HYPERTENSION

Dwi Lestari Partiningrum

Nephrology and Hypertension Division,
Internal Medicine Department
Medical Faculty Diponegoro University/
Kariadi Hospital
Hypertension
 Learning Objectives
1 Define Hypertension
2 Define the types of hypertension
3 Understand the risk factors of developing
essential hypertension.
4 Understand the end-organ damage due to
hypertension.
5 Understand the goals and objectives of treating
hypertension.
 definition of hypertension
 “ The level of Blood Pressure at
which the benefits (minus the risks
and costs) of action exceed the risks
and costs of (minus the benefit ) of
inaction”
(Kaplan 1983)

 SBP 140 mm Hg, DBP  90 mm

Hg.
 Hypertension is an important
public health challenge worldwide
Population (in millions) with
hypertension globally

Kearney PM, et al. Lancet. 2005;365:217-223.

 Percentage of US population with
hypertension

Population (%)
40

30 Men
Women
20

10

0
20–29 30–39 40–49 50–59 60+
Age
Whelton (1985)
 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 et.al, J Clin Invest 2009;11:611–614
 Decreased
Arterial
Obesity Compliance Endothelial
Dysfunction

Abnormal
High Blood Pressure is a Late
Abnormal Lipid
Metabolism
Glucose
Metabolism

Manifestation
Accelerated
of the Hypertension
Hypertension Neurohormonal
Atherogenesis Dysfunction
Syndrome
LV Hypertrophy Renal-Function
Neutel JM et all, Am J Hypertens, 1999; 12:215-223
and Dysfunction Changes
Abnormal Blood-Clotting
Insulin Mechanism
Metabolism Changes

Weber MA et al. J Hum Hypertens. 1991;5:417-423.

Dzau VJ et al. J Cardiovasc Pharmacol. 1993;21(suppl 1):S1-S5. 1996;275:1571-1576
 The ‘rule of halves’ – the need for effective
diagnosis and treatment of hypertension

Proportions of the general population who have

undiagnosed hypertension (160/95 mmHg) or who are
untreated or inadequately treated (Scotland, 1984-
1986)
 Undiagnosed hypertension
 Diagnosed but untreated
 Treated but uncontrolled
Men (n=1262)  Treated and controlled Women (n=1061)

Smith et al (1990)
Pathophysiology hypertension
 Natural history of hypertensive
disease
From endothelial dysfunction to target-organ damage

Endothelial Vascular Elevated Target-organ

dysfunction dysfunction BP damage
LVH
Nephropathy
Stroke
MI/CAD
Weber M. J Hypertens 2003;21 (Suppl 6):S37–S46
 Hypertension
JNC BP Classifications: SBP

220 Stage 4

210
200 Stage 3
Stage 3
190
180 ISH ISH
SBP 170 Stage 2 Stage 2 Stage 2
(mm Hg) 160
Border- Border-
150 line line Stage 1 Stage 1 Stage 1
140 No recommendations for
SBP in JNC I High- High-
normal normal Prehyper-
130 or JNC II Normal tension
Normal Normal
120
110
Optimal Optimal Normal

JNC I JNC II JNC III JNC IV JNC V JNC VI JNC 7

JNC IV. Arch Intern Med. 1988;148:1023-1038.

JNC I. JAMA. 1977;237:255-261. JNC V. Arch Intern Med. 1993;153:154-183.
JNC II. Arch Intern Med. 1980;140:1280-1285. JNC VI. Arch Intern Med. 1997;157:2413-2446.
JNC III. Arch Intern Med. 1984;144:1045-1057. Chobanian AV et al. JAMA. 2003;289:2560-2572.
 JNC-7 Blood Pressure
Classification
Blood Pressure Systolic blood Diastolic blood
Classification pressure pressure
(mm Hg) (mm Hg)
Normal < 120 < 80

Pre-hypertension 120-139 80-89

Stage 1 hypertension 140-159 90-99

Stage 2 hypertension > 160 > 100

Chobanian AV et al. JAMA 2003;289:2560-72.

