MANAGEMENT

HYPERTENSION IN FIRST
LEVEL HEALTH FACILITIES

VENICE CHAIRIADI, MD , FIHA

Hypertension
More Than Just High BP
A complex syndrome in which neurohumoral and
metabolic abnormalities influence development
and progression of vascular disease and clinical
events
A complex inherited syndrome of cardiovascular risk factors

Hypertension Syndrome

Giles,TD, JCI Suppl,2005

Proportion of deaths attributable to

leading risk factors worldwide (2000)
High blood pressure
Tobacco
High cholesterol
Underweight
Unsafe sex

Systolic blood pressure

greater than 115 mmHg

High BMI
Physical inactivity
Alcohol
Indoor smoke from solid fuels
Iron deficiency
0

Attributable Mortality
WHO 2000 Report. Lancet. 2002;360:1347-1360.

Hypertension

Alexandra L.C. Martiniuk et.al J. Hypertension 2007 ; 25 : 88-92

Cardiovascular Mortality Risk Doubles with Each

20/10 mmHg Increment in Systolic/Diastolic BP*
Cardiovascular mortality risk
8

8X
ris
k

6
4
2
0

1X
risk

115/75

2X
risk

135/85

4X
ris
k

155/95

175/105

Systolic BP/Diastolic BP (mmHg)

*Individuals aged 4069 years

Lewington et al. Lancet 2002;360:190313

CIRCADIAN RHYTHM

Hypertension. 2009;53: 363-9

JNC VII CLASSIFICATION

European Heart Journal, 2007; 28:1462-1536

JNC 6 (1997)

JNC 7 (2003)

Optimal

Normal

< 120 and <80

< 120 and < 80

Normal
< 130 and < 85

Prehypertension

High-normal

120-139 or 80-89

Hypertension

130-139 or 85-89

Stage 1

Stage 1

140-159 or 90-99

140-159 or 90-99

Stage 2
160-179 or 100-109

Stage 2

Stage 3

> 160 or > 100

> 180 or > 110

JNC VI. Arch Intern Med. 1997;157:2413-2446. JNC 7. JAMA. 2003; 289(19):2560

Hypertension : The Disease Continuum

Early Paradigm

Natural History of CVD Progression

Elevated BP

Target Organ Damage

Elevated BP

Target Organ Damage

More Recent Paradigm

Vascular Dysfunction
A Proposed Future Paradigm

Endothelial
Dysfunction

Vascular
Dysfunction

Elevated BP

Target Organ
Damage

LVH
Renal
Damage

MI

Angina
Pectoris

Stroke

THE CARDIOVASCULAR CONTINUUM

Coronary
thrombosis

Myocardial
infarction

Myocardial
ischaemia
STROKE

CAD

Atherosclerosis
LVH

Risk factors
smoking, HYPERTENSION,
cholesterol, diabetes

Sudden Death
Arrhythmia &
loss of muscle
Remodelling
Ventricular
dilatation
Congestive
heart failure

Death

Blood Pressure Reduction Is Critical:

the Lower, the Better
Meta-analysis of 61 prospective, observational studies
1 million adults
12.7 million person-years

2mm Hg
decrease in
mean SBP

*Epidemiologic studies, not clinical trials of hypertension agents.

Lewington
S et al. Lancet. 2002;360:1903-1913.
1/20/17

7% reduction
in risk of
ischemic heart
disease
10% reduction in
risk of stroke
mortality

Leading Causes of Death and Disability (DALYs)

1990

Rank

Cause

2020

% Rank

Cause

1
2
3

Lower respiratory infections

Diarrhoeal diseases
Perinatal conditions

8.2
7.2
6.7

1
2
3

Ischemic heart disease

Major depression
Road traffic accidents

5.9
5.7
5.1

4
5
6
7
8
9
10

Major depression
Ischemic heart disease
Cerebrovascular disease
Tuberculosis
Measles
Road traffic accidents
Congenital abnormalities

3.7
3.4
2.8
2.8
2.7
2.5
2.4

4 Cerebrovascular disease
5 COPD
6 Lower respiratory infections
7 Tuberculosis
8 War
9 Diarrhoeal diseases
10 HIV

4.4
4.2
3.1
3.0
3.0
2.7
2.6

Global Burden of Disease Study, 1996

Effects of Hypertension on The

Heart

Left Ventricular Hypertrophy

Vascular Disease:
-Atherosclerosis
-Arteriosclerosis

Left Ventricular
Hypertrophy
Independent Predictor of:
Myocardial infarction
Stroke
Heart Failure
Total Mortality
Sudden Death

