Hypertension

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Hypertension

Hypertension is high blood pressure. Blood pressure is the force of blood pushing against the walls of arteries as it flows through them. Arteries are the blood vessels that carry oxygenated blood from the heart to the body’s tissues. According to the U.S. Centers for Disease Control and Prevention (CDC), in 2004, hypertension killed over 2,900 people in the United States; which relates to about 7.8 people per 100,000 in the U.S. population.

As blood flows through arteries it pushes against the inside of the artery walls. The more pressure the blood exerts on the artery walls, the higher the blood pressure will be. The size of small arteries also affects the blood pressure. When the muscular walls of arteries are relaxed, or dilated, the pressure of the blood flowing through them is lower than when the artery walls narrow, or constrict.

Blood pressure is highest when the heart beats to push blood out into the arteries. When the heart relaxes to fill with blood again, the pressure is at its lowest point. Blood pressure when the heart beats is called systolic pressure. Blood pressure when the heart is at rest is called diastolic pressure. When blood pressure is measured, the systolic pressure is stated first and the diastolic pressure second. Blood pressure is measured

in millimeters of mercury (mm Hg). For example, if a person’s systolic pressure is 120 and diastolic pressure is 80, it is written as 120/80 mm Hg. The American Heart Association considers blood pressure less than 140 over 90 normal for adults.

Hypertension is a major health problem, especially because it has no symptoms. Many people have hypertension without knowing it. In the United States, about 50 million people age six years and older have high blood pressure. Hypertension is more common in men than women and in people over the age of 65 years than in younger persons. More than half of all Americans over the age of 65 years have hypertension. It is also more common in African-Americans than in white Americans.

History

Attempts to find effective ways to treat hypertension led researchers to uncover the methods by which the body regulates blood pressure; knowledge of that process is still evolving. In 1898, physiologists Robert Adolf Tigerstedt (1853–1923) and Per Gustaf Bergman (1874–1955) found that an enzyme produced by the kidneys affected blood pressure. American pathologist Henry Goldblatt (1891–1977) and colleagues confirmed the role of the kidneys in 1934, producing hypertension in dogs by constricting the kidney arteries. In 1940, Braun-Menendez in Argentina and Irvine Page and Oscar Helmer at the Cleveland Clinic in Ohio found that renin, the kidney enzyme, catalyzed the formation of angiotensin, a very potent vasoconstrictor (a substance that causes blood vessels to contract). In the 1950s, researchers discovered that renin causes the production of angiotensin I, which has little physiological effect but is stimulated by angiotensin converting enzyme to produce the vessel-constricting angiotensin II. In the 1960s, F. Gross and others further found that angiotensin stimulates production of the hormone aldosterone by the adrenal glands, which in turn promotes retention of sodium and water, boosting the fluid content of the circulatory system and, thus, the pressure on blood vessel walls. Angiotensins were also shown to act on the nervous system, stimulating release of the neurotransmitter norepinephrine, which signals the arterioles to constrict. This complex is called the reninangiotensin-aldosterone system. Exactly why the system malfunctions to produce hypertension is not yet known, except in the approximately 10% of cases in which high blood pressure is the result of specific, known physical disorders, particularly of the kidneys and adrenal glands.

Effective drug treatments to control high blood pressure were not developed until after World War II (1939–1945), although some early attempts at drug treatment were made. French surgeon Mathieu Jaboulay (1860–1913), in 1900, reported on his drastic approach to alleviate severe hypertension: sympathectomy, or the cutting of the nerves that stimulate blood vessel constriction. Two American doctors took a dietary approach; Frederick Allen promoted salt and water restriction in 1920, and Walter Kempner (1903–1997) put patients on a no-salt rice diet in the 1940s.

