kuliah hypertensi

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HYPERTENSI


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Initial Drug TherapyBP

ClasificationSBP*

mmHgDBP*

mmHgLifestyle

ModificationWithout Compelling

IndicationWith Compelling

Indications

Normal < 120 And < 80 EncourageNo antihypertensive

Drug (s) forcompelling

Prihypertension 120-139 Or 80-90 yes drug indicate indication***

Stage 1Hypertension

140-159 Or 90-99 yes

Thiazide-type

diuretics for most.May consider ACE Ior ARB, BB, CCB orcombination

Drug(s) for thecombinationindication*** otherantihypertensive

Stage 2

Hypertension > 160 Or > 100 Yes

Two drug combinationfor most** (usually

thiazide-type diureticand ACEI or ARB orBB or CCB).

drugs (diuretics,ACEI, ARB, BB,

CCB) as needed.

DBP, diastolic blood pressure; SBP, sysolic blood pressure; Drug abbreviations : ACEI, angiotensin converting enzyme

inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calsium channel blocker.

* Treatment determined by highest BP category. ** Initial combined therapy should be used cautiously in those at risk for

orthostatic hypotension, *** Treat patients with chronic kidney disease or diabetes to BP goal of < 130/80 mmHg

Classification and management of

blood pressure for adult*


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Recommended Drugs **

Compelling Indication*

DIURETIC

BB

ACEI

ARB

CCB

ALDO

ANT

Clinical Trials Basis***

Heart Failure ACC/AHA heart failure guideline, MERIT-HF COPERNICUS, CIBIS, SOLVD, AIRE,

ValHEFT, RALESPost myocardial infarction

ACC/AHA Post-MI guidelines, BHAT,SAVE, Capricorn , EPHESUS

High coronary disease risk ALLHAT, HOPE, ANBP2, LIFE,CONVINCE

Diabets NKF-ADA Guidelines, UKPDS, ALLHAT

Chronic kidney disease NKF Guidelines, Captopril trial, RENAAL,IDNT, REIN, AASKRecurrent stroke prevention PROGRESS

Compelling indications for anthihypertensive drugs are based on benefits from outcome studies or existing clinical guidelines;

the compelling indication is managed in parallel with the BP, ** Drug abbreviations : ACEI, angiiotensin converting enzyme

inhibitor; ARB, angiotensin receptor blocker; ALDO ANT, aldosterone antagonis; BB, beta-blocker; CCB , calsium channel blocker.*** Condition for which clinical trials demonstrate benefit of specific classes of anti hypertensive drugs

Clinical trial and guideline basis for compelling

indications for individual drug classes


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Classification of hypertension

according to aetiologyPrimary (essential) hypertension

Secondary hypertensionRenal hypertension Renoparenchymal hypertension; renovascular hypertension;

post-kidney transplant hypertension

Endocrine hypertension Pheochromocytoma; primary hyperaldosteronism (Conns

syndrome); deoxycorticosterone-producing tumours;

adrenogenital syndrome; Cushing's syndrome; primary

hyperrenism; acromegaly; hyperparathyroidism; endothelin-

producing tumours; hypo- and hyperthyroidism

Pregnancy-specific (Pre-) eclampsia; transient hypertension

hypertension

Cardiovascular hypertension Coarctation of the aorta; hyperkinetic heart syndrome;

aortic valve insufficiency; sclerosis of the aorta; severe

bradycardia; arteriovenous fistulae

Drug-/alimentation-induced Oral contraceptives; high-dose mineralcorticoids or

hypertension glucocorticoids; erythropoietin; cyclosporine; alcohol

licorice

Neurogenic hypertension Sleep apnoea syndrome; neurological disorders

Stimpel. Arterial Hypertension, 1996; Walter de Gruyter Berlin, New York.


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TABLE 6. Cardiovascular Risk Factors

Major risk factorsHypertension*

Age (older than 55 for men, 65 for women)

Diabetes mellitus*

Elevated LDL (or total) cholesterol or low HDL cholesterol*

Estimated GFR 60 mL/min

Family history of premature cardiovascular disease (men aged 55 or

women aged 65)

Microalbuminuria

Obesity* (body mass index 30 kg/m2)

Physical inactivity

Tobacco usage, particularly cigarettesTarget organ damage

Heart

Left ventricular hypertrophy

Angina/prior myocardial infarction

Prior coronary revascularization

Heart failure

Brain Stroke or transient ischemic attackDementia

Chronic kidney disease

Peripheral arterial disease

Retinopathy

GFR indicates glomerular filtration rate.*Components of the metabolic syndrome. Reduced HDL and elevated triglycerides are components

of the metabolic syndrome. Abdominal obesity is also a component of metabolic syndrome. Increased risk begins at approximately 55 and

65 for men and women, respectively. Adult Treatment Panel III used earlier age cutpoints to suggest the need for earlier action.


