Clinical Practice Guideline

Management of Hypertension

Dr.M.Emmanuel Bhaskar M.D

Associate Professor in Medicine
Sri Ramachandra University
Chennai, India
 Contents
1. Introduction - 1

2.Diagnosis and classification - 2

3.Initial evaluation and treatment approach - 4

4.Lifestyle modifications - 6

5.Treatment of a newly diagnosed patient - 9

6.Treatment of hypertension – special situations - 14

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Introduction

Sixty years back clinicians were not convinced about the beneficial effects of
treating hypertension. Patients suffering from hypertension were treated with only salt restriction and
that too only when the blood pressure is very high. The drugs used to treat hypertension had marked
adverse effects and hence poorly tolerated by patients. Unnecessary surgeries like cervical
sympathectomy were done . It was only after 1960 clinicians began to advise reasonable life style
modification and drug therapy in patients diagnosed with hypertension.

Management of hypertension has been completely transformed over the last 50

years. The credit goes to all the researchers involved in more than 250 clinical trials and observational
studies done to address various clinical questions on different categories of hypertensive subjects.
However ,despite a convincing evidence from the medical literature that adequate treatment of
hypertension will help in the prevention of major complications like stroke, myocardial infarction,
renal failure, retinopathy, heart failure, etc. the target blood pressure goal is not reached in most
hypertensive subjects. Further a large proportion of patients are under-diagnosed. Adding to it the
financial constraints in health care in developing countries have made the issue more complicated. But
when we look back on our clinical practice either in corporate settings or in the resource poor setting ,
it is the lack of commitment from the clinician and other health care personnel which is probably
responsible for the poor management of hypertension in the community especially in developing
countries like India.

In this document I have suggested recommendations for the evaluation and

management of hypertension based on published studies, international guidelines from professional
societies, expert opinions and my own experience in the treatment of hypertensive subjects.
The document has been divided into:
1.Diagnosis and classification of hypertension
2.Initial evaluation and approach to treatment of hypertension.
3.Life style modification in a patient with hypertension
4.Approach to drug therapy in a newly diagnosed hypertensive patient.
5.Treatment of hypertension in patients with additional co-morbidities.
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Diagnosis and classification of hypertension

Hypertension is defined as a blood pressure elevation of more than 140 mm Hg

systolic and/or a diastolic pressure of 90 mm Hg. The elevated BP should be confirmed on two separate
occasions preferably on different days. But in clinical practice we often face a dilemma of when to
label a patient as hypertensive based on a single reading. A blood pressure reading of >180 mm Hg
systolic or >110 mm Hg diastolic obviously may not require further confirmation . Also a blood
pressure reading of >160 mm Hg systolic or >100 mm Hg diastolic in the absence of conditions which
can transiently elevate BP [ ongoing pain, bladder retention, constipation, lack of sleep, fasting state,
recent exertion ,etc] may be considered as hypertension based on a single reading. However it is
preferable to make a decision in these patients with a BP of >160/100 mm Hg to reconfirm BP before
initiating drug therapy taking into consideration the presence of other cardiovascular risk factors like
diabetes , smoking, obesity, dyslipidemia, etc. Presence of multiple risk factors may warrant early
initiation of drug therapy while absence of additional risk factors should prompt reconfirmation of the
elevated BP at a later time before initiating drug therapy.

Individuals having a BP of 140-160 mm Hg systolic and 90-100 mm Hg

diastolic will require multiple recordings before a diagnosis of hypertension is made. Exemption will
be patients suffering from diabetes, nephropathy, coronary artery disease and cerebrovascular disease
who may need early initiation of drug therapy even at a blood pressure of >140/90 mmHg .

