortostatik  dosis diberikan
malam hari
•Dipertimbangkan hanya sebagai
terapi tambahan
•Dapat menguntungkan bagi
pasien dengan BPH
 Central Acting Agents
Heart
•Mekanisme : false neurotransmitters 
↓ sympathetic outflow  ↓ sympathetic
tone
•Contoh:
•Clonidine 0.75-0.6 mg bid,
Central Acting
Methyldopa 250 mg-1000 mg BID
Mechanism:
(Pregnancy), Reserpin 0,1 -0,25 mg QD
Clonidine •Monitor: HR (bradycardia)
•Efek samping: Mulut kering, ortostatik,
sedasi
• Penghentian  Rebound effect
 Vasodilators
Arteries •Mekanisme: Vasodilatasi langsung terhadap
arteriol melalui ↑ intracellular cAMP
•Contoh:
•Hydralazine 20-400 mg BID-QID
Dihydropyridine •Minoxidil 2.5-40 mg PO daily-BID
CCBs •Monitor: HR ( reflex tachycardia), Retensi
Na & air
Hydralazine
•Hydralazine alternatif pada gagal jantung
Minoxidil jika ACEI kontraindikasi
•Pertimbangkan penggunaan minoxidil pada
pasien refrakter dengan multi-drug
regimens
 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 Drug(s) for the

(SBP 140-159 or DBP 90-99
mmHg)
Thiazide-type diuretics
for most. May consider ACE-I,
ARB, BB, CCB or combination
(SBP 160 or DBP 100 mmHg)
Two-drug combination for
most (usually thiazide-type
diuretic and ACE-I or
ARB, or BB, or CCB)
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 JNC VII. JAMA 2003;289:2560-2572
receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker
JNC 7

48
JNC 7

49
50
50
 JNC 7 Compelling Indications
Diuretic βB ACEI ARB CCB AA

Heart failure     
Post-MI   
High CHD risk    
Diabetes     
Chronic kidney
 
disease
Recurrent stroke
prevention 

AA = aldosterone antagonist

Chobanian AV, et al. JAMA. 2003;289:2560-2572.

 2014 Hypertension JNC 8

Guideline Management Algorithm

 2014 Hypertension JNC 8

Guideline Management Algorithm

 Comparison
JNCJNC
8 8
Lifestyle modification
JNC 7 Lifestyle modification
Continue throughout management

Goal BP <140/90mmHg not achieved General population

<130/80 for diabetes and CKD Diabetes or CKD present
(no diabetes or CKD)

Initial drug choices

All ages All ages
≥60 years <60 years Diabetes present CKD present
No CKD with / without
Without compelling With compelling indications
indications diabetes
BP goal BP goal BP goal
<150/90 <140/90 <140/90 BP goal
Stage I HTN Stage II HTN
Thiazide type diuretic Any AHY drugs <140/90
2 drug combo for most
for most (diuretics, ACEI,
Usually thiazide type ARB, BB, CCB, as nonblack black
May consider ACEI, diuretics with ACEI or AB
ARB, BB, CCB or needed) Initiate thiazide-type Initiate thiazide-type Initiate ACEI or ARB,
or BB or CCB
combination diuretic diuretic alone or in combination
or ACEI or CCB, alone or CCB, alone or in with other drug class
or in combination combination
Not at goal BP

Select a drug treatment titration strategy

Optimize dosage or add drugs until goal BP is achieved A. Maximize 1st medication before adding 2nd or
Consider consultation with hypertension specialist B. Add 2nd med before reaching max. dose of 1st med or
C. Start with 2 med classes separately or as fixed-dose combination
 The BHS recommendations for combining blood
pressure-lowering drugs
55 years or black patients
<55 years at any age

Step 1 A C or D

Step 2 A + C or A + D

Step 3 A + C + D

Step 4 Add: further diuretic therapy or alpha-blocker or beta-blocker

Consider seeking specialist advice

A: ACE inhibitor or ARB, if ACE inhibitor intolerant

C: Calcium-channel blocker D: Diuretic (thiazide)
BHS, British Hypertension Society; ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker
National Collaborating Centre for Chronic Conditions. Hypertension: management in adults in primary care:
2006 update partial update. London: Royal College of Physicians, 2006
 Hypertension treatment strategy:
ESH/ESC 2007
Mild BP elevation Choose between: Marked BP elevation
Low/moderate CV risk High/very high CV risk
Conventional BP target Lower BP target

Single agent Two-drug combination

at low dose at low dose

If goal BP not achieved

Previous agent Switch to different Previous combination Add a third drug

at full dose agent at low dose at full dose at low dose

If goal BP not achieved

Two- to three-drug Full-dose Two-three-drug combination

combination monotherapy at effective doses

ESH/ESC Guidelines 2007

BP, blood pressure European Heart Journal. 2007;28:1462-1536
Hypertension Stage 1
BP ≥ 140/90 - ≤ 159/99 mmHg

Evaluate cardiovascular risk

Evaluate target organ damage
Evaluate compelling condition

Start lifestyle modification

Correction of cardiovascular risk factor
Treat the compelling condition

Defined total risk /absolute

Pharmacological management
HYPERTENSION STAGE 2
BP ≥ 166/100 mmHg

Pharmacological management

Evaluate cardiovascular risk

Evaluate target organ damage
Evaluate compelling condition

Additional lifestyle modification

Correction of cardiovascular risk factor
Treat the compelling condition
 Panduan Untuk Meningkatkan
Pengendalian Tekanan Darah
• Menginformasikan pasien tentang penyakit & obat yang digunakan
• Edukasi untuk monitor TD di rumah
• Edukasi perubahan gaya hidup
• Atasi masalah depresi jika ada
• Folow up pemeriksaan laboratorium / tahun, kecuali jika
diindikasikan lebih sering
• Sebaiknya gunakan obat dosis satu kali sehari
• Jika perlu pakai 1 tablet kombinasi
• Gunakan dosis kecil terlebih dahulu
• Anjurkan untuk minum obat di pagi hari segera setelah bangun
tidur
 Follow-up
• Hypertensive patients are recommended to be followed
at least every month
• Follow-up visits are used to:
– Increase the intensity of lifestyle and drug therapy,
– Monitor the response to therapy
– Assess adherence
 Criteria to Referal
a. Hypertension with complication
b. Hypertension resistant
c. Hypertension Crisis ( Emergency & Urgency)

64
THERE ARE MANY GOOD DRUGS

BUT THE PATIENTS NEED

A GOOD DOCTOR
The choice of initial drug is the most important
decision to be made in the treatment of
hypertension.
If the wrong initial choice is made, the blood
pressure may not respond, bothersome side-
effects may appear or other conditions worsen,
discouraging the patient from the overriding
necessity of persistence in achieving the goal of
therapy

Kaplan NM (Eur H J, 1999 ; I : L1-L4)

 CURICULLUM VITAE
dr. Stella Palar, SpPD, K-GH
Institusi:
• Divisi Ginjal Hipertensi
Bagian / KSM Ilmu Penyakit Dalam
FK Universitas Sam Ratulangi /
RSUP Prof dr. R.D. Kandou Manado
Pendidikan:
• Dokter : FK Unsrat – Manado 1988
• Spesialis Penyakit Dalam : FK Unsrat – Manado 2005
• Konsultan Ginjal Hipertensi: PAPDI 2012