What causes and how is orthostatic hypotension managed in patients?

Blood Pressure Gradually Dropping with Prolonged Standing: Causes

Blood pressure that gradually drops with prolonged standing is most commonly caused by medications (especially diuretics, vasodilators, and alpha-blockers), followed by autonomic nervous system dysfunction from conditions like diabetes or Parkinson's disease, and volume depletion. 1, 2

Diagnostic Criteria and Classification

Orthostatic hypotension is diagnosed when systolic blood pressure drops ≥20 mmHg or diastolic blood pressure drops ≥10 mmHg within 3 minutes of standing, or when systolic BP falls to <90 mmHg absolute. 1 For patients with baseline supine hypertension, use a more stringent threshold of ≥30 mmHg systolic drop to avoid overdiagnosis. 1

Three distinct patterns exist based on timing:

• Classical OH: BP drop occurs within 3 minutes of standing with sustained decrease 1
• Initial OH: More severe drop (>40 mmHg systolic and/or >20 mmHg diastolic) within 15 seconds of standing, with rapid spontaneous recovery within 40 seconds 1
• Delayed OH: BP drop meeting standard criteria but occurring beyond 3 minutes of standing, with slow progressive decrease 1

Primary Causes (In Order of Frequency)

1. Medications (Most Common Reversible Cause)

Medication review and discontinuation is the single most important intervention. 1

• Diuretics: Cause volume depletion and are among the most common culprits 2
• Vasodilators: Including nitrates, directly reduce vascular tone 2
• Alpha-adrenergic blockers: Impair vasoconstriction, particularly problematic in initial orthostatic hypotension 2
• Beta-blockers: Can worsen orthostatic symptoms 2
• Psychotropic drugs: Contribute to classical or delayed orthostatic hypotension 2

2. Autonomic Nervous System Dysfunction (Neurogenic OH)

Neurogenic OH is distinguished by a blunted heart rate response (<10 bpm increase) upon standing. 1, 2

Primary autonomic failure conditions:

• Multiple system atrophy: Widespread autonomic degeneration 2, 3
• Pure autonomic failure: Affecting peripheral autonomic nerves 2, 3
• Parkinson's disease: Often the earliest clinical manifestation 3, 2
• Dementia with Lewy bodies: Causes neurogenic orthostatic hypotension 2

Secondary autonomic failure:

• Diabetes mellitus: Autonomic neuropathy is a leading secondary cause 3, 2
• Amyloidosis: Autonomic nerve infiltration 2
• Spinal cord injuries: Result in autonomic dysfunction 2

3. Volume Depletion and Hypovolemia

Non-neurogenic OH from volume depletion shows preserved or enhanced heart rate response (>10 bpm increase) upon standing. 1, 2 This distinguishes it from neurogenic causes and indicates the compensatory mechanisms are intact. 2

4. Age-Related Physiologic Changes

Aging alone predisposes to orthostatic hypotension through multiple mechanisms:

• Stiffer hearts less responsive to preload changes 2
• Impaired compensatory vasoconstrictor reflexes 2
• Baroreflex dysfunction 2
• Reduced cerebral autoregulation 2

The prevalence increases dramatically with age: approximately 10% in all hypertensive adults, 30% in patients over 65 years, and up to 50% of older institutionalized adults. 1

5. Cardiovascular Causes

• Severe arteriosclerosis: Can cause pseudohypertension leading to orthostatic hypotension 2
• Cardiac dysfunction: While not the primary defect, decreased cardiac output in heart failure can worsen orthostatic hypotension 2

Pathophysiologic Mechanism

The fundamental defect is failure of peripheral vascular resistance to increase appropriately upon standing, not cardiac pump failure. 2 When standing, blood pools in dependent parts of the body. Normally, the autonomic nervous system provides compensatory vasoconstriction, increased heart rate, and enhanced cardiac contractility. 3

In neurogenic OH, cardiovascular sympathetic fibers fail to increase total peripheral vascular resistance upon standing, resulting in inadequate vasoconstriction and a blunted heart rate response. 2 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. 3

Proper Diagnostic Measurement

Measure BP after 5 minutes of supine rest, then at both 1 minute and 3 minutes after standing. 1 If initial bedside testing is negative but clinical suspicion remains high, extend standing time beyond 3 minutes to detect delayed OH. 1

Key measurement considerations:

• Patient must fast for 3 hours before testing 1
• Avoid nicotine, caffeine, or taurine-containing drinks on testing day 1
• Use validated BP device with appropriate cuff size 1
• Maintain arm at heart level during all measurements 1

Clinical Significance and Prognosis

Orthostatic hypotension is associated with a 64% increase in age-adjusted mortality in men over 70 years. 2 It accounts for 20-30% of syncope cases in older adults and significantly increases the risk of falls, cardiovascular disease, stroke, and cognitive dysfunction. 2, 4

Common Pitfalls

Asymptomatic orthostatic hypotension during hypertension treatment should not trigger automatic down-titration of therapy. 3 Intensive BP lowering treatment actually reduces the risk of orthostatic hypotension, possibly due to improvement in baroreflex function and reduced arterial stiffness. 3

Pseudohypertension in elderly patients with calcified arteries may lead to overtreatment of hypertension and iatrogenic OH. 1 Symptoms depend more on the absolute BP level reached than the magnitude of the fall—a patient dropping from 180/100 to 150/80 mmHg may be asymptomatic despite meeting diagnostic criteria. 1