There are two classifications for hypertension:

1. European society of hypertension [ESH] classification

2. Joint National Committee [JNC] classification of hypertension.

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1.European society of hypertension [ESH] classification:

CATEGORY Systolic BP in mm Hg Diastolic BP in mm Hg

Optimal <120 <80

Normal 120-129 80-84

High-Normal 130-139 85-89

Grade-1 Hypertension 140-159 90-99

Grade-2 Hypertension 160-179 100-109

Grade-3 Hypertension 180 and above 110 and above

Isolated Systolic Hypertension >140 <90

2.Joint National Committee [JNC] - 7 classification of hypertension:

CATEGORY Systolic BP in mm Hg Diastolic BP in mm Hg

Normal <120 <80

Pre-hypertension 120-139 80-89

Grade-1 Hypertension 140-159 90-99

Grade-2 Hypertension 160 and above 100 and above

Most hypertension experts favor the use of ESH classification since it takes into
consideration additional risk factors while deciding on drug therapy. Further more, unlike JNC which
labels a patient as pre-hypertensive if the BP is 120-139 mm Hg systolic and 80-89 mm Hg diastolic ,
the ESH considers them as high normal and avoids the labeling of pre-hypertension. Global experts
have raised concerns over JNC definition of pre-hypertension since it creates unnecessary anxiety in
otherwise healthy individuals.
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Initial evaluation and approach to treatment of Hypertension

Evaluation of a hypertensive patient should start with a good history to identify

risk factors for cardiovascular disease like smoking, sedentary life-style,impaired glucose tolerance or
diabetes, dyslipidemia, family history of premature coronary artery disease,etc. Additionally history
should include queries for possible secondary hypertension [thyroid dysfunction ,steroid intake,
cushings,pheochromocytoma,renal disease,etc] . Further questions should focus on complications of
hypertension like heart failure, TIA or stroke, coronary artery disease, peripheral arterial disease,etc.

This should be followed by a rapid clinical screening for complications of

hypertension and secondary causes of hypertension. The latter is especially important in individuals
with age less than 30 years or more than 65 years.

Points to remember while examining a hypertensive patient:

1. Check for pedal pulses.

2. Enquire for ongoing pain, lack of sleep, fasting state, bladder distension, constipation, recent
smoking if blood pressure is mild to moderately elevated before labelling the individual as
hypertensive. Reconfirm the elevated BP at later point of time as already mentioned in the
previous section.

3. Look for features of endocrine dysfunction [ hypothyroidism, hyperthyroidism,cushings

syndrome or cushingoid features]

4. Examine the cardiovascular system for features of heart failure or valvular heart disease.

5. Examine for renal bruit.

Clinical examination in most hypertensive patients does not reveal any abnormalities.
All hypertensive patients should be subjected to a basic battery of tests with the objective of identifying
end organ complications and additional comorbid conditions.
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The following investigations are mandatory in a newly diagnosed hypertensive patient:

1.Hb%, PCV
2.Random blood sugar.
3.Serum creatinine
4.Urine routine
5.ECG

The following investigations are desirable and every attempt should be made to counsel the
patient about the importance of these tests:
1.Fasting and post-prandial blood sugar
2.Fasting lipid profile
3.Urine for microalbuminuria [ Albumin creatinine ratio or an alternative test]
4.Echocardiography for assessment of left ventricular mass.

Approach to treatment of a newly diagnosed hypertensive patient:

Individuals diagnosed to have hypertension may be classified as high risk, moderate
risk and low risk for the purpose of initial drug therapy.

High Risk:
Individuals with a BP >140/90 mm Hg with cardiovascular disease or cerebrovascular disease or
diabetes
Those with Stage 2 hypertension [ SBP>160 mm Hg, DBP>100 mm Hg]
They should be treated with drug therapy along with lifestyle modifications.

Medium Risk:
Stage 1 hypertension [SBP>140 mm Hg, DBP>90 mm Hg] with one other risk factor [ male more than
55 years, female more than 65 years, smoking,dyslipidemia, obesity]
They may be offered life style modification for 2 to 3 months . After this period if BP >140/90 mm
Hg then start on drug therapy.

