Treating Hypertension

May 23, 2006 RSS Feed Print

Treatment of primary hypertension involves both lifestyle modifications and antihypertensive medications. The goal of treatment is to lower blood pressure and reduce the risk of complications from hypertension—specifically strokes, heart attacks, heart failure, and kidney disease. Most people with hypertension should aim to lower their blood pressure to less than 140/90 mm Hg. Those with diabetes or kidney disease have an even lower blood pressure goal—less than 130/80 mm Hg.

The same blood pressure goals apply to people with secondary hypertension. In these individuals, however, doctors often try to treat the underlying disorder, especially if blood pressure is difficult to control with lifestyle modifications and medications.

People experiencing a hypertensive emergency must seek immediate medical attention and have their blood pressure lowered with intravenous antihypertensive medication in the hospital. Blood pressure is lowered gradually to avoid precipitous drops in pressure that could lead to a stroke.

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Lifestyle changes

Lifestyle modifications proven to lower blood pressure include weight loss in people who are overweight, the Dietary Approaches to Stop Hypertension (DASH) diet, reduced salt intake, increased potassium intake, regular physical activity, and moderation of alcohol consumption.

These lifestyle modifications not only help lower blood pressure, but also improve the effectiveness of antihypertensive medication and lower the risk of cardiovascular disease. Studies show that the effects of these lifestyle changes are additive, and people who adopt more of them reap the most benefits.

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Weight loss

All people—whether or not they have hypertension—should aim for a body mass index (BMI) between 18.5 and 24.9. People with a BMI of 25 or more are considered overweight. BMI is a measure of weight in relation to height; it can be determined by multiplying weight in pounds by 704 and dividing the result by the square of height in inches. Studies show that for every 2.2 pounds of weight lost, blood pressure drops by about 1/1 mm Hg.

The DASH diet

The Dietary Approaches to Stop Hypertension (DASH) diet is an eating plan that is rich in fruits, vegetables, and low-fat dairy products and low in saturated fat, cholesterol, and total fat. The diet also includes whole-grain products, fish, poultry, and nuts. Red meat, sweets, and sugar-containing beverages are kept to a minimum, however.

Two major trials have evaluated the DASH diet. In the first trial, people who followed the DASH diet for eight weeks reduced their blood pressure by an average of 5.5/3.0 mm Hg, compared with people who ate a typical American diet (low in fruits and vegetables and high in fat). The benefits of the DASH diet were most pronounced in people with hypertension. In these individuals, the DASH diet lowered systolic pressure by 11 mm Hg, which is similar to the level of blood pressure reduction typically achieved with a single antihypertensive drug.

In the second trial, people who combined the DASH diet with a low salt intake (1,500 mg of sodium per day) for four weeks had an average blood pressure reduction of 9/5 mm Hg, compared with people who followed a typical American diet with a high salt intake. As in the first study, the benefits were greater in people with hypertension—their systolic blood pressure dropped by an average of 12 mm Hg.

Reduced salt intake

Research indicates that, on average, blood pressure levels rise with higher intakes of salt, and limiting salt may lower systolic blood pressure by 2 to 8 mm Hg. The effects of dietary salt on blood pressure tend to be greater in blacks, middle-aged and older adults, and people with hypertension or diabetes.

The Institute of Medicine recently issued new guidelines for salt intake in adults. They set an upper limit of 2,300 mg of sodiumdaily, and the following minimum requirements: 1,500 mg of sodium for adults under age 50; 1,300 mg for people age 50 to 70; and 1,200 mg for those above age 70. Reducing salt intake means not only avoiding the salt shaker while cooking and at meals but also reading nutrition labels and choosing foods that contain less than 140 mg of sodium per serving.

Other modifications

Potassium intake. Potassium is a mineral found in fruits, vegetables, dairy products, and beans. Increased intake of potassium has been shown to reduce blood pressure, as well as to reduce the rise in blood pressure that occurs with excessive salt consumption. According to 2004 guidelines from the Institute of Medicine, people should consume at least 4.7 grams of potassium per day.

