High Blood Pressure
(Hypertension)
What is high blood pressure?
High blood pressure or hypertension means high pressure (tension) in the arteries. The arteries are the vessels that carry blood from the pumping heart to all of the tissues and organs of the body. Hypertension does not mean excessive emotional tension, although emotional tension and stress can temporarily increase the blood pressure. High blood pressure is generally defined as a level exceeding 140/90 mm Hg that has been confirmed on multiple occasions. The systolic blood pressure, which is the top number, represents the pressure in the arteries as the heart contracts and pumps blood into the circulation. The diastolic pressure, which is the bottom number, represents the pressure in the arteries as the heart relaxes after the contraction. The diastolic pressure, therefore, reflects the minimum pressure to which the arteries are exposed.
An elevation of the systolic and/or diastolic blood pressure increases the risk of developing heart (cardiac) disease, kidney (renal) disease, hardening of the arteries (arteriosclerosis), eye damage, and stroke (brain damage). These complications of hypertension are often referred to as end-organ damage because damage to these organs is the end result of chronic (long duration) high blood pressure. Accordingly, the diagnosis of high blood pressure in an individual is important so that efforts can be made to normalize the blood pressure and, thereby, prevent the complications.
How is the blood pressure measured?
The blood pressure usually is measured with a small, portable instrument called a blood pressure cuff (sphygmomanometer) (Sphygmo in Greek means pulse, and a manometer measures pressure.). The blood pressure cuff basically consists of an air pump, a pressure gauge, and a rubber cuff. The instrument registers the blood pressure in units called millimeters of mercury (mm Hg).
The cuff is placed around the upper arm and inflated to a pressure that blocks the flow of blood in the main artery (brachial artery) that travels through the arm. Then, the pressure of the cuff on the arm and artery is gradually released. As the pressure decreases, the health practitioner listens with a stethoscope over the artery at the front of the elbow. The pressure at which the practitioner first hears a pulsation over the artery is the systolic pressure. As the cuff pressure decreases further, the pressure at which the pulsation finally stops is the diastolic pressure.
How clearly established is the normal level of blood pressure?
Even though most insurance companies, quite reasonably, consider high blood pressure to be 140/90 and higher for the general population, these levels may not be appropriate cut-offs for all individuals. As a matter of fact, many experts in the field of hypertension view blood pressure levels as a continuum, or range, from lower levels to higher levels. Such a continuum implies that there are no clear or precise cut-off values to separate normal blood pressure from high blood pressure.
For some people, blood pressure readings that are lower than 140/90 may be a more appropriate normal cut-off level. For example, in certain situations, such as in patients with long duration (chronic) kidney diseases that spill (lose) protein into the urine (proteinuria), the blood pressure is ideally kept at 125/75, or even lower. The purpose of reducing the blood pressure to this level in these patients is to slow the progression of kidney damage. Patients with diabetes (diabetes mellitus) may likewise benefit from blood pressure that is maintained at a level lower than 140/90. In addition, black persons, who have an increased risk for developing the complications of hypertension, may decrease this risk by reducing their diastolic blood pressure to 80 mm Hg or less.
What is isolated systolic hypertension?
Remember that the systolic blood pressure is the top number in the blood pressure reading and represents the pressure in the arteries as the heart contracts and pumps blood into the circulation. A systolic blood pressure that is persistently higher than 140 mm Hg is usually considered elevated, especially when associated with an elevated diastolic pressure (over 90). Isolated systolic hypertension, however, is defined as a systolic pressure that is above 160 mm Hg with a diastolic pressure that still is below 90. This disorder primarily affects older people and is characterized by an increased (wide) pulse pressure. The pulse pressure is defined as the difference between the systolic and diastolic blood pressures. An elevation of the systolic pressure without an elevation of the diastolic, as occurs in isolated systolic hypertension, therefore, increases the pulse pressure.
Once considered to be harmless, an elevation of the pulse pressure is now thought to lead to future health problems. In other words, a high pulse pressure is considered an important precursor or indicator of potential end-organ damage. Thus, an isolated systolic hypertension is associated with a 2 to 4 times increased future risk of an enlarged heart, a heart attack (myocardial infarction), a stroke (brain damage), and death from heart disease or a stroke. Clinical studies in patients with isolated systolic hypertension have indicated that a reduction in systolic blood pressure by at least 20 mm to a level below 160 mm Hg reduces these increased risks.
What is white coat hypertension?
A single elevated blood pressure reading in the doctor's office can be misleading because the elevation may be only temporary. Presumably, such an elevation is caused by the patient's anxiety that is related to the stress of the examination. In fact, the suggestion has been made that about one out of four people that are thought to have mild hypertension actually may have normal blood pressure when they are outside of the physician's office. This sort of elevated blood pressure, that is, an increase noted only in the doctor's office, is called white coat hypertension. The name, of course, suggests that the white coat, which is symbolic for the physician, induces the patient's anxiety and a passing increase in blood pressure. A diagnosis of white coat hypertension might imply that it is not a clinically important or dangerous finding.
However, caution is warranted in such an innocent interpretation of white coat hypertension. An elevated blood pressure that is induced by the stress and anxiety of a visit to the doctor may not necessarily always be a harmless finding. Other stresses in the patient's life may likewise cause elevations in the blood pressure that are not ordinarily being measured. Accordingly, monitoring the blood pressure at home or at a pharmacy can help estimate the frequency and consistency of higher blood pressure readings. Additionally, conducting appropriate tests to search for any complications of hypertension can help evaluate the significance of variable blood pressure readings.
What is borderline hypertension?
