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Background/Objectives: Aging-related physical changes and dysfunctions in the autonomic nervous system (ANS) often lead to orthostatic hypotension (OH) in older adults. OH negatively impacts both the physical and psychological well-being of those affected. Previous studies have demonstrated that the biofeedback-based integrated program (BBIP), a multicomponent intervention focused on heart rate variability biofeedback, effectively improves OH, as well as symptoms related to ANS function. This substudy aims to examine the effects of the BBIP on psychological health outcomes among community-dwelling older adults with OH. Methods: This study employed a non-randomized controlled trial design with a convenience sampling strategy. A total of 51 older adults with OH were recruited from two senior welfare centers and randomly assigned to either the intervention group (n = 27) or the control group (n = 24). The intervention group participated in a 12-week BBIP, which included weekly biofeedback sessions and group education on lifestyle modification to alleviate OH. Telephone counseling was also provided to promote compliance. Results: The intervention group showed significant improvements in health-related quality of life, depression, anxiety, and fall efficacy after the 12-week BBIP, whereas the control group exhibited no significant changes. There was a significant reduction in the percentage of participants in the intervention group reporting problems in all five dimensions of the EQ-5D (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Conclusions: The BBIP was effective in improving the psychological health outcomes of older adults with OH. Future studies should explore the long-term effects of the BBIP using a larger sample size and a randomized controlled trial design. [ABSTRACT FROM AUTHOR]

Blood pressure regulation is an automatic, moment-by-moment buffering of the blood pressure in response to physiological changes such as orthostasis, exercise and haemorrhage. This finely orchestrated reflex is called the baroreflex. It is a regulated arc of afferent, central and efferent arms. Multiple physiological changes occur with ageing that can disrupt this reflex, making blood pressure regulation less effective. In addition, multiple changes can occur with ageing-related diseases such as neurodegeneration, atherosclerosis, deconditioning and polypharmacy. These changes commonly result in orthostatic hypotension, hypertension or both, and are consistently associated with multiple adverse outcomes. In this article, we discuss the healthy baroreflex, and physiological and pathophysiological reasons for impaired baroreflex function in older people. We discuss why the common clinical manifestations of orthostatic hypotension and concomitant supine hypertension occur, and strategies for balancing these conflicting priorities. Finally, we discuss strategies for treating them, outlining our practice alongside consensus and expert guidance. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension. We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed. Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21–0.72; I2 = 47 %; p < 0.01), n = 6 studies), but also after AHT discontinuation (risk ratio 0.39 (95 % CI = 0.28–0.55; I2 = 0 %; p < 0.01), n = 2 studies). Postural BP drop did not change after initiation or augmentation of AHT (mean difference 1.07 (95 % CI = -0.49–2.64; I2 = 92 %; p = 0.18), n = 11 studies). The main reason for ten studies not to be included in the meta-analyses was absence of baseline OH data. Most of these studies reported OH incidences between 0 and 2 %. Studies were heterogeneous in OH assessment methods (postural change, timing of BP measurements, and OH definition). Risk of bias was moderate to serious in twenty studies. Results suggest that AHT initiation or augmentation decreases OH prevalence, implying that the risk of inducing OH may be overestimated in current AHT decision-making in older adults. However, the overall low level of evidence and the finding that AHT discontinuation reduces OH prevalence limit firm conclusions at present and highlight an important research gap. Future AHT trials in older adults should measure OH in a standardized protocol, adhering to consensus guidelines to overcome these limitations. • Risks of antihypertensive treatment (AHT) in older adults are unclear. • This paper summarizes evidence on orthostatic hypotension (OH) risk with AHT. • AHT initiation did not increase OH, but AHT discontinuation reduced OH prevalence. • OH assessment is heterogeneous and often not standardized to consensus guidelines. • Future standardized trials are needed to overcome this research gap. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.). [ABSTRACT FROM AUTHOR]

Orthostatic hypotension is a frequent cause of falls and syncope, impairing quality of life. It is an independent risk factor of mortality and a common cause of hospitalizations, which exponentially increases in the geriatric population. We present a management plan based on a systematic literature review and understanding of the underlying pathophysiology and relevant clinical pharmacology. Initial treatment measures include removing offending medications and avoiding large meals. Clinical assessment of the patients' residual sympathetic tone can aid in the selection of initial therapy between norepinephrine "enhancers" or "replacers." Role of splanchnic venous pooling is overlooked, and applying abdominal binders to improve venous return may be effective. The treatment goal is not normalizing upright blood pressure but increasing it above the cerebral autoregulation threshold required to improve symptoms. Hypertension is the most common associated comorbidity, and confining patients to bed while using pressor agents only increases supine blood pressure, leading to worsening pressure diuresis and orthostatic hypotension. Avoiding bedrest deconditioning and using pressors as part of an orthostatic rehab program are crucial in reducing hospital stay. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension (OH) is very common in older people and is encountered daily in emergency departments and medical admissions units. It is associated with a higher risk of falls, fractures, dementia and death, so prompt recognition and treatment are essential. In this review article, we describe the physiology of standing (orthostasis) and the pathophysiology of orthostatic hypotension. We focus particularly on aspects pertinent to older people. We review the evidence and consensus management guidelines for all aspects of management. We also tackle the challenge of concomitant orthostatic hypotension and supine hypertension, providing a treatment overview as well as practical suggestions for management. In summary, orthostatic hypotension (and associated supine hypertension) are common, dangerous and disabling, but adherence to simple structures management strategies can result in major improvements. [ABSTRACT FROM AUTHOR]

Background: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.Methods: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.Results: A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).Interpretation: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD. [ABSTRACT FROM AUTHOR]

Neurogenic orthostatic hypotension (nOH) is a subtype of orthostatic hypotension in which patients have impaired regulation of standing blood pressure due to autonomic dysfunction. Several primary and secondary causes of this disease exist. Patients may present with an array of symptoms making diagnosis difficult. This review article addresses the epidemiology, pathophysiology, causes, clinical features, and management of nOH. We highlight various pharmacological and non-pharmacological approaches to treatment, and review the recent guidelines and our approach to nOH. [ABSTRACT FROM AUTHOR]

