Overview of hypertension in adults

Authors Frank J Domino, MD Norman M Kaplan, MD Section Editor George L Bakris, MD Deputy Editor John P Forman, MD, MSc

Last literature review version 19.1: January 2011 | This topic last updated: February 14, 2011 (More)

INTRODUCTION The treatment of hypertension is the most common reason for office visits of non-pregnant adults to physicians in the United States and for use of prescription drugs [1]. Analysis of NHANES data from 1999-2000 and United States Census bureau information results in an approximately 29 to 31 percent incidence of hypertension in the 18 year and older population of the United States [2,3]. This translates into 58 to 65 million hypertensives in the adult population in the United States, which is substantially higher than the 43.2 million estimate derived from the 19881991 NHANES-III survey [3,4].

The number of patients with hypertension is likely to grow as the population ages, since either isolated systolic hypertension or combined systolic and diastolic hypertension occurs in over one-half of persons older than 65 years (figure 1) [5]. The rising incidence of obesity will also increase the number of hypertensive individuals [5]. (See "Treatment of hypertension in the elderly, particularly isolated systolic hypertension".)

Despite the prevalence of hypertension and its associated complications, control of the disease is far from adequate [6-8]. Data from NHANES show that only 34 percent of persons with hypertension have their blood pressure under control, defined as a level below 140/90 mmHg (table 1) [7]. Slightly higher rates of control were reported in a regional population study (approximately 45 and 55 percent of men and women, respectively, have controlled hypertension) [8].

There are numerous potential reasons for low rates of blood pressure control, including poor access to health care and medications, and lack of adherence with long-term therapy for a condition that is usually asymptomatic [9]. The latter may be particularly true when the therapy may interfere with the patient's quality of life and when its immediate benefits may not be obvious to the patient. Thus, hypertension will likely remain the most common risk factor for heart attack and stroke [10].

The definition, complications, diagnosis, evaluation, and management of hypertension are reviewed here. Detailed discussions of all of these issues are found separately. (See appropriate topic reviews.)

DEFINITIONS

Hypertension Major societies have published definitions of hypertension, as will be described below. Hypertension was defined as a blood pressure 140/90 mmHg. However, subsequent trials have identified groups of patients at higher risk in whom goal blood pressures below this value may be associated with improved outcomes. (See 'Goal blood pressure' below.)

The following definitions were suggested in 2003 by the seventh report of the Joint National Committee (JNC 7) based upon the average of two or more properly measured readings at each of two or more visits after an initial screen [7]:

Normal blood pressure: systolic <120 mmHgPrehypertension: systolic 120-139 mmHgHypertension:

mmHg mmHg

and diastolic <80 or diastolic 80-89

Stage 1: systolic 140-159 mmHg or diastolic 90-99 mmHg Stage 2: systolic 160 or diastolic 100 mmHg

Isolated systolic hypertension is considered to be present when the blood pressure is 140/<90 mmHg and isolated diastolic hypertension is considered to be present when the blood pressure is <140/90 mmHg.

These definitions apply to adults on no antihypertensive medications and who are not acutely ill. If there is a disparity in category between the systolic and diastolic pressures, the higher value determines the severity of the hypertension. The systolic pressure is the greater predictor of risk in patients over the age of 50 to 60 [11].

Similar but not identical definitions were suggested in the European Societies of Hypertension and Cardiology guidelines for the management of arterial hypertension that were published in 2007 [12]:

Optimal blood pressure: systolic <120 mmHg and diastolic <80 mmHgNormal: systolic 120-129 mmHg and/or diastolic 80-84 mmHgHigh normal: systolic 130-139 mmHg and/or diastolic 85-89 mmHgHypertension:

Grade 1: systolic 140-159 mmHg and/or diastolic 90-99 mmHg Grade 2: systolic 160-179 mmHg and/or diastolic 100-109 mmHg Grade 3: systolic 180 mmHg and/or diastolic 110 mmHg Isolated systolic hypertension: systolic 140 mmHg and diastolic <90 mmHg

The prevalence of the different types of hypertension (systolic and diastolic, isolated systolic, and isolated diastolic) was evaluated in a study of 26,587 subjects 35 years of age in five cities in China [13]. Systolic and diastolic hypertension were present in 18.4 percent, isolated systolic hypertension in 7.1 percent, and isolated diastolic hypertension in 6.7 percent [13].

Malignant hypertension Malignant hypertension refers to marked hypertension with retinal hemorrhages, exudates, or papilledema [14]. These findings may be associated with hypertensive encephalopathy. (See "Hypertensive emergencies: Malignant hypertension and hypertensive encephalopathy in adults".)

