HYPERTENSIONHYPERTENSION

SYAIFUL AZMI

Subdivision of Nephrology, Faculty of MedicineAndalas University

Padang

Buku pegangan.Buku pegangan.

• HARRISON : INTERNAL MEDICINE

• SUPARTONDO : ILMU OENYAKIT DALAM

• NORMAN KAPLAN : CLINICAL HYPERTENSION

Bahaya Bahaya HIPERTENSI HIPERTENSI (bila tdk dikendalikan)(bila tdk dikendalikan)

Kerusakan pada Organ Target Kerusakan pada Organ Target

StrokeStroke

RetinopatiRetinopati(buta)(buta)

• LVH LVH • Gagal Gagal JantungJantung• PJKPJK

Penyakit GinjalPenyakit Ginjalkhronikkhronik

• Gagal GinjalGagal Ginjal TerminalTerminal

Each mmHg BP reduction lowers the cardiovascular risk

• Meta-analysis of 61 prospective studies• 1 million patients• 12.7 million patient years

Lewington S, et al. Lancet 2002;360:1903–13

2 mmHgBP

reduction(systolic)

7% risk reductionCHD mortality

10% risk reduction

stroke mortality

Implications of small reductions in DBPImplications of small reductions in DBPfor primary preventionfor primary prevention

DBP, diastolic blood pressure; CHD, coronary heart disease

-21-16

-6

-46

-38

-15

-50

-40

-30

-20

-10

07.5 mmHg 5-6 mmHg 2 mmHg

CHDStroke

Ris

k re

duct

ion

(%)

DBP reduction

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

Section 1: Definition and Classification Section 1: Definition and Classification of Hypertensionof Hypertension

Definition and classification of Definition and classification of hypertension: ESH/ESC 2003hypertension: ESH/ESC 2003

Hypertension is defined as blood pressure 140/90 mmHg

Category Systolic(mmHg)

Diastolic(mmHg)

Optimal <120 <80Normal 120-129 80-84High normal 130-139 85-89Grade 1 hypertension (mild) 140-159 90-99Grade 2 hypertension (moderate) 160-179 100-109Grade 3 hypertension (severe) 180 110Isolated systolic hypertension 140 <90

ESH/ESC Guidelines 2003 J Hypertens 2003;21:1011-1053

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

Definition and classification of Definition and classification of hypertension: JNC VIIhypertension: JNC VII

Hypertension is defined as blood pressure 140/90 mmHg

Category Systolic(mmHg)

Diastolic(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 Definition and classification of hypertension: WHO/ISH 1999/2003hypertension: WHO/ISH 1999/2003

Hypertension is defined as blood pressure 140/90 mmHg

Category Systolic(mmHg)

Diastolic(mmHg)

Optimal <120 <80

Normal <130 <85

High-normal 130-139 85-89

Grade 1 hypertension (mild) Subgroup: borderline

140-159140-149

or 90-9990-94

Grade 2 hypertension (moderate) 160-179 or 100-109

Grade 3 hypertension (severe) 180 or 110

Isolated systolic hypertension Subgroup: borderline

140140-149

<90<90

2003 WHO/ISH Statement on Hypertension. J Hypertens 2003;21:1983-1992; 1999 WHO/ISH Guidelines for the

Management of Hypertension. J Hypertens 1999;17:151-183When a patient’s systolic and diastolic blood pressures fall into different categories, the higher category should apply

Section 2: Prevalence of HypertensionSection 2: Prevalence of Hypertension

Prevalence of hypertension*: Prevalence of hypertension*: North America and EuropeNorth America and Europe

01020304050607080

United

Stat

es

Canad

a

Europe Ita

ly

Sweden

Englan

dSpa

in

Finlan

d

German

y

Pre

vale

nce

(%)

MenWomenTotal

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

Prevalence of hypertension: AsiaPrevalence of hypertension: Asia

01020304050607080

China (

2000

/2001

)

Taiwan

(199

4)

Hong K

ong (

1997

)

Singap

ore (1

998)

Malays

ia (19

96)

Thaila

nd (1

991)

Philipp

ines (

1999

)

Indon

esia

(1994

)

India

(Mum

bai, 1

999)

Japa

n (19

92-95

)

Pre

vale

nce

(%)

MenWomenTotal

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: Prevalence of hypertension: Other countriesOther countries

01020304050607080

Ecuad

or (20

00)

Colombia

(200

2)

Israe

l (199

6)

Pre

vale

nce

(%)

MenWomenTotal

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 TABEL 4 Prevalensi Hipertensi Pada Populasi, Obese, TGT dan DM di SumBar Populasi, Obese, TGT dan DM di SumBar

20052005NO

KOTA POPULASI (%)

OBESE (%)

TGT (%)

DM(%)

12345678

P.PanjangBt.SangkarSolokPariamanPayakumbuhPainanBukittinggiPadang

22.323.426.122.919.116.026.611.8

22.423.424.622.217.617.737.612.0

26.332.533.335.6

326.636.438.225.3

33.342.241.240.018.429.428.623.1

RERATA 21.1 22.2 30.4 30.0

Section 3 : Classification of Section 3 : Classification of hypertensionhypertension

CLASSIFICATIONCLASSIFICATION• 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 Section 4 : Risk factors of HypertensionHypertension

Table Cardiovaskuler risk factorsTable Cardiovaskuler risk factorsMajor Risk Factors Hypertension*Cigarette* (body mass index 30 kg/m2)Physical inactivityDislipidemia*Diabetes mellitus*Microalbuminuria or estimated GFR < 60 mL/minAge (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 failureBrain• Stroke or transient ischemic attackChronic kidney diseasePeripheral arterial diseaseRetinopathyGFR, glomerular filtration rate* Components of the metabolic syndrome JNC VII 2003

