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1.
Biochem Biophys Res Commun ; 714: 149940, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38677008

ABSTRACT

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


Subject(s)
Aromatic-L-Amino-Acid Decarboxylases , Autoimmunity , Hypotension, Orthostatic , Female , Humans , Middle Aged , Aromatic-L-Amino-Acid Decarboxylases/deficiency , Autoantibodies/blood , Autoantibodies/immunology , Catecholamines , Dopamine/metabolism , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Serotonin/metabolism
2.
Parkinsonism Relat Disord ; 122: 106947, 2024 May.
Article in English | MEDLINE | ID: mdl-38547558

ABSTRACT

INTRODUCTION: Autonomic dysfunction (AuD) is a significant clinical challenge in patients with Dementia with Lewy Bodies (DLB). Manifestations of AuD such as orthostatic hypotension (OH) is associated with falls and decreased quality of life. Cardiac autonomic denervation is an early phenomenon in DLB and a potential contributor to OH. This retrospective study was undertaken to explore whether routine ECG tracings could be used to identify signs of autonomic dysfunction in DLB. METHODS: 18 patients with DLB and 18 age-matched patients with Alzheimer's disease (AD) were included. ECGs and clinical data were analyzed retrospectively for heart rate variability (HRV) and QTc interval prolongation. RESULTS: During an average of 10 years observation time (first to last ECG recording), the QTc interval increased in the DLB group, but not in the AD group. HRV was significantly lower at end of follow-up in the DLB group than in the AD group. DLB patients with OH had greater QTc prolongation. CONCLUSION: Longitudinal ECG analysis indicates that signs of AuD in DLB are reflected on routine ECG tracings. If confirmed in larger cohorts, this could influence risk stratification and help direct preventive measures.


Subject(s)
Alzheimer Disease , Electrocardiography , Heart Rate , Lewy Body Disease , Humans , Male , Female , Aged , Alzheimer Disease/physiopathology , Lewy Body Disease/physiopathology , Lewy Body Disease/complications , Heart Rate/physiology , Retrospective Studies , Aged, 80 and over , Long QT Syndrome/physiopathology , Long QT Syndrome/etiology , Disease Progression , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Middle Aged
3.
BMC Cardiovasc Disord ; 23(1): 503, 2023 10 10.
Article in English | MEDLINE | ID: mdl-37817090

ABSTRACT

AIM: To study effect of change in position (supine and standing) on pulmonary artery pressure (PAP) in ambulatory heart failure (HF) patients. METHODS: Seventeen patients with CardioMEMS® sensor and stable heart failure were consented and included in this single center study. Supine and standing measurements were obtained with at least 5 min interval between the two positions. These measurements included PAP readings utilizing the manufacturer handheld interrogator obtaining 10 s data in addition to the systemic blood pressure and heart rate recordings. RESULTS: Mean supine and standing readings and their difference (Δ) were as follows respectively: Systolic PAP were 33.4 (± 11.19), 23.6 (± 10) and Δ was 9.9 mmHg (p = 0.0001), diastolic PAP were 14.2 (± 5.6), 7.9 (± 5.7) and Δ was 6.3 mmHg (p = 0.0001) and mean PAP were 21.8 (± 7.8), 14 (± 7.2) and Δ was 7.4 mmHg (p = 0.0001) while the systemic blood pressure did not vary significantly. CONCLUSION: There is orthostatic variation of PAP in ambulatory HF patients demonstrating a mean decline with standing in diastolic PAP by 6.3 mmHg, systolic PAP by 9.9 mmHg and mean PAP by 7.4 mmHg in absence of significant orthostatic variation in systemic blood pressure or heart rate. These findings have significant clinical implications and inform that PAP in each patient should always be measured in the same position. Since initial readings at the time of implant were taken in supine position, it may be best to use supine position or to obtain a baseline standing PAP reading if standing PAP is planned on being used.


