According to the JNC 7 classification, hypertension is defined as blood pressure exceeding 140/90 mm Hg for adults age 18 years or older. It is one of the most common chronic conditions and a major risk factor for heart disease, stroke and renal diseases. It is the number one attributable risk for death throughout the world. However, it is both preventable and treatable in the majority of patients.

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According to a recent analysis t he estimated total number of adults with hypertension in 2000 was 972 million (more than a quarter of the world's adult population); 333 million in economically developed countries and 639 million in economically developing countries. The number of adults with hypertension in 2025 was predicted to increase by about 60% to a total of 1·56 billion. The projections for 2025 are based on the assumption that the country, age, and sex specific prevalence estimates will remain constant.

In India , it has been estimated that in year 2000, 60.4 million men and 57.8 million women were hypertensive. In 2025, t his number is predicted to increase to 107.3 million men and 106.2 million women. Therefore, India is said to be heading towards becoming the hypertension capital.

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In more than 95% of cases a specific underlying cause of hypertension cannot be found. Such patients are said to have essential hypertension.

The pathogenesis of essential hypertension is not clearly understood. Different investigators have proposed the kidney, the peripheral blood vessels and the sympathetic nervous system as the seat of the primary abnormality. In reality, the problem is probably multifactorial. Hypertension is more common in some ethnic groups, particularly American Blacks and Japanese, and approximately 40-60% is explained by genetic factors. Important environmental factors include a high salt intake, heavy consumption of alcohol, obesity, lack of exercise and impaired intrauterine growth. There is very little evidence that ‘stress' causes hypertension.

In about 5% of unselected cases, hypertension can be shown to be a consequence of a specific disease or abnormality leading to sodium retention and/or peripheral vasoconstriction secondary hypertension.

There are several ways in which hypertension can be classified, which are helpful for its diagnosis and clinical management. The two principal divisions are to classify it by its severity and by its underlying cause (primary, or essential hypertension versus secondary hypertension). A third major component is age as the pathophysiology of hypertension in younger and older people is quite different.

A. Classification by Severity

Hypertension: The JNC 7 classifies hypertension as blood pressure exceeding 140/90 mmHg for adults age 18 years or older. The classification is based on the average of two or more seated blood pressures, properly measured with well-maintained equipment, at each of two or more visits to the office as shown in Table 1.

Table 1. Classification of Blood Pressure [JNC 7]  

Blood Pressure Classification	Systolic Blood Pressure* mmHg	Diastolic Blood Pressure* mmHg
Normal	< 120	< 80
Prehypertension	120 – 139	80 – 89
Stage 1 hypertension	140 – 159	90 – 99
Stage 2 hypertension	≥ 160	≥ 100

* Classification determined by highest blood pressure category

 Prehypertension: JNC 7 has defined normal blood pressure as < 120 mmHg and < 80 mmHg. The intermediate levels, 120 to 139 and 80 to 89 mmHg are now defined as prehypertension. This group that has an intermediate level of risk of heart disease and stroke and may progress to definite hypertension. It is estimated that approximately 15 percent of blood pressure related deaths from coronary heart disease occur in individuals with blood pressure in the prehypertensive range.

Malignant Hypertension: Malignant hypertension is diagnosed not only by the height of the blood pressure, but also by the manifestations of target organ damage, particularly retinal hemorrhages and papilledema. Its importance lies in the fact that if untreated it has a 5-year survival rate of 1 percent. It can result from essential or secondary hypertension. Treatment of malignant hypertension has a dramatic effect on survival.

Isolated Systolic Hypertension: In many older adults; systolic blood pressure tends to rise and diastolic to fall. When the average systolic blood pressure is ≥ 140 mmHg and diastolic blood pressure is < 90 mmHg, the patient is classified as isolated systolic hypertensive. The increased pulse pressure (systolic-diastolic) and systolic pressure predict risk and determine treatment.

Isolated Systolic Hypertension of the Young: In older children and young adults, often athletic males, a high systolic pressure in the brachial artery, but normal diastolic and mean pressures is not an uncommon finding.

