High blood pressure (HBP), or hypertension, is the most common problem addressed in ambulatory care (see Table 1.3). The ambulatory management of this condition is a longitudinal process requiring skill in enlisting the patient's cooperation and in selecting, monitoring, and adjusting treatment. Hypertension has been studied extensively by epidemiologists and clinicians. The recommended care of patients with hypertension is based on findings from numerous clinical and epidemiologic studies.
Epidemiology
Prevalence and Incidence
Prevalence
As shown in data from the 1999–2000 National Health and Nutritional Examination Survey (NHANES) (Fig. 67.1), the prevalence of hypertension increases with age in all gender and race/ethnic subgroups. In this survey, hypertension was defined as a mean systolic blood pressure (SBP) on a single occasion of ≥140 mm Hg, a mean diastolic blood pressure (DBP) of ≥90 mm Hg, or current treatment for hypertension with prescribed medication.
The prevalence of isolated systolic hypertension, seen mainly in the elderly, is approximately 6% in persons 60 to 69 years old and approximately 18% in persons 80 years and older (1).
Of individuals with hypertension, approximately 75% have stage 1 hypertension, which is defined as SBP 140 to 159 mm Hg or DBP 90 to 99 mm Hg (see Clinical Classification). Therefore, in a typical practice, decisions must be made most often for patients with stage 1 hypertension.
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FIGURE 67.1. Hypertension prevalence by age and race/ethnicity in men and women. (From Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA 2003;290:199 , with permission.) |
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Incidence
An estimated 1.8 million adults in the United States develop hypertension each year (2). An analysis using data from the Framingham Study estimated the 4-year rates of new hypertension in persons with optimal, normal, or high–normal blood pressure (Table 67.1) (3). Four-year incidence varied from 5.3% for persons 35 to 64 years old to 49.5% for those 65 to 94 years old. Increasing age and increasing weight were major predictors of incident hypertension.
Secular Trends in Prevalence, Awareness, Treatment, and Control of High Blood Pressure
The Surgeon General of the United States has named a goal of controlled HBP (<140/<90) for 50% of all persons with hypertension by the year 2010 (4). The record of progress toward that goal has been reported by NHANES for 1988–2002 (5). There has been a gradual increase in the prevalence of HBP and in the proportion of hypertensive persons aware that they have HBP, persons on treatment, and persons with controlled HBP. Table 67.2 summarizes these data for the two major subgroups in the United States: whites and non-Hispanic blacks. Multivariate analysis of the data from 1999–2002 showed that three factors independently predict uncontrolled HBP: being non-Hispanic black, being female, and not completing high school (5).
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TABLE 67.1 Adjusted 4-Year Incidence of Hypertension According to Baseline BP Category (Framingham Study) |
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Primary Prevention
Many subgroups in the population have an increased risk for development of sustained hypertension, including people who are overweight or sedentary, have high–normal BPs, consume excessive amounts of salt or alcohol, are African American, or have a family history of hypertension. Clinical trials have shown that weight reduction, regular exercise (aerobic and low intensity), reduced salt or alcohol intake, and a diet rich in vegetables and fruits but low in animal fat can prevent the development of hypertension and reduce BP (6–8). Other lifestyle changes evaluated in clinical trials have been found to have inconsistent or unproved efficacy in the prevention or treatment of hypertension. These include stress reduction and increased intake of potassium, fish oil, magnesium, and dietary fiber (7).
The widespread adoption of measures known to help prevent hypertension and of other measures known to protect cardiovascular health (e.g., not smoking, control of
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hypercholesterolemia) would reduce significantly the cardiovascular morbidity in the population. Health care professionals can help by recommending these measures to all patients and especially to those who have a family history of hypertension or have prehypertension (see Clinical Classification). A later section of this chapter describes practical details regarding nonpharmacologic measures for controlling or preventing hypertension.
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TABLE 67.2 NHANES Data Showing Secular Trends in Prevalence of HBP, Awareness of HBP, Treatment of HBP, and Control of HBP |
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Risks and Risk Reduction
Risks Attending Untreated Hypertension
Risk Related to Blood Pressure
For the patient and the practitioner, the single most important concept in approaching hypertension is that HBP increases the risk of symptomatic vascular disease (stroke, coronary artery disease, congestive heart failure [CHF], renal insufficiency) during the patient's entire life. This concept was elucidated best by the longitudinal observations on subjects in the Framingham study, which used 140/90 mm Hg as the threshold BP for hypertension (9). A number of other longitudinal studies corroborated the major findings of Framingham study (10). Additional analyses of existing data have shown the following:
Coexisting Cardiovascular Risk Factors
Many subjects with hypertension have one or more other treatable risk factors. These risk factors may affect a patient's prognosis far more than does hypertension. This is illustrated by the fact that two hypothetical patients with the following risk-factor profiles have similar long-term cardiovascular risks:
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Age |
Cigarettes |
Total |
Diastolic |
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50 |
0 |
180 mg/day |
125 mm Hg |
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50 |
30 |
220 mg/dL |
95 mm Hg |
Baseline Target Organ Damage
In addition to BP level, age, gender, and other risk factors, coexisting cardiovascular abnormalities (target organ damage) increase the degree of risk. This is illustrated in Table 67.3, which summarizes findings in subgroups of
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placebo-treated subjects from the Veterans Administration Therapeutic Trial.
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TABLE 67.3 Placebo-Treated Subjects, Veterans Administration Trial: Impact of Blood Pressure and Cardiovascular Abnormalities on Attack Rate |
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Risk Reduction by Treatment of Hypertension
A number of placebo-controlled clinical trials completed between 1970 and 1985 demonstrated that pharmacologic treatment reduces risks inmiddle-aged adults with diastolic hypertension (13–18). In addition, placebo-controlled clinical trials reported between 1985 and 1997 showed convincingly that pharmacologic treatment also reduces morbidity and mortality in older persons with HBP, including those with isolated systolic hypertension (19, 20, 21, 22, 23).
A network meta-analysis (24) and a standard meta-analysis (25), both published in 2003, assessed the findings of all available placebo-controlled trials and head-to-head drug comparisons. Both of the very large data sets showed that the health benefits of first-line treatment of HBP with low-dose diuretics are equal to or exceed the benefits from first-line treatment with all other classes of antihypertensive drugs. Larger reductions in blood pressure produced larger reductions in risks (25). The health benefits measured were reduction in coronary heart disease, stroke, CHF, major cardiovascular events, cardiovascular disease mortality, and all-cause mortality. The conclusions from these meta-analyses concurred with the findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (26), the very large head-to-head trial of the low-dose diuretic chlorthalidone with the calcium antagonist amlodipine and the angiotensin-converting enzyme (ACE) inhibitor lisinopril.
More than half of subjects in the treatment arms of most clinical trials received second-line drugs to achieve treatment goals, and considerable uncertainty exists regarding the optimal regimen for individual patients (see Treatment of Hypertension). In addition, until completion of the placebo-controlled Hypertension in the Very Elderly Trial (HYVET), uncertainty will exist about the health impact of antihypertensive treatment of patients older than 80 years.
Relative Risk Reduction
Aggregate analysis of clinical trial results has shown that antihypertensive treatment is associated with a relative risk reduction of 35% to 40% in stroke incidence, 20% to 25% in myocardial infarction (MI), and >50% in CHF (27). Treatment also prevents the onset or worsening of renal insufficiency, although population-based data suggest that control of HBP among African Americans may not protect renal function as effectively as in whites (2).
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FIGURE 67.2. Matrix developed to help with decisions regarding the active treatment of hypertension based on blood pressure and other risk factors. Note that in 2006, diabetes would be regarded as a major risk factor. Shading patterns shown in boxes represent absolute risks during 10 years. (Adapted from Jackson R, Barham P, Bills J, et al. Management of raised blood pressure in New Zealand: a discussion document. BMJ 1993;307:107 , with permission.) |
Gender
Meta-analysis of data from seven clinical trials that included both men and women showed that the relative risk reduction attributable to treatment was similar for both genders (28).
Absolute Risk and Risk Reduction
As noted previously, the absolute risk of cardiovascular disease is much higher among patients with hypertension who are elderly and those with target organ damage or multiple risk factors. Figure 67.2 shows the combined impact of these patient characteristics on absolute risk. The absolute benefit of treatment also is higher when patients with these characteristics are treated. Assuming a relative
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risk reduction of approximately one third for combined cardiovascular events and using the information summarized in Fig. 67.2, it can be seen that the absolute benefits of treatment may differ greatly for patients with similar BPs. For example:
For the following reasons, the findings from randomized controlled trials may underestimate the potential benefits of BP lowering:
Gender
Absolute risk reduction differs by type of cardiovascular event in men and women (28). In women, the major benefit is reduction in stroke. This benefit is especially pronounced in African American women, a finding that is partly explained by the greater absolute risk of stroke in these women (29). In men, treatment prevents as many coronary disease events as cerebrovascular events. This difference is thought to reflect the greater absolute risk of coronary events in untreated men.
Nonpharmacologic Measures
In clinical trials, nonpharmacologic measures (weight reduction; salt restriction; physical activity; high-vegetable, low-fat Dietary Approaches to Stop Hypertension [DASH] diet; reduced alcohol consumption) have been shown to reduce BP in hypertensive subjects (30). The approximate impact of each of these measures on blood pressure is summarized later (see Treatment of Hypertension). Although no trial of nonpharmacologic measures has been designed to detect their impact on cardiovascular morbidity and mortality, they likely are efficacious (8,30).
Pathophysiology and Natural History of Essential Hypertension
An estimated 95% to 99% of hypertensive patients do not have an identifiable cause for their hypertension. Their problem has been designated essential hypertension, a condition whose antecedents probably are a mix of genetic and environmental factors. Several abnormal physiologic characteristics that have been demonstrated in essential hypertension provide a conceptual basis for understanding the clinical consequences of hypertension and the mechanisms of action of antihypertensive drugs.