Physical activity. Experts recommend engaging in moderate physical activity for at least 30 minutes on most days of the week. In a recent meta-analysis of more than 50 randomized, controlled trials, regular physical activity reduced blood pressure by an average of 4/3 mm Hg. Always talk to your doctor before beginning an exercise program.

Alcohol restriction. Moderate alcohol consumption—one or two drinks a day for most men and one drink a day for women and lighter-weight men—may lower systolic blood pressure by 2 to 4 mm Hg. Nondrinkers should not begin drinking to reduce their blood pressure.

Medications

When lifestyle modifications are insufficient to lower blood pressure to goal levels, doctors add antihypertensive medications to the treatment regimen. There are 10 classes of antihypertensive drugs, and each lowers blood pressure in a different way.

For people with stage 1 hypertension (140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic) who have no other health problems, a thiazide diuretic is most often prescribed along with lifestyle modifications. In the case of healthy people with stage 2 hypertension (160 mm Hg or higher systolic or 100 mm Hg or higher diastolic), a combination of two drugs is typically prescribed in addition to lifestyle modifications. The drug combination usually consists of a thiazide diuretic and an ACE inhibitor, angiotensin II receptor blocker, beta-blocker, or calcium channel blocker.

Many people with hypertension have other health conditions, and these individuals may require different or additional antihypertensive medications. For example, people with angina are usually prescribed a beta-blocker or calcium channel blocker to help relieve symptoms. People who have suffered a heart attack typically take an ACE inhibitor, beta-blocker, and aldosterone blocker to prevent another heart attack. In people with severe heart failure, a combination of an ACE inhibitor, beta-blocker, angiotensin II receptor blocker, aldosterone blocker, and loop diuretic is recommended.

For people who have had a stroke, taking a thiazide diuretic and an ACE inhibitor can reduce the risk of future strokes.

In people with diabetes, at least two antihypertensive medications are usually required to reach the blood pressure goal of 130/80 mm Hg. The best antihypertensive medications for people with diabetes are those that also lower the risk of diabetes complications. For example, thiazide diuretics, beta-blockers, ACE inhibitors, angiotensin II receptor blockers, and calcium channel blockers all reduce the risk of strokes and heart attacks in people with diabetes. In addition, ACE inhibitors and angiotensin II receptor blockers slow the progression of diabetic kidney disease.

People with kidney disease also have a blood pressure goal of 130/80 mm Hg, and they usually need three or more antihypertensive drugs to lower their blood pressure to this level. In these individuals, ACE inhibitors and angiotensin II receptor blockers are most effective in lowering blood pressure and slowing the progression of kidney disease. Because of reduced kidney function, loop diuretics rather than thiazide diuretics are commonly used.

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Diuretics

Often referred to as fluid or water pills, diuretics help reduce blood pressure by increasing the kidneys' excretion of sodium into the urine. These drugs also lower blood pressure by promoting the dilation of small blood vessels. There are three types of diuretics—thiazide diuretics, loop diuretics, and potassium-sparing diuretics. Each type of diuretic acts on a different site in the kidney.

Thiazide diuretics are the most commonly used diuretic. These drugs are inexpensive and need to be taken only once a day. In addition, they are at least as effective—if not more effective—than other classes of antihypertensive drugs. Loop diuretics are often used in people who also have heart failure or kidney disease. Potassium-sparing diuretics are used in combination with another type of diuretic, when that diuretic results in excessive loss of potassium.

The benefits of thiazide diuretics were demonstrated in a study called ALLHAT—the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial—published in 2002 in the Journal of the American Medical Association. The study looked at more than 42,000 people with hypertension who were age 55 and older and had at least one risk factor for heart disease. The participants were randomly assigned to receive either a thiazide diuretic (chlorthalidone), an ACE inhibitor (lisinopril), a calcium channel blocker (amlodipine), or an alpha-blocker (doxazosin).