Isolated Diastolic Hypertension: More commonly seen in some younger adults, the average systolic pressure remains < 140 mmHg but the diastolic is ≥ 90 mmHg. Although diastolic pressure is generally thought to be the best predictor of risk in patients younger than age 50 years, some prospective studies of isolated diastolic hypertension have indicated that the prognosis may be benign. Thus any patients in whom this diagnosis is made should be carefully followed.

White Coat Hypertension: In approximately 15 to 20 percent of people with stage 1 hypertension, blood pressure may only be elevated persistently in the presence of a healthcare worker, particularly a physician. When measured elsewhere, including while at work, the blood pressure is not elevated. When this phenomenon is detected in patients who are not taking medications, it is referred to as white coat hypertension or isolated office hypertension . The commonly used definition is a persistently elevated average office blood pressure of > 140/90 mmHg and an average awake ambulatory reading of < 135/85 mmHg.

White coat hypertension is generally thought to have a relatively benign prognosis, although in some patients it may progress to definite sustained hypertension. Hence all patients need to be followed indefinitely.

Masked Hypertension: The mirror image of white coat hypertension, masked hypertension is defined as a normal office blood pressure (< 140/90 mmHg) together with an elevated daytime pressure (> 135/85 mmHg). It was recognised only relatively recently, but is important because it is associated both with target-organ damage and an adverse prognosis.

Pseudohypertension: In some elderly patients the peripheral muscular arteries become very rigid and sometimes calcified. Consequently, the cuff has to be at a higher pressure to compress them, so that a falsely high blood pressure is recorded.

B. Classification by Cause

In more than 95 percent of cases of hypertension no single and reversible cause can be detected, and the terms essential and primary hypertension have been used. In approximately 5 percent of cases there is a definable cause of the hypertension therefore this type of hypertension is referred to as secondary hypertension (Table 2). From an epidemiologic point of view, the two most important causes for secondary hypertension are chronic kidney disease and sleep apnea.

Table 2. Some Secondary Causes of Hypertension  

Renal parenchymal disease Acute and chronic glomerulonephritis Chronic nephritis (e.g., pyelonephritis, radiation) Polycystic disease Diabetic nephropathy Hydronephrosis Neoplasms

Renovascular Renal artery stenosis/compression Intrarenal vasculitis Suprarenal aortic coarctation

Renoprival [renal failure, loss of kidney tissue]

Endocrine Disorders Renin-producing tumors Cushing syndrome Primary aldosteronism Pheochromocytoma [adrenal or extraadrenal chromaffin tumors] Acromegaly

Pregnancy-induced hypertension

Sleep apnea

Increased intracranial pressure [brain tumors, encephalitis]

Exogenous hormones and drugs [partial list] Glucocorticoids Mineralocorticoids Sympathomimetics Tyramine-containing foods and monoamine oxidase inhibitors Estrogen (e.g., oral contraceptive pills) Apparent mineralocorticoid excess (e.g., licorice) Nonsteroidal anti-inflammatory drugs Cyclosporine Excess alcohol use Drug abuse [e.g. amphetamines, cocaine)

C. Classification by Age

There is a fundamental difference between the genesis of hypertension in young and older patients.

Table 3: Differences between Hypertension in Younger and Older Patients  

Factor	Young (< 60 years)	Old (> 60 years)
Blood pressure increase	Systolic and diastolic	Systolic
Major cause	Hormonal	Mechanical
Hemodynamic change	Increased peripheral resistance	Increased arterial stiffness
Sleep apnea	Yes	No

Approach to Newly Diagnosed Hypertensive Patient

Hypertension occasionally causes headache but, provided there are no complications, most patients remain asymptomatic. The diagnosis is usually made at routine examination or when a complication arises. Therefore hypertension is referred to as a “silent killer”. A blood pressure check is advisable every 5 years in adults.

The objectives of the initial evaluation of a patient with high blood pressure readings are:

• To obtain accurate and representative measurements of blood pressure
• To identify contributory factors and any underlying cause (secondary hypertension)
• To assess the risk factors and quantify cardiovascular risk
• To detect any complications (target organ damage) that are already present
• To identify comorbidity that may influence the choice of antihypertensive therapy

These goals can usually be attained by a careful history, clinical examination and some simple investigations.

