Hypertension

HADI HARTONO, dr.SpJP, FIHA

JNC 7 Re-Classification of SBP/DBP

JNC VI (1997)
Optimal

JNC 7 (2003)

Normal

< 120 and <80

Normal < 130 and < 85 High-normal 130-139 or 85-89

< 120 and < 80

Prehypertension 120-139 or 80-89

Stage 1 140-159 or 90-99

Stage 1 140-159 or 90-99

Stage 2
160-179 or 100-109 Stage 3 > 180 or > 110
JNC VI. Arch Intern Med. 1997;157:2413-2446. JNC 7. JAMA. 2003; 289(19):2560-2572.

Stage 2 > 160 or > 100

The New Guidelines : Classification

-BP Classification Optimal Normal High normal Grade 1 Hypertension (mild) Grade 2 Hypertension (moderate) Grade 3 Hypertension (severe) Isolated Systolic Hypertension BP WHO-ISH 2003 <120 / <80 <130 / <85 130-139 / 85-89 140-159 / 90-99 (140-149 / 90-94) 160-179 /100-109 > 180 / >110 > 140 / < 90 BP ESH-ESC 2003 <120/<80 120-129 /80-84 130-139 / 85-89 140-159 / 90-99 160-179/100-109 > 180 / >110 >140 / < 90 Isolated Systolic Hypertension Stage 1 Hypertension Stage 2 Hypertension BP-JNC 7 Normal Prehypertension

Modified, 2005

Hypertension : The Disease Continuum

Early Paradigm

Natural History of CVD Progression

Elevated BP
More Recent Paradigm

Target Organ Damage

Natural History of CVD Progression

Elevated BP A Latest - Future Paradigm Vascular Dysfunction Target Organ Damage

Natural History of CVD Progression

Elevated BP Endothelial Dysfunction Atherosclerosis LVH Target Organ Damage Renal Damage MI

Angina Pectoris

Stroke

Modified,2005

Prevalence of hypertension The World Health Organization (WHO) estimates that > 20% (1 billion) of the worlds current adult population has

hypertension

WHO World Health Report, 2001

Lain-lain Lain-lain Kondisi Ibu Hamil Persalinan dan & defisiensi nutrisi Peny.Infeksi & parasit

Kecelakaan Peny.Respirasi Non infeksi Kanker

Infeksi Respirasi

CV

Diduga 30% dari kematian th 2000

WHO World Health Report, 2001

The global burden of cardiovascular disease in the 21st century

Total deaths*

Cardiovascular disease

Ischaemic heart disease

Number (millions) % of total deaths

Cerebrovascular disease

0
* Estimated deaths by 2020

10

20

30

40

50

60

70

80

Neal B, et al. Eur Heart J 2002; 4(Suppl. F): F2-F6.

Prevalence of hypertension*: North America and Europe

80 70
Men Women Total

Prevalence (%)

60 50 40 30 20 10 0

C an ad a

ly

Sw ed en En gl an d

* BP 140/90 mmHg or treatment with antihypertensive medication

U ni te d

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

Fi nl an d G er m an y

at es

pe

Eu ro

St

Sp ai n

Ita

Prevalence of hypertension: Asia

80 70 60 50 40 30 20 10 0
4) 01 ) (1 99 0/ 20
Women Total

Prevalence (%)

H on

C hi

Ph

Si

In

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]

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Hypertension control rates around the world are generally poor

Barriers to Achieve BP Goals

Poor compliance
Under aggressiveness of physician in HT treatment Wrong medication; not proper combination; medication interfering risk with BP control White coat HT Pseudo HT Secondary HT

Trends in awareness, treatment, and control of high blood pressure in adults ages 1874
National Health and Nutrition Examination Survey, Percent II 197680 Awareness Treatment Control 51 31 10

II (Phase 1) 198891
73 55 29

II (Phase 2) 199194
68 54 27

19992000 70 59 34

Sources: Unpublished data for 19992000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.

