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PLoS Medicine Nov 2021Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear.
METHODS AND FINDINGS
We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel-Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697).
CONCLUSIONS
Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antidepressive Agents; Antipsychotic Agents; Humans; Hypotension, Orthostatic; Placebos; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 34752479
DOI: 10.1371/journal.pmed.1003821 -
Aging Clinical and Experimental Research May 2022Over the latest years different studies have investigated the possible relationship between D deficiency and occurrence of orthostatic hypotension (OH), often reaching... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Over the latest years different studies have investigated the possible relationship between D deficiency and occurrence of orthostatic hypotension (OH), often reaching controversial results. We perform an update meta-analysis providing an update overview on the association between hypovitaminosis D and orthostatic hypotension (OH) in older adults.
METHODS
Data extraction was independently performed by two authors and based upon predefined criteria. The meta-analysis was performed using a random-effects model. Statistical heterogeneity between groups was measured using the Higgins I2 statistic.
RESULTS
Eight investigations enrolling 16.326 patients (mean age 75.5 years) met the inclusion criteria and were considered for the analysis. Patients with vitamin D deficiency were more likely to have OH compared to those without (OR: 1.36, 95% CI 1.14-1.63, p = 0.0001, I2 = 43.6%). A further sub-analysis, based on three studies, estimating the risk of OH in patients with hypovitaminosis D receiving antihypertensive treatment, did not reach the statistical significance (OR: 1.40, 95% CI 0.61-3.18, p = 0.418, I2 = 53.3%). Meta-regression performed using age (p = 0.12), BMI (p = 0.73) and gender (p = 0.62) as moderators did not reveal any statistical significance in influencing OH. Conversely, physical activity, Vitamin D supplementation and use of radioimmunoassay for the measurement of vitamin D serum levels showed a significant inverse relationship towards the risk of OH (Coeff.-0.09, p = 0.002, Coeff. - 0.12, p < 0.001 and Coeff. - 0.08, p = 0.03, respectively) among patients with hypovitaminosis D. A direct correlation between the administration of antihypertensive treatment and the risk of OH in older patients with low vitamin D level was observed (Coeff. 0.05, p < 0.001).
CONCLUSIONS
Hypovitaminosis D is significantly associated with OH in older adults and directly influence by the administration of antihypertensive drugs. Conversely, physical activity, vitamin D supplementation and use of radioimmunoassay as analytic method inversely correlated with the risk of OH in older patients.
Topics: Aged; Antihypertensive Agents; Humans; Hypotension, Orthostatic; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 34628636
DOI: 10.1007/s40520-021-01994-w -
Autonomic Neuroscience : Basic &... Nov 2021Syncope is not a common manifestation of COVID-19, but it may occur in this context and it can be the presenting symptom in some cases. Different mechanisms may explain...
BACKGROUND
Syncope is not a common manifestation of COVID-19, but it may occur in this context and it can be the presenting symptom in some cases. Different mechanisms may explain the pathophysiology behind COVID-19 related syncope. In this report, we aimed to examine the current frequency and etiology of syncope in COVID-19.
METHODS
A systematic review across PubMed, ISI Web of Knowledge and SCOPUS was performed, according to PRISMA guidelines, in order to identify all relevant articles regarding both COVID-19 and syncope.
RESULTS
We identified 136 publications, of which 99 were excluded. The frequency of syncope and pre-syncope across the selected studies was 4.2% (604/14,437). Unexplained syncope was the most common type (87.9% of the episodes), followed by reflex syncope (7.8% of the cases). Orthostatic hypotension was responsible for 2.2% of the cases and syncope of presumable cardiac cause also accounted for 2.2% of cases. Arterial hypertension was present in 52.0% of syncope patients. The use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors were not associated with an increased incidence of syncope (chi-square test 1.07, p 0.30), unlike the use of beta-blockers (chi-square test 12.48, p < 0.01).
CONCLUSION
Syncope, although not considered a typical symptom of COVID-19, can be associated with it, particularly in early stages. Different causes of syncope were seen in this context. A reevaluation of blood pressure in patients with COVID-19 is suggested, including reassessment of antihypertensive therapy, especially in the case of beta-blockers.
