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INTRODUCTION

1.1 Hypertension

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Throughout
most of the world till this day, “hypertension” is defined as long-lastingrise
in Blood Pressure equal to or greater than 140/90 mmHg. For diabetes and
chronic kidney disease, blood pressure should be maintained at levels
<130/80 mm Hg. Not all the professional experts are agreed to this but it is a significant monitoring in these types of patients.123 The normal physiology of cardiovascular system is thatblood is carried from heart to all other organs of the body through the vessels.With every heartbeat, it pumps blood into the vessels which are arteries, the vessels which carry oxygenated blood, and, the veins which bring back deoxygenated blood to the heart. Blood pressure is created by the force of blood pushing against the walls of blood vessels (arteries) as it is pumped and pushed by the heart. The higher the pressure the harder the heart has to pump the blood and the higher will be blood pressure.4 The pressure that is set at normal for evaluating hypertensive & normotensive situations is 120/80 mmHg systolic & diastolic respectively. Systolic blood pressure is the pressure generated by blood against the walls of arteries when the heart contracts while diastolic blood pressure is the pressure when heart is in rest phase between two consecutive beats.5The WHO describes high blood pressure exists when the systolic pressure is at least 140 mmHg or greater and the diastolic blood pressure exceeds at least 90 mmHg. In this definition, temporary increases in blood pressure by, for example, physical exertion, pregnancy or drugs, is not included. 6 In 2015, cardiovascular diseases (CVDs) were leading cause of death with approximately 18 million deaths worldwide that is 31% of all global death. 7In 2010, hypertension was among the two leading risk factors for global disease burden with 7% of global disability-adjusted life years and, the second was tobacco smoking.8Heart has its central function in running the body all the time throughout the life which makes it the most vital of all the organs of the body. It beats approximately 2.5 billion times on average in life where it supplies necessary nutrients and oxygen to all the cells of the body through circulation of blood. It also drains the deoxygenated blood back from cells which includes metabolic wastes also and thus helps the body to get rid of wastes accumulation in the cells. Heart catches different types of abnormalities either at birth known as congenital or in life known as acquired cardiovascular disorders. Hypertension is one of the acquired diseases mainly affecting the vessels primarily and the heart later on. As per World Health Organization report, in 2008, about 40% of populationhaving age above than 25 years had hypertension.9The prevalence of hypertension in adults is expected to grow from 26.4% (in 2000) to 29.2% in 2025.10Around the globe, 7.6 million premature deaths (about 13.5% of the total deaths worldwide) were attributed to raise blood pressure. About 54% of stroke and 47% of ischemic heart disease worldwide were attributable to hypertension.11The worldwide prevalence of hypertension is 40% with variation in ratios among different demographic regions of the world. It is also known as silent killer.Hypertension is the leading but preventable cause of death worldwide.   1.2 Classification of Hypertension: Hypertension is classified on various bases. We discuss them one by one 1.2.1 Essential hypertension: It is also known as primary hypertension. This type is diagnosed after a doctor observes that blood pressure of a patient is high on three or more visits and excludes all other causes of hypertension. Patients are symptomless, but may experience numerous headaches, fatigue, light-headedness, or nose bleeds. Even though the specific cause is unidentified yet, researchers do know that obesity; smoking, alcohol, diet, and genetics all play role in developing essential hypertension. 1.2.2 Secondary hypertension: The most common cause of secondary hypertension is an abnormality in the arteries supplying blood to the kidneys. Other causes include airway obstruction during sleep, diseases and tumours of the adrenal glands, hormone defects, thyroid disease, and too much salt intake or alcohol use. The good sign is that if the reason is known, hypertension may be treated. Additional Hypertension Types: Isolated Systolic, Malignant, and Resistant Isolated systolic hypertension, malignant hypertension, and resistant hypertension are all recognized hypertension types with specific diagnostic criteria. 1.2.3 Isolated systolic hypertension: In isolated systolic hypertension, the systolic pressure rises above 140, while the lower number stays near the normal range, below 90 mmHg. This type is most common in older people above age of 65 years and is caused by the loss of elasticity in the arteries. 1.2.4 Malignant hypertension: This type takes place in only about 1% of people with hypertension. It is more common in younger adult population, African-American men, and women who have pregnancy toxaemia. Malignant hypertension occurs when blood pressure rises veryrapidly. If diastolic pressure exceeds 130 mmHg, it may be malignant hypertension. This is a medical emergency and needs quick treatment in a hospital. Symptoms include numbness in the arms and legs, blurred vision, confusion, chest pain, and headache.     1.2.5 Resistant hypertension: If  a patient is on three different types antihypertensive medications and the blood pressure is still too high, its possibly resistant hypertension. This type is more common in people who are older, obese, female, African American, or have an underlying illness, such as diabetes or kidney disease.Gene's involvement is also consideredas associated risk factor.12As the aging process of the people progress with a rise in the obesity, the global burden of hypertension increases with every passing year.About 10% of patients who have hypertension diagnosed on clinical basis exhibit presence of resistant hypertension, defined as a SBP of 140 mm Hg or abovein spite oftaking at least three different classes of maximally tolerated doses of antihypertensive medications as their treatment, which also include a drug belongs to diuretic class in a suitable dose.13, 14, 15, 16 1.2.6 White coat hypertension: Generally known as white coat syndrome, a phenomenon in which patients have a blood pressure level above the normal range, when they visit a clinical setup, though they don't show this rise in normal routine settings. It is assumed that the occurrence of this rise of blood pressure in a clinical visit is due to anxiety that is experienced during visit to clinic.17 Daytime blood pressure is used as a reference in this case as it takes into account ordinary levels of daily stress. The term "masked hypertension" can be used to describe the contrasting occurrence, where a patient's blood pressure is above the normal range during daily living, although it isn't above the normal range when the patient is in a clinic setting. 18 1.3 Classification on basis of severity: The basic blood pressure stages in the WG-ASH (writing group American Society of Hypertension) definition/classification taken from JNC7. 19(Joint National Committee on Detection, Evaluation and treatment of High Blood Pressure) Normal ·         Resting blood pressure usually <120/80 mm Hg, although may be occasionally elevated ·         No identifiable risk factors for cardiovascular disease ·         No identifiable early markers of cardiovascular disease   Stage 1 (Pre-hypertension JNC7) ·         Early signs of functional or structural changes in the heart and small arteries ·         Blood pressure usually 120/80-139/89 mm Hg, although values ?140/90 mm Hg may be occasionally or intermittently observed ·         Includes individuals with multiple cardiovascular risk factors and early disease markers but no evidence of target organ damage   Stage 2 (Hypertension-I JNC7) ·         Progressive disease resulting from persistent functional and structural changes in blood pressure control mechanisms and in the heart and vasculature ·         Resting blood pressure frequently ?140/90 mm Hg and much higher with physiologic or psychological stressors ·         Identifiable or widespread disease markers of evidence of early target-organ damage may be present regardless of blood pressure levels Stage 3 (Hypertension-II JNC7) ·         All clinical evidence of target-organ damage or overt cardiovascular disease, regardless of blood pressure levels. ·         Sustained resting blood pressure may be ?140/90 mm Hg even when treated (>160/100 mm Hg not
uncommon)