MONICA JAKARTA Prevalence of hypertension Awareness Newly discovered Treated cases Adequately treated 1988(%) 14.9 56.1 43.9 50.9 10.0 1993 (%) 16.9 88.7 11.3 85.3 31.1 2000 (%) 17.9 88.0 12.0 79.4 39.9

PREVALENSI HIPERTENSI DI INDONESIA

Hypertension control rates around the world

<140/90 mmHg (%) United States 27 France 24 Canada 22 Italy 9 Egypt 8 England 6 Korea 5 China 3 Poland 2 <160/95 mmHg (%) Germany 23 Finland 21 Spain 20 Australia 19 Scotland 18 India 9 Zaire 3

JNC VI. Arch Intern Med 1997;157:2413-2446; Joffres MR, et al. Am J Hypertens 1997;10:1097-1102; Colhoun HM, et al. J Hypertens 1998;16:747-752; Chamotin B, et al. Am J Hypertens 1998;11:759-762; Marques-Vidal P, et al. J Hum Hypertens 1997;11:213-220

Factors influencing BP control

Efficacy

+
Adverse effects

+
Convenience

Various types of non-compliance & reasons offered

Refusal to take medication Discontinuation Reducing dosage Drug holiday whitecoat compliance Increasing dosage

Expense
Not convinced of need for drug Fear of adverse effects Dislike of taking drugs Cannot remember Perception that problem has been fixed

LaRosa, Arch Fam Med. 1995;9: 1169-1175

Strategies for Improving Adherence to Regimens

Clinician empathy increases patient trust, motivation, and adherence to therapy. Physicians should consider their patients cultural beliefs and individual attitudes in formulating therapy. Adherence to regimens for better therapeutic agents to help achieve optimal BP targets
SCU 2003

Impact of Hypertension

The chain of events leading to end-stage heart disease

Myocardial ischaemia Coronary thrombosis Myocardial infarction Arrhythmias/ loss of muscle

Coronary artery disease

Remodelling

Atherosclerosis LVH

Ventricular dilatation

Risk factors (cholesterol, high blood pressure, diabetes, insulin resistance)

Congestive heart failure

End-stage heart disease

Adapted from Dzau V, Braunwald E. Am Heart J 1991; 121: 1244-63.

Impact of high-normal BP on CV risk

16 14 Cumulative 12 10 incidence of 8 CV events 6 (%) 4 2 0 Men High-normal BP

Normal BP
Optimal BP

12 Cumulative 10 incidence of 8 CV events 6 4 (%) 2 0

Women

High-normal BP
Normal BP Optimal BP 0 2 4 6 Years 8 10 12

Optimal BP: <120/80 mmHg; normal BP: 120-129/80-84 mmHg; high-normal BP: 130-139/85-89 mmHg
Vasan RS, et al. N Engl J Med 2001;345:1291-1297

BP, blood pressure; CV, cardiovascular

High blood pressure

Millimeters are a matter

Millimetres matter
For individuals 40-70 years of age, each

increment of
20 mmHg in systolic BP or 10 mmHg in diastolic BP doubles the risk of CVD across the entire BP range from
BP, blood pressure; CVD, cardiovascular disease

115/75 to 185/115 mmHg

JNC VII. JAMA 2003;289:2560-2572

Millimetres matter
A 2-mmHg reduction in DBP would result in a 6% reduction in the risk of CHD and a 15% reduction in the risk of stroke and TIAs
the Framingham Heart Study and the National Health and Nutrition Examination Survey (NHANES)

DBP, diastolic blood pressure; CHD, coronary heart disease; TIA, transient ischaemic attack

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

Millimetres matter
It is estimated that in patients with stage 1 hypertension and additional cardiovascular risk factors, achieving a sustained 12-mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.
JNC VII 2003

Current Antihypertensive Therapy Reduces CV Events

Stroke Major CV Events CV Death

0
Average Reduction in Events, % 20 20%30% 40 60 30%40% 30%40%

Can we do better?