Low Risk:
Stage 1 hypertension with no other risk factors.
They may be offered life style modification for 5 to 6 months . After this period if BP >140/90 mm
Hg then start on drug therapy.
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Life-style modifications in a patient with Hypertension

Advice on lifestyle modification in a newly diagnosed hypertensive patient

should follow a proper understanding of the patient's lifestyle by the clinician. It is advisable to
strongly discourage ready made advice for all patients diagnosed with hypertension since it may lead to
poor outcomes in management. Clinicians should introduce lifesyle modifications in a gradual and
graded manner so as to improve compliance to our advice. A plan should be charted out for the initial 4
weeks after properly discussing the practical feasibility of the advice given. It is better to achieve a
moderate success on the long run than a transient success followed by total failure.

Lifestyle modification may be divided into:

1.Salt restriction and other dietary modifications
2.Exercise
3.Modification in habits like smoking, alcohol intake,etc

Salt restriction and other dietary modifications:

Salt restriction:
Epidemiological studies indicate worsening of hypertension with higher salt intake.
However the exact impact of salt restriction on BP is not clear. The Trial Of Non-pharmacological
intervention in the Elderly[ TONE] study showed that a 30-40 % reduction in sodium intake resulted in
a favourable lowering of BP and also decreased the amount of drugs required for treatment.
The Dietary Approach to Stop Hypertension [ DASH] trial also favoured dietary
restriction of sodium to about 6 g of salt per day. But a method to identify salt-sensitive individuals by
clinicians is still elusive.
Based on previous observational studies and recent randomized controlled trials it is
clear that moderate salt restriction of 6 g salt per day [equivalent to 2.5 g sodium] will help blood
pressure control along with other lifestyle modifications and medications.

Recommendation on salt intake:

All patients with hypertension should be advised to avoid add-on salt in their regular
diet and avoid food items with high salt content[ pickles, papads, chips, salt biscuits, fast foods, canned
juices and canned food, dry fish, fried food with added salt,etc].
With these restrictions the daily salt intake will be around 6g sodium chloride per day.
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A more strict salt restriction is not advisable especially during first diagnosis since it may lead to poor
compliance.However if BP target is not achieved with optimal drugs then a more strict salt
restriction[decreasing salt in routine food along with total avoidance of salt rich food] may be
attempted.

Other dietary modifications:

Potassium intake:
Most hypertensive experts feel that it is the ratio of sodium to potassium intake rather
than intake of either of it alone which decides the effect on blood pressure reduction.
There is not much evidence to support the use of increased potassium intake in patients
with hypertension except a few observational studies which indicate increased cardiovascular risk in
communities with a low potassium intake . In addition , the DASH trial favoured increased potassium
intake along with sodium restriction.
A potassium intake of 50-100 meq per day may be advisable in patients with
hypertension along with salt restriction. Having said that we need to know the potassium content of
common foods. A tomato soup [with 2 tomatos] has 15 meq of potassium, 2 small carrots will give 15
meq , one banana will give 15-20 meq and a cup of white beans have 20 meq of potassium. Consuming
food that is equivalent to 100 meq of potassium per day may be difficult but a potassium intake of 50
meq per day is definitely possible. Foods rich in potassium may be supplemented along with breakfast,
lunch and dinner. Intake of artificial preparations like syrup potassium chloride is not currently
recommended by global societies.
While advising potassium supplements we need to be prudent in avoiding them in
conditions where it may be contraindicated like renal failure, use of drugs which may increase
potassium, etc.
Intake of fish oil preparations has been shown to be beneficial for hypertensive patients.

Exercise:
Observational studies indicate that regular exercise of 20 – 30 minutes per day may
reduce systolic blood pressure by 5-10 mm Hg. Further , exercise helps in overall reduction in
cardiovascular risk and morbidity. On the other hand sedentary life style is strongly associated with all
components of metabolic syndrome [ hypertension, diabetes, dyslipidemia and obesity] and higher risk
for coronary artery disease.
Simple aerobic exercises like brisk walking, cycling or swimming for 20 -30 minutes per
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day for atleast 5 days a week is recommended for all hypertensive individuals if the treating clinician
finds no contraindications like marked coronary artery disease, stenotic valvular heart disease,
peripheral neuropathy,etc.

