Orthostatic hypotension (OH) is common among older people and is more prevalent in elderly with various disorders and on medications.
The objective of the study was to know the prevalence of orthostatic hypotension in healthy geriatric subjects.
Subjects and Methods:
The study group comprised of healthy non hypertensive, non diabetic elderly individuals aged 60 years and above (n=80) and another group, healthy aged 30 to 50 years age (n=80, mean age39.2±5.3). Orthostatic hypotension was defined as a decline in systolic/diastolic blood pressure of ≥20/10 mmHg when an individual changed from a supine to a standing position within 3 minutes of standing. Systolic and Diastolic blood pressure was measured in supine position and within 3 minutes of standing.
1 out of 80 (1.25%) in the elderly subjects was found to have orthostatic hypotension.
The study concluded that the orthostatic hypotension is less prevalent in healthy elderly subjects without any illness or without on any medications.
Orthostatic Hypotension; healthy; geriatric; blood pressure; young adults; medications.
OBJECTIVE—The aim of this study was to investigate the relationship between pre-diabetes and orthostatic hypotension and to examine the prevalence and correlates of orthostatic hypotension in community dwellers with normal glucose tolerance (NGT), pre-diabetes, and diabetes.
RESEARCH DESIGN AND METHODS—All participants were classified as having NGT (n = 1,069), pre-diabetes (n = 412), or diabetes (n = 157). Orthostatic hypotension was defined as a decline in systolic/diastolic blood pressure of ≥20/10 mmHg when an individual changed from a supine to a standing position. The cardiovagal response to standing was the ratio between the longest RR interval around beat 30 and the shortest RR interval around beat 15 after standing (30 max–to–15 min ratio).
RESULTS—The prevalences of orthostatic hypotension were 13.8, 17.7, and 25.5% in subjects with NGT, pre-diabetes, and diabetes, respectively. For all subjects, age, diabetes, hypertension, and a decreased 30 max–to–15 min ratio, but not pre-diabetes, were independently associated with orthostatic hypotension. Age, hypertension, and 30 max–to–15 min ratio were the correlates of orthostatic hypotension in NGT subjects. Age and hypertension were related to orthostatic hypotension in pre-diabetic subjects. A1C and hypertension were the determinants of orthostatic hypotension in diabetic subjects. Supine blood pressure was related to orthostatic hypotension in all subjects and subgroups.
CONCLUSIONS—Pre-diabetic subjects do not have a higher risk of orthostatic hypotension than subjects with NGT, although the risk of orthostatic hypotension is higher in diabetic subjects. Hypertension and supine blood pressure were risk factors for orthostatic hypotension in both pre-diabetic and diabetic subjects. Age and A1C were the correlates of orthostatic hypotension in pre-diabetic and diabetic subjects, respectively. The cardiovagal response to standing is an important determinant of orthostatic hypotension in subjects with NGT but not in pre-diabetic and diabetic subjects.
To describe the frequency of orthostatic hypotension and hypertension and associations with risk factors in a cohort of persons with long term type 1 diabetes (n=440) participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR).
Evaluations included detailed medical history, electrocardiography (ECG), and laboratory tests. Blood pressure (BP) was measured in supine and standing positions. Standing decrease in systolic (SBP) or diastolic (DBP) BP of at least 20 mmHg or 10 mmHg, respectively, was defined as orthostatic hypotension; increase of SBP from <140 to ≥ 140mmHg or DBP from < 90 to ≥ 90mmHg was defined as orthostatic hypertension.
Prevalence of orthostatic hypotension and orthostatic hypertension was 16.1% and 15.2%, respectively. Some ECG measurements of cardiac autonomic dysfunction were significantly associated with orthostatic hypotension. Association between SBP and orthostatic hypotension and orthostatic hypertension were significant (Odds Ratio (95% CI), 1.02 (1.01–1.05) and 1.02 (1.01–1.04), respectively) after adjusting for confounders. Interaction between SBP and age was observed. SBP was significantly associated with orthostatic hypotension and orthostatic hypertension in people ≤ 40 years old (1.35 (1.02–1.78) and 1.12 (1.05–1.18), respectively).