Topics: Autonomic Nervous System Diseases; COVID-19; Humans; Hypertension; Syncope
PubMed: 34500351
DOI: 10.1016/j.autneu.2021.102872 -
Clinical Obesity Dec 2021There have been increased reports of orthostatic intolerance post-bariatric surgery. However, the prevalence, pathophysiology and long-term outcomes have not been well... (Meta-Analysis)
Meta-Analysis
There have been increased reports of orthostatic intolerance post-bariatric surgery. However, the prevalence, pathophysiology and long-term outcomes have not been well described. Therefore, we sought to summarize evidence of orthostatic intolerance after bariatric surgery. We conducted a systematic review using PubMed, Scopus, CINAHL, Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant articles from the date of inception until 1st April 2020. Study selection, data extraction and quality assessment of the included studies were performed independently by two reviewers. The findings of the included studies were narratively reported. When feasible, a meta-analysis was done to summarize the relevant results. We included 20 studies (n = 19 843 participants) reporting findings of 12 prospective cohort studies, 5 retrospective cohort studies, 2 cross-sectional studies and one randomized controlled trial. The 5-year cumulative incidence of orthostatic intolerance was 4.2% (one study). Common clinical presentations of orthostatic intolerance were lightheadedness, dizziness, syncope and palpitation. The pooled data suggested improvement in overall cardiac autonomic function (sympathetic and parasympathetic) post-bariatric surgery. In addition, a significant systolic blood pressure drop may reflect a reset of the balance between the sympathetic and parasympathetic nervous systems after weight loss in the pooled analysis. Existing literature on orthostatic intolerance post-bariatric surgeries was limited or of low quality, and larger studies are needed to know the true incidence of orthostatic intolerance post-bariatric surgeries and the pathophysiology. We found one study reporting the 5-years cumulative incidence of orthostatic intolerance post-bariatric surgeries as only 4.2%. This could challenge the idea of increased orthostatic intolerance prevalence post-bariatric surgeries. Registration The review protocol was registered at the International Prospective Register of Systemic Reviews PROSPERO (CRD42020170877).
Topics: Bariatric Surgery; Cross-Sectional Studies; Humans; Orthostatic Intolerance; Prospective Studies; Retrospective Studies
PubMed: 34409762
DOI: 10.1111/cob.12483 -
American Family Physician Aug 2021
Meta-Analysis
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Hypotension, Orthostatic; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 34383445
DOI: No ID Found -
Clinical Parkinsonism & Related... 2021Frailty and Parkinson's disease (PD) are common conditions that increase with age. Independently, frailty and PD lead to increased morbidity and mortality for patients.... (Review)
Review
INTRODUCTION
Frailty and Parkinson's disease (PD) are common conditions that increase with age. Independently, frailty and PD lead to increased morbidity and mortality for patients. Few studies report on frailty in patients with PD. We performed a systematic review and -analysis of the prevalence, associations and outcomes of frailty in persons with PD.
METHODS
We searched four electronic databases and grey literature from inception to May 19, 2020, for articles which reported the prevalence, associations and outcomes of frailty in persons with PD.
RESULTS
One-thousand and sixty-three citations were identified, of which 127 articles were reviewed. Thirty studies were included. Twenty-eight studies were observational and the settings varied including 25 community and 5 inpatient studies.The most common frailty screening measures were the frailty phenotype and clinical frailty scale. The prevalence of frailty in PD using the FP was 0.38 (0.24-0.55) with I = 92.6% (p < 0.01). Frailty was associated with recurrent falls, cognitive impairment, dementia, orthostatic hypotension, fatigue, hallucinations, nursing home placement, dependency in activities of daily living and in-patient mortality. PD disease duration, motor impairment, non-tremor dominant PD (postural instability/gait difficulty dominant phenotype) and total daily levodopa dose were associated with frailty.
CONCLUSION
Frailty is common in PD. There is no agreed upon tool for identifying frailty, however, the importance of its identification is apparent given the high prevalence and the association between frailty and adverse outcomes in persons with PD. Future studies are required to guide clinicians in how best to identify and manage frail patients with PD.