Borderline hypertension is defined as mildly elevated blood pressure that is found to be higher than 140/90 mm Hg at some times and lower than that at other times. In the elderly, a somewhat higher systolic blood pressure, between 140 and 160 mm Hg, is considered a borderline value, as long as the diastolic pressure is below 90. As in the case of white coat hypertension, patients with borderline hypertension need to have their blood pressure taken on several different occasions and their end-organ damage assessed in order to establish whether their hypertension is significant.
Keep in mind that people with borderline hypertension may have a tendency, as they get older, to develop more sustained or higher elevations of blood pressure. Accordingly, they have a modestly increased risk of developing heart-related (cardiovascular) disease. Therefore, even if the hypertension does not appear to be significant initially, people with borderline hypertension should have continuing follow-up of their blood pressure and monitoring for the complications of hypertension.
If, during the follow-up of a patient with borderline hypertension, the blood pressure becomes persistently higher than 140/ 90 mm Hg, an anti-hypertensive medication is usually started. Even if the diastolic pressure remains at a borderline level (usually under 90 mm Hg, yet persistently above 85), however, treatment may be started in certain circumstances. (See the section below on the approach to the treatment of hypertension.)
What causes hypertension?
Two forms of high blood pressure have been described -- essential (or primary) hypertension and secondary hypertension. Essential hypertension is a far more common condition and accounts for 95% of the population with hypertension. The cause of essential hypertension is unknown. In secondary hypertension, which accounts for 5% of all cases, the high blood pressure is secondary to or caused by a specific abnormality in one of the organs or systems of the body. (Secondary hypertension is discussed further in a separate section below.)
Essential hypertension affects approximately 75 million Americans, yet, as mentioned, its basic cause or underlying defect is not known. Nevertheless, certain associations have been recognized in people with essential hypertension. For example, the condition develops only in groups or societies that have a fairly high intake of salt, exceeding 5.8 grams daily. In fact, salt intake may be a particularly important factor in relation to essential hypertension in a number of varied situations. Thus, excess salt may be involved in the hypertension that is associated with advancing age, black racial background, obesity , hereditary (genetic) susceptibility, and kidney failure (renal insufficiency).
Genetic factors are thought to play a prominent role in the development of essential hypertension. However, the genes for hypertension have not yet been identified. (Genes are tiny portions of chromosomes that produce the proteins that determine the characteristics of individuals.) The current research in this area is focused on the genetic factors that affect the renin-angiotensin-aldosterone system. This system helps to regulate blood pressure by controlling salt balance and the tone (state of elasticity) of the arteries.
Approximately 30 % of cases of essential hypertension are attributable to genetic factors. For example, in the United States, the incidence of high blood pressure is greater among blacks than among whites or Asians. Also, in individuals who have one or two parents with hypertension, high blood pressure is twice as common as in the general population. Rarely, certain unusual genetic disorders affecting the hormones of the adrenal glands may lead to hypertension. (These identified genetic disorders are actually considered secondary hypertension.)
As mentioned above, the underlying cause of essential hypertension is unknown. Nevertheless, it has been found that the vast majority of patients with essential hypertension have in common a particular abnormality of the arteries. That is, they have an increased resistance (stiffness or lack of elasticity) in the tiny arteries that are most distant from the heart (peripheral arteries or arterioles). The peripheral arteries supply blood containing oxygen and nutrients to all of the tissues of the body. (The arterioles are connected by capillaries in the tissues to the venous system (or the veins), which returns the blood to the heart and lungs.) Just what makes the peripheral arteries become stiff is not known. Yet, this increased peripheral artery resistance is present, as well, in those people whose essential hypertension is associated with genetic factors, obesity, lack of exercise, overuse of salt, and aging.
How do alcohol, coffee, and smoking influence blood pressure?
People who drink alcohol excessively (over two drinks per day) have a one and a half to two times increase in the frequency of hypertension. The association between alcohol and high blood pressure is particularly noticeable when the alcohol intake exceeds 5 drinks per day. Moreover, the connection is a dose-related phenomenon. In other words, the more alcohol that is consumed, the stronger is the link with hypertension.
Although smoking increases the risk of vascular complications (for example, heart disease and stroke) in people who already have hypertension, it is not associated with an increase in the development of hypertension. Nevertheless, smoking a cigarette can repeatedly produce an immediate, temporary rise in the blood pressure of 5 to10 mm Hg. Steady smokers however, actually may have a lower blood pressure than nonsmokers. The reason for this is that the nicotine in the cigarettes causes a decrease in appetite, which leads to weight loss. This, in turn, lowers the blood pressure.
In one study, the caffeine consumed in 5 cups of coffee daily caused a mild increase in blood pressure in elderly people who already had hypertension, but not in those who had normal blood pressures. What's more, the combination of smoking and drinking coffee in persons with high blood pressure may increase the blood pressure more than coffee alone. Limiting caffeine intake and cigarette smoking in hypertensive individuals, therefore, may be of some benefit in controlling their high blood pressure.
What are the causes of secondary hypertension?
As mentioned previously, 5% of people with hypertension have what is called secondary hypertension. This means that the hypertension in these individuals is secondary to (caused by) a specific disorder of a particular organ or blood vessel, such as the kidney, adrenal gland, or aortic artery.
Renal (kidney) hypertension
Diseases of the kidneys can cause secondary hypertension. This type of secondary hypertension is called renal hypertension because it is caused by a problem in the kidneys. One important cause of renal hypertension is the narrowing (stenosis) of the artery that supplies blood to the kidneys (renal artery). In younger individuals, usually women, the narrowing is caused by a thickening of the muscular wall of the arteries going to the kidney (fibromuscular hyperplasia). In older individuals, the narrowing generally is due to hard, fat-containing (atherosclerotic) plaques that are blocking the renal artery.