Background orthostatic hypotension (OH) is highly prevalent in older populations and is associated with reduced quality of life and increased mortality. Although non-pharmacologic therapies are recommended first-line, evidence for their use is lacking. Objective determine the efficacy of combination non-pharmacologic therapy for OH in older people. Methods a total of 111 orthostatic BP responses were evaluated in this prospective phase 2 efficacy study in 37 older people (≥60 years) with OH. Primary outcome was the proportion of participants whose systolic BP drop improved by ≥10 mmHg. Secondary outcomes include standing BP and symptoms. Comparison is made to the response rate of the most efficacious single therapy (bolus water drinking 56%). Therapeutic combinations were composed of interventions with known efficacy and tolerability: Therapy A- Bolus water drinking + physical counter-manoeuvres (PCM); Therapy B- Bolus water drinking + PCM + abdominal compression. Results the response rate to therapy A was 38% (95% confidence interval – CI 24, 63), with standing systolic BP increasing by 13 mmHg (95% CI 4, 22). Therapy B was efficacious in 46% (95% CI 31, 62), increasing standing systolic BP by 20 mmHg (95% CI 12, 29). Neither therapy had a significant effect on symptoms. There were no adverse events. Conclusions in comparison to single therapy, there is little additional benefit to be gained from combination non-pharmacologic therapy. Focussing on single, efficacious therapies, such as bolus water drinking or PCM, should become standard first-line therapy. [ABSTRACT FROM AUTHOR]

Background: Syncope is a common condition that may be prevented. There are non-pharmacological interventions that may be of benefit during the acute episode preceding syncope (presyncope), including physical counter-pressure maneuvers (PCM) or change of body position. We performed a systematic review of interventions that may be applied during presyncope as an immediate, first aid tactic. Methods: We searched Medline, Embase, and CINAHL and used the Grading of Recommendations Assessment, Development and Evaluation methods, and risk of bias assessments to determine the certainty of the evidence. We included randomized controlled trials (RCTs), non-randomized studies, and case series investigating adults and children with signs and symptoms of presyncope of suspected vasovagal or orthostatic origin who applied any intervention that could be used as an immediate, first aid intervention. We examined the following outcomes: prevention of syncope, adverse events, symptom improvement, and vital signs. We conducted a sub-group analysis based on the etiology of vasovagal or orthostatic presyncope. Results: We screened 5,160 titles and abstracts followed by 81 full text articles. We identified 8 studies meeting inclusion criteria, including 2 RCTs and 6 observational studies. All studies used PCM in adults and all were judged to be of low and very low certainty of evidence. For prevention of syncope, one RCT demonstrated benefit with the use of PCM (RR = 1.80 [1.26–1.89]), while observational studies failed to show benefit (RR = 1.31 [0.98 – 1.75]). Two RCTs showed benefit in symptom improvement (RR = 6.00 [2.21 – 8.61] and (RR = 1.57 [1.06 – 1.93]). Blood pressure (BP) improved with the use of PCM: systolic BP mean difference (MD) 21 mmHg higher (95% CI: 18.25 to 23.41 BPM) and diastolic BP MD 11 mmHg higher (95% CI: 9.39 to 13.10 mmHg higher). No adverse events were reported. Conclusion: While there is a minimal amount of evidence available and the findings were mixed, PCM may provide benefit for prevention of syncope during acute episodes of presyncope and may be tried in the first aid setting. No evidence was found for other non-pharmacologic interventions or for the use of PCM in children. [ABSTRACT FROM AUTHOR]

The article focuses on an individual participant meta-analysis investigating the impact of a lower blood pressure treatment goal or active therapy versus a standard blood pressure treatment goal or placebo on cardiovascular disease and all-cause mortality in patients.

Orthostatic hypotension (OH) is common in older people and is associated with a range of adverse outcomes. Although age‐related changes like decreased baroreflex sensitivity make older people prone to OH, medications are often a contributor. Diagnosis of OH can be challenging in older people, because the condition may present with atypical or non‐specific symptoms, such as visual disturbances, shortness of breath, mental fluctuation. Non‐pharmacological management is often a starting point for OH treatment. Fludrocortisone and midodrine remain the most studied drugs for pharmacological management, but newer agents are being tested. In this review we present the current evidence for existing and emerging treatments for OH and address the management of supine hypertension associated with the treatment of OH in patients with autonomic failure. In the management of OH, it is imperative that treatment is tailored to the individual, rather than focusing on attaining an arbitrary blood pressure target. [ABSTRACT FROM AUTHOR]

The article presents case study of a 71-year-old White male patient with autonomic imbalance and is dependent on nurses and caregivers for meals, medications, and assistance with basic care. It was observed that he had been resisting all attempts at standing and sitting and had been nonverbal for the entire duration of care.

