Management of Hypertension

Division of Nephrology and Hypertension

 Hypertension Guidelines
BP Classification SBP DBP

ESH 2003
Optimal <120 <80
Normal 120-129 80-84
High Normal 130-139 85-89
Grade 1 HT (mild) 140-159 90-99
Grade 2 HT (moderate) 160-179 100-109
Grade 3 (severe) >180 >110
Isolated systolic HT >140 <90

JNC VII
Normal <120 and <80
Prehypertension 120-139 or 80-89
Stage 1 HT 140-159 or 90-99
Stage 2 HT >160 or >100
SBP systolic Blood Pressure; DBP diastolic blood pressure
 Prehypertension
 NOT a DISEASE category
 Should encourage Lifestyle modification as
this group has an increased risk of becoming
hypertensive
 NOT candidates for drug therapy (unless
compelling indications ie DM etc goal
<130/80)
 Etiologic Classification:
 Primary or Essential Hypertension (95%)
 Secondary Hypertension (5-10%)
 Renal – GN, RAS, Renin tumors
 Endocrine – Cushing, Thyrotoxicosis
Myxdema, Pheochromocytoma, Acromegaly.
 Vascular – Coarctation of Aorta, Aortic
insufficiency.
 Neurogenic – Psychogenic, Intracranial
pressure, etc.
 Control of blood pressure
Blood pressure = Cardiac output x Peripheral resistance
Hypertension = Increased CO and/or Increased PR

Vasoconstriction
 Preload  Contractility
 Heart rate

 Fluid volume
Sympathetic Renin-
nervous angiotensin-
Renal sodium aldosterone
system
retention system
Excess Genetic
sodium factors
intake
Kaplan (1994)
Essential (Primary)
Hypertension
 Risk factors
 Race (More common and more severe in blacks)
 Age > 60 years
 Sex (men and postmenopausal women)
 Family history of CVD
 Smoking
 High cholesterol diet
 Co-existing disorders such as diabetes, obesity
and hyperlipidemia
 Sodium intake
 High intake of alcohol
 Sedentary life style
Secondary Hypertension
 Secondary Hypertension

 5-10%
 Renal – GN, RAS, Renin tumors
 Endocrine – Cushing, Thyrotoxicosis,
Pheochromocytoma, Acromegaly.
 Vascular – Coarctation of Aorta, Aortic
insufficiency.
 Neurogenic – Psychogenic, Intracranial
pressure.
 Endocrine hypertension

Secondary hypertension 6-8%

Renal 4-5%
Miscellaneous ~2%
Endocrine 1-2%
Primary hyperaldosteronism 0.3%
Cushing’s syndrome <0.1%
Pheochromocytoma <0.1%
COMPLICATIONS
 The risks of hypertension
 The risks of hypertension are well recognised
 Cerebrovascular disease: Thromboembolic,
Intra cranial bleed, TIA
 Cardiovascular disease: MI, HF, CAD
 LVH -- enhanced incidence of HF, ventricular
arrhythmias, death following MI, and sudden
cardiac death.
 Peripheral vascular disease
 Renal failure
 Impact of High-Normal Blood Pressure on the
Risk of Cardiovascular Disease
CUMULATIVE INCIDENCE OF CV EVENTS IN MEN WITHOUT HYPERTENSION ACCORDING TO BASELINE BLOOD PRESSURE

mmHg
(130-139)

(121-129)

(< 120)

N Engl J Med 2001;345:1291-7

DIAGNOSIS
 Diagnosis

 Based upon the average of > 2 properly

measured readings at each of > 2 visits (at least
3 to 6 visits, spaced over a period of weeks to
months)
 Apply to adults on no antihypertensive
medications and who are not acutely ill.
 If there is a disparity in category between the
systolic and diastolic pressures, the higher value
determines the severity of the hypertension.
 White coat hypertension