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TABLE 7. Identifiable Causes of Hypertension

Chronic kidney disease

Coarctation of the aorta

Cushing syndrome and other glucocorticoid excess states including

chronic

steroid therapy

Drug-induced or drug-related (see Table 18)Obstructive uropathy

Pheochromocytoma

Primary aldosteronism and other mineralocorticoid excess states

Renovascular hypertension

Sleep apnea

Thyroid or parathyroid disease


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Epidemiology

ofHypertension


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Factors affecting blood

pressureTemporary factors

Posture

Respiration

Emotion (eg, defencereaction white

coat hypertension)

Exercise

Meals Various drugs,

lifestyle

(tobacco, alcohol,

etc.)

Other factors

Age

Race Circadian variability

Temperature

Bladder distension

Pain


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Risk factors for the development

of hypertension

Hyperlipidaemia

Black race

Geneticpredisposition

Diabetes

mellitus

Lack of

exercise

Alcohol

Distress (?)

Obesity


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Blood Pressure in a Resting Subject


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Mechanisms Responsible for Blood

Pressure Variability


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Effect of SBP and DBP on

Age-Adjusted CAD Mortality:

MRFITCAD Death Rate per 10,000 Person-Years

100+ 90-99 80-89 75-79 70-74


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Organ Demagecaused by

Hypertension


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Ten-year risk for CHD by SBP and presence of other risk factors. Source: Derived from K.M. Anderson,

P.W.F. Wilson, P.M. Odell, W.B. Kannel. An updated coronary risk profile. A statement for health

professionals. Circulation

1991;83:356362.


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Hypertension and the risk of

further disease

Disease Relative risk(hypertensives versus normotensives)

Coronary artery disease 2- to 3-fold

Stroke 7-fold

Heart failure 2- to 3-fold

Peripheral vascular disease 2- to 3-fold


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Glagovs Coronary Remodeling


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Glagovs Coronary Remodeling

Hypothesis

Normal

vessel

Minimal

CAD

Regression

Severe

CAD

Expansion

overcome:

lumen narrows

Compensatory expansion

maintains constant lumen

Progression

Moderate

CAD

Adapted from Glagov et al. N Engl J Med. 1987;316:1371-1375.


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Diffuse Disease: Effect on

Angiographic Measurements

Measurements

% Diameter stenosi 25 17

Mean width segment (mm) 3.75 2.9

MLD (mm) 3.0 2.5

Plaque area (mm) 2.0 1.0

Arterial wall

Plaque

Lumen

de Feyter et al. Circulation. 1991;84:412-423.

.5 mm

3 mm

.5 mm

2.5 mm.5 mm

4 mm3 mm

2 mm2 mm

1 mm


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A

B

B

A

A

The Tight Stenosis Is Not the Active Lesion

Images supplied by Steven E. Nissen, MD, Cleveland Clinic.

BRupture

Site

Lipid Core

AtheromaLumen


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Unstable angina

or nonQ-wave

MI

Temporary resolution

of instability

Future high-risk

lesion

Acute

MI

Pathophysiology of ACS:

Disrupted Plaque

Adapted from Yeghiazarians et al. N Engl J Med. 2000;342:101-114.

Plaque

rupture

Thin cap

High

macrophage

content

Large lipid core

Incomplete

coronary

occlusion

Complete

coronary

occlusion Spontaneous lysis,

repair, and wall remodeling


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Myocardial infraction

Coronary thrombosis

Endstage heart

disease

Heart failure

Remodelling

Arrhytmia &loss of muscle

Sudden death

Myocardial ischaemia

Atherosclerosis, left

Ventricular hypertrophy

Coronary artery disease

Risk factors

(hypertension, low-

density lipoprotein,

diabetes mellitus, etc)

Ventricular dilation


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Figure 232-1. Patterns of ventricular hypertrophy. Specific patterns of ventricular remodeling occur in response to the imposed augmentation in

work load. A pattern of hypertrophic growth characterized as concentric, in which increased mass is out of proportion to chamber volume, is

particularly effective in reducing systolic wall stress (s) under conditions of heightened pressure load. In contrast, in volume overload conditions, in

which the major stimulus is diastolic loading, a predominant finding is a great increase in the cavity size or volume. Although there can be extensive

increases in mass, the relationship between mass and volume is either preserved or, in severe cases, reduced. The fundamental response is

generated by cellular hypertrophy. However, the configuration of the new contractile tissue is specific and offsets the mechanical stimulus.

