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Hypertension (Dallas, Tex. : 1979) Jul 2023Orthostatic hypotension (OH) has been associated with elevated risk of cardiovascular diseases (CVDs) and dementia risk. To better understand the OH-dementia...
BACKGROUND
Orthostatic hypotension (OH) has been associated with elevated risk of cardiovascular diseases (CVDs) and dementia risk. To better understand the OH-dementia association, we assessed the associations of OH with CVD and subsequent dementia in older adults and considered the temporality of CVD and dementia onset.
METHODS
This 15-year population-based cohort study included, at baseline, 2703 dementia-free participants (mean age, 73.7 years) who were divided into a CVD-free cohort (n=1986) and a CVD cohort (n=717). OH was defined as a systolic/diastolic blood pressure decline of ≥20/10 mm Hg after standing up from a supine position. CVDs and dementia were ascertained by physicians or identified from registers. Multistate Cox regressions were applied to assess the associations of OH with CVD and subsequent dementia in the CVD-free and dementia-free cohort. The OH-dementia association in the CVD cohort was examined with Cox regressions.
RESULTS
OH was present in 434 (21.9%) individuals in the CVD-free cohort and 180 (25.1%) individuals in the CVD cohort. OH was associated with a hazard ratio of 1.33 (95% CI, 1.12-1.59) for CVD. OH was not significantly associated with incident dementia in the absence of CVD occurring before dementia diagnosis (hazard ratio, 1.22 [95% CI, 0.83-1.81]). In the CVD cohort, individuals with OH had a higher dementia risk than those without OH (hazard ratio, 1.54 [95% CI, 1.06-2.23]).
CONCLUSIONS
The association between OH and dementia may partly be explained by the intermediate development of CVD. In addition, in people with CVD, those with OH may have a poorer cognitive prognosis.
Topics: Humans; Aged; Cardiovascular Diseases; Hypotension, Orthostatic; Cohort Studies; Blood Pressure; Risk Factors
PubMed: 37203439
DOI: 10.1161/HYPERTENSIONAHA.123.21210 -
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 -
Clinical Autonomic Research : Official... Jul 2017
Topics: Blood Pressure Monitoring, Ambulatory; Disease Management; Humans; Hypertension; Hypotension, Orthostatic
PubMed: 28620715
DOI: 10.1007/s10286-017-0437-3 -
Expert Review of Cardiovascular Therapy Nov 2015Orthostatic hypotension (OH) leads to a significant number of hospitalizations each year, and is associated with significant morbidity and mortality among affected... (Review)
Review
Orthostatic hypotension (OH) leads to a significant number of hospitalizations each year, and is associated with significant morbidity and mortality among affected individuals. Given the increased risk for cardiovascular events and falls, it is important to identify the underlying etiology of OH and to choose appropriate therapeutic agents. OH can be non-neurogenic or neurogenic (arising from a central or peripheral lesion). The initial evaluation includes orthostatic vital signs, complete history and a physical examination. Patients should also be evaluated for concomitant symptoms of post-prandial hypotension and supine hypertension. Non-pharmacologic interventions are the first step for treatment of OH. The appropriate selection of medications can also help with symptomatic relief. This review highlights the pathophysiology, clinical features, diagnostic work-up and treatment of patients with neurogenic OH.
Topics: Humans; Hypertension; Hypotension, Orthostatic
PubMed: 26427904
DOI: 10.1586/14779072.2015.1095090 -
Journal of Physiology and Pharmacology... Aug 2023Parkinson's disease (PD) often presents with autonomic dysregulation, leading to blood pressure irregularities such as neurogenic orthostatic hypotension (nOH),... (Review)
Review
Parkinson's disease (PD) often presents with autonomic dysregulation, leading to blood pressure irregularities such as neurogenic orthostatic hypotension (nOH), neurogenic supine hypertension (nSH), and postprandial hypotension (PPH). Unfortunately, these conditions remain prevalent and receive insufficient attention in scientific discourse. They not only cause complications like syncope, falls, and fractures but also result in long-term damage to vital organs, diminishing patients' quality of life. Early implementation of appropriate non-pharmacologic management is crucial to prevent severe adverse events later on. This review focuses on the types, clinical characteristics, mechanisms, and common non-pharmacologic management measures for PD complicated by abnormal blood pressure. By promoting early diagnosis, recognizing symptoms of abnormal blood pressure, and employing non-pharmacologic interventions such as health education, dietary adjustments, exercise, and Chinese medicine techniques, we aim to improve patients' symptoms and quality of life while providing practical guidance for managing PD-related blood pressure abnormalities.