The patient with established essential hypertension has an increase in peripheral arterial resistance (Fig. 67.3). This condition is hypothesized to be the final consequence of either or both of two mechanisms: inappropriate renal retention of salt and water or increased endogenous pressor activity. Serial studies on small numbers of subjects have suggested that a stage of increased cardiac output may precede the stage of increased peripheral resistance. This earlier stage may be manifested in some young hypertensives as a high resting heart rate. In general, however, evaluation of the individual patient with essential hypertension does not yield much information about the dominant mechanism contributing to that patient's HBP.
Figure 67.3 shows the major complications of untreated HBP. These complications can be seen as the clinical manifestations of two pathophysiologic processes that are
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operating during many silent years of increased peripheral resistance: trauma to the vessels in the arterial circulation, leading to accelerated atherosclerosis in large vessels and to obliterative changes (Fig. 67.4) or thinning and rupture in small vessels, and increase in the workload of the heart, leading to CHF or angina pectoris.
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FIGURE 67.3. Representation of the natural history of untreated essential hypertension. (Modified from Kaplan N. Clinical hypertension. 6th ed. Baltimore: Williams & Wilkins, 1994;110 , with permission.) |
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FIGURE 67.4. Hyperplastic arteriosclerosis in renal tissue from a patient with essential hypertension. |
Measuring the Blood Pressure
Standard Practices
In response to Environmental Protection Agency recommendations, mercury manometers were to be eliminated by the year 2005, and BP measurement was to be accomplished either by auscultation, using aneroid manometry, or by automated electronic manometry. It has been recommended that auscultatory BP measurement be used to diagnose HBP and to verify abnormal BPs obtained electronically (31). A number of factors can affect the level of BP measured by a sphygmomanometer (32). To ensure the validity of the measured BP and to ensure that comparable information is obtained in repeated observations, the following standard practices should be followed at each visit (33,34):
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FIGURE 67.5. Right: Bladder width is small for arm, and full cuff pressure is never applied to artery. An erroneously high pressure results. Left: Bladder width is adequate for arm, and full cuff pressure is applied to brachial artery. (Reproduced with permission from the American Heart Association.) |
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Special Situations
Atrial Fibrillation
In patients with atrial fibrillation, whose beat-to-beat stroke volume and BP differ because of varying intervals between ventricular beats, the average of several SBP and DBP values should be recorded.
Pseudohypertension
When the wall of the brachial artery is rigid from calcification, the cuff pressure needed to compress the artery may greatly exceed the intra-arterial pressure, and a very high cuff pressure may be assumed, incorrectly, to be the actual BP. This condition, which has been called pseudohypertension, can be tentatively diagnosed by the finding that the (presumably calcified) radial artery does not collapse when the pulse is obliterated during cuff inflation. However, substantial intraobserver and interobserver variability exist in the interpretation of this maneuver (35). Definitive diagnosis of pseudohypertension requires arterial catheterization to directly measure the BP, which then is compared with the cuff pressure. It is important to consider pseudohypertension in the evaluation of patients—usually older patients with widespread atherosclerosis—who describe hypotensive symptoms despite apparently normal or high cuff pressures. A practical approach to management when pseudohypertension is suspected is described later (see Orthostatic Symptoms).
White-Coat Hypertension and White-Coat Effect
Among patients with stage 1 hypertension in the physician's office (see Clinical Classification), ≥20% have normal average daytime BPs if measured at home (36). This pattern is referred to as white-coat hypertension. Many patients with apparent white-coat hypertension have normal BPs when the measurement is repeated after the patient has rested quietly in the office. The white-coat effect refers to an average office-measured BP that is higher than the average daytime BP. Up to 40% of patients have a white-coat effect of ≥20/10 mm Hg (37). This effect is largest in patients with stage 2 HBP. Although cohort studies have indicated that patients with white-coat hypertension do not have excess cardiovascular risks, cross-sectional studies have found increased risk of left ventricular hypertrophy (LVH) in such patients (38), and evidence indicates that some develop sustained HBP (i.e., elevated home and office pressures) (37). Management decisions for patients who demonstrate these patterns are discussed later (see Treatment of Hypertension: General Considerations).
Self-Measurement and Ambulatory Blood Pressure Monitoring
Self-measurement by the patient or someone else and ambulatory blood pressure monitoring (ABPM) are two ways in which the snapshot type of information obtained at office visits can be expanded. Critical assessment of experience with these two methods yields the following conclusions (37,39):
Home Self-Measurement Devices
Many devices are available, ranging from inexpensive units that require auscultation with a stethoscope to more expensive electronic units that display the BP digitally. These
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devices are reviewed periodically to help consumers select among them. Finger monitors are not accurate and should not be recommended (40). When a patient decides to measure BPs at home, it is essential to confirm at periodic office visits that the patient's technique is satisfactory and that similar pressures are obtained with the home monitoring device and the office unit.
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TABLE 67.4 Situations in Which Self-Measurement Devices or Automated Noninvasive Ambulatory Blood Pressure Monitoring Devices May Be Useful for Clinical Decisions |
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Ambulatory Blood Pressure Monitoring Devices
These are portable devices that measure cuff pressures frequently over a 24-hour period. Patients are instructed to hold the arm still during automatic cuff inflation and to keep a diary and report dizziness, headache, or other symptoms of interest. Reports display average daytime, nighttime, and 24-hour pressures; frequencies and temporal distribution of selected pressures; and the BP load (e.g., percentage of waking pressures >140/90 mm Hg or sleeping pressures >120/80 mm Hg). The American Society of Hypertension has selected as abnormal an overall average 24-hour SBP >135 mm Hg and DBP >85 mm Hg and has selected the following as “probable abnormal” awake or asleep BPs(39):
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Average Systolic BP |
Average Diastolic BP |
BP Load |
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Awake |
>140 |
>90 |
>30% above 140/90 |
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Asleep |
>125 |
>80 |
>30% above 120/80 |
Because there are no standard recommendations for the use of these types of aggregate data in decision making, ABPM is mainly useful in selected patients (Table 67.5). The charge for 24-hour monitoring ranges from $150 to $450.
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TABLE 67.5 Classification of Blood Pressure for Adults Aged 18 Years or Older (JNC-7) |
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Clinical trials comparing treatment decisions based on average office BPs to decisions based on average home BPs measured by ABPM (41) or self-monitoring (42) concluded that the latter decisions led to less intensive BP treatment and a better sense of well-being (ABPM) but did not reduce the overall cost of treatment.
Blood Pressure Variability
A number of psychological, biologic, and pharmacologic factors cause BP variability. These factors should be considered when determining the meaning of the measured BP in an individual patient and when following the standard approach to measuring the BP (described earlier).
Normal Patterns
In a 24-hour period, the average person's resting BP fluctuates (SBP 20–40 mm Hg; DBP 10–20 mm Hg) (37). The lowest BPs occur during sleep. These ranges occur in patients with normal BP and in hypertensive patients who are or are not taking antihypertensive drugs. During ordinary activities such as walking, talking on the telephone, attending a meeting, dressing, eating, and working at a desk, slight increases in both SBP (5–20 mm Hg) and DBP (5–10 mm Hg) may occur in untreated subjects. During and after vigorous exercise, SBP may rise as much as 60 mm Hg, and there may be a modest decrease in DBP.
Common causes of transient or short-term high BP are white-coat hypertension (see White-Coat Hypertension and White-Coat Effect); mental stress, both intellectual and psychological; self-medication with excessive amounts of nonprescription sympathomimetic decongestants; nicotine, caffeine, or alcohol use shortly before BP measurement; and alcohol or sedative–hypnotic withdrawal.
Common causes of transient or short-term decrease in a patient's BP are volume contraction during an illness that causes fluid losses or reduced intake; bed rest for several days; hospitalization with or without strict bed rest; and the postprandial state in elderly persons.
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Evaluation of the Hypertensive Patient
Clinical Classification
In its seventh report (JNC-7) issued in 2003, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure revised the national standards for clinical classification of adult patients with high BP (30). The JNC-7 classification (Table 67.5) differs in two ways from the classification published in 1997:
The JNC-7 recommendations for patients with prehypertension and stage 1 and 2 hypertension are discussed later (see Treatment of Hypertension).
The classification of patients should use values obtained by standard methods for BP measurement (detailed earlier) on two or more occasions after the initial detection of HBP. This approach is important because being labeled hypertensive can result in increased sick days, increased life insurance premiums, or employment restrictions for the patient (43). A variable characteristic such as BP will regress with repeated measurements to the person's usual level, which may be normal in some subjects whose initial BP is high. Two research findings underline the latter point. First, a sizable proportion of people who are found to be hypertensive at an initial screening visit do not have HBP at follow-up visits; and second, SBP and DBP predictably decrease when daily measurements are made over several weeks (44).
Clinical Presentation
Patients with HBP may present to physicians in several ways.
History of Hypertension
On their initial visit, many patients state that they have hypertension. For some of these patients, recorded BPs from other sources are available. Some are taking antihypertensive drugs, presumably for sustained hypertension. Based on this information, BP recordings made at the initial and followup visits, and clinical and laboratory data regarding target organs, the patient's hypertension usually can be classified with confidence.
High Initial Blood Pressure
In practice, patients found to have an elevated SBP or DBP should have their BP remeasured one or more times before being classified. Even very high initial BPs, especially when they are measured in emergency departments, may represent transient elevations.
Patients with transient high BPs or with BPs in the prehypertension range are at increased risk for development of sustained hypertension. They should be informed about this increased risk and advised to avoid excess salt and to follow other practices that reduce the likelihood of developing hypertension (see Primary Prevention).
Options for evaluating patients with suspected white-coat hypertension were described earlier (see Ambulatory Monitoring and Home Measurement).
Chronic Hypertension
Hypertension is chronic if the average SBP is ≥140 mm Hg or the average DBP is ≥90 mm Hg at multiple office visits. At a patient's first visit, evidence of chronic hypertension may be seen (e.g., preexisting electrocardiogram [ECG] shows LVH or, rarely, fundal hemorrhages or exudates are found on physical examination). Eyegrounds findings indicative of arteriolosclerosis (grade 1: narrowing of arteriolar lumen; grade 2: arteriovenous crossing changes) are less specific indicators of chronic hypertension and should not be substituted for BP measurements on multiple occasions. Most patients with chronic hypertension are in JNC stage 1 (Table 67.5) when they first present to the physician.
