A Rational Approach to the Treatment of Hypertension in Special Populations

Am Fam Physician. 1999 Jul 1;60(1):156-162.

Hypertension in blacks is usually characterized by low renin, expanded volume and sensitivity to salt. Diuretics are the preferred initial therapy, but response to calcium channel antagonists is also good. The blood pressure response to monotherapy with beta blockers or angiotensin-converting enzyme (ACE) inhibitors is blunted, but this effect is abolished with concomitant use of diuretics. The two major types of hypertension in older persons are isolated systolic hypertension and combined systolic and diastolic hypertension. Strong data support the treatment of combined hypertension in patients 60 to 79 years of age and isolated systolic hypertension in patients 60 to 96 years of age. Diuretics and long-acting dihydropyridine calcium channel antagonists are the recommended initial therapies for isolated systolic hypertension. More studies are necessary before recommendations can be made about the treatment of combined hypertension in patients 80 years of age and older.

The recently published guidelines from the sixth Joint National Committee (JNC VI)1 addressed management of hypertension in many special populations, including racial/ethnic minorities and older persons. This article focuses on management of hypertension in two subgroups, providing a rationale for the treatment recommendations as well as summarizing relevant data published in the year since the JNC report was published.

Hypertension in Black Patients

The prevalence of hypertension in adult black patients in the United States is 32.4 percent, compared with 23.3 percent in white patients.2 This increased prevalence is accompanied by an 80 percent higher rate of mortality associated with stroke, a 50 percent higher rate of mortality associated with heart disease and a striking, sixfold greater rate of hypertension-related end-stage renal disease.

PATHOPHYSIOLOGY

The pathophysiology of hypertension differs in black adults. For example, hypertension in this population is commonly of the low-renin type and, often, sensitivity of blood pressure to salt intake is increased, and the ability to excrete ingested salt is impaired (60 to 70 percent).3 This leads to an overall expansion of intravascular volume. Obesity is especially prevalent in black women and is associated with an increase in total body sodium content.4 Intake of dietary potassium is generally lower in blacks than in whites. Black patients may also have relatively higher levels of intracellular calcium.5 All of these factors are associated with an increased incidence of hypertension.

TREATMENT WITH LIFESTYLE MODIFICATIONS

The pathophysiologic characteristics of hypertension in blacks provide a rationale for a strong focus on lifestyle modifications for improvement of blood pressure. A reduction in body weight by an average of as little as 3.18 kg (7 lb) significantly reduces blood pressure.6 In normokalemic hypertensive patients, use of oral potassium supplements (about 60 mmol daily) may also significantly reduce blood pressure.7 This occurs, in part, because of a natriuretic effect of potassium.

Restricting dietary salt intake to less than 2,300 mg daily is particularly effective because of the salt sensitivity that is often present in these patients.8 Concerns about any claimed risks of clinically achievable long-term dietary salt restriction (e.g., myocardial infarction in men, mineral deficiencies, etc.) are exaggerated.9 Approximately 10 percent of hypertensive black adults (the percentage is higher in those who are markedly overweight) have an extremely high dietary sodium intake (i.e., 24-hour urinary sodium excretion of 200 to 400 mEq per 24 hours [200 to 400 mmol per day], equivalent to a sodium intake of 4,600 to 9,200 mg daily) that is not suspected by either the patient or the physician. In these patients, it is impossible to adequately control blood pressure without using a diuretic or providing very specific dietary counseling to identify food(s) high in sodium.

TREATMENT WITH ANTIHYPERTENSIVE DRUGS

The excellent blood pressure–lowering efficacy of diuretics and calcium channel antagonists in hypertensive black patients is related to their characteristic volume expansion, salt sensitivity and low renin profile. As recommended by JNC VI, diuretics should be used for initial therapy unless there is an absolute or relative contraindication (e.g., gout). Hydrochlorothiazide in a dosage of 12.5 to 25.0 mg daily is a good choice but, if the level of serum creatinine is 2 mg per dL (177 μmol per L) or more, thiazide diuretics are usually ineffective, and a loop-type diuretic should be substituted.10

Angiotensin-converting enzyme (ACE) inhibitors or beta blockers are less effective in lowering blood pressure in patients with a low renin profile. For example, with beta-blocker therapy, the average reduction in blood pressure of about 7/7 mm Hg in black patients compared with an average reduction of about 15/11 mm Hg in white patients.11 Increasing the dosage of the ACE inhibitor provides a slightly greater average lowering of blood pressure (to a total of about 10/8 mm Hg), but the decrease is still less than desirable.12 Ensuring a low dietary salt intake can improve the blood pressure response to ACE inhibitors in black patients.13