Risk factorsRisk 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 Section 5 : Pathophysiology and Pathogenesis of HypertensionPathogenesis of Hypertension

PATHOPHYSIOLOGY OF HYPERTENSIONPATHOPHYSIOLOGY 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 )

Angiotensinogen

Angiotensin I

Angiotensin II

Ellis ML, et al. Pharmacotherapy 1996;16:849-860;Carey RM, et al. Hypertension 2000;35:155-163

ATAT11 ATAT22

• Vasoconstriction• Aldosterone secretion• Catecholamine release• Proliferation• Hypertrophy

• Vasodilation• Inhibition of cell growth• Cell differentiation• Injury response• Apoptosis

BP

(-)

Renin-angiotensin-aldosterone systemRenin-angiotensin-aldosterone system

ReninRenin

Angiotensin-Angiotensin-converting converting

enzymeenzyme

Bradykinin

Inactive kinins

BP, blood pressure

Section 6 : Diagnosis of HypertensionSection 6 : Diagnosis of Hypertension

SYMPTOMSSYMPTOMS

Headache Nocturia Palpitation Dizziness Tinitus Epistaxis

Kaplan N , 2002

PHYSICAL EXAMINATIONPHYSICAL EXAMINATION

27

TABLE. IMPORTANT ASPECTS OF THE PHYSICAL TABLE. IMPORTANT ASPECTS OF THE PHYSICAL EXAMINATIONEXAMINATION

ACCURATE MEASUREMENT OF BLOOD PRESSUREGENERAL 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 TESTLABORATORY TEST

• ROUTINE LAB WORK UP• RISK FACTORS : BLOOD SUGAR, LIPID • PROFILE, ELECTROLYTES.• LAB OF TARGET ORGAN DEMAGE • PLASMA INSULIN, PLASMA RENIN

ACTIVITY

FUNDUSCOPY EXAMINATION : FUNDUSCOPY EXAMINATION : RETINOPATHYRETINOPATHY

CARDIAC ASSESSMENT : LVH, ARYTHMIA

CEREBRAL ASSESSMENT : ENCEPHALOPATHY

RENAL ASSESSMENT

Section 7 : Treatment GuidelinesSection 7 : Treatment Guidelines

Table Lifestyle modifications to manage hypertension *†Table Lifestyle modifications to manage hypertension *†

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

Modification Recommendation Approximate SBP Reduction (range)

Weight reduction Maintain normal body weight (body mass index 18.5-24.9 kg/m2)

5-20 mmHg/10 kg weight loss23-24

Adopt DASH eating plan Consume a diet rich in fruits, vegetables, and lowfat dairy products with a reduced content of saturated and total fat

8-14 mmHg25-26

Dietary sodium reduction Reduce dietary sodium intake to no more than 100 mmol per day (2.4 g sodium or 6 g sodium chloride)

2-8 mmHg25-27

Physical activity Engage in regular aerobic physical activity such as brisk walking (at least 30 min per day, most days of the week0

4-9 mmHg26-27

Moderation of alcohol consumption

Limit consumption to no more than 2 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

2-4 mmHg30

THE IDEAL ANTIHYPERTENSIVE AGENTTHE 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 drugsHistory of antihypertensive drugs

Directvasodilators

Alpha-blockers

Peripheralsympatholytics

Ganglion blockers

Veratrumalkaloids

Central 2 agonists

Calciumantagonists-non-DHPs

Beta-blockers

Thiazidediuretics

Calciumantagonists-

DHPs

ARBs

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

ACEinhibitors

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

Effectiveness and general tolerability

AASK MAP <92

Target BP (mmHg)

Multiple antihypertensive agents are needed to achieve target BP

Number of antihypertensive agents1

UKPDS DBP <85

ABCD DBP <75

MDRD MAP <92

HOT DBP <80

Trial 2 3 4

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

IDNT SBP <135/DBP <85

ALLHAT SBP <140/DBP <90

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 drugsMain 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 Clinical trial and guideline basis for compelling indications for individual drug classesclasses

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 2003Treatment strategy: WHO/ISH 2003

2003 WHO/ISH Statement on Hypertension.J Hypertens 2003;21:1983-1992

Compelling indication Preferred drugElderly with isolated systolic hypertension

Diuretic, DHPCCB

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 almost always included)

Beta-blocker, spironolactone

Left ventricular hypertrophy 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

Treatment initiation: JNC VIITreatment initiation: JNC VIINormal Pre-

hypertensionStage 1

hypertensionStage 2

hypertension

Lifestyle modification

Encourage Yes Yes Yes

Initial drug therapyWithout

compelling indication

No antihypertensive drug indicated

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)

With compelling indications

Drug(s) for compelling indications

Drug(s) for compelling indications; other antihypertensive drugs

(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 VIIGoals 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

JNC VII. JAMA 2003;289:2560-2572SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure

Hypertension treatment strategy: JNC VIIHypertension treatment strategy: JNC VIILifestyle modifications

Not at goal blood pressure (<140/90 mmHg)(<130/80 mmHg for patients with diabetes or chronic kidney disease)

Initial drug choicesWithout compelling

indicationsWith compelling

indications

Stage 1 hypertension(SBP 140-159 or DBP90-99 mmHg)Thiazide-type diuretics for most. May consider ACE-I, ARB, BB, CCBor combination

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

Drug(s) for the compelling indications

Other antihypertensiveDrugs (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.

JNC VII. JAMA 2003;289:2560-2572SBP, 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

Circumstances in which ACE Inhibitors and ARBs Should Not Be Circumstances in which ACE Inhibitors and ARBs Should Not Be UsedUsed

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

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