How does narrowing of the renal artery cause hypertension? First, the narrowed renal artery impairs the circulation of blood to the affected kidney. This deprivation of blood then stimulates the kidney to produce the hormones, renin and angiotensin. These hormones, along with aldosterone from the adrenal gland, cause a constriction and increased stiffness (resistance) in the peripheral arteries throughout the body, which finally, as mentioned previously, results in high blood pressure.
Renal hypertension is usually first suspected when high blood pressure is found in a young individual or a new onset of high blood pressure is discovered in an older person. Screening for renal artery narrowing then may include renal isotope (radioactive) imaging, ultrasonographic (sound wave) imaging, or magnetic resonance imaging (MRI) of the renal arteries. The purpose of these tests is to try to determine whether there is a restricted blood flow to the kidney. If any of these tests are abnormal or the doctor's suspicion of renal artery narrowing is high enough, a renal angiography (dye injected into the renal artery) is done. Angiography is the ultimate test to actually visualize the narrowed renal artery.
A narrowing of the renal artery may be treated by balloon angioplasty . In this procedure, the physician, guided by ultrasonographic imaging, threads a long narrow tube (catheter) into the renal artery. Once there, the renal artery is widened by inflating a balloon in the artery at the site of the narrowing. This procedure usually results in an improved blood flow and lower blood pressure. Moreover, the procedure also preserves the function of the kidney that has been partially deprived of its normal blood supply. Only rarely is surgery needed these days to open up the narrowing of the renal artery.
Any of the other types of chronic kidney disease can also cause hypertension in a manner similar to that of renal artery narrowing.
It is important to remember that not only can kidney disease cause hypertension, but hypertension can also cause kidney disease. Therefore, all patients with high blood pressure should be evaluated for the presence of kidney disease so that they can be treated appropriately.
Adrenal gland tumors
Two rare types of tumors of the adrenal glands are less common secondary causes of hypertension. (The adrenal glands sit right on top of the kidneys.) Both of these tumors produce excessive amounts of hormones (adrenal hormones) that cause high blood pressure. These tumors can be diagnosed from blood tests, urine tests, and imaging studies of the adrenal glands. Furthermore, surgery is often required to remove these tumors or the adrenal gland (adrenalectomy), which usually relieves the hypertension.
One of the types of adrenal tumors causes a condition that is called primary hyperaldosteronism because the tumor produces excessive amounts of the hormone aldosterone . In addition to the hypertension, this condition causes the loss of large amounts of potassium from the body into the urine, which results in a low level of potassium in the blood. Accordingly, hyperaldosteronism is generally first suspected in a person with hypertension when low potassium is also found in the blood. (Also, as previously mentioned, certain rare genetic disorders affecting the hormones of the adrenal gland can cause secondary hypertension.)
The other type of adrenal tumor that can cause secondary hypertension is called a pheochromocytoma . This tumor produces excessive catecholamines, which include several adrenalin-related hormones. The diagnosis of a pheochromocytoma is suspected in individuals who have sudden and recurrent episodes of hypertension that are associated with flushing, rapid heart beating (palpitations), and sweating, in addition to the symptoms associated with high blood pressure.
Coarctation of the aorta
Coarctation of the aorta is a rare hereditary disorder that is one of the most common causes of hypertension in children. This condition is characterized by a narrowing of a segment of the aorta, the main large artery coming from the heart. The aorta delivers blood to the arteries that supply all of the body's organs, including the kidneys.
The narrowed segment (coarctation) of the aorta generally occurs above the renal arteries, which causes a reduced blood flow to the kidneys. This lack of blood to the kidneys prompts the renin-angiotensin-aldosterone hormonal system to elevate the blood pressure. Treatment of the coarctation is usually the surgical correction of the narrowed segment of the aorta. Sometimes, balloon angioplasty (as described above for renal artery stenosis) can be used to widen (dilate) the coarctation of the aorta.
What do patients feel with high blood pressure?
Uncomplicated high blood pressure usually occurs without any symptoms. Therefore, hypertension has been labeled "the silent killer." In other words, the disease can progress without symptoms (silently) to finally develop any one or more of the several potentially fatal complications of hypertension. As a matter of fact, uncomplicated hypertension may be present and remain unnoticed for many years, or even decades. This happens when there are no symptoms and those affected fail to undergo periodic blood pressure screening.
Some people with uncomplicated hypertension, however, may experience symptoms such as headache, dizziness, shortness of breath, and blurred vision. The presence of symptoms can be positive in that they can prompt people to consult a doctor for treatment and make them more compliant in taking their medications. Not infrequently, however, a person's first contact with a physician may be after significant damage to the organs has occurred. In many cases, a person visits or is brought to the doctor or an emergency room with a heart attack , stroke, kidney failure , or impaired vision (due to damage to the back part of the retina). Greater public awareness and frequent blood pressure screening may help to identify patients with undiagnosed high blood pressure before significant complications have developed.
About one out of every 100 (1%) people with hypertension is diagnosed with severe high blood pressure (accelerated or malignant hypertension) at their first visit to the doctor. In these patients, the diastolic blood pressure (the minimum pressure) exceeds 140 mm Hg! Affected persons often experience severe headache, nausea, visual symptoms, dizziness, and sometimes kidney failure. Malignant hypertension is a medical emergency and requires urgent treatment to prevent a stroke (brain damage).
How is end-organ damage assessed in the hypertensive patient?