 "white-coat" or isolated office HT

 Approximately 20 to 25 % of pts
 persistent office HT but repeatedly normal
when measured at home, at work, or by
ABPM (ambulatory blood pressure
monitoring)
 more common in the elderly, but is infrequent
(< 5%) in pts with office DP 105 mmHg.
 Taken by a nurse or technician, rather than
the physician
 Masked hypertension

 Elevated out-of-office readings despite

normal office readings
 Cardiovascular risk: similar as patients
with sustained HT
 This is consistent with the risk of
hypertensive cardiovascular complications
 Indications for ABPM

 Suspected white coat HT

 Suspected episodic HT (eg, pheochromocytoma)
 HT resistant to increasing medication
 Hypotensive symptoms while taking
antihypertensive medications
 Autonomic dysfunction
EVALUATION
 Aim
 To determine the extent of target organ
damage.
 To assess the patient's overall
cardiovascular risk status.
 To rule out identifiable and often curable
causes of hypertension
 If HT diagnosed

Evaluate for Cardiovascular Risk Factors

Age,Fm Hx, Lipids, Obesity, microalbuminuria,
Inactivity, Smoking
Evaluate for Target Organ Damage
LVH or reduced EF,
Angina,stroke,dementia,Kidney disease,
PAD,retinopathy
Think about Secondary Hypertension with any
new onset Hypertension or uncontrolled
hypertension
 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
23
 Physical examination
 Goal is to assess for target organ damage
(such as retinopathy) and clues to secondary
causes
 BP, P, R
 Vascular (including check all pulses)
 Thyroid
 Heart and Lungs
 Abdomen
 Neurologic
 Laboratory testing

 Hematocrit, urinalysis, and routine blood

chemistries (glucose, creatinine,
electrolytes)
 Fasting lipid profile (total and HDL-C, TG)
 Electrocardiogram
 Additional tests
 Indicated in certain settings
 Testing for microalbuminuria - limited to
patients with diabetes - independent risk
factor for CVD
 Echocardiography - detect left ventricular
hypertrophy.
 Testing for renovascular hypertension
 Severe or refractory HT
 An acute rise in BP over a previously stable baseline
 Proven age of onset before puberty or above age 50.
 An acute ↑ Cr that is either unexplained or occurs after the
institution of therapy with an ACE-i or AIIRB
 Moderate to severe HT in a patient with diffuse
atherosclerosis or an incidentally discovered asymmetry in
renal disease.
 A systolic-diastolic abdominal bruit that lateralizes to one
side.
 Negative family history for HT.
 Moderate to severe HT in patients with recurrent episodes of
acute pulmonary edema or otherwise unexplained CHF.
 Testing for other causes of identifiable
hypertension
 Elevated creatinine, a calculated GFR < 60 mL/min per 1.73
m2, or proteinuria.
 Pheochromocytoma: paroxysmal elevations in BP - triad of
headache, palpitations, and sweating.
 Low-renin forms of hypertension (primary
hyperaldosteronism): unexplained hypokalemia 
Measurement of plasma renin activity (PRA) and
aldosterone concentration.
 Cushing's syndrome: cushingoid facies, central obesity,
ecchymoses, and muscle weakness.
 Coarctation of the aorta: decreased peripheral pulses and a
vascular bruit over the back.
TREATMENT
 Lifestyle Modification
Modification Approximate SBP reduction
(range)

Weight reduction 5–20 mmHg/10 kg weight loss

Adopt DASH eating 8–14 mmHg
plan

Dietary sodium 2–8 mmHg

reduction
Physical activity 4–9 mmHg
Moderation of 2–4 mmHg
alcohol consumption
Drug treatment
 INDICATIONS FOR INDIVIDUAL DRUG CLASSES
Compelling Diuretic -blocker ACE ARB CCB
indications inhibitor

Heart failure
• • • •
Post-MI
• •
• • • •
High coronary
disease risk

Diabetes
• • • • •
• •
Chronic
kidney disease

• •
Stroke
prevention
The JNC VII Report. JAMA 2003;289:2560-2572
Development of Antihypertensive Drugs
Reserpin (1949)
1950
HCT (1958)

