30: Hypertension

Hypertension in older (and younger) adults is defined according to Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VII (JNC 7) criteria as blood pressure (BP) >140/90 mm Hg based on the mean of two or more properly measured seated readings on each of two or more office visits.

Hypertension is very common among older adults. The prevalence of hypertension is as high as 63% in ages 60–79 years, and 74% in age ≥80 years. Hypertension is a major risk factor for cardiovascular and cerebrovascular morbidity and mortality. In 2008, 1 in 6 deaths were caused by heart disease and 1 in 18 deaths were caused by strokes in United States. Aging, higher body weight, smoking, reduced physical activity, and salt intake are major risk factors for hypertension.

In the presence of normal diastolic BP (<90 mm Hg), elevation in systolic BP is referred to as isolated systolic hypertension (ISH). Systolic pressure rises with age but diastolic pressure rises until about 55 years of age, and then gradually falls thereafter (Figure 30–1). Therefore, isolated diastolic hypertension is rare in the older adults. Diastolic hypertension, when present, usually occurs in combination with systolic hypertension in older adults (diastolic–systolic hypertension).

Elevated pulse pressure (PP), which is systolic pressure minus diastolic pressure, is increasingly being recognized as an important predictor of cerebrovascular and cardiac risk in older adults. PP increases with age in a manner parallel to the increase in systolic BP.

Hypertension in older adults is largely caused by increased arterial stiffness (collagen replacing elastin in the elastic lamina of the aorta), which accompanies aging. This leads to increased pulse wave velocity, causing late systolic blood pressure (SBP) augmentation and increasing myocardial oxygen demand. Reduction of forward flow also occurs, thus limiting organ perfusion. These undesirable alterations, combined with preexisting coronary stenosis or excessive drug-induced diastolic blood pressure (DBP) reduction, predisposes older adults to development of left ventricular hypertrophy and heart failure.

Endothelial dysfunction is another important contributor to BP elevation in older adults. Mechanical and inflammatory injury of aging arteries causes decreased availability of vasodilator nitric oxide (NO), which causes an unfavorable balance between vasodilators (such as NO), and vasoconstrictors (such as endothelin).

Autonomic dysregulation contributes to orthostatic hypotension (decrease in SBP >20 mm Hg and/or DBP >10 mm Hg after 3 minutes of standing), which is a risk factor for falls, syncope, and cardiovascular (CV) events. Autonomic dysregulation also leads to orthostatic hypertension, which is an increase in SBP upon assumption of upright posture, and is a risk factor for left ventricular hypertrophy (LVH), coronary artery disease (CAD), and silent cerebrovascular disease. There is no consensus definition for orthostatic hypertension, although studies have used the definition of a 20-mm Hg rise in SBP on standing up.

Age-related renal dysfunction, with glomerulosclerosis and interstitial fibrosis, is gradual and progressive. However, it can be hastened by acute insults or comorbid conditions. The resulting reduction in glomerular filtration rate (GFR) and other renal homeostatic mechanisms, such as membrane sodium/potassium–adenosine triphosphatase, results in increased intracellular sodium, reduced sodium–calcium exchange, volume expansion, and resultant hypertension. As reduced renal tubular mass provides fewer transport pathways for potassium excretion, older hypertensive patients are more prone to development of hyperkalemia.

Older adults exhibit increased sensitivity to salt, because of an age-related decrease in renal function and sodium/potassium–adenosine triphosphatase, with resultant inability of kidneys to excrete a sodium load.

Most older adults with hypertension have primary, or essential, hypertension. Secondary hypertension refers to hypertension with an identifiable and treatable cause. Renovascular hypertension caused by renal artery stenosis is the most common cause of treatable secondary hypertension in older persons. Other causes, such as obstructive sleep apnea (OSA), primary aldosteronism, and thyroid disorders, should always be considered in cases where BP remains above target despite 3 medications at moderate doses, and where history and physical exam suggest these disorders.