·        
Cardiovascular events
may have already occurred

·        
Aging and persistence
of other identifiable risk factors continue to exacerbate the risk of morbidity
and mortality

Classification 

Systolic BP (mm Hg) 

 

Diastolic BP (mm Hg) 

Normal 

<120  AND  <80  Pre-hypertension  120–139  OR  80–89  Hypertension Stage I  140–159  OR  90–99  Hypertension  Stage II ?160  OR  ?100            JNC 7: Classification of hypertension JNC; Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. 19   1.4 Risk Factors for hypertension: It is evident from a number of studies that anyone can develop hypertension because the pathology of primary hypertension is not established yet; however, age, race or ethnicity, overweight or obesity, gender, lifestyle, and a family history of high blood pressure can put a person in risk for developing high blood pressure. Some disease conditions can also lead to develop hypertension in the body which is termed as secondary hypertension. 1.4.1 Age Blood pressure has a tendency to rise as people become older with age. It is because the vessels lose their flexibility that is a particular property to adjust the volume of blood passing through them. However, the risk of pre-hypertension andhypertensionis increasing in children and teens also, possibly due to the rise in the number of overweight children and teens because of sedentary lifestyle.Hypertension and pre-hypertension have been observed to increase among children and adolescents since 1990s. 20, 21In the years 2003 to 2006, children and adolescents aged 8–17 years, the prevalence of pre-hypertension was approximately 14% in boys and 6% in girls, and the prevalence of hypertension was estimated to be 3%–4% in this age group in various studies. 20, 22, 23 1.4.2 Race/Ethnicity High blood pressure is more common in some races/ethnic groups while other have less or no prevalence of hypertension.Blacks develop high blood pressure more often than whites, Hispanics, Asians, Pacific Islanders, American Indians, or Alaska Natives. Black population also tends to develop hypertension in earlier life as compared to other races. 24 1.4.3 Overweight You are more likely to develop pre-hypertension or high blood pressure if you're overweight or obese. The terms "overweight" and "obese" refer to body weight that is greater than what is considered healthy for a certain height. 1.4.4 Gender Before age 55, men are more likely than women to develop high blood pressure. After age 55, women are more likely than men to develop high blood pressure.Kearney et al in his research in 2000 reported that the overall prevalence of hypertension was estimated to be 26.4% of the total world's population, out of which 26.6% were male and 26.1% were female. 25 This elicit that male gender is slightly at high risk of becoming hypertensive. 1.4.5 Lifestyle Habits Routine lifestyle habits can affect blood pressure. Some of them include: Eating too much sodium (> 1500mg/day)  or too little potassium
Lack
of physical activity
Drinking
too much alcohol
Stress
Smoking
and Tobacco use