The researchers followed the participants for an average of five years. The results clearly showed that the diuretic was superior to the ACE inhibitor and calcium channel blocker in terms of lowering blood pressure and preventing certain cardiovascular events. (The alpha-blocker portion of the study was stopped early because participants on this medication had a 25 percent increase in cardiovascular events relative to the diuretic.)

Low doses of thiazide diuretics are well tolerated. However, side effects can occur, including weakness, fatigue, malaise, sexual dysfunction, increased blood levels of glucose, triglycerides, calcium, and uric acid, and reduced blood sodium and HDL cholesterol levels. Thiazide and loop diuretics can also cause loss of potassium, which can lead to serious cardiac risks.

Beta blockers

These drugs block the actions of epinephrine and lower blood pressure by slowing heart rate and reducing cardiac output (the amount of blood pumped by the heart). They offer the additional benefit of reducing the heart's consumption of oxygen, which can help control angina.

Potential side effects of beta-blockers include wheezing in people who are sensitive to various allergens and irritants or who have preexisting lung disease, fatigue, drowsiness, malaise, depression, erectile dysfunction or decreased libido, increased blood triglyceride levels, and decreased HDL cholesterol levels.

Because beta blockers blunt the response to epinephrine, these drugs may cause problems if hypoglycemia (low blood sugar) develops in people taking insulin or certain oral drugs to control their diabetes. (Epinephrine release during hypoglycemia triggers symptoms that alert people that their blood sugar is too low and that they need to take actions to increase their blood sugar.)

Beta blockers may become less effective over time. This happens when the body compensates for the drop in blood pressure by increasing the retention of water and sodium, which causes blood pressure to rise again. Combining a beta-blocker with a diuretic may reduce this effect.

Calcium channel blockers

These drugs lower blood pressure by dilating arteries and, depending on the type of calcium channel blocker, by decreasing cardiac output as well. Like beta blockers, calcium channel blockers help alleviate symptoms of angina. Potential side effects include headache, dizziness, flushing, leg swelling, constipation, and slow or rapid heart rate with palpitations.

Past research suggested that calcium channel blockers might increase the risk of nonfatal heart attacks and deaths due to coronary heart disease, particularly in people treated with short-acting calcium channel blockers such as nifedipine. But in the recently published Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), people taking the calcium channel blocker amlodipine (Norvasc) were no more likely to have a heart attack or die of coronary heart disease over a five-year period than people taking the thiazide diuretic chlorthalidone (Thalitone).

However, in ALLHAT, people treated with a calcium channel blocker were 38 percent more likely to develop heart failure and 35 percent more likely to be hospitalized for heart failure, compared with people taking a diuretic. Also, other studies have found that calcium channel blockersmay adversely affect kidney function, compared with ACE inhibitors. As a result, calcium channel blockers are not recommended as a first-choice treatment for hypertension and should be used cautiously in people with heart failure or kidney disease.

ACE inhibitors

ACE inhibitors decrease blood pressure by reducing the formation of angiotensin II, a potent constrictor of blood vessels. A dry cough occurs in about 25 percent of people using ACE inhibitors. Uncommon adverse effects are rash and increased blood potassium levels. ACE inhibitors have no ill effects on libido or erectile function. A study comparing two commonly used ACE inhibitors, captopril (Capoten) and enalapril (Vasotec), found that captopril was associated with fewer side effects that decrease quality of life.

The Heart Outcomes Prevention Evaluation (HOPE) trial found that ACE inhibitors are appropriate for a wide range of people. The trial examined the effects of the ACE inhibitor ramipril (Altace) in more than 9,000 people with coronary heart disease, stroke, peripheral arterial disease, or diabetes and at least one other heart disease risk factor (hypertension, elevated cholesterol levels, or smoking). After five years, 14 percent of the participants taking ramipril had died or suffered a heart attack or stroke, compared with 18 percent of the patients taking a placebo. This translates into roughly 150 fewer heart attacks or strokes for every 1,000 people treated with ramipril over a four-year period. The ramipril patients were also about 30 percent less likely to develop diabetes.