The modern era of drug treatment for hypertension began with the introduction of reserpine in 1953. Reserpine was first derived from the snakeroot plant, Rauwolfia serpentina, long used by medical practitioners in India, both to lower blood pressure and induce relaxation. Rauwolfia was first mentioned in Western medical literature in a 1563 Portuguese work, but it was not studied seriously by Western-trained Indian physicians until 1931. The results of a clinical trial published by Dr. Rustom Jal Vakil (1911–1974) in 1949 caught the attention of Dr. Robert Wilkins, director of the hypertension clinic at Massachusetts General Hospital. Wilkins confirmed the hypotensive (anti-hypertensive) effect of Rauwolfia in 1952. The active ingredient was soon isolated and named reserpine; it was synthesized in 1956 by Robert Burns Woodward of Harvard University (Massachusetts). Reserpine was the first antihyperten-sive drug to achieve wide clinical use because of its nearly universal effectiveness. (It acts by interfering with transmission of norepinephrine.) It was also widely sold as a tranquilizer.

Other drugs took the place of reserpine as manufacturers and researchers focused their attention on anti-hypertensives beginning in the 1950s. The discovery of the first thiazide diuretic, benzothiadiazine, was reported in 1957 by the drug company Merck, Sharp and Dohme. Thiazide diuretics, which increase excretion of sodium chloride and water by stimulating the flow of urine, are widely used today to lower blood pressure. They may be taken in combination with methyldopa, an antihypertensive introduced in 1963, or with the beta-blockers, a new class of drugs that came on the market in 1964. James Black, senior pharmacologist at Imperial Chemical Industries of Great Britain, was responsible for the development of the first beta blocker, propranolol. American biochemist Raymond Ahlquist had suggested that epinephrine and norepinephrine transmit their signals—which cause an increase in heart rate and stronger contractions of the heart and blood vessels—to beta receptor sites on the heart muscle. In 1957, Black noted reports of a drug that blocked the stimulating effects of adrenaline on the heart, and set about creating a new chemical compound that would block the effects of epinephrine and norepinephrine at the beta receptor sites. This was accomplished by 1960, with the improved beta-blocker propranolol appearing in 1964. Beta blockers are now widely used to treat both angina and high blood pressure.

Two other antihypertensives were introduced in the 1980s. Calcium channel blockers work by blocking the channel that carries calcium to muscle cells; since calcium is required for contraction of the muscles in artery walls and affects the rate at which the heart beats, lowering calcium levels in muscle also lowers blood pressure. ACE (angiotensin converting enzyme) inhibitors interfere with the effect of an enzyme that stimulates angiotensin I to convert to the powerful vasoconstrictor angiotensin II and that also promotes the destruction of bradykinin, a powerful vasodilator (a substance that promotes the relaxation of blood vessels). Ferreira and his coworkers first found BPFs, factors that intensify the body’s reaction to bradykinin, in the venom of pit vipers in the 1960s. The BPFs inhibited the action of an enzyme that Erdos and associates showed was identical to angiotensin converting enzyme. BPFs were then synthesized, and in 1977 Cushman and his colleagues developed the first orally effective ACE inhibitor, captopril. Recently, it has been discovered that ACE inhibitors also reduce the rate of heart failure and progress of heart disease following heart attack.

Other drug treatments include sympathetic (adrenergic) nervous system blockers, which inhibit the sympathetic nervous system; vasodilators, which lower vascular resistance by dilating the blood vessels; and HMG-CoA reductase inhibitors, which are used with dietary modifications to reduce cholesterol levels. However, drug therapy, which usually includes side effects, is not the only way to treat hypertension. From the 1970s on, doctors have recommended exercise, weight loss, eliminating smoking, stress reduction, and a diet low in sodium, caffeine, alcohol, and cholesterol as a means of lowering blood pressure.

Advances are also being made in discovering the biological roots of hypertension. For example, in 1998 researchers reported that glucocorticoid (a specific group of corticoids, or adrenal cortex steroids) abnormalities may play a role in familial disposition to hypertension. Investigators also identified two oncogenes that may be related to sodium-related hypertension by affecting how sodium is released or retained by sodium channels in the kidneys. Variations of an ACE (angiotensin converting enzyme) gene, which encodes for an enzyme that helps regulate blood volume and controls salt and water balance, have also been linked to hypertension in men but not women.

