Selected Guidelines

Hypertension awareness, treatment, and control rates have increased over the past three decades.
Age-adjusted mortality rates for stroke and coronary heart disease (CHD) have declined during the same period and now appear to be leveling.
The incidence of end-stage renal disease and the prevalence of heart failure are rising.
Prevention and treatment of hypertension and target organ disease are still important public health challenges that must be addressed.

Definition

Hypertension is defined as a systolic blood pressure (SBP) of >= 140 mm Hg, a diastolic blood pressure (DBP) of >= 90 mm Hg, or the taking of antihypertensive medicines.
The positive relationship between SBP and DBP and cardiovascular risk is strong, continuous, graded, consistent, independent, predictive, and etiologically significant for those with and without CHD.
Classification of adult blood pressure is based on the average of two or more blood pressure readings taken at each of two or more visits after an initial screening.

Detection and Confirmation Techniques

Blood pressure should be measured in a standardized way using equipment that meets certification criteria.
Patients should be seated in a chair with their backs supported, with arms bared and supported at heart level. They should refrain from smoking or ingesting caffeine 30 minutes before the reading.
Measuring blood pressure in the supine and standing positions may be indicated under special circumstances.
Blood pressure measurements should begin after at least five minutes of rest.
The appropriate cuff size must be used to ensure accurate measurement; the bladder within the cuff should encircle at least 80% of the arm.
Measurements should be taken preferably with a mercury sphygmomanometer, a calibrated aneroid manometer, or a validated electronic device.
Both SBP (the first appearance of sound) and DBP (the disappearance of sound) should be recorded.
Two or more readings taken two minutes apart should be averaged. If the first two readings differ by more than 5 mm Hg, additional readings should be taken and averaged.
Clinicians should explain the meaning of blood pressure readings to patients and advise them of the necessity for periodic remeasurement.

(Additional information on blood pressure measurement can be found in the American Heart Association's Recommendations for Human Blood Pressure Determination by Sphygmomanometers and the American Society of Hypertension's Recommendations forRoutineBlood Pressure Measurement by Indirect Cuff Sphygmomanometry.)
Self-Measurement of Blood Pressure

Self-measurement may provide valuable information for the initial evaluation of patients with hypertension and for monitoring the response to treatment.
Self-measurement has the following main advantages:
- Distinguishing sustained hypertension from white-coat hypertension (a condition where blood pressure is consistently elevated in the physician's office or clinic, but is normal at other times);
- Assessing the patient's response to antihypertensive medication;
- Improving patient adherence to treatment; and
- Potentially lowering costs.
While there is no universally agreed-on upper limit of normal home blood pressure, readings of >= 135/85 mm Hg should be considered elevated.

Choice of Monitors for Personal Use

The mercury sphygmomanometer is considered the most accurate device for clinical use; however, it is not practical for home use.
Either validated electronic devices or aneroid sphygmomanometers that are proven to be accurate, according to standard testing, are recommended for use along with appropriate-sized cuffs.
Finger monitors are not accurate.
The accuracy of the patient's device should be periodically checked by comparing readings with simultaneously recorded auscultatory readings taken with a mercury device.

Ambulatory Blood Pressure Monitoring

A variety of commercial monitors which are reliable, convenient, easy to use, and accurate are available. They are typically programmed to take readings every 15 to 30 minutes throughout the day and night. They can then be downloaded onto a personal computer for analysis.
Blood pressure falls by 10% to 20% during the night in the majority of people; the change is more closely related to patterns of sleep and wakefulness than to the time of day.
Ambulatory blood pressure correlates more closely than clinic blood pressure with a variety of measures of target organ damage, such as left ventricular hypertrophy in hypertensive patients.
Ambulatory monitoring may identify a group at relatively low risk of morbidity.
Ambulatory monitoring is most clinically helpful and most commonly used in those with suspected white-coat hypertension.
Ambulatory monitoring is helpful in patients with apparent drug resistance, hypotensive symptoms with antihypertensive medications, episodic hypertension, and autonomic dysfunction.
Ambulatory monitoring should not be used indiscriminately, as in the routine evaluation of those with suspected hypertension.

Evaluation of Patients

The three objectives of evaluating patients with documented hypertension are to:
- Identify known causes of high blood pressure;
- Assess the presence or absence of target organ damage and cardiovascular disease, the extent of the disease, and the response to therapy; and
- Identify other cardiovascular risk factors or concomitant disorders that may define prognosis and guide treatment.

Medical History

Patients with known duration and levels of elevated blood pressure; symptoms of CHD, heart failure, cerebrovascular disease, peripheral vascular disease, renal disease, diabetes mellitus, dyslipidemia, and other comorbid conditions, gout, or sexual dysfunction; family history of high blood pressure, premature CHD, stroke, diabetes, dyslipidemia, or renal disease.
Symptoms suggesting causes of secondary hypertension and history of recent changes in weight.
Leisure-time physical activity and smoking or use of other tobacco; dietary assessment including intake of sodium, alcohol, saturated fat, and caffeine.
A list of all prescribed and over-the-counter medications, herbal remedies, and illicit drugs (some may raise blood pressure or interfere with the efficacy of antihypertensive medications).
Results and adverse effects of previous antihypertensive therapy.
Psychosocial and environmental factors, such as family situation, employment status and working conditions, and educational levels, which may affect hypertension control.