Angiotensin II receptor blockers

These drugs work by interfering with the action of angiotensin II, which raises blood pressure by constricting small blood vessels and stimulating the adrenal glands to produce the sodium-retaining hormone aldosterone. The drugs may also halt the overgrowth of smooth muscle cells in blood vessel walls. In addition to their blood pressure-lowering effects, angiotensin II receptor blockers also help slow the progression of kidney disease in people with or without diabetes.

Side effects may include headache, digestive upset, and upper respiratory tract infection, although these effects occurred at about the same frequency in people taking a placebo. People who develop a cough while taking an ACE inhibitor may switch to an angiotensin II receptor blocker to eliminate this side effect.

Alpha blockers

These drugs decrease blood pressure by blocking nerve impulses that constrict small arteries, thus lowering resistance to blood flow. They may cause orthostatic hypotension (lightheadedness on standing), especially in older patients, as well as weakness, fainting, drowsiness, headaches, and heart palpitations. In addition, they can lose their effectiveness over time when not used in combination with a diuretic. Alpha-blockers usually have beneficial effects on HDL cholesterol levels.

Alpha-blockers are not recommended as a first-choice therapy for hypertension. According to results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), people taking the alpha-blocker doxazosin (Cardura) had 25 percent more cardiovascular events and were twice as likely to be hospitalized for heart failure as people treated with a diuretic.

Central alpha agonists

Like alpha-blockers, these drugs lower blood pressure by blocking nerve impulses that constrict small arteries. Side effects include drowsiness, sleep disturbances, depression, dry mouth, constipation, fatigue, erectile dysfunction, and dizziness (especially in older people). These drugs should not be stopped abruptly and therefore should be taken only by people who are likely to adhere to their medication regimens. Because of a high frequency of side effects, central alpha agonists usually are used only when other medications are unable to control blood pressure adequately.

Peripheral-acting adrenergic antagonists

These medications reduce resistance to blood flow in small arteries by inhibiting the release of epinephrine and norepinephrine from nerves. Possible side effects include diarrhea and a profound drop in blood pressure when rising from a seated or reclining position or while exercising. These drugs are commonly used in people with severe hypertension.

Direct vasodilators

These drugs act directly on the smooth muscle of small arteries, causing these arteries to widen. They must be used in combination with both a diuretic and a beta-blocker to prevent fluid retention and rapid heartbeat. Excessive hair growth is an adverse side effect of minoxidil (Loniten). (This discovery led to the development of a topical form of the drug for the treatment of baldness.) Direct vasodilators are used only in people with hypertension that is difficult to control.

Aldosterone blockers

Eplerenone (Inspra) is the only drug approved in this class of antihypertensive medications. It works by blocking the activity of the hormone aldosterone. Side effects include dizziness, diarrhea, cough, fatigue, and flu-like symptoms. The drug should not be used by people with high blood potassium levels or those taking potassium supplements or potassium-sparing diuretics. People with diabetes or microalbuminuria (small amounts of protein in the urine) should avoid taking eplerenone as well.

Combination therapy

Most people with hypertension require two or more antihypertensive medications to get their blood pressure under control. Combining medications from different classes often results in greater reductions in blood pressure than using a single drug, because the actions of the drugs may complement each other. For example, diuretics reduce blood pressure by increasing the excretion of sodium and water by the kidneys. But in some people this effect stimulates the release of certain blood pressure-raising hormones to compensate for the drop in blood volume. Adding an ACE inhibitor blocks the actions of these hormones and improves blood pressure control.

Combination therapy can be achieved by taking a separate dose of each drug or using fixed-dose combination drugs (formulations of two different drugs combined in a single pill). Most fixed-dose combinations contain a thiazide diuretic and an ACE inhibitor, beta-blocker, angiotensin II receptor blocker, or central alpha agonist. A fixed combination of an ACE inhibitor and a calcium channel blocker is also available.

Content excerpted from the Johns Hopkins White Paper on Hypertension & Stroke.

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