[Modified from W Grossman et al in NR Alpert (ed): Perspectives in Cardiovascular Research. Myocardial Hypertrophy andFailure, vol 7. NewYork, Raven Press, 1993, with permission.]

D l t f h t f il i


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Compensated

concentric or eccentric hypertrophy

Sustained pressureoverload

Mechanical stretch

neurohormonal signalling

Genetic

factors Co-morbidities

Microvascular

abnormalities

Apoptosis

necrosis

Ischaemia Cell loss

Diastolic

dysfunction

Heart Failure

Altered

expression of

contractility

regulating

genes

Systolic

dysfunction

Decompensated

concentric hypertrophy

Decompensatedeccentric hypertrophy

Development of heart failure inthe hypertensive patient


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BP

Systolicdysfunction

Diastolicdysfunction

AB

LVH

Ejection fraction End diastolic volume LV dilation

Low cardiac output

syncrome

Ventriculararrhytmias

LV filling

pressure

Pulmonary venous

Congestion DyspneaBP = arterial blood pressure

LVH = left ventricular hypertrophy

Ejection fraction orEnd diastolic volume orLV size normal


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Characteristics of concentric (CON) vs

eccentric (ECC) hypertrophy and failure

Parameter CON ECC Failure

hypertrophy hypertrophy

1. Chamber size 2. Wall thickness 3. Myocyte length 4. Myocyte

cross-sectional area

5. Sarcomere assembly PLC (ANG II, Cytokines ?

signalling a1, ET) (CT-1,? TNF-a)


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The hypertension to heart failure continuum

Hypertension

LV hypertrophy Myocardial infarction

Remodelling

SystolicDiastolic

Symptoms Decreased tissueperfusion

Increasedhospitalisations

Coronary risk

factors

Death

Coronary artery

disease

LV dysfunction

Heart failure

LV dilation LV damage

Prognosis of Heart Fail re


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Prognosis of Heart Failure

Community Studies

40

50

60

70

80

90

100

0 1 3 6 12 24

Hillingdon (n = 220)

Framingham Men (n = 331)

Framingham Women (n = 321)

Months

50%Survival

Reported

Framingham 1993Hillingdon 1998

%


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Mortality in patients with heart failure

in the Framingham study

Mortality at time from Men Women

diagnosis of HF

2 years 37% 33%

6 years 82% 67%

Kannel (1991)


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Hypertensionand

Stroke

Influence of antihypertensive therapy on the


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Influence of antihypertensive therapy on the

incidence of stroke and coronary events

HDFP trial

MRC trial

12 others

All trials

HDFP trial

MRC trial

12 others

All trials

Strokes

102 : 158

60 : 109

127 : 217

(Heterogeneity X2=0.85 NS)

CHD events

275 : 343

222 : 234

174 : 194

(Heterogeneity X2=2.3 NS)

42% SD 62p


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Hipertensi menyebabkan :

Deg. hyaline (lipohialinosis) arteriol otak infark lakuner

Deg. Otot Polos arteriol otak berry

aneurysm perdarahan subkortikalhipertensif

Plak pada arteri basal otak karotis interna

bifukarsio karotis trombosis dan emboliarteri otak


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Hypertensionand

Renal Damage

Age adjusted relative risk of end stage renal


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Age-adjusted

relative risk

Klag (1991)

10

20

SBP

DBP

Age-adjusted relative risk of end-stage renal

disease due to any cause in the MRFIT study


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1.HT TD a.afferen gelung

glomerulus dan a.efferenmeningkat

2.AT2 penyempitan a.afferen hipertensi glomeruler

glomerulusklelorosis dan

proteinuria. Protenuria diseraptubulus fibrosis interstitium

gagal ginjal


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DASH indicates Dietary Approaches to Stop Hypertension. *For overall cardiovascular risk reduction, stop smoking. The effects ofimplementing these modifications are dose- and time-dependent and could be greater for some individuals.