Obstructive sleep apnea is a strong and independent risk factor for development and progression of hypertension, especially treatment-resistant hypertension and its CV and renal complications. Volume overload and fluid shifts, as well as increases in sympathetic activation, oxidative stress, inflammation, and release of vasoactive substances secondary to intermittent hypoxemia, contribute to BP elevation in patients with OSA.

Chronic inflammatory burden from inflammatory disorders can lead to arterial stiffness and thus hypertension. Also, the nonsteroidal antiinflammatory drugs (NSAIDs) used to treat these disorders can cause elevation of BP. Other drugs, such as cyclooxygenase-2 inhibitors, glucocorticoids, erythropoietin analogs, some disease-modifying antirheumatic drugs (eg, leflunomide), immunosuppressants (eg, cyclosporine and tacrolimus), and antidepressants (eg, higher doses of venlafaxine), may increase BP. Saw palmetto, St. John’s wort, licorice, ergotamine, and ergot-containing herbal preparations are associated with hypertension. Among street drugs, “herbal ecstasy,” cocaine (and cocaine withdrawal), nicotine (and nicotine withdrawal), and stimulants (eg, methylphenidate), are also associated with hypertension.

Pheochromocytomas are rare tumors, responsible for 0.5% cases of secondary hypertension, that usually present between 30 and 60 years of age. Intracranial tumors in structures close to glossopharyngeal nerve can lead to baroreceptor failure, which can present as volatile hypertension (abrupt increase in BP, lasting minutes to hours, and tachycardia), hypertensive crisis (severe, unremitting hypertension, tachycardia, and headache) or orthostatic tachycardia (increase in heart rate [HR] by >30 beats/min from the supine to upright position).

Four common conditions in older patients are associated with or complicate the diagnosis of hypertension: “white-coat” or “office” hypertension, postural or orthostatic hypotension, postprandial hypotension, and pseudohypertension.

White-coat hypertension is mild hypertension noted in the physician’s office but with repeatedly normal measurements at home, at work, or by 24-hour ambulatory blood pressure monitoring (ABPM). End-organ disease, such as LVH, hypertensive retinopathy, or nephropathy, is notably absent. White-coat hypertension commonly coexists with metabolic risk factors such as hypercholesterolemia and hyperinsulinemia. However, the Syst-Eur trial and subgroup analysis of older patients in the IDACO study groups indicates that untreated individuals with white-coat hypertension had similar CV risk as individuals with normal BP.

Orthostatic hypotension is a 20-mm Hg drop in systolic BP or a 10-mm Hg drop in diastolic BP when rising from a sitting position. It is prevalent in approximately 20% of community-dwelling individuals >65 years of age, and in 30% of those >75 years of age. Orthostatic hypotension is associated with diabetes, hypertension, low body mass index, Parkinson disease, multiple system atrophy, Lewy body dementia, and medications. Among antihypertensives, α blockers, combined α and β-blockers, nitrates and diuretics can cause or aggravate orthostatic hypotension. In addition, antidepressants (such as paroxetine, sertraline, venlafaxine, and trazodone) and antipsychotics (such as risperidone, olanzapine, and quetiapine) can cause orthostatic hypotension. Diastolic orthostatic hypotension measured 1 minute after standing up and systolic orthostatic hypotension measured 3 minutes after standing up are predictive of a high vascular mortality in older home-dwelling persons. Orthostatic hypotension is also associated with increased risk of falls in older adults. Older adults should be screened for orthostatic hypotension on routine encounters. If symptomatic, culprit medications should be tapered or discontinued. Following prolonged bed rest or inactivity (eg, following hospitalization), patients should be instructed to stand up gradually to reduce excessive pooling of blood in the lower extremities. Activities that reduce venous return to the heart, such as coughing, straining, and prolonged standing, should be avoided, especially in hot weather. Knee-high compression stockings may be helpful in mild cases. Waist-high compression stockings with abdominal binders may be needed in more severe cases. In patients with autonomic failure and supine hypertension, raising the head of the bed by 10–20 degrees at night can reduce hypertension, prevent overnight volume loss, and help restore morning BP upon standing. Liberal intake of salt and water to achieve a 24-hour urine volume of 1.5–2 L may attenuate fluid loss commonly seen in autonomic insufficiency. In older adults with orthostatic hypotension caused by deconditioning, an exercise regimen comprising swimming, recumbent biking, or rowing can help with symptoms.