Diuretics 1960
Verapamil (1963)
Furosemide (1964)
Propanolol (1965)
Beta blockers
1970
Nifedipin (1975)
CCBs
Prazosin (1977)
1-blockers 1980 Captopril (1981)

1990 Losartan (1995)

ACE-inhibitors
Valsartan

AT1-antagonists 2000 ?
Treatment Algorithm for Adults with Systolic-Diastolic
Hypertension without another compelling indication
TARGET <140/90 mmHg

INITIAL TREATMENT AND MONOTHERAPY

Lifestyle modification
therapy

Long-acting Beta-
Thiazide ACE-I ARB DHP-CCB blocker

Alpha-blocker
as initial
monotherapy

2003 Canadian Hypertension Education Program Recommendations.

 The Renin-Angiotensin System
Alternate Pathway
Circulating Local
Liver Tissue
Angiotensinogen
Non Renin pathways
- t-PA
Renin inhibitors Renin - Cathepsin G
- Tonin

Angiotensin I
Non-ACE pathways
ACE inhibitor Converting enzyme - Chymase
- CAGE
- Cathepsin G

Angiotensin II

Angiotensin
AII receptor blockers
receptors
 ACE INHIBITOR (ACEI)
Indikasi Spesifik dari ACEI
 Hipertensi ringan, sedang, berat
 Hipertensi disertai hipertropi ventrikel kiri
 Gagal jantung kiri
 Miokard infark disertai remodeling
 Diabetes disertai mikroalbuminuria
 Hipertensi disertai
 Penyakit vaskuler perifer
 Penyakit jalan nafas obstruktif menahun
 Depresi
 ACTIVATION AND BLOCKADE OF
NEUROHUMORAL SYSTEM IN CHF

RAA System SNS System

Angiotensin II Noradrenalin

ACE-I ß-Blocker

Hypertrophy, apoptosis, ischemia,

arrhythmia, remodelling, fibrosis
 WHERE β-BLOCKERS WORK
Sudden
death
Angina

Ventricular
Hypertension arrhythmias

Coronary
Myocardial LV Heart
Diabetes artery
infarction dysfunction failure
disease

Hyperlipidemia Cardiac Pump

Atrial failure
Hypertrophic rupture
fibrillation
cardiomyopathy

Mechanical
death
 Antihypertensive

Anti-ischemic

-blocking
agents

Antiarrythmic

Treatment for heart failure

 Not all -BLOCKERS are the same !

Non-selective with
NON SELECTIVE SELECTIVE alfa-blocking activity
Labetolol
ISA - ISA + ISA - ISA + Bucindolol
Carvedilol
Nadolol Pindolol Atenolol Acebutolol
Propanolol Penbutolol Esmolol Celiporlol
Timolol Alprenolol Metoprolol
Sotalol Oxprenolol Bisoprolol
Bisoprolol
Betaxolol
Treatment Algorithm for Adults with Systolic-Diastolic
Hypertension without another compelling indication
TARGET <140/90 mmHg

INITIAL TREATMENT AND MONOTHERAPY

Lifestyle modification
therapy

Long-acting Beta-
Thiazide ACE-I ARB DHP-CCB blocker

Alpha-blocker
as initial
monotherapy

2003 Canadian Hypertension Education Program Recommendations.

EFFEK KARDIOPROTEKTIF CALSIUM ANTAGONIST

MENURUNKAN KEBUTUHAN OKSIGEN MIOKARDIUM

• Menurunkan Tekanan Darah
• Menurunkan Denyut Jantung

MENEKAN KERUSAKAN SEL MIOKARDIUM AKIBAT

INFLIKS ION CA++ YANG BERLEBIHAN KE DALAM SEL
• Menekan peningkatan ion Ca++ di dalam sel miokardium
• Menekan penurunan ATP & CP di dalam sel miokardium