Subject(s)
Blood Pressure , Heart Failure , Hypotension, Orthostatic , Pulmonary Artery , Humans , Blood Pressure/physiology , Heart Failure/complications , Heart Failure/physiopathology , Heart Rate/physiology , Pulmonary Artery/physiopathology , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/physiopathology , Standing Position , Supine Position/physiology
5.
Hypertension ; 79(3): 638-647, 2022 03.
Article in English | MEDLINE | ID: mdl-34990207

ABSTRACT

BACKGROUND: Initial orthostatic hypotension (IOH) is defined by a large drop in blood pressure (BP) within 15 s of standing. IOH often presents during an active stand, but not with a passive tilt, suggesting that a muscle activation reflex involving lower body muscles plays an important role. To our knowledge, there is no literature exploring how sympathetic activation affects IOH. We hypothesized involuntary muscle contractions before standing would significantly reduce the drop in BP seen in IOH while increasing sympathetic activity would not. METHODS: Study participants performed 4 sit-to-stand maneuvers including a mental stress test (serial 7 mental arithmetic stress test), cold pressor test, electrical stimulation, and no intervention. Continuous heart rate and beat-to-beat BP were measured. Cardiac output and systemic vascular resistance were estimated from these waveforms. Data are presented as mean±SD. RESULTS: A total of 23 female IOH participants (31±8 years) completed the study. The drops in systolic BP following the serial 7 mental arithmetic stress test (-26±12 mm Hg; P=0.004), cold pressor test (-20±15 mm Hg; P<0.001), and electrical stimulation (-28±12 mm Hg; P=0.01) were significantly reduced compared with no intervention (-34±11 mm Hg). The drops in systemic vascular resistance following the serial 7 mental arithmetic stress test (-391±206 dyne×s/cm5; P=0.006) and cold pressor test (-386±179 dyne×s/cm5; P=0.011) were significantly reduced compared with no intervention (-488±173 dyne×s/cm5). Cardiac output was significantly increased upon standing (7±2 L/min) compared with during the sit (6±1 L/min; P<0.001) for electrical stimulation. CONCLUSION: Sympathetic activation mitigates the BP response in IOH, while involuntary muscle contraction mitigates the BP response and reduces symptoms. Active muscle contractions may induce both of these mechanisms of action in their pretreatment of IOH. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03970551.


Subject(s)
Blood Pressure/physiology , Heart Rate/physiology , Hypotension, Orthostatic/physiopathology , Muscle Contraction/physiology , Posture/physiology , Sympathetic Nervous System/physiopathology , Adult , Body Mass Index , Electrocardiography , Exercise Test , Female , Humans , Male , Vascular Resistance/physiology , Young Adult
6.
Hypertension ; 79(1): 50-56, 2022 01.
Article in English | MEDLINE | ID: mdl-34739766

ABSTRACT

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0-10) was 7 (interquartile range, 6-7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722-1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.


Subject(s)
Autonomic Nervous System Diseases/diagnosis , Autonomic Nervous System/radiation effects , Baroreflex/radiation effects , Radiotherapy/adverse effects , Aged , Autonomic Nervous System/physiopathology , Autonomic Nervous System Diseases/etiology , Autonomic Nervous System Diseases/physiopathology , Baroreflex/physiology , Blood Pressure/physiology , Blood Pressure/radiation effects , Female , Heart Rate/physiology , Heart Rate/radiation effects , Humans , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Male , Middle Aged , Norepinephrine/blood , Retrospective Studies , Severity of Illness Index , Valsalva Maneuver
8.
Am J Med ; 135(1): 24-31, 2022 01.
Article in English | MEDLINE | ID: mdl-34416163

ABSTRACT

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.


Subject(s)
Hypotension, Orthostatic/therapy , Disease Management , Humans , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/physiopathology , Inpatients
9.
Am J Respir Crit Care Med ; 205(3): 340-349, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34788206

ABSTRACT

Rationale: Congenital central hypoventilation syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia/hypoxia in CCHS raises the concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment. Objectives: To evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases versus controls. Methods: CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. Fifty CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (regional oxygen saturation) were continuously monitored. The cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated. Measurements and Main Results: HUT resulted in a greater mean BP decrease from baseline in CCHS versus controls (11% vs. 6%; P < 0.05) and a diminished increase in HR in CCHS versus controls (11% vs. 18%; P < 0.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx (P < 0.01) and a 29% increase in minutes of impaired autoregulation (P < 0.02) in CCHS versus controls (4.0 vs. 3.1 min). Conclusions: Cerebral autoregulatory mechanisms appear to be intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx/impaired autoregulation when BP is below the lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.


