Orthostatic hypotension is a major public health problem among the elderly, occurring in 30 percent of persons over the age of 75 years. Its incidence accounts for a sizable number of falls that might be prevented by better treatment of this disorder. The long- range objective of our proposal is to devise methods that are designed specifically for treating orthostatic hypotension in the elderly, whose problem is different from that in younger adults. Whereas the young often become hypotensive as a result of neurological (central or peripheral) dysfunction, we believe that orthostatic hypotension in elderly patients is due primarily to age-related changes of the vasculature itself. In general, the proposed investigation is intended (i) to quantify the role of cardiovascular changes in the etiology of orthostatic hypotension, and (ii) to assess particular therapeutic strategies that are based on delaying those cardiovascular changes that predispose the elderly to become hypotensive. Our Specific Aims are:

1) To quantify the variability, pattern and rate of progression of orthostatic hypotension in older persons. Subjects will be followed longitudinally to determine the time-course and severity of orthostatic hypotension, which will be measured using tilt-table and active standing procedures.

2) To determine the extent to which altered baroreflex, arterial compliance, and myocardial diastolic function predispose the elderly to develop orthostatic hypotension. We postulate the following roles for these factors in the etiology of the disease. As a result of noncompliant arteries, arterial pressure rises excessively in the supine position, leading to pressure diuresis and natriuresis, with consequent slight relative hypovolemia. When the individual later assumes an upright position, a small decrease in central intravascular volume produces a large pressure drop, again due to noncompliant arteries. Due to myocardial dysfunction, the person is unable to raise the pressure by increasing stroke volume. The individual is also unable to maintain cardiac output by cardioacceleration, and hypotension ensues.

3) To determine whether arrest or delay of the age-related cardiovascular changes observed in Aim 2 will also delay the progression of orthostatic hypotension in those patients. This will be attempted by using light non-isometric exercise conditioning, and/or converting enzyme inhibitor (captopril) therapy.

R01AG007225

1988-12-01

1993-11-30