Initial Physical Examination

Two or more blood pressure readings separated by two minutes with the patient either supine or seated and after standing for at least two minutes.
Verification in the contralateral arm (if the values are different, the higher value should be used).
Measurement of height, weight, and waist circumference.
Funduscopic examination for evidence of hypertensive retinopathy.
A neck examination to check for carotid bruits, distended veins, or an enlarged thyroid gland.
Examination of the heart for abnormalities in rate and rhythm, increased size, pericardial heave, clicks, murmurs, and third and fourth heart sounds.
Examination of the lungs for rales and evidence for bronchospasm.
Examination of the abdomen for bruits, enlarged kidneys, masses, and abnormal aortic pulsation.
Examination of the extremities for diminished or absent peripheral arterial pulsations, bruits, and edema.
A neurologic assessment.

Laboratory Tests and Other Diagnostic Procedures

Routine tests include urinalysis, complete blood cell count, blood chemistry (potassium, sodium, creatinine, fasting glucose, total cholesterol, and high-density lipoprotein cholesterol), and 12-lead electrocardiogram.
Optional tests include creatinine clearance, microalbuminuria, 24-hour urinary protein, blood calcium, uric acid, fasting triglycerides, low-density lipoprotein cholesterol, glycosylated hemoglobin, thyroid-stimulating hormone (thyrotropin), and echocardiography.
Tests for assessing cardiovascular status in selected patients include standard echocardiography, examination of structural alterations in arteries by ultrasonography, measurement of ankle/arm index, and plasma renin activity/urinary sodium determination.

Identifiable Causes of Hypertension

Additional diagnostic procedures may be necessary to determine causes of secondary hypertension, especially in patients:
- Whose age, history, physical examination, severity of hypertension, or initial laboratory findings suggest such causes;
- Whose blood pressures are responding poorly to drug therapy;
- With well-controlled hypertension where blood pressures begin to increase;
- With Stage 3 hypertension; and
- With sudden onset of hypertension such as labile hypertension or paroxysms of hypertension accompanied by headache, palpitations, pallor, and perspiration which suggest pheochromocytoma; abdominal bruits, especially those that lateralize to the renal areas or have a diastolic component, which suggest renovascular disease; abdominal or flank masses which may be polycystic kidneys; delayed or absent femoral arterial pulses and decreased blood pressure in the lower extremities which may indicate aortic coarctation; and truncal obesity with purple striae which suggests Cushing syndrome.
Examples of clues from laboratory tests include:
- Unprovoked hypokalemia (primary aldosteronism);
- Hypercalcemia (hyperparathyroidism); and
- Elevated creatinine levels or abnormal urinalysis (renal parenchymal disease).
Appropriate tests should be conducted when there is a high index of suspicion of an identifiable cause.

Genetics of Hypertension

Blood pressure levels are correlated among family members due to common genetic background, shared environment, or lifestyle habits.
Hypertension appears to be a polygenic and multifactorial disorder in which the interaction of several genes with each other and with the environment is important.

Risk Stratification
The risk for cardiovascular disease in hypertensive patients is determined by the level of blood pressure, the presence or absence of target organ damage, and other risk factors such as smoking, obesity, physical inactivity, dyslipidemia, and diabetes. These risk factors independently modify the risk for subsequent cardiovascular disease.

Risk Group A

This group includes patients with high-abnormal blood pressure or Stage 1, 2, or 3 hypertension who do not have clinical cardiovascular disease, target organ damage, or other risk factors.
Those with Stage 1 hypertension are candidates for a longer trial (up to one year) of vigorous life-style modification with blood pressure monitoring.
If the goal blood pressure is not achieved, pharmacologic therapy should be included.
Drug therapy is warranted for patients with Stage 2 or Stage 3 hypertension.

Risk Group B

This group includes those with hypertension who do not have clinical cardiovascular disease or target organ damage, but have one or more risk factors, except diabetes mellitus.
If multiple risk factors exist, clinicians should consider antihypertensive drugs as initial therapy.
Clinicians should strongly recommend life-style modification and management of reversible risk factors.

Risk Group C

This group includes hypertensive patients who have clinically manifest cardiovascular disease or target organ damage.
Some patients who have high-normal blood pressure and renal insufficiency, heart failure, or diabetes mellitus should be considered for prompt pharmacologic therapy.
Clinicians should recommend life-style modifications as adjunct treatment.

Potential for Primary Prevention of Hypertension

The need for preventing hypertension should be recognized before considering the active treatment.
An effective population-wide strategy to prevent blood pressure rise with age and to reduce overall blood pressure levels could affect overall cardiovascular morbidity and mortality as much or more than that of treating only those with established hypertension.
A diet rich in fruits, vegetables, and low-fat dairy foods, and reduced saturated and total fats significantly lowers blood pressure.
Life-style modifications should be recommended to the entire population.
Modifications that can be provided to the entire population, such as a reduction in the amount of sodium chloride added to processed foods, may be even more effective.

Goal

The goal of prevention and management of high blood pressure is to reduce morbidity and mortality by the least intrusive means.
This goal may be accomplished by achieving and maintaining SBP below 140 mm Hg and DBP below 90 mm Hg and lower if tolerated while controlling other modifiable risk factors for cardiovascular disease.
Treatment to lower levels may be useful, especially to prevent stroke, to preserve renal function, and to prevent or slow heart failure progression.
Life-style modifications with or without pharmacologic treatment may achieve this goal.

Life-style Modifications

Several life-style modifications are useful as the initial strategy or as an adjunct to antihypertensive therapy. Implementation of life-style modification, however, should not delay the initiation of antihypertensive therapy.

