Cause Of Orthostatic Hypotension Research Articles

A novel mechanism of idiopathic orthostatic hypotension and hypocatecholaminemia due to autoimmunity against aromatic l-Amino acid decarboxylase

Orthostatic hypotension (OH) is a common condition. Many potential etiologies of OH have been identified, but in clinical practice the underlying cause of OH is often unknown. In the present study, we identified a novel and extraordinary etiology of OH. We describe a first case of acquired severe OH with syncope, and the female patient had extremely low levels of catecholamines and serotonin in plasma, urine and cerebrospinal fluid (CSF). Her clinical and biochemical evidence showed a deficiency of the enzyme aromatic l-amino acid decarboxylase (AADC), which converts l-DOPA to dopamine, and 5-hydroxytryptophan to serotonin, respectively. The consequence of pharmacologic stimulation of catecholaminergic nerves and radionuclide examination revealed her catecholaminergic nerves denervation. Moreover, we found that the patient's serum showed presence of autoantibodies against AADC, and that isolated peripheral blood mononuclear cells (PBMCs) from the patient showed cytokine-induced toxicity against AADC. These observations suggest that her autoimmunity against AADC is highly likely to cause toxicity to adrenal medulla and catecholaminergic nerves which contain AADC, resulting in hypocatecholaminemia and severe OH. Administration of vitamin B6, an essential cofactor of AADC, enhanced her residual AADC activity and drastically improved her symptoms. Our data thus provide a new insight into pathogenesis and pathophysiology of OH.

Orthostatic Hypotension and Concomitant Paraneoplastic Syndromes: A Case Report

This case study discusses the incidence of a paraneoplastic autonomic neuropathy in an elderly male who had an otherwise negative work-up for their aetiology of orthostatic hypotension. This case illustrates the importance of trying to correctly identify the aetiology of orthostatic hypotension, which is often overlooked, and frequently diagnosed as idiopathic. Orthostatic hypotension is most prevalent in elderly populations and can be debilitating, leading to a higher incidence of falls and trauma. Thus, it is important to obtain further work-up when traditional treatments are ineffective. In patients with new and insidious onset of orthostatic hypotension, previous history of malignancy, and possible symptoms consistent with ongoing malignancy, it is imperative to consider paraneoplastic autonomic neuropathy as a potential cause of orthostatic hypotension.

Drug-Related Orthostatic Hypotension: Beyond Anti-Hypertensive Medications.

Orthostatic hypotension (OH) is an abnormal blood pressure response to standing, which is associated with an increased risk of adverse outcomes such as syncope, falls, cognitive impairment, and mortality. Medical therapy is one the most common causes of OH, since numerous cardiovascular and psychoactive medications may interfere with the blood pressure response to standing, leading to drug-related OH. Additionally, hypotensive medications frequently overlap with other OH risk factors (e.g., advanced age, neurogenic autonomic dysfunction, and comorbidities), thus increasing the risk of symptoms and complications. Consequently, a medication review is recommended as a first-line approach in the diagnostic and therapeutic work-up of OH, with a view to minimizing the risk of drug-related orthostatic blood pressure impairment. If symptoms persist after the review of hypotensive medications, despite adherence to non-pharmacological interventions, specific drug treatment for OH can be considered. In this narrative review we present an overview of drugs acting on the cardiovascular and central nervous system that may potentially impair the orthostatic blood pressure response and we provide practical suggestions that may be helpful to guide medical therapy optimization in patients with OH. In addition, we summarize the available strategies for drug treatment of OH in patients with persistent symptoms despite non-pharmacological interventions.

Orthostatic hypotension. Part 2: diagnosis and treatment

Since orthostatic hypotension is largely asymptomatic, performing an orthostatic challenge is considered as the main mean to diagnose it. One should try to define the causes of orthostatic hypotension in every single case as treating illness that lead to orthostatic hypotension will improve patient’s health outcomes. The main target for therapy should be improving patient’s functional status, reducing orthostatic symptoms as well as risk for falls and syncopes, but not maintaining arterial blood pressure within certain limits. The higher the doctors’ awareness of the methods used to diagnose the orthostatic hypotension, the better patient’s quality of life will be. The first part of the systematic review was published in the Innovative Medicine of Kuban, nr. 4, 2018.