Postprandial hypotension has been defined as a 20-mm Hg decrease in SBP, or a decrease in SBP from >100 mm Hg to below 90 mm Hg within 2 hours after a meal. Falls, syncope, strokes, transient ischemic attacks, angina, and myocardial infarctions can result, and postprandial hypotension is an independent predictor of mortality. Postprandial hypotension occurs in 25% to 38% of institutionalized older adults. It appears to be a result of blunted sympathetic response to normal physiologic postmeal decrease in BP. It is more common among older adults with Parkinson’s disease, diabetes, and essential hypertension. Polypharmacy, especially the use of diuretics and psychotropic medications, also appears to be a risk factor. Postprandial decreases in BP may be managed through a regimen of small frequent meals, limited dietary carbohydrates, and drinking water or coffee before meals. Among pharmacologic agents, α glucosidase inhibitors, guar gum, or premeal octreotide injections may aid in management.

Pseudohypertension is a significantly higher peripheral pressure (eg, brachial site) compared with a direct arterial measurement. Arterial rigidity from extensive atherosclerosis is considered to be responsible for this relatively rare phenomenon. Although it can be diagnosed by direct intraarterial measurement, this invasive technique is usually unnecessary. The presence of an Osler sign (a palpable radial artery when BP cuff is inflated above the systolic BP) is suggestive, but not diagnostic, of this condition. Pseudohypertension may be suspected in those who appear resistant to an adequate drug regimen, those who become very symptomatic to a gentle pharmacologic regimen, and those with very elevated BP but no clinical evidence of end-organ disease. Incidental radiographs of the distal extremities may reveal extensive arterial calcification.

Symptoms & Signs

Most older adults with hypertension are asymptomatic. A minority may present with dizziness, palpitations, or headache. A morning headache, usually occipital, may be characteristic of stage III hypertension. End-organ damage, such as stroke, congestive heart failure (CHF), or renal failure, may be the initial presentation.

Patient History

A history suggesting postprandial or orthostatic hypotension may be elicited. These syndromes may reflect longstanding hypertension or the presence of associated problems that need to be considered in treating hypertension.

Patient history should be directed toward the possibility of secondary hypertension, focusing on recent weight gain, polyuria, polydipsia, muscle weakness, history of headaches, palpitations, diaphoresis, weight loss, anxiety, and sleep history (eg, daytime somnolence, loud snoring, and early morning headaches).

Symptoms suspicious for target organ damage include headache, transient weakness or blindness, claudication, chest pain, and shortness of breath. Comorbid conditions such as diabetes mellitus, CAD, heart failure, chronic obstructive pulmonary disease, gout, and sexual dysfunction are important to elicit because they will have an impact on coronary risk factor stratification and choice of initial therapy.

Medication history should include previous BP medications, current prescription drugs, over-the-counter drugs (especially NSAIDs and cold medicines), and herbal supplements (especially St. John’s wort and saw palmetto). Lifestyle issues, including smoking, alcohol intake, drug use, regular exercise, and degree of physical activity, should be assessed. A dietary history targeting sodium (which can raise BP), fat intake (which can contribute to CV risk), and alcohol (which can raise BP if consumed in excessive amounts) is important as well.

Physical Examination

The physical examination focuses on the confirmation of hypertension and identification of possible secondary causes. Diagnosis of hypertension should be based on at least 3 different BP measurements on 2 or more separate office visits. Routine BP should be measured using an appropriate cuff size at heart level, while seated comfortably for at least 5 minutes. Orthostatic BP should be measured sitting, then standing after 1 then 3 minutes. It is advisable to check BP at least 1 hour after any consumption of alcohol, caffeine, or tobacco.

