INTRODUCTION — When autonomic reflexes are impaired or intravascular volume is markedly depleted, a significant reduction in blood pressure occurs upon standing, a phenomenon termed "orthostatic hypotension." Orthostatic hypotension can be asymptomatic or symptomatic. Symptoms can include dizziness, lightheadedness, syncope, muscle ache in the neck and shoulders, and even angina.
Symptomatic falls in blood pressure after standing or eating are a frequent clinical problem. The prevalence of orthostatic hypotension varies from 5 to 20 percent in different reports. Many disorders can cause orthostatic hypotension, which can also be a symptom of acute or chronic volume depletion as well as a side effect of drugs, particularly antihypertensives. A related problem, postprandial hypotension (a fall in blood pressure occurring 15 to 90 minutes after meals) is also common in older subjects.
Chronic orthostatic intolerance (COI) describes the association of lightheadedness, dizziness, faintness, or syncope that occurs with prolonged standing or upright posture. These symptoms may be sometimes associated with an exaggerated tachycardia but no fall in blood pressure, a disorder that is called the postural tachycardia syndrome (POTS).
This topic will review the pathogenesis and causes of orthostatic and postprandial hypotension. The treatment of these syndromes is discussed separately. POTS is also discussed separately. (See "Treatment of orthostatic and postprandial hypotension" and "Postural tachycardia syndrome".)
NORMAL BLOOD PRESSURE RESPONSE TO STANDING — Assumption of the upright posture results in the pooling of 500 to 1000 mL of blood in the lower extremities and splanchnic circulation, which initiates the following sequence [1]:
●A rapid decrease in venous return to the heart.
●The ensuing reduction in ventricular filling results in diminished cardiac output and blood pressure.
●The fall in blood pressure and thoracic volume provokes a compensatory reflex involving the central and peripheral nervous systems that increases sympathetic and reduces parasympathetic outflow (ie, baroreflex).
●The increase in sympathetic outflow raises peripheral vascular resistance, venous return, and cardiac output, thereby limiting the fall in blood pressure.
Because of these compensatory mechanisms, assumption of the erect posture normally leads to a small fall in systolic blood pressure (5 to 10 mmHg), an increase in diastolic blood pressure (5 to 10 mmHg), and an increase in pulse rate (10 to 25 beats per minute).
In patients with orthostatic hypotension, one or more of these compensatory mechanisms fail, leading to a decline in blood pressure with assumption of upright posture. (See 'Diagnosis' below.)
EPIDEMIOLOGY AND RISK FACTORS — The reported prevalence of orthostatic hypotension varies with age and the clinical setting [2].
Orthostatic hypotension is more common in older adults due at least in part to impaired baroreceptor sensitivity [3-6]. Epidemiologic surveys and meta-analyses have found orthostatic hypotension in as much as 24 percent of patients over age 65 [7-11]. In the Cardiovascular Health study, for example, the prevalence of orthostatic hypotension was 18 percent in subjects aged 65 years or older, although only 2 percent were symptomatic (defined as dizziness with standing) [7]. There was a modest association (odds ratio 1.4 to 1.9) with systolic hypertension when supine, carotid stenosis greater than 50 percent, and the use of oral hypoglycemic agents. There was only a weak association with the use of beta blockers and no association with other antihypertensive drugs (including diuretics).
However, other studies have found the use of antihypertensive medications to be related to orthostatic hypotension in older adults [8,12]. Other drugs associated with orthostatic hypotension, especially in older adults, are vasodilators, including nitrates and calcium channel blockers, antidepressants (eg, tricyclics), antipsychotics (eg, phenothiazines), opiates, and alcohol (table 1).
Orthostatic hypotension is a common reason for, or contributor to, hospitalization in older adult patients. A report from the Nationwide Inpatient Sample estimated an orthostatic hypotension hospitalization rate of 233 per 100,000 patients over 75 years of age, with a median length of stay of three days and an overall in-hospital mortality rate of 0.9 percent [3]. Among various inpatient series, the prevalence of orthostatic hypotension in older adult patients is as high as 60 percent [13,14].