Results showed that measurements derived from the ECG can help describe an individual at increased risk of having postural BP changes. Moreover, SBP was associated with postural BP changes among individuals who were < 40 years of age with long-term type 1 diabetes.
diabetes complications; hypertension; hypotension; prevalence; risk
Venlafaxine is not usually associated with risk of orthostatic hypotension. A 65-year-old US Caucasian female taking 225 mg/day of venlafaxine extended-release developed symptomatic orthostatic hypotension. The systolic and diastolic blood pressure dropped by 25 and 18 mm Hg, respectively, from supine position to standing position within 3 minutes. The patient was otherwise healthy and the orthostatic hypotension resolved with venlafaxine discontinuation. This was a probable venlafaxine adverse drug reaction according to the Naranjo scale. This case contributes to the scarce literature that indicates that clinicians need to be aware that occasionally venlafaxine can induce clinically significant orthostatic hypotension, particularly in geriatric patients. Our patient did not have orthostatic hypotension when she was taking venlafaxine at 60 years of age in higher venlafaxine doses (300 mg/day) but developed this adverse drug reaction when venlafaxine was restarted at the geriatric age. This case indicates that a history of prior tolerance to venlafaxine does not guarantee tolerance after 65 years of age. If a clinician decides to use venlafaxine in geriatric patients, the clinician should warn the patient about the risk of orthostatic hypotension and consider very slow titration and low doses.
Although orthostatic hypotension (OH) is more prevalent in old age, and in patients with diabetes, the prevalence of OH in older patients with type 2 diabetes mellitus is unknown.
To establish the prevalence of OH, and its association with falling, in home-dwelling older participants with and without type 2 diabetes.
Design and setting
A cross-sectional study in primary care in the Netherlands.
A total of 352 patients with type 2 diabetes, and 211 without participated in this study. OH was defined as a fall in blood pressure of at least 20 mmHg systolic or 10 mmHg diastolic after either 1 or 3 minutes in an upright position. Feelings of dizziness, light-headedness, or faintness during the standing period were documented as orthostatic complaints. Fall risk was assessed with a validated risk profile instrument.
The prevalence of OH was 28% (95% CI = 24% to 33%) and 18% (95% CI = 13% to 23%) in participants with and without type 2 diabetes, respectively. OH was not related to falling, while the presence of orthostatic complaints in itself was associated with both previous fall incidents as well as a high fall risk, even after adjustment for OH. The adjusted odds ratios were 1.65 (95% CI = 1.00 to 2.72) and 8.21 (95% CI = 4.17 to 16.19), respectively.
OH is highly prevalent in home-dwelling older people with and without type 2 diabetes. Those with orthostatic complaints had an increased risk for falling, whereas those with OH were not.
aged; diabetes mellitus type 2; falling; orthostatic hypotension; primary care
In a hypertensive patient with orthostatic hypotension, the changes in several haemodynamic indices with respect to posture were evaluated. In the upright position, systemic blood pressure was reduced as compared with the supine position, and peripheral vasodilation was present, as shown by an increase in Jantsch's index of the impedance plethysmographic tracings. Systolic time intervals remained unchanged with changes in posture. Propranolol 10 mg intravenously brought the response to normal. In fact, after beta-blockade in the standing position the blood pressure remained unchanged and normal peripheral vasoconstriction was observed. Similar results were seen during atrial pacing at a constant heart rate of 130 beats/minute. In this patient, propranolol appears to normalise the response to the posture change, by restoring normal vasoconstriction in the upright position.
To investigate the relationships between uncontrolled and controlled hypertension, orthostatic hypotension (OH), and falls in participants of the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study (N = 722, mean age 78.1).
Prospective population-based study.
Seven hundred twenty-two adults aged 70 and older living within a 5-mile radius of the study headquarters at Hebrew Rehabilitation Center in Boston.
