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Clinical Autonomic Research : Official... Jun 2022Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing... (Review)
Review
BACKGROUND
Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with "brain fog", which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope.
METHODS
We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias.
RESULTS
Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n = 10; VVS n = 1; OH n = 1; VVS and POTS n = 1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. "Brain fog" was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS.
CONCLUSION
In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals.
Topics: Fatigue; Humans; Hypotension, Orthostatic; Postural Orthostatic Tachycardia Syndrome; Quality of Life; Syncope; Syncope, Vasovagal; Tilt-Table Test
PubMed: 35689118
DOI: 10.1007/s10286-022-00868-z -
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 -
Clinical Cardiology Jun 2010The association of clinostatic hypertension (CH) and orthostatic hypotension (OH) is described as the "Hyp-Hyp phenomenon," and it has been found in about 5.5% of... (Review)
Review
BACKGROUND
The association of clinostatic hypertension (CH) and orthostatic hypotension (OH) is described as the "Hyp-Hyp phenomenon," and it has been found in about 5.5% of hypertensive patients and in up to 50% of patients with OH. The importance of CH/OH in clinical practice is mainly due to the presence of troublesome symptoms, end-organ damage, and difficulties in its clinical management.
HYPOTHESIS
The review focuses on the clinical problem of CH and review the international literature for the best management, including the diagnostic work-up and the taylored treatment for this kind of patients.
METHODS
A systematic review of the literature was conducted through MEDLINE research to focus the main controversial issues about CH/OH. Included topics: (1) the diagnostic work-up, (2) the association with dysautonomic failure and syncope, and (3) the treatment options and prevention of end-organ damage.
RESULTS
Current standard reference for OH diagnosis includes functional assessment of the cardiac vagal nervous system and the sympathetic adrenergic system. The association with dysautonomic failure and with syncope needs further investigation. Pharmacologic treatment of OH is aimed at controlling symptoms rather than restoring normotension. Midodrine is the only medication that has been put to multicenter placebo-controlled trial and subsequently approved by the U.S. Food and Drug Administration (FDA) for OH treatment. Short-acting oral antihypertensive agents at bedtime should be considered in patients with severe, sustained CH.
CONCLUSIONS
Data obtained from the literature review showed that clinical diagnosis of the Hyp-Hyp phenomenon is relatively simple, but it remains more difficult to establish the causal disease. In our opinion, it is advisable to define simple diagnostic standards for the selection of patients at risk of dysautonomic impairment so that a subsequent highly specific diagnostic work-up could be initiated.
Topics: Antihypertensive Agents; Autonomic Nervous System; Blood Pressure; Humans; Hypertension; Hypotension, Orthostatic; Midodrine; Predictive Value of Tests; Treatment Outcome; Vasoconstrictor Agents
PubMed: 20552588
DOI: 10.1002/clc.20722 -
Prevalence of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis.Parkinsonism & Related Disorders Dec 2011Although orthostatic hypotension (OH) is recognized as one of the main non-motor symptoms of Parkinson's disease (PD), there is inconsistent evidence about the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although orthostatic hypotension (OH) is recognized as one of the main non-motor symptoms of Parkinson's disease (PD), there is inconsistent evidence about the prevalence of OH in PD. To estimate the prevalence of OH in PD more precisely we conducted a systematic review of the literature.
METHODS
From PubMed and Embase searches with predefined inclusion criteria, we identified studies published up till December 2009. Prevalence numbers from studies were pooled using a non-linear random-effects meta-analysis.
RESULTS
We found 25 studies from which the prevalence of OH could be calculated. The pooled estimate of the point prevalence of OH in PD was 30.1% (95% CI: 22.9% to 38.4%). We found a large statistical heterogeneity between studies which could not be reduced by several subgroup analyses.
CONCLUSIONS
The estimated prevalence of OH in PD is 30%. However, due to the large heterogeneity between studies this pooled estimate should be interpreted with caution. More data from unselected population-based cohorts are needed.