The problem of a reduced blood pressure-lowering effect of beta blockers and ACE inhibitors is moot if diuretics are used as initial or second-line drug therapy in black patients with hypertension. The combination of diuretics and ACE inhibitors or beta blockers produces equivalent lowering of blood pressure in whites and blacks, perhaps as a result of diuretic-induced stimulation of renin release. This is true even for combination-type drugs that contain as little as 6.25 to 12.5 mg of hydrochlorothiazide.14 Most hypertensive black patients require two or more antihypertensive drugs to control systolic blood pressure to less than 140 mm Hg and diastolic blood pressure to less than 90 mm Hg, the current goals recommended by JNC VI for patients with uncomplicated hypertension. In the Veterans Affairs Cooperative Study,15 only 46 percent of black hypertensive patients with stage 1 or stage 2 disease achieved a diastolic blood pressure below 90 mm Hg with monotherapy.

JNC VI defined certain compelling indications for which there is strong evidence in favor of the use of specific classes of antihypertensive drugs.1 Examples include the use of beta blockers after myocardial infarction and the use of ACE inhibitors in patients with systolic heart failure (i.e., ejection fraction less than 40 percent) or those with type 1 diabetes (formerly known as insulin-dependent diabetes) with proteinuria. These compelling indications apply equally to black and white patients. However, there is evidence of significant underuse of these drugs for these conditions in both racial groups.16

In the absence of contraindications, special efforts should be made to ensure that black patients with hypertension who have had a myocardial infarction are receiving a beta blocker and that hypertensive black patients with systolic heart failure or diabetic nephropathy are receiving an ACE inhibitor. In these cases, the protective effect of the drugs is due to more than just reduction of blood pressure. In black hypertensive patients with type 2 (non–insulin-dependent) diabetic nephropathy, evidence now shows that non–dihydropyridine calcium channel antagonists (as well as ACE inhibitors) can slow the chronic progression of renal disease.17

These specific recommendations are summarized in Table 1.

TABLE 1

Special Therapeutic Recommendations for Management of Hypertension in Black Patients

Focus on lifestyle modifications (weight reduction, restricting dietary sodium and ensuring an adequate intake of potassium). About 10 percent of patients have a very high sodium intake.

Thiazide diuretics are preferred as initial therapy.

Calcium channel antagonists are also effective.

The blunted response to beta blockers and ACE inhibitors can be abolished by adding a diuretic.

Beta blockers are specifically indicated after myocardial infarction, and ACE inhibitors are specifically indicated in patients with systolic heart failure or diabetic nephropathy.


ACE = angiotensin-converting enzyme.

TABLE 1   Special Therapeutic Recommendations for Management of Hypertension in Black Patients

View Table

TABLE 1

Special Therapeutic Recommendations for Management of Hypertension in Black Patients

Focus on lifestyle modifications (weight reduction, restricting dietary sodium and ensuring an adequate intake of potassium). About 10 percent of patients have a very high sodium intake.

Thiazide diuretics are preferred as initial therapy.

Calcium channel antagonists are also effective.

The blunted response to beta blockers and ACE inhibitors can be abolished by adding a diuretic.

Beta blockers are specifically indicated after myocardial infarction, and ACE inhibitors are specifically indicated in patients with systolic heart failure or diabetic nephropathy.


ACE = angiotensin-converting enzyme.

Hypertension in Older Persons

Most of the randomized clinical trials on antihypertensive drug therapy in older and elderly persons primarily included those aged 60 to 79. Evidence-based data for management of octogenarians and beyond are available only for isolated systolic hypertension.18 Results from clinical trials that include large numbers of patients 80 years of age or older with combined hypertension should become available within the next five years.

PATHOPHYSIOLOGY

The most common type of hypertension in older persons is isolated systolic hypertension, defined as a systolic blood pressure of 140 mm Hg or more and a diastolic blood pressure of less than 90 mm Hg. Beyond the age of 55 years, the level of diastolic blood pressure typically decreases while the level of systolic blood pressure increases progressively. The underlying abnormality is increased vascular stiffness (decreased compliance), whereby little cushion is left to absorb and buffer the energy and pressure created by cardiac output. Both the combined (i.e., systolic blood pressure 140 mm Hg or more and diastolic blood pressure 90 mm Hg or more) and isolated systolic types of hypertension are characterized by increased total peripheral resistance.