Blood pressure (BP) was measured at baseline in the supine position and after 1 and 3 minutes of standing. Systolic OH (SOH) and diastolic OH at 1 and 3 minutes were defined as a 20-mmHg decline in systolic BP and a 10-mmHg decline in diastolic BP upon standing. Hypertension was defined as BP of 140/90 mmHg or greater or receiving antihypertensive medications (controlled if BP < 140/90 mmHg and uncontrolled if ≥140/90 mmHg). Falls data were prospectively collected using monthly calendars. Fallers were defined as those with at least two falls within 1 year of follow-up.
OH was highest in participants with uncontrolled hypertension; SOH at 1 minute was 19% in participants with uncontrolled hypertension, 5% in those with controlled hypertension, and 2% in those without hypertension (P≤.001)). Participants with SOH at 1 minute and uncontrolled hypertension were at greater risk of falls (hazard ratio = 2.5, 95% confidence interval = 1.3–5.0) than those with uncontrolled hypertension without OH. OH by itself was not associated with falls.
Older adults with uncontrolled hypertension and SOH at 1 minute are at greater risk for falling within 1 year. Hypertension control, with or without OH, is not associated with greater risk of falls in older community-dwelling adults.
hypertension; orthostatic hypotension; falls; elderly
Orthostatic hypotension (OH) is prevalent in hospitalized elderly patients. It is defined as a reduction in systolic blood pressure (SBP) of at least 20 mmHg and/or diastolic blood pressure (DBP) of at least 10 mmHg within 3 minutes of standing from a lying position. This observational cohort study describes the prevalence, association with symptoms, and risk factors for OH in medical, surgical, and trauma wards in a tertiary hospital and the differences in hemodynamic behaviors between OH-positive (OHP) and OH-negative (OHN) patients.
All 76 patients who were hemodynamically stable and able to stand from 4 hospital wards had noninvasive supine and orthostatic blood pressures (BPs) and pulse rates (PRs) measured over 4 days.
Mean age of the 76 patients included in the study was 67.8 ± 19.6 years. Overall prevalence of OH was 23.7% (95% CI: 14.7%-34.8%) with 21.2% (95% CI: 9.0%-38.9%) in medical, 31.8% (95% CI: 13.9%-54.9%) in surgical, and 19.0% (95% CI: 5.4%-41.9%) in trauma wards. OH had no association with symptoms (P = .53). We found no differences in age, number of comorbidities, and medication use between the OHN and OHP groups.
The two groups displayed very different hemodynamic responses. The OHN group demonstrated a statistically significant compensatory rise in BP and PR over time to orthostatic challenge, while the OHP group displayed the opposite effect with BP. There was no statistically significant compensatory increase in PR over time to standing in the OHP group.
OH is common and mostly asymptomatic. Routine measurements are recommended to detect cases in the hospital setting. Our study did not identify any significant risk factors for OH but rather confirmed the previous finding that underlying impairment in autonomic responses in individuals may have instead contributed to the development of OH.
Hemodynamic responses; orthostatic hypotension; prevalence; risk factors
Background: Pharmacological treatment of orthostatic hypotension is often limited because of troublesome supine hypertension.
Objective: To investigate a novel approach to treatment using acetylcholinesterase inhibition, based on the theory that enhanced sympathetic ganglion transmission increases systemic resistance in proportion to orthostatic needs.
Design: Prospective open label single dose trial.
Material: 15 patients with neurogenic orthostatic hypotension caused by: multiple system atrophy (n = 7), Parkinson's disease (n = 3), diabetic neuropathy (n = 1), amyloid neuropathy (n = 1), and idiopathic autonomic neuropathy (n = 3).
Methods: Heart rate, blood pressure, peripheral resistance index (PRI), cardiac index, stroke index, and end diastolic index were monitored continuously during supine rest and head up tilt before and one hour after an oral dose of 60 mg pyridostigmine.
Results: There was only a modest non-significant increase in supine blood pressure and PRI. In contrast, acetylcholinesterase inhibition significantly increased orthostatic blood pressure and PRI and reduced the fall in blood pressure during head up tilt. Orthostatic heart rate was reduced after the treatment. The improvement in orthostatic blood pressure was associated with a significant improvement in orthostatic symptoms.