Malignant hypertension is usually associated with diastolic pressures above 120 mmHg. However, it can occur at diastolic pressures as low as 100 mmHg in previously normotensive patients with acute hypertension due to preeclampsia or acute glomerulonephritis.

Hypertensive urgency Severe hypertension (as defined by a diastolic blood pressure above 120 mmHg) in asymptomatic patients is referred to as hypertensive urgency. There is no proven benefit from rapid reduction in BP in asymptomatic patients who have no evidence of acute end-organ damage and are at little short-term risk [15-17]. (See "Management of severe asymptomatic hypertension (hypertensive urgencies)".)

ESSENTIAL (PRIMARY) HYPERTENSION

Pathogenesis The pathogenesis of essential hypertension understood. A variety of factors have been implicated, including:

is

poorly

Increased sympathetic neural activity, with enhanced beta-adrenergic responsiveness. (See "Prehypertension and borderline hypertension".)Increased angiotensin II activity and mineralocorticoid excess. (See "Low-renin essential (primary) hypertension".)Hypertension is about twice as common in subjects who have one or two hypertensive parents and multiple epidemiologic studies suggest that genetic factors account for approximately 30 percent of the variation in blood pressure in various populations [18]. (See "Genetic factors in the pathogenesis of essential hypertension".)Reduced adult nephron mass may predispose to hypertension, which may be related to genetic factors, intrauterine developmental disturbance (eg, hypoxia, drugs, nutritional deficiency), and post-natal environment (eg, malnutrition, infections). (See "Possible role of low birth weight in the pathogenesis of essential hypertension".)

Risk factors The etiology of essential (idiopathic or primary) hypertension and secondary hypertension (due to a known cause) differ. A variety of risk factors have been associated with essential hypertension:

Hypertension tends to be both more common and more severe in blacks. (See "Hypertensive complications in blacks".)Hypertension in maternal, paternal or both parents is independently associated with the development of hypertension over the course of adult life [19].Evidence for a relationship between salt intake and essential hypertension continues to mount. It is likely that increased salt intake is a necessary but not sufficient cause for hypertension. (See "Salt intake, salt restriction, and essential hypertension".)Multiple studies show a clear association between excess alcohol intake and the development of hypertension. (See "Cardiovascular benefits and risks of moderate alcohol consumption", section on 'Hypertension'.)Obesity is associated with an increased prevalence and incidence of hypertension [20-22], and weight gain appears to be a main determinant of the rise in blood pressure (BP) that is commonly seen with aging [23]. (See "Obesity and weight reduction in hypertension".)Physical inactivity is associated with an increased risk of developing hypertension [24-26], and exercise is an effective means of lowering blood pressure. (See "Exercise in the treatment of hypertension", section on 'Efficacy'.) Dyslipidemia may also be associated with the development of hypertension, and is independent of obesity [21,27].Data are conflicting as to whether a high intake of fructose from sugar-sweetened beverages is [28] or is not [29] associated with an increased risk of developing hypertension. Hypertension may be more common among those with certain personality traits, such as hostile attitudes and time urgency/impatience [30].

SECONDARY HYPERTENSION A number of identifiable disorders may be associated with secondary hypertension, and the pathogenesis of hypertension is related to the underlying condition. (See "Who should be screened for renovascular or other causes of secondary hypertension?".)

Primary renal disease Hypertension is a frequent finding in both acute and chronic renal disease, particularly with glomerular or vascular disorders. (See "Hypertension in kidney disease".)Oral agents Oral contraceptives often raise the blood pressure within the normal range but can induce overt hypertension. (See "Effect of oral contraceptives and postmenopausal hormone therapy on blood pressure".)Drug-induced Chronic nonsteroidal antiinflammatory agents and many antidepressants can induce hypertension. Chronic alcohol intake and alcohol abuse can also raise blood pressure. (See "NSAIDs and acetaminophen: Effects on blood pressure and hypertension" and "Cardiovascular benefits and risks of moderate alcohol consumption", section on 'Hypertension'.)Pheochromocytoma About onehalf of patients with pheochromocytoma have paroxysmal hypertension, most of the rest have what appears to be essential hypertension. (See "Clinical presentation and diagnosis of pheochromocytoma" and "Treatment