Complications

Hypertension is serious because people with the condition have a higher risk for heart disease and other medical problems than people with normal blood pressure. Serious complications can be avoided by getting regular blood pressure checks and treating hypertension as soon as it is diagnosed.

If left untreated, hypertension can lead to the following medical conditions:

Arteriosclerosis, also called atherosclerosis,
Heart attack,
Stroke,
Enlarged heart, and
Kidney damage.

Arteriosclerosis is hardening of the arteries. The walls of arteries have a layer of muscle and elastic tissue that makes them flexible and able to dilate and constrict as blood flows through them. High blood pressure can make the artery walls thicken and harden. When artery walls thicken, the inside of the blood vessel narrows. Cholesterol and fats are more likely to build up on the walls of damaged arteries, making them even narrower. Blood clots can also get trapped in narrowed arteries, blocking the flow of blood.

Arteries narrowed by arteriosclerosis may not deliver enough blood to organs and other tissues. Reduced or blocked blood flow to the heart can cause a heart attack. If an artery to the brain is blocked, a stroke can result.

Hypertension makes the heart work harder to pump blood through the body. The extra workload can make the heart muscle thicken and stretch. When the heart becomes too enlarged it cannot pump enough blood. If the hypertension is not treated, the heart may fail.

The kidneys remove the body’s wastes from the blood. If hypertension thickens the arteries to the kidneys, less waste can be filtered from the blood. As the condition worsens, the kidneys fail and wastes build up in the blood. Dialysis or a kidney transplant are needed when the kidneys fail. About 25% of people who receive kidney dialysis have kidney failure caused by hypertension.

Causes and symptoms

Many different actions or situations can normally raise blood pressure. Physical activity can temporarily raise blood pressure. Stressful situations can make blood pressure go up. When the stress goes away, blood pressure usually returns to normal. These temporary increases in blood pressure are not considered hypertension. A diagnosis of hypertension made only when a person has multiple high blood pressure readings over a period of time.

The cause of hypertension is not known in 90 to 95% of the people who have it. Hypertension without a known cause is called primary or essential hypertension.

When a person has hypertension caused by another medical condition, it is called secondary hypertension. Secondary hypertension can be caused by a number of different illnesses. Many people with kidney disorders have secondary hypertension. The kidneys regulate the balance of salt and water in the body. If the kidneys cannot rid the body of excess salt and water, blood pressure goes up. Kidney infections, a narrowing of the arteries that carry blood to the kidneys, called renal artery stenosis, and other kidney disorders can disturb the salt and water balance.

Cushing syndrome and tumors of the pituitary and adrenal glands often increase levels of the adrenal gland hormones cortisol, adrenalin, and aldosterone, which can cause hypertension. Other conditions that can cause hypertension are blood vessel diseases, thyroid gland disorders, some prescribed drugs, alcoholism, and pregnancy.

Even though the cause of most hypertension is not known, some people have risk factors that give them a greater chance of getting hypertension. Many of these risk factors can be changed to lower the chance of developing hypertension or as part of a treatment program to lower blood pressure.

Risk factors for hypertension include:

Age over 60 years,
Male gender,
Race,
Heredity,
Salt sensitivity,
Obesity,
Inactive lifestyle,
Heavy alcohol consumption, and
Use of oral contraceptives.

Some risk factors for getting hypertension can be changed, while others cannot. Age, male gender, and race are risk factors that a person cannot do anything about. Some people inherit a tendency to get hypertension. People with family members who have hypertension are more likely to develop it than those whose relatives are not hypertensive. A person with these risk factors can avoid or eliminate the other risk factors to lower their chance of developing hypertension.