Conclusions: Acetylcholinesterase inhibition appears effective in the treatment of neurogenic orthostatic hypotension. Orthostatic symptoms and orthostatic blood pressure are improved, with only modest effects in the supine position. This novel approach may form an alternative or supplemental tool in the treatment of orthostatic hypotension, specially for patients with a high supine blood pressure.
Hemodynamic variables (blood pressure, cardiac output, heart rate, plasma volume, splanchnic blood flow, and peripheral subcutaneous blood flow) and plasma concentrations of norepinephrine, epinephrine, and renin were measured in the supine position and after 30 min of quiet standing. This was done in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously in the standing position in the diabetics with orthostatic hypotension, whereas moderate decreases were found in the other three groups. Upon standing, heart rate rose and cardiac output and plasma volume decreased similarly in the four groups. The increases in total peripheral resistance, splanchnic vascular resistance and subcutaneous vascular resistance were all significantly lower (P less than 0.025) in the patients with orthostatic hypotension compared with the other three groups. The increase in plasma norepinephrine concentrations in the patients with orthostatic hypotension was significantly lower (P less than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy.
The effect of withdrawing or continuing anti-hypertensive therapy on orthostatic blood pressure change in elderly hypertensive subjects was examined. Subjects meeting criteria for therapy withdrawal had supine and standing blood pressure measurements taken on treatment, and at 1, 3, 6, 9 and 12 months off treatment whilst receiving standard non-pharmacological advice to lower blood pressure. Subjects not meeting blood pressure criteria for treatment withdrawal or were unwilling to stop treatment had blood pressure measurements taken after 6 and 12 months whilst also receiving non-pharmacological advice. Orthostatic hypotension was defined as a mean systolic blood pressure fall > or = 20 mmHg on standing from a supine position. Forty-seven subjects (median age 76 years, range 65-84 years) had treatment withdrawn. Thirteen subjects (median age 73 years, range 68-82 years) continued on their treatment. Twelve months after treatment withdrawal there was a significant reduction in the number demonstrating orthostatic hypotension from 11 (23%) to four (11%) (P < 0.05), whilst the group continuing on treatment showed no change. In the withdrawal group those with orthostatic hypotension on treatment (n = 11) were older (79 versus 74 years, P = 0.05), had higher prewithdrawal systolic blood pressure (164 +/- 21 versus 147 +/- 17 mmHg, P = 0.02) compared to those without, although there was no difference in body mass index, gender, number or type of anti-hypertensive drugs taken. In elderly hypertensive subjects withdrawal of anti-hypertensive therapy and institution of non-pharmacological treatment can over several months reduce the prevalence of orthostatic hypotension.
Heart failure causes significant morbidity and mortality. Distinguishing risk factors for incident heart failure can help identify at-risk individuals. Orthostatic hypotension may be a risk factor for incident heart failure; however, this association has not been fully explored, especially in non-white populations.
The Atherosclerosis Risk in Communities study included 12,363 adults free of prevalent heart failure with baseline orthostatic measurements. Orthostatic hypotension was defined as a decrease of systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg with position change from supine to standing. Incident heart failure was identified from hospitalization or death certificate disease codes.
Over 17.5 years of follow up, orthostatic hypotension was associated with incident heart failure with multivariable adjustment (hazard ratio 1.54, 95% CI 1.30-1.82). This association was similar across race and gender groups. A stronger association was identified in younger individuals ≤55 years old (hazard ratio 1.90, 95% CI 1.41-2.55) than in older individuals >55 years old (hazard ratio 1.37, 95% CI 1.12-1.69, interaction p=0.034).
The association between orthostatic hypotension and incident heart failure persisted with exclusion of those with diabetes mellitus, coronary heart disease, and those on anti-hypertensives, psychiatric or Parkinson’s medications. However, exclusion of those with hypertension somewhat attenuated the association (hazard ratio 1.34, 95% CI 1.00-1.80).
We identified orthostatic hypotension as a predictor of incident heart failure among middle-aged individuals, particularly those 45-55 years of age. This association may be partially mediated through hypertension. Orthostatic measures may enhance risk stratification for future heart failure development.
