PRINCIPLE MANAGEMENT OF

HYPERTENSION

Nur Samsu
Division of Nephrology and Hypertension
2014

LEARNING OBJECTIVE:
After completing this module, the students be able to:
Explain the definitions of normal blood pressure,
prehypertension and hypertension
Explain the risk factors associated with essential hypertension
Describe and explain the secondary causes of hypertension
Explain the complication of hypertension
Describe white coat hypertension, mask hypertension, and
resistant hypertension
Evaluation and management of hypertension
Describe mode of action, indications and side-effects of
antihypertensive drugs

Case
A 40

years old sedentary man with a family history

of stroke sees you for a health maintenance visit.
His BP=150/100 mmHg and an LDL cholesterol of
170 mg/dl

Which one of the following would have the

greatest impact on decreasing his future risk of
stroke?
A)
B)
C)
D)

A program of regular physical exercise

Aspirin 80 mg daily
Reduction of LDL to <100 mg/dl
Reduction of BP to normal

Answer:
D)

Reduction of BP to normal

General Facts

Stroke is the 3rd leading cause of death in the

US
HTN is the most consistently powerful
predictor of stroke

Primary prevention of stroke. N Engl J Med 1995

Lowering BP results in 35-40% reduction in

stroke incidence
US Data
Primary prevention of stroke. N Engl J Med 1995

Hypertension
High BP
causescardiovascular risk
The most important
modifiable
factor 35% of all cardiovascular deaths
Commonest
of premature
50%cause
of all stroke
deathsdeath
Continuum
ofof
increasing
CV risk from SBP 115
25%
all CAD deaths
mmHg
50% of all congestive heart failure
CV mortality doubles for every 10/5 increase in BP
25%
of all premature deaths
> 120/70
mmHg
Commonest cause of CKD

High Worldwide Prevalence

of Hypertension
Germany
Finland
Spain
England
Sweden
Italy
Japan
Egypt
South Korea*
United States
Canada
Taiwan
0

10

20

30

40

50

60

70

Prevalence (%)
*South Korean data reflects men aged 30-59 with BP 140/90.
Wolf-Maier K et al. JAMA. 2003;289:2363-2369; WHO Collaborating Centre on Surveillance of Cardiovascular
Disease Web site.

Prevalensi Hipertensi di Indonesia

Pemeriksaan pada 2593 penduduk usia > 18,

Hipertensi (st 1 & 2) sebanyak 31% !
Riskesdas tahun 2007-2008

Pathogenesis of Primary Hypertension

Blood pressure
Hypertension

=
=

Cardiac output x Peripheral resistance

Increased CO and/or Increased PR
Vasoconstriction

Preload

Contractility
Heart rate

Fluid volume
Sympathetic
nervous
system

Renal sodium
retention
Excess
sodium
intake

Reninangiotensinaldosterone
system

Genetic
factors
Kaplan (1994)

Role of the Kidney in Hypertension

Renal-Body

Fluid Feedback System for LongTerm Blood Pressure Regulation

Mechanisms of Impaired Renal-Pressure
Natriuresis in Hypertension
Salt-Sensitive and Salt-Insensitive Hypertension
The Renin-Angiotensin System
Aldosterone
The Sympathetic Nervous System

Blood Pressure Distribution in the

Population According to Age
Men

Women

150

150

130

130
PP

110
80

80

70

70
30-3940-4950-5960-6970-79 80

Age

PP

110

30-3940-4950-5960-6970-79 80

Age

PP=Pulse Pressure.
Adapted from : Third National Health and Nutrition. Examination Survey, Hypertension
1995;25:305-13

Hypertension: a multifactorial entity

PATIENT 1 PATIENT 2

PATIENT 3

Renin-angiotensin system

Sympathetic nervous system

Renal Retention of Excess Sodium

Vasoconstriction / Vascular Hypertrophy

UKPDS: Tight Glucose vs Tight BP Control

and CV Outcomes

Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661.

Reprinted by permission, Harcourt Inc.

Improved identification,
diagnosis and treatment of
HYPERTENSION could
improve outcomes, reduce
hospital admissions and costs.

Hypertension Assessment

Initial Evaluation
Confirm

diagnosis (Repeat readings,

home BP, ABP)
Screen for secondary causes
Estimate CV risk status
Assess Target Organ Damage
Co-morbid conditions

BP MEASUREMENT
Which of the following factors
can lower blood pressure
readings?
A)Obese extremities
B)Caffeine ingestion
C)Narrow BP cuff
D)Supporting the patients
back
http://www.mco.edu/org/whl/images/belissi.jpg

BP MEASUREMENT
Answer:
D)Supporting the patients back
relaxes

the body, lowering BP an avg of 8 mmHg

SBP and DBP

Obese extremities
Caffeine ingestion
Narrow BP cuff

can result in false

elevations

Common problems in BP
measurement
Wrong

cuff size
Excess pressure of
stethoscope
Patient arm at the wrong level
White coat effect
Auscultatory Gap (silent gap)

A cuff with a bladder too small

for the patients arm will result in:
a.