As already mentioned, chronic high blood pressure can lead to an enlarged heart, kidney failure, brain or neurological damage, and changes in the retina at the back of the eyes. Examination of the eyes in patients with severe hypertension may reveal a narrowing of the small arteries, small hemorrhages (leaking of blood) in the retina, and swelling of the eye nerve. From this examination, the doctor can gauge the severity of the hypertension based upon the degree of retinal damage.
As noted previously, people with high blood pressure have an increased stiffness, or resistance, in the peripheral arteries throughout the tissues of the body. This increased resistance causes the heart muscle to work harder to pump the blood through these blood vessels. This increased workload can put a strain on the heart, which can lead to heart abnormalities that are usually first seen as enlarged heart muscle. Enlargement of the heart can be evaluated by chest x-ray , electrocardiogram , and most accurately by echocardiography (an ultrasound examination of the heart). Echocardiography is especially useful in determining the thickness (enlargement) of the left side (the main pumping side) of the heart. Heart enlargement may be a forerunner of heart failure, coronary (heart) artery disease, and abnormal heart rate or rhythms (cardiac arrhythmias). Proper treatment of the high blood pressure and its complications can reverse some of these heart abnormalities.
Blood and urine tests may be helpful in detecting kidney abnormalities in people with high blood pressure. (Remember that kidney damage can be the cause or the result of hypertension.) Measuring the serum creatinine in a blood test can assess the function of the kidneys. An abnormal (elevated) level of serum creatinine indicates damage to kidney function. In addition, the presence of protein in the urine (proteinuria) may reflect chronic kidney damage from hypertension, even if the kidney function (as represented by the blood creatinine level) is normal. In fact, protein in the urine alone signals the risk of a deterioration in kidney function if the blood pressure is not controlled. Even small amounts of protein (microalbuminuria) may be a signal of impending kidney failure from uncontrolled hypertension. Black patients with poorly controlled hypertension are at a higher risk than Caucasians for most end-organ damage and particularly kidney damage.
Uncontrolled hypertension can also lead to brain or neurological damage by causing strokes. The strokes are usually due to a hemorrhage (leaking blood) or a blood clot (thrombosis) of the blood vessels that supply the brain. The patient's symptoms and signs (findings on physical examination) are evaluated to assess the neurological damage. A stroke can cause weakness, tingling, or paralysis of the arms or legs and difficulties with speech or vision. Multiple small strokes can lead to dementia (impaired intellectual capacity). The best prevention for this complication of hypertension or, for that matter, for any of the complications, is control of the blood pressure.
Which lifestyle modifications are beneficial in treating hypertension?
Lifestyle modifications refer to certain specific recommendations for changes in diet and exercise. These modifications can lower the blood pressure as well as improve the patient's response to blood pressure medications. Dietary modifications include restricting salt and alcohol and reducing weight if the individual is overweight. The American Heart Association recommends that the consumption of dietary salt be less than 6 grams of salt per day in the general population and a lower level (for example, less than 4 grams) for people with hypertension. To achieve a diet containing less than 4 grams of salt, a person should not add salt to their food or cooking. Also, the amount of natural salt in the diet can be reasonably estimated from the labeling information provided with most purchased foods.
Obesity is common among hypertensive patients and its prevalence increases with age. In fact, obesity may be what determines the increased incidence of high blood pressure with age. Obesity can contribute to hypertension in several possible ways. For one thing, obesity leads to a greater output of blood because the heart has to pump out more blood to supply the excess tissue. The increased cardiac output then can raise the blood pressure. For another thing, obese hypertensive individuals have a greater stiffness (resistance) in their peripheral arteries throughout the body. Finally, obesity may be associated with a tendency for the kidneys to retain salt. Weight loss may help reverse problems related to obesity while also lowering the blood pressure. It has been estimated that the blood pressure can be decreased 0.32 mm Hg for every 1 kg (2.2 pounds) of weight lost.
Some obese people, especially if they are very obese, have a syndrome called sleep apnea . This syndrome is characterized by the periodic interruption of normal breathing during sleep. Sleep apnea may contribute to the development of hypertension in this subgroup of obese individuals. This happens because the repeated episodes of apnea cause a lack of oxygen ( hypoxia ). The hypoxia then causes the adrenal gland to release adrenalin and related substances. Finally, the adrenalin and related substances cause a rise in the blood pressure.
A regular exercise program may help lower blood pressure over the long term. For example, activities such as jogging, bicycle riding, or swimming for 30 to 45 minutes daily may ultimately lower blood pressure by as much as 5 to15 mm Hg. Moreover, there appears to be a relationship between the amount of exercise and the degree to which the blood pressure is lowered. Thus, the more you exercise (up to a point), the more you lower the blood pressure. The beneficial response of the blood pressure to exercise occurs only with aerobic (vigorous and sustained) exercise programs. Therefore, any exercise program must be recommended or approved by an individual's physician.
Medical Treatment Of Hypertension
What are the goals of anti-hypertensive treatment?
Keep in mind that high blood pressure is usually present for many years before its complications develop. The idea, therefore, is to treat hypertension early, before it damages critical organs in the body. Accordingly, increased public awareness and screening programs to detect early, uncomplicated hypertension are the keys to successful treatment. The point is that by treating high blood pressure successfully early enough, you can significantly decrease the risk of stroke, heart attack, and kidney failure.
The goal for patients with combined systolic and diastolic hypertension is to attain a blood pressure of 140/85 mm Hg. Bringing the blood pressure down even lower, as mentioned earlier, may be desirable in black patients and patients with diabetes or chronic kidney failure.
How is the treatment of hypertension started?
