Hypertension in the elderly: Some practical considerations

Detecting and treating renal artery stenosis

Though we do not intend to detail the diagnostic approaches and treatments for the various causes of secondary hypertension, we need to briefly mention those for renal artery stenosis.

According to the 2006 ACC/AHA guidelines on peripheral artery disease,²⁸ testing for renal artery stenosis is indicated only if a subsequent corrective procedure is a viable option.

Renal arteriography remains the gold standard for diagnosing renal artery stenosis. However, noninvasive imaging has largely replaced it.

Duplex Doppler ultrasonography, compared with angiography, has a sensitivity of 84% to 98% depending on operator experience, and a specificity of 62% to 99% for detecting renal artery stenosis.²⁹ Some of its limiting factors are the time needed to do the study, its steep learning curve and operator-dependence, and interference with the results by body fat and intestinal gas.

Computed tomographic angiography has a sensitivity of over 90% for detecting renal artery stenosis, and its specificity has been shown to be as high as 99% in certain studies.²⁹ Use of contrast can be a limiting factor in some clinical settings.

Magnetic resonance angiography also offers a sensitivity of 90% to 100% and specificities of 76% to 94% for detecting renal artery stenosis.²⁹ On the other hand, it is costly, and the gadolinium contrast solution used is nephrotoxic, though not as toxic as the contrast used in computed tomographic angiography.

As previously stated, these imaging studies should be used only if corrective measures will be undertaken if clinically significant renal artery stenosis is found. Even in such cases, revascularization may not be curative in all cases. Its effectiveness has been compared with that of medical management alone in a number of studies.^30,31 A meta-analysis³² of six key trials involving more than 1,200 patients showed no difference in systolic and diastolic blood pressures and other clinical outcomes, including all-cause mortality, between the two treatment groups over a 29-month follow-up period.

Hence, although we advise that causes of secondary hypertension be considered in cases of inappropriate hypertension, aggressive management must be pursued on a case-by-case basis.

CASE 2: DRUG ADVERSE EFFECTS

A 75-year-old Hispanic woman with a history of treated breast cancer was recently diagnosed with hypertension. Her blood pressure is controlled on amlodipine (Norvasc) 10 mg daily, and her blood pressure today is 128/80 mm Hg. Her only complaint during this office visit is some swelling of her ankles.

Edema and dihydropyridine calcium channel blockers

Like all drugs, antihypertensive medications come with their own set of adverse effects. These are more common as people age—hence the importance of identifying and effectively managing them in the elderly population.

Calcium channel blockers, especially the dihydropyridines—ie, nifedipine (Adalat), amlodipine, felodipine (Plendil), and isradipine (DynaCirc)—are known to cause peripheral vasodilation. Peripheral edema is a common dose-related effect in people on these drugs. In one study, median leg weight increased by 80 g after amlodipine 5 mg was given for 4 weeks, and by another 68 g on a 10-mg dose.³³

Ankle swelling, encountered more in women, can be very bothersome. The swelling is related to hyperfiltration of fluid into the interstitial space secondary to intracapillary hypertension. Calcium channel blockers predominantly cause arteriolar dilation by paralyzing the precapillary sphincter, thereby elevating intracapillary pressure.

Traditionally, physicians have lowered the dose of the calcium channel blocker, switched to another drug, or added a diuretic to alleviate the swelling. However, giving a diuretic for edema induced by a calcium channel blocker may not relieve the edema.³⁴

Peripheral edema is much less encountered when a calcium channel blocker is given with an inhibitor of the renin-angiotensin system.³⁵ A meta-analysis concluded that the incidence of peripheral edema was lowered by 38% with such a combination. The same study found angiotensin-converting enzyme (ACE) inhibitors significantly more efficacious for this effect than angiotensin receptor blockers (ARBs).³⁵

ACE inhibitors and ARBs are known to cause venodilation, thereby lowering intra-capillary pressure. It is probable that this effect helps remove the extra fluid sequestered in the capillary bed by the arteriolar dilation from the calcium channel blocker.

Pedal edema associated with use of a calcium channel blocker occurs much more commonly in the elderly than in the young. It is clearly dose-dependent, and the incidence peaks after 6 months of therapy. In the patient described above, adding a low dose of an ACE inhibitor or an ARB (if the patient is ACE inhibitor-intolerant) should relieve the swelling.

Hyponatremia and diuretics

Electrolyte imbalances are another common problem encountered in the elderly. Even though for years attention has been directed to the potassium level, hyponatremia has been equally associated with adverse effects in the elderly, such as an increased risk of fractures as shown in the Rotterdam study.³⁶

In 180 hypertensive inpatients, mean age 76.4, Sharabi et al³⁷ found the incidence of hyponatremia to be three times higher in women than in men (odds ratio 3.10, 95% confidence interval 2.07 to 4.67). Patients were 10 times more likely to be affected after age 65 and 14 times more likely after age 75. Most of the patients affected (74.5%) used a thiazide-type diuretic. Even though in many of the patients diuretics were used for more than 1 year before hyponatremia developed, susceptible patients—such as the frail elderly—can develop severe hyponatremia within days of starting to use a thiazide.³⁸

Severe hyponatremia is potentially life-threatening. Most cases are caused by thiazide rather than loop diuretics.³⁸ Thiazides inhibit electrolyte transport at the cortical diluting sites. As they decrease the glomerular filtration rate acutely, they increase proximal water reabsorption (making the plasma hypotonic), reducing water delivery distally. Loop diuretics, on the other hand, have their main effect at the thick ascending limb, reducing the osmolality at the medullary interstitium and not affecting proximal water reabsorption. Additionally, loop diuretics have a shorter half-life than thiazides, which makes hyponatremia more likely to happen with thiazides.

