Goals and Benefits of Treatment

The prevalence of hypertension increases with age, affecting 30/100 persons aged 55-65 years, 39/100 persons aged 65-74 years, and 42/100 persons aged >/= 75 years.[3] SBP increases steadily with age, whereas DBP increases until about age 55 years, declining thereafter. Therefore, the pulse pressure (the difference between SBP and DBP) widens with age.[38] These age-related changes in blood pressure are the result of structural changes occurring in large vessels, leading to increased arterial rigidity and decreased elasticity. Age-related decreased compliance contributes to the development of ISH, the most common form of hypertension among older adults. In addition, cardiac output and renal function are decreased and baroreceptor sensitivity is diminished in older adults. Many of these physiologic age-related changes affect the management of hypertension in older adults.[25,39] Age is a not a modifiable risk factor for cardiovascular disease, but hypertension is not a normal consequence of aging. Rather, hypertension accelerates the natural processes of aging in the cardiovascular system.[25]

Neither the definition of hypertension nor the goals of treatment change according to age: normal blood pressure is <130/<85 mm Hg; optimal blood pressure is <120/<80; and treatment is initiated when blood pressure is >/=140/90.[25,40] In hypertensive patients with diabetes, the goal is even lower, to <130/80 or <130/85,[41] and in patients with kidney failure or heart failure, blood pressure should be reduced even further.[42] In patients with renal disease and proteinuria (greater than 1 g/24 hr), blood pressure should be controlled to 130/85 mm Hg or lower (125/75 mm Hg).[42]

In the past, physicians have been reluctant to treat older patients with hypertension and multiple risk factors for cardiovascular disease, including diabetes and hypercholesterolemia, for fear that lowering blood pressure could cause more harm than good. However, it is now known that antihypertensive treatment confers more benefit to older adults than to the younger population because of the increased baseline risk in older patients. Lowering blood pressure reduces all-cause mortality, stroke, coronary artery disease events, heart failure, progression of renal disease, and progression to more severe forms of hypertension in patients of all ages.[4,40]

Another reason for reluctance to treat older patients with ISH has been the lack of appreciation that SBP elevation poses a higher risk than DBP elevation.[40] For many years, the importance of lowering SBP to <140 mm Hg has been under-emphasized. While SBP, DBP, and pulse pressure are strongly and directly related to the risk of coronary and cerebrovascular events, SBP is the single best predictor of cardiovascular events.[5] The Framingham Study cohort was used to identify potential candidates for antihypertensive therapy; SBP alone correctly identified 91% of patients who needed treatment vs. only 22% of patients classified by DBP alone.[43] Even stage 1 systolic hypertension (SBP 140-149 mm Hg) carries a 50% greater risk for a cardiovascular event compared with normal systolic pressure (SBP <140 mm Hg).[40]

Treating older adults at high risk for cardiovascular disease with antihypertensive therapy is more effective in preventing cardiovascular morbidity and mortality than treating those at lower risk.[44] For example, in persons with diabetes who participated in the Syst-Eur trial, the relative risk reduction was 73% for fatal and nonfatal stroke and 76% for cardiovascular mortality, compared with reductions of 42% and 26%, respectively, in nondiabetic patients (Figure).[19]

Figure. (click image to zoom) Data from the Systolic Hypertension in Europe trial showing adjusted relative hazard of overall and cardiovascular (CV) mortality as well as CV events, stroke, and cardiac events in diabetic patients (n=492) and nondiabetic patients (n=4203) Adapted with permission from N Engl J Med. 1999;340:677-684.[19] ©1999 Massachussetts Medical Society

There are benefits of calcium antagonist therapy in older adults in addition to stroke and cardiovascular event reduction. First, they are associated with few metabolic adverse effects. In the large, comparative International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) trial[45] of diuretic vs. calcium antagonist therapy, long-acting nifedipine (initial dose, 30 mg) was compared with a thiazide-potassium-retaining combination diuretic, hydrochlorothiazide (initial dose, 25 mg) and amiloride (5 mg). The diuretic group had more hyperglycemia and hyperuricemia and increased development of diabetes and gout. It also had more hypokalemia (6.2% vs. 1.9% in the nifedipine group). In the Systolic Hypertension in the Elderly Program (SHEP) study,[46] low-dose diuretic therapy (12.5-25 mg chlorthalidone) was associated with hypokalemia in 7.2% of the cases. In these (hypokalemia) patients, the event rates were similar to placebo. These results underscore the importance of maintaining normal potassium levels to achieve reduction in cardiovascular event outcomes.