Topics: Humans; Hypotension, Orthostatic; Parkinson Disease; Prevalence
PubMed: 21571570
DOI: 10.1016/j.parkreldis.2011.04.016 -
Seminars in Arthritis and Rheumatism Feb 2023Anecdotally, fibromyalgia syndrome (FMS) and connective tissue disorders (hypermobile Ehlers-Danlos Syndrome (hEDS), Hypermobility Spectrum disorders (HSD) and... (Review)
Review
BACKGROUND
Anecdotally, fibromyalgia syndrome (FMS) and connective tissue disorders (hypermobile Ehlers-Danlos Syndrome (hEDS), Hypermobility Spectrum disorders (HSD) and Generalized Joint Hypermobility (GJH)) manifest overlap in their diagnostic approach and symptomatic features. Understanding this overlap is important for accurate diagnosis and the success of subsequent management. This study therefore aimed to identify the prevalence of concomitant diagnosis of FMS and hEDS/HSD/GJH in adults and their shared symptomatic manifestations using a systematic review.
METHODS
MEDLINE (via EBSCO host) was systematically searched. Observational research (case-control or single group) studies were considered for inclusion, where adults screened for hEDS/HSD/GJH and FMS were compared in terms of diagnostic prevalence, and musculoskeletal and non-musculoskeletal manifestations. Studies on pediatric populations were excluded. The quality of the included studies was assessed using the National Institute of Health Quality Assessment of Case-Control Studies and Jonna Briggs Critical Appraisal checklist for prevalence studies. The review was registered prospectively in PROSPERO (CRD42020216283).
FINDINGS
The review included eleven studies: nine case-control studies and two single group studies. The prevalence of concomitant diagnosis of hEDS/HSD and FMS ranged from 68%-88.9% and from 8.0 to 64.2% for GJH and FMS. The prevalence and severity of a range of objective and patient-reported features were similar between hEDS/HSD and FMS, including joint pain (duration, persistence, SF-36-pain component score); joint swelling; muscle weakness; neurological problems; multidimensional pain inventory-activity; dysautonomia and total autonomic symptoms burden (including orthostatic intolerance, reflex syncope, vasomotor, gastrointestinal, diarrhea, constipation and pupillomotor domains); function; and quality of life. Shared symptomatic features between GJH and FMS were mean pain level, tender points count, total myalgia score and psychological impact.
INTERPRETATION
There may be overlapping symptomatology and diagnostic prevalence of FMS and hEDS/HSD/GJH. Clinicians should consider both diagnoses to ensure appropriate diagnosis and management.
Topics: Adult; Child; Humans; Fibromyalgia; Quality of Life; Connective Tissue Diseases; Ehlers-Danlos Syndrome; Joint Instability; Myalgia; Connective Tissue
PubMed: 36462303
DOI: 10.1016/j.semarthrit.2022.152127 -
The Cochrane Database of Systematic... May 2021Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate...
BACKGROUND
Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition.
OBJECTIVES
To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension.
SEARCH METHODS
We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries.
SELECTION CRITERIA
We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE.
MAIN RESULTS
We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.
Topics: Bias; Diabetes Mellitus; Domperidone; Dysautonomia, Familial; Fludrocortisone; Humans; Hypotension, Orthostatic; Observational Studies as Topic; Parkinson Disease; Pyridostigmine Bromide; Randomized Controlled Trials as Topic
PubMed: 34000076
DOI: 10.1002/14651858.CD012868.pub2 -
Medicine Sep 2017Orthostatic hypotension (OH) is a major clinical sign of cardiovascular autonomic dysfunction in diabetic patients. Our aim was to quantitatively evaluate the prevalence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Orthostatic hypotension (OH) is a major clinical sign of cardiovascular autonomic dysfunction in diabetic patients. Our aim was to quantitatively evaluate the prevalence and risk factors of OH in patients with diabetes mellitus (DM) and assess its prognosis.
METHODS
A comprehensive search of the PubMed, Embase, China National Knowledge Infrastructure, VIP Chinese Journal, Wanfang, and SINOMED databases was conducted for related published work up to September 25, 2016, and manually searched eligible studies from the references in accordance with the inclusion criteria.
RESULTS
We included 21 studies in the analysis, with a total sample size of 13,772. The pooled prevalence of OH in DM was 24% (95% confidence interval [CI]: 19-28%). Potential risk factors, that is, glycosylated hemoglobin A (HbA1c) (odds ratio [OR], 1.13, 95% CI, 1.07-1.20), hypertension (OR, 1.02, 95% CI, 1.01-1.02), and diabetic nephropathy (OR, 2.37, 95% CI, 1.76-3.19), were significantly associated with OH in DM. In addition, the prognosis of OH in DM was associated with higher risk of total mortality and cardiovascular events.