ESC 2013 Classification of Blood Pressure
Category SBP DBP

Optimal < 120 and < 80

Normal 120-129 and/or 80-84
High–Normal 130–139 and/or 85–89

Hypertension
Grade 1 140–159 and/or 90–99
Grade 2 160–179 and/or 100–109
Grade 3  180 and/or  110
Isolated Systolic HT  140 and < 90
 Types of hypertension

 Essential Hypertension
hypertension with no apparent cause 90-95%

 Secondary Hypertension
hypertension of known cause
 chronic renal diseases 2.5-5%
 Renovascular diseases 0.5-4%
 Oral contraceptive pills 0.2-1%
 Coarctation of the Aorta 0.1-1%
 Primary aldosteronism 0.1-0.5%
 Pheochromocytoma 0.1-0.2%
 Pathogenesis of Hypertension
 HTN develop gradually over a long period of time.
 The development of HTN requires the adjustment of
several compensatory mechanisms over time.
 Several hypothesis exists for the original pathogenesis
of HTN:
 Excess Na intake
 Renal Na retention
 RAS
 Stress & sympathetic over activity
 Peripheral resistance
 cell membrane and endothlial dysfunction
 Obesity
 insulin resistance
 Risk Factors
 Age
 Gender
 Race
 Genetic factors
 other:
 obesity
 high alcohol intake
 high Na intake
 abnormal renin values
 high stress level
 low birth weight
 drugs
 24-h blood pressure profile in a
hypertensive patient: the morning blood
pressure ‘surge’

Time of
Blood pressure (mm Hg)
180 awakening
Sleep

160

140

120

100

80
18:00 22:00 02:00 06:00 10:00 14:00
Time of day
Millar-Craig et al, 1978; Mancia et al, 1983
 Complications of Hypertension:
End-Organ Damage

Hypertension

Hemorrhage, LVH, CHD, CHF

Stroke

Peripheral
Vascular
Disease Renal Failure,
Retinopathy Proteinuria
CHD = coronary heart disease
CHF = congestive heart failure
LVH = left ventricular hypertrophy Slide Source
Hypertension Online
www.hypertensiononline.org
Chobanian AV, et al. JAMA. 2003;289:2560-2572.
 Vascular Complications
Komplikasi pada pembuluh darah

 Arterioscelorosis
  wall:lumen ratio
 remodeling
 Atherosclerosis
 Plaque
 Fibrous cap
 necrotic center

 Fibrinoid necrosis.
 Aortic dissection.
 Retinal complications
Venous
tapering
Increased light
reflexes from
Blurred arterioles
optic disc
 Hypertensive
retinopathy
Punctate
hard
exudate

Normal hemorrhage
 Cardiac complications
Left ventricular myocardium Coronary vascular bed
(myocardial factor) (coronary factor)

Hypertrophy Dilatation CAD Coronary

Microangiopathy

Decrease in contractility
Abnormal increase in c. resistance

Impairement in LV Impairment of O2 availability

fuction
Coronary insufficiency, MI
Heart failure Heart failure
The left ventricle is markedly thickened in this
patient with severe hypertension that was
untreated for many years. The myocardial fibers
have undergone hypertrophy.
This left ventricle is very thickened (slightly over 2 cm
in thickness), but the rest of the heart is not greatly
enlarged. This is typical for hypertensive heart
disease. The hypertension creates a greater pressure
load on the heart to induce the hypertrophy.
 CNS Complications

 Hypertensive encephalopathy
 Cerebral hemorrhage
 Ischemic stroke
 TIAs
 Renal Complications

 Benign arteriolar Nephrosclerosis

 Malignant arteriolar Nephrosclerosis
 Chronic Renal Failure
 Evaluation Objectives

 To identify known causes

 To assess presence or absence of target

organ damage and cardiovascular disease

 To identify other risk factors or disorders that

may guide treatment
 Evaluation Components

 Medical history

 Physical examination

 Routine laboratory tests

 Optional tests
 Medical History
 Duration and classification of hypertension
 Patient history of cardiovascular disease
 Family history
 Symptoms suggesting causes of hypertension
 Lifestyle factors
 Current and previous medications
 Physical Examination
 Blood pressure readings (2 or more)
 Verification in contralateral arm
 Height, weight, and waist circumference
 Funduscopic examination
 Examination of the neck, heart, lungs,
abdomen, and extremities
 Neurological assessment
 Laboratory Tests and Other
Diagnostic Procedures

 Determine presence of target organ damage

and other risk factors

 Seek specific causes of hypertension

 Laboratory Tests Recommended
Before Initiating Therapy
Urinalysis
Complete blood count
Blood chemistry (potassium, sodium, creatinine,
and fasting glucose)
Lipid profile (total cholesterol and HDL
cholesterol)
12-lead electrocardiogram
 Optional Tests and Procedures

