Initiation of droxidopa during hospital admission for management of refractory neurogenic orthostatic hypotension in severely ill patients.

Orthostatic hypotension (OH) is a common cause of hospitalization, particularly in the elderly. Hospitalized patients with OH are often severely ill, with complex medical comorbidities and high rates of disability. Droxidopa is a norepinephrine precursor approved for the treatment of neurogenic OH (nOH) associated with autonomic failure that is commonly used in the outpatient setting, but there are currently no data regarding the safety and efficacy of droxidopa initiation in medically complex patients. We performed a retrospective review of patients started on droxidopa for refractory nOH while hospitalized at Vanderbilt University Medical Center between October 2014 and May 2017. Primary outcome measures were safety, change in physician global impression of illness severity from admission to discharge, and persistence on medication after 180-day follow-up. A total of 20 patients were identified through chart review. Patients were medically complex with high rates of cardiovascular comorbidities and a diverse array of underlying autonomic diagnoses. Rapid titration of droxidopa was safe and well tolerated in this cohort, with no cardiovascular events or new onset arrhythmias. Supine hypertension requiring treatment occurred in four patients. One death occurred during hospital admission due to organ failure associated with end-stage amyloidosis. Treating physicians noted improvements in presyncopal symptoms in 80% of patients. After 6 months, 13 patients (65%) continued on droxidopa therapy. In a retrospective cohort of hospitalized, severely ill patients with refractory nOH, supervised rapid titration of droxidopa was safe and effective. Treatment persistence was high, suggesting that symptomatic benefit extended beyond acute intervention.

Association between Common Genetic Variants of α2A-, α2B-, and α2C-Adrenergic Receptors and Orthostatic Hypotension.

BACKGROUND: The genetic background associated with the dysregulation of orthostatic blood pressure remains poorly understood. The sympathetic nervous system plays a pivotal role in the regulation of blood pressure, as well as in response to positional changes. The essential role of adrenergic receptors in the sympathetic nervous system prompted us to hypothesize that common genetic variants of the α2-adrenergic receptor might contribute to the dysregulation of orthostatic blood pressure in general populations. This study is to explore the association between the polymorphisms of the α2-adrenergic receptor genes and the occurrence of orthostatic hypotension in Chinese populations. METHODS: The polymorphisms ADRA2A C-1291G (rs1800544), ADRA2B 301-303 I/D (rs28365031), and ADRA2C 322-325 I/D (rs61767072) were genotyped in 317 patients with orthostatic hypotension and 664 age- and gender-matched controls. Logistic regression analyses, adjusted for multiple comparisons, were used to determine the association between the allele/genotype of each ADRA2 gene and the risk of orthostatic hypotension. RESULTS: No significant association was found between the ADRA2A C-1291G, ADRA2B 301-303 I/D, and ADRA2C 322-325 I/D polymorphisms and orthostatic hypotension. CONCLUSIONS: We concluded that the common polymorphisms in the alpha2-adrenergic receptor gene is not associated with orthostatic hypotension risk in Chinese.

Orthostatic change in blood pressure and incidence of atrial fibrillation: results from a bi-ethnic population based study.

BACKGROUND: Autonomic fluctuations are associated with the initiation and possibly maintenance of atrial fibrillation (AF). However, little is known about the relationship between orthostatic blood pressure change, a common manifestation of autonomic dysfunction, and incident AF. METHODS: We examined whether supine-to-standing changes in systolic blood pressure (SBP) are associated with incident AF in 12,071 African American and white men and women aged 45-64 years, enrolled in the Atherosclerosis Risks in Communities (ARIC) study. Orthostatic hypotension (OH) was defined as a supine-standing drop in SBP by ≥20 mmHg or diastolic blood pressure by ≥10 mmHg. AF cases were identified based on study scheduled 12-lead ECG, hospital discharge ICD codes, and death certificates through 2009. RESULTS: OH was seen in 603 (5%) at baseline. During an average follow-up of 18.1 years, 1438 (11.9%) study participants developed AF. Incident AF occurred more commonly among those with OH than those without, a rate of 9.3 vs. 6.3 per 1000 person years, (p<0.001). The age, gender, and race adjusted hazard ratio (95%CI) of AF among those with OH compared to those without was 1.62 (1.34, 2.14). This association was attenuated after adjustment for common AF risk factors to HR 1.40 (1.15, 1.71), a strength similar to that of diabetes or hypertension with AF in the same model. A non-linear relationship between orthostatic change in SBP and incident AF was present after multivariable adjustment. CONCLUSIONS: OH is associated with higher AF incidence. Whether interventions that decrease OH can reduce AF risk remains unknown.

Mechanisms of efficacy of CBT for Cambodian refugees with PTSD: improvement in emotion regulation and orthostatic blood pressure response.