Modification in habits:

Avoidance of smoking and limiting alcohol intake is strongly encouraged for

all hypertensive patients . There is overwhelming evidence that they benefit individuals irrespective of
the underlying disease process.
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Approach to drug therapy in a newly diagnosed hypertensive patient

In this document you may find discussion on the choice of initial drug
therapy in a treatment-naive hypertensive patient who has no additional co-morbid conditions like
diabetes, coronary artery disease, cerebro-vascular disease, renal disease , dyslipidemia ,bronchial
asthma, etc.

The choice of drug therapy for a newly diagnosed hypertensive patient with
no co-morbid condition is quite vast and clinicians are often confused on best choice of drug therapy
for their patient.
While going through various studies on hypertension from the view point of
ideal drug for a newly diagnosed hypertensive patient with no co-morbid conditions , it appears that it
is very difficult to identify the drug of choice for this group.
The reason is :

1. No study has addressed this specific population since about half of hypertensive subjects on
diagnosis have at least one more cardiovascular risk factor. Further , a study on this population
is difficult since it may need a very long duration of follow-up to observe the outcomes which
are related to morbidity or mortality.

2. Large studies like UKPDS and ALLHAT was made up of population who had varying
cardiovascular risk factors. Though the patients were started on single drug therapy initially
during the course of the study additional drugs were added in at least 40% of the patients
whenever the optimal BP goal was not achieved by monotherapy. This makes outcome analysis
at the end of the study difficult.
Based on the above limitations it is obvious that identification of , “a drug of choice”,
for a hypertensive patient with no risk factors is nearly impossible.However, major studies like
ALLHAT , UKPDS, etc have clearly shown that it is the degree of hypertensive control achieved rather
than the type of drug used which decides the occurrence of outcomes like stroke, myocardial infarction,
etc.
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Hence it is prudent to conclude that a newly diagnosed hypertensive
patient with no additional cardiovascular risk or co-morbidities may be started on any of the
following agent:
1.Thiazide diuretic [ we use hydrochlorthiazide]
2.Dihydropyrimidine calcium channel blocker [ amlodipine, long acting nifedipine]
3.Angiotensin converting enzyme Inhibitor[enalapril, ramipril]
4.Angiotensin receptor blocker[ losartan]
5.Betablocker[atenolol]
Monotherapy may not be sufficient for at least half of patients diagnosed with grade 2
hypertension and nearly all grade 3 hypertensive patients. The European society of hypertension
recommends the following drug combinations when anti-hypertensive combinations are used :
1.Thiazide type diuretic and ACEI
2.Thiazide type diuretic and ARB
3.CCB and thiazide diuretic
4.CCB and ARB
5.CCB and ACEI
6.Betablocker and CCB .
In general thiazide diuretic should be the first line and should also be a
component of combination therapy.
ESH discourages the combination of Beta-blocker and thiazide diuretic due to
increased risk for development of metabolic syndrome[ especially glucose intolerance and
dyslipidemia].
Having discussed about the options of drug therapy in a newly diagnosed hypertensive
patient. We need to know about the practical aspects of different drug classes used to treat
hypertension.
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The spectrum of adverse effects given in the literature is very broad.
However clinical trials over the last 15 years has shown that many of the adverse effects
mentioned in standard pharmacology text books are relatively uncommon. A clinician probably
needs to know only about 5 to 6 anti-hypertensive drugs to be successful in treating hypertension. The
five most often prescribed class of anti-hypertensive drugs in clinical practice around the globe are:
1.Thiazide diuretics
2.Calcium channel blockers
3.Beta blockers
4.Angiotensin converting enzyme inhibitors [ACEI]
5.Angiotensin receptor blocker.[ARB]