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Therapyof

Hypertension

H t i T t t


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Hypertension in practice 2nd, Beevers & MacGregor

Hypertension Treatments

Rules of Halves

7 million pts

Hypertension

50 % Diagnosis50 % not diagnosed

50 % Treated50 % not treated

50 % well treated(12.5 % of allhypertensives)

50 %poorly controlled

Antihypertensive therapy and the


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Antihypertensive therapy and the

prevention of cardiovascular complications

Cumulative incidence of cardiovascular complications in hyper-

tensive patients with diastolic blood pressure of 90114 mmHg

Complications with lethal outcome (%) All cardiovascular complications (%)

Observation period (years) Observation period (years)

60

50

40

30

20

10

0

60

50

40

30

20

10

00 1 2 3 4 5 0 1 2 3 4 5

Control

Treated

Veterans Administration Cooperative Study Group (1970)

Blood pressure threshold levels for


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Country/ Diastolic Systolic Observation Threshold valueorganisation blood blood period with additional

pressure pressure risk factors(mmHg) (mmHg) (months) (mmHg)

WHO/ISH 95 160 36 140/90

Germany 95 160 36

USA* 90 140 36

95 150 36 90

UK 100 160 36 90

New Zealand 100 170 6 90

*Two different opinions are reflected for the USA in the JNC V

Blood pressure threshold levels for

initiating antihypertensive therapy


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AUTOREGULATION

BLOOD PRESURE = CARDIAC OUTPUT

Hypertension = Increased CO

PERIPHERAL RESISTANCE

Increased PR

Preload ContractillityFunction

constrictionStructural

hypertrophy

Fluid Volume VenousContractillity

Renal

sodiumretention

Decreasedfiltration

surface

Sympathetic

nervous over

activity

Renin

anglotensin

excess

Cell

membrane

alteration

Hyper

Insullinemia

Excess

sodium

infakeGenetic

alteration

Stress Obesity

Endothelumderived

factors

X

and or

Genetic

alteration

Classes of antihypertensive


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Classes of antihypertensive

agents

Diuretics thiazides and related agents

loop diuretics

K+-sparing diuretics

Sympatholytic drugs

centrally acting agents

adrenergic neurone-blocking

agents

adrenergic antagonists

a1 adrenergic antagonists

multiple-action neurohormonal

antagonists

Vasodilators arterial dilators

arterial and venous dilators

Ca2+

channel blockers

ACE inhibitors

Angiotensin II receptorantagonists

Goodman and Gilman (1996)


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PHYSIOLOGICAL ACTIONS OF -

ADRENERGIC RECEPTORS

ORGAN RECEPTOR TYPE RESPONSE TO STIMULATE

Heart

SA node 1 Increased heart rate

Atria 1 Increased contractility and

conduction velocity

AV node 1 Increased automaticity and

conduction velocity

His-Purkinje 1 Increased automaticity and

System conduction velocityVentricles 1 Automaticity, contractility and

conduction velocity

ArteriesPeriphera 2/ Dilatation/Contraction

Coronary 2/ Dilatation/Contraction

Carotid 2/ Dilatation/Contraction


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BETA-ADRENOCEPTOR BLOCKING DRUGS

Nonselective Selective With alpha-Blocking

Activity

Nadolol

Propranolol

TimololSatolol

Tertalolol

Pindolol

Carteolol

PenbutololAlprenolol

Oxprenolol

Dilevalol

Atenolol

Esmolol

MetoprololBevantolol

Bisoprolol

Betaxolol

Acebutol

(Practolol)Celiprolol

Labetalol

Bucindolol

Carvedilol

-

SA

+

ISA

-

ISA

+

ISA


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lanjutan


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lanjutan

lanjutan


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Source:Physicians Desk Reference. 57th ed. Montvale, NJ: Thomson PDR; 2003. *In some patients treated once daily, the antihypertensive

effect may diminish toward the end of the dosing interval (trough effect). BP should be measured just prior to dosing to determine if

satisfactory BP control is obtained. Accordingly, an increase in dosage or frequency may need to be considered. These dosages may

var from those listed in thePh sicians Desk Re erence, 57th ed. Available now or soon to become available in eneric re arations.


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