The prognosis for untreated chronic hypertension and the benefits of treatment were summarized earlier (see Risks and Risk Reduction).
Accelerated Hypertension
Hypertension is accelerated when there is clinical evidence of severe arteriolosclerosis, meaning either grade 3 or 4 hypertensive retinopathy (grade 3: hemorrhages or fresh exudates; grade 4: papilledema) or renal insufficiency for which there is no apparent cause except the hypertension. Before they develop evidence of accelerated hypertension, most of these patients have had very high BPs (i.e., JNC stage 2) for several years.
The prognosis in untreated accelerated hypertension is poor: approximately 95% of these patients die of cardiac, renal, or central nervous system complications within 5 years after initial presentation. Control of BP and use of dialysis (for those with end-stage renal disease) have dramatically improved the prognosis in these individuals.
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Hypertensive Emergency
A hypertensive emergency exists when elevation of the BP will predictably contribute to a catastrophic outcome within hours or days. Patients with one of two types of hypertensive emergency—hypertensive encephalopathy and dissecting aneurysm of the thoracic aorta—may present initially in an office setting. If either of these diagnoses is suspected, the patient should be transported immediately to a hospital emergency department for evaluation and treatment.
Hypertensive encephalopathy is the result of cerebral edema that develops gradually over 24 hours or longer in a patient with severe hypertension. In such a patient, global cerebral symptoms, such as headache, confusion, and irritability, usually have been present and progressive for hours or days. Papilledema may be present. Hypertensive encephalopathy should not be diagnosed until intracerebral mass or hemorrhage, which may also manifest with hypertension, has been excluded by computed tomographic (CT) scanning. Diffuse or focal white matter edema in the supratentorial compartment usually is seen on the scan (45).
Thoracic aortic dissection results from an expanding hematoma in the wall of the aorta. The patient with acute dissection usually has a history of known hypertension and presents with a story of sudden anterior chest pain or tearing pain in the back. Two noninvasive imaging modalities—CT and magnetic resonance imaging—are very sensitive and specific diagnostic tests for dissection. By definition, a proximal dissection involves the aorta between the aortic root and the left subclavian artery (palpated pulse intensity and BP levels may be decreased in either arm; there may be a murmur of aortic regurgitation); a distal dissection involves only that part of the aorta distal to the left subclavian artery.
The prognosis in encephalopathy or aortic dissection—if diagnosed before irreversible damage has occurred—depends on prompt hospitalization for antihypertension treatment and, for some patients with dissection, surgery. Despite the overwhelming threat to life without treatment, good outcomes can be achieved with appropriate intervention.
Hypertensive Urgency
The term hypertensive urgency is often used to categorize patients with severe hypertension (e.g., SBP ≥210 mm Hg or DBP ≥120 mm Hg) who may have evidence of target organ disease but are asymptomatic. Some authors advocate lowering the BP within a few hours using doses of oral medications with prompt onset of action. There is no evidence for benefit (but some evidence for harm, e.g., stroke, MI) in asymptomatic patients whose BP is treated hourly until the BP is lowered (37). As discussed later (see Treatment of Hypertension), with currently available drugs it usually is possible, and more appropriate, to control severe hypertension within a few days.
Baseline Evaluation: Overview
The baseline evaluation of patients with sustained hypertension has five objectives:
Table 67.6 lists by source the information that is recommended to accomplish these five objectives at baseline. These recommendations match the recommendations of the 2003 JNC-7 report (30).
Target Organ Status
At baseline evaluation, most patients with sustained hypertension, including those with accelerated hypertension, have no symptoms attributable to their hypertension. In the past, it was thought that headache, tinnitus, epistaxis, and dizziness were common symptoms of hypertension, but community-based studies have demonstrated that these symptoms are not more prevalent in hypertensive than in normotensive subjects (46).
The major morbidity of HBP is the result of cardiac, cerebral, and renal disease. Baseline information about the target organs affected by HBP often helps in making decisions about followup care (see Recommendations Regarding Initial Treatment).
Heart
A history of symptoms caused by CHF or coronary artery disease occasionally is obtained at the baseline evaluation. Auscultation of the heart commonly reveals accentuation of the aortic second sound and a systolic ejection murmur. Infrequent auscultatory findings include a systolic ejection sound at the base of the heart, paradoxical splitting of the second heart sound, or a short, high-pitched diastolic murmur at the base.
Evidence of LVH may be found at baseline evaluation, either on physical examination (left ventricular heave or fourth heart sound) or on the ECG. Chapter 66 describes the ECG criteria for LVH. The sensitivity of the ECG for detecting LVH is <50%, using the echocardiogram as the gold standard.
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TABLE 67.6 Recommended Baseline Evaluation of the Patient with Sustained Hypertension |
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Because of its cost, an echocardiogram to check for LVH should be considered only in situations where it may affect a treatment decision—such as a patient with stage 1 HBP, no other cardiovascular risk factors, and physical examination findings suggesting significant HBP (discussed earlier), or a patient with refractory stage 2 HBP, no other end-organ signs of HBP, and evidence suggesting white-coat hypertension (see earlier discussion).
The functional abnormalities associated with LVH have been studied extensively. In some asymptomatic patients, the ejection fraction (measured by echocardiogram) is normal during rest but shows a subnormal increase during exercise. In hypertensive patients with symptoms of left ventricular failure, echocardiographic studies have revealed that some have global left ventricular dysfunction; some have functional subaortic stenosis; some have a hyperkinetic left ventricle with a normal or high ejection fraction and diminished relaxation during diastole; and some in the latter group (usually older patients) have cavity obliteration during diastole (47). Because appropriate drug therapy for patients in these groups differs (see later sections), an echocardiogram is recommended for hypertensive patients with signs and symptoms of heart failure to ensure that the drugs selected for them likely will improve rather than worsen the heart failure.
Most symptoms of coronary artery disease in hypertensive patients are related to occlusive disease of the coronary arteries. Some hypertensive patients who describe exertional angina but have normal coronary arteriograms may have ischemia caused by increased resistance of the microvasculature of the myocardium (48).
Kidney
Simple tests of kidney status (urinalysis and serum creatinine concentration) are normal in the majority of hypertensive patients at baseline. In patients with a high baseline BP, the finding of an elevated creatinine concentration, proteinuria (sometimes >1 g/24 hours), or microscopic hematuria may signify accelerated hypertension. In such patients, other forms of renal or urologic disease should be excluded before these findings are attributed to hypertension. Microalbuminuria (albumin/creatinine ratio >30 mg/g in a spot urine sample) may occur, especially in patients with stage 2 HBP. Its prognostic significance in patients without diabetes is unknown, and checking for it is recommended as optional as part of the baseline evaluation (30).
Central Nervous System
A history of stroke or transient ischemic attacks, an asymptomatic carotid bruit, or neurologic findings of a remote stroke may be present at baseline evaluation, but most patients do not have evidence of cerebrovascular disease when they are first evaluated.
Eye
Ophthalmic symptoms attributable to HBP (decreased acuity from retinal hemorrhages or retinal detachment) are uncommon. Examination of the retina offers direct inspection of blood vessels affected by hypertension. Most patients with chronic hypertension have evidence of arteriolosclerosis (grade 1 or 2 hypertensive retinopathy), but these findings have little practical value because they are not specific for hypertension, and there is significant interobserver and intraobserver variability in detecting them. Grade 3 retinopathy (hemorrhages or exudates) should be sought in patients with stage 2 HBP; these changes are specific for accelerated hypertension.
Evaluation for Secondary Hypertension
Information obtained at baseline evaluation or during followup identifies those patients who may have hypertension secondary to a reversible cause. Because surgically curable causes of HBP are uncommon, only highly selected patients should undergo the costly evaluations needed to diagnose these problems.
Chronic Alcoholism
In some individuals, heavy, chronic alcohol use causes sustained hypertension. For patients found to have both HBP and alcoholism at baseline evaluation, BP control should be attempted initially through detoxification and treatment of the alcoholism (see Chapter 28). The BP becomes normal in those with alcohol-induced hypertension approximately 1 week after discontinuation of alcohol.
Concurrent Use of a Medication that Can Cause High Blood Pressure
This cause of HBP should be considered in any patient who is concurrently using one of the medications that occasionally cause BP elevation (see list in footnote to Table 67.6). Although there is a detectable increase in the BP in most women who take oral contraceptives, the BP usually remains within the normal range with preparations that contain <50 µg estrogen, the amount contained in currently prescribed products (see Chapter 100 for practical considerations related to oral contraceptives). Estrogen in the doses used for postmenopausal hormone replacement therapy, approximately one sixth the amount in oral contraceptives, usually does not cause the BP to rise. In one longitudinal study, women receiving hormone replacement therapy actually had less aging-related increase in SBP than women not receiving it (49). Because
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estrogen occasionally causes hypertension, women who take it should have their BP monitored. Cyclosporine commonly causes HBP related to generalized arterial vasoconstriction. It responds well to calcium antagonists.
To confirm that a medication is the cause of a patient's hypertension, there should be evidence that the patient had a normal BP before use of the medication, and the patient's BP should become normal within a few weeks after the medication is discontinued (if this can be done safely).
Renovascular Hypertension
It is estimated that ≤0.5% of all hypertensive patients have renovascular hypertension (RVH), which is hypertension caused by unilateral stenosis of the main or of a segmental renal artery (50). In patients younger than age 40 years, the cause usually is fibromuscular hyperplasia of the renal artery. In older patients, atherosclerosis of the renal artery is the usual cause. There probably is no racial or sexual predominance in the population of patients with RVH (51). Smoking is more common in all groups of patients with RVH (52).
A number of clinical findings increase the probability that a patient with HBP has RVH:
If a patient has one or more of these findings and is a candidate for surgery, the following choices can be presented:
Screening Tests
The major noninvasive screening tests for RVH currently available comprise one functional test (captopril scintirenography) and three imaging techniques (duplex ultrasonography, magnetic resonance angiography [MRA], CT angiography). The sensitivity and specificity of these tests have been the focus of many studies comparing them to contrast arteriography as the gold standard. The performance characteristics vary widely because of differences in the criteria set for an abnormal test (56).
