HYPERTENSION

Rafey MA, May 2013

Definition and Etiology
Normal or optimal blood pressure (BP) is defined as the level above which minimal
vascular damage occurs. Study demonstrated that a BP level lower than 115/75 mmHg
appears to better define optimal BP.

The Joint National Committee 7 (JNC 7), hypertension is defined as physician office
systolic BP level of ≥140mmHg and diastolic BP of ≥90mmHg. The JNC 7 defines
normal BP as a systolic BP <120mmHg and diastolic BP <80mmHg. The gray area
between systolic BP of 120-139 mmHg and diastolic BP of 80-89 mmHg is defined as
“prehypertension.
Prevalence and Risk Factors
One in 3 Americans over the age of 18 years suffers from hypertension.

The prevalence is higher among older individuals, women and non-Hispanic blacks.
Despite the increase in prevalence, recent data from the National Health and Nutrition
Examination Survey (NHANES) demonstrate an improvement in blood pressure control
(50%) among Americans with hypertension. However, the blood pressure control rate
remains suboptimal in people who have serious comorbid conditions such as chronic
kidney disease. In a survey of patients with chronic kidney disease, BP control was
found to be just 13.2%. On a global level, hypertension is a greater problem, with 13.5%
of all deaths attributed to BP-related diseases. Individuals in lower economic strata are
disproportionately afflicted with hypertension.

The prevalence of hypertension increases progressively with age. Results from the
Framingham study demonstrate that among middle-aged and elderly persons, the
residual lifetime risk of developing hypertension is 90%. In the majority of patients (95%),
hypertension is primary or idiopathic; there is no identifiable risk factor. The remainder of
these patients have hypertension caused by renovascular disease, primary
aldosteronism, etc.
Pathophysiology and Natural History
The role of altered salt excretion by the kidney as a central mechanism in the
development of hypertension was proposed by Arthur C. Guyton. According to Dr.
Guyton's hypothesis, there is impaired excretion of sodium ions by tubular epithelial cells
in the kidney. To maintain salt and water homoeostasis, the body adopts a pressure-
natriuresis approach that ultimately leads to an elevation in BP. Animal studies and
studies evaluating Mendelian forms of syndromes that manifest as hypertension and
hypotension, such as Bartter's syndrome and Liddle's syndrome, have provided insight
into the pathophysiology of hypertension.These data confirm that the basic problem in
conditions leading to alteration in BP lies in the genetic alteration of sodium transport in
renal epithelial cells. Several factors including aging, sympathetic overactivity, toxins,
and a low nephron number have been proposed as factors that could ultimately damage
the renal tubules and alter epithelial cells, resulting in defective sodium excretion.

In addition, several new conditions that can cause hypertension have been identified.
The metabolic syndrome, with insulin resistance and elevation in insulin levels, leads to
increased sympathetic activity and hypertension. In patients with obstructive sleep
apnea, activation of the sympathetic and renin angiotensin systems has been defined as
a possible mechanism for elevation in BP.
Diagnosis
A detailed history and physical examination is essential for identifying risk factors and
stratifying patients to target those who need more aggressive therapy to achieve goal
BP. The history should include details of dietary salt intake and should explore lifestyle
patterns and social and psychosocial stressors that could potentially affect BP levels.
Ophthalmologic assessment and funduscopic examination are simple techniques to
identify the severity of disease and target organ damage by grading retinal changes
Office Blood Pressure Measurement
Careful measurement of BP should be an integral part of any physical examination in a
physician's office. Because inaccuracies in blood pressure measurement can occur
frequently in clinical practice, the following guidelines should be followed when
measuring a patient's BP.The patient should be seated comfortably with the back
supported and the upper arm bared without constrictive clothing. The legs should not be
crossed. The arm should be supported at the level of the heart, and the bladder of the
BP cuff should encircle at least 80% of the arm circumference. The blood pressure
measuring device should be deflated at the rate of 2 to 3 mm/sec, and the first and last
audible sounds should be taken as the systolic and diastolic pressure respectively.
Neither the patient nor the observer should talk during the measurement.
Patterns of Blood Pressure
Based on 24-hour ambulatory BP monitoring and office BP readings, 4 patterns of BP
have been described.
Laboratory Tests
Baseline blood tests are recommended by JNC 7 to identify those individuals at risk for
hypertensive events (Table 1). In addition, laboratory tests can provide clues to the
etiology in those with resistant or secondary hypertension (Table 2).