Subject(s)
Brain/physiopathology , Homeostasis/physiology , Hypotension, Orthostatic/etiology , Hypoventilation/congenital , Oxygen/metabolism , Posture/physiology , Sleep Apnea, Central/physiopathology , Adolescent , Biomarkers/metabolism , Brain/metabolism , Case-Control Studies , Child , Female , Humans , Hypotension, Orthostatic/physiopathology , Hypoventilation/metabolism , Hypoventilation/physiopathology , Male , Oximetry , Sleep Apnea, Central/metabolism , Tilt-Table Test , Young Adult
10.
Sci Rep ; 11(1): 18976, 2021 09 23.
Article in English | MEDLINE | ID: mdl-34556776

ABSTRACT

Dizziness is common in Parkinson's disease (PD) patients. It is known that orthostatic hypotension (OH) is the main cause of such dizziness, but even without OH, quite a few PD patients complain of dizziness in the clinic. It can be regarded as non-specific because most of these patients have no neurological abnormalities. We hypothesized that this type of dizziness would be associated with vestibular function, although included patients did not have clinically confirmed vestibulopathy. We studied 84 patients without OH among 121 PD patients. Their clinical features and function were compared between patients with and without dizziness. Hoehn and Yahr stage (H&Y stage), the Unified Parkinson's Disease Rating Scale (UPDRS) part III, the Korean version of the Mini-Mental State Examination (K-MMSE), education years, disease duration, total levodopa equivalent daily dose (LEDD), the presence of dizziness, the dizziness severity, and orthostatic hypotension were tested. Vestibular evoked myogenic potentials (VEMPs) were used to characterize vestibular function. Ocular (oVEMPs) and cervical (cVEMPs) were recorded. oVEMPs in the right side showed significantly reduced potentials (p = 0.016) in PD patients with dizziness, but cVEMPs did not (all ps > 0.2). Bilateral absent oVEMP responses were more common in PD patients with dizziness (p = 0.022), but the frequencies of bilateral absent cVEMP responses were not different between the dizzy and non-dizzy groups (p = 0.898). Dizziness in PD patients without orthostatic hypotension may be associated with vestibular hypofunction. Our results provide evidence that can aid clinicians when making a treatment plan for patients with dizziness. i.e., strategies to enhance reduced vestibular function may be helpful, but this suggestion remains to be evaluated.


Subject(s)
Dizziness/physiopathology , Hypotension, Orthostatic/physiopathology , Parkinson Disease/complications , Vestibular Evoked Myogenic Potentials/physiology , Vestibule, Labyrinth/physiopathology , Aged , Dizziness/diagnosis , Dizziness/etiology , Female , Humans , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/etiology , Male , Middle Aged , Parkinson Disease/physiopathology , Prospective Studies , Vestibular Function Tests
11.
Am J Physiol Heart Circ Physiol ; 321(4): H716-H727, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34448635

ABSTRACT

Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies, and to explore the effect of simulated OH on cardiovascular and cerebrovascular function following SCI. Male Wistar rats (n = 34) were subjected to a sham or T3-SCI surgery and survived into the chronic period postinjury (i.e., 8 wk). Cardiac function was tracked via ultrasound pre- to post-SCI to demonstrate the clinical utility of our model. At study termination, we conducted left-ventricular (LV) catheterization and insonated the middle cerebral artery to investigate the hemodynamic, cardiac, and cerebrovascular response to a mild dose of LBNP that is sufficient to mimic clinically defined OH in rats with T3-SCI but not sham animals. In response to mimicked OH, there was a greater decline in stroke volume, cardiac output, maximal LV pressure, and blood pressure in SCI compared with sham (P < 0.034), whereas heart rate was increased in sham but decreased in SCI (P < 0.029). SCI animals also had an exaggerated reduction in peak, minimum and mean middle cerebral artery flow, for a given change in blood pressure, in response to LBNP (P < 0.033), implying impaired dynamic cerebral autoregulation. Using a preclinical SCI model of OH, we demonstrate that complete high thoracic SCI impairs the cardiac response to OH and disrupts dynamic cerebral autoregulation.NEW & NOTEWORTHY This is the first use of LBNP to interrogate the cardiac and cerebrovascular responses to simulated OH in a preclinical study of SCI. Here, we demonstrate the utility of our simulated OH model and use it to demonstrate that SCI impairs the cardiac response to simulated OH and disrupts dynamic cerebrovascular autoregulation.