Orthostatic Hypotension in a Complex Clinical Setting Use of the Heart Rate Increase/Systolic Blood Pressure Decrease Ratio as a Diagnostic Aid

A simple bedside test to distinguish neurogenic from non-neurogenic causes of orthostatic hypotension (OH) is the ratio of heart rate increase during OH to the simultaneous decrease in systolic blood pressure (SBP), i.e. the ΔHR/ΔSBP ratio. In a patient suffering from persistent OH we monitored the ΔHR/ΔSBP ratio to aid with a targeted therapy. During a six-week period four pairs of postural tests were performed, one in the fasting and the other in the postprandial state. Inconsistency of the ΔHR/ΔSBP ratio under the patient's apparently stable clinical condition was confusing. So, the ΔHR/ΔSBP ratio did not help in taking therapeutic decisions.

Management of Orthostatic Hypotension in Parkinson's Disease.

Orthostatic hypotension (OH) is a common non-motor feature of Parkinson’s disease that may cause unexplained falls, syncope, lightheadedness, cognitive impairment, dyspnea, fatigue, blurred vision, shoulder, neck, or low-back pain upon standing. Blood pressure (BP) measurements supine and after 3 minutes upon standing screen for OH at bedside. The medical history and cardiovascular autonomic function tests ultimately distinguish neurogenic OH, which is due to impaired sympathetic nerve activity, from non-neurogenic causes of OH, such as hypovolemia and BP lowering drugs. The correction of non-neurogenic causes and exacerbating factors, lifestyle changes and non-pharmacological measures are the cornerstone of OH treatment. If these measures fail, pharmacological interventions (sympathomimetic agents and/or fludrocortisone) should be introduced stepwise depending on the severity of symptoms. About 50% of patients with neurogenic OH also suffer from supine and nocturnal hypertension, which should be monitored for with in-office, home and 24 h-ambulatory BP measurements. Behavioral measures help prevent supine hypertension, which is eventually treated with non-pharmacological measures and bedtime administration of short-acting anti-hypertensive drugs in severe cases. If left untreated, OH impacts on activity of daily living and increases the risk of syncope and falls. Supine hypertension is asymptomatic, but often limits an effective treatment of OH, increases the risk of hypertensive emergencies and, combined with OH, facilitates end-organ damage. A timely management of both OH and supine hypertension ameliorates quality of life and prevents short and long-term complications in patients with Parkinson’s disease.

In This Issue

HomeCirculation ResearchVol. 122, No. 6In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published16 Mar 2018https://doi.org/10.1161/RES.0000000000000203Circulation Research. 2018;122:791JNK2/CaMKII Crosstalk Underlies Atrial Arrhythmias (p 821)Inhibiting JNK2 reduces the risk of atrial fibrillation, report Yan et al.Download figureDownload PowerPointCharacterized by a rapid and irregular heartbeat, atrial fibrillation (A-Fib) is associated with hypertrophy, heart failure, ischemia, and old age. Indeed, between 10 and 15% of 70- to 80-year olds develop A-Fib. However, in addition to A-Fib, the activity of the stress–response enzyme c-Jun N-terminal kinase (JNK) also increases with age, hypertrophy, heart failure, and ischemia, which prompted Yan and colleagues to investigate whether A-Fib and JNK share a more direct link. Focusing on JNK2, which is the major JNK isoform in the heart, the team confirmed that the activity of the enzyme is positively correlated with age in both human and mouse hearts. They then showed that elevating JNK2 activity in young mice caused abnormal intracellular calcium handling in the heart, and that JNK2 phosphorylated and activated the protein kinase CamKII, a known driver of arrhythmia. Moreover, inhibition of JNK2 in older animals prevented CamKII activation, aberrant calcium handling, and, most importantly, A-Fib susceptibility. As JNK2 inhibitors are currently under clinical investigation for the treatment of cancer and arthritis, these inhibitors may be attractive candidates for preventing or treating A-Fib.CYB561 and Orthostatic Hypotension (p 846)van den Berg et al discover a new mutation underlying orthostatic hypotension.Download figureDownload PowerPointOrthostatic hypotension—a sudden drop in blood pressure upon standing after lying or sitting—can cause dizziness, fainting, and even loss of consciousness. Although mild or occasional cases are common, in some people, the condition can be severe enough to be life-threatening. Some individuals with mutations in the enzyme dopamine β-hydroxylase (DβH), for example, have impaired production of the catecholamines, norepinephrine and epinephrine, and, as a result, dangerously low blood pressure. Now, van den Berg and colleagues have uncovered a new genetic cause of orthostatic hypotension. They found that 4 patients (2 sets of sisters) with severe, life-long illness and with catecholamine levels indicative of DβH deficiency, did not in fact have DβH mutations or reduced DβH activity. Instead, genetic analysis, including whole-exome sequencing, revealed that the women had homozygous mutations in the gene encoding cytochrome b561 (CYB561)—a transmembrane electron transporter. Investigations into the functional consequences showed that these mutations perturbed electron shuttling necessary for norephinephrine synthesis. Encouragingly, treatment with the norephinerine precursor L-dihydroxyphenylserine, while producing unpleasant side effects, increased blood pressure and relieved symptoms in all 4 patients.Vascular RvDn-3 DPA Reduce Systemic Inflammation (p 855)RvDn-3 DPA tempers the daily increase in leukocyte and platelet activation, report Colas et al.Download figureDownload PowerPointSpecialized proresolving mediators (SPMs) are recently identified molecules that promote the resolution of inflammation. Armed with the knowledge that inflammation naturally waxes and wanes at different periods of night and day, Colas and colleagues investigated whether SPM levels might also exhibit diurnal variation. They found that blood obtained from healthy volunteers at regular intervals over a 24-hour period had higher level of the SPM RvDn-3 DPA at night and that these levels dropped in the morning, coincident with increased leukocyte activation. Moreover, incubation of whole blood with RvDn-3 DPA caused a decrease in neutrophil, platelet, and monocyte activation. Because such leukocyte and platelet activation are linked with cardiovascular disease (CVD)—and to increased occurrence of adverse cardiovascular events in the morning—the team measured RvDn-3 DPA in patients with CVD. They found that, compared with healthy controls, people with CVD had lower levels of RvDn-3 DPA and that the diurnal regulation of the SPM RvDn-3 DPA was impaired. Taken together, these findings suggest that RvDn-3 DPA moderates the diurnal elevations in leukocyte activation and that loss of this regulation may lead to CVD. Previous Back to top Next FiguresReferencesRelatedDetails March 16, 2018Vol 122, Issue 6 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000203 Originally publishedMarch 16, 2018 PDF download Advertisement