Home and 24-hour ambulatory BP monitoring may help differentiate truly resistant hypertension from white-coat hypertension.

Frail older nursing home residents may exhibit increased variability in BP readings during the day, where BP is likely elevated before breakfast and falls after breakfast. To avoid overaggressive treatments in this high-risk population, it is advisable to diagnose hypertension based on multiple readings, both before and after meals, as well as supine and standing.

Laboratory Tests

Complete blood count, renal and metabolic panel, lipid profile, thyroid-stimulating hormone (TSH), urinalysis (to quantify proteinuria), and 12-lead electrocardiogram are included in the initial evaluation.

Evidence should be sought for end-organ target disease (ie, ophthalmologic vascular changes, carotid bruits, distended neck veins, third or fourth heart sound, pulmonary rales, and reduced peripheral pulses). A cognitive evaluation (eg, the Montreal Cognitive Assessment or St. Louis University Mental Status Exam) is also helpful in tracking longitudinal cognitive changes in the older hypertensive patient. Secondary causes, including renal bruits (renal artery stenosis); moon face, buffalo hump, and abdominal striae (Cushing syndrome); tremor, hyperreflexia, and tachycardia (thyrotoxicosis) should be assessed.

Older persons with hypertension have higher absolute risks of CV and cerebrovascular events. They are also more likely to have other comorbid conditions that worsen these outcomes. Thus, preventing target organ damage in older adults with hypertension is vital to reducing morbidity and mortality from hypertension. Target organ damage can occur overtly, in the form of stroke, acute myocardial infarction (MI), heart failure, or arrhythmia, or, more subtly, in the form of a neuropsychiatric deficit such as cognitive impairment. Atrial fibrillation is often a complication of hypertensive disease in older adults; 15% of strokes occur in people with atrial fibrillation. Diastolic dysfunction increases with age secondary to reduced vascular compliance and increased impedance to left ventricular ejection related to aging myocardium.

Other important complications include chronic renal insufficiency, end-stage renal disease, malignant hypertension, and encephalopathy. These disorders are most common with severe or poorly controlled hypertension.

Hypertension in mid-life (age 40–64 years) is a strong risk factor for cognitive impairment in late life (age >65 years). Hypertension is a known cause of vascular dementia (VaD) and studies have shown its effect on prevalence of Alzheimer dementia. However, there is no convincing evidence that lowering BP in late-life prevents the development of dementia or cognitive impairment in hypertensive patients without apparent prior cerebrovascular disease.

Thus, preventing organ damage in older adults is best accomplished by preventing and treating elevated BP in young and middle aged adults. As noted earlier, treatment of hypertension in older adults has substantial clinical benefit in stroke reduction. However, if life expectancy is less than 1 year, adapting targets to symptom reduction rather than stroke reduction may be considered.

Hypertension

The general objective of hypertension management for both community-dwelling and nursing home patients is to reduce morbidity and mortality by early diagnosis and treatment with the least-invasive and most cost-effective methods. Classification of hypertension, stratification for CV risks, and management strategies according to JNC 7 guidelines are shown in Table 30–1. Table 30–2 enumerates major risk factors. Little information is available to guide clinicians regarding hypertension management in octogenarians and nursing home residents, typically the frail, older adult group.

The National Institute for Health and Clinical Excellence (NICE) recommends aiming for a target BP below 140/90 mm Hg in people younger than 80 years of age with treated hypertension, and for a target clinic BP below 150/90 mm Hg in people age 80 years and older with treated hypertension. The American College of Cardiology Foundation and American Heart Association (ACCF/AHA) 2011 Expert Consensus recommends that an achieved SBP of 140–145 mm Hg, if tolerated, is acceptable in octogenarians. In patients with hypertension and chronic kidney disease (CKD) or diabetes mellitus (DM), JNC 7 recommends goal BP of <130/80 mm Hg irrespective of age, a target that may be too aggressive for most older adults.