Orthostatic hypotension can also occur in younger, middle-aged, or older subjects, who, in the absence of volume depletion (due to diuretics, hemorrhage, or vomiting), usually have baroreflex (ie, autonomic) failure.
ETIOLOGIES — Many disorders can cause orthostatic hypotension, with the major mechanisms being baroreflex dysfunction, severe volume depletion, adverse effects of medications, and chronic hypertension [1].
The relative frequencies of various causes of orthostatic hypotension vary according to the setting. Up to 40 percent of patients have no definite cause [4,15]. In one study from a tertiary center of 100 consecutive patients with moderate to severe orthostatic hypotension [15]:
●27 percent had underlying neurodegenerative disorders
●35 percent had autonomic failure due to diabetic neuropathy or paraneoplastic syndromes
●38 percent had no evidence of generalized autonomic dysfunction
●The use of antidepressant drugs was found to be a major overlooked cause
In addition, reflex syncope (also referred to as vasovagal or neurally mediated syncope) causes acute orthostatic hypotension due to a transient, paroxysmal dysfunction of the autonomic nervous system [16,17]. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".)
Baroreflex dysfunction — In patients with baroreflex dysfunction, orthostatic hypotension occurs because postganglionic sympathetic neurons do not release norepinephrine appropriately [1]. Blood pressure falls progressively after standing because the gravitational pooling of blood in the legs cannot be compensated by sympathetic vasoconstriction. This is referred to as neurogenic orthostatic hypotension (nOH). Subnormal norepinephrine release results in impaired vasoconstriction and reduced intrathoracic vascular volume, both of which contribute to orthostatic hypotension. The absence of an appropriate baroreflex-induced increase in heart rate as the blood pressure falls is a useful clinical clue to the presence of nOH. However, the presence of a heart rate increase does not exclude nOH (figure 1). By contrast, heart rate usually decreases acutely during reflex syncope [16]. (See 'Reflex syncope' below.)
The neurodegenerative diseases that most often produce clinically significant baroreflex dysfunction are the synucleinopathies described in the next section. Several types of neuropathy may also cause autonomic dysfunction.
Neurodegenerative disorders — Autonomic dysfunction, including baroreflex dysfunction causing nOH, is a common clinical feature of the synucleinopathies, which are characterized pathologically by cytoplasmic neuronal (Lewy bodies) or glial inclusions containing alpha-synuclein found in the brain and peripheral autonomic nerves of affected patients [18]. These include the following:
●Parkinson disease (PD) presents with motor abnormalities and varying degrees of autonomic failure. The prevalence of nOH increases with age and disease duration and is present in 20 to 60 percent of patients [19]. (See "Clinical manifestations of Parkinson disease", section on 'Autonomic dysfunction'.)
●Dementia with Lewy bodies (DLB) presents with cognitive impairment that is accompanied by parkinsonism and autonomic dysfunction. (See "Clinical features and diagnosis of dementia with Lewy bodies", section on 'Autonomic dysfunction'.)
●Multiple system atrophy (MSA) affects the central autonomic system but mostly spares peripheral autonomic neurons and has two phenotypes: parkinsonian and cerebellar, both with prominent autonomic failure [20]. (See "Multiple system atrophy: Clinical features and diagnosis".)
●Pure autonomic failure (PAF) presents with idiopathic autonomic failure as the sole clinical finding. While nOH is the most common presenting feature, erectile dysfunction and urinary and gastrointestinal symptoms may occur as well [21]. Patients with PAF may progress to develop PD or DLB [22,23] and, less frequently, MSA. However, some patients with PAF may retain the same phenotype for decades, suggesting that the neurodegenerative process remains confined to the peripheral autonomic neurons [24]. In those cases, patients have a substantially better prognosis than those with PD, DLB, or MSA [25].
Neuropathies — Baroreflex failure can result from peripheral neuropathies or from autoimmune blockade of ganglionic autonomic transmission:
●Small fiber peripheral neuropathies can affect postganglionic autonomic nerves and cause autonomic dysfunction [18]. Orthostatic hypotension, rarely the presenting feature, usually develops along with or after distal neuropathic pain and/or sensory loss, erectile dysfunction, and urinary or gastrointestinal symptoms.