Progression From Hypertension

to Heart Failure
Obesity
Diabetes

LVH

Diastolic
Dysfunction

Hypertension
Smoking
Dyslipidemia
Diabetes

Normal LV
Structure
and Function

CHF
MI

Systolic
Dysfunction

LV
Remodeling

Subclinical LV
Dysfunction

LVH, left ventricular hypertrophy; MI, myocardial infarction; CHF, chronic heart failure.
Vasan RS and Levy D. Arch Intern Med. 1996;156:1789-1796.

Overt Heart
Failure

CV Complications of Untreated
Hypertension (N=500)
50

50
45
40
35
Event 30
rate 25
(%) 20

18

15

16
12
8

10
5
0

2
Renal
Failure

Stroke

Enceph

MI, myocardial infarction; CHF, chronic heart failure.

Perera GA J. Chron Dis. 1955;1:33-42.

MI

Angina

CHF

Cumulative Incidence of Heart Failure

by Baseline Hypertension Status
25

Stage 2+

Men aged 60-69 y

Stage 1

20

25
20

Cumulative
15
Incidence
(%)
10

Normotensive 15

0
40

Women aged 60-69 y

Stage 2+
Stage 1

10

10 12 14 16

40

Men aged 70-79 y

Stage 2+

Normotensive
2

10 12 14 16

Women aged 70-79 y

30

Stage 2+
Stage 1

10

Stage 1
20
Normotensive
10

30
Cumulative
Incidence 20
(%)

10

12

14

2
Time (y)

Levy D et al. JAMA. 1996;275:1557-1562.

Normotensive
4

10

12

14

Population-Attributable Risks
for Development of CHF
AP
DM 5%
6%
LVH
4%
VHD
7%

MI
34%

Men

Women
HTN
39%

DM
12%

AP
5%
HTN
59%

LVH
5%
VH
D
8%

MI
12%

Population-attributable risk defined as:

(100 x prevalence x [hazard ratio 1])/(prevalence x [hazard ratio 1] + 1)
CHF, chronic heart failure; AP, angina pectoris; DM, diabetes mellitus; LVH, left ventricular hypertrophy;
VHD, valvular heart disease; HTN, hypertension; MI, myocardial infarction.
Levy D et al. JAMA. 1996;275:1557-1562.

Average annual rate/ 10,000

Blood Pressure and Risk of Congestive Heart Failure:

the Framingham Study

Normotensive
BP <140/90 mmHg
Hypertensive
BP >160/95 mmHg

Age at examination
Kannel et al. 1972

Integrated Perspective on CV Risk

Factors and Vascular Disease
Endothelial Dysfunction

S
m

o
k
i
n
g

D
Dys
ia
elial
b
ndot h
E
e
t
n
e
s
Ross. N Engl J Med. 1999;340:115-126.

matio
Inflam

H
yp
er
t

CV
Disease

Ross. N Engl J Med. 1999;340:115-126.

tress

en
si
on

D
ys
lip Stress & Inflammation
Oxidative
id
em
ia

Hypertension-thrombosis via Ang II

LDL

BP

Diabetes

Smoking

Oxidative Stress
Endothelial Dysfunction and Smooth Muscle
Activation
NO Local Mediators Tissue ACE, AII
Endothelin
Catecholamines
Vasoconstriction

PAI-1, Platelet
VCAM/ICAM
Aggregation,
Cytokines
Tissue Factor
Thrombosis

Inflammation

Proteolysis
Inflammation

Growth Factors
Cytokines
Matrix

Plaque Rupture Vascular Lesion

and Remodeling

Reprinted with permission from Dzau VJ. Hypertension. 2001;37:1047-1052.

HYPERTENSION:
THERAPEUTIC ISSUES

WHY ARE 50% OF HTN PATIENTS UNCONTROLLED

WHEN 85% HAVE HEALTH INSURANCE?