Three bedridden patients with severe orthostatic hypotension due to chronic autonomic failure were treated with pindolol (15 mg/day), a beta-adrenoceptor antagonist with partial agonist activity. While taking this drug the patients were free of orthostatic symptoms: they could walk, and standing blood pressure was maintained above 90/50 mm Hg. Supine heart rate rose during treatment by 12-21 beats/minute, and stroke volume and cardiac output by 12-24 ml and 1.5-3.1 l/min respectively. Supine blood pressure rose by 21-68 mm Hg systolic and 14-49 mm Hg diastolic. Pindolol 15 mg/day was therapeutically effective in these three patients with severe orthostatic hypotension due to chronic autonomic failure. Further studies in a larger series of patients are needed to confirm this result.
Eight healthy people (seven men and one woman, aged 19 to 31 years) were studied by radionuclide cardiography when supine before and 30 minutes after a standard meal (6300 kJ). Control investigations were performed on a different day within a week of the standard meal. There was a median increase in cardiac output of 62% that was attributable to a 17% increase in heart rate and a 41% increase in stroke volume. Blood pressure and concentrations of plasma catecholamines did not change. The median end diastolic and end systolic volumes of the left ventricle increased by 41% so that the left ventricular ejection fraction was unchanged. There were no significant changes during the control experiments. In healthy people a meal caused an appreciable increase in stroke volume and dilatation of the left ventricle. The activity of the sympathetic nervous system, as measured by plasma catecholamines, did not change much, and changes in blood volume alone did not seem to explain the haemodynamic response to the meal.
AIM--To determine whether inappropriately secreted vasodilatory peptides have a role in the pathogenesis of orthostatic (postural) hypotension, a recognised paraneoplastic effect of bronchial malignancies usually attributed to immune mediated destruction of autonomic ganglia. METHODS--Serum concentrations of three vasodilatory peptides, atrial natriuretic peptide (ANP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP), were measured in 111 patients with bronchial carcinoma and 35 controls prospectively screened for orthostatic hypotension (> 20 mmHg drop in systolic blood pressure on repeated occasions on standing from the supine position) and in whom other causes of this condition were excluded. RESULTS--Twenty two (20%) patients with carcinoma and two (6%) controls had orthostatic hypotension according to the criteria used. Serum concentrations of ANP, VIP and CGRP were elevated above normal in, respectively, 25 (23%), 10 (9%) and eight (7%) patients with carcinoma and in six (18%), zero and three (9%) controls. There was no correlation between orthostatic hypotension and concentrations of any of the vasodilatory peptides. CONCLUSION--Elevated serum concentrations of ANP and CGRP were no more frequent in subjects with bronchial carcinoma than in controls and could not be attributed to the tumour, although there was a possible association for VIP. Orthostatic hypotension was more common in patients with carcinoma, but there was no evidence that the peptides measured played a role in its pathogenesis.
Patients with Postural Tachycardia Syndrome (POTS) have excessive orthostatic tachycardia (>30 bpm) when standing from a supine position. Heart rate (HR) and blood pressure (BP) are known to exhibit diurnal variability, but the role of diurnal variability in orthostatic changes of HR & BP is not known. In this study, we tested the hypothesis that there is diurnal variation of orthostatic HR & BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR & BP were obtained on the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning than the evening (102±3 bpm [AM] vs. 93±2 bpm [PM]; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 bpm [AM] vs. 100±3 bpm [PM]; P=0.012) and controls (89±3 bpm [AM] vs. 80±2 bpm [PM]; P=0.005), when analyzed separately. There was no diurnal variability in orthostatic BP in POTS. More subjects met the POTS HR criterion in the morning compared with the evening (P=0.008). There was significant diurnal variability in orthostatic tachycardia, with a great orthostatic tachycardia in the morning compared to the evening in both patients with POTS and healthy subjects. Given the importance of orthostatic tachycardia in diagnosing POTS, this diurnal variability should be considered in the clinic as it may affect the diagnosis of POTS.