Subject(s)
Cerebrovascular Circulation , Hemodynamics , Hypotension, Orthostatic/physiopathology , Middle Cerebral Artery/physiopathology , Spinal Cord Injuries/physiopathology , Spinal Cord/physiopathology , Ventricular Function, Left , Adaptation, Physiological , Animals , Disease Models, Animal , Hypotension, Orthostatic/etiology , Lower Body Negative Pressure , Male , Rats, Wistar , Spinal Cord Injuries/complications , Thoracic Vertebrae , Time Factors
12.
Kidney Blood Press Res ; 46(5): 574-580, 2021.
Article in English | MEDLINE | ID: mdl-34284392

ABSTRACT

INTRODUCTION: Orthostatic hypotension (OH) affects 5-20% of the population. Our study investigates the presence of OH in diabetic nephropathy (DNP) patients and the factors affecting OH in comparison with nondiabetic chronic kidney disease (NDCKD) patients. METHOD: Patients presented to the nephrology clinic, and those who consented were included in the study. DNP was defined by kidney biopsy and/or clinical criteria. NDCKD patients of the same sex, age, and eGFR were matched to DNP patients. Demographic parameters and medications were obtained from the records. OH was determined by Mayo clinic criteria. The same researcher used an electronic device to measure blood pressure (BP). All samples were taken and analyzed the same day for biochemical and hematologic parameters and albuminuria. RESULTS: 112 (51 F, 61 M, mean age: 62.56 ± 9.35 years) DNP and 94 (40 F, 54 M, mean age: 62.23 ± 10.08 years) NDCKD patients were included. There was no significant difference between DNP and NDCKD groups in terms of OH prevalence (70.5 vs. 61.7%, p = 0.181). Male patients had significantly higher OH prevalence than female patients (74.7 vs. 60.0%, p = 0.026). There was no significant difference in change in systolic BP between the groups (24.00 [10.00-32.00] mm Hg vs. 24.00 [13.75-30.25] mm Hg, p = 0.797), but the change in diastolic BP was significantly higher in the DNP group (8.00 [2.00-13.00] mm Hg vs. 6.00 [2.00-9.00] mm Hg, p = 0.025). In the DNP group, patients with OH had significantly higher uric acid levels than those without OH (7.18 ± 1.55 vs. 6.36 ± 1.65 mg/dL, p = 0.017). And, 73.7% of patients on calcium channel blockers developed OH (p = 0.015), and OH developed in 80.6% of 36 patients on alpha-blockers (p = 0.049). CONCLUSION: OH prevalence is very high in CKD, and etiology of CKD does not have a statistically significant effect on the frequency of OH, despite a difference that could be meaningful clinically. Therefore, patients with CKD are checked for OH, with or without concurrent diabetes mellitus. Evaluation of postural BP changes should be a part of nephrology practice.


Subject(s)
Diabetic Nephropathies/complications , Hypotension, Orthostatic/complications , Renal Insufficiency, Chronic/complications , Aged , Blood Pressure , Diabetic Nephropathies/physiopathology , Female , Humans , Hypotension, Orthostatic/physiopathology , Male , Middle Aged , Renal Insufficiency, Chronic/physiopathology
14.
Neurol Res ; 43(11): 894-899, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34134609