Calcium antagonists may be advantageous in many older adults with concomitant disease including angina, peripheral vascular disease, gout, hyperlipidemia, and obstructive airway disease. In some studies, calcium antagonists have been shown to lower blood pressure more effectively than β blockers and ACE inhibitors in older patients.[23,47] Calcium antagonists have been shown to correct the underlying pathophysiologic abnormalities associated with hypertension in older adults, which are increased peripheral resistance and decreased arterial compliance.[25] In addition, they do not cause postural hypotension, an important consideration in older adults.[24,25]

Drawbacks of calcium antagonists, like some other antihypertensive agents, are characteristic classwide adverse effects, including dizziness, flushing, and headache, mainly due to vasodilation. Leg and ankle swelling (peripheral edema) also is distressing to many patients. Peripheral edema associated with calcium antagonists occurs in the absence of significant sodium retention and is not related to cardiac failure, although its exact cause is unclear. In a recent study[48] of 2000 men and women with essential hypertension who received monotherapy with a calcium antagonist, edema (n=272; 13.6%), headache (n=115; 5.8%), flushing (n=78; 3.9%), and rash (n=39; 2.0%) were the most commonly reported adverse events. Edema was reported more commonly by women (15.6% vs. 11.8%). Overall, more women reported adverse events (35.3% vs. 22.7%; p<0.001) and discontinued therapy due to adverse events (18.5% vs. 11.5%; p=0.04).

It addition to the possibility of adverse events, it is important to keep in mind when initiating antihypertensive therapy that older patients require lower initial doses and slow titration because of reduced muscle mass. Stiffness of blood vessels correlates with impaired baroreflex function, so that postural hypotension may occur upon standing. While pretreatment postural hypotension should not deter treatment, it does mandate caution, and blood pressures should be taken in both the standing and sitting positions. Further, renal function in older patients may require careful monitoring.[4,49]

Calcium antagonists are effective and safe when used for approved indications, although as with all antihypertensive drugs, care should be taken to carefully evaluate the risk-to-benefit ratio if these drugs are used in settings in which they are relatively contraindicated. There is the potential for adverse effects on myocardial function under certain circumstances; currently available DHPs have negative inotropic effects on the heart. For example, the negative inotropic activity of some calcium antagonists may precipitate or exacerbate symptoms of congestive heart failure in some patients. The use of calcium antagonists is not recommended for patients with left ventricular dysfunction or in patients who have suffered a myocardial infarction; their use in secondary prevention of myocardial infarction has not shown favorable effects. Calcium antagonists with negative inotropy should be avoided in ischemic cardiomyopathy as their use will further decrease the already deficient left ventricular function; nitrates or ACE inhibitors are preferred for this condition.[50]

The preferred agents for patients with hypertension and diabetes are ACE inhibitors or angiotensin receptor blockers due to their beneficial effects on proteinuria, kidney function, and cardiovascular outcomes.[41,51-53] However, the majority of diabetic patients require two or more agents to reach target blood pressure levels.[41] Data from SHEP, HOT,[30] and Syst-Eur[18] suggest that diuretics and DHP calcium antagonists in addition to, but not instead of, ACE inhibitors, were of benefit in the diabetic subgroups. The African American Study of Kidney Disease and Hypertension (AASK) trial data suggest that DHP calcium antagonists were not protective in nondiabetic African American patients with renal impairment.[51] In patients with type 2 diabetes and nephropathy, the angiotensin receptor blocker losartan had a renoprotective effect in the Reduction of Endpoints in NIDDM With the Angiotensin II Antagonist Losartan Study (RENAAL).[52] This was also observed when a calcium channel blocker was added to the therapy.

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This is a part of article Treatment of Hypertension in Older Patients: An Updated Look Taken from "Generic Adalat (Nifedipine) Information" Information Blog