orthostatic intolerance; diurnal variability; circadian; heart rate; blood pressure; tachycardia
Short-term elevations in ambient fine particulate matter (PM2.5) may increase resting systolic (SBP) and diastolic (DBP) blood pressure, but whether PM2.5 alters hemodynamic responses to orthostatic challenge has not been studied in detail. We repeatedly measured SBP and DBP during supine rest and 1 and 3 minutes after standing among 747 elderly (aged 78.3 ± 5.3 years, mean ± SD) participants from the MOBILIZE Boston Study. We used linear mixed models to assess the association between change in SBP (ΔSBP=standing SBP − supine SBP) and DBP (ΔDBP) upon standing and mean PM2.5 levels over the preceding 1 to 28 days, adjusting for meteorological covariates, temporal trends, and medical history. We observed a 1.4 (95% confidence interval (CI): 0.0, 2.8; p=0.046) mmHg higher ΔSBP and a 0.7 (95% CI: 0.0, 1.4; p=0.053) mmHg higher ΔDBP at 1 minute of standing per interquartile range increase (3.8 μg/m3) in mean PM2.5 levels in the past 7 days. ΔSBP and ΔDBP measured 3 minutes after standing were not associated with PM2.5. Resting DBP (but not SBP or pulse pressure) was positively associated with PM2.5 at longer averaging periods. Responses were more strongly associated with black carbon than sulfate levels. These associations did not differ significantly according to hypertension status, obesity, diabetes, or gender. These results suggest that ambient particles can increase resting DBP and exaggerate blood pressure responses to postural changes in elderly people. Increased vasoreactivity during posture change may be responsible, in part, for the adverse effect of ambient particles on cardiovascular health.
air pollution; environment; blood pressure; elderly; orthostatic; baroreflex; autonomic nervous system
syndrome (HVS) is a common disorder which is difficult to diagnose
because of somatic symptoms and its episodic nature. In previous
studies respiratory alkalosis in arterial blood was often found
during orthostatic tests in patients with HVS. The purpose of this
study was to assess these orthostatic changes by non-invasive pulmonary
gas exchange measurements and to evaluate whether these responses
discriminate patients with HVS from healthy subjects.
gases were collected with a face mask and pulmonary gas exchange was
measured after 10 minutes at rest and after eight minutes standing
upright in 16 patients with HVS and 13healthy control subjects. In
patients with HVS arterial blood samples were also drawn at rest and in
the standing position.
RESULTS—At rest the
variables of respiratory gas exchange did not differ significantly
between the groups. As a response to standing, minute ventilation
increased in both study groups but significantly more in the patients
with HVS (mean difference 5.4 l/min (95% CI 1.1 to 9.6)). The changes
in end tidal CO2 fraction (FETCO2) and in ventilatory equivalents for oxygen
(V̇E/V̇O2) and for
CO2 (V̇E/V̇CO2) during the
orthostatic test were also significantly larger in patients with HVS
than in healthy controls. During standing FETCO2 was significantly lower (mean difference
-1.1 kPa; 95% CI -1.5 to -0.6) and
V̇E/V̇O2 (mean difference
18.4; 95% CI 7.7to 29.0) and
difference 11.7; 95% CI 4.8 to 18.6) were significantly higher in HVS
patients than in healthy controls. By using the cut off level of 4%
for FETCO2 the sensitivity and specificity of
the test to discriminate HVS were 87% and 77%, respectively, and by
using the cut off level of 37 for
V̇E/V̇O2 they were 93%
and 100%, respectively. In the HVS patients arterial PCO2 and FETCO2 were
closely correlated during the orthostatic test
(r = 0.93, p<0.0001).
response to change in body position from supine to standing, patients
with HVS have an accentuated increase in ventilation which
distinguishes them from healthy subjects. These findings suggest that
non-invasive measurements of pulmonary gas exchange during orthostatic
tests are useful in the clinical evaluation of patients with
Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of antibody mediated impaired transmission across the autonomic ganglia resulting in severe autonomic failure. Some patients with AAG report cognitive impairment of unclear etiology despite treatment of autonomic symptoms.
To investigate the relationship between orthostatic hypotension, antibody titers and cognitive impairment in patients with AAG.
Academic medical center.
Three patients with AAG underwent neuropsychological testing before and after cycles of plasma exchange in both the seated and standing position to determine the effects of orthostatic hypotension and antibody titers on cognition.