of pheochromocytoma in adults".)Primary aldosteronism The presence of primary mineralocorticoid excess, primarily aldosterone, should be suspected in any patient with the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis. However, some patients have a normal plasma potassium concentration. (See "Approach to the patient with hypertension and hypokalemia".)Renovascular disease Renovascular disease is an important correctable cause of secondary hypertension. The frequency with which it occurs is variable. (See "Screening for renovascular hypertension".)Cushing's syndrome Moderate diastolic hypertension is a major cause of morbidity and death in patients with Cushing's syndrome. (See "Epidemiology and clinical manifestations of Cushing's syndrome".)Other endocrine disorders Hypertension may be induced by hypothyroidism, hyperthyroidism, and hyperparathyroidism. (See "Cardiovascular effects of hypothyroidism" and "Cardiovascular effects of hyperthyroidism".)Sleep apnea syndrome Disordered breathing during sleep appears to be an independent risk factor for awake systemic hypertension. (See "Cardiovascular effects of obstructive sleep apnea".)Coarctation of the aorta Coarctation of the aorta is one of the major causes of hypertension in young children [31]. (See "Clinical manifestations and diagnosis of coarctation of the aorta".)

COMPLICATIONS Hypertension is associated with a number of serious adverse effects. The likelihood of developing these complications varies with the blood pressure. The increase in risk begins as the blood pressure rises above 110/75 mmHg in all age groups (figure 2A-B) [32-34]. However, this relationship does not prove causality, which can only be demonstrated by randomized trials showing benefit from blood pressure reduction.

The increase in cardiovascular risk associated with hypertension is importantly affected by the presence or absence of other risk factors (figure 3) [35]. (See "Cardiovascular risks of hypertension".)

Hypertension is quantitatively the major risk factor for premature cardiovascular disease, being more common than cigarette smoking, dyslipidemia, and diabetes, the other major risk factors [36]. In older patients, systolic pressure and perhaps pulse pressure are more powerful determinants of risk than diastolic pressure [11,37].Hypertension increases the risk of heart failure at all ages with the hazard increasing with the degree of blood pressure elevation [38]. (See "Epidemiology and causes of heart failure".)Left ventricular hypertrophy is a common problem in patients with hypertension [39], and is associated with an enhanced incidence of

heart failure, ventricular arrhythmias, death following myocardial infarction, and sudden cardiac death (figure 4) [40]. (See "Clinical implications and treatment of left ventricular hypertrophy in hypertension".)Hypertension is the most common and most important risk factor for stroke, the incidence of which can be markedly reduced by effective antihypertensive therapy [41]. (See "Clinical diagnosis of stroke subtypes", section on 'Ecology and risk factors'.)Hypertension is the most important risk factor for the development of intracerebral hemorrhage [42]. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis".)Hypertension is a risk factor for chronic kidney disease and endstage renal disease (figure 5) [43,44]. It can both directly cause kidney disease, called hypertensive nephrosclerosis, and accelerate the progression of a variety of underlying renal diseases. (See "Clinical features and treatment of hypertensive nephrosclerosis" and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease".)Marked elevations in blood pressure can cause an acute, life-threatening emergency (table 2) [45]. (See "Hypertensive emergencies: Malignant hypertension and hypertensive encephalopathy in adults".)

DIAGNOSIS

Screening The optimal interval for screening for hypertension is not known. The 2007 United States Preventive Services Task Force (USPSTF) guidelines on screening for high blood pressure recommend screening every two years for persons with systolic and diastolic pressures below 120 mmHg and 80 mmHg, respectively (normal BP in JNC 7), and yearly for persons with a systolic pressure of 120 to 139 mmHg or a diastolic pressure of 80 to 89 mmHg (prehypertension in JNC 7) [46]. (See "Overview of preventive medicine in adults".)

The risk of developing hypertension in patients who do not have hypertension is not uniform, being higher in prehypertension than with normal blood pressure and in those with other risk factors for hypertension. These issues are discussed separately. (See "Prehypertension and borderline hypertension".)

Measurement Proper measurement and interpretation of the blood pressure is essential in the diagnosis and management of hypertension. Figure 6 outlines the recommendations that have been made to achieve maximum accuracy in this process (table 3) [47]. The preferred technique is

discussed in detail separately. (See "Technique measurement in the diagnosis of hypertension".)

of

blood

pressure

A recent study found no clinical difference in blood pressure readings from a bare arm compared to those measured over a sleeved arm [48].

In the absence of end-organ damage, the diagnosis of mild hypertension should not be made until the blood pressure has been measured on at least three to six visits, spaced over a period of weeks to months. Sequential studies have shown that the blood pressure drops by an average of 10 to 15 mmHg between visits one and three in patients who appear to have mild hypertension on a first visit to a new doctor, with a stable value not being achieved until more than six visits in some cases [49,50]. Thus, many patients considered to be hypertensive at the initial visit are in fact normotensive.