ABSTRACT

Introduction: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an important option in the treatment of motor symptoms and fluctuations in patients with advanced Parkinson's disease (PD). In addition to the improvement in motor symptoms, many studies have reported changes in some non-motor symptoms (NMS) after STN DBS.Method: 61 patients (42 males) who underwent STN DBS with advanced PD and 24 healthy controls (15 males) were included in the study. Autonomic symptoms (orthostatic hypotension, sweating, salivation) were assessed with a semi-structured questionnaire. Sympathetic skin responses (SSR) were studied by electrophysiological examination within 3-6 months after STN DBS.Results: SSR latency and amplitude were found between the control group and preoperative patients (P ≤ 0.01; p = 0.01, respectively), and between preoperative and postoperative patients (P ≤ 0.01; P ≤ 0.01, respectively). There was a statistically significant difference between the control group and postoperative patients (p = 0.005; p = 0.029, respectively). Orthostatic hypotension (29%) and sweating (48%) improved, but there was no change in the salivation.Discussion: We think that STN DBS applied in PD has not only motor symptoms and fluctuations, but also corrects autonomic dysfunctions such as sweating disorders and orthostatic hypotension; SSR is more sensitive and reliable in detecting autonomic dysfunction, independent of motor symptoms and fluctuations.


Subject(s)
Deep Brain Stimulation/methods , Hypotension, Orthostatic/physiopathology , Parkinson Disease/therapy , Sialorrhea/physiopathology , Sweating/physiology , Aged , Electrophysiology , Female , Humans , Hypotension, Orthostatic/etiology , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/physiopathology , Sialorrhea/etiology , Subthalamic Nucleus/physiology
17.
Ann Clin Transl Neurol ; 8(8): 1635-1645, 2021 08.
Article in English | MEDLINE | ID: mdl-34166574

ABSTRACT

OBJECTIVE: To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT). METHODS: Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations. RESULTS: We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19-98 sec) than in VVS (median 1571 sec, IQR 1381-1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%. INTERPRETATION: These new hemodynamic criteria reliably differentiate cOH from VVS.


Subject(s)
Blood Pressure/physiology , Heart Rate/physiology , Hypotension, Orthostatic/diagnosis , Practice Guidelines as Topic , Syncope, Vasovagal/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Hypotension, Orthostatic/physiopathology , Male , Middle Aged , Syncope, Vasovagal/physiopathology , Young Adult
18.
Neurology ; 97(8): e814-e824, 2021 08 24.
Article in English | MEDLINE | ID: mdl-34099524

ABSTRACT

OBJECTIVE: To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales. RESULTS: A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72). CONCLUSIONS: OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.


Subject(s)
Hypotension, Orthostatic/physiopathology , Lewy Body Disease/pathology , Parkinson Disease/pathology , Temporal Lobe/pathology , White Matter/pathology , Aged , Aged, 80 and over , Atrophy/pathology , Female , Humans , Hypotension, Orthostatic/etiology , Lewy Body Disease/complications , Lewy Body Disease/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Severity of Illness Index , Temporal Lobe/diagnostic imaging , White Matter/diagnostic imaging
19.
J Parkinsons Dis ; 11(3): 1335-1344, 2021.
Article in English | MEDLINE | ID: mdl-34024782

ABSTRACT

BACKGROUND: Orthostatic hypotension (OH) may antedate Parkinson's disease (PD) or be found in early stages of the disease. OH may induce a PD brain to chronic hypotensive insults. 18F-Florbetaben (18F-FBB) tracer has a high first-pass influx rate and can be used with positron emission tomography (PET) as a surrogate marker for early- and late-phase evaluation of cerebral perfusion and cerebral amyloidosis, respectively. OBJECTIVE: In this study, we evaluated whether 18F-FBB uptake in the early- and late-phases of PD was related to OH. This study manipulated the imaging modality to illustrate the physiology of cerebral flow with OH in PD (PD + OH). METHODS: A group of 73 early-stage PD patients was evaluated with a head-up tilt-test and 18F-FBB PET imaging. The cognitive status was assessed by a comprehensive battery of neuropsychological tests. PET images were normalized, and both early- and late-phase standardized uptake value ratios (SUVRs) of pre-specified regions were obtained. The associations between regional SUVRs and OH and cognitive status were analyzed. RESULTS: Twenty (27.4%) participants had OH. Thirteen (17.8%) patients were interpreted as having amyloid pathology based on regional 18F-FBB uptake. Early-phase SUVRs were higher in specific brain regions of PD + OH patients than those without OH. However, late-phase SUVRs did not differ between the groups. The early-phase SUVRs were not influenced by amyloid burden or by interaction between amyloid and orthostatic hypotension. Cognitive functions were not disparate when PD + OH patients were contrasted with non-OH patients in this study. CONCLUSION: Cerebral blood flow was elevated in patients with early PD + OH. This finding suggests augmented cerebral perfusion in PD + OH might be a compensatory regulation in response to chronic OH.