According to a 2001 meta-analysis of all published studies of these screening tests, CT angiography and gadolinium-enhanced MRA, using intra-arterial digital subtraction angiography as the gold standard, suggested that the sensitivity of these two tests was approximately 65% when stenosis ≥50% was used as the criterion for renal artery stenosis (57). In selecting a screening test for RVH, the following additional considerations may be helpful:
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patients, in whom atherosclerotic renal artery stenosis does not usually cause renin-dependent HBP.
Patient Experience
In captopril scintirenography, the patient receives an injection of tracer material and undergoes scintigraphic scanning twice: before and after receiving a standard dose of captopril. The two-stage procedure takes approximately 3 hours. If the patient currently is taking an ACE inhibitor or an angiotensin receptor blocker (ARB), it should be withheld on the day of the test. Other current antihypertensive medications can be continued. The test measures quantitative and qualitative changes in renal flow or filtration to detect asymmetry between the two kidneys. The test depends on the influence of captopril on the renal handling of radioactive tracers. In a kidney with significant renal artery stenosis, there is angiotensin II–mediated constriction of the postglomerular arterioles; captopril reduces or eliminates this construction, thus lowering the glomerular filtration rate and leading to a change in the renal handling of tracer materials. There may be a compensatory increase in glomerular filtration rate in the contralateral kidney, which magnifies the difference in handling of radiotracers.
The patient experience for the noninvasive imaging tests—MRA, CT angiography, and duplex ultrasonography—is similar to that described for neurologic evaluations in Chapter 86.
Anatomic Diagnosis
The patient in whom screening is positive for probable RVH—and some patients in whom the clinical suspicion of RVH is quite high— should be referred for intra-arterial renal angiography. Noninvasive study with intravenous digital subtraction angiography usually does not provide adequate detail to make a decision for intervention.
If arteriography shows unilateral renal artery stenosis and the patient has fibromuscular hyperplasia, percutaneous transluminal renal angioplasty (PTRA) is the revascularization treatment of choice. The cure rate is approximately 60% (55). Neither PTRA nor surgery has produced very satisfactory long-term results if renal artery stenosis caused by atherosclerosis is present; the cure rate is approximately 30% in these patients (55). Use of a stent after PTRA may improve long-term results.
Patient Experience: Renal Arteriography
The patient experience is similar to that described for cerebral arteriography in Chapter 86. For both studies, femoral artery catheterization is used, and, when a small catheter is used, the patient does not require hospital admission.
Kidney Disease
Kidney disease should be suspected as a possible cause of HBP in patients with a history of hematuria, stones, or recurrent pyelonephritis; in patients whose physical examination suggests large kidneys (e.g., from obstruction or polycystic disease) or a large bladder (after voiding); and in patients in whom the urinalysis suggests acute or chronic glomerulonephritis (i.e., proteinuria and/or many casts, especially red cell casts). A sonogram should be obtained in these patients. In patients with established chronic kidney disease (CKD) and small kidneys, it usually is not possible to determine whether the hypertension or the renal disease was the initial problem.
Mineralocorticoid Hypertension
The most common cause of mineralocorticoid hypertension (58) is hyperaldosteronism, and the most common clue to this cause is a baseline potassium level significantly below normal for which there is no explanation, such as diuretic use or gastrointestinal fluid loss. Hypertensive patients with this finding should be asked about excessive consumption of licorice, which contains glycyrrhetinic acid, a moiety with mineralocorticoidlike activity. Cases of hypertension that abated when the patient discontinued consuming large amounts of licorice are reported. Chapter 50 discusses in detail the ambulatory evaluation of a patient with suspected primary hyperaldosteronism.
Pheochromocytoma
Clues to the presence of pheochromocytoma (59,60) are a history of a hypermetabolic state (which may resemble hyperthyroidism) or of paroxysms of symptoms caused by increased sympathetic nervous system activity (tachycardia, palpitations, diaphoresis), with associated severe headaches. The absence of such symptom clusters virtually excludes the presence of pheochromocytoma. Paroxysms last from minutes to several hours, but usually <1 hour. Approximately 75% of patients with pheochromocytoma experience paroxysms at least once per week; the remaining patients experience either multiple attacks on most days or an attack only once every few months. These symptoms are especially important when there is no evidence for more common causes for them, such as hyperthyroidism (see Chapter 80), reactive hypoglycemia (see Chapter 81), migraine or cluster headaches (see Chapter 87), or panic attacks and other anxiety disorders (see Chapter 22).
Paroxysmal and persistent hypertension are equally common in patients with pheochromocytoma. Orthostatic hypotension, with or without symptoms, is present in some patients, presumably because of vasodilation caused by predominant β2 sympathetic activity.
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Additional findings that increase the prior probability of pheochromocytoma are a marked change in BP or heart rate in response to minor injury, parturition, or general anesthesia; a neurocutaneous syndrome (von Recklinghausen disease or von Hippel–Lindau syndrome); a blood relative with a pheochromocytoma; and type II multiple endocrine neoplasia (medullary carcinoma of the thyroid, parathyroid adenoma, or both, with symptoms suggesting pheochromocytoma).
Screening Tests
Because pheochromocytoma is uncommon, the best practice is to screen only those patients in whom clinical suspicion is high and to refer for consultation or more costly diagnostic evaluation only those patients with positive screening tests. Measurement of 24-hour urinary excretion of one or more of the three markers for increased pressor synthesis (catecholamines, metanephrines, and vanillylmandelic acid) is a screening test that has satisfactory performance characteristics. When used in a patient with an estimated 5% pretest probability of having a pheochromocytoma (e.g., a hypertensive patient with unexplained paroxysms of headache, tachycardia, and/or diaphoresis), excess excretion of any of the three markers would increase to 35% to 45% the probability (positive predictive value) that the patient has pheochromocytoma; normal results would increase from 95% to approximately 99% the probability (negative predictive value) that the patient does not have pheochromocytoma (61). An alternative test, measurement of the plasma level of normetanephrine or metanephrine, may have better performance characteristics but is not yet available for routine screening.
Diagnostic Tests
Patients with positive screening tests should undergo definitive diagnostic testing to localize the presumed tumor. This process has been improved by the availability of radioisotope scanning using labeled iodobenzylguanidine, followed by CT scanning or magnetic resonance imaging of the site that takes up this substance. Almost all pheochromocytomas are located in the adrenal glands; 1% to 3% may be located in the posterior mediastinum. Of these tumors, 90% can be totally removed at surgery. Up to 10% are found to be malignant at surgery.
Sleep Apnea
Sustained hypertension occurs in some patients with obstructive sleep apnea. From one small clinical trial, it appears that the hypertension abates in response to therapeutic but not subtherapeutic treatment with continuous positive airway pressure (62) (see Chapter 7).
Coarctation of the Aorta
Clues to the presence of this condition are hypertension in a relatively young patient (most are recognized in the pediatric age group); decreased BP in the lower extremities as suggested by diminished or absent femoral pulses and corroborated by auscultation over the popliteal artery using a large cuff; and evidence of collateral arterial circulation either on inspection of the trunk or on the plain chest radiograph, which may show poststenotic dilation of the aorta. In a minority of patients, the coarctation occurs proximal to the left subclavian artery, and the BP is high only in the right arm. The patient must undergo aortography to confirm the presence of a coarctation.
Status of Factors Modified by Treatment of Hypertension
Table 67.6 lists factors that should be addressed or documented at baseline because these factors may be modified as part of the treatment plan or as a consequence of treatment. They include information obtained from the history (patient's understanding of hypertension, usual diet, alcohol consumption, current medications), the physical examination (weight, BP, heart rate and rhythm, edema), and laboratory tests (creatinine, electrolytes, fasting glucose, complete blood count, uric acid, cholesterol, and urinalysis).
Status of Other Cardiovascular Risk Factors
Coexisting cardiovascular risk factors are common in patients with hypertension. They greatly affect a patient's long-term probability of morbidity and mortality (Fig. 67.2). Therefore, the baseline evaluation of a hypertensive patient should include checking for other risk factors, which should be considered in planning the overall management. These factors include gender, family history of premature cardiovascular disease, tobacco use (see Chapter 27), high-cholesterol or high-salt diet, hypercholesterolemia (see Chapter 82), sedentary living (see Chapter 16), stressful lifestyle, obesity (see Chapter 83), and diabetes mellitus (see Chapter 79).
Treatment of Hypertension
General Considerations
Goals of Treatment
When sustained hypertension has been confirmed, the goal of treatment is to reduce the patient's risk of future cardiovascular disease by restoring the BP to normal and controlling
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other risk factors. Normal BP is defined as office SBP <140 mm Hg and DBP <90 mm Hg, or home SBP <135 mm Hg and DBP <85 mm Hg (30). For diabetic patients and for patients with CHF or chronic renal failure, a BP <130/80 mm Hg is recommended (30). For patients in whom goal BPs cannot be attained, partial BP control confers some benefit (63).
Timetable
In patients who choose a nonpharmacologic regimen (discussed later), a trial of this approach for 6 to 12 months usually is needed to evaluate its impact on BP. When drug treatment is selected, a goal of satisfactory BP control without significant drug side effects usually can be achieved within 1 to 3 months.
White-Coat Hypertension and White-Coat Effect
The criteria for these two patterns were described earlier (see Measuring the Blood Pressure). The data are not adequate for defining BP goals or treatment recommendations for patients with white-coat hypertension. At least one large study showed similar 4-year rates of cardiovascular morbidity in patients with high office BPs (stages 1 or 2) who did or did not manifest a white-coat effect (lower, often still high, daytime BPs) and were treated based on their office BPs (64). As noted previously, the current consensus is that home BPs ≥135/85 mm Hg should be considered elevated, meaning that the goal home BPs for these and other patients should be less than these levels (30).