The ACCORD-BP trial (age range: 40–79 years) failed to show any reduction in fatal and nonfatal major CV events with lowering SBP to <120 mm Hg, when compared with target SBP <140 mm Hg, in diabetics at high risk for CV events. These results were supported by the INVEST diabetes subgroup analysis, where mean age group was 66 years. In the AASK trial (age 18–70 years), lowering mean arterial pressure (MAP) to a goal of <92 mm Hg, didn’t show any significant difference in all-cause mortality, CV death, or overall CV events, when compared to the usual MAP goal of 102–107 mm Hg, in African Americans with CKD. Consistent with difficulties in finding data for the oldest adults, the ACCORD-BP trial excluded those aged >79 years, whereas AASK trial excluded those aged >70 years. HYVET (Hypertension in the Very Elderly Trial), which targeted adults age >80 years and aimed reduction in BP to <150/80 mm Hg in the active treatment group, showed reduction in incidence of strokes, but a nonsignificant increase in all-cause mortality and CV mortality in the active treatment group compared to placebo. In the INVEST substudy on outcomes of treatment of hypertension in individuals with CAD age >80 years when compared with individuals age <80 years, there was persistence of “J-curve” relationship between lower BP (especially DBP) and increased all-cause mortality, nonfatal MI and nonfatal strokes in individuals age >80 years (Figure 30–2). Keeping in view this data, it is expected that JNC 8 guidelines will have a fresh outlook on this issue.

Management of hypertension in frail older adults should be tailored while keeping in mind the individual’s functional and cognitive status, and possible side effects of each management plan. The clinical benefit of treating hypertension in older adults appears within a year of treatment. Therefore, treatment of hypertension in older adults with limited life expectancy requires a review of benefits and risks of such therapy.

Nonpharmacologic Therapy—

Lifestyle interventions may benefit older adults with hypertension and can include the following:

1. Dietary sodium

   The USDA recommends reduction in dietary sodium intake to 2.3 g (6 g of sodium chloride) per day for adults 50 years or younger, and <1.5 g for adults >51 years, and those at high risk for vascular diseases. However, restricting sodium in frail elders may worsen or precipitate anorexia, malnutrition, sarcopenia and orthostatic hypotension. The TOHP and TONE trials which demonstrated long-term benefits of dietary salt reduction excluded very old subjects. The strongest evidence for dietary sodium recommendations for hypertension in older adults comes from the TONE trial, where there was clinical benefit to lowering dietary sodium to a mean of 2.3 g daily to adults up to the age of 70 years. There are no data in older adults supporting a 1.5-g sodium restriction.

2. Diet plan

   The Mediterranean diet has been shown to reduce all-cause mortality, and mortality as a result of cancer and CV disease in older adults. The Dietary Approaches to Stop Hypertension (DASH) diet includes whole grain products, fish, poultry, and nuts, with reduction in lean red meat, sweets, added sugars, and sugar-containing beverages. It is rich in potassium, magnesium, calcium, protein, and fiber. The DASH diet has shown reduction in BPs in short-term studies (with up to 8 weeks of follow-up) in middle-aged adults, but lacks long-term follow-up data in older adults.

3. Alcohol

   Heavy alcohol intake (>300 mL/week or 34 g/day) is strongly, significantly, and independently related to elevation in SBP and DBP. It is also associated with higher risk of CV events, strokes, and all-cause mortality compared with occasional drinking. Aging is associated with a number of physiologic changes suggesting increased sensitivity to alcohol, which can additionally lead to increased cognitive impairment, functional decline, and falls in this population. Moderate alcohol consumption (1 standard drink, or 14 grams of pure alcohol, per day) is associated with reduced risk of CV disease. Therefore, the U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommends that those age 65 years and older limit themselves to 1 alcoholic drink per day. However, further reduction may be considered in older adults experiencing cognitive impairment, falls, and functional decline, and for those who take prescription psychotropic medicines.

   A standard drink is 12 oz of beer with 5% alcohol, 5 oz of wine with 12% alcohol, or 1.5 oz of hard liquor with 40% alcohol.

