Blok10

Sistem Sirkulasi

Hypertension
Pujowaskito

Lab. IPD/ Jantung

FK Unjani / RS Dr. Dustira
Cimahi
 HYPERTENSION

 Worldwide  1 billion people

 USA  50 million people
 Prevalence in China 13.6%; Canada
22%; Egypt 26.3%
 Prevalence will be higher if there are no
effective preventions
Prevalence of high blood pressure by age and race or
ethnicity for men and women in the US population US
population 18 years of age and older.
80
Prevalence of hypertension (%)

Men *
60 *

40

20

0
80 *
Women *
60

40

20
* * * *
0
18-29 30-39 40-49 50-59 60-69 70-79 >80
Age (years)
Non-hispanic
Non-hispanic black
black Non-hispanic
Non-hispanic white
white Mexican
Mexican American
American
Effects of blood pressure on the risk of
cardiovascular disease
Average annual incidence rate per 10.000
100
90 CHD
80
70
60
50
40 Stroke
30
CHF
20
10
0
<100 120 140 180 >180
Systolic blood pressure (mmHg)
Source : Framingham study (after Gorlin)
 Neurohormonal control of blood pressure
Blood pressure = Cardiac output (CO) x Peripheral resistance (PR)
Hypertension = Increased CO and/or Increased PR

Vasoconstriction
 Preload  Contractility
 Fluid volume

 Fluid volume
Sympathetic Renin-
nervous angiotensin-
Renal sodium system aldosterone
retention system

Excess Genetic
sodium factors
intake
(Adapted from Kaplan, 1994)
Acute neurohormonal effects on blood
pressure homeostasis
Perfusion

 RAA  SNS

 Heart rate and cardiac output

 Sodium and water retention

 Blood pressure
 Chronic neurohormonal effects on
vascular structure
Perfusion

 RAA  SNS

 Myocardial hypertrophy

 Glomerular hypertention
and hypertrophy

 Vascular hypertrophy
Haemodynamic Transition from Hyperkinetic
to Typical Essential Hypertension

HEART RESISTANCE ARTERIOLES

Cardiac Beta adrenergic Wall/lumen Endothelial

compliance responsiveness ratio damage

Stroke Vaso-
Heart rate Vasodilation
volume constriction

CARDIAC OUTPUT VASCULAR RESISTANCE

PATOPHYSIOLOGY
The factors affecting cardiac output:
- sodium intake, renal function, &
mineralocorticoids
- the inotropic effects occur via extracellular
fluid volume augmentation
- an increase in heart rate and contractility

Peripheral vascular resistance is dependent

upon the sympathetic nervous system,
humoral factors, and local autoregulation

(Sharma,
2003)
Caused of Hipertension :
I. Primer / essential / idiopathic
II. Sekunder :
A. Renal
B. Endocrine
C. Coartation of the aorta
D. Pregnancy induced hypertension
E. Neurological disorder
F. Drug and other abused substancen
Diagnosis Rudnick, Danielson, Sinclair, et
et al et al al
Essential 94% 95.3% 92.1%
hypertension
Chronic Renal 5% 2.4% 5.6%
disease
Renovascular 0.2% 1.0% 0.7%
Disease
Coarctation of 0.2% - -
aorta
Primary - 0.1% 0.3%
aldosteronism
Cushing’s 0.2% 0.1% 0.1%
syndrome
Pheochromo- - 0.2% 0.1%
cytoma
Oral 0.2% 0.8% 1.0%
contraceptive
Number 665 1,000 3,783
patients:
JNC VII
Blood Pressure Classification
BP SBP DBP
Classification mmHg mmHg

Normal <120 and <80

Prehypertension 120–139 or 80–89
Stage 1 140–159 or 90–99
Hypertension
Stage 2 >160 or >100
Hypertension
JNC VII
CVD Risk Factors

- Hypertension*
- Cigarette smoking
- Obesity* (BMI >30 kg/m2)
- Physical inactivity
- Dyslipidemia*
- Diabetes mellitus*
- Microalbuminuria or estimated GFR <60 ml/min
- Age (older than 55 for men, 65 for women)
- Family history of premature CVD
(men under age 55 or women under age 65)
 JNC VII
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
Treatment
Overview of JNC VII
 Goals of therapy
 Lifestyle modification
 Pharmacologic treatment
• Algorithm for treatment of hypertension

 Classification and management of

BP for adults
 Followup and monitoring
Lifestyle Modification JNC VII
Modification Approximate SBP reduction
(range)
Weight reduction 5–20 mmHg/10 kg weight loss
Adopt DASH 8–14 mmHg
eating plan
Dietary sodium 2–8 mmHg
reduction
Physical activity 4–9 mmHg
Moderation of 2–4 mmHg
alcohol
consumption
 NEW TREATMENT APPROACH
Hypertension = disease of blood vessels