Weight Reduction

Excess body weight (body mass index of >=27) is correlated closely with increased blood pressure.
The deposition of excess fat in the upper part of the body (a waist circumference of >=34 in women, or >=39 in men) is associated with the risk for hypertension, dyslipidemia, diabetes, and CHD mortality.
Weight reduction of as little as 10 pounds reduces blood pressure in a large proportion of overweight people with hypertension.
Weight reduction enhances the blood pressure-lowering effect of concurrent antihypertensive agents and can significantly reduce concomitant cardiovascular risk factors, such as diabetes and dyslipidemia.
All patients with hypertension who are above their desirable weight should be prescribed an individualized, monitored weight reduction program that includes caloric restriction and increased physical activity.
Recidivism is common, but persistence may be rewarded by reduction of multiple cardiovascular risk factors and a step-down in antihypertensive drug therapy.
Anorectic agents should be used with caution because many can raise blood pressure; some may increase the risk for valvular heart disease and pulmonary hypertension.

Moderation of Alcohol Intake

Excessive alcohol consumption is an important risk factor for high blood pressure, can cause resistance to antihypertensive therapy, and is a risk factor for stroke.
Patients who drink alcohol should be counseled to limit daily intake to no more than one ounce of ethanol (eg, 24 ounces of beer, 10 ounces of wine, or two ounces of 100-proof whiskey).
Women and lighter-weight patients should be counseled to limit daily alcohol intake to no more than 0.5 ounces of ethanol per day.
Significant hypertension may develop during abrupt withdrawal from heavy alcohol consumption, but recedes in a few days.

Physical Activity

Regular aerobic physical activity can enhance weight loss and functional health status and reduce the risk for cardiovascular disease and all-cause mortality.
Sedentary individuals have a 20% to 50% increased risk of developing hypertension.
Blood pressure can be lowered with moderately intense physical activity (40% to 60% of maximum oxygen consumption), such as 30 to 45 minutes of brisk walking daily, for most days of the week.
Patients with cardiac or other serious health problems should have a thorough medical evaluation, often including a cardiac stress test, and possibly a referral to a specialist or medically-supervised exercise program.

Moderation of Dietary Sodium

There is a positive association between sodium intake and levels of blood pressure.
A reduction of 75 to 100 mmol/d in sodium intake lowers blood pressure. The effects are greater for older people and those with elevated blood pressures.
A diet with moderately reduced intake of sodium may be associated with other favorable effects, such as the ability to reduce the need for antihypertensive medication, reduce diuretic-induced potassium wastage, possibly regress left ventricular hypertrophy (LVH), and protect from osteoporosis and renal stones through a reduction in urinary calcium excretion.
Moderate sodium reduction to a level of no more than 100 mmol/d is recommended.
African-Americans, older people, and patients with hypertension or diabetes are more sensitive to changes in dietary sodium chloride than others in the general population.

Calcium Intake

Low dietary calcium intake is associated with an increased prevalence of high blood pressure.
An increased calcium intake may lower blood pressure in some patients, but the overall effect is minimal.
Currently there is no rationale for recommending calcium supplements to lower blood pressure.

Magnesium Intake

There is no data that justify recommending an increased magnesium intake to lower blood pressure.

Other Dietary Factors

Dietary therapy and, if necessary, drug therapy for dyslipidemia are important adjuncts in antihypertensive treatment.
Diets varying in total fat and proportions of saturated to unsaturated fats have little, if any, effect on blood pressure.
Large amounts of omega-3 fatty acids may lower blood pressure.
Caffeine may raise blood pressure, but there is no direct relationship between caffeine intake and elevated blood pressure in most epidemiologic surveys.
There are no data to demonstrate the effects of protein, varying proportions of carbohydrate, garlic, or onion in the diet on blood pressure.

Relaxation and Biofeedback

Emotional stress can raise blood pressure.
The role of stress management techniques in treating individuals with elevated blood pressure is uncertain.
Relaxation therapies and biofeedback have shown little effect in multiple controlled trials.
Available literature does not support the use of relaxation therapies for definitive therapy or for preventing hypertension.

Tobacco Avoidance for Overall Cardiovascular Risk Reduction

Smokers should be counseled repeatedly and unambiguously to stop smoking.
Patients who continue to smoke may not receive the full protection against cardiovascular disease from antihypertensive therapy.
Cardiovascular benefits of discontinuing tobacco use can be seen within a year in all age groups.
Lower amounts of nicotine contained in smoking cessation aids usually do not raise blood pressure. They are recommended with counseling and behavior interventions.
Ways to avoid or minimize weight gain after quitting smoking are often necessary.

Pharmacologic Treatment

The decision to begin pharmacologic treatment should include the degree of blood pressure elevation, the presence of target organ damage, and the presence of clinical cardiovascular disease or other risk factors.
Reducing blood pressure with drugs protects against stroke, heart failure, progression of renal disease, progression to more severe hypertension, and all-cause mortality.
Among older patients, treating hypertension is associated with an even more significant reduction in CHD.