TREATMENT WITH LIFESTYLE MODIFICATIONS

Data are few on the effectiveness of lifestyle modifications for the treatment of hypertension in patients aged 60 or older, although the recently completed Trial of Nonpharmacological Interventions in the Elderly (TONE)6 documented the efficacy of weight loss (in overweight patients), sodium restriction, or both in patients aged 60 to 79 years. A much smaller but well-designed trial demonstrated reduction of blood pressure (11.0/9.1 mm Hg) with restriction of sodium intake from 4,000 to 1,000 mg daily in patients aged 78 to 96 years.19 This degree of dietary sodium restriction is not achievable in most elderly hypertensive patients, although restriction toward a level of 2,300 mg daily (recommended by JNC VI) may more easily be accomplished.

TREATMENT WITH ANTIHYPERTENSIVE DRUGS

A meta-analysis of the treatment of hypertension in older persons (most of them 60 to 79 years of age) demonstrated clearly that drug therapy decreased the risk of stroke by an average of 32 percent.20 The reduction in coronary events was less impressive (about 14 percent) but still highly significant. In most of these trials, mortality related to all causes decreased but did not reach statistical significance. The trials primarily used diuretics and beta blockers. Adverse metabolic effects of diuretics (e.g., hypokalemia, hyperlipidemia, hyperglycemia) occur, but most are dose related. Biochemical abnormalities are less common with the lower dosages (i.e., equivalent to 12.5 to 25.0 mg of hydrochlorothiazide daily) that are currently recommended.

The impact of these adverse metabolic effects must be considered in the context of the risk of inadequate control of blood pressure. Table 2 shows that a small but statistically significant worsening of levels of cholesterol, triglyceride, glucose and serum potassium levels was observed in patients treated with diuretic-based therapy for isolated systolic hypertension in the Systolic Hypertension in the Elderly Program (SHEP).18 However, the remarkably good decrease in blood pressure (27/9 mm Hg) was associated with statistically significant reductions in fatal and nonfatal stroke (36 percent), cardiovascular disease (32 percent) and coronary heart disease (27 percent).18  Table 3 provides a summary of the beneficial effects of lowering blood pressure on stroke, according to age. Patients 80 years of age and older benefited as much as or more so than those aged 60 to 79 years. Isolated systolic hypertension is very treatable in patients aged 80 to 96 years. A good rule of thumb is to start low and go slow.21

TABLE 2

Beneficial Outcome with Diuretic-Based Therapy Despite Metabolic Abnormalities in 2,365 Elderly Patients with Isolated Systolic Hypertension

Variable Before therapy After therapy Average change

Cholesterol, mg per dL (mmol per L)

237 (6.10)

242 (6.25)

+ 6 (0.15)*

Triglycerides, mg per dL

145

166

+ 21*

Glucose, mg per dL (mmol per L)

108 (6.0)

115 (6.4)

+ 7 (0.4)*

Potassium, mEq per L (mmol per L)

4.5 (4.5)

4.1 (4.1)

−0.4* (−0.4)

Blood pressure, mm Hg

171/77

144/68

−27/−9*

Stroke (N)‡

103

−36%†

Cardiovascular disease (N)‡

289

−32%†

Coronary heart disease (N)‡

140

−27%†


N = number of patients.

*—P <0.05 for change from baseline.

†—P <0.05 versus group (N = 2,371) assigned to placebo.

‡—Fatal or nonfatal.

Information from Implications of the systolic hypertension in the elderly program. Hypertension 1993;21:335–43.

TABLE 2   Beneficial Outcome with Diuretic-Based Therapy Despite Metabolic Abnormalities in 2,365 Elderly Patients with Isolated Systolic Hypertension

View Table

TABLE 2

Beneficial Outcome with Diuretic-Based Therapy Despite Metabolic Abnormalities in 2,365 Elderly Patients with Isolated Systolic Hypertension

Variable Before therapy After therapy Average change

Cholesterol, mg per dL (mmol per L)

237 (6.10)

242 (6.25)

+ 6 (0.15)*

Triglycerides, mg per dL

145

166

+ 21*

Glucose, mg per dL (mmol per L)

108 (6.0)

115 (6.4)

+ 7 (0.4)*

Potassium, mEq per L (mmol per L)

4.5 (4.5)

4.1 (4.1)

−0.4* (−0.4)

Blood pressure, mm Hg

171/77

144/68

−27/−9*

Stroke (N)‡

103

−36%†

Cardiovascular disease (N)‡

289

−32%†

Coronary heart disease (N)‡

140

−27%†


N = number of patients.

