Causes of Orthostatic Hypotension
Medications are the most frequent cause of orthostatic hypotension, followed by autonomic nervous system dysfunction and volume depletion. 1
Medication-Induced Causes
Diuretics are among the most common culprits, causing orthostatic hypotension through volume depletion. 1 This class should be the first consideration when evaluating drug-induced orthostatic hypotension, particularly in elderly patients on multiple antihypertensive agents.
Vasodilators directly reduce vascular tone and impair the normal compensatory vasoconstriction needed upon standing:
- Nitrates 1
- Alpha-adrenergic blockers (particularly problematic with first doses) 1, 2
- Any vasoactive drugs can contribute to classical or delayed orthostatic hypotension 1
Cardiovascular medications frequently implicated include:
Psychotropic medications carry significant risk:
Centrally acting antihypertensives and adrenergic blockers are also common offenders. 2
Autonomic Nervous System Dysfunction (Neurogenic Causes)
The hallmark of neurogenic orthostatic hypotension is failure of cardiovascular sympathetic fibers to increase total peripheral vascular resistance upon standing, resulting in inadequate vasoconstriction and a blunted heart rate response (typically <10 beats per minute increase). 1
Primary Autonomic Failure
- Multiple system atrophy with widespread autonomic degeneration 1
- Pure autonomic failure affecting peripheral autonomic nerves 1
- Parkinson's disease 1
- Dementia with Lewy bodies 1
Secondary Autonomic Failure
- Diabetes mellitus causing autonomic neuropathy is the leading secondary cause 1, 3
- Amyloidosis with autonomic nerve infiltration 1
- Spinal cord injuries 1
- Auto-immune autonomic neuropathy 1
- Paraneoplastic autonomic neuropathy 1
The prevalence of orthostatic hypotension in conditions like diabetes and Parkinson's disease ranges from 10-30% in elderly patients. 3
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 This can result from:
Cardiovascular Causes
Cardiac pump failure can worsen orthostatic hypotension, though the primary defect remains inadequate peripheral vasoconstriction rather than cardiac dysfunction itself. 1 The European Heart Journal emphasizes that orthostatic hypotension is primarily a problem of autonomic nervous system dysfunction and vascular regulation, not a primary cardiac disorder. 1
Severe arteriosclerosis causing pseudohypertension can lead to orthostatic hypotension. 1 This is particularly relevant in elderly patients with calcified arteries, where overtreatment of apparent hypertension may cause iatrogenic orthostatic hypotension. 5
Impaired venous return and venous pooling contribute to orthostatic hypotension when one-way valves fail to prevent blood from pooling in dependent body parts. 6
Age-Related Physiologic Changes
Aging itself predisposes to orthostatic hypotension through multiple mechanisms:
- Stiffer hearts less responsive to preload changes 1
- Impaired compensatory vasoconstrictor reflexes 1
- Baroreflex dysfunction from age-related changes 1, 3
- Reduced cerebral autoregulation 1
The Honolulu Heart Study found orthostatic hypotension occurred in approximately 7% of men over 70 years and was associated with a 64% increase in age-adjusted mortality. 1 The prevalence ranges from 6% in community-dwelling elderly to 33% in elderly hospital inpatients, and up to 50% in older institutionalized adults. 1, 5
Endocrine Causes
Endocrine system disorders can contribute to orthostatic hypotension, though specific mechanisms vary by condition. 4
Clinical Significance
A sudden cessation of cerebral blood flow for 6-8 seconds or a decrease in systolic blood pressure to 60 mmHg is sufficient to cause loss of consciousness. 1 Orthostatic hypotension accounts for 20-30% of syncope cases in older adults and significantly increases the risk of falls, particularly backward falls. 1