Intensity of Blood Pressure Lowering
Because of the suggestion that an on-treatment DBP <85 mm Hg may increase risk (a “J-curve” effect), particularly in patients with pre-existing coronary artery disease (65), in the early 1990s some authorities recommended that the DBP should not be reduced to <85 mm Hg. However, no J-curve pattern was reported in the Systolic Hypertension in the Elderly Program (SHEP), in which the average on-treatment DBP was 68 mm Hg (21). The subsequent Hypertension Optimal Treatment (HOT) clinical trial, which was designed to compare the effects of on-treatment DBPs ≤90 mm Hg, ≤85 mm Hg, and ≤80 mm Hg, did not find evidence of a J-curve effect (66). A meta-analysis of seven large placebo-controlled clinical trials found an increased mortality risk in patients with the lowest SBPs or DBPs in both treatment and placebo groups. The authors concluded that the increased mortality was the result of poor health but not HBP treatment (67). In two groups of patients (those with diabetes and those with CKD), there is evidence that more intense BP lowering enhances the benefits of treatment (seePharmacologic Treatment: Specific Considerations).
Initiating and Adjusting Treatment
A recommended approach to initiating and adjusting treatment of HBP is summarized in the algorithm from JNC-7 shown in Fig. 67.6. Despite new data from clinical trials reported since publication of JNC-7, this algorithm, which emphasizes attaining target BPs, remains a valid guide for treatment of most patients.
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FIGURE 67.6. Algorithm for treatment of hypertension. (Adapted from Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003;289:2560 , with permission.) |
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Special considerations for the treatment of hypertension in adolescents, elderly persons, and pregnant women are discussed in later sections of this chapter.
For stage 1 HBP (sustained SBP 140–159 mm Hg or DBP 90–99 mm Hg), an individualized approach to initial treatment is appropriate. Figure 67.2 shows the graded impact of BP level, other risk factors, and clinical cardiovascular disease on the 10-year prognosis for hypertensive patients. Initial treatment with antihypertensive drugs would be appropriate for stage 1 patients with any major risk factor(history of a clinical cardiovascular event, silent ischemia, LVH, diabetes). The presence at baseline of multiple other cardiovascular risk factors (smoking, hypercholesterolemia, age older than 60 years, male gender, postmenopausal status, strong family history of cardiovascular morbidity) also favors initial drug treatment. For patients with stage 1 HBP who do not have these associated characteristics, it is reasonable to attempt nonpharmacologic treatment for up to 1 year, especially in those patients who voice a strong preference to try this approach.
For stage 2 HBP (sustained SBP ≥160 mm Hg or DBP ≥100 mm Hg), initial pharmacologic treatment is appropriate. JNC-7 recommends starting drugs from two classes, one of which usually should be a thiazidelike diuretic. This strategy recognizes that (a) two or more drugs have been needed to achieve BP control in more than half of subjects in clinical trials and (b) failure to advance pharmacologic treatment probably explains a substantial proportion of patients who are on treatment but are not controlled (Table 67.2).
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TABLE 67.7 Lifestyle Modifications to Manage Hypertensiona |
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Nonpharmacologic Treatment (Lifestyle Modification)
Measures Shown to be Efficacious
A number of nonpharmacologic modalities that require a lifestyle change can either prevent the development of HBP (see Primary Prevention) or lower BP. Although no clinical trials have determined the impact of any these measures on symptomatic cardiovascular disease, there is evidence that nonpharmacologic control of HBP may be as effective as pharmacologic control in preventing LVH (68).
Individual measures for which there is clinical trial evidence for effectiveness in lowering BP include reducing weight, following a healthy diet (the DASH diet), reducing daily intake of salt, and limiting alcohol intake (30,67,68,69,70,71,72,73,74,75). Table 67.7, from JNC-7, shows for each of these lifestyle changes the approximate reduction in SBP reported in clinical trials. Table 67.8, which can be copied for distribution to patients, summarizes what patients need to know in order to follow a low-salt diet. When giving this information to a patient, it is important to point out that approximately 75% of a person's daily intake of salt usually comes from processed foods.
Maintenance of lifestyle modification, and its benefits, requires ongoing motivation of the patient (see Chapter 4). As noted above, for motivated patients with stage 1 HBP and few or no associated risk factors, one or more lifestyle modifications can be tried as primary treatment. Additionally, these measures should be recommended, when pertinent, to all patients who are beginning treatment with
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antihypertensive drugs. As discussed later, when a patient continues to ingest a large amount of salt while taking diuretics, potassium wasting is increased. Therefore, salt restriction may both facilitate BP reduction and prevent excessive potassium loss in patients taking diuretics. Finally, among patients who are taking antihypertensive drugs, the lifestyle modifications listed in Table 67.7 may enable motivated patients to decrease or discontinue drugs and maintain control of their HBP (see Step-Down Therapy).
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TABLE 67.8 Information for Patients Who Are Advised to Follow a 2-g Sodium Diet |
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Physical Activities while Taking Antihypertensive Drug
Most patients want to be informed about the implications of hypertension and antihypertensive drug therapy for ordinary physical activity. Subjects with untreated hypertension have the same patterns of BP fluctuation during exercise as normotensive subjects, only at higher pressures. With vigorous exercise, the SBP rises (as much as 60 mm Hg) while the DBP may rise or fall slightly. Similar patterns usually are found in patients treated with antihypertensive drugs. The effects of a number of antihypertensives and other cardiovascular drugs on BP during exercise are summarized in Table 63.7. In general, it is reasonable to inform patients that their hypertension does not make them different and to reassure them that they can engage in all of their usual activities after beginning treatment for hypertension.
Dietary Potassium
Consuming a diet with substantial potassium content may facilitate the BP-lowering effects of weight reduction, salt restriction, or antihypertensive drugs (76). Increased potassium intake usually occurs as a consequence of changing to a low-sodium diet, which tends to contain more potassium-rich natural foods (e.g., fresh fruits and vegetables) in place of processed food. Because potassium deficiency may cause the BP to increase, maintenance of a normal serum potassium concentration (≥3.5 mEq/L) probably facilitates the BP-lowering effect of diuretics.
Cognitive and Behavioral Techniques
Cognitive and behavioral techniques include biofeedback, stress management, meditation, and muscle relaxation techniques. Critical assessment of clinical trials of these techniques does not support the efficacy of any of the techniques as a primary method for decreasing BP (77). Motivated patients may wish to use one of these techniques as an adjunct to another primary treatment strategy. Chapter 22describes muscle relaxation techniques useful for stress reduction.
Other Substances and Nutrients
Adequate intake of calcium and magnesium or supplemental garlic may promote BP reduction, but no evidence
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indicates that increased amounts of either of these nutrients should be recommended (37). Although fish oils may lower BP, they are associated with adverse effects that counterbalance the small benefit. Caffeine and nicotine may transiently raise BP, but their elimination does not lower BP. The amount of nicotine in nicotine substitution products used in smoking cessation aids described in Chapter 27 usually does not raise BP (78).
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TABLE 67.9 Compelling Indications for Individual Drug Classes |
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Pharmacologic Treatment: General Recommendations
To date, objective methods for selecting the most appropriate antihypertensive drug or combination of drugs for an individual patient have not been developed. Therefore, drug treatment for most patients should be initiated and adjusted using the strategies outlined in the algorithm in Fig. 67.6 and those in Table 67.9.
The recommendations shown in Fig. 67.6 for initial choice of antihypertensive drugs are based on clinical trials demonstrating that active drug treatment decreases morbidity and mortality. One or more large placebo-controlled trials or head-to-head equivalence trials have demonstrated this for each of the major classes of drugs: diuretics, β-blockers, ACE inhibitors, calcium antagonists, and ARBs (24,25). The evidence from trials in which a drug from each class was used as first-line treatment was pooled in two meta-analyses published in 2003 (24,25). A major clinical trial published after these meta-analyses, a head-to-head comparison of amlodipine and atenolol, suggested that atenolol may be inferior to other amlodipine HBP drugs. However, critical commentary on the trial concluded that effective BP lowering by any class of drug—or, as is often the case, two or more drugs from different classes—remains the best predictor of health benefit (79).
Table 67.9 lists clinical conditions for which there are compelling indications, supported by clinical trial results, for choosing individual drug classes. These indications are based on benefits attributable to BP lowering and/or treatment of a coexisting condition (e.g., β-blockers or ACE inhibitors for a post-MI patient, α-blockers for a patient with benign prostate hypertrophy). These indications and other factors that may guide drug selection are discussed in the next section.
The impact of most antihypertensive drugs on BP occurs within 1 to 7 days. For patients with stage 1 HBP, it is reasonable to evaluate the response to medications within 1 month. Patients with stage 2 hypertension, especially those with SBP ≥180 mm Hg or DBP ≥110 mm Hg, should be evaluated frequently until there is evidence that the BP is responding to the drugs and dosages prescribed.
Pharmacologic Treatment: Specific Considerations
Classes of Antihypertensive Drugs
For all available classes of antihypertensive drugs, Table 67.10 provides information about available products, dosages, and common side effects. Table 67.11 summarizes common drug–drug interactions.
Because drugs from each class of antihypertensive agents are available in preparations that are effective for 24 hours or longer, it is prudent to attempt to control a patient's BP with a once-a-day medication schedule.
Many proprietary antihypertensive drugs are substantially more expensive than generic preparations. Generic preparations are available for drugs from each class except the newest class, the ARBs (Table 67.10).
Monotherapy and Combination Therapy
Overview
Decisions about initiating and adjusting drug treatment of HBP were addressed in a landmark meta-analysis of
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placebo-controlled trials of diuretics, β-blockers, ACE inhibitors, ARBs, and calcium antagonists (80). This study found the following:
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TABLE 67.10 Oral Antihypertensive Drugsa |
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TABLE 67.11 Selected Drug Interactions with Antihypertension Therapy |
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The greater impact of low-dose combination therapy on BP reduction supports the JNC-7 recommendation to
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consider initiating two drugs for patients with stage 2 hypertension. The fact that side effects were less than additive in two-drug regimens indicates that side effects will only modestly limit the number of patients able to tolerate initial combination therapy.
Monotherapy with drugs from each class, with the exception of vasodilators, can be chosen initially. The vasodilators hydralazine and minoxidil usually require cotreatment with an adrenergic inhibitor to prevent reflex tachycardia. At least 50% of patients with stage 1 HBP reach their BP target with low-dose monotherapy alone. Increasing the dosage of the initial drug or adding another drug makes achievement of the BP target possible in most patients.