Measurement of blood pressure
A decision to embark upon antihypertensive therapy effectively commits the patient to life-long treatment, so it is vital that the blood pressure (BP) readings on which this decision is based are as accurate as possible.

Allow the patient to sit for several minutes in a quiet room before beginning blood pressure measurements. Measurements should be made, to the nearest 2 mmHg, in the sitting position with the arm supported, and repeated after 5 minutes rest if the first recording is high. In addition, the standing BP should be measured in elderly subjects, diabetics and those who may be suffering from postural hypotension. To avoid spuriously high recordings in obese subjects, the cuff should contain a bladder that encompasses at least two-thirds of the circumference of the arm. The diastolic pressure should be recorded at Korotkoff phase V (disappearance of sounds) and not phase IV (muffling of sounds).

Exercise, anxiety, discomfort and unfamiliar surroundings can all lead to a transient rise in BP. A series of automated ambulatory BP measurements, obtained over 24 hours or longer, provides a better profile than a limited number of clinic readings. Indeed, ambulatory BP measurements correlate more closely with evidence of target organ damage than casual BP measurements.

History

A comprehensive family history should be obtained with particular attention to hypertension, diabetes, dyslipidaemia, premature coronary heart disease, stroke, peripheral artery or renal disease.

Table 4. Guidelines for Family and Clinical History  

1. Duration and previous level of high BP  2. Indications of secondary hypertension family history of renal disease (polycystic kidney) renal disease, urinary tract infection, haematuria, analgesic abuse (parenchymal renal disease) drug/substance intake: oral contraceptives, liquorice, carbenoxolone, nasal drops, cocaine, amphetamines, steroids, non-steroidal anti-inflammatory drugs, erythropoietin, cyclosporine episodes of sweating, headache, anxiety, palpitation (phaeochromocytoma) episodes of muscle weakness and tetany (aldosteronism)  3. Risk factors family and personal history of hypertension and cardiovascular disease family and personal history of dyslipidaemia family and personal history of diabetes mellitus smoking habits dietary habits obesity; amount of physical exercise snoring; sleep apnoea personality 4. Symptoms of organ damage brain and eyes: headache, vertigo, impaired vision, transient ischaemic attacks, sensory or motor deficit heart: palpitation, chest pain, shortness of breath, swollen ankles kidney: thirst, polyuria, nocturia, haematuria peripheral arteries: cold extremities, intermittent claudication 5. Previous antihypertensive therapy Drug(s) used, efficacy and adverse effects 6. Personal, family and environmental factors

 Physical Examination

In addition to blood pressure, heart rate should be carefully measured (pulse counting over at least 30 s or longer if arrhythmias are reported) because the repeated finding of values above normal may be an indication of greater risk, increased sympathetic or decreased parasympathetic activity, or of heart failure. Physical examination should search for evidence of additional risk factors, for

signs suggesting secondary hypertension, and for evidence of organ damage. Waist circumference should be measured with the patient standing and body weight and height should be obtained to calculate body mass index.

Table 5. Physical examination for Secondary Hypertension, Organ Damage and Visceral Obesity

Signs suggesting secondary hypertension and organ damage Features of Cushing syndrome Skin stigmata of neurofibromatosis (phaeochromocytoma) Palpation of enlarged kidneys (polycystic kidney) Auscultation of abdominal murmurs (renovascular hypertension) Auscultation of precordial or chest murmurs (aortic coarctation or aortic disease) Diminished and delayed femoral pulses and reduced femoral BP (aortic coarctation, aortic disease) Signs of organ damage Brain: murmurs over neck arteries, motor or sensory defects Retina: fundoscopic abnormalities Heart: location and characteristics of apical impulse, abnormal cardiac rhythms, ventricular gallop, pulmonary rales, peripheral oedema Peripheral arteries: absence, reduction, or asymmetry of pulses, cold extremities, ischaemic skin lesions Carotid arteries: systolic murmurs Evidence of visceral obesity Body weight Increased waist circumference (standing position) M: > 102 cm; F: > 88 cm Increased body mass index [body weight (kg)/ height (m) 2 ] Overweight ≥25 kg/m 2 ; Obesity ≥30 kg/m 2

Investigations

All hypertensive patients should undergo a limited number of investigations. Additional investigations are appropriate in selected patients.