1.Thiazide diuretics:
Hydrochlorthiazide may be considered the representative of this drug class. Its
mechanism of action is relatively unclear. Initially it produces a decrease in plasma volume and
decrease in cardiac output producing lowering of blood pressure .But with continued therapy the
plasma volume and cardiac output is restored back to normal. On the long run it is believed to produce
vasodilatation . Patients who do not respond to thiazides may be exhibiting an increased renin-
angiotensin-aldosterone system activation [RAAS] . Addition of vasodilators like ACEI or ARB may
be beneficial for them.
The most important clinical adverse effect of this drug is probably sexual
dysfunction [ more common in males]. However the prevalence of sexual dysfunction with low doses
like 12.5 mg is not clear. Clinicians often worry about hypokalemia, hyperuricemia , hyperglycemia
and dyslipidemia with the use of thiazides. But studies involving this drug have shown that these
adverse effects are not of clinical concern in the general population except in selected group of
hypertensive subjects [ diabetes, dyslipidemia, renal failure,etc]. However this does not mean that
thiazides should be be totally avoided in these patients. It may be used in low doses like 12.5mg per
day. One condition in which the drug should be totally avoided is chronic renal failure.
The usual starting dose of hydrochlorthiazide is 12.5 mg per day. Doses above 25
mg per day is not clinically useful.
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2.Calcium channel blockers:
Nifedipine and Amlodipine may be considered the representatives of this drug class.
These non-dihydropyrimidine calcium channel blockers act by inhibiting the entry of calcium into
smooth muscle cells of the arteries thus producing vasodilatation and lowering of BP.
They are relatively safe . Common adverse effects are headache, ankle edema, reflux
esophagitis and constipation. It produces no electrolyte disturbance or deterioration in renal function.
The starting dose of Amlodipine is 5 mg [max-10 mg/day, higher doses produce more
adverse effects and less significant reduction in blood pressure ]. The starting dose of Nifedipine retard
is 10 mg bd [max 20 mg tds]. Short acting nifedipine available in the form of capsule should be

avoided. Plain nifedipine can be used in the place of retard preparations but it should be given at 8 th
hourly interval.

3.Beta-blockers:
Atenolol may be considered the representative of this class. They initially
decrease the cardiac output . With continued therapy the cardiac output normalizes but peripheral
resistance is permanently lowered producing the lowering in BP.
Common adverese effects are bradycardia, bronchospasm, sexual dysfunction
and depression. It can rarely produce hyperkalemia by a distal tubular mechanism.
It is contraindicated in patients with airway disease, unstable heart failure ,
peripheral vascular disease ,severe bradycardia and heart block. The starting dose of atenolol is 50 mg
per day[ max-100 mg per day].

4.Angiotensin converting enzyme inhibitor [ ACEI]:

Enalapril and ramipril may be considered as the representatives of this class.
They act by blocking RAAS resulting in vasodilatation and lowering of BP. Their effect on the renal
hemodynamics makes them the prefered agent in reducing proteinuria. However the same mechanism
makes them prone for precipitating renal failure and producing hyperkalemia often in conditions which
can alter renal hemodynamics like diarrhea, diuretic use, vasodilator use,etc.
Monitoring of creatinine and serum potassium is important while using this
drug. Additional adverse effect include cough which is due to bradykinin accumulation.
Starting dose of enalapril is 5 mg per day [ max-20 mg per day ,doses above 10
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mg per day may be associated with more renal side effects and need close monitoring]. Starting dose of
ramipril is 2.5 mg per day[ max-10 mg per day].