 Creatinine clearance  Thyroid-stimulating hormone

 Microalbuminuria  Plasma renin activity/ urinary
sodium determination
 24-hour urinary protein
 Limited echocardiography
 Serum calcium
 Ultrasonography
 Serum uric acid  Measurement of ankle/arm
 Fasting triglycerides index

 LDL cholesterol
 Glycosolated hemoglobin
 Examples of Identifiable
Causes of Hypertension
(secunder hypertension)

 Renovascular disease • Pheochromocytoma

 Renal parenchymal • Primary aldosteronism
disease
• Cushing syndrome
 Polycystic kidneys • Hyperparathyroidism
 Aortic coarctation • Exogenous causes
Components of Cardiovascular Risk in
Patients With Hypertension
 Major Risk Factors:
 Smoking
 Dyslipidemia
 Diabetes mellitus
 Age older than 60 years
 Sex (men or postmenopausal women)
 Family history of cardiovascular disease
 Components of CV risk stratification
hypertension Patients

 Major risk factors  Target organ damage TOG/

 smoking Clinical Cardiovascular
disease CCD
 dislypidemia
 heart disease
 DM  left ventricular hypertrophy
 Age >60  Angina/ prior MI
 Sex (men and post  Prior coronary
menopausal women) revascularisation
 heart failure
 Family history of CV
diseases  nephropathy
 Peripheral arterial disease
 Retinopathy
 Classification and Management
of BP for adults (JNC-VII 2003)
Initial drug therapy
BP SBP* DBP* Lifestyle
classification mmHg mmHg modification Without compelling With compelling
indication indications

Normal <120 and Encourage

<80

Pre 120– or 80– Yes No antihypertensive Drug(s) for

hypertension 139 89 drug indicated. compelling
indications. ‡

Stage 1 140– or 90– Yes Thiazide-type diuretics

Hypertension 159 99 for most. May consider Drug(s) for the
ACEI, ARB, BB, CCB, or compelling
combination. indications.‡
Other
Stage 2 >160 or >100 Yes Two-drug combination antihypertensive
Hypertension for most† (usually drugs (diuretics,
thiazide-type diuretic ACEI, ARB, BB,
and ACEI or ARB or BB CCB) as needed.
or CCB).
*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.
 Goals of Therapy

 Reduce hypertension Target Organ Damage

morbidity and mortality.

 Treat to BP <140/90 mmHg or BP <130/80 mmHg

in patients with diabetes or chronic kidney disease.
 Benefits of Lowering BP

Average Percent Reduction

Stroke incidence 35–40%

Myocardial infarction 20–25%

Heart failure 50%

 Barriers to Reaching BP Targets

Patient factors Lack of Physician factors

knowledge/awarene Physician inertia
ss (ie. Reluctance to treat
aggressively
Poor compliance

Complexity of
therapeutic regimen

Side effects

Smoking
Concomitant drug
therapy
Alcohol
Cost of medication and
related care

Environment factors Burnier. Am J Hypertens 2006;19:1190-6

Munger. AMJC 2000;6 (suppl 1):211-21
Strategies to Dose of Antihypertensive Drugs
 Comparisons to Other Guidelines
BP Goal JNC-7 JNC-8 ASH/ISH ESC/ES CHEP
H
Age < 60 <140/90 <140/90 <140/90 <140/90 <140/90

Age 60- <140/90 <150/90 <140/90 <140/90 <140/90

79
Age 80+ <140/90 <150/90 <150/90 <150/90 <150/90

Diabetes <130/80 <140/90 <140/90 <140/85 <130/80

CKD <130/80 <140/90 <140/90 <130/90 <140/90

Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8.