Vascular biology altered

Treat vasculature

Therapeutic
options

ACE AT1 Calcium Diuretics* Others

Inhibitors ß-
blockers channel
Blockers*
blockers
* Minimal evidence of effects on endothelial function
 Benefits of Lowering BP

Average Percent Reduction

Stroke incidence 35–40%

Myocardial infarction 20–25%

Heart failure 50%

Algorithm for Treatment of Hypertension JNC VII
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 With Compelling

Indications Indications

Stage 1 Hypertension Stage 2 Hypertension Drug(s) for the compelling

(SBP 140–159 or DBP 90–99 (SBP >160 or DBP >100 mmHg) indications
mmHg) 2-drug combination for most Other antihypertensive drugs
Thiazide-type diuretics for most. (usually thiazide-type diuretic and (diuretics, ACEI, ARB, BB, CCB)
May consider ACEI, ARB, BB, CCB, ACEI, or ARB, or BB, or CCB) as needed.

or combination.
Not at Goal
Blood Pressure

Optimize dosages or add additional drugs

until goal blood pressure is achieved.
Consider consultation with hypertension
specialist.
Classification and Management of BP for adults
BP SBP* DBP* Lifestyle Initial drug therapy
classifica- mmH mmH modifi- Without compelling With compelling
tion g g cation indication indications

Normal <120 and Encou-

<80 rage
Prehyper- 120– or 80– Yes No antihypertensive Drug(s) for
tension 139 89 drug indicated. compelling
indications. ‡
Stage 1 140– or 90– Yes Thiazide-type diureticsDrug(s) for the
Hyperten- 159 99 for most. May compelling
sion consider ACEI, ARB, indications.‡
BB, CCB, or Other
combination. antihypertensive
Stage 2 >160 or Yes Two-drug combination drugs (diuretics,
Hyperten- >100 for most† (usually ACEI, ARB, BB,
sion thiazide-type diuretic CCB) as
and ACEI or ARB or needed.
BB or CCB).
 Guidelines for selecting drug treatment of hypertension
Class of drug Compelling Possible
Indications Indications
Diuretics Heart failure Diabetes
Elderly patients
Systolic hypertension
Beta-Blockers Angina Heart failure
After myocardial infarct Pregnancy
Tachyarrhythmias Diabetes
ACE Inhibitor Heart failure
Left ventricular dysfunction
After myocardial infarct
Diabetic nephropathy
Calcium Angina Peripheral vascular disease
Antagonists Elderly patients
Systolic hypertension
Alpha-Blockers Prostatic hypertrophy Glucosa intolerance
Dyslipidemia
Angiotensin II Side effects with other grug classes, Heart failure
Antagonists for example, ACE inhibitor cough
 (cont’d)
Guidelines for selecting drug treatment of hypertension
Class of drug Compelling Possible
Contraindications Contraindications
Diuretics Gout Dyslipidemia
Sexually active males
Beta-Blockers Asthma and chronic Dyslipidemia
obstructive pulmonary disease Athletes and physically
Heart blocka active patients
Peripheral vascular disease
ACE Inhibitor Pregnancy
Bilateral renal artery stenosis
Hyperkalaemia
Calcium Heart blockb Congestive heart failurec
Antagonists
Alpha-Blockers Orthostatic hypotension
Angiotensin II Pregnancy
Antagonists Bilateral renal artery stenosis
Hyperkalaemia
a
Grade 2 or 3 atrioventricular block
b
Grade 2 or 3 atrioventricular block with verapamil or diltiazem
c
Verapamil or diltiazem
 Compelling Indications for
Individual Drug Classes JNC VII
Compelling Indication Initial Therapy Options Clinical Trial Basis

Heart failure THIAZ, BB, ACEI, ARB, ACC/AHA Heart Failure

ALDO ANT Guideline, MERIT-HF,
COPERNICUS, CIBIS,
SOLVD, AIRE, TRACE,
ValHEFT, RALES

Postmyocardial BB, ACEI, ALDO ANT ACC/AHA Post-MI

infarction Guideline, BHAT,
SAVE, Capricorn,
EPHESUS

High CAD risk THIAZ, BB, ACE, CCB ALLHAT, HOPE,

ANBP2, LIFE,
CONVINCE
 Compelling Indications for
Individual Drug Classes
JNC VII

Compelling Indication Initial Therapy Options Clinical Trial Basis

Diabetes THIAZ, BB, ACE, NKF-ADA Guideline,

ARB, CCB UKPDS, ALLHAT

NKF Guideline,
Chronic kidney ACEI, ARB Captopril Trial,
disease RENAAL, IDNT, REIN,
AASK

Recurrent stroke THIAZ, ACEI PROGRESS

prevention
Haemodynamic profiles associated with long term
administration of antihypertensive drugs
Drugs Heart Cardiac Total Plasma Plasma Renal
rate output peripheral volume renin blood
resistance activity flow
Diuretics
-blockers
without ISA
with ISA
-blockers
Calcium antagonists or
ACE inhibitors
Angiotensin II ??
receptor antagonists