5.Angiotensin receptor blocker:

Losartan may be considered the representative of this class. Blood pressure
reduction is due to the blockade of RAAS . Adverse effect profile is the same as that of ACEI except
for cough. Starting dose of Losartan is 50 mg per day [ max-100 mg per day]
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Treatment of hypertension in patients with additional co-morbidities

I. Hypertension in a Diabetic with no proteinuria:

Drug therapy in a hypertensive diabetic who has no proteinuria

should focus on a tight blood pressure control of 130/80 mm Hg with anti-hypertensive agents.
ESH discourages betablockers and thiazide diuretics as first line agents in diabetes in view of
the increased risk of dyslipidemia associated with their use. But when compelling indications
like coronary artery disease are present, then they should be used. There is some data which
indicates that ACEI prevents appearance of microalbuminuria in Type-II diabetes. This fact is
well established in patients with Type-I diabetes. There is also some data indicating benefits of
ARBs in Type-II diabetes. Most hypertensive experts consider ACEI or ARB as the first drug
option for patients with diabetes. Though thiazides are not the first option for diabetics , when
two drugs are used then the second drug should be a low-dose thiazide like 12.5 mg of
hydrochlorthiazide [ higher doses are not advisable]. The reason for considering thiazides as the
best second drug in diabetes is due to the favorable effect of thiazide in preventing myocardial
infarction and stroke.

In conclusion , ACEI or ARB may be considered the drug of first

choice in patients with diabetes who are hypertensive. Blood pressure control is of paramount
importance in diabetics to prevent unfavourable outcomes. Beta-blockers and thiazide is not
desirable as first-line agents. When additional anti-hypertensive drug is needed then a low dose
thiazide is the preferred option. Close monitoring of serum creatinine and potassium is required
when ACEI or ARB is used. If follow-up of the patient is in doubt then avoid ACEI or ARBs. In
those instances a CCB may be used.

II. Hypertension in a Diabetic with proteinuria/nephropathy:

Guidelines on preferred anti-hypertensive therapy in this group is

more clear than for any other group. In patients with early nephropathy [as evidenced by
microalbuminuria alone] or overt nephropathy [ overt proteinuria with or without elevated
creatinine] ACEI and ARB have been clearly shown to regress proteinuria or prevent further
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progression of proteinuria. In patients with proteinuria the target BP is 120/70 mm Hg as

evidenced by multiple studies. After adequate control of BP if the patient continues to have
significant proteinuria then the anti-hypertensive therapy should be further intensified with the
objective of decreasing proteinuria. In clinical practice ACEI or ARB is used when there is any
grade of proteinuria along with a creatinine of less than 2 mg/dl. Even though evidence favours
ACEI or ARB in patients with elevated creatinine [ upto 5 mg/dl] the complication of this
approach is high since patients in clinical practice are not intensively monitored compared to
clinical trial patients.

The same approach may be followed in non-diabetic patients

with hypertensive nephropathy

III. Hypertension with coronary artery disease:

This group of patients will be usually on a regimen which contains

betablocker. Hence the dillemma in decision making occurs when a second drug is required for
adequate BP control. Available evidence point towards thiazides or ACEI/ARB as the desirable
option when a second drug is needed.

IV. Hypertension with bronchial asthma:

As already mentioned Beta-blockers should be avoided in patients

with bronchial asthma in view of possible bronchospasm. Due to the accumulation of
bradykinin ACEI can aggravate cough in these patients. But the benefits of ACEI should be
properly weighed before avoiding them. ARBs do not produce cough and obviously the
alternative option for these patients who develop or have worsening of cough with ACEI.

V. Hypertension with dyslipidemia:

We know that Beta-blockers and thiazide diuretics worsen

dyslipidemia. But it is also known that myocardial infarction and stroke are the major
complications of dyslipidemia in the long term. Given the benefit of these drugs in these
patients these drugs should not be considered as contraindicated in this group. While using beta-
blockers and thiazides in patients with dyslipidemia clinicians should ensure adequate control of
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lipid parameters with suitable lipid lowering agents. In other words these drugs can still be used
if the number of cardiovascular risk factors are more or if compelling indications like coronary
artery disease is present.