An approach to the clinical assessment and management of syncope in adults.

Syncope, defined as a brief loss of consciousness due to an abrupt fall in cerebral perfusion, remains a frequent reason for medical presentation. The goals of the clinical assessment of a patient with syncope are twofold: (i) to identify the precise cause in order to implement a mechanism-specific and effective therapeutic strategy; and (ii) to quantify the risk to the patient, which depends on the underlying disease,rather than the mechanism of the syncope. Hence, a structured approach to the patient with syncope is required. History-taking remains the most important aspect of the clinical assessment. The classification of syncope is based on the underlying pathophysiological mechanism causing the event, and includes cardiac, orthostatic and reflex (neurally mediated) mechanisms. Reflex syncope can be categorised into vasovagal syncope (from emotional or orthostatic stress), situational syncope (due to specific situational stressors), carotid sinus syncope(from pressure on the carotid sinus, e.g. shaving or a tight collar), and atypical reflex syncope (episodes of syncope or reflex syncope that cannot be attributed to a specific trigger or syncope with an atypical presentation). Cardiovascular causes of syncope may be structural(mechanical) or electrical. Orthostatic hypotension is caused by an abnormal drop in systolic blood pressure upon standing, and is defined asa decrease of >20 mmHg in systolic blood pressure or a reflex tachycardia of >20 beats/minute within 3 minutes of standing. The main causes of orthostatic hypotension are autonomic nervous system failure and hypovolaemia. Patients with life-threatening causes of syncope should be managed urgently and appropriately. In patients with reflex or orthostatic syncope it is important to address any exacerbating medication and provide general measures to increase blood pressure, such as physical counter-pressure manoeuvres. Where heart disease is found to bet he cause of the syncope, a specialist opinion is warranted and where possible the problem should be corrected. It is important to remember that in any patient presenting with syncope the main objectives of management are to prolong survival, limit physical injuries and prevent recurrences. This can only be done if a patient is appropriately assessed at presentation, investigated as clinically indicated, and subsequently referred to a cardiologist for appropriate management.