Thiazides
Initial monotherapy with a low dose of a thiazide-type diuretic (e.g., 12.5–25 mg hydrochlorothiazide daily) is appropriate for most patients (30). The rationale for this recommendation is that the diuretic arms of multiple clinical trials have shown clinical benefits equal to or better than the benefits in the nondiuretic arms of these trials.
α-Blockers
Because of the increased incidence of heart failure in patients taking the α-blocker doxazosin in a head-to-head comparison of drugs from the major classes, α-blockers should not be selected for initial monotherapy (81). An exception to this is patients prescribed α-blocker treatment to control symptoms from benign prostate hypertrophy (see Chapter 53).
β-Blockers
Although they lower BP, β-blockers, particularly atenolol, the first-line β-blocker in a number of clinical trials, have not been shown to benefit health as much as other BP-lowering drugs (82,83). Because of these findings, beta blockers generally should not be used for monotherapy but do have a role as adjuncts to drugs in other classes.
Fixed-Dose Combination Tablet
Drugs from two or more classes of antihypertensive agents (usually a low-dose thiazide diuretic plus a nondiuretic) are available in a number of fixed-dose combinations. The appropriate combination tablets may provide additional convenience at no extra cost.
Drug Combinations with Beneficial or Risky Synergies
Two antihypertensive drug combinations have been shown to have beneficial synergistic effects:
Certain two-drug combinations may have potentially harmful synergistic effects:
Adding a Diuretic
The addition of a diuretic has been shown to enhance the antihypertensive effect of all nondiuretic drugs. Therefore, in a patient who does not achieve control with one of the nondiuretic drugs, the addition of a low dosage of a thiazide-type diuretic should be considered. Higher doses of a thiazide, a more potent loop diuretic, or a potassium-sparing diuretic may be needed in some patients who have edema from sodium retention. An especially potent regimen—the combination of a loop diuretic (e.g., furosemide) with a low dosage of a diuretic active at the distal convoluted tubule (e.g., a thiazide or metolazone)—occasionally is needed to control volume overload in a patient whose hypertension is related to this condition.
Demographic Characteristics
African-American subjects respond less often than whites to ACE inhibitor and β-blocker monotherapy and more often to monotherapy with diuretics or calcium antagonists. When their HBP is controlled with combinations of any BP-lowering drugs, the health benefits of treatment appear to be similar (84). In many older patients with isolated systolic HBP, low-dose thiazide-type diuretic or long-acting dihydropyridine calcium antagonist monotherapy controls the BP and reduces morbidity and mortality (21,22). Gender has not been correlated with selected advantages or disadvantages of any classes of antihypertensive drugs. Because the potent vasodilator minoxidil causes marked hirsutism, it is not an acceptable medication for women. Additional considerations in managing hypertension in adolescents, older patients, and pregnant patients are discussed in later sections of this chapter.
Miscellaneous Coexisting Medical Conditions
Coexisting medical conditions may influence the selection of antihypertensive drugs. Table 67.9 lists compelling
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indications for each class of drugs, indicating that there is evidence for drug-specific benefits from randomized controlled trials.
Nondiabetic Chronic Kidney Disease
Based on trials that have compared multiple drugs, it appears that ACE inhibitors and ARBs may have a selective renoprotective effect in patients with nondiabetic CKD (30). On the other hand, BP reduction with drugs from all classes has delayed the progression of CKD. A 2004 meta-analysis of clinical trials that used ACE inhibitors and other classes of drugs confirmed that in CKD patients who excrete >1 g/day of protein, (a) an on-treatment SBP of 110 to 129 mm Hg was associated with the lowest risk of CKD progression and (b) an on-treatment SBP <110 mm Hg was associated with an increased risk of progression (85). The on-treatment BP goal of <130/80 mm Hg recommended by JNC-7 (Fig. 67.6) would be appropriate for the majority of CKD patients who excrete <1 g/day of protein. In addition to nondiuretic drugs, large doses of loop diuretics may be needed to control volume in patients with advanced CKD.
Diabetes Mellitus
HBP is up to twice as common in diabetic patients as in matched nondiabetic individuals. An association exists between type 2 diabetes, hypertension, and the insulin-resistant state known as the metabolic syndrome (hyperinsulinemia, dyslipidemia, and obesity) (86). Nonpharmacologic lifestyle changes that decrease insulin resistance (weight reduction and increased exercise) theoretically may be especially important in treating this subset of hypertensive patients.
The JNC-7 recommendation of an on-treatment goal of ≤130/80 mm Hg for diabetic patients (30) is supported by the findings of the HOT Trial, which showed that more aggressive antihypertensive drug treatment reduces both microvascular (nephropathy, retinopathy) and macrovascular complications of type 2 diabetes (66). Two drug comparison trials showed significantly lower cardiovascular event rates among diabetic patients taking ACE inhibitors versus dihydropyridine calcium antagonists (87,88). Although calcium antagonists were used in the HOT trial, the findings from these two trials suggest that other classes may be more beneficial. In this regard, it is important to recognize that cotreatment with diuretics was fundamental to BP control in a large proportion of subjects in the latter trials, and that subsequent analyses of data from many trials have shown that diabetic subjects in low-dose diuretic arms had health outcomes equivalent or superior to outcomes for diabetics in the nondiuretic arms (89,90). Prevention of CKD was not assessed in these trials.
In patients with type 1 diabetes and established nephropathy (urine albumin ≥30 mg/day), ACE inhibitors should be used because they have been shown to reduce proteinuria and delay loss of renal function even in nonhypertensive diabetic patients (91). Cotreatment of type 1 patients with maximum tolerated doses of both ACE inhibitors and ARBs has been shown to reduce proteinuria more than treatment with an ACE inhibitor alone, but the clinical consequences of this aggressive approach are not yet known (92).
In patients with type 2 diabetes and established nephropathy and HBP, ACE inhibitors and ARBs have been studied extensively. Both classes of drugs confer renoprotection that may exceed that conferred by other BP-lowering drugs (30).
A potential unique role for ACE inhibitors in type 2 diabetic patients was found in the Microalbuminuria, Cardiovascular, and Renal Outcomes in Heart Outcomes Prevention Evaluation (MICRO-HOPE) trial. In this placebo-controlled trial, addition of the ACE inhibitor ramipril at a fixed dose (10 mg) to patients’ current regimens reduced microvascular and macrovascular end points in diabetic patients (93). The benefit of treatment was at least partly independent of BP lowering, suggesting that ramipril and other ACE inhibitors have a unique vascular protective effect in diabetes.
Pretreatment and posttreatment standing BPs should always be measured in diabetic patients. When orthostasis is found, presumably caused by neuropathy, the standing pressure should be monitored and included in treatment decisions.
Left Ventricular Hypertrophy
The finding of LVH on either a baseline ECG or an echocardiogram is a powerful independent predictor of cardiovascular morbidity (94). LVH may regress when BP is reduced by weight reduction, salt restriction, or antihypertensive drugs from all classes except direct vasodilators (95). To date, an ARB (losartan), in a head-to-head comparison with a β-blocker (atenolol), has been shown to have an advantage in reducing LVH (94). A meta-analysis of several small studies has also suggested an advantage for ACE inhibitors (96). It is possible that LVH represents a treatable risk factor independent of HBP. This conclusion is tentatively supported by subgroup analyses of Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial data showing that treatment-related lower left ventricular mass is associated with lower rates of end points independent of the degree of BP reduction (94).
In the subset of patients with symptoms of heart failure and echocardiographic evidence for diastolic dysfunction, a calcium channel blocker or a β-blocker may provide symptomatic relief as the result of a modest decrease
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in contractility (47). In the short term, these drugs do not appear to decrease the late-diastolic stiffness present in these patients (97). Over a longer period (3 years), diastolic function does improve in association with regression of LVH in patients treated with ACE inhibitors (98).
Cost of Antihypertensive Drugs
Brand name drugs, especially newer drugs, typically cost the patient more than $1 per dose. Even generic drug prices fluctuate according to what manufacturers choose to charge. The least expensive generic regimens ($10–$40 per month) are monotherapy with a generic product (Table 67.10). When combination therapy is needed, a combination product may be less expensive than the component drugs purchased separately.
Drug–Drug Interactions
Table 67.11 provides drug interaction information that may be important in selecting and monitoring both antihypertensive agents and other drugs. This information is not exhaustive. Today, pharmacists usually can provide prompt responses to queries about drug interactions.
Drug Side Effects
Table 67.10 lists the most common side effects for each class or subclass of antihypertensive drugs.
Modification of the regimen may be needed if drugs control the hypertension but cause troublesome side effects. After any drug is initiated, the patient should be encouraged to discuss any drug-associated disturbances, such as reduced mental alertness, mood change, or impairment in physical exercise or sexual activity. From 5% to 20% of enrollees discontinue therapy in the trials of most antihypertensive drugs because of such side effects, and many notice minor side effects as long as they are taking antihypertensive drugs. Even taking a placebo for hypertension is associated commonly with side effects. For many side effects, the frequency is similar in active-drug and placebo patients.
Evidence-based review of the literature (37) and practical experience led to the following conclusions regarding a number of important symptomatic side effects:
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standing BP should be measured when symptoms are present—either at home by the patient or in the office—because profound but transient orthostatic hypotension can occur in some patients (see Problems in the Course of Treatment).
In many clinical trials, quality-of-life indices have been used to measure the impact of antihypertensive drugs on patients’ energy levels, mental health, physical abilities, and social functioning. In one study, patients taking each of the major classes of drugs or placebo reported modest improvement in most of these measures 4 years after starting treatment (99).
Serum Lipids and Aspirin Use
The clinical approach to two factors that affect cardiovascular risk—serum lipids and aspirin—is related to antihypertensive drug use.
Lipids
Although thiazide diuretics at low dosages can cause a short-term increase in total cholesterol and β-blockers may decrease high-density lipoprotein cholesterol and increase triglyceride levels (100), these unfavorable effects did not persist in a 4-year study of monotherapy that compared a low-dose thiazide diuretic, a β-blocker, an ACE inhibitor, a nondihydropyridine calcium antagonist, and a long-acting α-blocker (101). JNC-7 recommends that any lipid abnormality be addressed according to current guidelines (see Chapter 82) and that antihypertensive drugs, including low-dose diuretics, be used according to the scheme shown in Figure 67.6 (30).