Diabetes mellitus is the most common cause of autonomic neuropathy; the duration or severity of diabetes does not correlate with the development of this syndrome. Acquired and hereditary amyloidosis, Sjögren's disease and other collagen vascular disorders, renal failure, vitamin B12 deficiency, toxins, certain infections (syphilis, Lyme, HIV, Chagas), sarcoidosis, and porphyria are other causes of autonomic neuropathy [26-28]. (See "Screening for diabetic polyneuropathy" and "Overview of polyneuropathy".)
Prominent autonomic symptoms, including orthostatic hypotension as well as episodes of hypertension and tachycardia due to involvement of afferent baroreflex neurons, can be a feature of acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) as well [1]. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)
●Autoimmune autonomic impairment with ganglionic nicotinic acetylcholine receptor (nAChR) autoantibodies (autoimmune autonomic ganglionopathy) is usually associated with subacute (less than three months) clinical onset of dysautonomia. In addition to orthostatic hypotension, patients also have dry eyes and dry mouth, severe upper gastrointestinal dysautonomia, large pupils that react poorly to light and accommodation, and neurogenic bladder [29,30]. There is usually no objective sensory loss or motor or myotatic reflex changes. Patients are young to middle-aged adults and are more likely to be female than male (ratio 2:1). Other autoimmune disorders may be present. Detection of the nAChR antibodies at titers higher than 0.2 nmol/L confirms the diagnosis [31,32]. (See "Immune-mediated neuropathies", section on 'Neuropathies associated with hematologic conditions'.)
Severe nOH is a feature of acute sensory and autonomic neuronopathy, a rare disorder characterized by severe sensory and autonomic deficits with preservation of motor function. It is presumed to be autoimmune, but no specific antibodies have been identified [33]. (See "Approach to the patient with sensory loss", section on 'Sensory neuronopathies'.)
●Paraneoplastic autonomic neuropathy can occur in association with anti-Hu antibodies (also known as type 1 antineuronal nuclear antibody [ANNA-1]), most often in patients with small cell lung cancer, but it can be seen in other malignancies. Also associated with paraneoplastic autonomic neuropathy are Purkinje cell cytoplasmic antibodies type 2 (PCA-2) and antibodies to the neuron cytoplasmic protein, collapsin response-mediator protein-5 (CRMP-5). The nAChR antibodies discussed above are sometimes paraneoplastic as well [34]. Bowel hypomotility, intestinal obstruction, bladder dysfunction, orthostatic hypotension, pupillomotor and sudomotor dysfunction, and xerophthalmia are prominent clinical findings. (See "Paraneoplastic syndromes affecting spinal cord, peripheral nerve, and muscle", section on 'Autonomic neuropathy'.)
●Familial dysautonomia (Riley-Day syndrome) is a hereditary sensory and autonomic neuropathy (HSAN type 3) caused by mutations in ELP1. It has autosomal recessive inheritance and is expressed at birth with impaired pain and temperature sensation, along with autonomic dysfunction due to afferent baroreflex failure. Patients experience recurrent hypertensive episodes with severe retching, vomiting, and excessive sweating combined with orthostatic hypotension. (See "Hereditary sensory and autonomic neuropathies", section on 'HSAN3 (Familial dysautonomia)'.)
Hereditary forms of amyloidosis, including those associated with transthyretin (TTR) mutations, are associated with orthostatic hypotension, syncope, cardiomyopathy, gastroparesis, and length-dependent peripheral neuropathy [35]. (See "Overview of amyloidosis".)
Familial autonomic ganglionopathy due to a pathologic variant in the CHRNA3 gene leads to low norepinephrine levels and is associated with nOH, miosis, and constipation [36]. Other extremely rare genetic disorders that may lead to autonomic failure through impairment of neurotransmitter synthesis or signal transduction include beta-hydroxylase deficiency [37], aromatic amino acid decarboxylase deficiency [38], Menkes disease [39], and CYB561 mutations [40].