 

1.4.6
Family History

A
family history of high blood pressure increases the risk of developing pre-hypertension
or hypertension. People having hypertension in their family are at risk of
getting it as compared to others who don`t have a family history. Some people
have a high sensitivity to sodium and salt, which may increase their risk for
high blood pressure and may run in families.

1.4.7 Diabetes

Diabetes,
a disorder of the endocrine system in which body is either unable to produce
Insulin or it cannot utilize insulin despite production. Insulin is a hormone
secreted by Pancreas that regulates sugar levels in the blood under different
circumstances according to needs of the body. Diabetes also increases the risk
of cardiovascular diseases, in which hypertension is one of them. Diabetes
increases levels of sugar in the blood to rise abnormally.About 60% of diabetic
patients have hypertension. 26

1.5 Causes of High Blood Pressure

Changes,
either from genes or the environment, in the body’s normal functions
may cause high blood pressure. Some known causes are discussed below:

1.5.1
Biology and High Blood Pressure

It
is being studied through ongoing researches that how internal changes in normal
body functions cause high blood pressure. The significant factors which are
considered to be affected in high blood pressure include:

Kidney
Fluid and Salt Balances

The
kidneys usuallycontrol the levels of salt in the body by retaining sodium and
water and expelling unwanted amount ofpotassium. Imbalance in this function of
the kidney can expand circulating blood volumes, which can lead to rise in blood
pressure.27

Renin-Angiotensin-Aldosterone
System

This
system of the body makes two different hormones, angiotensin and aldosterone.
Angiotensin constricts blood vessels, which develops the pressure of blood in
these vessels. Aldosterone is responsible for regulation of fluid and salt
levels by the kidneys. Increased levels or action of aldosterone may affect
this function of kidney, leading to increased blood volumes and ultimately high
blood pressure.

Sympathetic
Nervous System Activity

The
sympathetic nervous system has a central role in blood pressure regulation,
including heart rate, blood pressure, and breathing rate. It is under studies
to observe the relation of SNS with increase in blood pressure. Although
uncertain, but the case is strong that in hypertension, we are now on the edge
of successful “mechanisms to management” shift, with the use of catheter-based
renal sympathetic nerve ablation for treating drug-resistant hypertension. 28

Blood
Vessel Structure and Function

Changes
in the internal structure and endothelial function of small and large arteries
may contribute to high blood pressure. In up to date researches, it has become
clear that structural changes inside arteries, referred to as remodelling, can
be the reason for losing flexibility found in arterial walls which can
contribute in the development of hypertension. 29,
30

1.5.2
Genetic Causes of High Blood Pressure

Most
of the understandings that body internal functions are involved in the increase
of blood pressure have come from genetic studies. Hypertension is more common
in patients having a family history of it. Large numbers of studies have identified
many genes and mutations in them associated with hypertension, some of them
exist in the renal salt regulatory and renin-angiotensin-aldosterone pathways. 31
However, these known genetic factors only responsible for 2-3% of all
cases. Recent studies suggest involvement ofcertain changes in DNA during
embryological stages inside motherbody also may cause the development of hypertension
later in life.

 

1.5.3
Other Medical Causes of High Blood Pressure

Certain
other known medical conditions which can cause hypertensionare chronic kidney
disease, sleep apnea, thyroid problems, or certain tumours. This happens
because these conditions change the activity of body for example, sodium and
water regulation, hormones levels in the blood, which also contribute in
causing secondary hypertension.