White coat hypertension and ambulatory monitoring Approximately 20 to 25 percent of patients with mild office hypertension (diastolic pressure 90 to 104 mmHg) have what is called "white-coat" or isolated office hypertension in that their blood pressure is repeatedly normal when measured at home, at work, or by ambulatory blood pressure monitoring [51]. This problem is more common in the elderly, but is infrequent (less than 5 percent) in patients with office diastolic pressures 105 mmHg. One way to minimize the white coat effect is to have the blood pressure in the office taken by a nurse or technician, rather than the physician (figure 6) [52].

Ambulatory blood pressure monitoring (ABPM), which typically involves automated inflation of the BP cuff and recording of the blood pressure at preset intervals (usually every 15 to 20 minutes during the day and every 30 to 60 minutes during sleep), can be used to confirm or exclude the presence of white coat hypertension in patients with persistent office hypertension but normal blood pressure readings in the ambulatory setting [53].

A more detailed discussion of white coat hypertension and ambulatory blood pressure monitoring is provided separately. (See "Ambulatory blood pressure monitoring and white coat hypertension in adults".)

Masked hypertension 24-hour monitoring of larger populations has revealed a significant number of patients with elevated out-of-office readings despite normal office readings (eg, masked hypertension) [54]. Cardiovascular risk appears to be elevated in such patients to a similar extent as patients with sustained hypertension [55].

This is consistent with the risk of hypertensive cardiovascular complications (including the development and regression of left ventricular hypertrophy) being more closely correlated with 24-hour or daytime ambulatory monitoring than with the office pressure. (See "Ambulatory blood pressure monitoring and white coat hypertension in adults".)

Indications for ABPM In addition to patients with suspected white coat hypertension, ambulatory monitoring should be considered in the following circumstances:

Suspected episodic hypertension (eg, pheochromocytoma)Hypertension resistant to increasing medicationHypotensive symptoms while taking antihypertensive medicationsAutonomic dysfunction

(See "Ambulatory blood pressure monitoring and white coat hypertension in adults", section on 'Indications for ABPM'.)

EVALUATION Once it has been determined that the patient has persistent hypertension, an evaluation should be performed to ascertain the following information:

To determine the extent of target organ damage.To assess the patient's overall cardiovascular risk status. (See "Overview of the risk factors for cardiovascular disease".)To rule out identifiable and often curable causes of hypertension.

Most patients with presumed essential hypertension undergo a relatively limited work-up because extensive laboratory testing is of limited utility. However, it is important to be aware of the clinical clues suggesting the possible presence of one of the causes of secondary hypertension (table 4),

which is an indication for a more extensive evaluation. Many of these disorders can be cured, leading to partial or complete normalization of the blood pressure; but it is not cost-effective to perform a complete evaluation in every hypertensive patient. These issues are discussed in detail elsewhere. (See "Initial evaluation of the hypertensive adult" and "Who should be screened for renovascular or other causes of secondary hypertension?".)

History The history should search for those facts that help determine the presence of precipitating or aggravating factors (including prescription medications, non-prescription nonsteroidal antiinflammatory agents, and alcohol consumption), the natural course of the blood pressure, the extent of target organ damage, and the presence of other risk factors for cardiovascular disease (table 5).

Physical examination The main goals on the physical examination are to evaluate for signs of end-organ damage (such as retinopathy) and for evidence of a cause of secondary hypertension (table 6).

Laboratory testing The only testing that should be routinely performed includes [7,12]:

Hematocrit, urinalysis, routine blood chemistries (glucose, creatinine, electrolytes), and estimated glomerular filtration rateFasting (9 to 12 hours) lipid profile (total and HDL-cholesterol, triglycerides)Electrocardiogram

Additional tests Additional tests may be indicated in certain settings:

Testing for microalbuminuria is at present primarily limited to patients with diabetes to screen for early nephropathy, although it is increasingly recognized to be an independent risk factor for cardiovascular disease [56]. A discussion of screening for microalbuminuria among nondiabetics with hypertension is presented separately. (See "Microalbuminuria and cardiovascular disease" and "Epidemiology of chronic kidney disease".)Limited echocardiography is a more sensitive method to detect left ventricular hypertrophy than the ECG and is considerably less expensive than a complete echocardiographic examination. The main indication for

echocardiography is to detect possible end-organ damage in a patient with borderline blood pressure values, thereby identifying some patients who would not be treated based upon clinical criteria alone [57]. (See "Clinical implications and treatment of left ventricular hypertrophy in hypertension", section on 'Indications for echocardiography in hypertensive patients'.)

