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Management Hypertension Against

Target Organ Damage :

expert recommendation and the application

in the daily practice


CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS
AGE 18 AND OLDER (JNC VI 1997)

Category Systolic (mm Hg) Diastolic (mm Hg)

Optimal < 120 and <80

Normal < 130 and <85

High-normal 130-139 or 85-89

Hypertension

Stage 1 140-159 or 90-99

Stage 2 160-179 or 100-109

Stage 3 180 or 110


RISK STRATIFICATION AND TREATMENT (JNC VI 1997)

Blood Pressure Risk Group A Risk Group B Risk Group C


(mmHg) (No Risk Factors (At Least 1 Risk (TOD/CCD and/or
No TOD/CCD) Factor, Not Including Diabetes, With or
Diabetes; No TOD/ Without Other Risk
CCD) Factors)
High-normal Lifestyle Lifestyle Drug therapy
(130-139/85-89) modification modification

Stage 1 Lifestyle Lifestyle Drug therapy


(140-159/90-99) modification modification
(up to 12 months) (up to 6 months)
Stage 2 and 3 Drug therapy Drug therapy Drug therapy
(169 / 100)
Blood Pressure Measurement

n Patients
should be seated with back supported and
arm bared and supported.
n Patients
should refrain from smoking or ingesting
caffeine for 30 minutes prior to measurement.
n Measurement should begin after at least 5 minutes of
rest.
n Appropriate cuff size and calibrated equipment should
be used.
n Both SBP and DBP should be recorded.
n Two or more readings should be averaged.
Trends in Awareness, Treatment, and Control of High Blood Pressure in Adults
With Hypertension Aged 18 to 74 Years (JNC VII 2003)

National Health and Nutrition Examination Surveys, Weighted %

III (Phase I, III (Phase 2,


II (1976-1980) 1988-1991) 1991-1994) 1999-2000
Awareness 51 73 68 70
Treatment 31 55 54 59
Control 10 29 27 34
Classification and Management of Blood Pressure for Adults Aged 18 years or older (JNC VII 2003)

Management

Initial Drug Therapy

BP Systolic Diastolic Lifestyle


Classifications BP, mm Hg* BP, mmHg* Modification Without Compelling With compelling
Indications indications
Normal < 120 and < 80 Encourage

Pre-hypertension 120 139 or 80 89 Yes No antihypertensive drug Drug(s) for the compelling
indicated indications

Stage 1 hypertension 140 159 or 90 99 Yes Thiazide-type diuretics for Drug(s) for the compelling
most; may consider ACE indications
inhibitor, ARB, -blocker, Other antihypertensive
CCB, or combination drugs (diuretics, ACE
inhibitor, ARB, -blocker,
CCB) as needed
Stage 2 hypertension 160 or 100 Yes 2-Drug combination for most Drug(s) for the compelling
(usually thiazide-type indications
diuretic and ACE inhibitor Other antihypertensive
or ARB or -blocker or drugs (diuretics, ACE
CCB) inhibitor, ARB, -blocker,
CCB) as needed
Progress of the National High Blood Pressure
Education Program (JNC VI)

n Increased awareness, treatment, and control


n Decreased morbidity and mortality from stroke and
coronary heart disease (CHD)

Goal of Therapy (JNC VII) :

The Reduction of Cardiovascular and Renal Morbidity


and Mortality
Cardiovascular Risk Factors
Major Risk Factors
Hypertension
Cigarette smoking
Obesity (BMI30)
Physical inactivity
Dyslipidemia
Diabetes Mellitus
Microalbuminuria or estimated GFR < 60 mL/min
Age (>55 years for men, > 65 years for women)
Family history or premature cardiovascular disease
(men <55 years or women 65 years)
Cardiovascular Risk Factors (Cont)

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
Algorithm for Treatment of Hypertension
Lifestyle Modifications

Not at Goal BP
(<140/90 mm Hg 0r <130/80 mm Hg for Those With Diabetes
or Chronic Kidney Disease