PubMed: 34316672
DOI: 10.1016/j.prdoa.2021.100095 -
Age and Ageing Sep 2021Initial orthostatic hypotension (OH) is a clinical syndrome of exaggerated transient orthostasis associated with higher risks of falls, frailty and syncope in older... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Initial orthostatic hypotension (OH) is a clinical syndrome of exaggerated transient orthostasis associated with higher risks of falls, frailty and syncope in older adults.
OBJECTIVE
To provide a prevalence estimate of initial OH in adults aged 65 years or older.
METHODS
Literature search of MEDLINE (from 1946), Embase (from 1947) and Cochrane Central Register of Controlled Trials was performed until 6 December 2019, using the terms 'initial orthostatic hypotension', 'postural hypotension' and 'older adults'. Articles were included if published in English and participants were 65 years or older. Random effects models were used for pooled analysis.
RESULTS
Of 5,136 articles screened, 13 articles (10 cross-sectional; 3 longitudinal) reporting data of 5,465 individuals (54.5% female) from the general (n = 4,157), geriatric outpatient (n = 1,136), institutionalised (n = 55) and mixed (n = 117) population were included. Blood pressure was measured continuously and intermittently in 11 and 2 studies, respectively. Pooled prevalence of continuously measured initial OH was 29.0% (95% CI: 22.1-36.9%, I2 = 94.6%); 27.8% in the general population (95% CI: 17.9-40.5%, I2 = 96.1%), 35.2% in geriatric outpatients (95% CI: 24.2-48.1%, I2 = 95.3%), 10.0% in institutionalised individuals (95% CI: 2.4-33.1%, I2 = 0%) and 21.4% in the mixed population (95% CI: 7.0-49.6, I2 = 0%). Pooled prevalence of intermittently measured initial OH was 5.6% (95% CI: 1.5-18.9%, I2 = 81.1%); 1.0% in the general population (95% CI: 0.0-23.9%, I2 = 0%) and 7.7% in geriatric outpatients (95% CI: 1.8-27.0%, I2 = 86.7%).
CONCLUSION
The prevalence of initial OH is high in older adults, especially in geriatric outpatients. Proper assessment of initial OH requires continuous blood pressure measurements.
Topics: Accidental Falls; Aged; Blood Pressure; Cross-Sectional Studies; Female; Frailty; Humans; Hypotension, Orthostatic; Male; Prevalence
PubMed: 34260686
DOI: 10.1093/ageing/afab090 -
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 -
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 -
Current Hypertension Reports May 2021The aim of this review article was to summarize the cardiovascular and blood pressure profile regarding Parkinson disease patients and to provide an update on the recent... (Review)
Review
PURPOSE OF REVIEW
The aim of this review article was to summarize the cardiovascular and blood pressure profile regarding Parkinson disease patients and to provide an update on the recent advancements in the field of the diagnosis and management of blood pressure abnormalities in these patients. Our goal was to guide physicians to avoid pitfalls in current practice while treating patients with Parkinson disease and blood pressure abnormalities. For this purpose, we searched bibliographic databases (PubMed, Google Scholar) for all publications published on blood pressure effects in Parkinson disease until May 2020. Furthermore, we highlight some thoughts and potential perspectives for the next possible steps in the field.
RECENT FINDINGS
Blood pressure dysregulation in patients with Parkinson's disease has several implications in clinical practice and presents an ongoing concern. Compared with chronic essential hypertension, the syndrome of combined neurogenic orthostatic hypotension and supine hypertension in Parkinson's disease has received little attention. If left untreated, hypertension may lead to cardiovascular disease whereas hypotension may lead to fall-related complications, with tremendous impact on the quality of life of affected individuals. The effect of blood Epressure control and the risk of death from cardiovascular disease in Parkinson disease are largely unexplored. Blood pressure abnormalities in Parkinson disease present bidirectional relationship and the rationale for treating and controlling hypertension in persons with Parkinson disease and concurrent neurogenic orthostatic hypotension and/or supine hypertension is compelling. Further research is warranted in order to clarify the mechanisms, clinical implications, and potential reversibility of compromised cardiovascular function, in persons with Parkinson disease.
Topics: Blood Pressure; Humans; Hypertension; Hypotension, Orthostatic; Parkinson Disease; Quality of Life
PubMed: 33961147
DOI: 10.1007/s11906-021-01146-5