Testing for renovascular hypertension Renovascular hypertension is likely the most common correctable cause of secondary hypertension. The incidence of this condition varies with the clinical setting. It probably occurs in less than 1 percent of patients with mild hypertension [58]. In comparison, between 10 and 45 percent of white patients with severe or malignant hypertension have renal artery stenosis [59]. (See "Who should be screened for renovascular or other causes of secondary hypertension?".)

Radiographic testing for renovascular disease is indicated only in patients in whom the history is suggestive and in whom a corrective procedure will be recommended if significant renal artery stenosis is detected.

The following are settings in which renovascular hypertension or another cause of secondary hypertension should be suspected:

Severe or refractory hypertension, including retinal hemorrhages or papilledema; bilateral renovascular disease may be present in those patients who also have a plasma creatinine above 1.5 mg/dL (132 mol/L).An acute rise in blood pressure over a previously stable baseline this includes renovascular disease superimposed upon underlying and often well-controlled essential hypertension.Proven age of onset before puberty or above age 50.An acute elevation in the plasma creatinine concentration that is either unexplained or occurs after the institution of therapy with an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (in the absence of an excessive reduction in blood pressure). (See "Renal effects of ACE inhibitors in hypertension".)Moderate to severe hypertension in a patient with diffuse atherosclerosis or an incidentally discovered asymmetry in renal disease. A unilateral small kidney (9 cm) has a 75 percent correlation with the presence of large vessel occlusive disease.A systolic-diastolic abdominal bruit that lateralizes to one side. This finding has a sensitivity of approximately 40 percent (and is therefore absent in many patients) but has a specificity as high as 99 percent [60]. Systolic bruits alone are more sensitive but less specific. The patient should be supine, moderate pressure should be placed on the diaphragm of the

stethoscope, and auscultation should be performed in the epigastrium and all four abdominal quadrants.Negative family history for hypertension.Moderate to severe hypertension in patients with recurrent episodes of acute (flash) pulmonary edema or otherwise unexplained congestive heart failure.

The recommended tests will vary based upon renal function and the clinical suspicion of renovascular disease. (See "Screening for renovascular hypertension".)

Testing for other causes of identifiable hypertension Other causes of identifiable hypertension also must be excluded in the appropriate settings.

The presence of primary renal disease is suggested by an elevated plasma creatinine concentration, a calculated GFR below 60 mL/min per 1.73 m2, or proteinuria. (See "Hypertension in kidney disease".)Pheochromocytoma should be suspected if there are paroxysmal elevations in blood pressure (which may be superimposed upon stable chronic hypertension), particularly if associated with the triad of headache (usually pounding), palpitations, and sweating. (See "Clinical presentation and diagnosis of pheochromocytoma".)Measurement of plasma renin activity and aldosterone concentration is usually performed only in patients with possible low-renin forms of hypertension, such as primary hyperaldosteronism. Otherwise unexplained hypokalemia is the primary clinical clue to the latter disorder in which the plasma aldosterone to plasma renin activity ratio should be obtained as a screening test. (See "Approach to the patient with hypertension and hypokalemia".)Cushing's syndrome (including that due to corticosteroid administration) is usually suggested by the classic physical findings of cushingoid facies, central obesity, ecchymoses, and muscle weakness. (See "Epidemiology and clinical manifestations of Cushing's syndrome".)The sleep apnea syndrome should be suspected in obese individuals who snore loudly while asleep, awake with headache, and fall asleep inappropriately during the day. (See "Cardiovascular effects of obstructive sleep apnea".)Coarctation of the aorta is characterized by decreased or lagging peripheral pulses and a vascular bruit over the back. (See "Clinical manifestations and diagnosis of coarctation of the aorta".)Hypertension may be induced by both hypothyroidism, suspected because of suggestive symptoms or an elevated plasma thyroid stimulating hormone level, and primary hyperparathyroidism, suspected because of otherwise unexplained hypercalcemia. (See "Cardiovascular effects of hypothyroidism" and "Cardiovascular effects of hyperthyroidism".)

TREATMENT

Benefits of blood pressure control In clinical trials, antihypertensive therapy compared to placebo has been associated with significant 20 to 25 percent reduction in the incidence of major cardiovascular events (eg, stroke, heart failure, and myocardial infarction) [61].