Age-related reduced baroreceptor sensitivity — In addition to the above disorders, a decrease in baroreceptor sensitivity is assumed to be involved in the milder, frequent form of orthostatic hypotension seen in older adult patients.
●One study, for example, showed a diminished response in older patients to tilt (a baroreceptor-mediated response) but not to non-baroreceptor-mediated stimuli such as the cold pressor test or isometric exercise [41]. The reduced baroreceptor response in older adults (when compared with younger controls) was seen in both hypertensive and normotensive subjects.
●Another study, measuring blood pressure and heart rate responses to the Valsalva maneuver, found that both the vagal and adrenergic components of the baroreceptor reflex became blunted with increasing age, each independent of the other [5].
Volume depletion — Acute or subacute volume depletion (due to diuretics, hyperglycemia, hemorrhage, or vomiting) is usually an easily recognizable cause of orthostatic hypotension. Patients with significant anemia or severe intravascular volume depletion may experience orthostatic hypotension despite normal autonomic reflexes.
Chronic hypovolemia, a frequent feature of autonomic failure, exacerbates orthostatic symptoms. Normally, norepinephrine increases sodium reabsorption in the proximal tubule [42]. This is an appropriate response to minimize sodium losses when reductions in effective circulating blood volume stimulate reflex sympathetic activity. Thus, a reduction in sympathetic activity, as in autonomic dysfunction, will increase urinary sodium excretion until a new steady state is achieved at a lower plasma volume [43]. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Regulation of effective arterial blood volume'.)
Medications — Orthostatic hypotension is a common side effect of medications, particularly antihypertensive agents (table 1). Many medications can precipitate or exacerbate symptoms of orthostatic hypotension through a variety of mechanisms, including peripheral vasodilation, autonomic dysfunction, and volume depletion [44]. In a meta-analysis of 69 trials that included more than 27,000 patients, medications associated with the highest odds of orthostatic hypotension were beta-adrenergic blockers (odds ratio [OR] 7.76, 95% CI 2.51-24.03) and tricyclic antidepressants (OR 6.3, 95% CI 2.86-13.91) [45]. Alpha-adrenergic antagonists, centrally acting alpha-adrenergic agonists, and second-generation antipsychotic medications were also associated with elevated odds of orthostatic hypotension. Sodium-glucose co-transporter 2 (SGLT2) inhibitors were also associated with a modestly increased odds of orthostatic hypotension in this analysis.
Hypertension — Although antihypertensive drugs may cause acute orthostasis, untreated or undertreated chronic hypertension may be associated with the development of orthostatic hypotension. This may occur in part due to age-related baroreflex dysfunction and by nocturnal hypovolemia from hypertension-induced pressure natriuresis [1,46]. Chronic hypertension also potentiates blood pressure variability which, in turn, may exacerbate orthostatic hypotension and lead to further baroreflex dysfunction [47]. A meta-analysis of nearly 18,500 patients in nine blood pressure treatment trials showed that, in patients with hypertension, long-term intensive blood pressure treatment was associated with a reduced risk of asymptomatic orthostatic hypotension (odds ratio 0.93, 95% CI 0.86-0.99) [48].
Others — Orthostatic hypotension may also be a clinical feature of cardiac pump failure (aortic stenosis, pericarditis/myocarditis, arrhythmias) [44].
The clinical features of adrenal insufficiency (and less commonly pheochromocytoma) may also include orthostatic hypotension [44]. (See "Clinical manifestations of adrenal insufficiency in adults", section on 'Postural hypotension'.)
RELATED CONDITIONS
Postprandial hypotension — In postprandial hypotension, blood pressure falls occur within one to two hours after a meal [2].
Postprandial hypotension is common in older subjects and patients with diabetes and different types of autonomic failure [49]. Among older residents of nursing homes, for example, 24 to 36 percent have a 20 mmHg or greater fall in systolic blood pressure within 75 minutes after eating a meal [50]. In another series of 401 consecutive older adult patients with hypertension referred to an outpatient cardiology clinic, 73 percent were found to have a 20 mmHg or greater fall in systolic blood pressure within two hours after a meal [51]. Postprandial hypotension may occur even when lying supine.