Initial Drug Choice

Hypertension Without Hypertension With


Compelling Indications Compelling Indications

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


(Systolic BP 140-159 mm Hg (Systolic BP 160 mmHg or Compelling Indications
or Diastolic BP 90-99 mm Hg) Diastolic BP 100 mm Hg)
Other Antihypertensive Drugs
Thiazide-Type Diuretics for Most 2-Drug Combination for Most (Diuretics, ACE inhibitor, ARB,
(Usually Thiazide-Type -blocker, CCB) as Needed
May Consider ACE inhibitor, ARB,
Diuretic and ACE inhibitor or
-Blocker, CCB, or Combination
ARB or -Blocker or CCB)

Not at Goal BP

Optimize Dosages or Add Additional Drugs Until Goal BP is Achieved


Consider Consultation With Hypertension Specialist
Lifestyle Modifications to Manage Hypertension

Modification Recommendation Approximate Systolic BP


Reduction, Range

Weight reduction Maintain normal body weight 5-20 mm Hg/10-Kg weight


(BMI, 18.5-24.9 loss

Adopt DASH eating Consume a diet rich in fruits, 8-14 mm Hg


plan vegetables, and low-fat dairy
products with a reduced content of
saturated and total fat
Dietary sodium Reduce dietary sodium intake to no 2-8 mm Hg
reduction more than 100 mEq/L (2.4 g sodium
or 6 g sodium chloride)
Physical activity Engage in regular aerobic physical 4-9 mm Hg
activity such as brisk walking (at
least 30 minutes per day, most days
of the week
Moderation of alcohol Limit consumption to no more than 2 2-4 mm Hg
consumption drinks per day (1 oz or 30 mL
ethanol [eg, 24 oz beer, 10 oz wine,
or 3 oz 80-proof whiskey]) in most
men and no more than 1 drink per
day in women and lighter-weight
persons
Oral Antihypertensive Drugs
Usual Dose, Daily
Class Drug (Trade Name) Range, mg/d Frequency
Thiazide diuretics Chlorothiazide (Diuril) 125-500 1

Chlorthalidone (generic) 12.5-25 1

Hydrochlorothiazide 12.5-50 1
(Microzide, HydroDIURIL)
Polythiazide (Renese) 2-4 1

Indapamide (Lozol) 1.25-2.5 1

Metolazone (Mykrox) 0.5-1.0 1

Metolazone (Zaroxolyn) 2.5-5 1

Loop diuretics Bumetanide (Bumex) 0.5-2 2

Furosemide (Lasix) 20-80 2

Torsemide (Demadex) 2.5-10 1

Potassium-sparing diuretics Amiloride (Midamor) 5-10 1-2

Triamterene (Dyrenium) 50-100 1-2

Aldosterone-receptor blockers Eplerenone (Inspra) 50-100 1-2

Spironolactone (Aldactone) 25-50 1-2


Oral Antihypertensive Drugs (cont)
Usual Dose, Daily
Class Drug (Trade Name) Range, mg/d Frequency
-Blockers Atenolol (Tenormin) 25-100 1

