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Clinical Autonomic Research : Official... Aug 2021To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults.
PURPOSE
To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults.
METHODS
Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis.
RESULTS
Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias.
CONCLUSION
Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020.
Topics: Adult; Blood Pressure; Caffeine; Databases, Factual; Humans; Hypotension, Orthostatic
PubMed: 34143333
DOI: 10.1007/s10286-021-00814-5 -
Frontiers in Cardiovascular Medicine 2022Syncope (transient loss of consciousness and postural tone) and presyncope are common manifestations of autonomic dysfunction that are usually triggered by orthostasis....
PURPOSE
Syncope (transient loss of consciousness and postural tone) and presyncope are common manifestations of autonomic dysfunction that are usually triggered by orthostasis. The global impact of syncope on quality of life (QoL) is unclear. In this systematic review, we report evidence on the impact of syncope and presyncope on QoL and QoL domains, identify key factors influencing QoL in patients with syncopal disorders, and combine available data to compare QoL between syncopal disorders and to population normative data.
METHODS
A comprehensive literature search of academic databases (MEDLINE (PubMed), Web of Science, CINAHL, PsycINFO, and Embase) was conducted (February 2021) to identify peer-reviewed publications that evaluated the impact of vasovagal syncope (VVS), postural orthostatic tachycardia syndrome (POTS), or orthostatic hypotension (OH) on QoL. Two team members independently screened records for inclusion and extracted data relevant to the study objectives.
RESULTS
From 12,258 unique records identified by the search, 36 studies met the inclusion criteria (VVS: = 20; POTS: = 13; VVS and POTS: = 1; OH: = 2); 12 distinct QoL instruments were used. Comparisons of QoL scores between patients with syncope/presyncope and a control group were performed in 16 studies; significant QoL impairments in patients with syncope/presyncope were observed in all studies. Increased syncopal event frequency, increased autonomic symptom severity, and the presence of mental health disorders and/or comorbidities were associated with lower QoL scores.
CONCLUSION
This review synthesizes the negative impact of syncope/presyncope on QoL and identifies research priorities to reduce the burden of these debilitating disorders and improve patient QoL.
PubMed: 35224062
DOI: 10.3389/fcvm.2022.834879 -
BMC Family Practice Jan 2021Postural hypotension (PH), the reduction in blood pressure when rising from sitting or lying 0to standing, is a risk factor for falls, cognitive decline and mortality.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postural hypotension (PH), the reduction in blood pressure when rising from sitting or lying 0to standing, is a risk factor for falls, cognitive decline and mortality. However, it is not often tested for in primary care. PH prevalence varies according to definition, population, care setting and measurement method. The aim of this study was to determine the prevalence of PH across different care settings and disease subgroups.
METHODS
Systematic review, meta-analyses and meta-regression. We searched Medline and Embase to October 2019 for studies based in primary, community or institutional care settings reporting PH prevalence. Data and study level demographics were extracted independently by two reviewers. Pooled estimates for mean PH prevalence were compared between care settings and disease subgroups using random effects meta-analyses. Predictors of PH were explored using meta-regression. Quality assessment was undertaken using an adapted Newcastle-Ottawa Scale.
RESULTS
One thousand eight hundred sixteen studies were identified; 61 contributed to analyses. Pooled prevalences for PH using the consensus definition were 17% (95% CI, 14-20%; I = 99%) for 34 community cohorts, 19% (15-25%; I = 98%) for 23 primary care cohorts and 31% (15-50%; I = 0%) for 3 residential care or nursing homes cohorts (P = 0.16 between groups). By condition, prevalences were 20% (16-23%; I = 98%) with hypertension (20 cohorts), 21% (16-26%; I = 92%) with diabetes (4 cohorts), 25% (18-33%; I = 88%) with Parkinson's disease (7 cohorts) and 29% (25-33%, I = 0%) with dementia (3 cohorts), compared to 14% (12-17%, I = 99%) without these conditions (P < 0.01 between groups). Multivariable meta-regression modelling identified increasing age and diabetes as predictors of PH (P < 0.01, P = 0.13, respectively; R = 36%). PH prevalence was not affected by blood pressure measurement device (P = 0.65) or sitting or supine resting position (P = 0.24), however, when the definition of PH did not fulfil the consensus description, but fell within its parameters, prevalence was underestimated (P = 0.01) irrespective of study quality (P = 0.04).