Blood pressure that is persistently higher than 140/ 90 mm Hg usually is treated with lifestyle modifications and medication. If the diastolic pressure remains at a borderline level (usually under 90 mm Hg, yet persistently above 85), however, treatment also may be started in certain circumstances. These circumstances include borderline diastolic pressures in association with end-organ damage, systolic hypertension, or factors that increase the risk of cardiovascular disease, such as age over 65 years, black race, smoking, hyperlipemia (elevated blood fats), or diabetes.
Any one of the several classes of medications may be started, except the alpha-blocker medications. The alpha-blockers are used only in combination with another anti-hypertensive medication in specific medical situations. (See the next section for a more detailed discussion of each of the several classes of anti-hypertensive medications.)
In some particular situations, certain classes of anti-hypertensive drugs are preferable to others as the first line (choice) drugs. For example, ACE inhibitors or ARB drugs are the drugs of choice in patients with heart failure, chronic kidney failure (in diabetics or non-diabetics), or heart attack (myocardial infarction) that weakens the heart muscle (systolic dysfunction). Also, beta-blockers are sometimes the preferred treatment in hypertensive patients with a resting tachycardia (racing heart beat when resting) or an acute (rapid onset, current) heart attack.
Patients with hypertension may sometimes have a co-existing, second medical condition. In such cases, a particular class of anti-hypertensive medication or combination of drugs may be chosen as the first line (initial) approach. The idea in these cases is to control the hypertension while also benefiting the second condition. For example, beta-blockers may treat chronic anxiety or migraine headache as well as the hypertension. Also, the combination of an ACE inhibitor and an ARB drug can be used to treat certain diseases of the heart muscle (called cardiomyopathies) and certain kidney diseases, as well as the hypertension.
In some other situations, certain classes of anti-hypertensive medications should not be used (are contraindicated). For example, the non-dihydropyridine type of calcium channel blockers should not be used in patients with heart failure or certain abnormal heart rates or rhythms (arrhythmias). On the other hand, these drugs may be beneficial in treating certain other arrhythmias. Also, some drugs, such as clonidine and minoxidil , because they are so powerful, are usually relegated to second or third line choices for treatment. That is, they are used only after all of the first line drugs have been tried without success. Finally, see the section below on pregnancy for the anti-hypertensive drugs that are appropriate or inappropriate for use in pregnant women.
When is combination therapy used?
The use of combination drug therapy for hypertension is not uncommon. At times, using smaller amounts of one or more agents in combination can minimize side effects while maximizing the anti-hypertensive effect. For example, diuretics, which also can be used alone, are more often used in a low dose in combination with another class of anti-hypertensive medications. In this way, the diuretic has fewer side effects while it improves the blood pressure-lowering effect of the other drug. Diuretics also are added to other anti-hypertensive medications when a patient with hypertension also has fluid retention and swelling (edema).
The ace inhibitors or angiotensin receptor blockers may be useful in combination with most other anti-hypertensive medications. Another useful combination is that of a beta-blocker with an alpha-blocker in patients with high blood pressure and enlargement of the prostate gland in order to treat both conditions simultaneously. Caution is necessary, however, when combining two drugs that both lower the heart rate. For example, adding a beta-blocker to a non-dihydropyridine calcium channel blocker (diltiazem or verapamil) warrants caution. Patients receiving a combination of these two classes of drugs need to be monitored carefully to avoid an excessively slow heart rate ( bradycardia ).
When is emergency treatment needed?
In a hospital setting, injectable drugs may be used for the emergency treatment of hypertension. The most commonly used agents in this situation are sodium nitroprusside (Nipride) and labetalol (Normadyne). As already mentioned, emergency medical therapy may be needed for patients with severe (malignant) hypertension. In addition, emergency treatment of hypertension may be necessary in patients with short duration (acute) congestive heart failure, dissecting aneurysm (dilation or widening) of the aorta, stroke, and toxemia of pregnancy (see below).
Which medications are used to treat hypertension?
Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB)
The ACE inhibitors and the ARB drugs both affect the renin-angiotensin hormonal system, which, as mentioned previously, helps regulate the blood pressure. The ACE inhibitors work by blocking (inhibiting) an enzyme that converts the inactive form of angiotensin to its active form. The active form of angiotensin constricts or narrows the arteries, but the inactive form cannot. With an ACE inhibitor as a single drug treatment (monotherapy), 50 to 60 percent of Caucasians usually achieve good blood pressure control. Black patients may also respond, but they require higher doses and frequently do best when an ACE inhibitor is combined with a diuretic. (Diuretics are discussed below.)
As an added benefit, ACE inhibitors may reduce an enlarged heart (left ventricular hypertrophy) in patients with hypertension. These drugs also appear to slow the deterioration of kidney function in patients with hypertension and protein in the urine (proteinuria). Moreover, they have been particularly useful in slowing the progression of kidney dysfunction in hypertensive patients with kidney disease resulting from diabetes. Accordingly, ACE inhibitors are usually are the first line drugs of choice to treat high blood pressure in cases that also involve congestive heart failure , chronic kidney failure in both diabetics and non-diabetics, and heart attack (myocardial infarction) that weakens the heart muscle (systolic dysfunction).
Patients who are treated with ACE inhibitors who also have kidney impairment should be monitored for further deterioration in kidney function and high serum potassium. In fact, these drugs may be used to reduce the loss of potassium in people who are being treated with diuretics that tend to lose potassium. ACE inhibitors have few adverse effects. One bothersome side effect, however, is a chronic cough. The ACE inhibitors include enalapril (Vasotec), captopril (Capoten), lisinopril (Zestril and Prinivil), benazepril (Lotensin), and quinapril (Accupril).