Betaxolol (Kerlone) 5-20 1

Bisoprolol (Zebeta) 2.5-10 1

Metoprolol (lopressor) 50-100 1-2

Metoprolol extended release (tropol XL) 50-100 1

Nadolol (Corgard) 40-120 1

Propranolol (Inderal) 40-160 2

Propranolol long-acting (Inderal LA) 60-180 1

Timolol (Blocadren) 20-40 2

-Blockers with intrinsic Acebutolol (Sectral) 200-800 2


sympathomimetic activity
Penbutolol (Levatol) 10-40 1

Pindolol (generic) 10-40 2

Combined and -blockers Carvedilol (Coreg) 12.5-50 2

Labtalol (normodyne, Trandate) 200-800 2


Oral Antihypertensive Drugs (cont)
Usual Dose, Daily
Class Drug (Trade Name) Range, mg/d Frequency
ACE Inhibitor Benazepril (lotensin) 10-40 1-2
Captopril (Capoten) 25-100 2
Enalapril (Vasotec) 2.5-40 1-2
Fosinopril (Monopril) 10-40 1
Lisinopril (Prinivii, Zestril) 10-40 1
Moexipril (Univasc) 7.5-30 1
Perinodpril (Aceon) 4-8 1-2
Quinapril (Accupril) 10-40 1
Ramipril (Altace) 2.5-20 1
Trandolapril (Mavix) 1-4 1
Angiotensin II antagonists Candesartan (Atacand) 8-32 1
Combined and -blockers Eprosartan (Tevetan) 400-800 1-2
Irbesartan (Avapro) 150-300 1
Losartan (Cozaar) 25-100 1-2
Olmesartan (Benicar) 20-40 1
Telmisartan (Micardis) 20-80 1
Valsartan (Diovan) 180-420 1
Oral Antihypertensive Drugs (cont)
Usual Dose, Daily
Class Drug (Trade Name) Range, mg/d Frequency
Calsium channel blockers- Diltiazem extended release 180-420 1
non-dihydropyridines (Cardizem CD, Dilacor XR, Tiazac)
Diltiazem extended release 120-540 1
(Cardizem LA)
Verapamil immediate release 80-320 2
(Calan, Isoptin)
Verapamil long-acting 120-360 1-2
(calan SR, Isoptin SR)
Verapamil-coer (Covera, HS, 120-360 1
Verelan PM)
Calcium channel blockers- Amlodipine (Norvasc) 2.5-10 1
dihydropyridines
Felodipine (Plendil) 2.5-20 1
Isradipine (Dynacirc CR) 2.5-10 2
Nicardipine sustained release 60-120 2
(Cardene SR)
Nifedipine long-acting (Adalat CC, 30-60 1
Procardia XL)
Nisoldipine (Sular) 10-40 1
Oral Antihypertensive Drugs (cont)

Usual Dose, Daily


Class Drug (Trade Name) Range, mg/d Frequency
1-Blockers Doxazosin (Cardural) 1-16 1
Prazosin (Minipress) 2-20 2-3
Terazosin (Hytrin) 1-20 1-2
Central 2-agonists and other Clonidine (Catapres) 0.1-0.8 2
centrally acting drugs
Clonidine patch (Catapres TTS) 0.1-0.3 1 weekly

Methyldopa (Aldomet) 250-1000 2


Reserpine (generic) 0.05-0.25 1
Guanfacine (generic) 0.5-2 1
Direct vasodilator Hydralazine (Apresoline) 25-100 2
Minoxidil (Loniten) 2.5-80 1-2
Combination drug for Hypertension

Combination Type Fixed-Dose Combination, mg* Trade Name


ACE inhibitors and CCBs Amlodipine/benazepril hydrochloride Lotrel
(2.5/10, 5/10, 5/20, 10/20)
Enalapril maleate/felodipine (5/5) Lexxel
Trandolapril/verapamil (2/180, 1/240, Tarka
2/240, 4/240)
ACE inhibitors and diuretics Benazepril/hydrochlorothiazide (5/6.25, Lotensin HCT
10/12.5, 20/12.5, 20/25)
Captopril/hydrochlorothiazide (25/15, Capozide
25/25, 50/15, 50/25)
Enalapril maleate/hydrochlorothiazide Veseretic
(5/12.5, 20/25)
Lisinopril/hydrochlorothiazide (5/12.5, Prinzide
10/25)
Moexipril HCI/hydrochlorothiazide Uniretic
(7.5/12.5, 15/25)
Quinapril HCI/hydrochlorothiazide Accuretic
(10/12.5, 20/12.5, 20/25)
Combination drug for Hypertension (cont)
Combination Type Fixed-Dose Combination, mg* Trade Name
ARBs and diuretics Candesartan cilexetil/hydrochlorothiazide Atacand HCT
(16/12.5, 32/12.5)
Eprosartan mesylate/hydrochlorothiazide Tevetan HCT
(600/12.5, 600/25)
Irbesartan/hydrochlorothiazide (75/12.5), Avalide
150/12.5, 300/12.5)
Losartan potassium/hydrochlorothiazide Hyzaar
(50/12.5, 100/25)
Telmisartan/hydrochlorothiazide Micardis HCT
(40/12.5, 80/12.5)
Valsartan/hydrochlorothiazide (80/12.5, Diovan HCT
160/12.5)
-Blockers and diuretics Atenolol/chlorthalidone (50/25, 100/25) Tenoretic
Bisoprolol fumarate/hydrochlorothiazide Ziac
(2.5/6.25, 5/6.25, 10/6.25)
Propranolol LA/hydrochlorothiazide Inderide
(40/25, 80/25)
Metoprolol tartrate/hydrochlorothiazide Lopressor HCT
(50/25, 100/25)
Nadolol/bendroflumethiazide (40/5, 80/5) Corzide
Timolol maleate/hydrochlorothiazide Timolide
(10/25)
Combination drug for Hypertension (cont)