Drug Therapy Considerations

A low dose of the initial drug choice should be used for most patients, slowly titrating upward at a schedule dependent on the patient's age, needs, and responses.
The optimal formulation should provide 24-hour efficacy with a once-daily dose, with at least half of the peak effect remaining at the end of the 24 hours. Long-acting formulations that provide 24-hour efficacy are preferred over short-acting agents for the following reasons: adherence is better with once-daily dosing; fewer tablets incur lower cost for some agents; control of hypertension is persistent and smooth rather than intermittent; protection is provided against risk for sudden death, heart attack, and stroke secondary to the abrupt increase of blood pressure after overnight sleep; and twice-daily dosing may offer similar control at a lower cost.
Combinations of low doses of two agents from different classes provide additional antihypertensive efficacy, thereby minimizing the likelihood of dose-dependent adverse effects.
Very low doses of a diuretic can potentiate the effect of the other agent without causing adverse metabolic effects. Low-dose combinations with an ACE inhibitor and a nondihydropyridine calcium antagonist may reduce proteinuria more than either drug administered alone.
Combinations of a dihydropyridine calcium antagonist and an ACE inhibitor induce less pedal edema than the calcium antagonist alone.
Drugs with similar modes of action may offer additive effects, such as metolazone and a loop diuretic in renal failure.
Angiotensin-converting enzyme inhibitors provide beneficial effects in a variety of hypertension-related processes, including heart failure from systolic dysfunction and nephropathy.
Angiotensin II receptor blockers produce hemodynamic effects similar to those of ACE inhibitors without the most common adverse effect, a dry cough.
Angiotensin II receptor blockers should be used primarily in patients in whom ACE inhibitors are indicated, but who are unable to tolerate them.
Some antihypertensive agents, such as direct-acting, smooth-muscle vasodilators central alpha-2 agonists, and peripheral adrenergic antagonists are not suited for initial monotherapy because of adverse effects in many patients.
Reserpine has a prolonged therapeutic effect and is better tolerated in low doses (0.5-0.10 mg/d), but the patient should be warned of possible depression.
Direct-acting smooth-muscle vasodilators (eg, hydralazine hydrochloride and minoxidil) often induce reflex sympathetic stimulation of the cardiovascular system and also fluid retention.
Immediate-release nifedipine has precipitated ischemic events and in large doses may increase coronary mortality in those who have had a myocardial infarction. This agent should be used only with great caution.
There are inconsistent reports of adverse health effects of short-acting or immediate-release formulations of nifedipine, diltiazem hydrochloride, and verapamil hydrochloride.
Using combination tablets and generic formulations may lower the costs of medications.
Patients should be advised to check prices at several sources.

Drug Interactions

Some drug interactions may be helpful, such as diuretics that act on different sites in the nephron (eg, furosemide and thiazides), increase natriuresis and diuresis. Certain calcium antagonists reduce the required amount of cyclosporine.
Non-steroidal anti-inflammatory drugs may blunt the action of diuretics, beta-blockers, and ACE inhibitors.

Dosage and Follow-Up

Therapy for most patients (uncomplicated hypertension, Stages 1 and 2) should start with the lowest dosage to prevent adverse effects of too great or too abrupt a reduction in blood pressure.
If blood pressure remains uncontrolled after one to two months, the next dosage level should be prescribed.
Most antihypertensive drugs can be given once daily. This should be the goal to improve patient adherence.
Home or office blood pressure measurement in the early morning, before patients have taken their daily dose, is useful in ensuring adequate modulation of the surge in blood pressure after arising.
Measurements in the late afternoon or evening help monitor control over the day.
Treatment goals based on out-of-office measurements should be lower than those based on recordings in the office.

Initial Drug Therapy

If there are no indications for another type of drug, a diuretic or ß-blocker should be given because numerous randomized clinical trials have shown a reduction in morbidity and mortality with these agents.
If the response to the initial drug is inadequate after reaching the full dose, two options for subsequent therapy should be considered:
- If the patient is tolerating the first drug, add a second drug from another class.
- If the patient is having significant adverse effects or no response, substitute a drug from another class.

High-Risk Patients

Drug therapy should begin with minimal delay. It may be necessary to begin treatment with more than one drug.
It is often necessary to add a second or third drug after a short interval if control is not achieved.
The intervals between changes in the treatment should be decreased, and the maximum dose of some drugs may be increased.
Patients with an average SBP of >=200 mm Hg and an average of DBP of >=120 mm Hg need more immediate therapy. If symptomatic target organ damage is present, they may require hospitalization.

Step-Down Therapy

Decreasing the dosage and number of antihypertensive drugs should be considered after hypertension has been controlled effectively for at least one year.
The reduction should be made in a deliberate, slow, and progressive way.
Step-down therapy is more often successful in patients who also make life-style modifications.
Patients whose drugs have been discontinued should have scheduled follow-up visits because blood pressure usually rises again to hypertensive levels, sometimes months or years after discontinuance.

J-Curve Hypothesis

Lowering DBP too much may increase the risk for coronary events by lowering diastolic perfusion pressure in the coronary circulation-the J curve hypothesis.
The J-curve concern may be more relevant to individuals with both hypertension and preexisting coronary disease and to those with pulse pressure >60 mm Hg.
Data also support a progressive reduction in both cerebrovascular disease and renal disease with even greater reductions in blood pressure.
All available evidence supports the value of the reduction of DBP and SBP at all ages to the levels achieved in clinical trials (DBP below 90 mm Hg and SBP below 140 mm Hg in those with isolated systolic hypertension).
In trials of patients with isolated systolic hypertension, no increase in cardiovascular morbidity and mortality has been seen, despite further reductions of DBP.

Follow-Up Visits

Achieving and maintaining target blood pressure often requires continuing encouragement for life-style modifications and drug adjustment.
Most patients should be seen within one to two months after the initiation of therapy to determine the adequacy of hypertension control, the degree of patient adherence, and any adverse effects.
Associated medical problems, including target organ damage, other major risk factors, and laboratory test abnormalities, should play a part in determining the frequency of patient follow-up.
Once blood pressure is stabilized, follow-up at three- to six-month intervals is recommended.
In older patients and those with orthostatic symptoms, monitoring should include blood pressure measurement in the seated position and after standing quietly for two to five minutes.

Strategies for Improving Adherence to Therapy and Control of High Blood Pressure

The choice and application of specific strategies should depend on the individual patient characteristics.
Pharmacists should be encouraged to monitor patients' use of medications, to provide information about potential adverse effects, and to avoid drug interactions.
Nurse-managed clinics offer ways to improve adherence and outcomes.
Other members of the healthcare team, such as those who offer counseling in nutrition or exercise, should be used.

