Orthostatic Hypotension Screening in Older Adults Taking Antihypertensive Agents

Kenneth M. Madden, MSc, MD, FRCP, VITALITY (Vancouver Initiative to Add Life To Years) Group, Department of Medicine, University of British Columbia, Vancouver, BC.

Orthostatic hypotension (OH), while not itself a disease, is an important physical finding in the setting of unexplained syncope or falls. All antihypertensive medications directly interfere with the normal cardiovascular responses (increased venous return, tachycardia, and vasoconstriction) to orthostatic stress. Regular screening for this condition in older adults with hypertension, as well as careful titration of antihypertensive medications, can greatly improve both mortality and quality of life in this vulnerable population.
Keywords: orthostatic hypotension, postural vitals, antihypertensives, syncope, geriatric medicine.

Introduction
Orthostatic hypotension (OH) is an important physical finding in the setting of unexplained syncope or falls. Orthostatic hypotension is arbitrarily defined by the American Academy of Neurology as a reduction in the systolic blood pressure of at least 20 mm of mg, or a reduction in the diastolic blood pressure of at least 10 mm of mg within 3 minutes of standing.¹ This condition becomes clinically significant when cerebral hypoperfusion occurs that results in lightheadedness, visual changes (dimming or blurring), leg weakness, headache, cognitive slowing, or loss of consciousness.² Concomitant vascular disease may also result in more unusual presentations such as angina or transient ischemic attacks.³ Orthostatic hypotension has shown a direct negative association with the risk of myocardial infarction,⁴ stroke risk, and overall increased mortality.⁵

Asymptomatic OH has been shown in a large longitudinal study to have a prevalence of 16% in community-dwelling adults age 65 or more,⁶ rising to 68% in hospitalized older adults.⁷ Risk factors for OH include age,⁸ supine hypertension, autonomic dysfunction (due to diabetes or Shy-Drager syndrome),⁹ hypovolemia, or immobility.¹⁰ However, the most common iatrogenic cause of OH in older adults is due to the adverse effects of medications, especially antihypertensive agents.¹¹

The Physiology of Orthostasis
In the supine position, a person’s blood volume is distributed equally within the body. But after one minute of standing, approximately 500 mL of blood has moved to the vasculature in the legs. Thirty minutes of standing results in approximately 15% of plasma volume transferred to the interstitial tissue. This loss of fluid explains why some individuals experience orthostatically associated syncope after more prolonged periods of ambulation, as opposed to immediately upon standing.¹²

When assuming an upright posture, a person normally maintains blood pressure through a variety of mechanisms (Figure 1). Lower limb musculature contracts, resulting in an increase in venous return to the heart; the decrease in blood pressure with standing activates the arterial baroreflex¹³ and produces tachycardia and peripheral vasoconstriction; there is also activation of the renin-angiotensin-aldosterone axis, and increased production of other vasoactive agents such as endothelin and vasopressin. Many of these compensatory mechanisms are impaired by the pharmacodynamic effects of antihypertensive medications.¹⁴

 

Medications and Orthostatic Hypotension
A previous investigation of adult ambulatory veterans age 75 years and older has demonstrated that 55% of these patients have OH, with 33% experiencing symptoms.¹¹ This study examined the relationship between the prescription of antihypertensives, alpha-blocking agents, diuretics, antidepressants, and antipsychotic agents and the presence of OH in the general population. The risk of OH was positively associated with the number of potentially OH-producing medications prescribed, with the prevalence of OH in patients receiving none, 1, 2, and greater than 3 of these agents being 35, 58, 60, and 65% respectively.¹¹

Antihypertensive Medications and Orthostatic Hypotension
All antihypertensive medications directly interfere with normal cardiovascular response to orthostatic stress. One potential consequence of antihypertensive agents is impaired venous return. The normal