*—P <0.05 for change from baseline.

†—P <0.05 versus group (N = 2,371) assigned to placebo.

‡—Fatal or nonfatal.

Information from Implications of the systolic hypertension in the elderly program. Hypertension 1993;21:335–43.

TABLE 3

Effect of Age on the Benefit of Diuretic-Based Therapy in Older Patients with Isolated Systolic Hypertension

Age range (years) Active treatment Placebo
Number of patients Stroke rate* Number of patients Stroke rate*

60 to 69

972

3.9

992

5.2

70 to 79

1,062

5.4

1,060

8.6

≥80

331

7.5

319

14.0


*—Five-year rate of fatal or nonfatal stroke per 100 patients.

Information from Implications of the Systolic Hypertension in the Elderly Program. Hypertension 1993;21:335–43.

TABLE 3   Effect of Age on the Benefit of Diuretic-Based Therapy in Older Patients with Isolated Systolic Hypertension

View Table

TABLE 3

Effect of Age on the Benefit of Diuretic-Based Therapy in Older Patients with Isolated Systolic Hypertension

Age range (years) Active treatment Placebo
Number of patients Stroke rate* Number of patients Stroke rate*

60 to 69

972

3.9

992

5.2

70 to 79

1,062

5.4

1,060

8.6

≥80

331

7.5

319

14.0


*—Five-year rate of fatal or nonfatal stroke per 100 patients.

Information from Implications of the Systolic Hypertension in the Elderly Program. Hypertension 1993;21:335–43.

Some concern has been expressed about the recommendation to use beta blockers as first-line therapy in elderly hypertensive patients without other complications. As summarized in a recent review by Messerli and associates,22 beta blockers reduced the risk of cerebrovascular events but were inferior to diuretics for prevention of coronary heart disease or cardiovascular mortality.

In the recent Systolic Hypertension in Europe (Syst-Eur) trial,23 a long-acting dihydropyridine calcium channel antagonist (nitrendipine [Baypress]) was compared with placebo in the treatment of isolated systolic hypertension. The study was stopped after two years because of the beneficial effects of the calcium channel antagonist. A decrease in systolic blood pressure of 23 mm Hg was associated with a 42 percent reduction in fatal and nonfatal stroke and a 26 percent reduction in coronary artery disease events.

In the Syst-Eur trial, the beneficial cardiovascular effects of a long-acting dihydropyridine calcium channel antagonist in older, high-risk patients quieted earlier concerns about the potential for adverse cardiovascular outcomes with the use of calcium channel antagonists.24 Beneficial long-term cardiovascular effects of another long-acting calcium channel antagonist (felodipine [Plendil]) were also observed in the Hypertension Optimal Treatment (HOT) study.25

Two recent studies26,27 reported superiority of an ACE inhibitor versus a calcium channel antagonist for reduction of cardiovascular events in hypertensive patients with diabetes. Both of these trials, however, were relatively small (less than 250 patients assigned to treatment with a calcium channel antagonist) and reported on secondary rather than primary trial end points; one used open-label medications. These studies probably demonstrate a beneficial effect of ACE inhibitors rather than a detrimental effect of calcium channel antagonists.28

The HOT trial25 used a long-acting calcium channel antagonist as primary therapy and included 1,501 diabetic patients in whom there was a significant 51 percent decrease in major cardiovascular events in those assigned to control of diastolic blood pressure to less than 80 mm Hg. Hence, either an ACE inhibitor or a long-acting dihydropyridine-type calcium channel antagonist can be appropriate therapy in patients with diabetes and hypertension but no other complications. The recent UK Prospective Diabetes Study Group Report,29 however, indicated that more than 25 percent of hypertensive patients with diabetes required three or more antihypertensive drugs to lower blood pressure to less than 150/85 mm Hg. The earlier SHEP study on isolated systolic hypertension30 included 551 diabetic patients and demonstrated an excellent decrease in the risk of cardiovascular events with diuretic-based therapy.