Subject(s)
Cerebrovascular Circulation , Hypotension, Orthostatic , Parkinson Disease , Aniline Compounds , Cerebrovascular Circulation/physiology , Humans , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/diagnostic imaging , Hypotension, Orthostatic/physiopathology , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Parkinson Disease/physiopathology , Positron-Emission Tomography , Stilbenes
20.
BMC Cardiovasc Disord ; 21(1): 213, 2021 04 27.
Article in English | MEDLINE | ID: mdl-33906603

ABSTRACT

BACKGROUND: Orthostatic hypotension (OH) and orthostatic hypertension (OHT) are often unrecognized in clinical care for diabetic individuals, yet they are associated with increased risk for adverse cardiovascular outcomes. We aimed to determine the prevalence of the abnormal orthostatic blood pressure (BP) responses, and associated factors among diabetic individuals in ambulatory care for diabetes in southwestern Uganda. METHODS: We conducted a cross-sectional study among diabetic individuals aged 18-65 years at Mbarara Regional Referral Hospital, southwestern Uganda from November 2018 to April 2019. We obtained demographic and clinical data including a detailed medical history, and glycemic profile. BP measurements were taken in supine position and within 3 min of standing. We defined OH in participants with either ≥ 20 mmHg drop in systolic BP (SBP) or ≥ 10 mmHg drop in diastolic BP (DBP) after assuming an upright position. OHT was defined in participants with either a ≥ 20 mmHg rise in SBP, or ≥ 10 mmHg rise in DBP after assuming an upright position. Multivariate logistic regression was used to identify factors associated with OH and OHT. RESULTS: We enrolled 299 participants, with a mean age of 50 years (SD ± 9.8), and mean HbA1c of 9.7% (SD ± 2.6); 70% were female. Of the 299 participants, 52 (17.4%; 95% CI 13.3-22.2%) met the definition of OH and 43 (14.4%; 95% CI 10.6-18.9%) were classified as having OHT. In multivariable models, factors associated with diabetic OH were older age (OR = 2.40 for 51-65 years vs 18-50 years, 95% CI 1.02-5.67, P = 0.046), diabetic retinopathy (OR = 2.51; 95% CI 1.14-5.53, P = 0.022), higher resting SBP ≥ 140 mmHg (OR = 3.14; 95% CI 1.31-8.7.56, P = 0.011), and history of palpitations (OR = 2.31; 95% CI 1.08-4.92, P = 0.031). Self-report of palpitations (OR = 3.14; 95% CI 1.42-6.95, P = 0.005), and higher resting SBP ≥ 140 mmHg (OR = 22.01; 95% CI 1.10-4.42, P = 0.043) were associated with OHT. CONCLUSION: OH and OHT are common among diabetic individuals in ambulatory diabetes care in southwestern Uganda. Orthostatic BP measurements should be considered as part of routine physical examination to improve detection of OH and OHT, especially among older diabetics with complications of the disease. Future studies to assess the health and prognostic implications of OH and OHT among diabetics in the region are warranted.


Subject(s)
Blood Pressure , Hospitals , Hypertension/epidemiology , Hypotension, Orthostatic/epidemiology , Posture , Adolescent , Adult , Aged , Ambulatory Care , Cross-Sectional Studies , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Female , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/physiopathology , Male , Middle Aged , Prevalence , Referral and Consultation , Risk Assessment , Risk Factors , Uganda/epidemiology , Young Adult
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