ISA = intrinsic sympathomimetic activity;

ACE = angiotensin-converting enzyme
Adapted from Burnier et al (1990)
 Renin-Angiotensin Aldosterone
System
Non-ACE pathways  Vasoconstriction
(eg, chymase)  Cell growth
 Na/H2O retention
 Sympathetic activation
Angiotensinogen

Renin Angiotensin I AT1

Angiotensin II
ACE
Aldosterone AT2

Cough,  Vasodilation
Inactive  Antiproliferation
angioedema  Bradykinin fragments (kinins)
Benefits?
 Diuretics
Diuretics -blockers
-blockers

ACE
ACE inhibitors/
inhibitors/ Calcium
Calcium
ARB
ARB antagonists
antagonists

11-Blockers

 -Blockers
 Reasons For Combination

• Potentiation / Synergism
• Fewer side effects
• Additive properties
• Complementary properties
• Complementary actions on specific target organs
• Fixed – Combination compliance
 Central BP and -BLOCKERS
effects

 Baroreceptor
Baroreceptor Carotid sinus
reflexes
reflexes 
?

Sinus rate
Stellate NE
Stroke volume
ganglion  Cardiac output
E 

Terminal
Renin Angio I neurone
 Angio II
NE


Systemic Initial rise

vascular then fall
resistance
 GOOD ANTIHYPERTENSIVE EFFECT
Sinus rate Renin inhibiton

Bradycardia
Bradycardia

Negative
Negativeinotropy
inotropy

Less
Less
bronchopasm
bronchopasm

1-SELECTIVE

Metabolic
Fewer peripheral effects
Circulatory
Similar cardiac and antihypertensive effects
NONSELECTIVE
(1-2)
More marked pulmonary and peripheral effects

-Antagonist
-Antagonist may
may be either 11-cardioselective
be either -cardioselective or
or non-cardioselective (11-- 22
non-cardioselective (
antagonism).
antagonism).
Vasodilatory -Blockers
Vasodilatory -Blockers

Vascular resistance (%)

110 Increasing
Increasing
vasodilation
vasodilation
VASODILATORY
-BLOCKERS

90

PINDOLOL

80 100
Cardiac output (%)
22 STIMULATION (ISA)
Ca2+
ADDED
-BLOCKADE
Ca2+
2+

cAMP + calmodulin Carvedilol

myosin
heads actin-myosin interaction

Other mechanisms
Smooth muscle relaxes
Classification Calcium Antagonists

Generation:
First Second Third Latest

Verapamil Felodipine Amlodipine Lercanidipine

Nifedipine Isradipine (hydrophilic) (lipophilic)
Diltiazem Nicardipine
Nimodipine
Nisoldipine
Nitrendipine

Prototype Tissue selectivity Tissue selectivity Tissue selectivity

gradual onset gradual onset
Plasma controlled membrane-controlled
J Clin Basic Cardiol 1999;2:155
 BETA-BLOCKERS – DIURETICS

1.  Plasma renin activity

2. Beta-blockers have some mild antialdosterone
3. For black and whites
4. For isolated systolic hypertension, stroke,
myocardial infarction.
ACE inhibitors / AIIRA – Betablockers

1. Younger patients with a high renin status

or high sympathoadrenergic tone
2. After acute myocardial infarction :
a.  risk of subsequent arrhythmias
b.  progressive ventricular dilatation
c.  exercise tolerance
Beta-blockers – Calcium Antagonists

1.  cardiac output,  peripheral resistance

2. To maintain endothelial intergrity
3.  plasma renin activity
4.  insulin resistance, lipid profiles
5.  left ventricular hypertrophy
6. Hypertension + angina pectoris
7. Hypertension + arrhythmias.
A Goal of Antihypertensive Therapy

“Therefore, a primary goal of

antihypertensive therapy perhaps
should be to reduce sympathoadrenal
activity and plasma catecholamine
levels - at the very least,
antihypertensive drugs should not
increase them.”

Izzo Am J Hypertens 1989; 2: 305S-312S

JNC VII

Goals of Therapy

 Reduce CVD and renal morbidity and

mortality
 Treat to BP <140/90 mmHg or
BP <130/80 mmHg in patients with
diabetes or chronic kidney disease
 Achieve SBP goal especially in
persons >50 years of age.
 JNC VII
Follow-up and Monitoring

 Patients should return for followup and adjustment

of medications until the BP goal is reached.

 More frequent visits for stage 2 HTN or with

complicating comorbid conditions.

 Serum potassium and creatinine monitored 1–2

times per year.
 Follow-up and Monitoring JNC VII
(continued)

 After BP at goal and stable, followup visits at 3- to 6-

month intervals.

 Comorbidities, such as heart failure, associated

diseases, such as diabetes, and the need for
laboratory tests influence the frequency
of visits.