An inaccurately high reading

b.

An inaccurately low reading

Effect of cuff size on manual BP measurement.

An inappropriately small BP cuff yields erroneously high values for BP because
the pressure within the cuff is incompletely transmitted to the underlying artery

Secondary Hypertension
1. Identifiable underlying cause:
kidney disease
renal artery stenosis
hyperaldosteronism
pheochromocytoma
2. Represents approximately 10% of all hypertension
3. Has specific therapy, and is potentially curable
4. Often distinguishable from essential hypertension on
clinical grounds

Secondary Hypertension
Primary Causes
Essential Hypertension
Secondary Causes
Renal Parenchymal Disease
(CKD)
Renovascular HTN
All Endocrine HTN
Drug Induced HTN
Coarctation of the Aorta

90-95%
2-6%
1-4%
1%
1%
0.1-1.0%

How common is primary hyperaldosteronism?

Prevalence of unrecognized primary aldosteronism in patients with hypertension

Author
Gordon et al.
Kumar et al.
Kreze et al.
Lim et al.
Loh et al.
Fardella et al.
Schwartz et al.
Rossi et al.

Country
Australia
India
Slovakia
United Kingdom
Singapore
Chile
United States
Italy

No. screened Prevalence

199
103
115
465
350
305
117
1,046

8.5%
8.7%
13.0%
9.2%
4.6%
9.5%
12.0%
6.3%

When to Screen for 2 HTN:

Clinical Clues
Severe

or refractory HTN
An acute rise in BP over a previously stable
baseline
An acute elevation in the plasma creatinine
concentration that is either unexplained or
occurs after ACEI or ARB therapy
Age of onset before puberty or above 50
Negative FH for hypertension especially if <
30 and non-obese

Risk Factors of Clinical Events

BP

level

Calculated

CV risk (estimated from factors

such as age, gender, smoking history etc.)

Presence

of target organ damage

Presence

of established CV disease

Concomitant

disease associated with CV risk

(e.g. diabetes or CKD)

FRAMINGHAM RISK CALCULATOR

Blood Pressure and Cardiovascular Risk:

ESHESC Guidelines
BP (mmHg)
Grade 3

Other RF,
OD or
disease

Normal

High normal

Grade 1

Grade 2

SBP 120129
or DBP 8084

SBP 130139
or DBP 8589

SBP 140159
or DBP 9099

SBP 160179
or DBP 100109

SBP 180
or DBP 110

No other RF

Average risk

Average risk

Low added
risk

Moderate
added risk

High added
risk

12 RF

Low added
risk

Low added
risk

Moderate
added risk

Moderate
added risk

Very high
added risk

3 RF, MS,
OD or
diabetes

Moderate
added risk

High added
risk

High added
risk

High added
risk

Very high
added risk

Established
CV or renal
disease

Very high
added risk

Very high
added risk

Very high
added risk

Very high
added risk

Very high
added risk

MS = metabolic syndrome
OD = subclinical organ damage
RF = risk factors

Reproduced from the Task Force of ESHESC. J Hypertens 2007;25:110587

Copyright 2007, with permission from Lippincott Williams and Wilkins

Complications of Hypertension:
End-Organ Damage
Hypertension

Hemorrhage,
Stroke

Retinopathy

LVH, CHD, CHF

Peripheral
Vascular
Disease

CHD = coronary heart disease

CHF = congestive heart failure
LVH = left ventricular hypertrophy
Chobanian AV, et al. JAMA. 2003;289:2560-2572.

Renal Failure,
Proteinuria
Slide Source
Hypertension Online
www.hypertensiononline.org

Co-morbid conditions
Hypertension Syndrome!!
Its More Than Just Blood Pressure
Obesity

Decreased
Arterial
Compliance

Endothelial
Dysfunction
Abnormal
Glucose
Metabolism

Abnormal Lipid
Metabolism

Hypertension

Accelerated
Atherogenesis
LV Hypertrophy
and Dysfunction

Abnormal
Insulin
Metabolism

Neurohormonal
Dysfunction

Renal-Function
Changes
Blood-Clotting
Mechanism
Changes

Kannel WB. JAMA. 1996;275:1571-1576. Weber MA et al. J Hum Hypertens.