Aspirin
Low-dose aspirin should be considered according to the guidelines summarized in Chapter 62 only when HBP is controlled because of the increased risk for hemorrhagic in patients with uncontrolled HBP (30).
Step-Down Therapy
Patients who are taking one or more antihypertensive drugs may want to take measures that enable them to reduce or discontinue drug treatment. Based on the results of a clinical trial in middle-aged adults, approximately one third of patients who have reduced their weight and restricted their salt intake can maintain control of their HBP without previously administered antihypertensive drugs (102). Similarly, approximately one third of older patients receiving monotherapy for HBP were able to maintain normal BP when drugs were discontinued after 3 months of lifestyle change (salt restriction and/or weight reduction) (103).
Promoting Adherence to Pharmacologic Treatment
Chapter 4 discusses in detail adherence to treatment as a generic feature of ambulatory care. Because poor adherence is common in patients with hypertension, the problem has been studied extensively. Nonjudgmental statements such as the following have been shown to be effective in eliciting accurate information from patients for whom antihypertensive drugs are prescribed: “People often have difficulty taking their medicines for one reason or another, and we are interested in finding out any problems that occur so that we can understand them better.” After this statement, patients are asked whether they ever miss taking tablets and are encouraged to discuss any problems they are having with taking medicine.
Certain strategies have been shown to improve adherence to antihypertension treatment. Several of these strategies should be used routinely. More intensive strategies should be used for patients who appear to be especially noncompliant (see Chapter 4).
Strategies recommended for all patients include the following:
For patients who admit poor compliance, the reason should be explored and addressed (see Practical Approaches for Detecting and Addressing Noncompliance in Chapter 4).
For patients with uncontrolled hypertension in whom poor compliance is suspected but not admitted, the following strategies have been shown to help:
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Problems in the Course of Treatment
The following problems occur during the long-term treatment of many patients with HBP: treatment-induced increase in serum creatinine concentration, instability in BP control, orthostatic symptoms, and intercurrent illness.
On-Treatment Increase in Serum Creatinine Concentration
After a long period of uncontrolled HBP (the situation that obtains for most patients when their asymptomatic HBP is identified), the glomerular afferent arterioles do not vasodilate as well as they normally would when there is a reduction in the systemic BP. This explains the modest increase (often 20%–25%, e.g., from 0.8 mg% to 1.0 mg%) in creatinine concentration after reduction of BP. This signifies a physiologic, not a structural, impact on the kidneys and does not constitute a reason for changing treatment that has achieved the goal BPs named by JNC-7 (Fig. 67.6) (104).
Instability in Blood Pressure Control
General Approach
Most patients in whom satisfactory control has been achieved will have at some followup visits either uncontrolled HBP or, less often, overcontrolled HBP. At those visits, one usually can identify the probable cause and design a plan to restore satisfactory control. In assessing loss of BP control for which the cause is unclear, it is always useful to check the BP in both arms (to rule out “pseudocontrol” in an arm that may have a stenotic artery proximal to the brachial artery) and to review the most recent visit when the BP was controlled and ask, “What is different today?” Table 67.12 summarizes the differential diagnosis of instability in BP control, divided into common and uncommon causes. Before revising a patient's regimen, a prompt followup visit should be scheduled to determine whether the loss of control is persistent.
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TABLE 67.12 Differential Diagnosis of Instability in Blood Pressure Control |
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Home monitoring of the BP, either by the patient or by someone else, can be useful in assessing apparent loss of response to antihypertensive drugs. If this strategy is used, the patient should obtain and document the following information: BP, arm, position, heart rate, and time since last dose of each medication. If one plans to rely on data from home monitoring, it is advisable to have the patient (or family member) bring the device to the office periodically to check technique and accuracy.
Noncompliance
Noncompliance, or overcompliance, often can be identified by nonjudgmental inquiry, as described earlier (see Promoting Adherence to Pharmacologic Treatment and Chapter 4). Patients who have deliberately discontinued medications will often explain their reasons.
Some patients omit their medications on the day of the visit. Others take their medications consistently but incorrectly. Because the cause may be an error in dispensing of medication, patients who report that they are complying should be asked to telephone the office and read the information on their medication bottles or to bring their medication bottles to the next visit.
For patients with uncontrolled BPs who report taking their medication correctly, this claim can be evaluated further by having them take their medicine under supervision in the office and then measuring the BP response for several hours.
Changes in Salt Consumption or Weight Gain
Increase in salt consumption may lead to a positive sodium balance, which can blunt the effects of antihypertensive drugs. Because of increased thirst, this problem is
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not uncommon in the summer months. The converse situation—negative sodium balance from inadequate replacement of sweat—may cause an overresponse to antihypertensive drugs. Increased salt consumption should be suspected whenever loss of BP control is associated with a weight gain of 2 to 3 lb (1 kg) or more, with or without edema. A brief review of the patient's current diet often helps support this hypothesis. Management consists of having the patient resume moderate sodium restriction or substituting more potent diuretic treatment. Temporary use of furosemide (e.g., 20–40 mg daily for a few days) to eliminate excess sodium often is useful in this situation. For patients in whom sodium overload is a recurrent problem, furosemide in dosages adjusted by the patient to maintain a stable weight is effective.
If the patient's weight gain is associated with increased caloric intake, then reduced caloric intake leading to weight reduction may restore the response to antihypertensive medications (see Chapter 83).
Psychological Stress or Somatic Pain
In a patient who is adhering faithfully to treatment, intercurrent psychological stress or physical pain may explain the failure to respond as usual to antihypertensive drugs. The cause probably is an increase in sympathetic nervous system activity accompanying psychological stress or marked pain, for example, that resulting from injury or worsening of an existing musculoskeletal or other condition. In these situations, the previous response to antihypertensive medication should be restored when the stress or pain subsides.
Stress may be associated only with visits to a physician's office (see White-Coat Hypertension and White-Coat Effect), especially if the patient is being seen by a new physician, and the rise in BP may be strictly transient. This problem can be minimized by ensuring that the patient is at ease before the BP is measured and by repeating the measurement later during the visit if the initial pressure is high. If stress is suspected as the reason for elevated office BPs, home BP measurements may provide better information for judging the effectiveness of treatment and may spare patients from inappropriate increases in antihypertensive drugs and the associated side effects.
Excess Alcohol or Withdrawal from Alcohol
Because hypertension can occur as a manifestation of excessive alcohol intake or of alcohol withdrawal, it is important to check for alcohol abuse in a patient with previously controlled hypertension (see Chapter 28). Unstable BP control caused by alcohol withdrawal probably is most common in patients whose medical appointments occur after a weekend.
Concurrent Medications
A number of prescribed and over-the-counter (OTC) medications may attenuate the response to some or most antihypertensive drugs (Table 67.11, footnote to Table 67.6). Some drugs can potentiate the response to antihypertensive medications (Table 67.11). Antagonism of antihypertensive agents has been assessed for two common classes of drugs, both available in OTC and prescription formulations: (a)decongestants containing sympathomimetics, which may raise the BP but do not impair the response to antihypertensives when the recommended OTC dosage is taken, and (b) nonsteroidal anti-inflammatory drugs, some of which raise BP, interfere with the response to antihypertensives, or both.
Sleep Apnea
Sleep apnea can cause HBP or explain instability in response to antihypertension treatment in some patients. This has two implications for patient care: (a) inquire about symptoms of sleep apnea in nonresponding patients (see Chapter 7) and (b) consider effective treatment of sleep apnea as the explanation when a patient's HBP is easier to control after the patient's sleep problem has been identified and treated (105).
Hypertension that Becomes Refractory to Treatment
Rarely, a patient's BP becomes refractory to previously effective drugs and no explanation is identified. In such patients, two questions must be answered:
Resistant Hypertension
Occasionally, a newly diagnosed patient does not respond to a variety of antihypertensive drugs at high dosages (106).
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Apparent resistant hypertension can be assessed by direct observation of response to drugs during several hours in the office. The following regimens, each of which can be given in forms that allow once-a-day dosing, may be particularly effective in controlling resistant hypertension:
If no regimen controls the BP in a patient with resistant hypertension, evaluation for a surgically treatable cause of hypertension, especially RVH, is indicated (see Renovascular Hypertension).
Orthostatic Symptoms
Many patients taking antihypertensive drugs describe brief orthostatic dizziness or faintness, particularly when they first stand up in the morning. Usually, either sitting for a few minutes before standing or a modest reduction in drug dose alleviates the problem.
At times, a patient who has satisfactory BPs at office visits describes pronounced orthostatic symptoms lasting 1 hour or longer after taking medicine. In this situation, it is important to reduce or discontinue the medication promptly. If such a patient has severe hypertension when not taking medication, it is helpful to observe the patient's response to medication in the office before reducing medications.
Occasionally a patient—usually an older person—describes orthostatic symptoms related to medications at a time when the standing BP is measured as normal or high. In patients with known atherosclerosis (e.g., carotid bruits), this may be caused by positional cerebral ischemia (107). In these patients, the problem also may be pseudohypertension, a measurement artifact caused by a difficult-to-compress calcified brachial artery (see Measuring the Blood Pressure). For practical purposes, when either positional cerebral ischemia or pseudohypertension is suspected, a trial of less (or no) antihypertensive drugs is appropriate. If the patient's symptoms improve, it is reasonable to withhold antihypertensive drugs or to prescribe doses that do not cause the symptoms.
Intercurrent Illness
During long-term treatment, most hypertensive patients develop acute or chronic conditions that require adjustment of their antihypertensive drugs. For patients with selected chronic conditions, one or more antihypertensive drugs may be advantageous or inappropriate, for example, β-blockers in hard to control asthma or chronic obstructive pulmonary disease, or diuretics in recurrent gout. Several common intercurrent problems require extra caution with any antihypertensive drug regimen.