4. Exercise

   Increasing physical activity to 30–45 minutes of aerobic activity 4 or more days per week. If this is not attainable, any increase in physical activity is likely to be beneficial.

5. Weight reduction

   An obese older adult has a body mass index (BMI) >30 kg/m². The TONE trial showed reduction in BP with weight loss through physical exercise and dietary restrictions. However, it excluded individuals >80 years old and those with chronic diseases. Population data in older adults suggest that being underweight poses as great a threat to physical disability as being excessively obese. A 12-year follow-up of mortality data of the weight loss intervention group of TONE trial failed to show any mortality benefit over the non–weight-loss intervention group. Therefore, moderate weight loss should be encouraged in obese older adults, only if consistent with functional and nutritional goals.

6. Smoking cessation

   Older adults should be encouraged to quit smoking, with the assistance of nicotine patches, gums, etc. Bupropion and varenicline may be prescribed while monitoring for adverse effects.

7. Polypharmacy

   Medications that can potentially impair BP control (eg, venlafaxine, NSAIDs) should be stopped if clinically possible, weighing benefits and risks of such treatments.

8. Dark chocolate

   Polyphenol-rich dark chocolate has been shown to lower BP in various studies. Clinical outcome data (eg, stroke reduction) are not available.

   Use of nonpharmacologic measures to control hypertension in the nursing home setting may be limited because residents are often impaired in their activities of daily living, and unable to participate in moderate exercise. Also, weight loss is a problem rather than a goal for most nursing home residents. If their diet is restricted in salt or animal and dairy fat, they may lose weight, strength, muscle mass, bone density and essential nutrients.

Pharmacologic therapy—

Antihypertensive medication improves CV and cerebrovascular outcomes in older adults with BP ≥160/90 mm Hg. The absolute benefit of hypertension treatment tends to be greater in men, in patients age 70 years or older, in those with previous CV complications, and in the presence of wider PP. The key to achieving maximal benefit and minimal risk in older adults is to “start low and go slow.” Lower initial doses of antihypertensives minimize the risk of postural and postprandial hypotension as well as ischemic symptoms, especially in frail older adults. Choice of initial antihypertensive agent thus depends on comorbidities and side effects. If the baseline BP is more than 20/10 mm Hg above goal or optimal reduction in BP is not achieved with one agent, a second agent can be added while weighing benefits and risks of such therapy on individual basis.

Special attention should be paid to frail patients and octogenarians when initiating a new antihypertensive medication. They should be seen frequently, with updated medical history and assessment for any new adverse effects, especially dizziness or falls. Standing BP should always be checked to identify excessive orthostatic decline. Although BP values below which vital organ perfusion is impaired in octogenarians are unknown, SBP <130 and DBP <65 mm Hg should be avoided.

Route of administration may be an issue in nursing home residents with dysphagia and those who are unwilling to take pills. A low dose clonidine or nitroglycerin patch may be beneficial in BP management in these situations, while monitoring for potential adverse effects, particularly from clonidine. Because orthostatic and postprandial hypotension may contribute to the risk of falling, it may be appropriate to titrate antihypertensives based on readings obtained in standing posture. Also, BP tends to be highest before breakfast in the nursing home resident, and falls after breakfast. So titration of antihypertensives should be done based on multiple readings during various times of the day.

Table 30–2 summarizes data on antihypertensive agents commonly used in older patients.

Diuretics—

Thiazide and related diuretics are the preferred first-line treatment in older adults and have proved particularly effective in blacks and in salt-sensitive hypertensive patients. Diuretics have been shown to lower cerebrovascular and CV morbidity and mortality, decrease left ventricular mass, and prevent heart failure. Diuretics are a reasonable choice for diabetics based on findings of ALLHAT trial, which indicated that despite the slightly higher incidence of diabetes in the thiazide treatment group of the trial, there was no significant difference in clinical events in diabetic patients assigned to either diuretic, angiotensin-converting enzyme (ACE) inhibitor or calcium channel blocker regimen. In low doses, thiazides have advantages of low cost and possible preservation of bone mineral density in older women. Side effects of thiazides include increased insulin resistance, hypokalemia, hypomagnesemia, hyponatremia, hypercalcemia, orthostatic hypotension, urinary incontinence, sexual dysfunction, and exacerbation of gout. Thiazides may be ineffective in patients with a creatinine clearance of <30 mL/min and can be replaced by loop diuretics (eg, furosemide) when a diuretic agent is necessary.