JNC VI1  has recommended new treatment goals for patients with uncomplicated versus complicated hypertension. These are summarized in Table 4. Reduction of blood pressure to less than 130/85 mm Hg was recommended for hypertensive patients with renal failure or diabetes, and reduction of blood pressure to less than 125/75 mm Hg was recommended for patients with proteinuria of 1 g or more daily. These optimal targets will be difficult to achieve and will often require the use of two or more antihypertensive drugs in addition to lifestyle modifications.

TABLE 4

New Treatment Goals Recommended by JNC VI*

Condition Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)

Hypertension

< 140

< 90

Isolated systolic hypertension

< 140

Diabetes mellitus

< 130

< 85

Renal failure

< 130

< 85

Proteinuria > 1 g daily

< 125

< 75


*—JNC VI = Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Information from The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413–46 [Published erratum in Arch Intern Med 1998;158:573].

TABLE 4   New Treatment Goals Recommended by JNC VI*

View Table

TABLE 4

New Treatment Goals Recommended by JNC VI*

Condition Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)

Hypertension

< 140

< 90

Isolated systolic hypertension

< 140

Diabetes mellitus

< 130

< 85

Renal failure

< 130

< 85

Proteinuria > 1 g daily

< 125

< 75


*—JNC VI = Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Information from The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413–46 [Published erratum in Arch Intern Med 1998;158:573].

The HOT trial25 alleviated concerns about any risk that might be associated with decreasing the diastolic blood pressure into the range of 80 to 89 mm Hg in older hypertensive patients. Maximal benefits of therapy were observed with systolic blood pressure levels between 130 and 140 mm Hg and diastolic blood pressure levels of 80 to 85 mm Hg. Average levels of systolic blood pressure below 130 mm Hg or diastolic blood pressure below 80 mm Hg were not achieved in the study.

Occasionally, patients may have persistent, severe elevations of systolic blood pressure despite compliance with a regimen of multiple medications and lifestyle modifications. In these patients, it is sometimes useful to try the addition of nitrates. Duchier and associates31 compared placebo with 20 mg of sustained-release isosorbide dinitrate (Isorbid) twice daily. After four months, systolic blood pressure had decreased by 30 mm Hg in the group taking nitrate, compared with a reduction of 14 mm Hg with placebo. A more recent double-blind, placebo-controlled study noted a 17 mm Hg decrease in systolic blood pressure and a significant 17 mm Hg lowering of pulse pressure in patients using 20 mg of isosorbide dinitrate twice daily.32 Great caution is indicated to ensure that the patient is not also taking sildenafil (Viagra), because of the risk of marked hypotension with concomitant use of sildenafil and nitrates.33

Specific recommendations for the management of hypertension in older persons are summarized in Table 5.

TABLE 5

Special Therapeutic Recommendations for Hypertension in Older Persons

In patients with isolated systolic hypertension, use diuretics (preferred) or long-acting dihydropyridine calcium channel antagonists as primary therapy.

Treat isolated systolic hypertension even in patients 80 years of age and older.

In patients with combined hypertension, reduce blood pressure to less than 140/90 mm Hg in those with no other complications and to less than 130/85 mm Hg in those with diabetes or renal failure.

TABLE 5   Special Therapeutic Recommendations for Hypertension in Older Persons

View Table

TABLE 5

Special Therapeutic Recommendations for Hypertension in Older Persons

In patients with isolated systolic hypertension, use diuretics (preferred) or long-acting dihydropyridine calcium channel antagonists as primary therapy.

Treat isolated systolic hypertension even in patients 80 years of age and older.

In patients with combined hypertension, reduce blood pressure to less than 140/90 mm Hg in those with no other complications and to less than 130/85 mm Hg in those with diabetes or renal failure.

The Author

W. DALLAS HALL, M.D., is a member of the Southern Society of Clinical Investigation, the American Heart Association (AHA) Council of Geriatric Cardiology and the AHA Council of Cardiovascular Disease Epidemiology. He has been principal investigator in several National Institutes of Health clinical trials. He completed his medical education at Emory University School of Medicine and Grady Memorial Hospital, Atlanta.

Address correspondence to W. Dallas Hall, M.D., 1100 Parker Place, Atlanta, GA 30324. Reprints are not available from the author.

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This article is one in a series developed in collaboration with the American Heart Association. Guest editor of the series is Rodman D. Starke, M.D., Senior Vice President of Science and Medicine, American Heart Association, Dallas.


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