Objective: To investigate the relationship of hospital admissions due to unexplained syncope and orthostatic hypotension (OH) with subsequent cardiovascular events and mortality.Methods: We analysed a population-based prospective cohort of 30 528 middle-aged individuals (age 58±8 years; males, 40%). Adjusted Cox regression models were applied to assess the impact of unexplained syncope/OH hospitalisations on cardiovascular events and mortality, excluding subjects with prevalent cardiovascular disease.Results: After a median follow-up of 15±4 years, 524 (1.7%) and 504 (1.7%) participants were hospitalised for syncope or OH, respectively, yielding 1.2 hospital admissions per 1000 person-years for each diagnosis. Syncope hospitalisations increased with age (HR, per 1 year: 1.07, 95% CI 1.05 to 1.09), higher systolic blood pressure (HR, per 10 mm Hg: 1.06, 95% CI 1.01 to 1.12), antihypertensive treatment (HR: 1.26, 95% CI 1.00 to 1.59), use of diuretics (HR: 1.77, 95% CI 1.31 to 2.38) and prevalent cardiovascular disease (HR: 1.59, 95% CI 1.14 to 2.23), whereas OH hospitalisations increased with age (HR: 1.11, 95% CI 1.08 to 1.12) and prevalent diabetes (HR: 1.82, 95% CI 1.23 to 2.70). After exclusion of 1399 patients with prevalent cardiovascular disease, a total of 473/464 patients were hospitalised for unexplained syncope/OH before any cardiovascular event. Hospitalisation for unexplained syncope predicted coronary events (HR: 1.85, 95% CI 1.49 to 2.30), heart failure (HR: 2.24, 95% CI 1.65 to 3.04), atrial fibrillation (HR: 1.84, 95% CI 1.50 to 2.26), aortic valve stenosis (HR: 2.06, 95% CI 1.28 to 3.32), all-cause mortality (HR: 1.22, 95% CI 1.09 to 1.37) and cardiovascular death (HR: 1.72, 95% CI 1.23 to 2.42). OH-hospitalisation predicted stroke (HR: 1.66, 95% CI 1.24 to 2.23), heart failure (HR: 1.78, 95% CI 1.21 to 2.62), atrial fibrillation (HR: 1.89, 95% CI 1.48 to 2.41) and all-cause mortality (HR: 1.14, 95% CI 1.01 to 1.30).Conclusions: Patients discharged with the diagnosis of unexplained syncope or OH show higher incidence of cardiovascular disease and mortality with only partial overlap between these two conditions. [ABSTRACT FROM AUTHOR]

Objective: Blunted tachycardia during hypotension is a characteristic feature of patients with autonomic failure, but the range has not been defined. This study reports the range of orthostatic heart rate (HR) changes in patients with autonomic failure caused by neurodegenerative synucleinopathies.Methods: Patients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation.Results: We identified 402 patients with orthostatic hypotension (OH) who had normal sinus rhythm. Of these, 378 had impaired sympathetic activation (ie, neurogenic OH) and based on their neurological examination were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy. The remaining 24 patients had preserved sympathetic activation and their OH was classified as nonneurogenic, due to volume depletion, anemia, or polypharmacy. Patients with neurogenic OH had twice the fall in systolic blood pressure (SBP; -44 ± 25 vs -21 ± 14 mmHg [mean ± standard deviation], p < 0.0001) but only one-third of the increase in HR of those with nonneurogenic OH (8 ± 8 vs 25 ± 11 beats per minute [bpm], p < 0.0001). A ΔHR/ΔSBP ratio of 0.492 bpm/mmHg had excellent sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic from nonneurogenic OH (area under the curve = 0.96, p < 0.0001). Within patients with neurogenic OH, HR increased more in those with multiple system atrophy (p = 0.0003), but there was considerable overlap with patients with Lewy body disorders.Interpretation: A blunted HR increase during hypotension suggests a neurogenic cause. A ΔHR/ΔSBP ratio < 0.5 bpm/mmHg is diagnostic of neurogenic OH. Ann Neurol 2018;83:522-531. [ABSTRACT FROM AUTHOR]

Despite autonomic dysfunction after spinal cord injury (SCI) being the major cause of death and a top health priority, the clinical management options for these conditions are limited to drugs with delayed onset and nonpharmacological interventions with equivocal effectiveness. We tested the capacity of electrical stimulation, applied transcutaneously over the spinal cord, to manage autonomic dysfunction in the form of orthostatic hypotension after SCI. We assessed beat-by-beat blood pressure (BP), stroke volume, and cardiac contractility (dP/dt; Finometer), as well as cerebral blood flow (transcranial Doppler) in 5 individuals with motor-complete SCI (4 cervical, 1 thoracic) during an orthostatic challenge with and without transcutaneous electrical stimulation applied at the TVII level. During the orthostatic challenge, all individuals experienced hypotension characterized by a 37 ± 4 mm Hg decrease in systolic BP, a 52 ± 10% reduction in cardiac contractility, and a 23 ± 6% reduction in cerebral blood flow (all p < 0.05), along with severe self-reported symptoms. Electrical stimulation completely normalized BP, cardiac contractility, cerebral blood flow, and abrogated all symptoms. Noninvasive transcutaneous electrical spinal cord stimulation may be a viable therapy for restoring autonomic cardiovascular control after SCI. [ABSTRACT FROM AUTHOR]

Neurogenic orthostatic hypotension, postprandial hypotension and exercise-induced hypotension are common features of cardiovascular autonomic failure. Despite the serious impact on patient's quality of life, evidence-based guidelines for non-pharmacological and pharmacological management are lacking at present. Here, we provide a systematic review of the literature on therapeutic options for neurogenic orthostatic hypotension and related symptoms with evidence-based recommendations according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Patient's education and non-pharmacological measures remain essential, with strong recommendation for use of abdominal binders. Based on quality of evidence and safety issues, midodrine and droxidopa reach a strong recommendation level for pharmacological treatment of neurogenic orthostatic hypotension. In selected cases, a range of alternative agents can be considered (fludrocortisone, pyridostigmine, yohimbine, atomoxetine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, octreotide, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin), though recommendation strength is weak and quality of evidence is low (atomoxetine, octreotide) or very low (fludrocortisone, pyridostigmine, yohimbine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin). In case of severe postprandial hypotension, acarbose and octreotide are recommended (strong recommendation, moderate level of evidence). Alternatively, voglibose or caffeine, for which a weak recommendation is available, may be useful. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla. [ABSTRACT FROM AUTHOR]