80

100 CV=cardiovascular.
Neal B et al. Lancet. 2000;356:19551964.

Dont wait to treat hypertension

Awaiting overt signs and symptoms of coronary disease before treatment is no longer justified.
In some respects, the occurrence of symptoms may be regarded more properly as a medical failure than as the initial indication for treatment.
William B. Kannel, MD Department of Medicine Boston University Medical Center SCU 2003

Goals of Treatment in Hypertension (JNC 7)

Reduce CVD morbidity and mortality. Treat to BP < 140 / 90 mmHg or BP < 130 / 80 mmHg in patients with diabetes or chronic kidney disease (compelling indication). Achieve SBP goal especially in persons >50 years of age.

Benefits of Lowering BP:

35 40% mean reduction in stroke incidence > 50% reduction in CHF 20 25 reducion in myocardial infarction
JAMA May 21, 2003

Algorithm for Treatment of Hypertension

Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling Indications With Compelling Indications

Stage 1 Hypertension (SBP 140159 or DBP 9099 mmHg) Thiazid for most,may consider ACEI,ARB,BB,CCB

Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg) 2-drug combination for most

Drug(s) for the compelling indications

Other antihypertensive drugs

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

JNC 7 , Jama May 21,2003

Hypertension treatment strategy: WHO/ISH 2003 Regardless of the blood pressure level, all patients should adopt appropriate lifestyle modifications

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

Lifestyle Modification
Modification Weight reduction Adopt DASH eating plan Dietary sodium reduction Physical activity Moderation of alcohol consumption Approximate SBP reduction (range) 520 mmHg/10 kg weight loss 814 mmHg 28 mmHg 49 mmHg 24 mmHg
SCU 2003

Therapeutic strategies of hypertension ESH-ESC guidelines 2003

J.hypertension 2003 ,21, 1011 - 1053

Choose between Single agent at low dose 2 drug combination at low dose

If goal BP not achieved

Previous agent at full dose Switch to different Agent at low dose Previous combination at full dose Add a third drug at low dose

If goal BP not achieved

2-3 drug combination
3 drug combination at effective dose

Choice of antihypertensive therapy: ESH/ESC 2003 Main benefits are due to BP lowering Specific drug classes may differ in their effects Drugs are not equal in adverse-event profiles Major drug classes are suitable for initiation and maintenance of therapy Choice of drug will be influenced by patient experience and preference, and cost and risk profile Long-acting drugs that provide once-daily, 24-hour efficacy are preferable
ESH/ESC Guidelines 2003. J Hypertens 2003;21:1011-1053

BP, blood pressure

Key Messages in Hypertension

The most effective therapy prescribed by the careful clinician will control HTN only if patients are motivated.

Motivation improves when patients have positive experiences with, and trust in, the clinician.

Empathy builds trust and is a potent motivator.

The responsible physicians judgment remains paramount.

Development of Antihypertensive Drugs

Reserpin (1949)
1950 HCT (1958)

Diuretics Beta blockers

1960

Verapamil (1963)
Furosemide (1964) Propanolol (1965)

1970
Nifedipin (1975)

CCBs 1-blockers ACE-inhibitors

Prazosin (1977) 1980

Diltiazem (1980) Amlodipine (1987)

Captopril (1981)

Bisoprolol (1988)
1990 Losartan (1995) Valsartan

AT1-antagonists

2000 ?

Choice of antihypertensive drugs (1) The main benefits of antihypertensive therapy are due to lowering of blood pressure per se JNC 7. There is also evidence that specific drugs classes may differ in some effect, or in special groups of patients (Compelling Indication)

ESH-ESC 2003

Choice of antihypertensive drugs (2) The major classes of antihypertensive agents diuretics, beta-blockers, calcium antagonists, ACEI, ARB are suitable for the initiation and maintenance of therapy

ESH-ESC 2003

Main classes of antihypertensive drugs

Diuretics
Inhibit the reabsorption 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

Possible combinations of antihypertensive agents

Diuretics

Beta-blockers

Angiotensinreceptor blockers

Alpha-blockers

Calcium channel blockers

ACE inhibitors
Guidelines Committee. J Hypertens 2003; 21: 1011-53.