Resistant Hypertension

Hypertension should be considered resistant if it cannot be reduced to below 140/90 mm Hg in patients who adhere to an adequate and appropriate triple-drug regimen that includes a diuretic, with all three drugs prescribed in near maximal doses.
In older patients with isolated systolic hypertension, resistance is considered failure of an adequate triple-drug regimen to reduce SBP to below 160 mm Hg.
The most common cause of true resistance is volume overload due to inadequate diuretic therapy.
If the goal blood pressure cannot be reached without intolerable adverse effects, even suboptimal reduction of blood pressure contributes to decreased morbidity and mortality.
Patients who have resistant hypertension or are unable to tolerate antihypertensive therapy may benefit from referral to a hypertension specialist.

Emergencies

Hypertensive emergencies are those that need immediate blood pressure reduction to prevent or limit target organ damage. Examples include hypertensive encephalopathy, intracranial hemorrhage, unstable angina pectoris, acute myocardial infarction, acute left ventricular failure with pulmonary edema, dissecting aortic aneurysm, or eclampsia.
The initial goal in hypertensive emergencies is to reduce mean arterial blood pressure by no more than 25% (within minutes to two hours), then toward 160/100 mm Hg within two to six hours, avoiding excessive falls in pressure that may precipitate renal, cerebral, or coronary ischemia.
Most hypertensive emergencies can be treated initially with parenteral administration of an appropriate agent.
Sublingual nifedipine is not recommended for hypertensive emergencies due to several serious adverse effects and the inability to control the rate or degree of fall in blood pressure. It is also not recommended routinely in postoperative or nursing home patients when blood pressure rises beyond a predetermined level. In these instances it is recommended to identify and address the causes of elevated blood pressure, such as pain or a distended urinary bladder.

Urgencies

Hypertensive urgencies are those that need a reduction in blood pressure within a few hours. Examples include upper levels of Stage 3 hypertension, hypertension with optic disc edema, progressive target organ complications, and severe perioperative hypertension.
Hypertensive urgencies can be managed with oral doses of drugs with a relatively fast onset of action. Drug choices include loop diuretics, ß-blockers, ACE inhibitors, alpha-2 agonists, or calcium antagonists.

Different Ethnic Groups

The prevalence of hypertension differs among racial and ethnic groups.
American Indians have the same prevalence as, or a higher prevalence than, the general population.
Hispanics generally have a blood pressure that is the same as or lower than that of non-Hispanic whites, despite a high prevalence of obesity and type 2 diabetes mellitus.
South Asians are more responsive to various antihypertensive medications than whites.
In African-Americans the earlier onset of hypertension, the higher prevalence, and the greater rate of Stage 3 hypertension are accompanied by an 80% higher stroke mortality rate, a 50% higher heart disease mortality rate, and a 320% greater rate of hypertension-related end-stage renal disease than in the general population.
African-Americans receiving adequate treatment achieve similar overall declines when compared with whites, and may experience a lower incidence of cardiovascular disease. Often, they do not receive treatment until blood pressure has been elevated for a long time.
Hypertension awareness, treatment, and control in those with lower socioeconomic status require more focused hypertension education and intervention programs.

Hypertension in Children and Adolescents

Blood pressure at the 95th percentile or greater is considered to be elevated.
Clinicians should be alert to the possibility of identifiable reasons for hypertension in younger children.
Life-style interventions should be recommended with pharmacologic therapy for higher levels of blood pressure.
Doses of antihypertensive medication should be smaller and adjusted very carefully.
Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not recommended for pregnant or sexually active girls.
Uncomplicated elevated blood pressure alone should not be a reason to restrict asymptomatic children from physical activities.
Anabolic steroid hormones for bodybuilding are not recommended.
Clinicians should make efforts to identify other risk factors (eg, smoking) in children and if present, interventions should be made.

Hypertension in Women
Large, long-term clinical trials of antihypertensive treatment have shown no clinically significant sex differences in blood pressure response and outcomes.

Hypertension Associated with Oral Contraceptives

Hypertension is two to three times more common in women taking oral contraceptives, especially in obese and older women, than in those not taking the medication. If hypertension develops in women taking oral contraceptives, it is prudent to stop their use.
Clinicians should counsel women 35 years and older who smoke cigarettes to quit. If they continue to smoke, they should be encouraged to stop taking oral contraceptives.
If high blood pressure persists, if the risks for pregnancy are found to be greater than the risks for hypertension, and if other contraceptive methods are not suitable, then oral contraceptives may have to be continued and therapy for high blood pressure begun.
No more than a six-month supply of contraceptives should be prescribed in order to measure blood pressure on a semi-annual basis.

Hypertension in Pregnancy

The goal for women with chronic hypertension in pregnancy is to minimize the short-term risk of elevated blood pressure to the mother while avoiding therapy that compromises the well being of the fetus.
If started before pregnancy, diuretics and most other antihypertensive medications, except ACE inhibitors and angiotensin II receptor blockers, may be continued.
Methyldopa is recommended for women whose hypertension is first diagnosed during pregnancy.
Beta-blockers compare favorably with methyldopa in efficacy and are considered safe in the latter part of pregnancy. Their use in early pregnancy may be associated with growth retardation of the fetus.
Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not recommended due to serious neonatal problems, including renal failure and death.

Preeclampsia

Preeclampsia is increased blood pressure accompanied by proteinuria, edema, or both and at times by abnormalities of coagulation and renal and liver function that may progress rapidly to a convulsive phase, eclampsia.
The benefits of prophylactic low-dose aspirin or supplemental calcium to prevent preeclampsia have not been confirmed.

Hormone Replacement Therapy and Blood Pressure Response

Hypertension is not considered a contraindication to postmenopausal estrogen replacement therapy.
Blood pressure does not increase significantly with hormone replacement therapy in most women with and without high blood pressure.
Hormone replacement therapy has a beneficial effect on overall cardiovascular risk factor profiles.
A few women may experience a rise in blood pressure attributable to estrogen therapy.
All women treated with hormone replacement therapy should have their blood pressure monitored more frequently after such therapy is begun.
The effect of transdermal estrogen and progestogen on blood pressure has not been determined.