CONCLUSIONS
PH prevalence in populations relevant to primary care is substantial and the definition of PH used is important. Our findings emphasise the importance of considering checking for PH, particularly in vulnerable populations, to enable interventions to manage it. These data should contribute to future guidelines relevant to the detection and treatment of PH.
PROSPERO
CRD42017075423.
Topics: Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Hypotension, Orthostatic; Prevalence
PubMed: 33388038
DOI: 10.1186/s12875-020-01313-8 -
Frontiers in Cardiovascular Medicine 2022Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment... (Review)
Review
Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, "crash" position, and bending foreword. CPM were assessed in laboratory-based studies ( = 28), the community setting ( = 4), both laboratory and community settings ( = 3), and during blood donation ( = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living.
PubMed: 36312294
DOI: 10.3389/fcvm.2022.1016420 -
Annals of Internal Medicine Jan 2021Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).
PURPOSE
To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.
DATA SOURCES
MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.
STUDY SELECTION
Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.
DATA EXTRACTION
2 investigators independently abstracted articles and rated risk of bias.
DATA SYNTHESIS
5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH ( for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged.
LIMITATIONS
Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available.
CONCLUSION
Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension.
PRIMARY FUNDING SOURCE
National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753).
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Hypotension, Orthostatic
PubMed: 32909814
DOI: 10.7326/M20-4298 -
Neurology Jul 2021To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at...
OBJECTIVE
To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester.
METHODS
We performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests).
RESULTS
A total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group ( < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period.
CONCLUSIONS
ABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.
Topics: Afferent Pathways; Autonomic Nervous System Diseases; Baroreflex; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Retrospective Studies
PubMed: 33947784
DOI: 10.1212/WNL.0000000000012149 -
Journal of Clinical Neurology (Seoul,... Mar 2023Neurogenic orthostatic hypotension (nOH) is one of the most important nonmotor symptoms in patients with α-synucleinopathies. Atomoxetine is a selective norepinephrine...
Effects of Atomoxetine for the Treatment of Neurogenic Orthostatic Hypotension in Patients With Alpha-synucleinopathies: A Systematic Review of Randomized Controlled Trials and a Focus-Group Discussion.
BACKGROUND AND PURPOSE
Neurogenic orthostatic hypotension (nOH) is one of the most important nonmotor symptoms in patients with α-synucleinopathies. Atomoxetine is a selective norepinephrine transporter blocker that is a treatment option for nOH. This systematic review and expert focus-group study was designed to obtain evidence from published data and clinical experiences of Korean movement-disorder specialists about the efficacy and safety of atomoxetine for the pharmacological treatment of nOH in patients with α-synucleinopathies.
METHODS
The study comprised a systematic review and a focus-group discussion with clinicians. For the systematic review, multiple comprehensive databases including MEDLINE, Embase, Cochrane Library, CINAHL, PsycInfo, and KoreaMed were searched to retrieve articles that assessed the outcomes of atomoxetine therapy. A focus-group discussion was additionally performed to solicit opinions from experts with experience in managing nOH.
RESULTS
The literature review process yielded only four randomized controlled trials on atomoxetine matching the inclusion criteria. Atomoxetine effectively increased systolic blood pressure and improved OH-related symptoms as monotherapy or in combination with other drugs. Its effects were pronounced in cases with central autonomic failure, including multiple-system atrophy (MSA). Atomoxetine might be a safe monotherapy regarding the risk of supine hypertension.
CONCLUSIONS
Atomoxetine is an effective and safe option for short-term nOH management, which could be more evident in patients with central autonomic dysfunction such as MSA. However, there is a paucity of evidence in the literature, and data from the focus-group discussion were inadequate, and so further investigation is warranted.