PP.17.23

Objective: Accurate diagnosis of haemodynamic instability is difficult in the emergency department. We need to rule out immediately the life threatening conditions which could evolve with such clinical findings but after, it could be a “long way” to the correct diagnosis. Design and method: A case report with an unexpected cause of orthostatic hypotension. Results: This is the case of a patient aged 73 with newly diagnosed uncomplicated type II diabetes, without known arterial hypertension, who presented in the emergency department with resting tachycardia, occipital headache and clinically significant orthostatic hypotension (faintness, 60mmHg decrease in SBP). In emergency we ruled out subarachnoid hemorrhage, acute hemorrhagic syndrome and pulmonary embolism by chest CT. We also ruled out acute coronary syndrome, atrioventricular or aortic obstruction by echocardiography and laboratory investigations. Orthostatic hypotension is maintained for 48 hours despite aggressive fluid reppletion, the patient relating intermittent episodes of occipital headache, nonspecific chest pain, sweating and flush occurring especially during emotional stress conditions (venipuncture) or mictionary effort. Monitoring BP/24 h reveals values rising to 220/140mmHg with spontaneous remission which rise the suspicion of pheochromocytoma. The dosage of free plasma metanefrines indicate values more than 10 times the upper limit of normal and abdominal CT identified a tumor on the right adrenal looking compatible with pheochromocytoma. Treatment with alpha and beta blockers was started and, after 2 weeks, the patient was referred to surgery. The pathological examination revealed alveolar growth pattern in anastomosed cords and in difuse, solid areas, marked cytological and nuclear pleomorphism of cells, nuclear inclusions, hipercromatism, confirming the diagnosis of pheochromocytoma. The evolution at 1 month was favorable with normalisation of blood pressure values and glycemia. Conclusions: The typical clinical presentation of pheochromocytomas is constant elevated blood pressure or normal blood pressure with significant paroxysm related to variant stimulus. However, in some undiagnosed situations with long evolution, there is an important constriction of the vascular space leading to significant orthostatic hypotension which can further hide the real diagnosis. We appreciate it is worthy to keep in mind this “edge” diagnosis after excluding the most common causes of orthostatic hypotension.

PP.17.30

Objective: Recently, it has been revealed that orthostatic hypotension (OH) is a risk factor associated with the onset of cardiovascular disease (CVD). Increased arterial stiffness and autonomic nervous dysfunction is considered to be one of the important causes of OH. However, there are few reports of the association between arterial stiffness, autonomic nervous function and OH. Therefore, we evaluated the interconnectedness of arterial stiffness, autonomic nervous function and OH in patients with atherosclerosis risk factors. Design and method: We studied 652 patients having atherosclerosis risk factors such as hypertension, dyslipidemia and diabetes mellitus. Cardio-ankle vascular index (CAVI) was measured as an index of arterial stiffness. Blood pressure and heart rate measurements were performed during sit-to-stand orthostatic stress test to evaluate the heart rate variability (HRV) and orthostatic change in blood pressure and heart rate. Results: A significant negative correlation was found between orthostatic systolic blood pressure (SBP) change and CAVI (P < 0.001). LogLF (low frequency component) at all phase (rest phase, initial orthostatic phase and delayed orthostatic phase) and logHF (high frequency component) at all phase (except delayed orthostatic phase) had significant negative correlation with age. LogLF at all phase and logHF at all phase (except resting phase) had significant positive correlation with initial orthostatic SBP change. CAVI had a significant negative correlation with logLF at all phase and logHF at all phase (except delayed orthostatic phase). In the multiple regression analysis, initial orthostatic SBP change had a significant correlation with CAVI, logLF and logHF while orthostatic stress test, independent of age and gender (CAVI; P < 0.001, log LF at initial orthostatic phase; P = 0.020, logLF at delayed orthostatic phase; P = 0.026 and logHF at delayed orthostatic phase; P = 0.004). Conclusions: In patients with atherosclerosis risk factor, increased arterial stiffness and decreased HRV independently associated with orthostatic blood pressure decrease regardless of age and gender while their interrelationship exists. Decreased HRV caused by decreased baroreflex sensitivity while orthostatic stress may be one of the important mechanisms that links OH with CVD.

Orthostatic Hypotension: Mechanisms, Causes, Management.

Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP control fails. Such regulation depends on the baroreflexes, normal blood volume, and defenses against excessive venous pooling. OH is common in the elderly and is associated with an increase in mortality rate. There are many causes of OH. Aging coupled with diseases such as diabetes and Parkinson's disease results in a prevalence of 10-30% in the elderly. These conditions cause baroreflex failure with resulting combination of OH, supine hypertension, and loss of diurnal variation of BP. The treatment of OH is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension. The practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension. It is possible to achieve these goals with a combination of fludrocortisone, a pressor agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers. We provide a pragmatic guide on patient education and the patient-orientated approach to the moment to moment management of OH.

