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How to control blood pressure ?

Atma Gunawan
Subspecialist of Nephrology and
Blood Pressure Classification
(JNC VII ; office BP)
BP Classification SBP mmHg DBP mmHg

Normal <120 and <80

Prehypertension 120139 or 8089

Stage 1 Hypertension 140159 or 9099

Stage 2 Hypertension >160 or >100

Denitions and classication of office BP levels (mmHg)* (ESH-ESC)

SBP >140 mmHg DBP >90 mmHg

Category Systolic Diastolic

Optimal <120 and <80

Normal 120129 and/or 8084

High normal 130139 and/or 8589

Grade 1 hypertension 140159 and/or 9099

Grade 2 hypertension 160179 and/or 100109

Grade 3 hypertension 180 and/or 110

Isolated systolic hypertension 140 and <90

* The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated
systolic hypertension should be graded 1, 2, or 3 according to systolic BP values in the ranges indicated.
Who should measure BP ?

Mancia,, Hypertension 1987;9;209

Variations in the measurement of blood
pressure between doctors and nurses
Frequency distribution of Frequency distribution of
systolic blood pressure diastolic blood pressure

J. Roy. Coll. gen. Practit., 1971, 21, 698

Circadian BP : nocturnal dipping and
AM surge


+20% Systolic
170 +38%
Blood Pressure (mm Hg)




+57% +38%
90 Diastolic

0 3 6 9 12 15 18 21
Clock Time (hours)

Millar-Craig M. Lancet 1978;i:795

Circadian variation in disease
Based on meta-analysis of studies:
5-12 AM (awakening hours)
~50% higher risk of Stroke
~40% higher risk of Myocardial Infarction
~30% higher risk of Sudden Cardiac Death
Theoretically, antihypertensive medicines that
are particularly efficacious over 24 hours with
sustained or peak effect in the morning hours
may reduce the incidence of CV events more
Melatonin circadian
Failure of the BP to
fall by at least 10
percent during
sleep is called
Frequently in post
menopause, sleep
smoker, high salt
diet, lack of
physical activity,
Blood pressure monitoring

Home BP : measured at 7 AM and 7 ABPM (ambulatory blood

PM, at least 3 days pressure monitoring)
2013 ESH/ESC Guidelines for the management of arterial hypertension

Definitions of hypertension by office and out-of-office BP levels

Category Systolic BP Diastolic BP

(mmHg) (mmHg)

Office BP 140 and 90

Ambulatory BP

Daytime (or awake) 135 and/or 85

Nighttime (or asleep) 120 and/or 70

24-h 130 and/or 80

Home BP 135 and/or 85

BP, blood pressure.

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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11-year risk of cardiovascular mortality for
10mm Hg increase in office, home, and
ambulatory BP (Pamela Study, n= 1412)

Circulation 2005, 111:1777-1783

White coat hypertension

Office BP persistently 140/90mmHg

Normal daytime ambulatory (<130135/85mmHg) or
home (<135/85 mmHg) BP
Masked hypertension
Office BP persistently normal (<140/90mmHg)
Elevated ambulatory ( 130/80mmHg) or home
( 135/85mmHg) BP
10 to 40 percent of patients who are normotensive by
conventional clinic measurement
47% developed to sustained HT
Cardiovascular risk: similar as with sustained HT
The prognosis of masked hypertension

J Hypertension 2007;25:2193-98
Treatment strategies in white-coat
and masked hypertension

(ESH-ESC 2013)
BP target JNC VIII (2014)
Aged 18 yrs to <60 yrs , CKD,
DM :
SBP < 140 mmHg
DBP < 90 mmHg

Aged 60 yrs :
SBP <150 mmHg
DBP <90 mmHg
JNC VIII Guideline Management


Add third medication if not at

goal blood pressure
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.

2013 ESH/ESC Guidelines for the management of arterial hypertension

Monotherapy vs. drug combination strategies to achieve target BP

Mild BP elevation Choose between Marked BP elevation

Low/moderate CV risk High/very high CV risk

Single agent Twodrug combination

Switch Previous agent Previous combination Add a third drug

to different agent at full dose at full dose

Full dose Two drug Switch Three drug

monotherapy combination to different twodrug combination
at full doses combination at full doses

Moving from a less intensive to a more intensive therapeutic strategy

should be done whenever BP target is not achieved.
BP, blood pressure; CV, cardiovascular.