30% No Rx

Younger
Male
Hispanic
0-1 visits/y

20% Rxd
Most on 1-2 meds
Men
AA, age, CKD,
obese
2 visits/y

Public education
Active screening
Improved access
to care

Therapeutic
efficiency
Therapeutic
inertia

Circulation 2011; 124:1046

adherence
MMWR 2011; 60:103

MANAGEMENT OF
HYPERTENSION

Non-pharmacological/ lifestyle
Pharmacological

Eur Heart Journal. 2007; 28, 1462-536

Suggested target blood pressures during

antihypertensive treatment. Systolic and diastolic
blood pressures should both be attained, e.g.
<140/85 mmHg means less than 140 mmHg for
systolic blood pressure and less than 85 mmHg for
diastolic blood pressure
Clinic BP (mmHg)

No diabetes
Optimal treated BP pressure
Audit Standard

Diabetes
<140/85

<150/90

<130/80
<140/80

Audit standard reflects the minimum recommended levels of blood pressure control.
Despite best practice, the Audit Standard will not be achievable in all treated hypertensives.
For ambulatory (mean daytime) or home blood pressure monitoring - reducing these targets by
~10/5 is recommended.

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
Stage 1
Hypertension (SBP
140-159 or DBP 9099 mmHg) Thiazidetype diuretics for
most. May consider
ACEI, ARB, BB, CCB,
or combination

With Compelling
Indications

Stage 2 Hypertension
(SBP 160 or DBP 100
mmHg) Two-drug
combination for most
(usualy Thiazide-type
diuretics ACEI, ARB, BB,
CCB)

Drug(s) for the

compelling indications
Other
antihypertensive
drugs (diuretics, ACEI,
ARB, BB, CCB) as
needed

Not at Goal Blood Pressure

Optimized dosages or add additional drugs until goal blood
pressure is achieved consider consultation with
hypertension specialist

JNC VII, 2003

Lifestyle Modifications
Modification
Weight reduction

Approximate SBP reduction

(range)
520 mmHg/10 kg weight loss

Adopt DASH eating plan

814 mmHg

Dietary sodium reduction

28 mmHg

Physical activity

49 mmHg

Moderation of alcohol
consumption

24 mmHg

Non-pharmacological interventions
Measures that lower blood pressure:

weight
salt intake
alcohol consumption
physical exercise
fruit & vegetable consumption

Measures to reduce cardiovascular risk:

Stop smoking
saturated fat, poly- & mono-unsaturates
oily fish consumption
total fat intake
BHS Guidelines 1999

Lifestyle measures
Maintain normal weight for adults (body mass index 20-25
kg/m2)
Reduce salt intake to <100 mmol/day (<6g NaCl or <2.4 g
Na+/day)
Limit alcohol consumption to 3 units/day for men and 2
units/day
for women
Engage in regular aerobic physical exercise (brisk walking
rather
than weight lifting) for 30 minutes per day, ideally
on most of days
of the week but at least on three days of
the week
Consume at least five portions/day of fresh fruit and
vegetables
Reduce the intake of total and saturated fat

Drug treatment of hypertension

Diuretic
Calcium-channel
blocker
Beta-blocker

ACE-inhibitor
Angiotensin receptor
blocker
(Alpha-blocker)

Most hypertensives will need 2 drugs to control

BP
Drug combinations may be synergistic

ISH Spring Meeting. 2010

CCB + ACE I/ARB :

The Synergies of Counter-Regulation (1)

CCB
Arteriodilation
Peripheral oedema
Effective in low-renin patients
Reduces cardiac ischaemia

BP

Synergistic
BP reduction
Complementary
clinical benefits

Mistry et al. Expert Opin Pharmacother. 2006;7:575581;

Sica.
34 Drugs. 2002;62:443462; Quan et al. Am J Cardiovasc Drugs. 2006;6:103113.

CCB
RAS activation
No renal or CHF
benefits

CCB +ACE I/ ARB :

The Synergies of Counter-Regulation
(2)
CCB
Arteriodilation
Peripheral oedema
Effective in low-renin patients
Reduces cardiac ischaemia

ACEi/ARB
Venodilation
Attenuates peripheral oedema
Effective in high-renin patients
No effect on cardiac ischaemia

BP

Synergistic
BP reduction
Complementary
clinical benefits

Mistry et al. Expert Opin Pharmacother. 2006;7:575581; Sica. Drugs. 2002;62:443462;

Quan
35 et al. Am J Cardiovasc Drugs. 2006;6:103113.