1991;5:417-423. Dzau VJ et al. J Cardiovasc Pharmacol. 1993;21(suppl 1):S1-S5.

Men

None
19%

Women

Four
8%
Three
22%

One
26%

Two
25%

Comorbidities:
Obesity
Glucose
intolerance
Hyperinsuline
mia
Reduced HDL-C
Elevated LDL-C
Elevated TG
LVH

None
17%

Four
12%
Three
20%

One
27%

Two
24%

>50% have 2 or more

comorbidities
Kannel WB. Am J Hypertens. 2000:13:3S-10S.

Hypertension Management

Lifestyle Modification
Modification

Approximate SBP reduction

(range)

Weight reduction

520mmHg/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

Hasil POLL (on-line)

Seberapa rutin Anda berolahraga?
1.
2.
3.
4.
5.
6.

Setiap hari (469) : 9%

Dua hari sekali (331) : 7%
Seminggu 2 kali (640) : 13%
Seminggu sekali (1064) : 21%
Sebulan sekali (361) : 7%
Hampir tidak pernah (2140) : 43%

Indications for Pharmacotherapy

(Strongly consider prescription)

Average DBP > 90 mmHg and:

Hypertensive with Target-organ damage or
Independent cardiovascular risk factors
Elevated systolic BP
Cigarette smoking
Abnormal lipid profile
Strong family history of premature CV disease
Truncal obesity
Sedentary Lifestyle

Average DBP > 80 mmHg in a patient with diabetes or CKD

CHEP 2013

Choose the antihypertensive

medication!!!
Alpha Blocker

Renin Inhibitors

AT1Antagonist

2 - agonists
Ganglionic
blockers
Vasodilators
Diuretic

Dr. Rx
Rational

Drug of
choice

ACE Inhibitor
-Blocker
Ca++ Antagonist

Anti-Hypertensive Drugs: Sites of Action

Symphatetic
Activity

Renin inhibitors

Renin

BLOCKERS
Cardiac
Output

Thiazids

ACE-i
ARBs

Calsium Antagonist+

BLOCKERS
HYDRALAZINE

PERIPHERAL
VASCULAR
RESISTENCE

Factors affecting choice of

antihypertensive drug
CV

risk profile of the patient

Comorbidities / Coexisting disorders
Target organ damage
Severity

of hypertension
Interactions with drugs used for concomitant
conditions
Age
Ethnicity
Tolerability of the drug
Cost of the drug

39

Positive Indications for Drugs Used in the

Treatment of Hypertension
Clinical Condition

Suitable Drug

Edema, Dsypnea

Diuretic

Hypokalemia

Eplerenone, ACE Is

Sinus Tachycardia

-blocker

Ventricular Ectopies

-blocker

Angina

-blocker

Severe Renal Impairment

Furosemide > thiazide

LV dysfunction (HF)
or post-MI

ACE Is/ARBs

Contraindications for Various

Antihypertensive Drugs
Clinical Condition: Contraindicated Drugs:
Diabetes Thiazide and
Hypokalemia
loop diurectics
Elderly, living alone
All posturally acting drugs
Depression
Reserpine, -blockers
Angina
Vasodilators
Asthma
Non-selective -blockers
Cardiac Failure Verapamil
Vascular Disease
Non-selective -blockers

Goals of Therapy

2014 Guideline for Management of High Blood Pressure JNC 8

Blood pressure targets

Non-diabetic

patients aged less than 80 years:

target clinic BP < 140/90 mmHg

target ambulatory BP or home BP < 135/95 mmHg

Non-diabetic

patients aged over 80 years

target

clinic BP < 150/90 mmHg

target ambulatory BP or home BP < 145/85 mmHg
Patients

with diabetes

target

clinic BP < 140/80 mmHg (< 130/80 mmHg if

kidney, eye or cerebrovascular disease)
BHS NICE

Multiple Antihypertensive Agents are Needed to

Reach BP Goal
Trial (SBP achieved)
MDRD (132 mmHg)
HOT (138 mmHg)
RENAAL (141 mmHg)
AASK (128 mmHg)
ABCD (132 mmHg)
IDNT (138 mmHg)
UKPDS (144 mmHg)
ASCOT-BPLA (136.9 mmHg)
ALLHAT (138 mmHg)
ACCOMPLISH (132 mmHg)
Initial 2-drug combination therapy

2
3
4
Average no. of antihypertensive medications

Bakris et al. Am J Med 2004;116(5A):30S8; Dahlf et al. Lancet 2005;366:895906

Jamerson et al. Blood Press 2007;16:806; Jamerson et al. N Engl J Med 2008;359:241728