Acute Illness
All patients with hypertension have intercurrent acute illnesses. The following factors, which increase a person's sensitivity to antihypertensive drugs, may accompany some of the intercurrent illnesses:
If lower BPs are documented or if the patient describes orthostatic symptoms, short-term decrease or withholding of antihypertensive drugs will protect the patient from the additional morbidity of hypotension or electrolyte depletion (e.g., in a patient taking diuretics). The patient's usual antihypertensive regimen should be resumed gradually as the BP returns to hypertensive levels. In some situations (e.g., after major surgery), the previous regimen may not be needed for 1 month or longer.
New Stroke or Myocardial Infarction
In patients who are stable after a transient ischemic attack or completed stroke, one large placebo-controlled study of antihypertensive treatment (ACE inhibitor first-step treatment and add-on diuretic treatment if needed) showed a major reduction in the occurrence of second strokes and other cardiovascular events (108). This benefit was observed only in those subjects who received both drugs. There was no on-treatment BP goal. Average reduction in SBP and DBP was 12 and 5 mm Hg, respectively. Importantly, this study enrolled only stable poststroke or TIA patients. Theoretical reasons exist for not lowering BP aggressively in the acute phase of an ischemic stroke (109).
The hypertensive patient who has experienced a recent MI may have a normal BP or less severe hypertension during convalescence. Because this fall in BP may be transient, the BP should be evaluated at least monthly in the first 3 to 4 months after discharge.
Clinical trials have shown that the prognosis in survivors of MI, with or without a history of HBP, is improved
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when an ACE inhibitor is used in conjunction with other drugs (β-blockers, antiplatelet therapy, and statins) that favorably impact prognosis. However, this added benefit from ACE inhibitors has not been shown in patients in the lowest-risk group: those with no CHF, left ventricular dysfunction, diabetes, or elevated low-density lipoprotein cholesterol (110).
Preplanned Surgery
Chapter 93 discusses antihypertensive therapy in relation to preplanned surgery.
Hypertension in Selected Subgroups
Hypertension in Adolescents
Epidemiology
No longitudinal or clinical trial data relating BP level or treatment of HBP to health outcomes in adolescents and children are available.
In young adults (age 18–29 years), the crude prevalence of hypertension, defined as ≥140/90 mm Hg, varies from approximately 0.5% (white women) to approximately 7% (African-American men) (111). Both the prevalence and the incidence of HBP are higher in adolescents who are overweight or become overweight. The cutoff level of hypertension in children ≤17 years of age has been arbitrarily established by defining HBP as the 95th percentile BP for each age and gender group, according to height (Table 67.13). The cutoff levels for SBP and DBP are higher for taller adolescents (112).
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TABLE 67.13 95th Percentile of Blood Pressure in Boys and Girls Aged 3 to 17 Years, According to Heighta |
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Recommendations
In 2004, the U.S. Task National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents defined a BP >120/80 mm Hg as prehypertension in adolescents and recommended the following approach for adolescents with SBP or DBP levels approaching or above the 95th percentile (Table 67.13) (112):
For patients whose BPs remain above the 95th percentile despite nonpharmacologic measures, pharmacologic treatment is recommended. The goal is a BP below the 95th percentile for the patient's age and height. The baseline evaluation and the principles for selecting individual antihypertensive drugs for adolescents are essentially the same as for adults. However, because of their teratogenic effects, ACE inhibitors and ARBs should not be used by pregnant women and should not be prescribed to sexually active teenage girls unless they are using effective birth control measures.
Adolescents who do not respond to treatment or who have “red flags” for secondary hypertension should be
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evaluated for treatable causes of their HBP (see Evaluation for Secondary Hypertension).
Because of the psychological and social stresses associated with adolescence, the care of a chronic condition such as hypertension requires special considerations in this age group (see Chapter 11).
Hypertension in the Elderly
Hypertension is common in older patients (Fig. 67.1), and the risks associated with systolic and diastolic hypertension increase substantially with each decade of life and with the coexistence of other major risk factors (Fig. 67.2). Evidence indicates that SBP and perhaps an elevated pulse pressure (SBP minus DBP) are the strongest predictors of morbidity in older persons with HBP (12,113,114).
Recommendations
The recommendations for older patients in JNC-7 (30) are based on the findings from multiple clinical trials (19, 20, 21, 22, 23). One of these trials, the Systolic Hypertension—Europe (Syst-Eur) trial for patients with isolated systolic hypertension, showed that first-line treatment with a long-acting dihydropyridine calcium antagonist had an effect similar in magnitude to that of diuretic-based regimens used in earlier trials (22). The principal JNC-7 recommendations for older patients are the following:
Several general points about the published clinical trials in older patients are helpful in making decisions for individual patients:
Caveats Regarding Drug Treatment
Several special characteristics of older persons should be considered when deciding how to treat their hypertension.
Orthostatic hypotension unrelated to drugs is fairly common in elderly patients. The explanation may be an increase in sedentary activity or blunting of autonomic reflexes. Therefore, it is important to obtain baseline and followup standing BPs (including standing after walking) in older patients taking antihypertensive drugs.
Both pseudohypertension and white-coat hypertension (see Measuring the Blood Pressure) may be more prevalent in older persons, especially those who describe orthostatic symptoms despite apparent high pressures at office visits and in those who have no target organ disease.
Other characteristics of older subjects that increase the risks associated with antihypertensive drugs include the following:
Chapter 12 discusses these and other characteristics that are important in the care of older persons. Three precautions minimize the risks of antihypertensive drugs in older patients: using the lowest recommended dosage and increasing the dosage slowly, keeping the drug schedule simple, and decreasing or discontinuing drugs if signs or symptoms of significant orthostatic hypotension or other annoying side effects develop.
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Hypertension in Pregnancy
This section addresses BP and HBP assessment and management in women who are pregnant or lactating. For nonpregnant women, longitudinal studies have delineated the risks of HBP, and clinical trials have demonstrated the benefits of treatment. The negligible impact on BP of oral contraceptives and estrogen replacement in most women was addressed earlier (see Evaluation for Secondary Hypertension).
Normally, SBP does not change during pregnancy, but DBP falls by approximately 10 mm Hg during the first and second trimesters, then reverts to the prepregnancy level in the third trimester. The maximal fall occurs between weeks 13 and 20. It probably is caused by the general vasodilation that accompanies pregnancy. Increased renin and aldosterone levels also occur in normal pregnancy.
Hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg) is present or develops in 6% to 8% of pregnant women in the United States.
Based on previous records or patient history, it should be possible at the first prepartum visit to decide for most women whether they usually are normotensive or have chronic hypertension. This decision is helpful in managing the following four categories of hypertension, which have been defined by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy (116):
This classification, which names gestational hypertension as a distinct category, differs from that issued previously.
Chronic Hypertension in Pregnancy
Chronic hypertension is defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg diagnosed before pregnancy or appearing before week 20 of pregnancy. It is more common in pregnant women who are in their thirties because of the increased prevalence of hypertension with age.
There are two important questions to consider in patients with chronic hypertension:
Preeclampsia/Eclampsia
Preeclampsia is a pregnancy-induced syndrome in which the clinical data must be carefully considered before making the diagnosis, in particular to distinguish it from pre-existing chronic hypertension and gestational hypertension. A number of factors increase the risk for developing preeclampsia (Table 67.14). Untreated preeclampsia is associated with a high incidence of fetal mortality and maternal morbidity, especially the convulsive syndrome known as eclampsia. The major pathophysiologic derangement in preeclampsia is placental hypoperfusion caused by abnormal implantation of the trophoblast. This state leads to endothelial damage, which initiates the release of compounds that cause generalized vasospasm, reduced plasma volume and cardiac output, decreased glomerular filtration rate, and compromised perfusion of the placenta, kidneys, liver, and brain.
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TABLE 67.14 Risk Factors for Preeclampsia |
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Diagnosis
The criteria for diagnosis of preeclampsia are as follows:
In the absence of proteinuria, preeclampsia is highly suspected when increased BP appears accompanied by headache, blurred vision, and abdominal pain, or by abnormal laboratory test results, specifically low platelet counts and abnormal liver enzyme values.
The development of new, generalized edema during the last trimester is another manifestation of preeclampsia. Dependent edema alone is not a predictor of preeclampsia; it is seen in approximately one third of pregnant women whose BP remains normal.
Eclampsia is defined as the occurrence in a woman with preeclampsia of seizures that cannot be attributed to other causes.
Treatment
Most preeclampsia develops late in the third trimester, when the fetus is mature, and delivery, the definitive treatment, can be planned promptly. The usual predelivery management of preeclampsia, under the supervision of the patient's obstetrician, is hospital admission, modified bed rest, frequent monitoring of maternal BP and fetal status, and antihypertensive drugs. Clinical trials have not shown clear benefits from any of these measures (117).
Preeclampsia resolves within 6 weeks after delivery. Approximately 25% of primigravidas with preeclampsia develop the condition during a future pregnancy. However, epidemiologic studies have shown that women with a history of preeclampsia do not have an increased risk for developing chronic hypertension (118).
Prevention
No measures have been shown convincingly to prevent preeclampsia. Salt restriction and aspirin, previously thought to be efficacious, have been no better than placebo in large clinical trials. This is also true for calcium supplementation, although it may decrease the risk of one component of preeclampsia, hypertension.
Preeclampsia Superimposed on Clinical Hypertension
There is ample evidence that preeclampsia may occur in women who have chronic hypertension. The diagnosis of superimposed preeclampsia is highly likely with the following findings:
Gestational Hypertension
Gestational hypertension is defined as the development of new HBP after week 20 of pregnancy without proteinuria. In some, it may be an early manifestation of preeclampsia; in others, it may be previously unrecognized chronic HBP. The final determination that a woman does not have the preeclampsia syndrome can be made only after delivery. Without treatment, the outcome of pregnancy in women with this form of HBP usually is good.
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Management of Hypertension during Lactation
Because breast-feeding is practiced widely, some women who require antihypertensive drugs seek advice regarding breast-feeding (119). Most drugs appear in breast milk, but the calculated dose consumed by the suckling infant ranges from 0.001% to 5% of the standard therapeutic dose tolerated by infants without toxicity. Based on what is known of antihypertensive drugs, the following drugs, if needed, are regarded as compatible with lactation: atenolol, propranolol, methyldopa, captopril, and hydrochlorothiazide.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.
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