ACEi/ARB
RAS blockade
CHF and renal
benefits

CCB
RAS activation
No renal or CHF
benefits

How to choose anti-hypertensive therapy

ACE inhibitor (AII antagonist)
or
-blocker
B

Calcium antagonist

One drug:
Younger, non-black
Older, black
C or D
Two drugs: (A or B) + (C or D)
Three drugs: (A or B) + C + D

Diuretic

A or B

Venous Fluid Leakage Induced by

CCBs

ie et al. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:4273; White et al. Clin Pharmacol Ther.
86;39:4348; Gustaffson. J Cardiovasc Pharmacol. 1987;10:S121S131.

 Gets Reduced by Co-administration of ACEI/ARBs

Opie et al. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:4273; White et al. Clin Pharmacol Ther.
1986;39:4348; Gustaffson. J Cardiovasc Pharmacol. 1987;10:S121S131; Messerli et al. Am J Cardiol.
2000;86:11821187.

ACE inhibitor is more

than just blocking the
renin-angiotensin system

ACE inhibitors are recommended in a wide majority of

patients - JNC 7 Guideline -

Aldo Ant

CCB

ARB

ACEI

BB

Compelling
Indication*

Diuretic

Recommended
Drugs
Clinical trial basis

Heart Failure

ACC/AHA Heart Failure Guideline, MERITHF,

COPERNICUS, CIBIS, SOLVD, AIRE, TRACE,
ValHEFT, RALES, CHARM

Postmyocardial
Infarction

ACC/AHA Post-MI Guideline, BHAT, SAVE,

Capricorn, EPHESUS

High Coronary Disease

Risk

ALLHAT, HOPE, ANBP2, LIFE, CONVINCE,

EUROPA, INVEST

Diabetes

NKF-ADA Guideline, UKPDS, ALLHAT

Chronic Kidney Disease

NKF Guideline, Captopril Trial, RENAAL, IDNT,

REIN, AASK

Recurrent Stroke
Prevention

PROGRESS

Multiple mechanisms of ACEI

Vasculoprotective effects
Blood pressure lowering
Direct antiatherogenic
Cardioprotective effects
Enhance endogenous fibrinolysis
Preload and afterload
Inhibit platelet aggregation
LV mass
Antimigratory for mononuclear cells
Sympathetic stimulation
Matrix formation
Reperfusion injury
Improve endothelial function
Improved myocardial
Antioxidant
remodeling
Anti-inflammatory
Protection from plaque rupture
Improved arterial compliance and tone

Angiotensin II reduction / bradykinin increase

Lonn E et al. Eur Heart J. 2003;5(suppl):A43-8.

Compelling and possible indications, contraindications, and

cautions for the major classes of antihypertensive drugs
Compelling
indications

Possible
indications

Beta-blockers

MI,
Angina

Heart failure

CCBs
(dihydropyridine)
CCBs
(rate limiting)

Elderly, ISH

Angina

Angina

Elderly

Class of drug

Thiazide/thiazide- Elderly
like diuretics
ISH
Heart failure
2 o stroke
prevention

Caution

Compelling
contraindications

Heart failure,
PVD,
Diabetes
(except with
CHD)
-

Asthma/COPD,
Heart block

Combination
with betablockade

Heart block
Heart failure

Gout

Hypertension. 2003; 42:120652

TERAPI ANTI HIPERTENSI

ISH Spring Meeting. 2010

ISH Spring Meeting. 2010

Obat

HL

Onset

Durasi

PPT

Bioav
(%)

Lisinopril

12 jam

1-6 jam

24 jam

6-8 jam

25

Ramipril

13-17
jam

4 jam

24 jam

2-4 jam

50-60%

Perindopril

3-10
jam

1,5 jam

24 jam

1 jam

75 %

Trandolapril

6-10
jam

4 jam

24 jam

1 jam

80 %

Enalapril

1,3 jam

1-4 jam

12-24
jam

1 jam

60 %

Losartan

1,5-2
jam

6 jam

24 jam

11,5jam

25%

Valsartan

6-9 jam

2 jam

6-8 jam

2-4 jam

25 %

Medscape, drugs, conditions, procedures, 2011

Other medications for hypertensive

patients
Secondary prevention
(including patients with type 2 diabetes)
(1) Aspirin: use for all patients unless
contraindicated
(2) Statin: use sufficient doses to reach targets if
patient is aged up to at least 80 years with a
total cholesterol concentration 3.5 mmol/l
(3) Vitamins no benefit shown, do not prescribe

Provides powerful and

smart BP reductions
and
high
24h
BP
control
including
patients with addedrisk such as diabetes
and obese

ThankYou