What are the potential causes of orthostatic hypotension in a patient without a prior hypertension diagnosis?

Potential Causes of Orthostatic Hypotension

Orthostatic hypotension results from either medications, autonomic nervous system dysfunction, volume depletion, or age-related cardiovascular changes—with medications being the single most common reversible cause in clinical practice. 1

Medication-Induced Causes (Most Common)

Medications are the most frequent cause of orthostatic hypotension and should be the first consideration in any patient presenting with this condition. 1

• Diuretics cause volume depletion and are among the most common culprits in medication-induced orthostatic hypotension 1
• Vasodilators, including nitrates, directly reduce vascular tone and contribute to orthostatic hypotension 1
• Alpha-adrenergic blockers impair vasoconstriction and are particularly problematic in initial orthostatic hypotension 1
• Beta-blockers can worsen orthostatic symptoms 1
• Psychotropic drugs are frequently implicated 1
• Any vasoactive drugs can contribute to classical or delayed orthostatic hypotension 1

Autonomic Nervous System Dysfunction (Neurogenic Causes)

In neurogenic orthostatic hypotension, cardiovascular sympathetic fibers fail to increase total peripheral vascular resistance upon standing, resulting in inadequate vasoconstriction and a characteristically blunted heart rate response (usually <10 beats per minute increase). 1, 2

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 a leading secondary cause 1
• Amyloidosis with autonomic nerve infiltration 1
• Spinal cord injuries resulting in autonomic dysfunction 1
• Auto-immune autonomic neuropathy and paraneoplastic autonomic neuropathy (less common) 1

Volume Depletion and Hypovolemia (Non-Neurogenic Causes)

Severe volume depletion causes non-neurogenic orthostatic hypotension with a preserved or enhanced heart rate response, distinguishing it from neurogenic causes. 1

• Excessive diuresis 1
• Blood loss 3
• Dehydration 4

Age-Related Physiologic Changes

Aging itself predisposes to orthostatic hypotension through multiple mechanisms, making elderly patients particularly vulnerable even without other identifiable causes. 1

• Stiffer hearts less responsive to preload changes 1
• Impaired compensatory vasoconstrictor reflexes 1
• Baroreflex dysfunction from age-related changes 1
• Reduced cerebral autoregulation 1
• 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 1

Cardiovascular Causes

• Severe arteriosclerosis causing pseudohypertension can lead to orthostatic hypotension 1
• Decreased cardiac output due to poor ventricular function in heart failure can worsen orthostatic hypotension, though the primary defect remains inadequate peripheral vasoconstriction 1

Special Variants by Timing

Initial Orthostatic Hypotension

• Characterized by a BP decrease on standing of >40 mmHg systolic and/or >20 mmHg diastolic within 15 seconds of standing 5, 6
• BP spontaneously and rapidly returns to normal, so symptoms are brief (<40 seconds) but may still cause syncope 5

Delayed Orthostatic Hypotension

• Defined as orthostatic hypotension occurring beyond 3 minutes of head-up tilt or active standing 5, 6
• Characterized by a slow progressive decrease in BP 5
• May represent a mild form of classical orthostatic hypotension, especially if associated with Parkinsonism or diabetes 5
• Common in elderly persons due to stiffer hearts sensitive to preload decrease and impaired compensatory vasoconstrictor reflexes 5

Key Clinical Distinction

The fundamental pathophysiology centers on failure of peripheral vascular resistance to increase appropriately upon standing, not cardiac pump failure—though cardiac dysfunction can contribute. 1 The heart rate response during standing helps distinguish neurogenic (blunted <10 bpm increase) from non-neurogenic causes (preserved or enhanced increase). 1, 2