Based on the results of a randomized controlled trial, we examined a model of the mechanisms of efficacy of culturally adapted cognitive-behavior therapy (CBT) for Cambodian refugees with pharmacology-resistant posttraumatic stress disorder (PTSD) and comordid orthostatic panic attacks (PAs). Twelve patients were in the initial treatment condition, 12 in the delayed treatment condition. The patients randomized to CBT had much greater improvement than patients in the waitlist condition on all psychometric measures and on one physiological measure-the systolic blood pressure response to orthostasis (d = 1.31)-as evaluated by repeated-measures MANOVA and planned contrasts. After receiving CBT, the Delayed Treatment Group improved on all measures, including the systolic blood pressure response to orthostasis. The CBT treatment's reduction of PTSD severity was significantly mediated by improvement in orthostatic panic and emotion regulation ability. The current study supports our model of the generation of PTSD in the Cambodian population, and suggests a key role of decreased vagal tone in the generation of orthostatic panic and PTSD in this population. It also suggests that vagal tone is involved in emotion regulation, and that both vagal tone and emotion regulation improve across treatment.

Orthostatic hypotension, hypotension and cognitive status: early comorbid markers of primary dementia?

OBJECTIVE: Few studies have explored the relationship between orthostatic hypotension (OH) and cognition. The aim of this study was to examine the association of OH with cognitive impairment and decline in a cohort of Chinese elderly, and its effect modification by blood pressure (BP) status at baseline. METHOD: Among 2,321 community-living older adults, free of cardiovascular disease and stroke, baseline BP measurements were used to determine the presence of OH and categorize participants as hypotensives, normotensives or hypertensives. The Mini-Mental State Examination (MMSE) was used to assess cognitive impairment (MMSE score <24). Cognitive decline (decrease in MMSE score by > or =1) was assessed from 1 to 2 years of follow-up for 1,347 participants without baseline cognitive impairment. RESULTS: Mean age of the subjects was 65.5 years and 381 (16.6%) showed OH. OH was not associated with cognitive impairment overall. However, among hypotensives, OH increased the odds of cognitive impairment (OR = 4.1, 95% CI = 1.11-15.1), while hypertensives with OH showed reduced odds of cognitive impairment (OR = 0.48, 95% CI = 0.26-0.90). Among cognitively intact participants, OH was not associated with cognitive decline overall or in BP subgroups. CONCLUSION: The increased risk of cognitive impairment in hypotensives with OH suggests that hypotension with OH may be an early comorbid marker of a primary incipient dementia.

Orthostatic panic attacks among Vietnamese refugees.

Viewed historically and cross-culturally, orthostatic-induced dizziness, i.e., dizziness caused by standing up from a sitting or a lying position, forms a key aspect of many syndromes: irritable heart (American Civil War), effort syndrome (World War I and World War II), chronic fatigue syndrome (contemporary USA), Gulf War syndrome (contemporary USA), and orthostatic dysregulation (contemporary Japan). Among Vietnamese refugees attending a psychiatric clinic, this study documents a high rate of orthostatic panic (OP), as well as certain processes seemingly generating these panic attacks, viz., flashbacks and culturally specific catastrophic cognitions. Case examples are used to demonstrate OP's phenomenology and relevance to clinical care. To illustrate the mechanisms producing OP, we adduce the multiplex model of panic generation. Culturally appropriate care of Vietnamese refugees should include assessment and treatment of OP.

Blacks and whites differ in responses, but not tolerance, to orthostatic stress.

This study tested the hypothesis that normotensive black males differ from white males in their autonomic and cardiovascular responses to severe orthostatic stress. College age men (9 blacks, 9 whites) underwent graded lower body negative pressure (LBNP; 10 mmHg steps of 6 min each) to either -100 mmHg or presyncope. LBNP tolerance between the two groups did not differ (LBNP tolerance index: 378 +/- 34 vs 404 +/- 1 9mmHg.min, blacks vs whites). Responses to LBNP common to all subjects (< or = -40 mmHg), including spontaneous baroreflex sensitivity (sequence technique), did not differ between groups except whites experienced an earlier and more pronounced decline in total peripheral conductance than blacks (P < 0.01). At test termination, the heart rate variability measure of low frequency/high frequency ratio increased more in blacks than whites (5.2 +/- 1.1 vs 2.7 +/- 0.7 units; P < 0.05) while cardiac output and total peripheral conductance were lower in whites (both P < 0.05). These data suggest that blacks and whites have similar LBNP tolerances. They maintain blood pressure equally well when exposed to graded LBNP to presyncope, yet they differ in their mechanisms for doing so.

Correlates of postural hypotension in a community sample of elderly blacks and whites.

Postural hypotension is thought to be prevalent among the elderly, but few community-based studies of this condition have been conducted. In addition, little is known about postural hypotension in blacks despite well documented racial differences in hypertension and stroke. Data on 659 elderly (greater than or equal to 60 years of age) participants in a survey of two rural, biracial townships were analyzed to describe the frequency and correlates of postural hypotension. Twelve percent of the 659 adults experienced a drop of 10 mmHg or greater in systolic blood pressure on going from sitting to standing (supine measures were not available). This degree of postural hypotension was twice as common for whites as for blacks (14.5% vs 7.5%, P = 0.01). Postural hypotension was associated with elevated sitting blood pressure and showed positive but statistically non-significant relationships with anti-hypertensive medications and leanness. The association between race and postural hypotension persisted after adjusting for these and other risk factors (OR = 2.2, 95% CI:1.2,4.0).