MENINGKATKAN PENYEDIAAN OKSIGEN MIOKARDIUM

• Menghilangkan spasme koroner
• Meningkatkan aliran darah sub-endokardium
• Menurunkan denyut jantung
(memperpanjang periode diastolik)
• Menekan sklerosis koroner

EFEK : Anti – Aritmia

Combination Drugs of
Hypertension

Diuretics ACE Inhibitor (ARB)

 - blocker C.C. Blocker

 PERCENTAGE OF PATIENTS WHO
NEEDED COMBINATION THERAPY
COOPE

INSIGHT

MRC1

NORDIL

STOP1

Syst-Eur

Average

0 10 20 30 40 50 60 70 80 90 100
% OF PATIENTS
 POSSIBLE COMBINATIONS OF DIFFERENT
CLASSES OF ANTIHYPERTENSIVE
AGENTS
DIURETICS

BETHA BLOCKERS AT1- RECEPTOR

BLOCKERS

ALFA BLOCKERS
CALCIUM
ANTAGONISTS

ACE INHIBITORS
Efective drug combinations

 Diuretic and -blocker

 Diuretic and ACE Inhibitor or AIIRA
 Calcium antagonist (dihydropyridine)
and -blocker.
 Calcium antagonist and ACE
inhibitor.
 -Blocker and -blocker
 Factors affecting choice of
antihypertensive drug
 The cardiovascular risk profile of the
patient
 Coexisting disorders
 Target organ damage
 Interactions with other drugs used for
concomitant conditions
 Tolerability of the drug
 Cost of the drug
Antihypertensive drug strategies
 Reduce cardiac output
 -adrenergic blockers
 Ca2+ Channel blockers
 Dilate resistance vessels
 Ca2+ Channel blockers
 Renin-angiotensin system blockers
 1 adrenoceptor blockers
 Nitrates
 Reduce vascular volume
 Diuretics
 Direct vasodilators
Anti-Hypertensive Drugs: Sites of Action
Symphatetic
Activity 

Renin 

β BLOCKERS
Cardiac
Output 

Thiazids
ACE-i
ARBs
Calsium Antagonist+

α BLOCKERS
PERIPHERAL
HYDRALAZINE VASCULAR
RESISTENCE 
Choice of Pharmacological
Treatment

Associated risk factors?

or
Target organ damage/complications?
or
Concomitant diseases/conditions?

NO YES

Treatment in the Individualized

absence of compelling Treatment
indication (with compelling
indications)
 Drug therapy for hypertension

Class of drug Example Initiating dose Usual

(LD) MD

Diuretics HCT 12.5 mg o.d. 12.5-25 mg o.d.

-blockers Atenolol 25-50 mg o.d. 50-100 mg o.d.

CCB Amlodipine 2.5-5 mg o.d. 5-10 mg o.d.

ACE- inhibitors Lisinopril 2.5-5 mg o.d. 5-20 mg o.d.

ARB Losartan 25-50 mg o.d. 50-100 mg o.d.

 Choosing the right antihypertensive

Condition Preferred drugs Other drugs that can be Drugs to be

used avoided

Asthma CCBs -blockers/ARB/Diuretics/ -blockers

ACE-i

Diabetes -blockers/ACE-i/ CCBs Diuretics/

mellitus ARB -blockers

High -blockers ACE-i/ARB/ CCB -blockers/

cholesterol Diuretics
levels
Elderly CCBs -blockers/ACE-i/
patients ARB/- blockers

BPH - blockers -blockers/ ACE-i/ ARB/

Diuretics/ CCBs
 JNC 7 Medication Algorithm
Initial Drug Choices

Without Compelling Indications With Compelling Indications

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

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

Not at Goal BP

Optimize dosages or add additional drugs

until goal BP is achieved.
Consider consultation with hypertension
specialist.
 Aggressive BP Goals:
Consensus Across Treatment Guidelines
Organization Patient Type BP Goals (mm Hg)