Background: Subthalamic deep brain stimulation (STN-DBS) is an established treatment for the motor complications of Parkinson's disease (PD) and may have beneficial effects on non-motor symptoms (NMS). However, the acute effect of STN stimulation on NMS has only been explored in small PD cohorts with short post-surgical follow-up.Objective: To study NMS response to an acute stimulation challenge in an STN-DBS PD population with a medium/long-term post-surgical follow-up.Methods: 32 STN-DBS PD patients were tested twice (MED OFF/STIM OFF and MED OFF/STIM ON). MDS-UPDRS-III, blood pressure (BP) assessment, a visual analogue scale for pain and fatigue and State Trait Anxiety Scale score were evaluated during both stimulation conditions. NMS were assessed with MDS-UPDRS-I, Non-Motor Symptoms Scale, Geriatric Depression Scale and the Neuropsychiatric Inventory scale.Results: Mean (SD) age was 62.5 (±13.3) years, mean disease duration 18.7 (±5.1) years, mean post-surgical follow-up 4.6 (±1.3) years, and the mean reduction of levodopa equivalent daily dose after surgery was 58.9% (±25.4%). Mean (SD) motor response to stimulation was 40% (15%). STN stimulation significantly improved anxiety (mean 18% ± 19%, P < 0.005) and fatigue (mean 25% ± 51%; P < 0.05), while pain, although improved did not reach statistical significance. With stimulation ON, BP significantly decreased during orthostatism (P < 0.05) and there was a significant increase in asymptomatic orthostatic hypotension (P < 0.05).Conclusions: Acute STN stimulation improves anxiety and fatigue but decreases orthostatic BP in PD, several years after surgery. These effects should be considered when assessing long-term effect of DBS. [ABSTRACT FROM AUTHOR]

Background: Droxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460).Methods: Efficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined.Results: Droxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies.Conclusions: Droxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials.Trial Registration: ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010. [ABSTRACT FROM AUTHOR]

Background Orthostatic hypotension ( OH) is common in Parkinson's disease ( PD), but the relation between the results of orthostatic blood pressure tests and orthostatic symptoms in daily life is not clear. Methods We performed a cross-sectional study in an incident nontertiary care cohort of PD patients with additional recruitment of PD patients from our own outpatient clinic. We recruited sex- and age-matched controls. All participants underwent orthostatic blood pressure tests using continuous blood pressure measurements. Orthostatic symptoms experienced in daily life were assessed using autonomic symptom questionnaires ( SCOPA- AUT and COMPASS-31). Results A total of 83 PD patients and 35 controls were included. Mean patient age was 69.2 years (standard deviation [ SD]: 10.0). Mean disease duration was 6.6 years ( SD, 0.8). The estimated prevalence of OH in PD was 24.1% (95% confidence interval: 16.2-34.3). There was no significant difference between PD patients with and without OH regarding reported daily orthostatic symptoms. Alternative OH criteria did not substantially improve this. Conclusions Perceived orthostatic symptoms in daily life have no clear association with the results of a single orthostatic blood pressure test. Better diagnostic strategies are needed. [ABSTRACT FROM AUTHOR]

Background Orthostatic hypotension ( OH) is a sustained fall in blood pressure on standing that can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions, particularly in the elderly (233 per 100,000 patients >75 years of age in the United States). OH can result from volume depletion, blood loss, large varicose veins, medications, or because of defective activation of sympathetic nerves and reduced norepinephrine release on standing (i.e., neurogenic OH). Methods and Findings A literature review shows that neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson's disease, multiple system atrophy, and pure autonomic failure, and it is commonly associated with supine hypertension. Several pharmacological and nonpharmacological therapeutic options are available. Conclusions Here we review the epidemiology, diagnosis, and management of neurogenic OH, and provide an algorithm for its treatment, emphasizing the importance of removing aggravating factors, implementing nonpharmacologic measures, and selecting appropriate pharmacological treatments. [ABSTRACT FROM AUTHOR]

Background and purpose Evidence for effective treatment options for orthostatic hypotension ( OH) in Parkinson's disease ( PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. Methods This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. Results Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. Conclusions Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: orthostatic hypotension (OH) is a common disabling condition associated with increased morbidity and mortality. Much of the evidence available is derived from younger populations with chronic neurological disease leading to uncertainty for the diagnosis and management of older people. Objective: to provide an overview of recent and emerging evidence for the diagnosis, management and prognosis of OH in older persons. Methods: a narrative review of recent studies, emerging therapies and relevant regulatory updates. Findings: revisions to the diagnostic criteria for OH include the duration of the blood pressure drop, specific criteria for initial and delayed OH and OH with hypertension. Non-drug therapies remain the first-line treatment option and Comprehensive Geriatric Assessment appears to result in lower rates of OH. Recent evidence concerning withdrawal of causative medication is inconsistent. Midodrine has recently become the only licenced medication for OH in the UK. Other emerging treatments include atomoxetine and droxidopa but these require further evaluation. Many other agents may be used but are not supported by high-quality evidence. The increase in mortality associated with OH is less apparent in older people. Summary: OH remains common in older people, the new diagnostic criteria address some of the previous uncertainty but evidence concerning withdrawal of antihypertensives is conflicting. Midodrine is now the only licenced medication for OH in the UK, but non-drug therapies remain first line and fludrocortisone may be considered before midodrine. We may see other agents such as droxidopa becoming increasingly used over the coming years. [ABSTRACT FROM AUTHOR]

Benign joint hypermobility syndrome (BJHS) and postural orthostatic tachycardia syndrome (POTS) are two common conditions which are frequently overlooked. While patients with BJHS are known to attend rheumatology, orthopedic, and medical outpatient departments for years with polyarthralgia; POTS is commonly misdiagnosed as anxiety neurosis or panic attack. Described first in 1940, POTS is one of the common causes of orthostatic symptoms in females. POTS is defined as orthostatic intolerance associated with tachycardia exceeding 120 beats/min (bpm) or an increase in the heart rate (HR) of 30 bpm from baseline within 10 min of changing the posture from a lying to standing position, in the absence of long-term chronic diseases and medications that affect the autonomic or vascular tone. Classified as primary and secondary, the underlying pathophysiological mechanism is assumed to be a failure of peripheral vascular resistance to increase sufficiently in response to orthostatic stress, and consequently, venous pooling occurs in the legs resulting in decreased venous return to the heart. This is compensated by an increase in HR and inotropy. We present a case of BJHS, who reported to us with recurrent episodes of syncope and presyncope and was diagnosed to have POTS secondary to his hypermobility syndrome. Although the tilt-table test is the gold standard for diagnosis of POTS, this case highlights the importance of bedside tests in evaluation of orthostatic symptoms and in diagnosis of relatively common but frequently overlooked syndrome. [ABSTRACT FROM AUTHOR]