Angiotensin-converting enzyme inhibitors & receptor blockers—

Because of well-known renoprotective effects of ACE inhibitors and ACE receptor blockers (ARBs) in type 2 diabetes, current guidelines suggest using one of these agents as first-line drugs in older adults with both diabetes and hypertension. ACE inhibitors also appear to improve vascular outcomes in high-risk patients, including diabetics and those with established vascular disease. The LIFE study showed reduced CV mortality and incidence of stroke in individuals with ISH when treated with losartan (ARB) compared to atenolol (β-blocker). ARBs are also used when there is intolerance to ACE inhibitors (because of cough). There is no long-term data available on aliskiren, which is the only available drug in the class of direct renin inhibitors.

β Blockers—

Older adults are less responsive than younger adults to β blockers and are less likely to have BP control with β-blocker as a sole agent. In addition, compared with diuretics, β blockers may offer less reduction in cerebrovascular and CV events in older antihypertensive patients. However, they are effective in older adults with CAD for secondary prevention of MI, for rate control with exercise in atrial fibrillation, and for reducing mortality and hospital readmission in patients with left ventricular systolic dysfunction.

Calcium channel blockers—

Nitrendipine (not currently available in United States), a dihydropyridine calcium channel blocker (CCB) related to amlodipine and felodipine, significantly decreases the risk of cerebrovascular morbidity and mortality. Dihydropyridine CCBs are available in the United States and include nifedipine, amlodipine, and felodipine. The ACCOMPLISH trial showed that amlodipine-based regimen may be more effective than a thiazide-based regimen in reducing CV events in high-risk patients, including diabetics, and is a good alternative choice for diabetics. However, CCBs are a heterogeneous group, and the benefits of one class of CCBs may not necessarily be extrapolated to another. Diltiazem and verapamil, two commonly used nondihydropyridine CCBs, have negative inotropic and chronotropic effects on left ventricular systolic function compared with amlodipine or felodipine. They may be used as adjunctive agents in patients with renal parenchymal disease and resistant hypertension but should be used with caution in systolic dysfunction.

α Blockers—

Low doses of selective α₁-adrenergic antagonists (eg, terazosin, doxazosin) may be useful for managing hypertension in the setting of benign prostatic hypertrophy. Their major side effects are orthostatic hypotension, reflex tachycardia, and headache. The findings of slightly increased risk of stroke and CV events and a doubled risk of CHF in the doxazosin arm compared with chlorthalidone in the ALLHAT trial, suggest that the α-antagonists should not be chosen as a first-line antihypertensive agent.

Aldosterone antagonists—

Aldosterone antagonists (spironolactone and eplerenone) are often beneficial in resistant hypertension due to primary hyperaldosteronism and OSA, including in African Americans.

Combination drugs—

JNC 7 recommends that combination drug therapy be initiated for stage II hypertension (SBP ≥160 or DBP ≥100 mm Hg). In the ALLHAT trial, approximately half of the high-risk older adults with hypertension required combination therapy. Participants on lisinopril and amlodipine were more likely to require combination therapy than those assigned chlorthalidone. This finding supports the JNC recommendation that a diuretic be a primary choice for an antihypertensive agent.

Combination drugs potentiate antihypertensive activity by acting at different sites simultaneously. Formulations that combine low doses of different classes of drugs improve BP control while minimizing the adverse effects of either drug. These drugs may, in some cases, be priced competitively with either of the combination agents, reducing the patient’s out-of-pocket expenses as well. Lower cost, increased ease of compliance, and potential for fewer side effects make combination drugs attractive for use in older adults once the need for more than one agent is established.