For patients who develop a chronic cough on an ACE inhibitor, an ARB drug is a good substitute. ARB drugs work by blocking the angiotensin receptor (binder) on the arteries. As a result, the angiotensin is not able to work on the artery. (Recall that angiotensin is a hormone that constricts the arteries.) The ARB drugs appear to have many of the same advantages as the ACE inhibitors, but without the associated cough. Accordingly, they are also suitable as first line agents to treat hypertension. ARB drugs include losartan (Cozaar), irbesartan (Avapro), valsartan (Diovan), and candesartan (Atacand).
In patients who have hypertension in addition to certain second diseases, a combination of an ACE inhibitor and an ARB drug may be effective in controlling the hypertension and also benefiting the second disease. For example, while treating hypertension, this combination of drugs can reduce the loss of protein in the urine (proteinuria) in certain kidney disorders and perhaps help strengthen the heart muscle in certain diseases of the heart muscle (cardiomyopathies). Note that both the ACE inhibitors and the ARB drugs are not to be used (contraindicated) in pregnant women. (See the section below on pregnancy.) Beta-blockers
The sympathetic nervous system is a part of the nervous system that helps to regulate certain involuntary (autonomic) functions in the body, including those of the heart and blood vessels. As part of that system, beta-receptors (receivers that respond to stimuli) in the heart increase the heart rate and the strength of heart contractions (pumping action). Beta-blockers acting on the heart, therefore, slow the heart rate and reduce the force of cardiac contraction. Meanwhile, beta-receptors in the smooth muscle of the peripheral arteries in tissues throughout the body and in the smooth muscle of the lung airways serve to relax these muscles.
Accordingly, beta-blockers cause contraction of the smooth muscle of the peripheral arteries and thereby decrease the blood flow to the tissues throughout the body. As a result, the patient may experience, for example, coolness in the hands and feet. Likewise, in response to the beta-blockers, the airways are squeezed (constricted) by the contracting smooth muscle. This squeezing (impingement) on the airway causes wheezing, especially in individuals with a tendency for asthma . In short, beta-blockers reduce both the force of the heart's pumping action and the blood pressure that the heart generates in the arteries.
Beta-blockers remain useful medications in treating hypertension, especially in patients with a fast heartbeat while resting (tachycardia), cardiac chest pain (angina), or a recent heart attack (myocardial infarction). For example, beta-blockers appear to improve long-term survival when given to patients who have had an acute heart attack. Whether beta-blockers can prevent heart problems (are cardio-protective) in patients with hypertension any more than other anti-hypertensive medications, however, is uncertain. Beta-blockers do seem to help treat chronic anxiety or migraine headaches in people with hypertension. The common side effects of these drugs include depression , fatigue, nightmares, sexual impotence in males, and increased wheezing in people with asthma. The beta-blockers include atenolol (Tenormin), propranolol (Inderal), and metoprolol (Toprol). Diuretics
Diuretics are among the oldest known medications for treating hypertension. They work in the tiny tubes (tubules) of the kidneys to remove salt from the body. Diuretics may be used as single drug treatment (monotherapy) for hypertension. More frequently, however, low doses of diuretics are used in combination with other anti-hypertensive medications to enhance the effect of the other medications.
The diuretic hydrochlorothiazide (Hydrodiuril) works in the far end (distal) part of the kidney tubules. In a low dose of 12.5 to 25 mg per day, this diuretic may improve the blood pressure-lowering effects of other anti-hypertensive drugs. The idea is to treat the hypertension without causing the adverse effects that are sometimes seen with the higher doses of hydrochlorthiazide. These side effects include potassium depletion and elevated levels of triglyceride (fat), uric acid , and glucose (sugar).
Occasionally, when salt retention causing swelling (edema) is a major problem, the more potent loop diuretics may be used in combination with other anti-hypertensive medications. (The loop diuretics are so called because they work in the loop segment of the kidney tubules to eliminate salt.) The most commonly used diuretics to treat hypertension include hydrochlorthiazide, the loop diuretics, furosemide (Lasix) and torsemide (Demadex), the combination of triampterene and hydrochlorothiazide (Dyazide), and metolazone (Zaroxolyn). Note that diuretics probably should not be used in pregnant women. (See the section below on pregnancy.) Calcium channel blockers
Calcium channel blockers inhibit the movement of calcium into the muscle cells of the heart and arteries. The calcium is needed for these muscles to contract. These drugs, therefore, lower blood pressure by decreasing the force of the heart's pumping action (cardiac contraction) and relaxing the muscle walls of the arteries. Three major types of calcium channel blockers are used. One type is the dihydropyridines, which do not slow the heart rate or cause other abnormal heart rates or rhythms (cardiac arrhythmias). These drugs include amlodipine (Norvasc), sustained release nifedipine (Procardia XL, Adalate CC), felodipine (Plendil), and nisoldipine (Sular).
The other two types of calcium channel blockers are referred to as the non-dihydropyridine agents. One type is verapamil (Calan SR) and the other is diltiazem (Cardizem, Tiazac, Dilacor). Both the dihydropyridines and the non-dihydropyridines are very useful when used alone or in combination with other anti-hypertensive agents. The non-dihydropyridines, however, are not recommended (contraindicated) in congestive heart failure or with certain arrhythmias. Sometimes, however, these same dihydropyridines are useful in preventing certain other arrhythmias.