Main Outcome Measures
Patient responses to neuropsychological tests were measured by percent change from baseline in the seated and standing positions pre- and post-plasma exchange to determine the effects of orthostatic hypotension and antibody titers on cognition.
Orthostatic hypotension and elevated antibody titer were associated independently with neuropsychological impairment (P<0.05), particularly in domains of executive function, sustained attention, and working memory. Cognitive dysfunction improved, even in the seated normotensive position, after plasmapheresis and consequent reduction in antibody levels.
The data presented in this study demonstrate reversible cognitive impairment is independently associated with both orthostatic hypotension and elevated nicotinic acetylcholine receptor autoantibodies thereby expanding the clinical spectrum of autonomic ganglionopathy and, in so doing, providing an additional treatable cause of cognitive impairment.
Autoimmune autonomic ganglionopathy; autonomic failure, orthostatic hypotension, cognitive impairment
AIM—To analyse the immediate response of heart rate variability (HRV) in response to orthostatic stress in unexplained syncope.
SUBJECTS—69 subjects, mean (SD) age 42 (18) years, undergoing 60° head up tilt to evaluate unexplained syncope.
METHODS—Based on 256 second ECG samples obtained during supine and upright phases, spectral analyses of low (LF) and high frequency (HF) bands were calculated, as well as the LF/HF power ratio, reflecting the sympathovagal balance. All variables were measured just before tilt during the last five minutes of the supine position, during the first five minutes of head up tilt, and just before the end of passive tilt.
RESULTS—Symptoms occurred in 42 subjects (vasovagal syncope in 37; psychogenic syncope in five). Resting haemodynamics and HRV indices were similar in subjects with and without syncope. Immediately after assuming the upright posture, adaptation to orthostatism differed between the two groups in that the LF/HF power ratio decreased by 11% from supine (from 2.7 (1.5) to 2.4 (1.2)) in the positive test group, while it increased by 11.5% (from 2.8 (1.5) to 3.1 (1.7)) in the negative test group (p = 0.02). This was because subjects with a positive test did not have the same increment in LF power with tilting as those with a negative test (11% v 28%, p = 0.04), while HF power did not alter. A decreased LF/HF power ratio persisted throughout head up tilt and was the only variable found to discriminate between subjects with positive and negative test results (p = 0.005, multivariate analysis). During the first five minutes of tilt, a decreased LF/HF power ratio occurred in 33 of 37 subjects in the positive group and three of 27 in the negative group. Thus a decreased LF/HF ratio had 89% sensitivity, 89% specificity, a 92% positive predictive value, and an 86% negative predictive value.
CONCLUSIONS—Through the LF/HF power ratio, spectral analysis of HRV was highly correlated with head up tilt results. Subjects developing syncope late during continued head up tilt have a decrease in LF/HF ratio immediately after assuming the upright posture, implying that although symptoms have not developed the vasovagal reaction may already have begun. This emphasises the major role of the autonomic nervous system in the genesis of vasovagal (neurally mediated) syncope.
Keywords: heart rate variability; vasovagal syncope; head up tilt test
Orthostatic hypotension is a chronic, debilitating illness that is difficult to treat. The therapeutic goal is to improve postural symptoms, standing time, and function rather than to achieve upright normotension, which can lead to supine hypertension. Drug therapy alone is never adequate. Because orthostatic stress varies with circumstances during the day, a patient-oriented approach that emphasizes education and nonpharmacologic strategies is critical. We provide easy-to-remember management recommendations, using a combination of drug and non-drug treatments that have proven efficacious.
Postural orthostatic tachycardia syndrome (POTS) is characterised by the development of excessive tachycardia on standing with maintained blood pressure. We report a case of POTS in a 20-year-old girl with type 1 diabetes who presented with a 3-week history of lethargy, fatigue and orthostatic intolerance. Examination revealed a postural rise in heart rate of over 50 bpm with maintained blood pressure. This was associated with symptoms of light-headedness. Cardiac structure and function as assessed by ECG and ECHO were normal as was thyroid and adrenal function. POTS was confirmed with tilt table testing. Treatment was initiated with increased fluid intake, fludrocortisone and bisoprolol with improvement. POTS is a disabling condition which can significantly limit a patient’s activities and working capacity and should be considered in a young, otherwise well patient who presents with orthostatic intolerance and a postural rise in heart rate.