However, percent reduction does not tell the absolute benefit which is dependent upon the incidence of cardiovascular complications. In the aggregate, antihypertensive therapy for four to five years prevented a coronary event in 0.7 percent of patients and a cerebrovascular event in 1.3 percent for a total benefit of approximately 2 percent; this included a reduction in cardiovascular mortality of 0.8 percent (figure 7) [62]. Thus, 100 patients must be treated for four to five years to prevent a complication in two. It is presumed that these statistics underestimate the true benefit of treating mild hypertension, since the trials were of too short duration (five to seven years) to determine efficacy in a longer term disease. (See "Hypertension: Who should be treated?".)

Equal if not greater benefits have been shown with the treatment of elderly hypertensive patients (over age 65), most of whom have isolated systolic hypertension. Because the elderly start at such higher overall cardiovascular risk, short term reductions in their hypertension provide apparently greater benefits than that observed in younger patients. (See "Treatment of hypertension in the elderly, particularly isolated systolic hypertension".)

Who should be treated? Using the above definitions from JNC 7, the following general approach can be used to determine which patients with hypertension require antihypertensive therapy [7,63,64]. This approach largely includes the recommendations of JNC 7 for risk stratification and treatment and assumes accurate measurement of the blood pressure (table 7) [7]. A review of the potential errors involved with the procedure is available elsewhere. (See "Technique of blood pressure measurement in the diagnosis of hypertension".)

All patients should undergo appropriate nonpharmacologic modification (table 8). (See 'Nonpharmacologic therapy' below.)

(lifestyle)

The following decisions about antihypertensive medications are generally not made until there has been an adequate trial of nonpharmacologic therapy.

In the absence of end-organ damage, a patient should not be labeled as having hypertension unless the blood pressure is persistently elevated after three to six visits over a several month period. In one study, for example, there was a mean 15/7 reduction in blood pressure in untreated patients between the first and third visits to a new physician [49]. This difference has prognostic importance. The Medical Research Council Mild Hypertension Trial found a close correlation between cardiovascular risk and the systolic pressure measured three months after entry into the trial [65]. In contrast, a transient increase in systolic pressure at entry due to a white coat response was not associated with increased risk. During the initial evaluation period before a therapeutic decision is made, patients should also be encouraged to measure their blood pressure at home or work.Antihypertensive medications should generally be begun if the systolic pressure is persistently 140 mmHg and/or the diastolic pressure is persistently 90 mmHg in the office and at home despite attempted nonpharmacologic therapy [7,66,67]. Starting with two drugs may be considered in patients with a baseline blood pressure above 160/100 mmHg. This strategy may increase the likelihood that target blood pressures are achieved in a reasonable time period, but should be used cautiously in patients at increased risk for orthostatic hypotension (such as diabetics and the elderly). (See "Choice of therapy in essential hypertension: Recommendations".)

There is some evidence supporting a lower goal blood pressure in patients with atherosclerotic cardiovascular disease and patients with chronic kidney disease complicated by proteinuria. The supportive data are presented separately. (See "What is goal blood pressure in the treatment of hypertension?" and "Blood pressure management in patients with atherosclerotic cardiovascular disease", section on 'Goal blood pressure' and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease", section on 'Goal blood pressure'.)Patients with office hypertension, normal values at home, and no evidence of end-organ damage should undergo ambulatory blood pressure monitoring to see if they are truly hypertensive. (See "Ambulatory blood pressure monitoring and white coat hypertension in adults".)In a number of conditions (eg, atrial fibrillation, heart failure, post-myocardial infarction), certain antihypertensive drugs are given to improve survival or the underlying disease and other drugs are

contraindicated, independent of the blood pressure (table 9). (See "Indications and contraindications to the use of specific antihypertensive drugs".)

Nonpharmacologic therapy Treatment of hypertension generally begins with nonpharmacologic therapy (also called lifestyle modification), including moderate dietary salt restriction, weight reduction in obese patients, avoidance of excess alcohol intake, and regular aerobic exercise (table 8) [7,31,68].