Hypertension Management Algorithm

ESH-ESC 2013

Mancia et al. Eur Heart J 2013;34(28):2159-219

Strategies to Dose Antihypertensive Drugs

Strategy

Description

Start one drug, titrate to maximum

dose, and then add a second drug

Start one drug and then add a second

drug before achieving maximum dose
of the initial drug

Begin with 2 drugs at the same time,

either as 2 separate pills or as a single
pill combination

2014 Guideline for Management of High Blood Pressure JNC 8

Combination of antihypertension

The Foundation of a Modern Blood

Pressure Treatment Regimen
BP lowering

Structural
regression

Metabolic
benefits

CVD
Protection

Reno
Protection

Tolerability

Combination Therapy

ESH/ESC

JNC VII

Guidelines Worldwide Acknowledge That Most Patients

Need Combination Therapy to Achieve BP Goals
Most patients with hypertension will require two or more
antihypertensive medications to achieve their BP goals
When BP is > 20/10 mmHg above goal, consideration should be
given to initiating therapy with two drugs

Combination treatment should be considered as first choice when there

is high CV risk
i.e., in individuals in whom BP is markedly above the hypertension
threshold (> 20/10 mmHg), or associated with multiple risk factors
sub-clinical organ damage, diabetes, renal or CV disease

Many patients will require more than one drug to achieve adequate BP
control
Pathophysiological reasoning suggests that adding an ACE-I/ARB to
a CCB or a diuretic (or vice versa in the younger group) are logical
combinations

NICE
JSH

The Japanese Society of

Hypertension Committee for
Guidelines for the
Management of Hypertension
2009

The use of two or three drugs in combination is often necessary to

achieve the target BP control
A low dose of a diuretic should be included in this combination

Chobanian et al. JAMA. 2003;289:25602572; Mancia et al. Eur Heart J. 2007;28:14621536; http://www.nice.org.uk/
download.aspx?o=CG034fullguideline (accessed January 2010); Ogihara et al. Hypertens Res. 2009;32:3107.

Advantages of Multiple-mechanism
Therapy: Efficacy
Multiple-mechanism therapy results in a greater BP reduction
than seen with its single-mechanism components1,2
Components

with a different mechanism of action

interact on complementary pathways of BP control1
Each component can potentially neutralize counterregulatory mechanisms, e.g.
Diuretics

reduce plasma volume, which in turn stimulates

the RAS and thus increases BP; addition of a RAS
blocker attenuates this effect1,2

Multiple-mechanism

therapy may result in BP

reductions that are additive2
1.Sica DA. Drugs 2002;62:44362.

Sica. Drugs 2002;62:44362

2
Quan
al. Am Cardiovasc,
2006;6:103-13
Quan 2.
et al.
Am Jet
Cardiovasc
Drugs 2006;6:10313
1

Combination of Antihypertension
DIURETIC EFFECTS

JG Cells
Volume
Depletion

Renin

ACE INHIBITOR
_

More
renin
release

Angiotensin II
_
Distal
tubule

Less Na+
reabsorbed
Opie (2001)

Vasoconstriction
Na+
diuresis

ARB

Combination of antihypertension
ACE
INHIBITOR

-BLOKADE
_

DIURETIC
Na+

Renin

ARB

Vasoconstriction
_
Na+ loss
Opie (2001)

Ca2+ ANTAGONISTS

Advantages of Multiple-mechanism
Therapy: Safety/Tolerability
Multiple-mechanism therapy may have an improved tolerability
profile compared with its single-mechanism components 1,2

Components

of multiple-mechanism therapy can

be given at lower dosages to achieve BP goal
than those required as monotherapy
therefore better tolerated1,2
Compound-specific adverse events can be
attenuated, e.g.,1,2
RAS

blockers may attenuate the edema that is caused

by CCBs
1.Sica DA. Drugs 2002;62:44362.

Drugs
2.2Sica.
Quan
et al.2002;62:44362
Am Cardiovasc, 2006;6:103-13
Quan et al. Am J Cardiovasc Drugs 2006;6:10313
1

Ideal
combination

Useful Dual Combinations

For additive hypotensive effect in dual therapy
Combine an agent from
Column 1 with any in Column 2

Column 1

Column 2

Thiazide diuretic

Beta adrenergic blocker

Long-acting calcium
channel blocker*

ACE Inhibitor
ARB

* Caution should be exercised when using a non DHP-CCB and a beta-blocker

Dual Combinations
For additive hypotensive effect
Combine an agent from Column 1 with any in Column 2