1.6 Signs and Symptoms

Myth:
People with hypertension will pass through symptoms, such as nervousness,
sweating, and trouble in sleeping or cheek redness.

Truth:
Hypertension is symptomless, in most of the cases best termed as a “silent
killer.” If persistent high blood pressure values are neglected and the appearance
of symptoms is waited then it becomes a life threatening condition.

1.7 Investigations32

Hypertension: Investigation of all patients

Urinalysis for blood, protein and glucose
Blood urea, electrolytes and creatinine
N.B. Hypokalaemic
alkalosis may indicate primary
hyperaldosteronism but is
usually due to diuretic therapy
Blood glucose
Serum total and HDL cholesterol
Thyroid function tests
12-lead ECG (left ventricular hypertrophy,
coronary artery disease)

 

1.8 Treatment32

Optimal target blood pressures 1                                          

Age    

Clinic BP

Ambulatory/ home BP 2

<80 yrs <140/90 mmHg <135/85 mmHg ? 80 yrs           < 150/90 mmHg <140/85 mmHg 1Both systolic and diastolic values should be attained 2Average BP during waking hours     1.8.1 Pharmacological treatment: Many types of medications, collectively called as antihypertensive drugs, are commonly used for treating hypertension. The first line therapy is disputed.33 The Cochrane collaboration, WHO, and the US guidelines suggest low dose thiazide diuretic as first line treatment.33343536 The UK guidelines recommends calcium channel blockers (CCB) in preference for people above 55 years, and angiotensin converting enzyme inhibitors (ACE-I) used first line for younger people.37 In Japan starting with any one of six classes of medications including: CCB, ACEI/ARB, thiazide diuretics, beta-blockers, and alpha-blockers areacceptable, while in Canada and Europe all of these but alpha-blockers are recommended as options.3833 When compared to placebo group, beta-blockers are considered successful in stroke reduction, but have no well established effect on coronary artery disease.39 Some of the medications used to treat hypertension include: Beta-blockers:They slow heart rate and heart beats with less force. This decrease the volume of blood pushed in the arteries, which lowers blood pressure. Diuretics:The volume of blood is also increased by high levels of sodium and fluid in the body. This high volume can also increase blood pressure. Diuretics, also known as water pills, act on kidneys and make them excrete excess sodium from your body. As the sodium level goes down, fluid volume decreases, which ultimately lower blood pressure. ACE inhibitors: Angiotensin is an enzyme that causes constriction in blood vessels. ACE (angiotensin converting enzyme) inhibitors prevent the formation of angiotensin which helpswalls of blood vessels remain relax and blood pressure does not increase. Angiotensin II receptor blockers (ARBs): This drug prevents angiotensin from binding with its receptors. It has some additional benefits in avoiding adverse effects of ACEI. Calcium channel blockers: Excess amount of calcium in the smooth muscles of heart results in harder forceful heartbeats. If we reduce these levels then the force of the heartbeats will also decrease which will help in lowering blood pressure. Alpha-2 agonists:It reduces nerve impulses coming from brain to the vessels which are responsible for increase tone of smooth muscles in the arteries. This helps smooth muscles of vessels remain relax and blood pressure is reduced. 1.8.2 Combination Therapy The majority of people need more than one type of medication to lower their blood pressure.For example, people with blood pressure greater than 160/100 mmHg, American Heart Association recommend initial therapy with one type from thiazide class and the other from ACEI, ARB or CCB. An ACEI and CCB combine treatment can also be used.40 In some situations combination drug therapy should be avoided keeping the consequential effects on the body in mind. Such drug therapy can worsen the body condition by causing other organs deteriorate from their normal function. Some unacceptable drug combination includes use of Verapamil or Diltiazem (CCB) with beta-blockers or dual renin–angiotensin system blockade (ACEI+ ARB), renin–angiotensin system blockers and beta-blockers, beta-blockers and centrally acting medications.41       1.9 Prevention of high blood pressure By living a healthy lifestyle, blood pressure can be kept in a healthy range that can lower risk for other heart diseases and stroke. A healthy lifestyle includes: Eating a healthy diet Maintaining a healthy weight Getting enough physical activity Not smoking. Limiting alcohol use Healthy Diet Choosing healthy dietcan help in avoiding high blood pressure and its complications. Make sure to eat plenty of fresh fruits and vegetables. Eating foods low in salt (sodium) and high in potassium can lower your blood pressure. The DASH (Dietary Approaches to Stop Hypertension) eating plan is one healthy diet that is proven to help people lower their blood pressure.

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