Orthostatic hypotension secondary to CRMP-5 paraneoplastic autonomic neuropathy

The collapsin response mediator protein 5 (CRMP-5) autoantibody is one of only several paraneoplastic antibodies associated with autonomic neuropathy. Such paraneoplastic neuropathies manifest with a constellation of autonomic abnormalities. We present a unique case of orthostatic hypotension as the sole feature of a CRMP-5 paraneoplastic autonomic neuropathy in a patient with small cell lung cancer. Given the poor prognosis of paraneoplastic autonomic dysfunction, it is important to accurately diagnose the cause of orthostatic hypotension occurring on a background of malignancy.

Orthostatic Hypotension Does Not Increase Cardiovascular Risk in the Elderly at a Population Level

The general belief that orthostatic hypotension (OH) predisposes to cardiovascular events is based on sparse and contradictory data, rarely derived from population studies. A total of 1,016 men and women aged ≥65 years was studied in a 12-year epidemiological population-based study. Cardiovascular events were detected in subjects with and without OH (blood pressure (BP) decrease ≥20mm Hg for systolic or ≥10mm Hg for diastolic), and Cox analysis was performed including OH as an independent variable. In univariate analysis, coronary (20.2% vs. 13.1%, P = 0.05), cerebrovascular (13.1% vs. 8.4%, P = 0.05), and heart failure (HF) events (20.2% vs. 13.8%, P = 0.03) were apparently more incidental in subjects with OH than in those without OH. Nevertheless, after adjusting for age, gender, and systolic BP as confounders, OH did not act as a cardiovascular predictor (relative risk for cerebrovascular events 1.33, 95% confidence interval (CI), 0.78-2.2, for coronary events 1.25, CI 0.82-1.88, for HF 1.07, CI 0.71-1.62, for arrhythmias 0.82, CI 0.40-1.37, and for syncope 0.58, CI 0.13-2.71). Although OH seems to be a predictor of coronary, cerebrovascular, and HF events, no predictive role was found in models that include biological confounders. Independent of the cause of OH, age and systolic BP, which are positively associated with OH, fully explain the greater incidence of cardiovascular events and the greater cardiovascular risk observed in subjects with OH.

Orthostatic Hypotension

Orthostatic hypotension (OH) has traditionally been associated with falls (). However, data has been inconsistent, and some believe that more research in the area is needed before a true link can be made (A. ). OH, a drop in systolic pressure of ≥ 20 points or in diastolic pressure of ≥ 10 points within 3 minutes of standing as compared to the reading while supine may be accompanied by tachycardia, syncope, dizziness, visual changes, and death. Pathophysiological causes of OH include the dependent pooling of blood in organs and the periphery, compromised venous return and stroke volume, and changes in cardiac and baroreceptor function. Hypertension, diet, mobility, and medications may also contribute to the disorder. The treatment goal is to educate the patient, eliminate physiological causes, omit contributing medications, and resort to pharmacologic means as needed (). Thorough knowledge about OH can assist home care nurses in assessing for and educating patients about the disorder. This manuscript will discuss the pathophysiology, contributing diagnoses and drug classes, signs and symptoms, treatment, and implications for home care and hospice nurses related to orthostatic hypotension.

Severe orthostatic hypotension in a diabetic patient may not be due to diabetic autonomic neuropathy

This lesson describes an unusual case of a man who was recently diagnosed with type 1 diabetes and who presented with severe orthostatic hypotension. As his diabetes was recent in onset, well controlled, and he had no other signs of microvascular disease, other causes of orthostatic hypotension were sought. His serum and cerebrospinal fluid were strongly positive for Borrelia burgdorferi IgG, suggesting a diagnosis of Lyme neuroborreliosis. Autonomic instability in Lyme, while rare, has been previously reported.

Hypotension orthostatique sévère et tumeur intramédullaire. À propos d’un cas et revue de la littérature

A 55-year-old woman presented with bilateral neuropathic pain of the upper limbs, motor palsy of the right arm, urinary dysfunction, and postural dizziness. MRI showed an intramedullary cervical tumor with a solid portion extended from C1 to C3 surrounded by a cystic portion. A macroscopic complete resection was performed and histological examination confirmed the diagnosis of ependymoma. Postoperatively, the patient's neuropathic pain and postural dizziness worsened, with syncopal attack while upright because of severe orthostatic hypotension (OH). On physical examination, her supine systolic blood pressure was 130 mmHg and fell to 80 mmHg while sitting with no change in heart rate. We found motor palsy of the left arm, bilateral ataxia, and urinary retention. Three months later, the patient was still bedridden, notably because of the OH. After 6 months, with the association of preventative measures of OH and high doses of a direct α1-adrenoreceptor agonist, a vasoconstricting agent, the patient recovered an independent gait permitting her to walk unassisted. The main causes of OH include medication, nonneurogenic causes such as cardiac insufficiency, and central or peripheral neurogenic causes such as diabetic insufficiency. Brainstem tumors are known to provide severe OH but this symptom has been seldom described in a purely spinal cord lesion. We report an interesting case of severe OH that had complicated the surgical treatment of a high cervical spinal cord ependymoma and we review the literature.

