Reawakening of interest in aldosterone and aldosterone antagonists: implications for treatment of cardiovascular disease.
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Biomedical subjects
Publications and source records attributed to G E Sander.
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Increases in blood pressure (BP), particularly systolic BP, have traditionally been considered to be a normal or "physiologic" component of the aging process. However, it is now clear that elevated BP, particularly systolic BP, represents a pathophysiologic manifestation of altered cardiovascular physiology and structure, ultimately manifesting as increased cardiovascular morbidity and mortality (myocardial infarction, stroke, and total cardiovascular death rates). More than one half of the population aged 65 or older have hypertension, defined as BP > or = 140/90 mm Hg. Framingham data indicate that the risk of coronary heart disease increases with lower diastolic BP at any level of systolic BP > or = 120 mm Hg, thus further stressing the importance of pressure-induced arterial vascular compliance changes and introducing pulse pressure as an important predictor of cardiovascular risk. Geriatric hypertension is generally of a salt-sensitive nature and often associated with impaired baroreflex function. Reduction in sodium intake is important and effective in older patients, and should be initiated before or together with drug therapy. Encouraging data from clinical trials now strongly support the aggressive anti-hypertensive treatment of elderly patients. A recent meta-analysis of eight outcome trials evaluating the risks of treated and untreated isolated systolic hypertension has demonstrated a 30% reduction in combined fatal and nonfatal stroke, a 26% reduction in fatal and nonfatal cardiovascular events, and a 13% reduction in total mortality. Those drugs effective in younger patients also appear effective in the elderly; low-dose thiazides (alone or in combination with potassium sparing agents), beta blockers, long-acting dihydropyridine calcium antagonists, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all have demonstrated efficacy. In selecting an agent, it is important to consider comorbid disease states, and to recognize the potential of all nonsteroidal anti-inflammatory drugs, whether conventional or cyclooxygenase-2 specific, to increase BP or interfere with other antihypertensive agents. In general, the elderly should be treated to target BP levels identical to those suggested for younger patients, although a more gradual reduction to target, perhaps with an intermediate BP goal of < 160 mm Hg, may be advisable.
Rapidly accumulating clinical data have repeatedly demonstrated not only the critical importance of even small increases in blood pressure as a pathophysiologic factor in the development of cardiovascular disease, particularly in individuals with diabetes mellitus, but also the therapeutic necessity of more aggressive blood pressure reduction and the achievement of progressively lower blood pressure targets in reducing cardiovascular event rates. JNC VI has defined optimal blood pressure as or=140/80 mm Hg. Target blood pressures are now 1 gm/24 hours. Achieving such target pressures is increasingly difficult, particularly in diabetic patients with chronic renal disease, who require complex multidrug antihypertensive regimens. This review attempts to provide some suggestions for constructing such antihypertensive regimens, and provides considerations for the appropriate use of diuretics and the most effective drug combinations. Factors potentially contributing to drug resistant hypertension include such problems as failure to maximize drug dosing, suboptimal diuretic use, noncompliance, and possible confounding effects of such concomitant medications as nonsteroidal and anti-inflammatory drugs or decongestants. The issues underlying drug-resistant hypertension are listed, together with strategies for overcoming this problem.