The etiology of postprandial hypotension is not understood completely. Affected patients have inadequate sympathetic compensation to meal-induced pooling of blood in the splanchnic circulation, leading to impaired maintenance of cardiac output and systemic vascular resistance [50]. Postprandial hypotension has been associated with an elevated risk of cardiovascular events and mortality [52]. Other possible contributors include vasodilatation induced by insulin or vasoactive gastrointestinal peptides.
Reflex syncope — Orthostatic hypotension occurs acutely and transiently in reflex syncope. Vasovagal, neurocardiogenic, carotid sinus hypersensitivity, and syncope associated with micturition and defecation are examples of reflex syncope.
The clinical syndrome of reflex syncope differs from that of orthostatic hypotension. In the latter, sympathetic efferent activity is chronically impaired, and upon standing, blood pressure always falls. By contrast, in reflex syncope, the failure of sympathetic efferent vasoconstrictor traffic (and hypotension) occurs episodically and typically in response to a trigger (emotional stress, painful or noxious stimuli, etc). During reflex syncope, concomitant with withdrawal of sympathetic efferent activity, parasympathetic (vagal) activity increases, slowing the heart (figure 1) [16]. The pathogenesis and clinical features of vasovagal and other reflex syncopes are discussed separately. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".)
Postural tachycardia syndrome and chronic orthostatic intolerance — Chronic orthostatic intolerance (COI) is the term used to describe the association of lightheadedness, dizziness, faintness, or syncope that occurs with prolonged standing or upright posture.
Younger patients have been described with COI who develop a variety of symptoms such as fatigue, lightheadedness, exercise intolerance, and cognitive impairment with assumption of the upright position. These symptoms are associated with an exaggerated tachycardia but no fall in blood pressure. This disorder has been called postural tachycardia syndrome (POTS). POTS is discussed separately. (See "Postural tachycardia syndrome".)
Supine hypertension — Supine hypertension is a condition that occurs while lying horizontally, unlike typical arterial hypertension which is present irrespective of body positioning. Supine hypertension is a common treatment-limiting complication of orthostatic hypotension.
Supine hypertension is common in neurodegenerative conditions associated with orthostatic hypotension. The prevalence of supine hypertension in Parkinson disease is 30 to 50 percent, 40 percent in multiple system atrophy, and 50 to 70 percent in pure autonomic failure. Supine hypertension in patients with chronic autonomic failure can result in end-organ damage [53,54], higher incidence of cardiovascular events, and shorter survival [55]. The blood pressure threshold that requires treatment and the target to prevent organ damage in this setting is uncertain.
Orthostatic hypertension — Some patients with baroreflex dysfunction may develop hypertension in response to standing. Such patients have impairment in afferent neuronal mechanoreceptors. This may lead to fluctuations in blood pressure including hypertension when standing due to a lack of afferent inhibition of sympathetic outflow [1,56,57]. Associated symptoms may include headache, flushing, and anxiety. These symptoms may occur in patients with familial dysautonomia, those with acute Guillain-Barré syndrome, and those with structural damage of the carotid body [58,59]. (See "Hereditary sensory and autonomic neuropathies", section on 'HSAN3 (Familial dysautonomia)' and "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis", section on 'Clinical features' and "Carotid endarterectomy", section on 'Location and influence of the carotid baroreceptor'.)
SYMPTOMS — Symptoms of orthostatic hypotension typically occur in response to sudden orthostatic change but also after meals, exertion, and prolonged standing [18]. Symptoms result from cerebral hypoperfusion and include generalized weakness, sensations described as dizziness or lightheadedness, visual blurring or darkening of the visual fields, and, in severe cases, loss of consciousness (syncope). Less frequently, orthostatic hypotension leads to angina or stroke.
Complaints less easily recognized as hypotensive in origin, such as generalized weakness, fatigue, cognitive slowing, and leg buckling, may also occur. Neck pain and headache localized in the suboccipital, posterior cervical, and shoulder region (the "coat-hanger headache"), are reported by 50 to 90 percent of patients according to different case series [60-63].