In patients who develop hyponatremia secondary to diuretic use, appropriate treatment includes stopping the medication, restricting water intake, and repleting electrolyte stores.³⁸ As with any cause of chronic hyponatremia, correction must be cautiously monitored and not hastily done.

Therefore, we advise adding a thiazide diuric with caution in the elderly, and we advise avoiding thiazides in patients with high water or alcohol intake.

CASE 3: DEMENTIA AND HYPERTENSION

A 74-year-old man with long-standing hypertension, gout, and chronic obstructive pulmonary disease was recently diagnosed with Alzheimer dementia. He takes enalapril (Vasotec) 10 mg daily for his blood pressure. His blood pressure is 130/78 mm Hg.

Dementia is one of the most important and common neurologic disorders in the elderly. With the rise in average life expectancy, its magnitude has grown to cause a substantial emotional and economic burden on society and health care.

Midlife hypertension has been demonstrated to be an important modifiable risk factor for late-life cognitive decline,³⁹ mild cognitive impairment,⁴⁰ and dementia of all causes.⁴¹ It has been suggested that hypertension might be part of the pathogenesis of dementia, and targeting high blood pressure might prevent its onset.

Moreover, a significant reduction in both Alzheimer and vascular dementia was demonstrated (risk reduction 55%) with the use of a long-acting dihydropyridine calcium channel blocker (nitrendipine) in the Syst-Eur study.⁴² However, data from studies such as Systolic Hypertension in the Elderly Program (SHEP) and the HYVET substudy of cognitive function assessement⁴³ showed no difference in dementia between placebo and active therapy with chlorthalidone (Hygroton) (in SHEP) or indapamide (Lozol) (in the HYVET substudy).

Disorders of calcium homeostasis are associated with the brain’s aging process. Probably, the neuroprotective effect of nitrendipine seen in Syst-Eur was due to its ability to affect this process, independent of its blood pressure-lowering effect.

In another prospective study, people over 60 years of age who complained of subjective memory loss showed a significant and positive association between memory scores and the use of calcium channel blockers (+0.14 ± 0.09 in users vs −0.12 ± 0.06 in nonusers; P = .016) independently of age, sex, white matter hyperintensities, and carotid wall cross-sectional area, all of which were associated with worse memory scores.⁴⁴

Drugs that block the renin-angiotensin system have also been proposed to delay the onset and slow the progression of dementia.⁴⁵ A small randomized, controlled trial suggested that centrally active ACE inhibitors—those that cross the blood-brain barrier, such as captopril (Capoten), lisinopril (Prinivil), ramipril (Altace), and fosinopril (Monopril)—slow cognitive decline in Alzheimer dementia more than non-centrally active ACE inhibitors or calcium channel blockers.⁴⁶

Sink et al⁴⁷ examined data from participants in the Cognition Substudy of the Cardiovascular Health Study⁴⁸ on the effect of ACE inhibitors on cognitive decline. ACE inhibitors, as a class, showed no benefit in reducing the risk of dementia compared with other antihypertensive drug classes. However, centrally active ACE inhibitors, compared with other medications, were associated with a 65% reduction in cognitive decline per year of drug exposure (P = .01). Non-centrally active ACE inhibitors worsened cognitive decline.

It appears that the brain’s renin-angiotensin system plays a role in the pathogenesis of dementia. Indeed, ACE has been shown to degrade amyloid-beta protein, and its level was increased in brain tissue of Alzheimer patients postmortem.⁴⁹

The relationship between blood pressure and cognitive function appears to be curvilinear, so that low blood pressure in late life is also associated with dementia and Alzheimer dementia.⁵⁰ In 5,816 patients age 65 and older, Morris et al⁵¹ calculated the percentile scores of four cognitive tests according to the level of blood pressure. Patients with systolic blood pressures of 100 mm Hg, 120 mm Hg, and 180 mm Hg scored lower on the Mini Mental State Examination than those in the 140 to 160 mm Hg range. Patients with diastolic blood pressures between 80 and 90 mm Hg appeared to have the best cognitive function. This further emphasizes that blood pressure control must be pursued in the very elderly, albeit less aggressively. The MIND substudy of the SPRINT trial⁹ is likely to shed more light on this relationship.

When needed for optimal blood pressure control in a hypertensive patient at risk of dementia, a calcium channel blocker of the dihydropyridine type or a centrally active ACE inhibitor, or both, is preferable.