Diagnosis

Because hypertension does not cause symptoms, it is important to have blood pressure checked regularly. Blood pressure is measured with an instrument called a sphygmomanometer. A cloth-covered rubber cuff is wrapped around the upper arm and inflated. When the cuff is inflated, an artery in the arm is squeezed to momentarily stop the flow of blood. Then, the air is let out of the cuff while a stethoscope placed over the artery is used to detect the sound of the blood spurting back through the artery. This first sound is the systolic pressure, the pressure when the heart beats. The last sound heard as the rest of the air is released is the diastolic pressure, the pressure between heart beats. Both sounds are recorded on the mercury gauge on the sphygmomanometer.

Normal blood pressure is defined by a range of values. Blood pressure lower than 140/90 mm Hg is considered normal. A blood pressure around 120/80 mm Hg is considered the best level to avoid heart disease. A number of factors such as pain, stress, or anxiety can cause a temporary increase in blood pressure. For this reason, hypertension is not diagnosed on one high blood pressure reading. If a blood pressure reading is 140/90 or higher for the first time, the physician will have the person return for another blood pressure check. Diagnosis of hypertension usually is made based on two or more readings after the first visit.

Systolic hypertension of the elderly is common and is diagnosed when the diastolic pressure is normal or low, but the systolic is elevated, e.g., 170/70 mm Hg. This condition usually co-exists with hardening of the arteries (atherosclerosis).

Blood pressure measurements are classified in stages, according to severity:

Normal blood pressure: less than 130/85 mm Hg,
High normal: 130 to 139/85 to 89 mm Hg,
Mild hypertension: 140 to 159/90 to 99 mm Hg,
Moderate hypertension: 160 to 179/100 to 109 mm Hg,
Severe hypertension: 180 to 209/110 to 119, and
Very severe hypertension: 210/120 or higher.

A typical physical examination to evaluate hypertension includes:

Medical and family history,
Physical examination,
Ophthalmoscopy: Examination of the blood vessels in the eye,
Chest x-ray,
Electrocardiograph (ECG), and
Blood and urine tests.

The medical and family history help the physician determine if the patient has any conditions or disorders that might contribute to or cause the hypertension. A family history of hypertension might suggest a genetic predisposition for hypertension.

The physical examination may include several blood pressure readings at different times and in different positions. The physician uses a stethoscope to listen to sounds made by the heart and blood flowing through the arteries. The pulse, reflexes, height, and weight are checked and recorded. Internal organs are palpated, or felt, to determine if they are enlarged.

Because hypertension can cause damage to the blood vessels in the eyes, the eyes may be checked with a instrument called an ophthalmoscope. The physician will look for thickening, narrowing, or hemorrhages in the blood vessels.

A chest x ray can detect an enlarged heart, other vascular (heart) abnormalities, or lung disease.

An electrocardiogram (ECG) measures the electrical activity of the heart. It can detect if the heart muscle is enlarged and if there is damage to the heart muscle from blocked arteries.

Urine and blood tests may be done to evaluate health and to detect the presence of disorders that might cause hypertension.

Treatment

There is no cure for primary hypertension, but blood pressure can almost always be lowered with the correct treatment. The goal of treatment is to lower blood pressure to levels that will prevent heart disease and other complications of hypertension. In secondary hypertension, the disease that is responsible for the hypertension is treated in addition to the hypertension itself. Successful treatment of the underlying disorder may cure the secondary hypertension.

Treatment to lower blood pressure usually includes changes in diet, getting regular exercise, and taking antihypertensive medications. Patients with mild or moderate hypertension who do not have damage to the heart or kidneys may first be treated with lifestyle changes.

Lifestyle changes that may reduce blood pressure by about 5 to 10 mm Hg include:

Reducing salt intake,
Reducing fat intake,
Losing weight,
Getting regular exercise,
Quitting smoking,
Reducing alcohol consumption, and
Managing stress.