Table 6. Laboratory Investigations  

Routine tests Fasting plasma glucose Serum total cholesterol Serum LDL-cholesterol Serum HDL-cholesterol Fasting serum triglycerides Serum potassium Serum uric acid Serum creatinine Estimated creatinine clearance or glomerular filtration rate Haemoglobin and haematocrit Urinalysis (complemented by microalbuminuria via dipstick test and microscopic examination) Electrocardiogram Recommended tests Echocardiogram Carotid ultrasound Quantitative proteinuria (if dipstick test positive) Ankle-brachial BP Index Fundoscopy Glucose tolerance test (if fasting plasma glucose >5.6 mmol/L (100 mg/dL) Home and 24 h ambulatory BP monitoring Pulse wave velocity measurement (where available) Extended evaluation Further search for cerebral, cardiac, renal and vascular damage. Mandatory in complicated hypertension Search for secondary hypertension when suggested by history, physical examination or routine tests: measurement of renin, aldosterone, corticosteroids, catecholamines in plasma and/or urine; arteriographies; renal and adrenal ultrasound; computer assisted tomography; magnetic resonance imaging

Genetic Analysis

There is often a family history of high blood pressure in hypertensive patients, suggesting that inheritance contributes to the pathogenesis of this disorder. A

number of mutations in genes encoding for major blood pressure controlling systems has been recognized in humans, but their exact role in the pathogenesis of essential hypertension is still unclear. Genetic analysis is done in developed nations.

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Hypertension leads to adverse events in the blood vessels, central nervous system, retina, heart, and kidneys through two related mechanisms, both of which involve the effects of increased pressure on the arteries. The first is the effects on the structure and function of the heart and arteries, and the second is the acceleration of the development of atherosclerosis. The former is directly the result of the blood pressure, whereas the latter requires an interaction with other risk factors for cardiovascular disease, most importantly cholesterol. Thus strokes are closely related to the direct effects of blood pressure, whereas coronary heart disease is related to atherosclerosis, and the relationship between blood pressure and events in steeper for stroke than for coronary heart disease (CHD) events.

Figure 1 : Range of hypertensive cardiovascular disease from prehypertension to target-organ damage and end-stage disease

Data from numerous observational epidemiologic studies provide persuasive evidence of the direct relationship between blood pressure and cardiovascular disease. Between the ages of 40 and 70 years, each 20-mmHg increment of systolic pressure (and 10-mmHg of diastolic pressure) is associated with a doubling in the risk of stroke.

Component of blood pressure and risk: A continuing debate in the field of hypertension is the relative importance of the different components of the arterial pressure have in determining cardiovascular risk. There are four candidates; systolic, diastolic, pulse and mean pressure.

An analysis by Franklin and coworkers examined the Framingham Heart Study data and provided an elegant solution to this apparent paradox. In subjects younger than age 50 years the best predictor of risk was a high diastolic pressure, but in those older than age 60 years systolic pressure was the best predictor, and the relationship between diastolic pressure and risk was now negative, so that a low diastolic pressure was related to higher risk.

Pulse pressure: It is well known that systolic pressure increases readily with age, but after the age of 50 years diastolic pressure starts to fall. A number of studies suggest that the pulse pressure may be the best predictor of risk in the elderly. In the JNC 7, however, there is no mention of pulse pressure as a as a predictor.

Mean pressure: Mean pressure is another potential candidate as a risk marker. It is customarily defined as diastolic pressure plus one-third of the pulse pressure. The reason why mean pressure is a better predictor of stroke may be that it is closer to diastolic than to systolic pressure, and many studies have shown that the relationship between diastolic pressure and stroke is steeper than for coronary events, whereas no studies have shown that a very low diastolic pressure predicts stroke.