Symptoms of orthostatic hypotension vary in severity from mild to incapacitating; severely afflicted patients are unable to leave the supine position without experiencing presyncope or syncope [64,65]. In rare cases, orthostatic hypotension has been linked to cardiovascular and cerebrovascular events [7,66,67]. By contrast, some patients with orthostatic hypotension are asymptomatic.
Up to 50 percent of patients with orthostatic hypotension, often those who have underlying baroreflex dysfunction, also have systolic hypertension when seated or supine. This is referred to as neurogenic supine hypertension. The management of neurogenic supine hypertension is challenging as treatment of neurogenic supine hypertension can exacerbate orthostatic hypotension [55,68].
Patients with orthostatic hypotension are also at risk for other associated conditions. (See 'Complications' below.)
DIAGNOSTIC EVALUATION
Diagnosis — Orthostatic hypotension is diagnosed by comparing blood pressure readings in the supine and standing positions. The threshold of change for orthostatic hypotension is [2]:
●A reduction of 20 mmHg or more in systolic pressure
●A reduction of 10 mmHg or more in diastolic pressure
Techniques to measure blood pressure — Blood pressure is taken initially after five minutes of supine rest then again after the patient has been standing for two to five minutes. Alternative techniques may be performed for symptomatic patients not meeting diagnostic criteria with initial testing.
●Continuous blood pressure monitoring may be warranted for symptomatic patients with short-lived fluctuations in blood pressure not identified with initial intermittent blood pressure measurements [69]. This is performed by using a noninvasive system (eg, plethysmography) that avoids multiple inflations of a sphygmomanometer cuff. For these patients, conventional blood pressure cuff pressures may not be taken rapidly enough to avoid missing the transient blood pressure fall often associated with immediate orthostatic hypotension during change of posture [63].
Continuous measurements are also used in the evaluation of patients with orthostatic hypotension to identify other related disorders such as vasovagal syncope or afferent baroreflex failure [1]. (See 'Patients with baroreflex dysfunction' below.)
●Blood pressure measurement with tilt table testing may be performed for patients with delayed orthostatic hypotension. These patients may have milder abnormalities of sympathetic adrenergic function, suggesting the possibility that this phenomenon may be an earlier form of impairment. In one study, 108 of 230 patients investigated with tilt table testing had abnormal test results [70]. In more than half of these, orthostatic hypotension occurred after five minutes of tilt, and in 40 percent it occurred after 10 minutes. (See 'Patients with baroreflex dysfunction' below.)
The heart rate typically rises to compensate for a postural reduction in blood pressure. In (nonneurogenic) orthostatic hypotension due to volume depletion, the heart rate normally rises immediately on standing. The absence of an appropriate baroreflex-induced increase in heart rate as the blood pressure falls is a useful clinical clue to the presence of neurogenic orthostatic hypotension in the setting of autonomic failure; however, the presence of a heart rate increase does not exclude autonomic failure.
The ratio between the increase in heart rate and the fall in blood pressure provides the most sensitive and specific bedside differentiator between neurogenic (ie, due to baroreflex failure) and nonneurogenic orthostatic hypotension (ie, due to volume depletion). An increase of ≤0.5 beats/minute for every 1 mmHg drop in systolic blood pressure during tilt-table testing or active standing may be useful to diagnose neurogenic orthostatic hypotension [71,72].
An increase in heart rate of >30 beats per minute in the absence of orthostatic hypotension suggests postural tachycardia syndrome (POTS), which usually does not include orthostatic hypotension. (See "Postural tachycardia syndrome".)
Additional testing — For patients diagnosed with orthostatic hypotension, additional testing should be performed to identify treatable conditions that may be causative or contributory and to distinguish between neurogenic and nonneurogenic orthostatic hypotension. Specific testing varies by clinical features and examination findings in patients with orthostatic hypotension. Relevant features to elicit in a history and examination to help guide testing include [63,73]:
●Detailed medication list, prescription and nonprescription. Some of the medications associated with orthostatic hypotension are shown in the table (table 1).
●Recent medical history of potential volume loss (vomiting, diarrhea, fluid restriction, fever).
●Medical history of congestive heart failure, malignancy, diabetes, alcoholism.