Combination Type Fixed-Dose Combination, mg* Trade Name


Centrally acting drug and Methyldopa/hydrochlorothiazide (250/15, Aldoril
diuretic 250/25, 500/30, 500/50)
Reserpine/chlorothiazide (0.125/250, Diupres
0.25/500)
Reserpine/hydrochlorothiazide Hydropres
(0.125/25, 0.125/50)
Diuretic and diuretic Amiloride HCI/hydrochlorothiazide (5/50) Moduretic
Spironolactone/hydrochlorothiazide Aldactone
(25/25, 50/50)
Triamterene/hydrochlorothiazide Dyazide, Maxzide
(37.5/25, 50/25, 75/50
Clinical Trial and Guideline Basis for Compelling Indications for Individual Drug Classes

Recommended Drugs
High-Risk Conditions
With Compelling Diuretic -blocker ACE ARB CCB Aldosterone Clinical Trial Basis
Indications inhibitor Antagonist

Heart failure ACC/AHA Heart Failure


Guideline, MERIT-HF,
COPERNICUS, CIBIS,
SOLVD, AIRE, TRACE,
ValHEFT, RALES
Post-myocardial ACC/AHA, Post-MI Guideline,
infarction BHAT, SAVE, Capricorn,
EPHESUS
High coronary disease ALLHAT, HOPE, ANBP2, LIFE,
risk CONVINCE

Diabetes NKF-ADA Guideline, UKPDS,


ALLHAT

Chronic kidney NKF Guideline, Captopril Trial,


disease RENAAL, IDNT, REIN,
AASK
Recurrent stroke PROGRESS
prevention
Causes of Resistant Hypertension
Improper blood pressure measurement
Volume overload and pseudotolerance
Excess sodium intake
Volume retention from kidney disease
Inadequate diuretic therapy
Drug-induced or other causes
Noadherence
Inadequate doses
Inappropriate combinations
Nonsteroid anti-inflammatory drugs; cyclooxygenase 2 inhibitors
Cocaine, amphetamines, other illicit drugs
Sympathomimetics (decongestans, anorectics)
Oral contraceptives
Adrenal steroids
Cyclosporine and tacrolimus
Erythropoietin
Licorice (including come chewing tobacco)
Selected over-the-counter dietary supplements and medicines (eg, ephedra,
ma haung, bitter orange)
Associated conditions
Obesity
Excess alcohol intake
Identifiable causes of hypertension
Sleep apnea
Drug-induced or drug-related
Chronic kidney disease
Primary aldosteronism
Renovascular disease
Chronic steroid therapy and Cushing syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease
I. The 7th Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure has just published.

The summary of the report are described as follows;


1. In persons older that 50 years, systolic blood
pressure (BP) of more than 140 mmHg is a much
more important cardiovascular disease (CVD)
risk factor than diastolic BP.
2. The risk of CVD, beginning at 115/75 mmHg,
doubles with each increment of 20/10 mmHg;
individuals who are normotensive at 55 years of
age have a 90% lifetime risk for developing
hypertension.
3. Individuals with a systolic BP of 120 to 139 mmHg or
a diastolic BP of 80 to 89 mmHg should be
considered as pre-hypertensive and require health-
promoting lifestyle modifications to prevent CVD.
4. Thiazide-type diuretics should be used in drug
treatment for most patients with uncomplicated
hypertension, either alone or combined with drugs
from other classes. Certain high-risk conditions are
compelling indications for the initial use of other
antihypertensive drug classes (angiotensin-
converting enzyme inhibitors, angiotensin receptor
blockers, beta-blockers, calcium channel blockers).
5. Most patients with hypertension will require 2 or
more antihypertensive medications to achieve goal
BP (< 140/90 mmHg, or < 130/80 mmHg for patients
with diabetes or chronic kidney disease).
6. If BP is more than 20/10 mmHg above goal BP,
consideration should be given to initiating therapy
with 2 agents, 1 of which usually should be
thiazide-type diuretic.
7. The most effective therapy prescribed by the most
careful clinician will control hypertension only if
patients are motivated.
II. What are the changing points in JNC7 from JNC6?