Column 1
Beta blocker

Column 2
Diuretic

?
ACE-i / ARB

?
CCB

?
* Caution should be exercised when using a non DHP-CCB and a beta-blocker

Aged under
55 years

Aged over 55 years

or black person of
African or
Caribbean family
origin of any age
C

Step 1

A+ C

Step 2

A+ C + D

Step 3

Resistant hypertension

Step 4

Summary of
antihypertensive
drug treatment

A ACE-I or ARB
C CCB
D Thiazide-like diuretic

A + C + D + consider further
diuretic, or alpha- or
beta-blocker
Consider seeking expert advice

BHS-NICE 2013

Free
Combinatio
n (FC)

?
Fixed Dose
Combinatio
n (FDC)

Advantages of
Fixed Dose Vs. Free Combinations
Fixed Dose

Free

Simplicity of treatment

Compliance

Efficacy

Tolerability

+*

Price

Flexibility

+**

++

*Lower doses generally used in single-pill combinations

**An increasing number of single-pill combinations are becoming available with a range of doses
+ = potential advantage

ESHESC Recommendations for Combining BP-lowering

Drugs and Availability as Single-pill Combinations
Diuretics
Angiotensin
receptor blockers
(ARBs)

-blockers

Calcium channel
blockers (CCBs)

-blockers

ACE inhibitors
Available as a single-pill combination
Less frequently used/combination used as necessary
The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society
Force for
ESHESC.
J Hypertens 2007;25:110587
of Cardiology (ESC). 2007 guidelines for the management of arterialTask
hypertension.
J Hypertens
2007;25:110587.

Crises Hypertension

LEARNING OBJECTIVE:
After completing this module, the students be able
to:
Describe the definitions of hypertensive crises
Describe the etiology and pathophysiology of
hypertensive crises
Describe the clinical manifestation of hypertensive
crises
Evaluation and management of hypertensive
crises

Terminology
Hypertensive

crises/emergency

sudden

increase in BP
elevated systolic and diastolic, with DBP >120
acute end organ damage: CNS, kidney, heart
pregnancy >169/109
Hypertensive

urgency

severe

elevation in BP w/o acute or obvious organ

damage (but at high risk for such)

Malignant

HTN- post op

Pathogenesis
Untreated

Sudden

essential hypertension

withdrawal / non-adherence to

antihypertensive drug therapy

Increase

in sympathetic tone (stress, drugs)

Renovascular

hypertension, renal parenchymal

diseases, pheochromocytoma, or primary
hyperaldosteronism.
Pressure damages vascular endothelium
Platelets and fibrin activate

Hypertensive emergencies:
Clinical Manifestations
Hypertensive encephalopathy, hemorrhage,
or stroke
Acute aortic dissection
Acute pulmonary edema, respiratory failure
AMI/USA
Eclampsia
ARF/AKI
Microangipathic hemolytic anemia

Patient evaluation
Medical

history
Physical examination
Laboratory evaluation
serum
urine
Medication profile
Drug use
Fundoscopy
EKG, CXR, head CT, echo

Principles of Therapy for

Hypertensive Emergencies
First,

Do Ho Harm
Patients must be hospitalized
Time

frame - consider risk level

Treated with parenteral
BP goal
Urgency:

gradual; DBP to 110 in 24-48 hours

Emergency: MAP < 20 to 25% in 1 to 2 hours
IV infusion is prefer than bolus
Avoid sublingual nifedipine
Hypertension,Brian C. Poole and Anitha Vijayan in Nephrology and
Subspeciality Consult,Lippincott Williams and Wilkins,2004

Complications of rapid BP reduction in

severe hypertension
Widening

neurologic deficits
Retinal ischemia: blindness
Acute myocardial infarction
Deteriorating renal function

Simple Approach to Hypertensive Crisis

BP > 220/120 mmHg
Neurological sign
(encephalopathy or stroke)
Retinopathy grade 3-4
Severe chest pain
(Ischemia or dissecting
aneurism)
Pulmonary edema
Eclampsia
Cathecolamine excess
Acute renal failure
EMERGENCY
Intravenous therapy

Headache
No neurological signs
No target organ damage
URGENCY
Identify the cause
In panic attacks or anxiety
use analgesic, anxiolytics
Otherwise use oral
antihypertensive agents
recheck in 6-24 hours

Hypertension is More Than Just Blood Pressure

Treatment of hypertension not just for lowering blood

pressure

Patients with DM and CKD require more aggressive BP

control

Majority of patients require >2 drugs to achieve BP goal

The use of combination therapy is appropriate as initial

treatment

Many guidelines recommends initial combination therapy in

patients > 20/10 mm Hg over goal BP