What Causes Orthostatic Hypotension
Medications are the most frequent cause of orthostatic hypotension, followed by autonomic nervous system dysfunction and volume depletion. 1
Medication-Induced Causes
The most common culprit medications include:
- Diuretics cause volume depletion and represent one of the most frequent medication-induced causes 1
- Vasodilators (including nitrates) directly reduce vascular tone, contributing to blood pressure drops upon standing 1
- Alpha-adrenergic blockers impair vasoconstriction and are particularly problematic in initial orthostatic hypotension 1
- Beta-blockers can worsen orthostatic symptoms through their cardiovascular effects 1
- Psychotropic drugs are another common medication class that contributes to orthostatic hypotension 1
- Cardiovascular medications are responsible for almost half of syncope episodes in elderly patients 2
Autonomic Nervous System Dysfunction
Primary Autonomic Failure
- Multiple system atrophy with widespread autonomic degeneration causes neurogenic orthostatic hypotension 1
- Pure autonomic failure affecting peripheral autonomic nerves leads to inadequate vasoconstriction 1
- Parkinson's disease with associated autonomic failure is a major cause 3
Secondary Autonomic Failure
- Diabetes mellitus causing autonomic neuropathy is the most common endocrine cause, representing an advanced stage of autonomic dysfunction 1, 3
- Amyloidosis with autonomic nerve infiltration causes secondary autonomic failure 1
Mechanism of 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
Volume Depletion and Hypovolemia
- Severe volume depletion causes non-neurogenic orthostatic hypotension with a preserved or enhanced heart rate response (distinguishing it from neurogenic causes) 1
- Excessive diuresis from any cause can lead to volume depletion 1
- Blood loss results in inadequate circulating volume 4
Cardiovascular Causes
- Severe arteriosclerosis causing pseudohypertension can lead to orthostatic hypotension 1
- Cardiac impairment affecting the heart's ability to respond to postural changes 5
Age-Related Physiologic Changes
Aging itself predisposes to orthostatic hypotension through multiple mechanisms:
- Stiffer hearts that are less responsive to preload changes 1
- Impaired compensatory vasoconstrictor reflexes that fail to adequately respond to postural changes 1
- Baroreflex dysfunction from age-related changes in autonomic regulation 1
- Reduced cerebral autoregulation contributing to symptoms 1
- In the Honolulu Heart Study, orthostatic hypotension occurred in approximately 7% of men over 70 years and was associated with a 64% increase in age-adjusted mortality 1
Clinical Pitfalls and Important Considerations
- Prevalence varies dramatically by setting: 6% in community-dwelling elderly versus 33% in elderly hospital inpatients 1, 3
- Multiple causes often coexist in frail elderly patients, with a median of five risk factors for syncope or falls 2
- Supine hypertension commonly coexists with orthostatic hypotension in autonomic failure, complicating both diagnosis and treatment 3
- Delayed orthostatic hypotension may take longer than 3 minutes to develop in elderly patients, requiring extended monitoring 2
- Atypical presentations are common in the elderly—up to one-third present with falls rather than classic syncope symptoms 2