●Orthostatic heart rate changes. (See 'Baroreflex dysfunction' above.)
●Evidence on neurologic history and examination or family history of parkinsonism, ataxia, peripheral neuropathy, or dysautonomia (eg, abnormal pupillary response, history of constipation or erectile dysfunction). (See 'Neurodegenerative disorders' above and 'Neuropathies' above.)
Up to one-third of patients will have no identified cause despite extensive evaluation [4].
Testing for most patients — Laboratory testing (hematocrit, electrolytes, blood urea nitrogen, creatinine, glucose) and a 12-lead electrocardiogram should be obtained in selected patients to evaluate for underlying anemia or dehydration or heart disease when there is reason to suspect these conditions, or when the cause of orthostatic hypotension is otherwise unclear.
Plasma norepinephrine concentration should be obtained to help guide medication selection for patients starting pharmacotherapy (algorithm 1). (See "Treatment of orthostatic and postprandial hypotension", section on 'Stepwise approach and monitoring'.)
Patients with neuropathy — When the history or examination suggests a neuropathy (distal sensory loss, areflexia), electromyography and nerve conduction studies may be useful to characterize the abnormality. However, normal nerve conduction studies do not exclude a small-fiber neuropathy, which is associated with autonomic dysfunction. Fasting blood sugar, syphilis serology, serum protein electrophoresis, and other testing may be used to identify the underlying cause. (See "Overview of polyneuropathy", section on 'Diagnostic evaluation'.)
Patients with baroreflex dysfunction — Noninvasive autonomic testing, including beat-to-beat blood pressure and heart rate changes induced by Valsalva maneuver or other standardized stimuli can be obtained to ascertain abnormal baroreflex function in patients with orthostatic hypotension (thus distinguishing them from those with volume depletion or severe physical deconditioning) and to localize the site of abnormality. Detailed autonomic testing is not widely available but can be useful in documenting the type and characteristics of the autonomic dysfunction and establishing prognosis. Regardless of the cause, treatment of orthostatic hypotension is symptomatic. (See "Treatment of orthostatic and postprandial hypotension".)
Children — Sustained orthostatic hypotension in children usually indicates a genetic or autoimmune disorder affecting the autonomic nervous system. This is typically accompanied by other non-autonomic manifestations of the underlying disorder. Specific evaluations, including genetic testing, might be required. (See 'Neuropathies' above.)
COMPLICATIONS — Patients with orthostatic hypotension are at risk for other medical complications due to complications of orthostasis or a shared underlying pathophysiology.
●Falls – Orthostatic hypotension, particularly when symptomatic, can cause falling, which has significant associated morbidity, particularly in a frail older adult population [9,74]. In one study of older nursing home resident patients, orthostatic hypotension was associated with an increased risk of recurrent falls (relative risk 2.6) [75]. (See 'Symptoms' above.)
●Cardiovascular disease – According to several population-based studies, orthostatic hypotension is a risk factor for cardiovascular and all-cause mortality, usually due to underlying causes and associated diseases [26,67,76-83]. A prospective study using ambulatory blood pressure monitoring in 374 older adults (age 70.2 ± 8.5 years) found that systolic orthostatic hypotension was a strong predictor of future cardiovascular events (hazard ratio [HR] 2.4) [84]. Orthostatic hypotension has also been linked to a risk of congestive heart failure [85-87] and atrial fibrillation [88].
For patients with asymptomatic orthostatic hypotension who have untreated or undertreated chronic hypertension, intensive treatment with antihypertensive medications may reduce the risk of cardiovascular complications. In a meta-analysis of nine blood pressure treatment trials that included 2592 patients with hypertension and asymptomatic orthostatic hypotension, intensive blood pressure treatment was associated with a reduced risk of cardiovascular disease and death (hazard ratio 0.83, 95% CI 0.7-1.0) [89]. Treatment benefit for patients with asymptomatic orthostatic hypotension was similar to those without. This benefit did not apply to patients with low systolic blood pressure when standing or with symptomatic orthostatic hypotension.
