Orthostatic hypotension

Orthostatic hypotension is defined as a significant decrease in blood pressure (systolic blood pressure ≥ 20 mm Hg and/or diastolic blood pressure ≥ 10 mm Hg) that occurs on assuming an upright position. It is increasingly common with older age and can be caused by neurogenic factors (e.g., neurodegenerative disorders such as Parkinson disease) or nonneurogenic factors (e.g., volume depletion, medications). Clinical features include lightheadedness, syncope, and falls, though many patients are asymptomatic. Orthostatic vital signs confirm the diagnosis. Management focuses on symptom relief through nonpharmacologic measures such as increased fluid and salt intake and the use of compression garments. Pharmacologic therapy (e.g., midodrine, droxidopa) is reserved for refractory symptoms.

• Prevalence ^[1]
  • Increases with age
  • 16–30% of individuals > 65 years of age ^[1]
  • 10% of individuals with hypertension ^[1]
• Associated with increased all-cause mortality and cardiovascular comorbidity ^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Causes of orthostatic hypotension are classified as neurogenic or nonneurogenic; multiple causes may coexist. ^[3]

Nonneurogenic orthostatic hypotension ^[2][4][5]

Conditions associated with low cardiac output and/or systemic vascular resistance can cause nonneurogenic orthostatic hypotension, e.g.:

• Dehydration and hypovolemia
• Medications (e.g., vasodilators, heart rate-lowering agents, diuretics)
• Venous pooling (e.g., due to prolonged bed rest) ^[6]
• Cardiac causes (e.g., heart failure, arrhythmias)
• Endocrine disorders (e.g., diabetes mellitus, adrenal insufficiency, hypothyroidism)
• End-stage renal disease
• Physiologic changes of aging, pregnancy, and the postpartum period

Alpha-blockers (e.g., doxazosin, terazosin) are a common cause of orthostatic hypotension in older men with hypertension and benign prostatic hyperplasia. ^[5]

Neurogenic orthostatic hypotension ^[5][7]

• Neurodegenerative disorders (e.g., Parkinson disease, Parkinson-plus syndromes, pure autonomic failure)
• Peripheral autonomic neuropathies, including:
  • Diabetic autonomic neuropathy ^[2]
  • Amyloid neuropathy
  • Immune-mediated and paraneoplastic syndrome neuropathies
  • Vitamin B₁₂ deficiency
• Spinal cord or traumatic brain injuries ^[2]

Age-related loss of baroreceptor sensitivity contributes to orthostatic hypotension in older adults. ^[2]

Causes of nonneurogenic orthostatic hypotension may aggravate pre-existing neurogenic orthostatic hypotension. ^[3]

• Normal response to upright posture: counterregulation with sufficient reflex tachycardia and peripheral vasoconstriction to maintain a stable blood pressure
• Pathologic response to upright posture: in individuals with orthostatic hypotension, insufficient counterregulation (due to autonomic dysfunction, hypovolemia, and/or medications) → dependent splanchnic and lower-extremity blood pooling → hypotension (may be symptomatic or asymptomatic)
• Symptomatic orthostasis: orthostatic hypotension → decreased organ perfusion (e.g., cerebral hypoperfusion resulting in syncope)

• Often asymptomatic
• Orthostatic symptoms caused by organ hypoperfusion
  • Cerebral: lightheadedness, blurry vision, cognitive impairment, orthostatic syncope
  • Pulmonary: orthostatic dyspnea
  • Cardiac: orthostatic angina
  • Musculoskeletal: coat hanger pain
• Features suggestive of the underlying cause (e.g., Parkinsonism, clinical features of dehydration)

Orthostatic symptoms are typically relieved by returning to the supine position ^[3][5]

General principles ^[2]

• Confirm orthostatic hypotension by measuring orthostatic vital signs.
• Perform tilt table test if the orthostatic vital signs are inconclusive or the patient cannot stand safely.
• Assess heart rate (HR) response to help distinguish between nonneurogenic and neurogenic orthostatic hypotension.
• Order targeted additional tests to identify underlying causes of nonneurogenic orthostatic hypotension.

Conduct a medication review and volume status assessment in all patients with orthostatic hypotension. ^[2]

Orthostatic vital signs ^[2][4]

• Method
  • Measure BP and HR after lying supine for 5 minutes.
  • Repeat BP and HR after standing for 3 minutes. ^[2][3]
  • Document any symptoms experienced.
• Findings
  • Nonsignificant change in vitals: normal
  • Sustained hypotension (↓ SBP ≥ 20 mm Hg and/or ↓ DBP ≥ 10 mm Hg) ; ^[3][5]
    • Within 3 minutes of standing: classic orthostatic hypotension ^[2]
    • Beyond 3 minutes of standing: delayed orthostatic hypotension ^[3]
  • Heart rate compensation ratio
    • < 0.5 beats/minute/mm Hg: suggests neurogenic orthostatic hypotension
    • ≥ 0.5 beats/minute/mm Hg: suggests nonneurogenic orthostatic hypotension
  • Significant HR increase without hypotension: suggests POTS

Additional evaluation ^[2]