Background: Orthostatic hypotension (OH) in Parkinson's disease (PD) is a common non-motor sign that can be hard to recognize and treat. OH prevalence and treatment in institutionalized PD-patients remains unknown. Objective: The aim of this study was to explore the prevalence and prescribed treatments of OH in institutionalized patients with PD. Method: A cross-sectional study of nursing homes in the south-east of the Netherlands identified 64 residents with PD (inclusion criteria: MMSE >18). Assessments included blood pressure measurement, both supine and in the upright position (after 1 minute and after 3 minutes of standing), and 2 questions on cardiovascular items including falls of the validated Non-Motor Symptom Scale (NMSS).OHwas defined according to the consensus guidelines.OHwas considered as 'probably symptomatic' if patients had a concomitant frequency score >1 on the selected NMSS items, and 'probably asymptomatic' for a frequency score of 0. If OH was not present, but patients had a frequency score >1, OH was considered as 'possibly symptomatic'. Results: The prevalence of OH was 51.6%, almost equally divided into probably symptomatic and probably asymptomatic cases. Another 20.6% had possibly symptomatic OH. Importantly, only two patients with symptomatic OH had an OH diagnosis noted in their medical records. Five received domperidone, one received fludrocortison and none received midodrine. Conclusion: One half of institutionalized PD patients had OH, of whom half were probably symptomatic. OH was rarely noted in the medical records, suggesting underdiagnosis. Finally, OH was rarely treated, suggesting undertreatment. [ABSTRACT FROM AUTHOR]

Background: Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. Objective: The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. Methods: This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. Results: A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Conclusions: Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms. [ABSTRACT FROM AUTHOR]

Background: Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the number needed to treat (NNT) and the number needed to harm (NNH). Methods: Data collected in randomized, placebo-controlled clinical studies in adults with a clinical diagnosis of symptomatic nOH were pooled for efficacy and safety analyses. NNT and NNH were calculated as reciprocals of the risk difference (difference in event rates) for droxidopa versus placebo. Results: The NNT for droxidopa for improvement in OHSA Item 1 was <10. The NNH for adverse events (AEs) leading to discontinuation in the pooled studies was 81. The likelihood of being helped or harmed (LHH) calculated from pooled analysis of the NNT for ≥2 units of improvement in OHSA Item 1 score and the NNH for discontinuations due to AEs were 7.8, 8.8, 3.1, and 3.5 for weeks 1, 2, 4, and 8 after randomization, respectively. Conclusions: Droxidopa is efficacious for treatment of nOH, with an NNT below 10 and an acceptable tolerability profile with NNH ranging from 23 to 302 in the pooled analysis of frequently occurring AEs. Based on the LHH for the pooled analysis at week 1, droxidopa is 7.8 times more likely than placebo to show a clinical benefit than result in discontinuation because of an AE. Trial Registrations: ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010. [ABSTRACT FROM AUTHOR]

Neurogenic orthostatic hypotension and supine hypertension are common manifestations of cardiovascular dysautonomia in Parkinson's disease and related synucleinopathies. Because these disorders are haemodynamic opposites, improvement in one might be achieved at the expense of worsening of the other. Thus, management decisions necessitate assessment of the individual risks for patients with coexistent neurogenic orthostatic hypotension and supine hypertension. Whereas neurogenic orthostatic hypotension poses risks for falls and can be associated with cognitive impairment in the short term, chronic supine hypertension can be associated with stroke and myocardial infarction in the long term. Because few clinical trial data exist for outcomes in patients with coexistent neurogenic orthostatic hypotension and supine hypertension, clinicians need to balance, on the basis of comorbidities and disease staging, the potential immediate benefits of treatment for neurogenic orthostatic hypotension and the long-term risks of supine hypertension treatment in each patient. Future research needs to focus on ascertaining a safe degree of supine hypertension when treating neurogenic orthostatic hypotension; the effectiveness of nocturnal antihypertensive therapy in patients with coexistent neurogenic orthostatic hypotension and supine hypertension; and the prevalence, scope, and therapeutic requirements for managing neurogenic orthostatic hypotension that manifests with falls or cognitive impairment, but without postural lightheadedness or near syncope. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of orthostatic hypotension (OH) among the elderly population in Singapore, as defined by a decline in blood pressure upon a change in position, is not well-established. Studies associate OH with clinically significant outcomes such as falls. This study aims to determine the prevalence of OH among elderly patients attending a public primary care clinic (polyclinic) for chronic disease management, and examine the relationships between postulated risk factors and OH.Methods: Patients aged ≥ 65 years attending a typical polyclinic in Geylang were identified and targeted for recruitment at the study site. A questionnaire on symptoms and postulated risk factors was administered, followed by supine and standing blood pressure measurements. Cross-sectional analysis was performed with independent sample t-test for continuous data and chi-square test for categorical data. Prevalence rate ratios with 95% confidence interval were calculated for the latter.Results: A total of 364 multiethnic patients participated in the study. The prevalence of OH was 11.0%. Older age, comorbidities such as cardiac failure and kidney disease, being physically inactive at work, fatigue, self-reported dizziness in the past year, and the use of loop diuretics were found to be significantly associated with OH.Conclusion: About one in ten elderly patients at a local polyclinic was affected by OH, which was associated with multiple factors. Some of these factors are modifiable and can be addressed to reduce the incidence of OH. [ABSTRACT FROM AUTHOR]