CONCLUSION
The pooled prevalence of OH in DM appears high. HbA1c, hypertension, and diabetic nephropathy are risk factors for OH in DM. OH indicates poor prognosis in diabetic patients. Attention should be focused on diabetic patients with the stated risk factors to prevent OH.
Topics: Diabetes Mellitus; Humans; Hypotension, Orthostatic; Prevalence; Prognosis; Risk Factors
PubMed: 28885363
DOI: 10.1097/MD.0000000000008004 -
Autonomic Neuroscience : Basic &... Dec 2023To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination.
METHODS
We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series.
RESULTS
We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05).
CONCLUSION
Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Postural Orthostatic Tachycardia Syndrome; Demography
PubMed: 38000119
DOI: 10.1016/j.autneu.2023.103132 -
Clinical Cardiology Jul 2023Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have... (Meta-Analysis)
Meta-Analysis Review
Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have investigated vitamin D levels in VVS patients. In this systematic review and meta-analysis, we aim to review these studies to find possible associations between vitamin D deficiency and vitamin D levels with VVS. International databases including Scopus, Web of Science, PubMed, and Embase were searched with keywords related to "vasovagal syncope" and "vitamin D." Studies were screened and the data were extracted from them. Random-effect meta-analysis was conducted to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for vitamin D levels in comparison to VVS patients and controls. Also, VVS occurrence was measured and the odds ratio (OR) and 95% CI were calculated for comparison of vitamin D deficient cases and nondeficient individuals. Six studies were included with 954 cases investigated. Meta-analysis showed that patients with VVS had significantly lower vitamin D serum levels in comparison to non-VVS cases (SMD -1.05, 95% CI -1.54 to -0.57, p-value < .01). Moreover, VVS occurrence was higher in vitamin D-deficient individuals (OR 5.43, 95% CI 2.40 to 12.27, p-value < .01). Our findings which show lower vitamin D levels in VVS patients can have clinical implications in order for clinicians to pay attention to this when approaching VVS. Further randomized controlled trials are certainly warranted to assess the role of vitamin D supplementation in individuals with VVS.
Topics: Humans; Tilt-Table Test; Syncope, Vasovagal; Syncope; Vitamin D Deficiency; Vitamin D
PubMed: 37226313
DOI: 10.1002/clc.24035 -
Ageing Research Reviews Jun 2023Autonomic dysfunction and frailty are two common and complex geriatric syndromes. Their prevalence increases with age and they have similar negative health outcomes. In... (Meta-Analysis)
Meta-Analysis Review
Autonomic dysfunction and frailty are two common and complex geriatric syndromes. Their prevalence increases with age and they have similar negative health outcomes. In PubMed and Web of Science we screened studies identifying a relationship between autonomic function (AF) and frailty in adults aged ≥ 65 years. Twenty-two studies of which two prospective and 20 cross-sectional were included (n = 8375). We performed a meta-analysis for the articles addressing orthostatic hypotension (OH). Frailty was associated with 1.6 higher odds of suffering from consensus OH (COH) {OR= 1.607 95%CI [1.15-2.24]; 7 studies; n = 3488}. When measured for each type of OH the largest trend was seen between initial OH (IOH) and frailty {OR= 3.08; 95%CI [1.50-6.36]; 2 studies; n = 497}. Fourteen studies reported other autonomic function alterations in frail older adults with 4-22% reduction in orthostatic heart rate increase, 6% reduction in systolic blood pressure recovery, 9-75% reduction in most common used heart rate variability (HRV) parameters. Frail older adults were more likely to have impaired AF. Diagnosis of frailty should promptly lead to orthostatic testing as OH implicates specific treatment modalities, which differ from frailty management. As IOH is most strongly correlated with frailty, continuous beat to beat blood pressure measurements should be performed when present at least until cut-off values for heart rate variability testing are defined.
Topics: Aged; Humans; Frail Elderly; Frailty; Prospective Studies; Cross-Sectional Studies; Hypotension, Orthostatic
PubMed: 37028604
DOI: 10.1016/j.arr.2023.101925