Hypertension in Older Persons

In older persons, SBP is a better predictor of CHD, cardiovascular disease, heart failure, stroke, end-stage renal disease, and all-cause mortality than DBP.
Elevated pulse pressure (SBP-DBP), which indicates reduced vascular compliance in larger arteries, may be a better marker of increased cardiovascular risk than either SBP or DBP alone. This is especially relevant to older patients who frequently have an isolated elevation of SBP (>=140 mm Hg with a DBP below 90 mm Hg).
Patients with Stage 1 isolated systolic hypertension are at significantly increased cardiovascular risk.
Primary hypertension is the most common form of hypertension in older people.
Clinicians should measure blood pressure in older persons with special care because some have pseudohypertension (falsely high sphygmomanometer readings) due to excessive vascular stiffness. Some older patients, especially women, may have white coat hypertension and excessive variability in SBP.
Clinicians should consider pseudohypertension or white coat hypertension in the absence of target organ damage, and should obtain readings outside the office.
Blood pressure in older patients should always be measured in the standing, as well as the seated or supine positions because they are more likely than younger patients to have an orthostatic fall in blood pressure.
Hypertension therapy in older people, as in younger people, should begin with life-style modifications. If the goal blood pressure is not achieved, then pharmacologic treatment is recommended.
The starting dose in older patients should be about half of that for younger patients.
Thiazide diuretics or beta-blockers in combination with thiazide diuretics are recommended due to efficacy in reducing mortality and morbidity in older people with hypertension.
The goal of therapy in older patients should be the same as in younger patients (<140/90 mm Hg); an interim goal of SBP below 160 mm Hg may be necessary in those patients with marked systolic hypertension.
While any reduction in blood pressure appears to have benefit, the closer to normal the greater the benefit.
Drugs that exaggerate postural changes in blood pressure (peripheral adrenergic blockers, alpha-blockers, and high dose diuretics) or drugs that can cause cognitive dysfunction (central alpha 2 agonists) should be used with caution.

Patients with Hypertension and Coexisting Cardiovascular Diseases

Cerebrovascular Disease

Clinically evident cerebrovascular disease calls for antihypertensive treatment.
After the occurrence of an acute ischemic cerebral infarction, it is recommended that treatment be withheld (unless blood pressure is very high) until the situation has been stabilized.
Even when treatment has been withheld temporarily, the eventual goal is to lower blood pressure gradually while avoiding orthostatic hypotension.
Those with acute ischemic strokes who are treated with fibrinolytic agents need careful blood pressure monitoring, especially over the first 24 hours after beginning treatment.
SBP of >=180 mm Hg or DBP of >=105 mm Hg may be controlled with intravenous agents with careful monitoring for worsening of the neurologic status.

Coronary Artery Disease

Patients with coronary artery disease and hypertension are considered at particularly high risk for cardiovascular morbidity and mortality.
Excessively rapid lowering of blood pressure, particularly when it causes reflex tachycardia and sympathetic activation is not recommended.
Blood pressure should be lowered to the usual target range of <140/90 mm Hg and even lower if angina persists.
Beta-blockers or calcium antagonists may be useful in patients with hypertension and angina pectoris, but short-acting calcium antagonists are not recommended.
Following myocardial infarction, ß-blockers without intrinsic sympathomimetic activity should be given because they reduce the risk of subsequent myocardial infarction or sudden cardiac death.
Angiotensin-converting enzyme inhibitors are also helpful after myocardial infarction, especially with left ventricular systolic dysfunction, in order to prevent subsequent heart failure and to reduce mortality.
If ß-blockers are ineffective or contraindicated, verapamil or diltiazem may be prescribed because they are known to reduce cardiac events and mortality modestly following non-Q-wave myocardial infarction, and after myocardial infarction with preserved left ventricular function.
Some patients with hypertension, particularly when accompanied by severe LVH, may have angina without evidence of coronary atherosclerosis.
Treatment should be aimed at blood pressure control, reversal of LVH, and avoidance of tachycardia, which may exacerbate the supply-demand mismatch.

LVH

LVH is a major independent risk factor for sudden cardiac death, myocardial infarction, stroke, and other cardiovascular events.
Development of LVH permits cardiac adaptation to the increased afterload imposed by elevated arterial pressure.
Antihypertensive agents (except direct vasodilators such as hydralazine and minoxidil), weight reduction, and decrease of excessive salt intake are capable of reducing increased left ventricular mass and wall thickness.
The regression of electrocardiographic evidence of LVH is associated with a reduction in the risk for cardiovascular events, but such reversal offers no benefits beyond that offered by reduction of blood pressure.
Electrocardiography is useful to detect left atrial hypertrophy, LVH, and myocardial ischemia and arrhythmia.
Echocardiography is more sensitive and specific for identifying LVH but is too expensive for routine use. However, the cost may be justified in patients with untreated Stage 1 hypertension, no cardiovascular risk factors, no evidence of clinical cardiovascular disease, and no target organ damage.