Patients whose blood pressure remains higher than 139/90 will most likely be advised to take antihypertensive medication. Numerous drugs have been developed to treat hypertension. The choice of medication will depend on the stage of hypertension, side effects, other medical conditions the patient may have, and other medicines the patient is taking.

Patients with mild or moderate hypertension are initially treated with monotherapy, a single antihypertensive medicine. If treatment with a single medicine fails to lower blood pressure enough, a different medicine may be tried or another medicine may be added to the first. Patients with more severe hypertension may initially be given a combination of medicines to control their hypertension. Combining antihypertensive medicines with different types of action often controls blood pressure with smaller doses of each drug than would be needed for monotherapy.

Antihypertensive medicines fall into several classes of drugs:

Diuretics,
Beta-blockers,
Calcium channel blockers,
Angiotensin converting enzyme inhibitors (ACE inhibitors),
Alpha-blockers,
Alpha-beta blockers,
Vasodilators,
Peripheral acting adrenergic antagonists, and
Centrally acting agonists.

Diuretics help the kidneys eliminate excess salt and water from the body’s tissues and the blood. This helps reduce the swelling caused by fluid buildup in the tissues. The reduction of fluid dilates the walls of arteries and lowers blood pressure.

Beta-blockers lower blood pressure by acting on the nervous system to slow the heart rate and reduce the force of the heart’s contraction. They are used with caution in patients with heart failure, asthma, diabetes, or circulation problems in the hands and feet.

Calcium channel blockers block the entry of calcium into muscle cells in artery walls. Muscle cells need calcium to constrict, so reducing their calcium keeps them more relaxed and lowers blood pressure.

ACE inhibitors block the production of substances that constrict blood vessels. They also help reduce the build-up of water and salt in the tissues. They are often given to patients with heart failure, kidney disease, or diabetes. ACE inhibitors may be used together with diuretics.

Alpha-blockers act on the nervous system to dilate arteries and reduce the force of the heart’s contractions.

Alpha-beta blockers combine the actions of alpha and beta blockers.

Vasodilators act directly on arteries to relax their walls so blood can move more easily through them. They lower blood pressure rapidly and are injected in hypertensive emergencies when patients have dangerously high blood pressure.

Peripheral acting adrenergic antagonists act on the nervous system to relax arteries and reduce the force of the heart’s contractions. They usually are prescribed together with a diuretic. Peripheral acting adrenergic antagonists can cause slowed mental function and lethargy.

Centrally acting agonists also act on the nervous system to relax arteries and slow the heart rate. They are usually used with other antihypertensive medicines.

KEY TERMS

Arteries —Blood vessels that carry blood to organs and other tissues of the body.

Arteriosclerosis —Hardening and thickening of artery walls.

Cushing syndrome —A disorder in which too much of the adrenal hormone, cortisol, is produced; it may be caused by a pituitary or adrenal gland tumor.

Diastolic blood pressure —Blood pressure when the heart is resting between beats.

Hypertension —High blood pressure.

Renal artery stenosis —Disorder in which the arteries that supply blood to the kidneys constrict.

Sphygmomanometer —An instrument used to measure blood pressure.

Systolic blood pressure —Blood pressure when the heart contracts (beats).

Vasodilator —Any drug that relaxes blood vessel walls.

Ventricles —The two lower chambers of the heart; also the main pumping chambers.

Prognosis

There is no cure for hypertension. However, it can be well controlled with the proper treatment. Therapy with a combination of lifestyle changes and antihypertensive medicines usually can keep blood pressure at levels that will not cause damage to the heart or other organs. The key to avoiding serious complications of hypertension is to detect and treat it before damage occurs. Because antihypertensive medicines control blood pressure, but do not cure it, patients must continue taking the medications to maintain reduced blood pressure levels and avoid complications.

Prevention

Prevention of hypertension centers on avoiding or eliminating known risk factors. Even persons at risk because of age, race, or sex or those who have an inherited risk can lower their chance of developing hypertension.

The risk of developing hypertension can be reduced by making the same changes recommended for treating hypertension.