Diabetes & Hypertension

Type 2 diabetes is 2.5 times more likely to develop in individuals with preexisting hypertension compared with those with normal BP and greatly increases CV risk. Treatment options are discussed in individual drug sections.

Hypertension in African Americans

The first-line agent in African Americans with uncomplicated hypertension should be a thiazide diuretic. CCBs effectively lower BP and decrease CV events, especially stroke in this population, and can be a good alternative or second choice. Renin-angiotensin-aldosterone system (RAAS) inhibitors appear less effective than other drug classes in decreasing BP in older African Americans, unless combined with diuretics or CCB.

Hypertension & Chronic Kidney Disease

Treatment with an ACE inhibitor or ARB is recommended in presence of proteinuria >300 mg/day or concomitant history of heart failure. However, the AASK trial failed to demonstrate any reduction in CV outcomes with β blocker versus ACE inhibitor versus amlodipine CCB regimen in treatment of hypertension in African American patients with CKD.

Hypertension & Heart Failure

Older adults with hypertension and systolic heart failure (HF) should be treated with a diuretic, β-blocker, ACE inhibitor, and aldosterone antagonist in absence of hyperkalemia or significant renal dysfunction. If a patient cannot tolerate ACE inhibitor, an ARB should be used. Older African American patients with hypertension and HF may also benefit from combination of hydralazine and isosorbide dinitrate. Hypertension and asymptomatic left ventricle dysfunction should be treated with β-blocker and ACE inhibitor. If HF is refractory to conventional therapy, work-up for renal artery stenosis should be pursued as renal revascularization may improve HF in hypertensive patients.

Diastolic HF is very common in the older adults. Fluid retention should be adequately treated with loop diuretics, hypertension should be controlled, and comorbidities should be treated. No specific drug class demonstrates superior clinical outcomes at this time.

Resistant Hypertension

Hypertension is considered resistant if BP cannot be reduced to goal with an appropriate triple-drug regimen, including a diuretic (plus ACE inhibitor, CCB, β-blocker, or ARB) and if each of the 3 drugs is at or near maximum recommended doses. With ISH in older adults, resistant hypertension is defined as the inability to lower systolic BP to <160 mm Hg with a similar regimen.

The common causes of resistant hypertension include patient nonadherence to the prescribed medications and diet, a suboptimal medication regimen, drug interaction, pseudotolerance (salt, water retention), and office hypertension. Secondary hypertension and pseudohypertension should also be considered.

In hypertensive patients with OSA who are overweight, the cornerstone of treatment is weight loss, which improves sleep efficiency and oxygenation and lowers BP. In the absence of dramatic reductions in etiologic factors for OSA, these patients generally require lifetime treatment with continuous positive airway pressure to reduce the number of hypoxemic events. Addition of the mineralocorticoid-receptor antagonist spironolactone to conventional antihypertensive-drug regimens has been shown to reduce the severity of OSA and to lower BP in patients with OSA and resistant hypertension.

A patient’s adherence to dietary salt moderation can be estimated by obtaining a 24-hour urine collection for sodium. If the patient’s hypertension remains resistant, other medications can be added to the triple therapy. Clonidine in tablet form or by transdermal patch, or another centrally acting sympatholytic agent, can be considered in low doses to avoid side effects of sedation and orthostatic hypotension. Minoxidil, reserpine, and hydralazine are used cautiously because of their high rates of side effects in older patients.

American College of Cardiology. www.acc.org

American Heart Association. www.americanheart.org

American Society of Hypertension. www.ash-us.org

Cardiosource. www.cardiosource.com

Centers for Disease Control and Prevention. www.cdc.gov/nchs/fastats/hypertens.htm

Lifeclinic. www.bloodpressure.com

National Heart, Lung, and Blood Institute. www.nhlbi.nih.gov

National Institute of Alcohol Abuse and Alcoholism. Module 1: Epidemiology of Alcohol Problems in the United States. http://pubs.niaaa.nih.gov/publications/Social/Module1Epidemiology/Module1.html