What causes orthostatic hypotension in the elderly?

Causes of Orthostatic Hypotension in the Elderly

Orthostatic hypotension in the elderly is primarily caused by medications (especially diuretics, vasodilators, and alpha-blockers), age-related physiologic changes affecting autonomic function, and autonomic nervous system dysfunction from conditions like diabetes and Parkinson's disease. 1

Medication-Induced Causes (Most Common)

Medications are the most frequent cause of orthostatic hypotension in elderly patients and should be the first consideration in any evaluation. 1

High-Risk Medications:

• Diuretics cause volume depletion and are among the most common culprits 2, 1
• Vasodilators (including nitrates) directly reduce vascular tone 1
• Alpha-adrenergic blockers impair vasoconstriction 1
• Beta-blockers worsen orthostatic symptoms 1
• ACE inhibitors and calcium antagonists have more pronounced effects in elderly due to altered pharmacokinetics 2, 3
• Antipsychotic agents, tricyclic antidepressants, antihistamines, dopamine agonists/antagonists, and narcotics all precipitate syncope 2
• Trazodone is specifically associated with significant orthostatic hypotension risk in older adults 4

The effects of these drugs are exacerbated in the elderly because of loss of peripheral autonomic tone that occurs with aging. 2

Age-Related Physiologic Changes

Normal aging itself predisposes to orthostatic hypotension through multiple mechanisms, independent of disease states. 1

Key Age-Related Alterations:

• Reduced baroreceptor response impairs compensatory vasoconstriction 2, 1
• Decreased heart rate response to orthostatic stress 2
• Stiffer hearts less responsive to preload changes 1
• Reduced cerebral autoregulation 1
• Diminished thirst sensation and reduced ability to preserve sodium and water 2
• Impaired compensatory vasoconstrictor reflexes 2, 1

These physiological changes, combined with frequent use of multiple medications, create substantial risk for orthostatic intolerance. 2

Autonomic Nervous System Dysfunction

Neurogenic Orthostatic Hypotension:

In neurogenic orthostatic hypotension, cardiovascular sympathetic fibers fail to increase total peripheral vascular resistance upon standing, resulting in inadequate vasoconstriction and a blunted heart rate response (usually <10 beats per minute). 1

Primary Autonomic Failures:

• Multiple system atrophy with widespread autonomic degeneration 1
• Pure autonomic failure affecting peripheral autonomic nerves 1
• Parkinson's disease (unexplained syncope may be the first manifestation) 2, 5

Secondary Autonomic Failures:

• Diabetes mellitus causing autonomic neuropathy 2, 1, 5
• Amyloidosis with autonomic nerve infiltration 1

The prevalence of orthostatic hypotension is 10-30% in elderly patients with these conditions. 5

Volume Depletion and Cardiovascular Causes

• Severe volume depletion causes non-neurogenic orthostatic hypotension with preserved or enhanced heart rate response 1
• Baroreflex dysfunction from age-related changes 2, 1
• Severe arteriosclerosis causing pseudohypertension can lead to orthostatic hypotension 2, 1

Important Caveat on Pseudohypertension:

When peripheral arteries become very rigid from advanced arteriosclerosis, the cuff pressure overestimates true blood pressure. 2 Patients may be inadvertently overdosed with antihypertensive medications, resulting in orthostatic hypotension and other side effects. 2 This is particularly common in elderly patients with longstanding diabetes or chronic renal failure. 2

Clinical Significance and Epidemiology

Orthostatic hypotension occurred in approximately 7% of men over 70 years in the Honolulu Heart Study and was associated with a 64% increase in age-adjusted mortality compared with controls. 2, 1

• Prevalence ranges from 6% in community-dwelling elderly to 33% in elderly hospital inpatients 1
• Strong correlation exists between severity of orthostatic hypotension and premature death, as well as increased falls and fractures 2
• Accounts for 20-30% of syncope cases in older adults 1

Multifactorial Nature in the Elderly

In elderly patients, multiple origins of syncope and orthostatic hypotension frequently coexist and need to be addressed simultaneously. 2 The median number of risk factors for syncope or falls in frail elderly patients is five. 6

Key Contributing Factors:

• Polypharmacy with drug interactions 2
• Multiple coexisting diseases (heart disease, gait disorders, cardiovascular deconditioning) 2
• Carotid sinus hypersensitivity (under-recognized cause accounting for up to 30% of unexplained syncope in elderly) 2, 6
• Postprandial hypotension (frequently confused with transient ischemic attacks) 2
• Alcohol consumption 2