Central versus peripheral arterial pressure: In older patients with stiff arteries the central aortic systolic pressure is similar to the brachial pressure, whereas in younger subjects with compliant arteries, it is substantially lower.

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Goals of treatment

The primary goal of treatment of the hypertensive patient is to achieve the maximum reduction in the long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible risk factors identified,

and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure ‘‘per se''.

Treatment Targets

BP should be reduced to at least below 140/90 mmHg (systolic/diastolic), and to lower values, if tolerated, in all hypertensive patients. Target BP should be at least<130/80 mmHg in diabetics and in high or very high risk patients, such as those with associated clinical conditions (stroke, myocardial infarction, renal dysfunction, proteinuria).

Initiation of Antihypertensive Therapy

The decision to start antihypertensive treatment should be based on two criteria, i.e. the level of systolic and diastolic blood pressure and the level of total cardiovascular risk. This is illustrated in Fig. 2.

Fig. 2: Initiation of Antihypertensive Treatment

ESH-ESC 2007 Guidelines

The Benefits of Treating Hypertension

It is well established that treating hypertension reduces the rate of strokes by 35 to 40 percent, coronary heart disease events by 20 to 25 percent, and congestive heart failure by up to 50 percent, and that the benefits of antihypertensive treatment are more closely related to the change of blood pressure than how it is lowered. In a patient with stage I hypertension (blood pressure 140 to 159/90 to 99 mmHg) it has been estimated that a reduction of 12 mmHg over a 10-year period will prevent 1 death for every 11 patients treated.

Table 7: Effects of Hypertension Treatment on Morbid Events  

Event	Average Percent Reduction
Stroke	35 – 40%
Myocardial infarction	20 – 25%
Heart failure	50%

Treatment Strategies

Lifestyle changes

Lifestyle measures should be instituted, whenever appropriate, in all patients, including subjects with high normal blood pressure and patients who require drug

treatment. The purpose is to lower blood pressure, to control other risk factors and clinical conditions, and to reduce the number and doses of antihypertensive agents which might have to be subsequently used. The lifestyle measures that are widely agreed to lower blood pressure or cardiovascular risk, and that should be considered in all patients are:

• Smoking cessation: Smoking is a powerful CV risk factor and cessation may be the single most effective lifestyle measure for prevention of large number of CV diseases. Nicotine replacement therapy, bupropion therapy or varenicline may be considered to facilitate smoking cessation.
• Weight reduction in the overweight: Healthy eating should be promoted - Increase in fruit and vegetable intake (4-5 serving or 300 mg/day) and decrease in saturated and total fat intake should be encouraged.
• Moderation of alcohol consumption: The relationship between alcohol consumption, BP levels and prevalence of hypertension is linear. The guidelines recommend a daily intake of =20-30 gm ethanol per day for male patients with hypertension and 10-20 mg / day for female patients.
• Physical activity: Even moderate level of exercise can lower BP, reduce body weight, fat, waist circumference and increase insulin sensitivity and HDL cholesterol levels. Sedentary patients are recommended to undertake 35-40 minutes of moderate intensity, primarily endurance activity daily (eg. walking, jogging, swimming). This can be supplemented with resistance exercise. However in patients with poorly controlled hypetension exercise should be discouraged or postponed.
• Reduction of salt intake (The recommended adequate daily sodium intake has been recently reduced from 100 to 65 mmol/day corresponding to 3.8 g/day of sodium chloride, which may be currently difficult to achieve. An achievable recommendation is less than 5 g/day sodium chloride (85 mmol/day).

However, lifestyle changes should never delay unnecessarily the initiation of drug treatment, especially in patients at higher levels of risk.

Pharmacological therapy

The main benefits of antihypertensive therapy are due to lowering of BP per se.

Classes of antihypertensive agents suitable for the initiation and maintenance of antihypertensive treatment, alone or in combination are:

• Thiazide diuretics
• Calcium antagonists
• ACE inhibitors
• Angiotensin receptor antagonists
• Beta-blockers

Because in many patients more than one drug is needed, emphasis on identification of the first class of drugs to be used is often futile. Nevertheless,

there are many conditions for which there is evidence in favour of some drugs versus others either as initial treatment or as part of a combination.