Hypotension Unawareness in Profound Orthostatic Hypotension

Background Clinicians depend on history given by the patients when considering the diagnosis of orthostatic hypotension. Methods Patients with a decrease in systolic blood pressure more than 60 mm Hg from baseline during a head-up tilt table test were included. They were classified according to their symptoms during the head-up tilt table test. Localization of the cause of orthostatic hypotension was sought in each of these groups. Results Eighty-eight (43%) patients had typical symptoms, 49 (24%) had atypical symptoms, and 68 (33%) were asymptomatic. The average decrease in systolic blood pressure was 88 mm Hg, 87.5 mm Hg, and 89.8 mm Hg in the typical, atypical, and asymptomatic groups, respectively ( P = .81). Patients reported severe dizziness with a similar frequency as lower extremity discomfort. Backache and headache also were common atypical complaints. Patients with peripheral cause of dysautonomia were able to sustain the longest upright position during the head-up tilt table test (21 minutes, compared with central dysautonomia [15 minutes]) ( P = .005). There was no correlation between the cause of dysautonomia and the occurrence of symptoms during the head-up tilt table test ( P = .58). Conclusion A third of the patients with severe orthostatic hypotension are completely asymptomatic during the head-up tilt table test, and another quarter have atypical complaints that would not lead physicians toward the diagnosis of orthostatic hypotension. These findings suggest that they might not provide adequate information in diagnosing profound orthostatic hypotension in a subset of patients with this disorder.

The consensus statement on the definition of orthostatic hypotension: a revisit after 13 years

The consensus statement on the definition of orthostatic hypotension: a revisit after 13 years

Neurogenic Orthostatic Hypotension

Orthostatic hypotension (OH) is defined as a persistent, consistent, orthostatic fall in systolic blood pressure of ≥20 mm Hg or diastolic pressure of ≥10 mm Hg by 3 minutes of standing up.1 Acute, unexpected, episodic falls in blood pressure while standing, as in neurocardiogenic syncope, do not satisfy criteria for OH. Medical records for ≈0.4% of all hospitalizations in the United States include OH as a diagnosis, and of these ≈17% have OH as the primary diagnosis.2 OH is associated with increased mortality in middle-aged adults3 and occurs especially commonly in the elderly, with a prevalence in the United States of ≈12%.4 The rate of hospitalization for nonacute OH increases exponentially with age.2 Therefore, as the US population ages, the prevalence of OH and the incidence of OH-related morbidity are likely to increase. OH can be an asymptomatic sign or manifest as symptoms that range from lightheadedness to loss of consciousness. In our experience, patients with OH do not typically present with recurrent syncope because they come to recognize and respond to premonitory symptoms such as generalized weakness, dizziness, fading vision, or lightheadedness that are relieved by lying down. Instead, OH patients often present with orthostatic intolerance and recurrent falls, an important risk factor for hip fracture and head trauma. Moreover, OH often occurs concurrently with supine hypertension, which can be severe.5 The combination of OH and supine hypertension poses a challenging clinical dilemma because the clinician must balance the risk of chronic high blood pressure versus the immediate risk of falls and consequent morbid events. Many causes of OH have been identified. The listing in Table 1⇓ stratifies these in terms of drugs, secondary nonneurogenic causes, secondary neurogenic causes, and primary neurogenic causes. Accordingly, the clinical approach to a patient with OH …

Current pharmacologic treatment for orthostatic hypotension

Orthostatic hypotension is treated effectively with the combined use of non-pharmacological and pharmacological interventions. Patients should be counseled as to the nature of the underlying disorder and reversible causes of orthostatic hypotension should be removed. Should symptoms persist, pharmacological treatment is implemented. First line pharmacotherapeutic interventions include volume repletion in combination with alpha-adrenoreceptor agonists. If unsuccessful there are several supplementary agents with different mechanisms of action that may provide an additive effect.