Dietary salt restriction A low salt diet will usually lower high blood pressure and may prevent the onset of hypertension. In well-controlled randomized trials, the overall impact of moderate sodium reduction is a fall in blood pressure in hypertensive and normotensive individuals of 4.8/2.5 and 1.9/1.1 mmHg, respectively (figure 8) [69,70]. The recommendation is to reduce dietary intake from the usual 150 to 200 meq/day down to 100 meq/day (approximately 2.3 g of sodium or 6 g of salt [one gram of sodium equals 44 meq; one gram of sodium chloride contains 17 meq of sodium]) [7]. (See "Salt intake, salt restriction, and essential hypertension".)Weight loss Weight loss in obese individuals can lead to a significant fall in blood pressure. The decline in blood pressure induced by weight loss can occur in the absence of dietary sodium restriction [71], but even modest sodium restriction (a decline in intake of 20 to 40 meq/day) may produce an additive antihypertensive effect [72]. The weight loss-induced decline in BP generally ranges from 0.5 to 2 mmHg for every 1 kg of weight lost (figure 9) [73]. (See "Diet in the treatment and prevention of hypertension" and "Obesity and weight reduction in hypertension".)DASH diet The DASH diet consists of increased intake of fruits and vegetables and low-fat dairy products and can be combined with salt restriction. (See "Diet in the treatment and prevention of hypertension", section on 'DASH trial' and "Diet in the treatment and prevention of hypertension", section on 'Low sodium DASH'.)Exercise Long-term aerobic exercise regimens have in most studies had a beneficial effect on the systemic blood pressure. (See "Exercise in the treatment of hypertension".)Limited alcohol intake Women who consume two or more alcoholic beverages per day and men who have three or more drinks per day have a significantly increased incidence of hypertension compared to nondrinkers [24,74]; this effect is dose-related and is most prominent when intake exceeds five drinks per day [75]. On the other hand, decreasing alcohol intake in individuals who drink excessively significantly lowers blood pressure [76], and moderate alcohol use appears to reduce the risk of cardiovascular disease. (See "Cardiovascular benefits and risks of moderate alcohol consumption".)

The aggregate effect of moderate alcohol intake in patients with underlying hypertension is uncertain. An alcohol intake of one to two drinks per day appears to reduce cardiovascular risk, as it does in normotensive subjects [77]. (See "Cardiovascular benefits and risks of moderate alcohol consumption", section on 'Hypertension'.)Comprehensive intervention The benefits of comprehensive lifestyle modification with all five of the above modalities were examined in the PREMIER trial [78,79]. At 18 months, there was a lower prevalence of hypertension (22 versus 32 percent), and less use of antihypertensive medications (10 to 14 versus 19 percent), although the difference was not statistically significant. Similarly, among baseline hypertensive patients in the two intervention groups, there was a trend for a lower prevalence of hypertension (40 versus 63 percent), and less use of antihypertensive medications (20 versus 40 percent). (See "Diet in the treatment and prevention of hypertension", section on 'PREMIER trial'.)Patient education Patient education is an important nonpharmacologic intervention, and has been demonstrated to result in improved blood pressure control [80]. In addition to education of patients by their clinicians, blood pressure control may be improved when patients with hypertension hear the personal stories of their peers with hypertension. This novel approach was examined in 299 black patients with hypertension from a single inner-city clinic who were randomly assigned to watch one of two types of DVDs [81]. The intervention group received DVDs depicting peers from the clinic population who told their personal stories of dealing with and managing their blood pressure; the control group received DVDs containing a series of nonspecific health tips. After six months, those who watched the DVDs containing patient stories had a significantly greater 6.4 mmHg reduction in systolic blood pressure. Other Other nonpharmacologic therapies that may be beneficial include adequate potassium intake and cessation of smoking:

Adequate potassium intake may contribute to the control of hypertension [82]. However, this must be implemented with caution in patients at risk for hyperkalemia, such as those with chronic kidney disease or hypoaldosteronism. (See "Potassium and hypertension".)Although smoking itself does not appear to cause persistent hypertension, it markedly increases the cardiovascular risk in hypertensive patients. (See "Smoking and hypertension".)

Drug treatment

General efficacy The 2007 American Heart Association statement on the treatment of blood pressure in ischemic heart disease, the 2007 European Society of Hypertension/European Society of Cardiology guidelines on the management of hypertension, and meta-analyses from 2008 and 2009 concluded that the amount of blood pressure reduction is the major determinant of reduction in cardiovascular risk in patients with hypertension, not the choice of antihypertensive drug [61,66,67,83]. Some patients have an indication for a specific drug or drugs that is unrelated to essential hypertension, which will influence the choice of therapy (table 9). (See "Indications and contraindications to the use of specific antihypertensive drugs".)

Initial monotherapy in uncomplicated hypertension In the absence of a specific indication, there are three main classes of drugs that are used for initial monotherapy: thiazide diuretics, long-acting calcium channel blockers (most often a dihydropyridine), and ACE inhibitors or angiotensin II receptor blockers. It is the attained blood pressure, not the specific drug(s) used, that is the primary determinant of outcome. Beta blockers are not commonly used for initial monotherapy in the absence of a specific indication, since they may have an adverse effect on some cardiovascular outcomes, particularly in older patients. (See "Choice of therapy in essential hypertension: Recommendations".)