Table 1. Baseline blood tests recommended by JNC 7

Routine tests

Electrocardiogram

Urinalysis

Blood glucose, and hematocrit

Serum potassium, creatinine, or the corresponding estimated glomerular filtration rate, and calcium

Lipid profile, after 9- to 12-hour fast, that includes high-density and low-density lipoprotein cholesterol, and
triglycerides

Optional test

Measurement of urinary albumin excretion or albumin/creatinine ratio

More extensive testing for identifiable causes is not generally indicated unless blood pressure control
is not achieved.
Table 2. Laboratory tests and their clues to etiology in patients with
resistant or secondary hypertension

Laboratory Test Possible Clinical Implication Change in Management

Urinalysis Renal disease Lower blood pressure goal

Serum potassium Primary aldosteronism, Cushing Further evaluation for secondary

syndrome hypertension

Serum creatinine Renal disease and renovascular Further evaluation and more aggressive
disease therapy

Hematocrit Polycythemia Further evaluation

Electrocardiogram Left ventricular hypertrophy More aggressive therapy

Fasting lipid Elevated risk for cardiovascular events Aggressive lifestyle modifications
profile

Summary

 Proper technique of BP measurement should be an integral part of the evaluation

and management of hypertension.
 Home blood pressure recording is now recommended as an inexpensive and
accurate method of measuring blood pressure.
 Patterns of BP based on ambulatory BP monitoring play an important role in
altering therapy and outcomes.
 Laboratory examination helps in stratifying patients who will need more extensive
evaluation and aggressive therapy.
Table 3: Classification of Blood Pressure (BP)

Classification Systolic BP (mmHg) Diastolic BP (mmHg)

Normal <120 And <80

Prehypertension 120-139 Or 80-89

Stage 1 hypertension 140-159 Or 90-99

Stage 2 hypertension ≥160 Or ≥100

Table 4: Lifestyle modifications to manage hypertension.*†2

Approximate SBP
Modification Recommendation
Reduction Range

Weight reduction Maintain normal body weight (body mass index, 18.4– 5-20 mmHg;
2
24.9 kg/m ) 10-kg weight loss

Adopt DASH eating Consume diet rich in fruits, vegetables, low-fat dairy 8-14 mmHg
plan products, with reduced content of saturated and total fats

Dietary sodium Reduce dietary sodium intake to no more than 100 2-8 mmHg
reduction mmol/day (2.4g sodium or 6g sodium chloride)

Physical activity Engage in regular aerobic physical activity (e.g., brisk 4-9 mmHg
walking) at least 30 min/day, most days of the week

Moderation of alcohol Most men: limit consumption to no more than two 2-4 mmHg
consumption drinks/day‡
Most women and those who weigh less than normal: no
more than one drink/day

DASH, Dietary Approaches to Stop Hypertension; SBP, systolic blood pressure

* For overall cardiovascular risk reduction, stop smoking.
† The effects of implementing these modifications are dose- and time-dependent and could be more
effective for some patients.
‡ 1 oz or 30 mL ethanol: 12 oz beer, 5 oz wine, 1.5 oz of 80-proof whiskey.
 Medical Treatment
Table 5. Classification and management of blood pressure for adults.2

Initial Drug Therapy

SBP,* DBP,* Lifestyle With Compelling Without Compelling

BP Classification
mm Hg mm Hg Modifications Indications Indications

Normal <120 And Encourage

<80

Prehypertension 120- Or80- Yes No antihypertensive Drug(s) for compelling

139 89 drug indicated indications†

Stage 1 140- Or90- Yes Thiazide-type Drug(s) for the

Hypertension 159 99 diuretics for most. compelling
May consider ACEI, indications.‡ Other
ARB, BB, CCB, or antihypertensive drugs
combination (diuretics, ACEI, ARB,
BB, CCB) as needed