JNC-8 Appointed Panel Members Report

JamesPA, et al. JAMA. doi:10.1001/jama.2013.284427

 Lifestyle Modifications to
Prevent and Manage Hypertension

• Reduce weight • Moderate consumption of:

• alcohol
• sodium
• saturated fat
• cholesterol

• Maintain adequate intake of dietary:

• potassium
• Increase • calcium
physical • magnesium
activity

 Avoid tobacco

(JNC VI. Arch Intern Med. 1997)

 Lifestyle Modifications
Approximate Systolic Blood
Modification Recommendation Pressure Reduction
(mm Hg)a
Weight loss Maintain normal body weight (body mass 5–20 per 10-kg weight loss
2
index 18.5–24.9 kg/m )

DASH-type Consume a diet rich in fruits, vegetables, 8–14

dietary patterns and low-fat dairy products with a reduced
content of saturated and total fat
Reduced salt Reduce daily dietary sodium intake as 2–8
intake much as possible, ideally to 65 mmol/day
(1.5 g/day sodium, or 3.8 g/day sodium
chloride)
Physical activity Regular aerobic physical activity (at least 4–9
30 min/day, most days of the week)
Moderation of Limit consumption to 2 drinks/day in men 2–4
alcohol intake and 1 drink/day in women and lighter-
weight persons

DASH, Dietary Approaches to Stop Hypertension.

a Effects of implementing these modifications are time and dose dependent and could be greater for

some patients.

DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy:A Pathophysiologic Approach, 7th Edition:
54
http://www.accesspharmacy.com/
 2013 ESH/ESC Guidelines for the management of arterial hypertension

Lifestyle changes for hypertensive patients

Recommendations to reduce BP and/or CV risk factors

Salt intake Restrict 5-6 g/day

Moderate alcohol intake Limit to 20-30 g/day men,

10-20 g/day women

Increase vegetable, fruit, low-fat dairy intake

BMI goal 25 kg/m2

Waist circumference goal Men: <102 cm (40 in.)*

Women: <88 cm (34 in.)*

Exercise goals ≥30 min/day, 5-7 days/week

(moderate, dynamic exercise)

Quit smoking

* Unless contraindicated. BMI, body mass index.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357
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 Development of Antihypertensive Therapies
Effectiveness

Tolerability

1940s 1950 1957 1960s 1970s 1980s 1990s 2005+

Direct Alpha ACE ARBs Renin Inh
vasodilators blockers inhibitors
Peripheral Thiazide
sympatholytics diuretics
Central alpha2 DHP CCBs
Ganglion blockers agonists
Veratrum Non-DHP
The primary goal of treatment is to
alkaloids CCBs achieve maximum reduction in
Beta blockers
total CV risk, through treatment of
elevated BP and all associated
DHP, dihydropyridine; CCB, calcium channel blocker; ARB, angiotensin II receptor blocker.
reversible risk factors
ESH/ESC 2007
How to combine
2013 ESH/ESC Initiation of Antihypertensive Treatment
ESH/ESC 2013

Mancia G, et al. J Hypertens 2013;31:1281–1357

 JNC 8 Algorithm for the Treatment
of Hypertension
Lifestyle modifications

Set BP goal and initiate BP lowering medicationbased on age, DM and CKD

NO DM and CKD With DM or CKD

All age, DM All age, CKD

Age ≥ 60 y.o. Age < 60 y.o. with no CKD w/ or w/o DM

Nonblack Black Initiate ACEI or

Initiate Diuretik, ARB alone or in
ACEI, ARB or Initiate Diuretik, or combination w/
CCB alone or in CCB alone or in other drug class (a)
combination (a) combination

James PA, et al. JAMA. December 18, 2013

 Select a drug treatment titration strategy
a. Maximize 1st med before adding 2nd
b. Add 2nd med before reaching max dose of 1st med
c. Start w/ 2 med classes separately or as fixed-dose combination
At goal BP? Yes
No
Reinforce med and lifestyle adherence.
A & B: add and titrate diuretics or ACEI or ARB or CCB (use med class
not previously selected & avoid combined use of ACEI & ARB).
C: titrate dose of initial med to max

At goal BP? Yes

No
Reinforce med and lifestyle adherence.
Add & titrate diuretic or ARB or ACEI or CCB (use med class not
previously selected & avoid combined use of ACEI & ARB)

At goal BP? Yes

No
Reinforce med and lifestyle adherence.
Add additional med class (eg BB, AA or others) & or refer to MD
w/ expertise in HT management

No At goal BP? Yes Continue

current
treatment &
a: ACEI & ARB should not be used in combination monitoring (b)
b: If BP fails to be maintained at goal, reenter the algorithm where appropriate based on the
current individual therapeutic plan James PA, et al. JAMA. December 18, 2013
 Treatment of Systolic-Diastolic Hypertension without
Other Compelling Indications

TARGET <140/90 mmHg

Lifestyle modification
A combination of 2 first line drugs may be
considered as initial therapy if the blood
Initial therapy pressure is >20 mmHg systolic or >10
mmHg diastolic above target

