What causes orthostatic hypotension?

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

Pathophysiologic Mechanism

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

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-related orthostatic hypotension 1

Cardiovascular Causes

• Severe arteriosclerosis causing pseudohypertension can lead to orthostatic hypotension 1
• Cardiac impairment affecting the heart's ability to respond to postural changes contributes to orthostatic hypotension 4

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
• 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 Distinctions

Distinguishing neurogenic from non-neurogenic causes is critical:

• Neurogenic OH shows a blunted heart rate increase (<10 bpm) upon standing 1
• Non-neurogenic OH (hypovolemia, medications) shows a preserved or enhanced heart rate increase 1

Common complication: Supine hypertension commonly coexists with orthostatic hypotension in autonomic failure, complicating treatment goals 3

Prevalence varies by setting: 6% in community-dwelling elderly to 33% in elderly hospital inpatients, accounting for 20-30% of syncope cases in older adults 1