Topics: Humans; Parkinson Disease; Blood Pressure; Quality of Life; Hypotension, Orthostatic; Hypertension
PubMed: 37865954
DOI: 10.26402/jpp.2023.4.01 -
Clinical Autonomic Research : Official... Sep 2019Neurogenic orthostatic hypotension is a prominent and disabling manifestation of autonomic dysfunction in patients with hereditary transthyretin (TTR) amyloidosis... (Review)
Review
PURPOSE
Neurogenic orthostatic hypotension is a prominent and disabling manifestation of autonomic dysfunction in patients with hereditary transthyretin (TTR) amyloidosis affecting an estimated 40-60% of patients, and reducing their quality of life. We reviewed the epidemiology and pathophysiology of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis, summarize non-pharmacologic and pharmacological treatment strategies and discuss the impact of novel disease-modifying treatments such as transthyretin stabilizers (diflunisal, tafamidis) and RNA interference agents (patisiran, inotersen).
METHODS
Literature review.
RESULTS
Orthostatic hypotension in patients with hereditary transthyretin amyloidosis can be a consequence of heart failure due to amyloid cardiomyopathy or volume depletion due to diarrhea or drug effects. When none of these circumstances are apparent, orthostatic hypotension is usually neurogenic, i.e., caused by impaired norepinephrine release from sympathetic postganglionic neurons, because of neuronal amyloid fibril deposition.
CONCLUSIONS
When recognized, neurogenic orthostatic hypotension can be treated. Discontinuation of potentially aggravating medications, patient education and non-pharmacologic approaches should be applied first. Droxidopa (Northera), a synthetic norepinephrine precursor, has shown efficacy in controlled trials of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis and is now approved in the US and Asia. Although they may be useful to ameliorate autonomic dysfunction in hereditary TTR amyloidosis, the impact of disease-modifying treatments on neurogenic orthostatic hypotension is still uninvestigated.
Topics: Amyloid Neuropathies, Familial; Humans; Hypotension, Orthostatic
PubMed: 31452021
DOI: 10.1007/s10286-019-00623-x -
Journal of the American Medical... Dec 2021Orthostatic hypotension (OH) and orthostatic intolerance symptoms are common in older community-dwelling adults and are associated with reduced quality of life and... (Observational Study)
Observational Study
OBJECTIVES
Orthostatic hypotension (OH) and orthostatic intolerance symptoms are common in older community-dwelling adults and are associated with reduced quality of life and detrimental health outcomes. This study aimed to determine the prevalence, co-occurrence and determinants of OH and orthostatic intolerance symptoms in geriatric rehabilitation inpatients.
DESIGN
Observational, longitudinal cohort, "REStORing the health of acutely unwell adulTs" (RESORT).
SETTING AND PARTICIPANTS
Geriatric rehabilitation inpatients (n = 1505) of a tertiary teaching hospital in Melbourne, Australia.
METHODS
OH was defined as a drop in systolic blood pressure by ≥20 mm Hg and/or diastolic blood pressure by ≥10 mm Hg within three 3 of moving from supine to a standing or sitting position. Symptoms were recorded following the 3 minutes. Determinants included sociodemographics, reason for admission, cognitive health, nutritional status, physical performance, frailty, morbidity, medication use, length of stay (LOS), and number of geriatric conditions. Independent t-tests, Mann-Whitney U tests or χ tests were used to analyze differences between inpatients with and without OH and symptoms. Logistic regression analyses were used to ascertain the determinants.
RESULTS
OH and orthostatic intolerance symptoms were prevalent in 19.8% (standing: 21.4%, sitting: 18.2%) and 22.6% (standing: 25.0%, sitting: 20.2%) of inpatients, respectively. Symptoms were reported by 32.8% of inpatients with OH and 20.1% without OH. Higher number of comorbidities and geriatric conditions, low functional independence, and longer LOS were determinants of OH. Female gender, higher number of morbidities and geriatric conditions, low functional independence, depression risk, poor physical performance, musculoskeletal and "other" reasons for admission, and long LOS during geriatric rehabilitation were determinants of symptoms.