Signs or symptoms of impaired autonomic regulation of the circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial noradrenergic innervation, detected by cardiac sympathetic neuroimaging. About 30–40% of PD patients have orthostatic hypotension (OH), defined as a persistent, consistent fall in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within three minutes of change in position from supine to standing. Neuroimaging evidence of cardiac sympathetic denervation is universal in PD with OH (PD+OH). In PD without OH about half the patients have diffuse left ventricular myocardial sympathetic denervation, a substantial minority have partial denervation confined to the inferolateral or apical walls, and a small number have normal innervation. Among patients with partial denervation the neuronal loss invariably progresses over time, and in those with normal innervation at least some loss eventually becomes evident. Thus, cardiac sympathetic denervation in PD occurs independently of the movement disorder. PD+OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. PD+OH patients have failure of both the parasympathetic and sympathetic components of the arterial baroreflex. OH in PD therefore seems to reflect a “triple whammy” of cardiac and extra-cardiac noradrenergic denervation and baroreflex failure. In contrast, most patients with multiple system atrophy, which can resemble PD+OH clinically, do not have evidence for cardiac or extra-cardiac noradrenergic denervation. Catecholamines in the neuronal cytoplasm are potentially toxic, via spontaneous and enzyme-catalyzed oxidation. Normally cytoplasmic catecholamines are efficiently taken up into vesicles via the vesicular monoamine transporter. The recent finding of decreased vesicular uptake in Lewy body diseases therefore suggests a pathogenetic mechanism for loss of catecholaminergic neurons in the periphery and brain.
The effect of a balanced liquid meal on supine and postural blood pressure (BP) responses was investigated in three groups of patients with chronic autonomic failure; 10 with associated neurological impairment (multiple system atrophy (MSA), Shy-Drager syndrome) and seven without (of which five had pure autonomic failure (PAF); and two had a deficiency of the enzyme dopamine beta hydroxylase, DBH-deficiency). All had marked postural hypotension. Subjects with normal autonomic function were also studied. In MSA and PAF food lowered supine BP substantially, with a more rapid and greater fall in PAF. After food, the levels of BP reached were considerably lower because of the reduced supine BP and many had to be returned to the horizontal position earlier than before. Ingestion of a similar volume of water alone had no effect in MSA or PAF. In DBH deficiency, food had variable but minimal effects on BP while supine and during head-up tilt. In subjects with normal autonomic function food did not affect BP. The BP responses to food thus varied in the three groups with chronic autonomic failure. The influence of food on both supine and postural BP therefore should be considered in the clinical and laboratory assessment of autonomic dysfunction and in relation to therapeutic approaches, designed to alleviate postural hypotension.
White matter hyperintensities (WMH) in magnetic resonance imaging (MRI) scans of the brain, and orthostatic hypotension (OH) are both common in older people. We tested the hypothesis that OH is associated with WMH.
Secondary care outpatient clinics in geriatric medicine and old age psychiatry in western Norway.
160 older patients with mild dementia, diagnosed according to standardised criteria.
OH was diagnosed according to the consensus definition, measuring blood pressure (BP) in the supine position and within 3 minutes in the standing position. MRI scans were performed according to a common protocol at three centres, and the volumes of WMH were quantified using an automated method (n = 82), followed by manual editing. WMH were also quantified using the visual Scheltens scale (n = 139). Multiple logistic regression analyses were applied, with highest vs. lowest WMH quartile as response.
There were no significant correlations between WMH volumes and systolic or diastolic orthostatic BP drops, and no significant correlations between Scheltens scores of WMH and systolic or diastolic BP drops. In the multivariate analyses, only APOEε4 status remained a significant predictor for WMH using the automated method (p = 0.037, OR 0.075 (0.007–0.851)), whereas only age remained a significant predictor for WMH scores (p = 0.019, OR 1.119 (1.018–1.230)).
We found no association between OH and WMH load in a sample of older patients with mild dementia.