Cardiac Failure

Hypertension continues to be the major cause of left ventricular failure in the United States.
Structural alterations in the left ventricle (LVH or left ventricular remodeling with dilation) as well as myocardial ischemia from coronary artery atherosclerosis may contribute to the development of heart failure.
Control of elevated arterial pressure using life-style changes and drug therapy improves myocardial function and prevents and reduces heart failure and cardiovascular mortality.
After myocardial infarction, ACE inhibitors prevent subsequent heart failure and, when used alone or in conjunction with digoxin or diuretics, reduce morbidity and mortality.
The alpha-beta-blocker carvedilol added to ACE inhibitors is beneficial, and in one trial the angiotensin II receptor blocker losartan potassium was superior to captopril in reducing mortality.
The dihydropyridine calcium antagonists amlodipine besylate and felodipine are safe in treating angina and hypertension in patients with advanced left ventricular dysfunction when used in addition to ACE inhibitors, diuretics, or digoxin; other calcium antagonists are not recommended.
When ACE inhibitors are contraindicated or not tolerated, the vasodilator combination of hydralazine and isosorbide dinitrate is also effective.

Peripheral Arterial Disease

Hypertension is one of the major risk factors for the development of carotid atherosclerosis and peripheral arterial disease with intermittent claudication and aneurysms. Although there is no data confirming that hypertensive therapy is beneficial, trials from dissecting aortic aneurysms suggest a reduction in deaths.
Patients with Hypertension and Other Coexisting Diseases

Renal Parenchymal Disease

Hypertensive nephrosclerosis is among the most common causes of progressive renal disease, especially in African-Americans.

Strategies for slowing progressive renal failure in patients with hypertension:
- Early detection of hypertensive renal damage is necessary.
- Evaluation should include a urinalysis to detect proteinuria or hematuria and possibly renal sonography to exclude lower tract obstruction, polycystic kidney disease, and to determine the size of the kidneys.
- Reversible causes of renal failure should be treated.
- Blood pressure should be controlled to 130/85 mm Hg or lower (125/75 mm Hg) in those with proteinuria in excess of 1 g per 24 hours.
- If dietary protein restriction is implemented, close attention should be paid to total energy intake to prevent malnutrition.
- Dietary potassium and phosphorus should be restricted in patients with creatinine clearances below 30 mL/min to prevent hyperkalemia and help prevent secondary hyperparathyroidism.

Antihypertensive Drug Recommendations

Reducing hypertension slows the progress of renal failure.
All classes of antihypertensive drugs are effective. Multiple antihypertensive medications may be needed.
ACE inhibitors are effective in patients with type 1 diabetic nephropathy, in patients with proteinuria >l1 g per 24 hours, and in patients with renal insufficiency.
ACE inhibitors should be used with caution in patients with a creatinine level of >=265.2 umol/L (3 mg/dL).
An initial transient decrease in glomerular filtration rate may happen during the first three months of treatment as blood pressure is lowered.
If patients are euvolemic and creatinine rises 88.4 umol/L (1 mg/dL) above baseline levels, creatinine and potassium should be remeasured after a few days. If they remain persistently elevated, clinicians should consider the possibility of renal artery stenosis and ACE inhibitors or angiotensin II receptor blockers should be discontinued. These drugs can markedly reduce renal perfusion in those with bilateral renal artery stenosis or renal artery stenosis to a solitary kidney.
Thiazide diuretics are not effective with advanced renal insufficiency (serum creatinine level >=221.0 umol/L {>=2.5 mg/dL}). Loop diuretics are needed, often in large doses.
A combination of a loop diuretic with a long-acting thiazide diuretic, such as metolazone, is effective in patients resistant to a loop diuretic alone.
Potassium-sparing diuretics are not recommended for patients with renal insufficiency.

Renovascular Disease

Hemodynamically significant renal artery stenosis may be associated with all stages of hypertension, but is more common with Stage 3 or resistant hypertension; when it is bilateral, it can lead to reduced kidney function.
Clinical clues to renovascular disease include:
- Onset of hypertension before the age of 30 years, especially without a family history or recent onset of significant hypertension after 55 years of age;
- An abdominal bruit, especially if it continues into diastole and is lateralized;
- Accelerated or resistant hypertension;
- Recurrent (flash) pulmonary edema;
- Renal failure of uncertain cause, especially with a normal urinary sediment;
- Coexisting, diffuse atherosclerotic vascular disease, particularly in heavy smokers; and
- Acute renal failure precipitated by antihypertensive therapy, especially ACE inhibitors or angiotensin II receptor blockers.
Captopril-enhanced radionuclide renal scan, duplex Doppler flow studies, and magnetic resonance angiography may be used as noninvasive screening tests in patients with signs of renovascular disease.
A definitive diagnosis of renovascular disease requires renal angiography, which carries some risk, especially radio-contrast-induced acute renal failure or atheroembolism in older patients.
Results of percutaneous transluminal renal angioplasty (PTRA) have been excellent and comparable to surgical revascularization in young patients with fibromuscular dysplasia.
Individuals with normal renal function and atherosclerotic renal artery stenosis that is focal, unilateral, and nonostial, without widespread vascular disease, are managed similarly to patients with fibromuscular dysplasia.
Renal artery stenting is an important adjunct to PTRA, being used to counteract elastic recoil and abolish the residual stenosis sometimes seen after PTRA.
While many patients with high-grade renal artery stenosis remain stable for prolonged periods, if blood pressure is well controlled, surgical revascularization or PTRA with renal artery stenting may be necessary to preserve renal function.

Diabetes Mellitus

Blood pressure should be taken in the supine, sitting and standing positions in all patients with diabetes mellitus in order to detect evidence of autonomic dysfunction and orthostatic hypotension.
Antihypertensive drug therapy should be initiated along with life-style modifications, particularly weight loss, to reduce arterial blood pressure to below 130/85 mm Hg.
Angiotensin-converting enzyme inhibitors, a-blockers, calcium antagonists, and diuretics in low doses are preferred due to fewer adverse effects on glucose homeostasis, lipid profiles, and renal function.
Patients with diabetes who are treated with diuretics and ß-blockers have a similar or greater reduction of CHD and total cardiovascular events when compared with persons without diabetes.
ACE inhibitors are preferred in patients with diabetic nephropathy.
Angiotensin II receptor blockers may be used if ACE inhibitors are contraindicated or not well tolerated.
Calcium antagonists offer renoprotection.
Metabolic disturbances and hypertension respond to weight loss, exercise, insulin-sensitizing agents, vasodilating antihypertensive drugs, and certain lipid-lowering drugs in obese patients with hypertension.

