Causes of Orthostatic Hypotension
Primary Etiologic Categories
Orthostatic hypotension results from three fundamental mechanisms: medication effects, autonomic nervous system dysfunction, and volume depletion, with medications being the most common reversible cause. 1
Medication-Induced Orthostatic Hypotension
Medications represent the most frequent cause of orthostatic hypotension and should be the first consideration in any evaluation. 1
- Diuretics cause volume depletion and are among the most common culprits 2, 1
- Vasodilators including nitrates directly reduce vascular tone 2, 1
- Alpha-adrenergic blockers impair vasoconstriction and are particularly problematic in initial OH 2, 1
- Beta-blockers can worsen orthostatic symptoms 2
- Psychotropic drugs including trazodone cause significant orthostatic hypotension, especially in older adults 3, 1
- Any vasoactive drugs can contribute to classical or delayed OH 2, 1
Autonomic Nervous System Dysfunction (Neurogenic OH)
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 (typically <10 beats per minute increase). 2, 1
Primary Autonomic Failure
- Parkinson's disease with autonomic involvement 1, 4
- Multiple system atrophy with widespread autonomic degeneration 2, 1
- Pure autonomic failure affecting peripheral autonomic nerves 2
- Dementia with Lewy bodies 2
Secondary Autonomic Failure
- Diabetes mellitus causing autonomic neuropathy 2, 5
- Amyloidosis with autonomic nerve infiltration 2
- Spinal cord injuries disrupting autonomic pathways 2
- Autoimmune autonomic neuropathy 2
- Paraneoplastic autonomic neuropathy 2
- Chronic kidney failure 2
The key pathophysiologic defect involves degeneration of autonomic nuclei within the central nervous system and/or peripheral autonomic denervation, leading to failure of the baroreceptor reflex arc. 2 The afferent pathway from arterial baroreceptors in the carotid arteries and aortic arch to the medulla oblongata, or the efferent pathway regulating heart rate and vascular tone, becomes impaired. 2
Volume Depletion and Hypovolemia
Severe volume depletion causes non-neurogenic orthostatic hypotension with a preserved or enhanced heart rate response (unlike neurogenic causes). 2, 1
- Excessive diuresis from aggressive diuretic therapy 1
- Blood loss from any source 5
- Dehydration from inadequate fluid intake or excessive losses 5, 6
Cardiovascular Causes
- Cardiac insufficiency with impaired cardiac output 6
- Impaired venous return due to venous pooling 6
- Severe arteriosclerosis causing pseudohypertension (rigid arteries resist compression, leading to falsely elevated readings and potential overtreatment) 2
Age-Related Physiologic Changes
Aging itself predisposes to orthostatic hypotension through multiple mechanisms, with prevalence reaching 90% in patients over 70 years with clinical suspicion. 7
- Stiffer hearts less responsive to preload changes 2
- Impaired compensatory vasoconstrictor reflexes 2
- Baroreflex dysfunction from age-related changes 2, 5
- Reduced cerebral autoregulation 2
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. 2
Endocrine Disorders
- Adrenal insufficiency affecting mineralocorticoid and glucocorticoid production 5
- Other endocrine system disorders 5
Clinical Distinction: Neurogenic vs. Non-Neurogenic
The orthostatic heart rate response distinguishes neurogenic from non-neurogenic causes: 2, 1
- Neurogenic OH: Heart rate increase is blunted (usually <10 bpm) because autonomic control is impaired 2, 1
- Non-neurogenic OH: Heart rate increase is preserved or enhanced as the baroreceptor reflex remains intact 2, 1
Important Clinical Pitfall
Approximately 50% of patients with neurogenic orthostatic hypotension also suffer from supine and nocturnal hypertension, creating a challenging management scenario. 4 This occurs because the same autonomic dysfunction that prevents vasoconstriction when standing also prevents vasodilation when supine, leading to dangerous blood pressure extremes. 4