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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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

The Japanese Society of

Hypertension Committee for
The use of two or three drugs in combination is often necessary

Guidelines for the to achieve the target BP control

Management of Hypertension
2009 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;
download.aspx?o=CG034fullguideline (accessed January 2010); Ogihara et al. Hypertens Res. 2009;32:3107.
Multiple antihypertensive agents
are needed to achieve target BP
Number of antihypertensive agents
Trial Target BP (mmHg) 1 2 3 4


IDNT SBP <135/DBP <85

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

DBP, diastolic blood pressure; MAP, mean arterial Lewis EJ, et al. N Engl J Med 2001;345:851-860;
pressure; SBP, systolic blood pressure Cushman WC, et al. J Clin Hypertens 2002;4:393-404
Combination Therapy Versus Monotherapy in Reducing Blood
Pressure: Meta-analysis on 11,000 Participants from 42 Trials
Low-dose therapy has the advantage of reducing adverse effects that, with the exception of ACEI/ARB, are strongly dose related; for 2
classes (thiazides and calcium channel blockers), for example, adverse effects are 80% lower at half-standard than standard dose. The
prevalence of adverse effects from combining 2 drugs at half-standard dose would therefore, for most combinations, be lower than
with 1 drug at standard dose.

The extra blood pressure reduction from combining drugs from 2 different classes is
approximately 5 times greater than doubling the dose of 1 drug

Wald et al. Am J Med 2009;122:290300

2013 ESH/ESC Guidelines for the management of arterial hypertension

Possible combinations of classes of antihypertensive drugs

Thiazide diuretics

-blockers Angiotensin-receptor

Other Calcium
antihypertensives antagonists

ACE inhibitors

Green continuous lines: preferred combinations; green dashed line: useful combination (with some limitations); black
dashed lines: possible but less well tested combinations; red continuous line: not recommended combination. Although
verapamil and diltiazem are sometimes used with a beta-blocker to improve ventricular rate control in permanent atrial
fibrillation, only dihydropyridine calcium antagonists should normally be combined with beta-blockers.

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
Medical Education & Information for all Media, all Disciplines, from all over
the World Powered by
Ineffective combinations
ONTARGET: ACE-I and ARB are accompanied by a significant
excess of cases of ESRD
ACE-I/ARB and BB : produces little additional blood pressure
reduction compared with either monotherapy. Commonly combined
to reduce reinfarction rates and to improve survival.
BB and diuretic : increase the risk of glucose intolerance, the
development of new-onset diabetes,fatigue, and sexual dysfunction.
BB and antiadrenergic drugs (clonidine,methyldopa,reserpine) : little
effect in lowering BP, frequent exaggerated rebound.
HCT is ineffective if creatinine level > 2.5 mg/dL. Switch to
Doxazosin or spironolactone can be added to triple therapy in
patients with resistant hypertension
Preferred hypertension treatment in specific conditions
Condition Drug
Asymptomatic organ damage
LVH LVH ACE inhibitor, calcium antagonist, ARB
Asymptomatic atherosclerosis Calcium antagonist, ACE inhibitor
Microalbuminuria ACE inhibitor, ARB
Renal dysfunction ACE inhibitor, ARB
Clinical CV event
Previous stroke Any agent effectively lowering BP
Previous myocardial infarction BB, ACE inhibitor, ARB
Angina pectoris BB, calcium antagonist
Heart failure Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor antagonists
Aortic aneurysm BB
Atrial fibrillation, prevention Consider ARB, ACE inhibitor, BB or mineralocorticoid receptor antagonist
Atrial fibrillation, ventricular rate control BB, non-dihydropyridine calcium antagonist
ESRD/proteinuria ACE inhibitor, ARB
Peripheral artery disease ACE inhibitor, calcium antagonist
ISH (elderly) Diuretic, calcium antagonist
Metabolic syndrome ACE inhibitor, ARB, calcium antagonist
Diabetes mellitus ACE inhibitor, ARB
Pregnancy Methyldopa, BB, calcium antagonist
Blacks Diuretic, calcium antagonist
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BB, beta-blocker; BP, blood pressure; CV, cardiovascular; ESRD, end-stage renal
ISH, isolated systolic hypertension; LVH, left ventricular hypertrophy.
Compelling indications for hypertension treatment
Class Contraindications
Compelling Possible
Diuretics Gout Metabolic syndrome
(thiazides) Glucose intolerance

Beta-blockers Asthma Metabolic syndrome

AV block (grade 2 or 3) Glucose intolerance
Athletes and physically active patients
COPD (except for vasodilator beta-blockers)

Calcium antagonists Tachyarrhythmia

(dihydropyridines) Heart failure

Calcium antagonists AV block (grade 2 or 3, trifascicular block)