Many of the calcium channel blockers come in a short-acting form and a long-acting (sustained release) form. The short-acting forms of the calcium channel blockers, however, may have adverse long-term consequences, such as strokes or heart attacks. These effects are presumably due to the wide fluctuations in the blood pressure and heart rate that occur during treatment. The fluctuations result from the rapid onset and short duration of the short-acting compounds. When the calcium channel blockers are used in sustained release preparations, however, less fluctuation occurs. Accordingly, the sustained release forms of calcium channel blockers are probably safe for long-term use. The main side effects of these drugs include constipation , swelling (edema), and a slow heart rate (only with the non-dihydropyridine types). Alpha-blockers
Alpha-blockers lower blood pressure by blocking alpha-receptors in the smooth muscle of peripheral arteries throughout the tissues of the body. The alpha-receptors are part of the sympathetic nervous system, as are the beta-receptors. The alpha-receptors, however, serve to narrow (constrict) the peripheral arteries. Accordingly, the alpha-blockers cause the peripheral arteries to widen (dilate) and thereby lower the blood pressure.
Recent evidence, however, suggests that using alpha-blockers alone as a first line drug choice for hypertension may actually increase the risk of heart-related problems, such as heart attacks or strokes. Alpha-blockers, therefore, should not be used as an initial drug choice for the treatment of high blood pressure. Examples of alpha-blockers include terazosin (Hytrin) and doxazosin (Cardura).
Alpha-blockers are particularly useful in patients with enlargement of the prostate gland (which usually occurs in older men) because these drugs reduce the problems associated with urinating. Alpha-blockers alone, however, have a relatively small blood pressure-lowering effect. Accordingly, when hypertension coexists with prostatic enlargement, another anti-hypertensive medication should be used together with an alpha-blocker. For example, tamsulosin (Flomax) is an alpha-blocker that works well in combination with other anti-hypertensive medications. Such a combination can relieve urinating problems without causing an excessive decrease in the blood pressure. An excellent combination drug for this purpose is labetalol (Normodyne), which contains an alpha-blocker and a beta-blocker mixed together. Clonidine
Clonidine (Catapres) is an antihypertensive drug that works centrally. That is, it works in a control center for the sympathetic nervous system in the brain. The drug is referred to as a central alpha agonist because it stimulates alpha-receptors in the brain. The result of this central stimulation, however, is to decrease the sympathetic nervous system outflow and to decrease the stiffness (resistance) of the peripheral arteries. Clonidine lowers the blood pressure, therefore, by relaxing (dilating or widening) the peripheral arteries throughout the body. This drug is useful as a second or third line drug choice for lowering blood pressure when other anti-hypertensive medications have failed. It also may be useful on an as-needed basis to control or smooth out fluctuations in the blood pressure. This drug tends to cause dryness of the mouth and fatigue so that some patients do not tolerate it. Clonidine comes in an oral form or as a sustained release skin patch.
Minoxidil
Minoxidil is the most potent of the drugs that lower blood pressure by dilating the peripheral arteries. This drug, however, does not work through the peripheral sympathetic nervous system, as do the alpha and beta-blocker drugs, or through the control center in the brain, as does clonidine. Rather, it is a muscle relaxant that works directly on the smooth muscle of the peripheral arteries throughout the body. Minoxidil is used for patients who have not responded to any other medications. It must be combined with a beta-blocker or clonidine to prevent an increase in the heart rate and with a diuretic to prevent retention of fluid (swelling). Minoxidil may also increase hair growth.
What about the patient's compliance with medication regimes?
When uncomplicated hypertension has not caused symptoms, as often happens, some patients tend to forget about their medications. Patients also tend to fail to take their medications as prescribed (non-compliance or non-adherence) if they are causing side effects. Remember that quality of life issues are very important, especially with regard to compliance with prescribed blood pressure medications. Thus, certain anti-hypertensive medications may cause such side effects as fatigue and sexual impotence. These side effects understandably can have profound effects on the patient's quality of life and compliance with treatment. Likewise, more resistant cases of hypertension that require more medication may cause more adverse effects, and, therefore, less compliance.
In dosing schedules that require taking medication 2 to 4 times a day (split dose), some patients will remember to take their medicine only some of the times. In contrast, medications that can be given once daily tend to be remembered more regularly.
Expensive blood pressure medications, especially if insurance does not cover the costs, may also reduce compliance. The reason for this is that people attempt to save money by skipping doses of the prescribed medication. Remember that the least expensive medication regimes use generic (not brand name) drugs, such as are readily available for some of the diuretics and beta-blockers. Reduced costs of medication may also be achieved by lifestyle changes such as losing weight, reducing dietary sodium, decreasing consumption of alcohol, and exercising regularly. If these changes in lifestyle are effective, the patient may require less medication.
What about hypertension during pregnancy?
Women with pre-existing hypertension may become pregnant. These patients have an increased risk of developing preeclampsia or eclampsia (toxemia) of pregnancy. These conditions usually develop during the last three months (trimester) of pregnancy. In preeclampsia, which can occur with or without pre-existing hypertension, affected women have hypertension, protein loss in the urine (proteinuria), and swelling (edema). In eclampsia (toxemia), convulsions also occur and the hypertension may require prompt treatment. The foremost goal of treating the high blood pressure in toxemia is to keep the diastolic pressure below 105 mm Hg in order to prevent a brain hemorrhage in the mother.
Hypertension that develops before the 20th week of pregnancy almost always is due to pre-existing hypertension and not toxemia. High blood pressure that occurs only during pregnancy, called gestational hypertension, may start late in the pregnancy. These women, however, do not have proteinuria, edema, or convulsions. Furthermore, gestational hypertension appears to have no ill effects on the mother or the fetus. This form of hypertension resolves shortly after delivery, although it may recur with subsequent pregnancies.