●Cognitive impairment – Orthostatic hypotension has been associated with the development of cognitive impairment and dementia. In a Swedish longitudinal, population-based cohort analysis of 2532 older adults followed for 12 years, orthostatic hypotension was associated both with the development of dementia (HR 1.4, 95% CI 1.1-1.8) and with the progression from mild cognitive impairment to dementia (HR 1.5, 95% CI 1.1-2.3) [90]. The cumulative incidence of dementia was higher for those with orthostatic hypotension compared with those without both among patients with baseline cognitive impairment (31 versus 21 percent) and those without (16 versus 13 percent). Similar results were observed in the Atherosclerosis Risk in Communities (ARIC) study, which followed 11,709 participants for over 25 years and found that those with orthostatic hypotension at baseline had a higher risk of dementia (HR 1.54, 95% CI 1.20-1.97) [91].
The mechanisms underlying this association are uncertain. Repeated episodes of hypotension and cerebral hypoperfusion may result in neuronal injury. One study found that orthostatic hypotension was associated with periventricular white matter lesion burden [92], which in turn is a marker of vascular cognitive impairment in some studies. In addition, orthostatic hypotension and cognitive impairment can be both prodromal manifestations of an underlying neurodegenerative disease, such as dementia with Lewy bodies [24].
Other studies examining an association between orthostatic hypotension and cognitive decline or dementia have had conflicting results but have been criticized for methodologic flaws. These include varying lengths of follow-up, use of different measures for cognitive assessment and, most importantly, whether concomitant supine hypertension or the degree of blood pressure variability was considered [55,93-98].
●Others – Orthostatic hypotension, particularly when disabling, is associated with impaired quality of life. While anxiety, depression, and other psychosocial problems appear to be associated with orthostatic hypotension, the direction of a possible causal relationship is unclear and may be mediated in part by medications [99-101].
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Orthostatic hypotension (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology – Orthostatic hypotension is more common in older patients and may affect up to 20 percent of patients over the age of 65 years. (See 'Epidemiology and risk factors' above.)
●Causes of orthostatic hypotension – Several conditions may cause or contribute to orthostatic and postprandial hypotension including:
•Baroreflex dysfunction from neurodegenerative diseases, peripheral neuropathies, or age-related changes (see 'Baroreflex dysfunction' above)
•Volume depletion due to diuretics, hemorrhage, or vomiting (see 'Volume depletion' above)
•Antihypertensive and other medications (table 1), particularly in older adults (see 'Medications' above)
•Chronic hypertension, via baroreflex dysfunction and nocturnal pressure-induced natriuresis (see 'Hypertension' above)
●Distinguishing features of related conditions – Patients with reflex (also called vasovagal) syncope, outside the acute event, have normal blood pressure response to standing. Patients with postural tachycardia syndrome (POTS) complain of symptoms that are similar to those of orthostatic hypotension but have no orthostatic hypotension on examination. Some patients with baroreflex dysfunction may develop hypertension in the supine position or even in response to standing. (See 'Related conditions' above.)
●Clinical features – Symptoms of orthostatic hypotension occur in response to an orthostatic change (sometimes exacerbated by recent meal, heat, exertion) and include generalized weakness, sensations described as dizziness or lightheadedness, visual blurring or darkening of the visual fields, and, in severe cases, loss of consciousness (syncope). Some patients with orthostatic hypotension are asymptomatic. (See 'Symptoms' above.)
●Diagnosis – Orthostatic hypotension is diagnosed when, within two to five minutes of quiet standing (after a five-minute period of supine rest), one or two of the following is present (see 'Diagnosis' above):
•A reduction of 20 mmHg or more in systolic pressure
•A reduction of 10 mmHg or more in diastolic pressure
For patients diagnosed with orthostatic hypotension, further testing should be performed to identify treatable conditions that may be causative or contributory, in particular medications and potential volume loss. (See 'Additional testing' above.)
●Complications – Orthostatic hypotension is a risk factor for cardiovascular and all-cause mortality, can cause falls and attendant morbidity, and is associated with cognitive decline as well as comorbid psychiatric symptoms. (See 'Complications' above.)
ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Roy Freeman, MD and Norman Kaplan, MD, who contributed to earlier versions of this topic review.
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