ADA Diabetes <130/80

ISHIB African American <140/90

Plus DM or proteinuria >1 g/24 h <130/80

JNC 7 Uncomplicated HTN <140/90

With DM, CKD <130/80

NKF Albuminuria (>300 mg/d or >200 mg/g creatinine), <130/80

with or without diabetes
Proteinuria (protein to creatinine ratio “Consider even
>500-1000 mg/g) lower than
<130/80”
WHO-ISH Low risk for CVD SBP<140
Presence of DM, target organ damage,
or associated clinical conditions <130/80

ADA: American Diabetes Association; ISHIB: International Society on Hypertension in Blacks; JNC 7: The Seventh Report of the
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
NKF: National Kidney Foundation; WHO-ISH: World Health Organization/International Society on Hypertension
Indications for specific
drugs
 ACE inhibitors
 First-line therapy in
- HF or asymptomatic LV dysfunction
- ST elevation MI
- non-ST elevation MI + anterior infarct, diabetes,
or systolic dysfunction
- in patients with proteinuric CRF.
 Combination therapy with an ARB appears to be
beneficial in patients with HF and proteinuric CRF
 ARBs

 Indications for and efficacy are not

different from those with ACE inhibitors.
 Particularly indicated in patients who do
not tolerate ACE inhibitors (mostly
because of cough).
 Beta blockers
 Without ISA should be given after an AMI
and to stable patients with HF or
asymptomatic LV dysfunction.
 Evidence: no better than other drugs
against MI and are inferior to other drugs
against stroke.
 Given for rate control in patients with AF,
for control of angina, and for symptom
control in a number of other disorders
 Diuretics
 Low dose TZD (eg, 12.5 to 25 mg HCT)  better
cardioprotection than an ACE inhibitor or a CCB in patients
with risk factors for CAD, including LVH, type 2 diabetes,
previous MI or stroke, current cigarette smoking habits,
hyperlipidemia, or atherosclerotic cardiovascular disease.
 TZD should be prescribed in the absence of an indication for
any other specific drug(s) or when goal BP has not been
attained.
 Aldosterone antagonist is indicated in patients with advanced
HF who have relatively preserved renal function and, in
patients with less severe disease, for the treatment of
hypokalemia.
 Calcium channel blockers
 There are no absolute indications for CCB
in hypertensive patients.
 Can be given for rate control in patients
with AF or for control of angina.
 CCB may be preferred in patients with
obstructive airways disease
 Antihypertensive therapy:
Side-effects and Contraindications

Class of Main side-effects Contraindications/

drugs Special Precautions
Diuretics Electrolyte Hypersensitivity, Anuria
(e.g. HCT) imbalance,
 level of total and
C-LDL,, glucose
levels, UC, ↓C-
HDL
-blockers Impotence, Hypersensitivity, Bradycardia,
(e.g. atenolol) Bradycardia, Conduction disturbances,
fatique Diabetes, Asthma, Severe
cardiac failure
 Antihypertensive therapy:
Side-effects and Contraindications

Class of drugs Main side-effects Contraindications/

Special Precautions
CCB (e.g. Pedal edema, Non-DHP CCBs (e.g diltiazem)–
Amlodipine, Headache Hypersensitivity, Bradycardia,
Diltiazem) Conduction disturbances, CHF, LV
dysfunction.
DHP CCBs–Hypersensitivity
-blockers (e.g. Postural hypotension Hypersensitivity
Doxazosin)
ACE-inhibitors Cough, Hypertension, Hypersensitivity, Pregnancy,
(e.g. Lisinopril) Angioneurotic edema Bilateral renal artery stenosis
A-II RB Headache, Dizziness Hypersensitivity, Pregnancy,
Bilateral renal artery stenosis
 Goals of Therapy
 HTN: <140/90; Diabetics: <130/80; Renal
failure: <130/80; Proteinuria (>1 gm/24 hrs):
<125/75
 Base medication decisions on:
 compelling indications
 comorbid conditions
 side effect profile
 drug interactions
 cost
 Always favor the long-acting formulations