The use of medications for hypertension during pregnancy is controversial. The key question is, "At what level should the blood pressure be maintained?" For one thing, the risk of untreated mild to moderate hypertension to the fetus or mother during the relatively brief period of pregnancy probably is not very large. Furthermore, lowering the blood pressure too much can interfere with the flow of blood to the placenta and thereby impair fetal growth. So, some sort of a compromise must be met. Accordingly, not all mild or moderate hypertension during pregnancy needs to be treated with medication. If it is treated, however, the blood pressure should be reduced slowly and not to very low levels, perhaps not below140/80.
The anti-hypertensive agents used during pregnancy need to be safe for normal fetal development. The beta-blockers, hydralazine (an old vasodilator), labetalol, alpha methyldopa (Aldomet), and more recently, the calcium channel blockers have been advocated as suitable medications for hypertension during pregnancy. Certain other anti-hypertensive medications, however, are not recommended (they are contraindicated) during pregnancy. These include the ACE inhibitors, the ARB drugs, and probably the diuretics. Ace inhibitors may aggravate a diminished blood supply to the uterus (uterine ischemia) and cause kidney dysfunction in the fetus. The ARB drugs may even lead to death of the fetus. Diuretics can cause depletion of the blood volume and so impair placental blood flow and fetal growth.
Is alternative medicine used to treat hypertension?
Alternative medicine, also called integrative or complementary medicine, features the use of non-traditional (at least in the western world) techniques for treatment. For example, self-relaxation approaches to the therapy of hypertension include yoga , biofeedback , and meditation . These techniques can, in fact, be effective in lowering the blood pressure, at least temporarily. In order to produce sustained reductions in the blood pressure, however, these techniques may require hours of diligent adherence daily. Therefore, they are generally practical only for few, highly motivated individuals with hypertension. Acupuncture has not yet been established as a standard or proven therapy for hypertension in the western world.
Certain herbal remedies have blood pressure-lowering components that may well be effective in treating hypertension. Most herbal remedies are available as food supplements and the Food and Drug Administration (FDA) does not approve them as drugs. Therefore, herbal treatments for hypertension have not yet been adequately evaluated in scientifically controlled clinical trials for effectiveness and safety. In particular, their long-term side effects are unknown. Furthermore, a major problem with most herbal treatments is that their contents are not standardized. Moreover, the ways in which herbal treatments work to lower blood pressure are not known. Currently, therefore, herbal remedies are usually not recommended for the treatment of hypertension.
What new class of anti-hypertensive drug is currently being tested?
A new class of anti-hypertensive drug, called a vasopeptidase blocker (inhibitor), has been developed. Uniquely, it works on two different systems at the same time. It blocks that part of the renin-angiotensin-aldosterone hormonal system that narrows (constricts) the peripheral arteries. It also blocks that part of the body's salt regulating system that conserves salt. Accordingly, this class of drug decreases the blood pressure by simultaneously dilating the peripheral arteries and increasing the body's loss of salt (natriuresis).
One such drug that is currently being studied is called omapatrilat. In laboratory animals with high blood pressure, this drug reduces the blood pressure and appears to protect the end-organs (heart, kidney, and brain) from damage by the high blood pressure. Moreover, the drug dilates the peripheral arteries, which increases blood flow to all tissues, and improves cardiac function in hypertensive patients with heart failure. Not yet approved by the FDA, omapatrilat is undergoing further testing to evaluate its effectiveness and safety. - High blood pressure (hypertension) is designated as either essential (primary) hypertension or secondary hypertension and is defined as a consistently elevated blood pressure exceeding 140/90 mm Hg.
- In essential hypertension (95% of people with hypertension), no specific cause is found, while secondary hypertension (5% of people with hypertension) is caused by an abnormality somewhere in the body, such as in the kidney, adrenal gland, or aortic artery.
- Essential hypertension may run in some families and occurs more often in the black population, although the genes for essential hypertension have not yet been identified.
- High salt intake, obesity, lack of regular exercise, excessive alcohol or coffee intake, and smoking may all adversely affect the outlook for the health of an individual with hypertension.
- High blood pressure is called "the silent killer" because it usually causes no symptoms for many years, even decades, until it finally damages certain critical organs.
- Poorly controlled hypertension ultimately can cause damage to blood vessels in the eye, thickening of the heart muscle and heart attacks, hardening of the arteries (arteriosclerosis), kidney failure, and strokes.
- Heightened public awareness and screening of the population are necessary to detect hypertension early enough so that it can be treated before damage has occurred to the critical organs.
- Lifestyle adjustments in diet and exercise and compliance with medication regimes are important factors in determining the outcome for people with hypertension.
- Several classes of anti-hypertensive medications are available, including ACE inhibitors, ARB drugs, beta-blockers, diuretics, calcium channel blockers, and alpha-blockers.
- Most anti-hypertensive medications can be used alone or in combination: some are used only in combination; some are preferred over others in certain specific medical situations; and some are not to be used (contraindicated) in other situations.
- The goal of therapy for hypertension is to bring the blood pressure down to 140/85 in the general population and to even lower levels in diabetics, blacks, and people with certain chronic kidney diseases.
- Screening, diagnosing, treating, and controlling hypertension early in its course can significantly reduce the risk of developing strokes, heart attacks, or kidney failure.
- New clinical guidelines for high blood pressure were issued on May 14, 2003 by the National Heart, Lung, and Blood Institute of the NIH. The guidelines feature a blood pressure category called pre-hypertension (systolic 120 - 139 / diastolic 80 - 89), for which lifestyle modifications are recommended. For more about the new guidelines, please see the Doctor's View, "New Blood Pressure Guidelines" written by Frederick Hecht, M.D.
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