Stage 2 ≥160 Or≥100 Yes Two-drug

Hypertension combination for
most† (usually
thiazide-type diuretic
and ACEI or ARB or
BB or CCB)
Table 6: Clinical Trial and Guideline Basis for Compelling Indications for
Individual Drug Classes

Recommended Drugs Clinical Trial Basis†

Compelling Aldo
Diuretic BB ACEI ARB CCB
Indication* ANT

Heart failure √ √ √ √ √ ACC/AHA heart failure guideline,

MERIT-HF, COPERNICUS, CIBIS,
SOLVD, AIRE, TRACE, ValHEFT,
RALES

Postmyocardial √ √ √ ACC/AHA post-MI guideline, BHAT,

infarction SAVE, Capricorn, EPHESUS

High coronary √ √ √ √ ALLHAT, HOPE, ANBP2, LIFE,

disease risk CONVINCE

Diabetes √ √ √ √ √ NKF-ADA guideline, UKPDS, ALLHat

Chronic kidney √ √ NKF guideline, captopril trial, RENAAL,

disease IDNT, REIN, AASK

Summary

 Classification of hypertension is based on BP levels as well as comorbidities such

as heart disease, diabetes, and renal disease.
 Lifestyle intervention should be recommended for patients with prehypertension
and all stages of hypertension.
 Compelling indications mandate therapy with specific medications.
Secondary Hypertension
Table 7: Workup and management of secondary hypertension
Cause of Secondary
Diagnostic Tests
Hypertension
Renovascular Renal duplex ultrasonography, CT or MR
disease angiography, renal angiogram.
Primary Plasma aldosterone renin ratio, salt
aldosteronism loading test for confirmation, CT scan of
adrenal and adrenal vein sampling for
localization.
Cushing syndrome Dexamethasone suppression test, salivary
cortisol levels, CT adrenal gland.
Pheochromocytoma Plasma metanephrines, 24-hour urinary
metanephrines and catecholamines, CT,
MRI, metaiodobenzylguanidine scan if CT
or MRI are not conclusive.
Coarctation of aorta Echocardiogram, MR angiography,
aortogram.
Renovascular Renal duplex ultrasonography, CT or MR
disease angiography, renal angiogram.
ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker (antagonist); CT, computed
tomography; FMD, fibromuscular dysplasia; MR, magnetic resonance; MRI, magnetic resonance
imaging.
Management
Balloon angioplasty in patients with
FMD; medical management with
ACE inhibitor or ARB in combination
with a diuretic for patients with
atherosclerotic renal artery disease.
In a patient with adrenal hyperplasia
or bilateral functional adrenal
adenoma, medical therapy with
aldosterone antagonist.
In a patient with unilateral functional
adenoma, adrenalectomy of the
affected adrenal gland.
Treat primary cause for excess
cortisol levels.
Adrenalectomy of the affected
adrenal gland.
Angioplasty or surgical correction.
Balloon angioplasty in patient with
FMD; medical management with
ACE inhibitor or ARB in combination
with a diuretic for patient with
atherosclerotic renal artery disease.
Hypertensive Emergencies

Approximately 1% of Americans with hypertension are estimated to be affected by

hypertensive crises. Hypertensive crisis broadly covers both hypertensive urgency and
emergency. JNC 7 defines hypertensive emergency as severe elevation in BP
(>180/120 mmHg) complicated by evidence of impending or progressive target organ
dysfunction and damage.2 When severe elevation in BP occurs without acute target
organ dysfunction or damage, it is defined as hypertensive urgency.