Syncope, defined as a transient loss of consciousness secondary to global cerebral hypoperfusion, is common in the general population. The single most helpful “test” in the evaluation of patients with syncope is a thoughtful history, with recent evidence that structured histories are remarkably effective in arriving at a diagnosis. In addition to the history, physical examination, and electrocardiogram, arriving at a diagnosis of syncope can involve monitoring and provocative strategies. The majority of patients with syncope have neurally mediated syncope and a favourable prognosis. The management of neurally mediated syncope continues to largely revolve around education, avoidance of triggers, reassurance, and counter-pressure maneuvers. The evidence surrounding medical therapy in vasovagal syncope is not strong to date. Pacemaker therapy is reasonable in older patients with recurrent, unpredictable syncope with pauses, but should be considered as a last resort in younger patients. [ABSTRACT FROM PUBLISHER]

Background and Methods To investigate the possible efficacy of an elastic abdominal binder to control orthostatic hypotension ( OH) associated with Parkinson's disease ( PD), 15 patients with PD and OH were enrolled in a single-blind crossover study with elastic abdominal versus placebo binder on two different days, separated by a 1-day interval, followed by a 4-week open-label follow-up. Results Intervention significantly reduced blood pressure fall upon tilting. The mean difference (standard deviation; 95% confidence intervals) between abdominal binder versus placebo was +10 mm Hg (10.2; +3.5, +16.5; P = 0.006). No significant effect on supine mean blood pressure values was observed compared to placebo ( P = 0.3). Symptoms of OH decreased significantly during follow-up ( P = 0.003), as assessed by means of the Orthostatic Hypotension Questionnaire. Conclusions Our findings suggest that elastic abdominal binders may be a simple complementary tool to alleviate OH in PD. [ABSTRACT FROM AUTHOR]

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI. [ABSTRACT FROM AUTHOR]

Background: Impaired blood pressure (BP) stabilisation after standing, defined using beat-to-beat measurements, has been shown to predict important health outcomes. We aimed to define the relationship between individual classes of antihypertensive agent and BP stabilisation among hypertensive older adults. Methods: Cross-sectional analysis from The Irish Longitudinal Study on Ageing, a cohort study of Irish adults aged 50 years and over. Beat-to-beat BP was recorded in participants undergoing an active stand test. We defined grade 1 hypertension according to European Society of Cardiology criteria (systolic BP [SBP] 140-159mmHg ± diastolic BP [DBP] 90-99mmHg). Outcomes were: (i) initial orthostatic hypotension (IOH) (SBP drop ≥40mmHg ± DBP drop ≥20mmHg within 15 seconds [s] of standing accompanied by symptoms); (ii) sustained OH (SBP drop ≥20mmHg ± DBP drop ≥10mmHg from 60 to 110s inclusive); (iii) impaired BP stabilisation (SBP drop ≥20mmHg ± DBP drop ≥10mmHg at any 10s interval during the test). Outcomes were assessed using multivariable-adjusted logistic regression. Results: A total of 536 hypertensive participants were receiving monotherapy with a renin-angiotensin-aldosterone-system inhibitor (n = 317, 59.1%), beta-blocker (n = 89, 16.6%), calcium channel blocker (n = 89, 16.6%) or diuretic (n = 41, 7.6%). A further 783 untreated participants met criteria for grade 1 hypertension. Beta-blockers were associated with increased odds of initial OH (OR 2.05, 95% CI 1.31–3.21) and sustained OH (OR 3.36, 95% CI 1.87–6.03) versus untreated grade 1 hypertension. Multivariable adjustment did not attenuate the results. Impaired BP stabilisation was evident at 20s (OR 2.59, 95% CI 1.58–4.25) and persisted at 110s (OR 2.90, 95% CI 1.64–5.11). No association was found between the other agents and any study outcome. Conclusion: Beta-blocker monotherapy was associated with a >2-fold increased odds of initial OH and a >3-fold increased odds of sustained OH and impaired BP stabilisation, compared to untreated grade 1 hypertension. These findings support existing literature questioning the role of beta-blockers as first line agents for essential hypertension. [ABSTRACT FROM AUTHOR]

Background: Atropine is an anticholinergic drug which is commonly used in clinical practice. The effect of parasympathetic block with atropine on dynamic cerebrovascular regulation remains unclear. This study was aimed to identify effects of vagolytic atropine on cerebrovascular response during acute orthostatic hypotension in humans. Methods: Continuous middle cerebral blood flow velocity (CBFV, transcranial Doppler) and arterial blood pressure (ABP, Finometer) were measured during a sit-to-stand procedure in 10 healthy subjects with placebo and vagolytic (10 µg/kg) doses of atropine. Cerebral vascular tone was assessed by cerebrovascular resistance (CVR = ABP / CBFV). Dynamic cerebral autoregulation was also assessed by transfer function analysis of ABP and CBFV. Results: During the standing session, ABP fell to a similar extent in both groups by an average of 23 to 25 mmHg (26% to 29%). CBFV also fell in all subjects but significantly more in vagolytic atropine (-15.0 ± 7.0 cm/s) compared with placebo (-12.0 ± 5.8 cm/s, P < 0.05). CVR was decreased significantly in the placebo group during posture change (1.56 ± 0.44 vs. 1.38 ± 0.38, P < 0.05), in contrast, lesser decreased in the atropine group (1.60 ± 0.50 vs. 1.53 ± 0.42, P = 0.193). Transfer function coherence in the very-low-frequency range was significantly increased in the atropine group during the standing session (0.55 ± 0.14), compared with the sitting session (0.45 ± 0.14, P = 0.006). Conclusions: These data present that vagolytic atropine attenuates cerebral vasodilation response to acute orthostatic hypotension, suggesting the use of atropine may need care in patients with cerebrovascular disease with vagal impairment. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension (OH), a proxy for sympathetic adrenergic failure, is the most incapacitating sign of autonomic failure. Orthostatic dizziness (OD) is known to be the most common symptom of OH. However, recent studies have demonstrated that 30-39 % of patients with OH experienced rotatory vertigo during upright posture (i.e., orthostatic vertigo, OV), which challenges the dogma that OH induces dizziness and not vertigo. A recent population-based study on spontaneously occurring OD across a wide age range showed that the one-year and lifetime prevalence of OD was 10.9 and 12.5 %, respectively. Approximately 83 % of patients with OD had at least one abnormal autonomic function test result. So far, 11 subtypes of OD have been proposed according to the pattern of autonomic dysfunction, and generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions was the most common type. Four different patterns of OH, such as classic, delayed, early, and transient type have been found in patients with OD. The head-up tilt test and Valsalva maneuver should be performed for a comprehensive evaluation of sympathetic adrenergic failure in patients with OD/OV. This review summarizes current advances in OH presenting OD/OV, with a particular focus on the autonomic dysfunction associated with OD. [ABSTRACT FROM AUTHOR]