JNC 6 JNC 7

1 Optimal BP < 120/80 mmHg Normal BP < 120/80 mmHg


Normal BP < 130/85 mmHg Pre-
BP 2 hypertension 120-139/80-89 mmHg
High-normal BP 130-139/85-89 mmHg BP
Classification
Stage 2 BP 160-179/100-109 mmHg
3 Stage 2 BP > 160/100 mmHg
Stage 3 BP > 180/110 mmHg

For patients For patients


with diabetes with diabetes
Taget BP < 135/85 mmHg < 130/80 mmHg
or kidney or kidney
disease disease

Diuretic (and
Without Without
First 1 Diuretics or Beta-blocker antihypertensive drug*2 can
complications complications
recommended be combined.)
drugs at 1st
stage With Antihypertensive drug *1 With Antihypertensive drug *2
2
complications depending on complication complications depending on complication
Diuretic and
Without Antihypertensive drug *1 Without
First 1 antihypertensive drug *2
complications depending on complication complications
recommended depending on complication
drugs at 2nd
With Antihypertensive drug *1 With Antihypertensive drug *2
stage 2
complications depending on complication complications depending on complication

*1: Diuretic Beta-blocker, ACE-Inhibitor, ARB, CCB and Vasodilator


*2: Diuretic Beta-blocker, ACE-Inhibitor, ARB, CCB and Aldosterone Antagonist
III. Goal of Therapy and the Target Blood Pressure
1. The JNC 7 Guideline mentions that the ultimate public
health goal of antihypertensive therapy is the
reduction of cardiovascular and renal morbidity and
mortality.
2. The target blood pressure remains unchanged as
<140/90 mmHg.
For patients with diabetes or chronic kidney disease
the target blood pressure should be <130/80 mmHg.
IV. Classification and Management of Blood Pressure for Adults
Aged 18 years or Older

The new classification of hypertension and the management of BP are provided in


the guideline as shown in the following table.

Initial Drug Thrapy


BP SBP DBP Lifestyle Without
With Compelling
Classification mmHg mmHg Modification Compelling
Indication
Indication
< 120
Normal < 80 Encourage - -
and
No Drug(s) for the
Pre- 120-139
80-89 Yes antihypretensive compelling
hypretension or
drug indicated indication
Diuretics and/or
Drug(s) for the
Stage 1 140-159 ACE-I, ARB, Beta-
90-99 Yes compelling
hypertension or blocker, CCB, or
indication
combination
Diuretic and Drug(s) for the
Stage 2 > 160
> 100 Yes other compelling
hypretension or
combination indication
V. Guideline basis for compelling indications for individual
drug classes
The JNC 7 guideline mentions that the certain high-risk
conditions are compelling indications for the initial use of
other antihypertensive drug classes, such as ACE-Is, ARBs,
beta-blockers, CCBs.
The compelling indications for antihypertensive drugs are
based on benefits from outcome studies or existing clinical
guideline; the compelling indication is managed in parallel
with the blood pressure; ex, ACC/AHA Heart Failure
Guideline, MERIT-HT, COPERNICUS, CIBIS, SLOVD, AIRE,
TRACE, ValHEFT, RALES, ACC/AHA Post-MI Guideline, BHAT,
SAVE, Capricorn, EPHESUS, ALLHAT, HOPE, ANBP2, LIFE,
CONVINCE, NKF-ADA Guideline, UKPDS, NKF Guideline,
Captopril Trial, RENAAL, IDNT, REIN, AASK, PROGRESS.
Recommended Drugs

High-Risk
Conditions Beta- Aldosterone
Diuretic ACE Inhibitor ARB CCB
withCompelling Blocker Antagonist
Indication

Heart Failure

Post-myocardial
infarction

High coronary
disease risk

Diabetes

Chronic kidney
disease

Recurrent stroke
prevention
VI. Implication
1. Only diuretic become the first recommended
drug for the patients with hypertension, and all
kinds of antihypertensive drugs, such as ACE-
Is, ARBs, beta-blockers, CCBs can be
combined with diuretic in the case BP is not
well-controlled.
2. The patients with compelling indications ACE-
Is, ARBs, Beta-Blockers, CCBs etc. should be
used despite of the stage of the BP
classification based on the recently published
mega trials and the existing clinical guideline.
3. Especially, ACE-Is can be applied for all kinds
of compelling indications.