Hypertensive emergencies are more common in patients with essential hypertension

(20%-30% in Caucasians and 80% in African Americans). Factors such as renal failure,
heart failure, cerebrovascular accidents, and nonadherence to antihypertensive therapy
are associated with hypertensive crisis. Illicit drug use is an important cause for
hypertensive crisis. The pathophysiology of hypertensive crisis remains unclear. It has
been proposed that an acute increase in humoral factors leads to systemic
vasoconstriction and increased vascular resistance causing elevation in blood pressure.
Very high BP in turn causes shear stress and endothelial injury thereby further
aggravating blood pressure levels and hypertensive crisis.36

Patients with hypertensive emergencies may present with hypertensive encephalopathy,

intracerebral hemorrhage, acute myocardial infarction, acute left ventricular failure with
pulmonary edema, unstable angina pectoris, dissecting aortic aneurysm, or eclampsia.
When evaluating patients with severe hypertension, it is important to distinguish
hypertensive urgency from hypertensive emergency as the treatment plan is based on
the diagnosis. Patients with hypertensive emergency require immediate BP lowering (by
25%) within minutes to an hour and then gradually to 160/110 mmHg over next 2 to 6
hours in order to prevent or limit target organ damage. Rapid lowering of BP to near
normal levels is avoided as it could lead to renal, cerebral and coronary ischemia. These
patients require monitoring in intensive care units and parenteral anti-hypertensive
medications (Table 9). In contrast, for patients with hypertensive urgency, blood
pressure can be lowered gradually over 24-48 hours.
Table 9. Intravenous Agents for Hypertensive Emergencies

Agent Onset Duration Advantages Disadvantages

Nitroprusside Immediate 1-2 minutes Potent, titratable Cyanide, isocyanide

Nitroglycerine 2-5 minutes 3-5 minutes Coronary perfusion Tolerance, variable efficacy

Fenoldopam <5 minutes 5-10 Renal perfusion Increased intraocular pressure

minutes

Hydralazine 10-20 3-8 hours Eclampsia Tachycardia, headache

minutes

Nicardipine 5-15 minutes 1-4 hours CNS protection Avoid in CHF and cardiac
ischemia

Enalaprilat 15-30 6 hours CHF, acute LV Avoid in MI

minutes failure

CNS, central nervous system; CHF, congestive heart failure; LV, left ventricular; MI, myocardial
infarction.

Summary

 Underlying history of hypertension is an important factor in patients who develop

hypertensive crisis.
 Triaging patients with hypertensive emergencies early and initiating parenteral
antihypertensive therapy helps to limit target organ damage.
 Overly rapid lowering of BP to normal levels in patients with hypertensive
emergencies should be avoided as it can cause renal, cerebral, and coronary
ischemia.
Conclusions
Hypertension is an important modifiable risk factor. Although a majority of patients with
hypertension remain asymptomatic, a careful early evaluation identifies those with or at
risk for target organ damage with left ventricular hypertrophy and microalbuminuria, both
of which portend serious future cardiovascular and renal events. Early identification of
these patients and achieving BP goals could reverse early end-organ damage and
improve outcomes in these patients. Analysis of the data from Framingham Heart study
demonstrates that a 2-mmHg reduction in blood pressure would result in 14% reduction
in the risk of stroke and transient ischemic attacks, and a 6% reduction in risk of
coronary heart disease. The effective management of hypertension is therefore an
important primary health care objective in managing cardiovascular and renal disease.

It must be emphasized that accurate measurement of blood pressure is of fundamental

importance in management of hypertension. It is also important to identify the modifiable
risk factors that can help improve blood pressure control and reduce cardiovascular and
renal damage. Certain classes of medications appear to have a more beneficial effect
than others in managing high-risk patients with hypertension leading to the
recommendation of compelling indications. Thus anti-hypertensive therapy should be
tailored and personalized based on an individual's health profile. For instance, in
patients with hypertension associated with unusual features such as early onset of
severe hypertension or clinical features such as palpitations and diaphoresis, further
evaluation for secondary hypertension is recommended as these conditions are
potentially curable. On the other hand, patients with severely elevated hypertension and
with evidence of target organ dysfunction or damage need to be triaged early and
started on parenteral antihypertensive therapy to lower cardiovascular and renal
morbidity and mortality.