All patients

• Blood tests
  • BMP: to assess for electrolyte disturbances, hyperglycemia, or renal impairment
  • CBC: to evaluate for anemia or infection
  • TSH: to screen for thyroid disorders
  • Serum vitamin B₁₂ and methylmalonic acid levels: to rule out neuropathy from B₁₂ deficiency ^[5]
• ECG: to identify arrhythmias, ischemia, and/or structural heart disease

Patients with neurogenic orthostatic hypotension

• Screen for supine hypertension.
• Consider referral to neurology to evaluate underlying cause of autonomic dysfunction. ^[3]

General principles ^[5]

• Management focuses on reducing symptoms, preventing falls, and optimizing quality of life.
• Reduce or stop offending medications.
• Provide patient and family education on self-management strategies.
• Consider pharmacological therapy for refractory symptoms.

Nonpharmacological management of orthostatic hypotension ^[2][7]

Provide patient and family education on self-management strategies, e.g.:

• Avoidance of exacerbating factors (e.g., hot and/or humid conditions, large meals, prolonged standing)
• Adequate hydration (e.g., intake of 2–2.5 L of fluid/day) if no contraindications ^[2]
• Increased salt intake (e.g., at least 2–3 g of sodium intake) ^[2]
• Waist-high compression garments to reduce venous pooling
• Physical counterpressure maneuvers (e.g., leg-crossing, squatting) to prevent or manage acute symptoms
• Exercise to prevent deconditioning: Activities that do not require an upright posture may be better tolerated (e.g., swimming, rowing). ^[5]

Use increased fluid and salt intake with caution in patients with orthostatic hypotension and hypertension. ^[1]

Pharmacotherapy ^[2][5][7]

Consider pharmacotherapy if symptoms persist despite nonpharmacological management; approach is based on the clinical picture and patient preference.

• Sympathomimetics (first-line) to increase peripheral vascular resistance
  • Midodrine ^[2]
  • Droxidopa ^[5]
• Intravascular volume expanders (e.g., fludrocortisone)
• Acetylcholinesterase inhibitors (e.g., pyridostigmine)
• Norepinephrine reuptake inhibitors (e.g., atomoxetine)

• Definition: a significant decrease in SBP that occurs within 2 hours of eating ^[5]
• Pathophysiology: incompletely understood; likely due to splanchnic venous pooling triggered by vasodilatory peptide release associated with postprandial gastric and esophageal distention ^[5]
• Risk factors ^[5][8]
  • Older age
  • Neurological disorders (e.g., Alzheimer disease, Parkinson disease, diabetic autonomic neuropathy)
• Clinical features ^[5]
  • Often asymptomatic
  • Symptoms similar to orthostatic hypotension that develop after eating
• Diagnosis
  • Serial BP measurements for up to 2 hours after a meal ^[7][9]
    • SBP decrease > 20 mm Hg from preprandial baseline
    • Or postprandial SBP ≤ 90 mm Hg when preprandial SBP ≥ 100 mm Hg
  • If diagnosis is not confirmed on standard measurement, consider an activity diary with ambulatory blood pressure monitoring (ABPM). ^[5][10]
  • Consider referral to neurology to evaluate the underlying cause of autonomic dysfunction. ^[3]
• Treatment ^[7]
  • Initiate nonpharmacological management of orthostatic hypotension.
  • Additionally, advise patients to:
    • Avoid large, high-carbohydrate meals.
    • Allow foods to cool to room temperature before eating.
    • Reduce alcohol intake.
    • Avoid physical activity or quickly standing after meals.
  • Consider pharmacotherapy for refractory symptoms (e.g., octreotide).

• Definition: elevated SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg measured after ≥ 5 minutes in the supine position ^[11]
• Epidemiology: common in patients with neurogenic orthostatic hypotension
  • Parkinson disease: 21–46% ^[11]
  • Multiple system atrophy: ∼ 50% ^[11]
  • Pure autonomic failure: ∼ 70% ^[11]
• Clinical features ^[12]
  • Often asymptomatic
  • Headaches
  • Nocturia
  • Sleep disturbances
• Diagnosis ^[12]
  • Indications: Screen all patients with neurogenic orthostatic hypotension for supine hypertension.
    • At diagnosis
    • After initiation of pharmacotherapy for orthostatic hypotension
    • If suggestive symptoms develop
  • Diagnostic studies
    • Confirm diagnosis with supine BP measurements after 5 minutes of rest.
    • Consider ABPM to characterize nocturnal BP profile.
• Management ^[1][13]
  • Nonpharmacological therapy for orthostatic hypotension
  • If pharmacotherapy for orthostatic hypotension is indicated:
    • Avoid drugs that may worsen supine hypertension (e.g., droxidopa).
    • Consider omitting the nighttime dose of antihypotensive medication (e.g., droxidopa).
  • Nighttime hypertension may be controlled by short-acting antihypertensives (e.g., nitroglycerin patches, losartan).

In supine hypertension, pressure natriuresis during sleep leads to nocturia and overnight volume loss, which exacerbates morning orthostatic hypotension. ^[12]

Antihypotensive drugs used in the treatment of orthostatic hypotension may exacerbate supine hypertension. ^[1]