(verapamil, diltiazem) Severe LV dysfunction
Heart failure

ACE inhibitors Pregnancy Women with child bearing potential

Angioneurotic oedema
Bilateral renal artery stenosis

Angiotensin receptor blockers Pregnancy Women with child bearing potential

Bilateral renal artery stenosis

Mineralocorticoid Acute or severe renal failure (eGFR <30 mL/min)

receptor antagonists Hyperkalaemia

A-V, atrio-ventricular; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; LV, left
Secondary hypertension
Secondary causes of hypertension
The most common were renal disease
Endocrine 11%
Renovascular diseases 10%
Clinical features of secondary hypertension

Disorder Suggestive clinical features

General Severe or refractory hypertension
Accelarated BP in stable condition
Age less than 30 years with no family history of hypertension and
no obesity
An acute elevation in serum creatinine after administration of -
Elevated serum creatinine concentration
Triad of headache (usually pounding), palpitations, and sweating
Unexplained hypokalemia
Cushingoid facies
Symptoms of hyper/hypothyroidism
Hypertension treatment is
simple, but why become
pandemic and hardly to
achieve target BP ?
Top 10 causes of death

WHO media center, May 2014

World Health Day 2013
(WHO press release, April 2013)
Hospital discharges for cardiovascular disease (United States: 19702007).

Roger V L et al. Circulation. 2011;123:e18-e209

Reasons for Lack of Responsiveness to
Hypertension Therapy
Patient factors : obesity , high salt diet, LVH, non adherence
Late to start a combination
Misdiagnosis : white coat hypertension, mask hypertension, non dipping
hypertension, pseudohypertension
Secondary hypertension : sleep disturbances, renal parenchymal
disease,primary aldosteronism, renal artery stenosis, cushing disease,
Drug-related causes : Doses too low, Inappropriate combinations, Rapid
inactivation , Drug interactions (Glucocorticoids, NSAIDs, phenothiazines,
oral contraceptives, Sympathomimetics, nasal decongestans, cyclosporine,
Increased prevalence of HT and DM in
US, associated with obesity

JAMA, 2003; 289: 76-79

Obesity and hypertension
Framingham Heart Study suggest that 78% of
new cases of hypertension in men and 65% in
women are related to excess body weight
Every 10-pound weight gain is associated with
an estimated 4.5-mm Hg increase in systolic
blood pressure

Curr Opin Cardiol. 1996;11:490495.

Prev Med. 1987;16:234251
Correlates of prevalent hypertension among the study subjects: results
of multiple logistic regression analyses(a)

a Age, sex, marital status, religion, past history of smoking were not statistically significant
b BMI = body mass index.
c Figures in parentheses are standard errors.
d Figures in italics are 95% confidence intervals.
e By self-report.
Bulletin of the World Health Organization, 2001, 79 (6)
Obesity and hypertension

Obesity, Real and theoretical links connecting

obesity to hypertension.

Curr Diab Rev. 2010; 6: 58-67 Goodfriend T L , and Calhoun D A Hypertension.

Resistant hypertension in visceral obesity

The survey was performed on 5065 hypertensive patients with visceral obesity.
BP control was analyzed on the basis of office and home BP measurements.
Patients reporting non-compliance were excluded from the study.
The percentage of RH was 13.9%. RH was more frequent only in obese with
BMI35 and <40kg/m2 (16.2%) and in morbidly obese individuals (26.5%).
Patients with BMI35 and <40kg/m2 and with morbid obesity were receiving
three-drug therapy more frequently than patients with visceral obesity and
BMI<30kg/m2. A multiple regression analysis revealed that obesity was
associated with RH independent from longer than 5-year period of
antihypertensive therapy, diabetes, smoking cigarettes, cardiovascular disease
and heart failure. The analysis of home BP measurement revealed that in
11.1% of patients RH was in fact white coat hypertension.