Combination therapy Single agent therapy does not control the blood pressure in some patients at diagnosis (particularly those more than 20/10 mmHg above goal) and, over time, in an increasing proportion of patients who were initially controlled with monotherapy (eg, approximately 40 percent at five years in the ALLHAT trial compared to approximately 30 percent at one year) [84]. (See "Choice of therapy in essential hypertension: Recommendations", section on 'Combination therapy'.)

Goal blood pressure The goal blood pressures presented below refer to the levels at which more intensive antihypertensive therapy to produce a further reduction in BP is not recommended. These goals are in keeping with the JNC 7 and assume that the patient is at average risk (eg, uncomplicated hypertension) [7].

The goal of antihypertensive therapy in patients with uncomplicated combined systolic and diastolic hypertension is a blood pressure of below 140/90 mmHg; treatment goals are determined by the higher BP category.

Similar goals have been recommended for nondiabetic patients with coronary heart disease. (See "What is goal blood pressure in the treatment of hypertension?" and "Secondary prevention of cardiovascular disease: Risk factor reduction", section on 'Goal blood pressure'.)

A number of clinical trials suggest possible benefit from a lower blood pressure goal in two settings: atherosclerotic cardiovascular disease and proteinuric chronic kidney disease. These issues are discussed elsewhere. (See "Blood pressure management in patients with atherosclerotic cardiovascular disease", section on 'Goal blood pressure' and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease", section on 'Goal blood pressure'.)

For the rapidly growing population of hypertensive individuals over age 65 with isolated systolic hypertension (eg, a diastolic blood pressure below 90 mmHg), caution is needed not to reduce the diastolic blood pressure to less 65 mmHg to attain a goal systolic pressure less than 140 mmHg, since such low diastolic pressures have been associated with an increased risk of stroke [64,85]. Thus, the level of systolic blood pressure that is reached with two or three antihypertensive agents (even if greater than 140 mmHg) may be a more reasonable interim goal in such individuals [31]. (See "Treatment of hypertension in the elderly, particularly isolated systolic hypertension" and "Secondary prevention of stroke: Risk factor reduction".)

These recommendations assume that the blood pressure is being gradually reduced, since acutely lowering blood pressure in patients with severe underlying hypertension can clearly lead to deleterious cerebrovascular and coronary events. (See "Management of severe asymptomatic hypertension (hypertensive urgencies)".)

Resistant hypertension Some patients have hypertension that is seemingly resistant to conventional medical therapy. Resistance is usually defined as a diastolic blood pressure (BP) above 95 to 100 mmHg despite intake of three or more antihypertensive medications.

One or more of the following problems usually contributes to the inability to adequately lower the blood pressure in this setting [7,86]:

Suboptimal therapyExtracellular volume expansionPoor compliance with medical or dietary therapySecondary hypertensionOffice or "white coat" hypertensionPseudohypertensionIngestion of substances that can elevate the blood pressure

(See "Definition, risk factors, and evaluation of resistant hypertension" and "Treatment of resistant hypertension".)

Discontinuing therapy Some patients with mild hypertension are well controlled, often on a single medication. After a period of years, the question arises as to whether antihypertensive therapy can be gradually diminished or even discontinued.

Several studies that have evaluated the effect of discontinuation of treatment have shown that between 5 and 55 percent of patients remain normotensive for at least one to two years [87]; a larger fraction of patients do well with a decrease in the number and/or dosage of medications taken [88,89].

Gradual discontinuation of therapy is most likely to be effective in patients with mild initial hypertension who are well controlled on a single drug and who can often be maintained on nonpharmacologic therapy such as weight loss and sodium restriction [87]. More gradual tapering of drug dosage is indicated in well-controlled patients taking multiple drugs [90]. (See "Can therapy be discontinued in well-controlled hypertension?".)

Abrupt cessation of therapy with a short-acting beta-blocker (such as propranolol) or the short-acting alpha-2-agonist clonidine can lead to a potentially fatal withdrawal syndrome. Gradual discontinuation of these agents over a period of weeks (including switching to longer-acting drugs of the same class such as atenolol or methyldopa) should prevent this problem. (See "Withdrawal syndromes with antihypertensive therapy".)

INFORMATION FOR PATIENTS Educational materials on this topic are available for patients. (See "Patient information: High blood pressure in adults" and "Patient information: High blood pressure treatment in adults" and "Patient information: High blood pressure, diet, and weight".)

We encourage you to print or e-mail these topic reviews, or to refer patients to our public web site, www.uptodate.com/patients, which includes these and other topics.

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