Thiazide Long-acting Beta-

ACEI ARB
diuretic CCB blocker*

CONSIDER
• Nonadherence Dual Combination
• Secondary HTN
• Interfering drugs or
*Not indicated as first line
lifestyle
Triple or Quadruple Therapy therapy over 60 y
• White coat effect

2009 Canadian Hypertension Education Program Recommendations

 Drugs to be preferred in specific conditions
Condition Drugs Other Drugs
Asymptomatic
ISH (elderly) Diuretic, calcium antagonist
organ damage
ACE inhibitor, calcium Metabolic ACE inhibitor, ARB, calcium
LVH
antagonist, ARB syndrome antagonist
Asymptomatic Calcium antagonist, ACE
Diabetes mellitus ACE inhibitor, ARB
atherosclerosis inhibitor
Methyldopa, BB, calcium
Microalbuminuria ACE inhibitor, ARB Pregnancy
antagonist

Renal Blacks Diuretic, calcium antagonist

ACE inhibitor, ARB
dysfunction
Clinical CV Events Drugs
Previous stroke Any agent effectively lowering BP
Previous myocardial infarction BB, ACE inhibitor, ARB
Angina pectoris BB, calcium antagonist
Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor
Heart failure
antagonists
Aortic aneurysm BB
Consider ARB, ACE inhibitor, BB or mineralocorticoid receptor
Atrial fibrillation, prevention
antagonists
Atrial fibrillation, ventricular rate
BB, non-dihydropyridine calcium antagonist
control
ESRD/proteinuria ACE inhibitor, ARB
JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427
 The Seventh Report of
the Joint National Committee

Compelling
Indications Diuretic ßB ACEI ARB CCB AA

Heart failure     
Post-MI   
High CAD risk    
Diabetes     
Chronic kidney
disease
 
Recurrent
stroke  
prevention
AA, aldosterone antagonist; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II-receptor blocker; βB, ß-blocker;
CCB, calcium channel blocker; MI, myocardial infarction;
CAD, coronary artery disease.
Chobanian AV, et al. JAMA. 2003;289(19):2560-2572.
 Follow Up
 Follow up within 1-2 months after initiating therapy.

 Recognize that high-risk patients often require high

dose or combination therapies and shorter intervals
between changes in medications.

 Consider reasons for lack of responsiveness if blood

pressure is uncontrolled after reaching full dose.

 Consider reducing dose and number of agents after

 1 year at or below goal.
 Hypertensive Emergencies
and Urgencies
 Emergencies require immediate blood
pressure reduction to prevent or limit target
organ damage.

 Urgencies benefit from reducing blood

pressure within a few hours.

 Elevated blood pressure alone rarely requires

emergency therapy.

 Fast-acting drugs are available.

 Pregnant Women
 Chronic hypertension is high blood pressure present
before pregnancy or diagnosed before 20th week of
gestation.
 Preeclampsia is increased blood pressure that occurs
in pregnancy (generally after the 20th week) and is
accompanied by edema, proteinuria, or both.
 ACE inhibitors and angiotensin II receptor blockers
are contraindicated for pregnant women.
 Methyldopa is recommended for women diagnosed
during pregnancy.
 Older Persons
 Hypertension is common.
 SBP is better predictor of events than DBP.
 Pseudohypertension and “white-coat hypertension”
may indicate need for readings outside office.

 Primary hypertension is most common cause, but

common identifiable causes (e.g., renovascular
hypertension) should be considered.
 Renal Disease
 Hypertension may result from renal disease that
reduces functioning nephrons.
 Evidence shows a clear relationship between
high blood pressure and end-stage renal disease.

 Blood pressure should be controlled to < 130/85

mm Hg or lower (< 125/75 mm Hg) in patients
with proteinuria in excess of 1 gram per 24
hours.

 ACE inhibitors work well to control blood

pressure and slow progression of renal failure.
 Diabetes Mellitus
 Drug therapy should begin along with lifestyle
modifications to reduce blood pressure to < 130/85
mm Hg.
 ACE inhibitors,α-blockers, calcium antagonists, and
low dose-diuretics are preferred.

 Insulin resistance or high peripheral insulin levels

may cause hypertension, which can be treated with
lifestyle changes, insulin-sensitizing agents,
vasodilating antihypertensive drugs, and lipid-
lowering agents.