CONCLUSIONS AND IMPLICATIONS
OH and orthostatic intolerance symptoms occur in one-fifth of geriatric rehabilitation inpatients, however, the co-occurrence is low and determinants differ. Poorer health in patients with orthostatic intolerance symptoms highlights the need to assess symptoms in clinical practice, independent of an OH diagnosis.
Topics: Aged; Blood Pressure; Female; Humans; Hypotension, Orthostatic; Inpatients; Orthostatic Intolerance; Prevalence; Quality of Life
PubMed: 34478695
DOI: 10.1016/j.jamda.2021.08.014 -
International Journal of Cardiology.... Mar 2021Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this... (Review)
Review
BACKGROUND
Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this systematic review was to determine the prevalence of orthostatic intolerance symptoms in older adults with initial orthostatic hypotension.
METHODS
MEDLINE (from 1946), EMBASE (from 1974) and Cochrane were searched to December 6th 2019 using the terms "initial orthostatic hypotension", "postural hypotension" and "older adults". Study selection involved the following criteria: published in English; mean or median age 65 years and diagnosis of initial orthostatic hypotension encompassed a decrease in systolic blood pressure by ≥ 40 mmHg and/or diastolic blood pressure by ≥ 20 mmHg within a maximum of 1 min following a postural change.
RESULTS
Of 8311 articles, 12 articles reporting initial orthostatic hypotension prevalence in 3446 participants with a mean age of 75 (6 SD) years (56.5% female) were included. Five initial orthostatic hypotension definition variations were utilised and symptoms were reported in six articles (968 participants, mean age 73.4 (6.1 SD) years, 56% female). The prevalence of symptoms in older adults with initial orthostatic hypotension ranged from 24 to 100% and was dependent on variations in timing or the inclusion of symptoms in the initial orthostatic hypotension definition.
CONCLUSIONS
Where orthostatic intolerance symptoms were reported, a large proportion of older adults with a diagnosis of initial orthostatic hypotension were symptomatic. However, the literature on initial orthostatic hypotension and orthostatic intolerance symptoms is scarce and a variety of definitions of initial orthostatic hypotension are utilised.
PubMed: 33884364
DOI: 10.1016/j.ijchy.2020.100071 -
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 -
Journal of the Neurological Sciences Jun 2024Orthostatic hypotension (OH) is associated with an increased risk of dementia, potentially attributable to cerebral hypoperfusion. We investigated which patterns and...
BACKGROUND
Orthostatic hypotension (OH) is associated with an increased risk of dementia, potentially attributable to cerebral hypoperfusion. We investigated which patterns and characteristics of OH are related to cognition or to potentially underlying structural brain injury in hemodynamically impaired patients and healthy reference participants.
METHODS
Participants with carotid occlusive disease or heart failure, and reference participants from the Heart-Brain Connection Study underwent OH measurements, neuropsychological assessment and brain MRI. We analyzed the association between OH, global cognitive functioning, white matter hyperintensity (WMH) volume and brain parenchymal fraction with linear regression. We stratified by participant group, severity and duration of OH, chronotropic incompetence and presence of orthostatic symptoms.
RESULTS
Of 337 participants (mean age 67.3 ± 8.8 years, 118 (35.0%) women), 113 (33.5%) had OH. Overall, presence of OH was not associated with cognitive functioning (β: -0.12 [-0.24-0.00]), but we did observe worse cognitive functioning in those with severe OH (≥ 30/15 mmHg; β: -0.18 [-0.34 to -0.02]) and clinically manifest OH (β: -0.30 [-0.52 to -0.08]). These associations did not differ significantly by OH duration or chronotropic incompetence, and were similar between patient groups and reference participants. Similarly, both severe OH and clinically manifest OH were associated with a lower brain parenchymal fraction, and severe OH also with a somewhat higher WMH volume.
CONCLUSIONS
Severe OH and clinically manifest OH are associated with worse cognitive functioning. This supports the notion that specific patterns and characteristics of OH determine its impact on brain health.
Topics: Humans; Female; Hypotension, Orthostatic; Male; Aged; Magnetic Resonance Imaging; Brain; Middle Aged; Neuropsychological Tests; Hemodynamics; Cognition; White Matter; Heart Failure
PubMed: 38723328
DOI: 10.1016/j.jns.2024.123026