Multiple Antihypertensive Agents Are Needed to Achieve Target BP

Average No. of Antihypertensive Agents Trial Target BP (mm Hg) UKPDS ABCD DBP <85 DBP <75

MDRD
HOT AASK IDNT

MAP <92
DBP <80 MAP <92 SBP/DBP 135/85

UKPDS = United Kingdom Prospective Diabetes Study; ABCD = Appropriate Blood Pressure Control in Diabetes; MDRD = Modification of Diet in Renal Disease; HOT = Hypertension Optimal Treatment; AASK = African American Intervention Study of Kidney Disease; IDNT = Irbesartan Diabetic Nephropathy Trial. Bakris GL et al. Am J Kidney Dis. 2000;36:646-661. Lewis EJ et al. N Engl J Med. 2001;345:851-860.

Treatment initiation: JNC VII

Normal Prehypertension
Yes

Stage 1 hypertension
Yes

Stage 2 hypertension
Yes

Lifestyle modification

Encourage

Initial drug therapy Without 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
JNC VII. JAMA 2003;289:2560-2572

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

Clinical Trial and Guideline Basis for Compelling Indications for Individual Drug Classes

Compelling Indication
Heart failure Post-MI High coronary disease risk Diabetes Chronic kidney disease Recurrent stroke prevention
3/12/2014

BB

ACEI

ARB

CCB

Ald Ant

Clinical Trial Basis

ACC/AHA Heart failure Guideline, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE,TRACE, ValHEFT, RALES

ACC/AHA Post-Mi Guideline, BHAT, SAVE, Capricorn, EPHESUS,EUROPA,Valiant ALLHAT, HOPE, ANBP2, LIFE, CONVINCE ,valiant NKF-ADA Guideline, UKPDS, ALLHAT,LIFE,CHARM. NKF Guideline, Captopril Trial, RENAAL, idnt, REIN, AASK

PROGRESS

46

Modified - JNC 7 - 2005

Renin-angiotensin-aldosterone system
(-)
Renin Angiotensin I
Angiotensinconverting enzyme

Angiotensinogen

Bradykinin

Angiotensin II

Inactive kinins

BP

AT1
Vasoconstriction Aldosterone secretion Catecholamine release Proliferation Hypertrophy

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

BP, blood pressure

Inhibition of the RAAS by ACE inhibitors AND ARB

(-)
Renin Angiotensin I
Nonrenin NonACE
Angiotensinconverting enzyme

Angiotensinogen

ACE inhibitor

Bradykinin

ARB

Angiotensin II

Inactive kinins

BP

AT1
Vasoconstriction Aldosterone secretion Catecholamine release Proliferation Hypertrophy

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

RAAS, renin-angiotensin-aldosterone system; ACE, angiotensin-converting enzyme; BP, blood pressure

ARBs Prevent Angiotensin II Escape

Angiotensinogen Renin
Non ACE-dependent pathways to ANG II production

Angiotensin I

Bradykinin

X
Angiotensin II X
AT1 Receptor
AT2 Receptor

Degradation Products

Calcium Channel Blocker

Calcium-Channel Blockers (= Ca antagonist)
bekerja dengan menghambat masuknya ion kalsium melewati slow channel pada membran sel Berdasarkan struktur kimia tdp 2 golongan :

1. Dihidropiridin : Amlo, Felo, Nife, Nikar-DIPIN 2. Non dihidropiridin: Diltiazem, verapamil

CCB Mechanism of Action

KRISIS HIPERTENSI
1 % dari penderita hipertensi Penyebab : pengobatan UnAdequate Tekanan darah lebih dari 180 / 120

a. Hipertensi Emergency
Bilamana terjadi kelainan target organ, yaitu : CNS, Jantung, Ginjal, Mata Keluhan :
Chest pain Dyspneu Headache Blur vision Abdomenal Pain Oliguria

Harus segera diturunkan menuju normal

b. Hipertensi Urgency
Tekanan di atas 180 / 120 Belum ada keluhan target organ damage Boleh diobati sambil rawat jalan