Background: Although a diversity of neurotransmitters and hormones participate in controlling blood pressure, norepinephrine released from postganglionic sympathetic nerve terminals is an important mediator of the rapid regulation of cardiovascular function required for homeostasis of cerebral perfusion. Hence, neurogenic orthostatic hypotension (NOH) often represents a deficiency of noradrenergic responsiveness to postural change.Research Design and Methods: PubMed searches with 'orthostatic hypotension' and 'norepinephrine' as conjoint search terms and no restriction on language or date, so as to survey the pathophysiologic and clinical relevance of norepinephrine deficiency for current NOH interventions and for future directions in treatment and research.Results: Norepinephrine deficiency in NOH can arise peripherally, due to cardiovascular sympathetic denervation (as in pure autonomic failure, Parkinson's disease, and a variety of neuropathies), or centrally, due to a failure of viscerosensory signals to generate adequate sympathetic traffic to intact sympathetic nerve endings (as in multiple system atrophy). Nonpharmacologic countermeasures such as pre-emptive water intake may yield blood-pressure increases exceeding those achieved pharmacologically. For patients with symptomatic NOH unresponsive to such strategies, a variety of pharmacologic interventions have been administered off-label on the basis of drug mechanisms expected to increase blood pressure via blood-volume expansion or vasoconstriction. Two pressor agents have received FDA approval: the sympathomimetic midodrine and more recently the norepinephrine prodrug droxidopa.Conclusions: Pressor agents are important for treating symptomatic NOH in patients unresponsive to lifestyle changes alone. However, the dysautonomia underlying NOH often permits blood-pressure excursions toward both hypotension and hypertension. Future research should aim to shed light on the resulting management issues, and should also explore the possibility of pharmacotherapy selectively targeting orthostatic blood-pressure decreases. [ABSTRACT FROM AUTHOR]

In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient’s risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension – for which the long-term prognosis in patients with NOH is yet to be established – must sometimes be balanced by the need to address a patient’s immediate risks. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension (OH) leads to a significant number of hospitalizations each year, and is associated with significant morbidity and mortality among affected individuals. Given the increased risk for cardiovascular events and falls, it is important to identify the underlying etiology of OH and to choose appropriate therapeutic agents. OH can be non-neurogenic or neurogenic (arising from a central or peripheral lesion). The initial evaluation includes orthostatic vital signs, complete history and a physical examination. Patients should also be evaluated for concomitant symptoms of post-prandial hypotension and supine hypertension. Non-pharmacologic interventions are the first step for treatment of OH. The appropriate selection of medications can also help with symptomatic relief. This review highlights the pathophysiology, clinical features, diagnostic work-up and treatment of patients with neurogenic OH. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to research on deep brain stimulation and its possible benefits in treating those with Parkinson's Disease.

Nonmotor manifestations in Parkinson's disease (PD) encompass a range of clinical features, including neuropsychiatric problems, autonomic dysfunction, sleep disorders, fatigue, and pain. Despite their importance for patients' quality of life, the evidence base for their treatment is relatively sparse. Nevertheless, the last few years have seen a number of new trials starting that specifically address nonmotor features as an outcome measure in clinical trials. Large randomized, controlled trials in the last 3 years reported improvement of psychosis with the new selective serotonin 5-HT2A inverse agonist pimavanserin and of postural hypotension with the oral norepinephrine precursor droxidopa. Smaller new randomized, controlled trials support the effectiveness of Deep Brain Stimulation and opiates for pain, of rivastigmine for apathy and piribedil for apathy post-DBS, group cognitive behavioral therapy for depression and/or anxiety, continuous positive airway pressure for sleep apnea in PD and doxepin for insomnia, and of solifenacin succinate and transcutaneous tibial nerve stimulation for urinary symptoms. A number of new smaller or open trials as well as post-hoc analyses of randomized, controlled trials have suggested usefulness of other treatments, and new randomized, controlled trials are currently ongoing. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension (OH) is a common cardiovascular disorder, with or without signs of underlying neurodegenerative disease. OH is diagnosed on the basis of an orthostatic challenge and implies a persistent systolic/diastolic blood pressure decrease of at least 20/10 mm Hg upon standing. Its prevalence is age dependent, ranging from 5% in patients <50 years of age to 30% in those >70 years of age. OH may complicate treatment of hypertension, heart failure, and coronary heart disease; cause disabling symptoms, faints, and traumatic injuries; and substantially reduce quality of life. Despite being largely asymptomatic or with minimal symptoms, the presence of OH independently increases mortality and the incidence of myocardial infarction, stroke, heart failure, and atrial fibrillation. In this review, we outline the etiology and prevalence of OH in the general population, summarize its relationship with morbidity and mortality, propose a diagnostic and therapeutic algorithm, and delineate current challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Background and purpose Most patients with multiple system atrophy (MSA) develop autonomic dysfunction; however, orthostatic hypotension is not always present. Failure of the vasoconstrictor response is thought to be responsible for orthostatic hypotension, but the degree of impairment of this response in patients with MSA is unclear. We assessed autonomic function in patients with MSA by evaluating the vasoconstrictive response during a head-up tilt test and determining its relationship to orthostatic hypotension. As an additional examination, the efficacy of norepinephrine in treating orthostatic hypotension was also assessed. Methods The study included 82 patients with MSA and 28 controls. Measures of total peripheral resistance were obtained during a head-up tilt test. Norepinephrine was administered to the patients lacking a vasoconstrictive response to evaluate its ability to treat orthostatic hypotension. Results At a 60° tilt, orthostatic hypotension occurred in 47.6% of the patients and 0% of controls. Reduction in total peripheral resistance from baseline at a 60° tilt was observed in 69.5% of the patients and 0% of controls. In patients with MSA, changes in systolic blood pressure from the baseline at a 60° tilt correlated positively with changes in the total peripheral resistance (r = 0.69, p < 0.0001). Norepinephrine prevented the reduction of total peripheral resistance and development of orthostatic hypotension. Conclusions A large number of patients with MSA with and without orthostatic hypotension have an impaired peripheral vasoconstrictive response, suggesting a high frequency of cardiovascular dysautonomia with an associated risk of developing orthostatic hypotension. A norepinephrine infusion was effective for treating orthostatic hypotension. [ABSTRACT FROM AUTHOR]

Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure (BP) on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy (MSA), pure autonomic failure (PAF), and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise BP by acting at the neurovascular junction to increase vascular tone. This article summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. [ABSTRACT FROM AUTHOR]

Patients with neurogenic orthostatic hypotension (OH) typically have impaired sympathetic nervous system tone and therefore low levels of upright plasma norepinephrine (NE) (noradrenaline). We report a subset of patients who clinically have typical neurogenic OH but who paradoxically have elevated upright levels of plasma NE. We retrospectively studied 83 OH patients evaluated at the Vanderbilt Autonomic Dysfunction Center between August 2007 and May 2013. Based on standing NE, patients were dichotomized into a hyperadrenergic OH group [hyperOH: upright NE ≥ 3.55 nmol/l (600 pg/ml), n=19] or a non-hyperadrenergic OH group [nOH: upright NE < 3.55 nmol/l (600 pg/ml), n=64]. Medical history and data from autonomic testing, including the Valsalva manoeuvre (VM), were analysed. HyperOH patients had profound orthostatic falls in blood pressure (BP), but less severe than in nOH [change in SBP (systolic blood pressure): -53± 31 mmHg compared with -68± 33 mmHg, P=0.050; change in DBP (diastolic blood pressure): -18± 23 mmHg compared with -30±17 mmHg, P=0.01]. The expected compensatory increase in standing heart rate (HR) was similarly blunted in both hyperOH and nOH groups [84± 15 beats per minute (bpm) compared with 82± 14 bpm; P=0.6]. HyperOH patients had less severe sympathetic failure as evidenced by smaller falls in DBP during phase 2 of VM and a shorter VM phase 4 BP recovery time (16.5± 8.9 s compared with 31.6± 16.6 s; P<0.001) than nOH patients. Neurogenic hyperOH patients have severe neurogenic OH, but have less severe adrenergic dysfunction than nOH patients. Further work is required to understand whether hyperOH patients will progress to nOH or whether this represents a different disorder. [ABSTRACT FROM AUTHOR]

Study design:Prospective study of two cases.Objectives:To describe the effects of electrical stimulation (ES) therapy in the 4-week management of two sub-acute spinal cord-injured (SCI) individuals (C7 American Spinal Injury Association Impairment Scale (AIS) B and T9 AIS (B)).Setting:University Malaya Medical Centre, Kuala Lumpur, Malaysia.Methods:A diagnostic tilt-table test was conducted to confirm the presence of orthostatic hypotension (OH) based on the current clinical definitions. Following initial assessment, subjects underwent 4 weeks of ES therapy 4 times weekly for 1 h per day. Post-tests tilt table challenge, both with and without ES on their rectus abdominis, quadriceps, hamstrings and gastrocnemius muscles, was conducted at the end of the study (week 5). Subjects' blood pressures (BP) and heart rates (HR) were recorded every minute during pre-test and post-tests. Orthostatic symptoms, as well as the maximum tolerance time that the subjects could withstand head up tilt at 60°, were recorded.Results:Subject A improved his orthostatic symptoms, but did not recover from clinically defined OH based on the 20-min duration requirement. With concurrent ES therapy, 60° head up tilt BP was 89/62 mm Hg compared with baseline BP of 115/71 mm Hg. Subject B fully recovered from OH demonstrated by BP of 105/71 mm Hg during the 60° head up tilt compared with baseline BP of 124/77 mm Hg. Both patients demonstrated longer tolerance time during head up tilt with concomitant ES (subject A: pre-test 4 min, post-test without ES 6 min, post-test with ES 12 min; subject B: pre-test 4 min, post-test without ES 28 min, post-test with ES 60 min).Conclusions:Weekly ES therapy had positive effect on OH management in sub-acute SCI individuals. [ABSTRACT FROM AUTHOR]

Orthostatic hypotension is common in Parkinson's disease. The current recommended management of orthostatic hypotension related to Parkinson's disease involves first general measures and then medications with little risk of severe adverse side effects. [ABSTRACT FROM AUTHOR]

The population is ageing, and there are now 11 million adults aged 65 years and over living in the UK (Office for National Statistics, 2013). Most older people live in their own homes, and less than half a million (405 000) live in care homes (LaingBuisson, 2014). Every year, around 30% of older adults living in the community fall at least once (Gillespie et al, 2012). This means that 3.18 million older people fall every year at home. This article uses a case history approach to illustrate how health professionals can identify and treat modifiable risk factors for falls and reduce the risk of harm when risks remain. [ABSTRACT FROM AUTHOR]