The choice of a specific drug or a drug combination, and the avoidance of others, should take into account the following:

• The previous favourable or unfavourable experience of the individual patient with a given class of compounds
• The effect of drugs on cardiovascular risk factors in relation to the cardiovascular risk profile of the individual patient
• The presence of subclinical organ damage, clinical cardiovascular disease, renal disease or diabetes which may be more favourably treated by some drugs than others
• The presence of other disorders that may limit the use of particular classes of antihypertensive drugs
• The possibilities of interactions with drugs used for other conditions.

Table 8. Antihypertensive treatment: Preferred drugs  

Subclinical organ damage LVH ACEI, CA, ARB Asympt. atherosclerosis CA, ACEI Microalbuminuria ACEI, ARB Renal dysfunction ACEI, ARB Clinical event Previous stroke Any BP lowering agent Previous MI BB, ACEI, ARB Angina pectoris BB, CA Heart failure diuretics, BB, ACEI, ARB, Antialdosterone agents   Atrial fibrillation     Recurrent ARB, ACEI   Permanent BB, non-dihydropiridine, CA ESRD/proteinuria ACEI, ARB, loop diuretics Peripheral artery disease CA Condition ISH (elderly) Diuretics, CA Metabolic syndrome ACEI, ARB, CA Diabetes mellitus ACEI, ARB Pregnancy CA, methyldopa, BB Blacks Diuretics, CA Abbreviations: LVH: left ventricular hypertrophy; ISH: isolated systolic hypertension; ESRD: renal failure; ACEI: ACE inhibitors; ARB: angiotensin receptor antagonists; CA: calcium antagonists; BB:beta-blockers

ESH-ESC 2007 Guidelines

Monotherapy versus combination therapy

Regardless of the drug employed, monotherapy allows to achieve BP target in only 20-30% hypertensive patients. Hence, use of more than one agent is necessary to achieve target BP in the majority of patients. A vast array of effective and well tolerated combinations is available. Initial treatment can make use of monotherapy or combination of two drugs at low doses with a subsequent increase in drug doses or number, if needed.

Fig. 3: Monotherapy versus Combination Therapy Strategies ( ESH-ESC 2007 Guidelines)

Fig. 4: Possible combinations between some classes of antihypertensive drugs. The preferred combinations in the general hypertensive population are represented as thick lines. The frames indicate classes of agents proven to be beneficial in controlled intervention trials ( ESH-ESC 2007 Guidelines).

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Hypertension can be defined as a rise in blood pressure that increases risk for cerebral, cardiac, and renal events. According to year 2000 estimates more than a quarter of the world's adult population is hypertensive and it is predicted to increase by about 60% to a total of 1·56 billion by 2025. In India , it has been estimated that in year 2000, 60.4 million men and 57.8 million women were hypertensive. In 2025, t his number is predicted to increase to 107.3 million men and 106.2 million women. Therefore, India is said to be heading towards becoming the hypertension capital.

In more than 95% of cases a specific underlying cause of hypertension cannot be found. Essential hypertension usually clusters with other cardiovascular risk factors such as ageing, being overweight , insulin resistance , diabetes, and hyperlipidaemia. Hypertension is a major risk factor for cardiovascular mortality and morbidity through its effects on target organs like the brain, heart, and kidney.

Lifestyle measures should be instituted in all patients for prevention and control of high blood pressure. All antihypertensive drugs lower blood pressure and this decline is the best determinant of cardiovascular risk reduction. However, differences between drugs exist with respect to reduction of target-organ disease and prevention of major cardiovascular events. Most hypertensive patients need two or more drugs for blood-pressure control. With the availability of effective and safe antihypertensive drugs , hypertension can be controlled and complications avoided.

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4. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217–23
5. Global burden of blood-pressure-related disease, 2001. Lancet 2008; 371: 1513–18
6. India – Diabetes capital of the world: Now heading towards hypertension. JAPI 2007; Vol 55: 323-324
7. Hurst 's The Heart. 12 th edition; Vol 2: 1551-1627

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