European Journal of Internal Medicine

Volume 23, Issue 7, Pages 643648, October 2012
dan makanlah makanan yang halal lagi baik dari apa
yang telah dirizkikan kepadamu dan bertaqwalah kepada
Allah dan kamu beriman kepada-Nya (Surat Al Maidah :
Makan dan minumlah kalian, namun jangan berlebih-
lebihan (boros) karena Allah tidak mencintai orang-orang
yang berlebih-lebihan. (Al-Araf:31).
Nabi shollallahu alaihi wa sallam: Kami adalah suatu
kaum yang tidak akan makan sampai kami lapar, dan
apabila kami makan maka kami berhenti sebelum
Sleep disturbances
Short sleep
National surveys in USA have shown a decline in self-reported sleep
duration over the past 50 years by 1.5 to 2 hours.
>30% of Americans report sleeping less than 6 h/night
Short sleep : <5 h/day or 5 h per night
Other definition short sleep: <6 h/night or <6 h per day
In children the definition of short sleep was <10 h/day or < 10 h
per night
Effect of short sleep :
- longer exposures to elevated sympathetic nervous system
- raise blood pressure and heart rate (non-dipping HT)
- increase aldosterone levels
ABPM on a sleep-insufficient day and a normal workday
recorded by portable multibiomedical (PMB)
Means of ambulatory blood pressure on a Effects of Insufficient Sleep on
sleep-insufficient day and a normal workday Autonomic Nervous System Activity

Urinary excretion Routine Sleep- P

norepinephrine Workday Insufficient
nmol/g Day

Sleep period 12439 16878 <.05

Waking hours 23049 270 68 <.05

24 Hours 19446 22358 <.05

Tochikubo et al. [16]. Hypertension 1996; 27: 1318-1324

Sleep duration to risk of hypertension incidence: a meta-
analysis of prospective cohort studies .
(a) Short sleep duration. (b) Long sleep duration

Hypertension Research (2013) 36, 985995

Meta-Analysis of Short Sleep Duration and Obesity in

SLEEP, Vol. 31, No. 5, 2008

Baseline polysomnographic data of the subject
with normotension, controlled hypertension and resistant


Dialah yang menjadikan untukmu
malam (sebagai) pakaian, dan tidur
untuk istirahat, dan Dia menjadikan
siang untuk bangun berusaha (Al-
Furqaan Ayat : 47)
Obstructive sleep apnea
At least 10 apneic and hypopneic episodes (min 10
seconds) per sleep hour
10% of 30-60 years of age (5% of woman and 15% of men)
Superimposed recordings of the electrooculogram (EOG),
electroencephalogram (EEG), electromyogram (EMG), ECG (EKG),
sympathetic nerve activity (SNA), respiration (RESP), and blood
pressure (BP) during REM sleep in a patient with OSA
All Htn CAD
Drug Stroke or CHF
Resistant TIA Nieto Shafer
Basetti JAMA Card 1999
Circ 1999
Logan 2000
J Htn 2001 1999
Treatment of sleep apnea

Behavioral factors :
- weight loss
- no alcohol and smoking,
and no sedatives before
- avoidance of supine sleep
position but lateral
Spironolactone 25-50 mg/d
Nasal CPAP Continuous positive
airway pressure
Oral dental devices
Surgical procedures :
UPP, nasal
Maxiofacial surgery,tracheostomy
Can antihypertensive medications
reduced or stopped?
Patients in effective BP control for an
extended period, it may be possible to
reduce the number and dosage of drugs.
Reduction of medications should be made
BP control is accompanied by healthy
BP should be checked frequently because
of the risk of reappearance of hypertension.
Discontinuation of antihypertensive
N : 2765

Medical Research Council Working Party of Mild

Hypertension, Br Med J 1986; 293:988.
A case
A 65-year-old woman with a long-standing history of hypertension
comes for follow-up. Her medications include atenolol (100 mg
daily), hydrochlorothiazide (12.5 mg daily), lisinopril (40 mg daily),
and na-diclofenac (25 mg twice daily for osteoarthritis). She does
not smoke . Her body-mass index (the weight in kilograms divided
by the square of the height in meters) is 32. Her systolic and
diastolic blood pressures (measured three times while she was
seated) range from 164 to 170 mm Hg and 92 to 96 mm Hg,
respectively, and the pulse rate is 72 per minute. Funduscopic of her
ocular fundi reveals arteriolar narrowing. The results of
cardiovascular examination are normal. The serum potassium level
is 3.8 meq per liter, and the serum creatinine level is 1.2 mg per
deciliter ; there is no microalbuminuria. How should this patient be
further evaluated and treated?
Oral antihypertensive drugs*
Oral antihypertensive drugs* (continued)
ACEIs, angiotensin converting enzyme inhibitors; BBs, beta blockers; CCBs, calcium channel blockers
* In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval
(trough effect).
BP should be measured just prior to dosing to determine if satisfactory BP control is obtained. Accordingly, an increase
in dosage or frequency may need to be considered. These dosages may vary from those listed in the Physicians Desk
Reference (57th ed.).
Available now or becoming available soon in generic preparations.
Source: Physicians Desk Reference. 57th ed. Montvale, NJ: Thompson PDR, 2003.