History and exam
Key diagnostic factors
common
presence of risk factors
Important risk factors include normal ageing, especially if associated with physical deconditioning from prolonged bed rest; medications that affect sympathetic tone (e.g., tamsulosin, antihypertensive agents); dehydration (especially in older patients taking diuretics); and underlying medical conditions that affect autonomic nerve function (e.g., diabetes mellitus, Parkinson's disease, multiple system atrophy).[7][18]
postural light-headedness, syncope, and other symptoms of cerebral hypoperfusion
Symptoms of cerebral hypoperfusion are essential in the evaluation of orthostatic hypotension (OH). They occur in the upright posture and are the result of inadequate perfusion of the brain, and improve on sitting or lying down when gravity passively restores cerebral perfusion. Syncope may result from cerebral hypoperfusion.
Additional symptoms of hypoperfusion include visual changes, weakness, fatigue, trouble concentrating, and pain across the neck and shoulders.
Increased ventilation and dyspnoea also occur during OH, and can result in constriction of the cerebral blood vessels and worsening of cerebral hypoperfusion.
Other diagnostic factors
common
parkinsonian features
Parkinsonian features (e.g., resting tremor, slowness, paucity of movement, decreased arm swing when walking) suggest a problem with motor pathways. In the early stages, these abnormalities can be mild. REM sleep behaviour disorder (acting out dreams) and inability to discriminate smells (anosmia) can be other indicators of the early stages of Parkinson's disease. The same disease process can also affect pathways that control the outflow of sympathetic nerves to the blood vessels. The prevalence of orthostatic hypotension in patients with multiple system atrophy and Parkinson's disease is markedly increased.
cerebellar ataxia
Multiple system atrophy (MSA, or Shy-Drager syndrome) affects autonomic pathways and can result in orthostatic hypotension. Ataxia of gait and ataxia of speech (cerebellar dysarthria) are the most common clinical features of the cerebellar form of MSA. Limb ataxia may also occur, but it is less common.
weight loss
Unintentional weight loss can be a sign of cancer. In a patient with an acute- or subacute-onset orthostatic hypotension, unintentional weight loss may suggest a paraneoplastic syndrome in which the autoimmune process damages the autonomic nervous system.
resting tachycardia or impaired heart rate variation
May be a feature of diabetic loss of parasympathetic nerves innervating the heart. This results in an increase in resting heart rate and diminished heart rate variability during deep breathing.
abnormal gastrointestinal motility
Symptoms of abnormal gastrointestinal motility (e.g., nausea, postprandial vomiting, bloating, loss of appetite, early satiety, constipation, ileus, abdominal pain) are common in patients with autonomic neuropathy. The incidence of constipation (<3 bowel movements/week) is increased in patients with Parkinson's disease, and can precede the development of overt parkinsonian features by many years.
erectile dysfunction and lack of ejaculation
Erection requires vascular and autonomic integrity. Erectile dysfunction is common in older men and is almost universal in men with autonomic failure. It is often associated with lack of ejaculation. The two features together suggest an underlying autonomic abnormality affecting parasympathetic function (erection) and sympathetic function (ejaculation).
anhidrosis, heat intolerance, dry skin, focal hyperhidrosis
Autonomic failure is often associated with abnormalities in sweat function, and patients with autonomic failure frequently report diminished sweating (anhidrosis), limiting their tolerance of hot environments. This is in contrast to patients with vasovagal syncope, who will frequently describe a cold sweat before an impending faint.
urinary frequency, urgency, nocturia
Problems with bladder function are common in patients with autonomic failure and may be incorrectly attributed to benign prostatic hypertrophy in older men. Urinary frequency, urgency, and retention have been reported in patients with Parkinson's disease. It is common in multiple system atrophy and as the disease progresses, postvoid residual urinary volume increases and patients may require self-catheterisation.
Nocturia is extremely common in patients with autonomic failure and occurs as a result of loss of circadian blood pressure rhythm. Instead of the normal night-time 'dipping', blood pressure throughout the night while lying flat in bed is elevated in patients with autonomic failure. As a result, there is an increase in fluid and sodium loss overnight, causing nocturia. Excessive fluid loss overnight results in worsening of symptoms of orthostatic hypotension in the morning.
Risk factors
strong
older adult age
Ageing is associated with an increase in resting sympathetic tone, a decrease in parasympathetic tone, and impairment of baroreflex sensitivity (i.e., the compensatory increase in heart rate as blood pressure falls).[7]
These physiological changes predispose to orthostatic hypotension (OH), although overall, clinically significant symptomatic OH is relatively uncommon in healthy elderly people.[23]
frailty and physical deconditioning
Prolonged bed rest and general frailty can make normal age-related reduction in baroreflex buffering clinically significant, leading to symptomatic OH. It can also cause skeletal and cardiac muscle atrophy, leading to reduced cardiac output.[23]
use of drugs that impair sympathetic tone
Medications such as alpha-blockers (including tamsulosin, used for treating conditions such as benign prostatic hypertrophy), central sympatholytics (including tizanidine, used as a muscle relaxant, and methyldopa), tricyclic antidepressants, phosphodiesterase-5 inhibitors (used to treat erectile dysfunction), and some antihypertensive agents (including beta-blockers), increase the likelihood of OH.[15][18]
volume depletion/anaemia
A major risk factor for orthostatic hypotension (OH), especially in older patients taking diuretics. Because blood pressure is dependent on intravascular volume, anaemia may exacerbate OH by reducing red blood cell mass and blood viscosity.
autonomic neuropathy (e.g., diabetes mellitus)
Any disease causing peripheral neuropathy can affect autonomic nerves. Many patients with diabetes have detectable autonomic abnormalities, but clinically significant orthostatic hypotension (OH) is more common in long-standing diabetes.[19][20]
Toxins and antineoplastic agents can also produce autonomic neuropathy and therefore OH.
Parkinson's disease
Protein (alpha-synuclein) deposits can occur in peripheral autonomic nerves and autonomic ganglia, which can produce autonomic abnormalities, including clinically significant OH.[21]
dementia with Lewy bodies
Protein (alpha-synuclein) deposits can occur in peripheral autonomic nerves and autonomic ganglia, which can produce autonomic abnormalities, including clinically significant OH.[21]
multiple system atrophy
Protein (alpha-synuclein) deposits can occur in central autonomic pathways, which can produce autonomic abnormalities, including clinically significant OH.[21]
hypertension
Strongly correlated with orthostatic hypotension for complex reasons, principally because of the reduced diastolic filling and arterial stiffness that is prevalent among hypertensive patients, as well as the exaggerated threshold effect for patients with high supine or seated baseline blood pressure.[15]
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