PubMed: 36647224
DOI: 10.3988/jcn.2022.0018 -
Age and Ageing Apr 2023Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension.
METHODS
We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events.
RESULTS
46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90).
CONCLUSIONS
The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.
Topics: Humans; Antihypertensive Agents; Hypotension, Orthostatic; Hypotension; Blood Pressure; Syncope; Hypertension; Randomized Controlled Trials as Topic
PubMed: 37014001
DOI: 10.1093/ageing/afad044 -
Journal of the American Medical... Sep 2019Nonpharmacologic therapies are often recommended as a first-line treatment for orthostatic hypotension (OH). However, the true effect of nonpharmacologic therapy remains...
OBJECTIVES
Nonpharmacologic therapies are often recommended as a first-line treatment for orthostatic hypotension (OH). However, the true effect of nonpharmacologic therapy remains unclear, particularly in the older population. We undertook a systematic review evaluating the efficacy of nonpharmacologic interventions in older people with OH to provide evidence-based recommendations.
DESIGN
Systematic review of systematic reviews.
SETTING AND PARTICIPANTS
MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews, CINHAL, and PsycINFO were searched up to June 2018. Two reviewers identified eligible systematic reviews from which primary studies were selected. We included both randomized and nonrandomized studies that evaluated any type of nonpharmacologic intervention and reported outcomes of change in postural drop in systolic blood pressure (SBP) and/or orthostatic symptoms measured using any validated instrument. The Cochrane risk of bias tool was used, with recommendations based on the GRADE approach.
RESULTS
Eleven trials were included. Meta-analysis of lower limb compression showed a reduction in the postural drop in SBP of 9.83 mmHg [95% confidence interval (CI) -12.56, -7.11], whereas abdominal compression showed a larger reduction in postural drop in SBP of 12.30 mmHg (95% CI -18.20, -6.39). Compression therapy was also beneficial in reducing OH symptoms. However, the quality of the evidence for compression therapy was very poor. One study each was identified for sleeping with head-up (SHU), home-based resistance training (HBRT), and multicomponent intervention but did not significantly reduce postural SBP drop. Bolus water drinking was effective in 1 study but the study was of low quality.
CONCLUSIONS/IMPLICATIONS
There is no high-quality evidence to recommend any of the nonpharmacologic therapies for the management of OH in older people. Yet, we make a weak recommendation for lower limb and abdominal compression therapy based on very low quality evidence. Large-scale trials are warranted in older people to substantiate the efficacy of nonpharmacologic therapies in OH.
Topics: Aged; Aged, 80 and over; Humans; Hypotension, Orthostatic; Middle Aged
PubMed: 31109911
DOI: 10.1016/j.jamda.2019.03.032 -
Journal of Clinical Hypertension... Aug 2019The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta-analysis was conducted... (Meta-Analysis)
Meta-Analysis
The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta-analysis was conducted in hopes of producing progress on this topic. A systematic database search was performed in electronic databases, including the Chinese Biomedical Database (CBM), PubMed, Web of Science, and the Cochrane Library. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by a random-effects model. Statistical heterogeneity was assessed with Cochran's Q test and the I statistic. From 1462 potentially eligible records, 15 studies met the inclusion criteria. Subjects with OH had a high risk of heart failure (HF) and atrial fibrillation (AF) (pooled HR 1.34, 95% CI 1.17-1.52, P < 0.001 and pooled HR 1.51, 95% CI 1.28-1.79, P < 0.001, respectively). This meta-analysis also showed significant associations between OH and the risks of developing coronary heart disease (CHD) (pooled HR 1.44, 95% CI 1.18-1.75, P < 0.001) and myocardial infarction (MI) (pooled HR 1.52, 95% CI 1.12-2.06, P = 0.008). Our study suggests that OH is positively associated with high risks of HF and AF. Moreover, it may be related to high risks of CHD and MI.
Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Diseases; Coronary Disease; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Myocardial Infarction; Prevalence; Prospective Studies; Risk Factors; Sensitivity and Specificity
PubMed: 31290595
DOI: 10.1111/jch.13613