Dyslipidemia

Aggressive management is necessary for the coexistence and increased risk for dyslipidemia and hypertension.
Great emphasis is recommended on weight control, reduced intake of saturated fat, cholesterol, sodium chloride, and alcohol. Increased physical activity in patients with elevated lipids and high blood pressure is also recommended.
In high doses, thiazide diuretics and loop diuretics can induce short-term increases in levels of total plasma cholesterol, triglycerides, and low-density lipoprotein cholesterol; dietary modifications can reduce or eliminate these effects.
Beta-blockers reduce the rate of sudden death, overall mortality, and recurrent myocardial infarction in those with previous myocardial infarction.
Alpha-blockers may lower serum cholesterol concentration to a modest degree and increase high-density lipoprotein cholesterol.
Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium antagonists, and central adrenergic agonists have clinically neutral effects on the levels of serum lipids and lipoproteins.
Aggressive lipid reduction, especially with b-hydroxy-b-methylglutaryl CoA (HMG-CoA) reductase inhibitors (statins) provides both primary and secondary protection against CHD and stroke.
Changes in life-style and hypolipidemic agents should be used to reach goals in patients with hypertension and hyperlipidemia.

Sleep Apnea

Sleep apnea is more common in patients with hypertension and is associated with a number of adverse clinical consequences.
Undiagnosed sleep apnea may explain the difficulty in controlling hypertension in some patients.

Bronchial Asthma or Chronic Airway Disease

Beta-blockers and alpha-beta-blockers are not recommended for patients with asthma since they may aggravate the condition.
Topical ophthalmic application of ß-blockers, such as timolol maleate, may worsen asthma.
ACE inhibitors are safe in most patients with asthma.
If a cough related to ACE inhibitor use occurs, clinicians should consider angiotensin II receptor blockers as an alternative.
Cromolyn sodium, ipratropium bromide, or corticosteroids by inhalation are safe for nasal congestion in hypertensive patients.

Gout

Hyperuricemia is common in patients with untreated hypertension and may reflect a decrease in renal blood flow.
All diuretics can increase serum uric acid levels, but rarely induce acute gout.
Diuretics are not recommended for patients with gout.
Diuretic-induced hyperuricemia does not need treatment in the absence of gout or urate stones.

Patients Undergoing Surgery

A blood pressure of >=180/110 mm Hg is associated with a greater risk of perioperative ischemic events. Surgery should be delayed until blood pressure is lowered.
Patients without prior antihypertensive therapy may be best treated with cardioselective ß-blocker therapy before and after surgery.
Adequate potassium supplementation should be given to correct hypokalemia well in advance of surgery.
Surgical candidates who are controlling their blood pressure adequately with medication should be kept on their regimen until the time of surgery. Therapy should be reinstated as soon as possible after surgery.
If oral intake must be interrupted, parenteral therapy with diuretics, adrenergic inhibitors, vasodilators, ACE inhibitors, or transdermal clonidine hydrochloride may be prescribed to prevent the rebound hypertension that may occur after sudden discontinuation of some adrenergic-inhibiting agents.

Miscellaneous Causes for Increased Blood Pressure

Cocaine

Most cocaine-dependent individuals are normotensive. There is no evidence to suggest that ongoing cocaine abuse causes chronic hypertension.
Cocaine abuse needs to be considered in all patients presenting to an emergency room with hypertension-related problems.
Clues include chest pain, tachycardia, dilated pupils, combativeness, altered mental state, and seizures.
Cocaine may induce severe ischemia from coronary and cerebral vasoconstriction and acute renal failure due to rhabdomyolysis.
Nitroglycerin is indicated to reverse cocaine-related coronary vasoconstriction; its antihypertensive effectiveness may be inadequate making other parenteral agents necessary.
Nonselective ß-blockers such as propranolol are not recommended due to the risk of a paradoxical rise in blood pressure as well as coronary vasoconstriction due to the exaggerated effect of catecholamines on unblocked alpha receptors.

Amphetamines

Acute amphetamine toxicity is similar to that of cocaine but lasts longer; cerebral and systemic vasculitis and renal failure may occur.
Treatment for amphetamine toxicity is comparable to that of cocaine toxicity.

Immunosuppressive Agents

Immunosuppressive regimens based on cyclosporine, tacrolimus, and steroids raise blood pressure in 50% to 80% of patients with solid organ transplants.
When cyclosporine is used alone in nontransplant patients, hypertension occurs in 25% to 30% of patients.
The rise in blood pressure indicates widespread vasoconstriction.
Therapy should be based on vasodilation, often including dihydropyridine calcium antagonists; diuretics may exaggerate prerenal azotemia and may precipitate gout.

Erythropoietin

Recombinant human erythropoietin raises blood pressure in 18% to 45% of patients when used to treat end-stage renal disease.
High blood pressure is produced by a rise in systemic vascular resistance, partly related to direct vascular effects of recombinant human erythropoietin, and is not closely related to hematocrit or viscosity.
Management should include optimal volume control, antihypertensive agents, and sometimes reducing the erythropoietin dose or changing administration from an intravenous to a subcutaneous route.

Other Agents

Chemicals and toxins, such as mineralocorticoids and derivatives, anabolic steroids, monoamine oxidase inhibitors, lead, cadmium, and bromocriptine may induce hypertension.

(This article is available at www.ama-assn.org/internal.com.)