Orthostatic hypotension and symptomatic subclinical orthostatic hypotension increase risk of cognitive impairment: an integrated evidence review and analysis of a large older adult hypertensive cohort.
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ABSTRACT: Aims
Systematically reviewing the literature found orthostatic hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall.Method and results
Participants aged ≥80 years, with hypertension, were from the Hypertension in the Very Elderly Trial (HYVET) cohort. Orthostatic hypotension was defined as a fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position. Subclinical orthostatic hypotension with symptoms (SOH) was defined as a fall
SUBMITTER: Peters R
PROVIDER: S-EPMC6122132 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDroxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460).MethodsEfficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined.ResultsDroxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies.ConclusionsDroxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials.Trial registrationClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.
| S-EPMC5427571 | biostudies-literature
Project description:BackgroundBoth measured orthostatic hypotension and symptomatic orthostasis are common in PD but their relationship is unclear.ObjectiveWe aim to determine clinical predictors of both measured orthostatic hypotension and reported symptomatic orthostasis in PD, including the impact of "on"/"off" status and seasons, and to determine the correlation between measured OH and subjective orthostasis.MethodsWe analyzed BP readings, demographic and disease state predictors for both 1. Measured blood pressure OH criteria and 2. The subjective report of orthostatic symptoms, using logistic regression analyses from an initial "on" motor state clinical visit in all PD patient visits. We then correlated subjective orthostasis symptoms with BP measurements. We also compared intra-subject BP measures in PD patients seen in both "on" and "off" states, and when seen "on" in both summer and winter.Results723 consecutive visits over 2 years identified 250 unique PD individuals. Subjective orthostasis was reported by 44 % and "on" measured OH (>20 drop in SBP or 10 DBP upon standing) was seen in 30 %. Measured OH did not significantly correlate with any assessed clinical feature or specific medicine. Subjective orthostasis correlated most with older age, dementia, and L-dopa use. Subjective orthostasis correlated equally with absolute lower measured standing SBP and the drop in SBP from sitting to standing. Compared to the "off" state, "on" state showed lower sitting and standing SBP, more than DBP, but no significant change in BP drop upon standing. Seasons did not impact measured BP.ConclusionsBoth OH and symptomatic orthostasis are common. Dopaminergic medications did not cause traditionally defined OH but lowered all SBP (sitting and standing) and thus reduced pulse pressure, possibly by increasing arteriole compliance simply by reducing motor tone, as this BP-lowering effect may be specific to Parkinsonism.
| S-EPMC11298931 | biostudies-literature
Project description:BackgroundInitial 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.MethodsMEDLINE (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.ResultsOf 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.ConclusionsWhere 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.
| S-EPMC7803043 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that orthostatic hypotension (OH) might cause cerebral hypoperfusion and injury, we examined the longitudinal relationship between OH or orthostatic symptoms and incident neurologic outcomes in a community population of older adults.MethodsCardiovascular Health Study participants (≥65 years) without dementia or stroke had blood pressure (BP) measured after lying down for 20 minutes and after standing 3 for minutes. Participants reported dizziness immediately upon standing and any dizziness in the past 2 weeks. OH was defined as a drop in standing systolic/diastolic BP ≥20/≥10 mm Hg. We determined the association between OH or dizziness with (1) MRI brain findings (ventricular size, white matter hyperintensities, brain infarcts) using linear or logistic regression, (2) cognitive function (baseline and over time) using generalized estimating equations, and (3) prospective adjudicated events (dementia, stroke, death) using Cox models. Models were adjusted for demographic characteristics and OH risk factors. We used multiple imputation to account for missing OH or dizziness (n = 534).ResultsPrior to imputation, there were 5,007 participants (mean age 72.7 ± 5.5 years, 57.6% women, 10.9% Black, 16% with OH). OH was modestly associated with death (hazard ratio [HR] 1.11; 95% confidence interval 1.02-1.20), but not MRI findings, cognition, dementia, or stroke. In contrast, dizziness upon standing was associated with lower baseline cognition (β = -1.20; -1.94 to -0.47), incident dementia (HR 1.32; 1.04-1.62), incident stroke (HR 1.22; 1.06-1.41), and death (HR 1.13; 1.06-1.21). Similarly, dizziness over the past 2 weeks was associated with higher white matter grade (β = 0.16; 0.03-0.30), brain infarcts (OR 1.31; 1.06-1.63), lower baseline cognition (β = -1.18; -2.01 to -0.34), and death (HR 1.13; 1.04-1.22).ConclusionsDizziness was more consistently associated with neurologic outcomes than OH 3 minutes after standing. Delayed OH assessments may miss pathologic information related to cerebral injury.
| S-EPMC7682840 | biostudies-literature
Project description:BACKGROUND:Although orthostatic hypotension (OH) is a well-recognized manifestation of neuropathy and hypovolemia, its contribution to cardiovascular disease (CVD) risk is controversial. METHODS AND RESULTS:Participants with OH, defined as a decrease in blood pressure (systolic ?20 mm Hg or diastolic ?10 mm Hg) from the supine to standing position, were identified during the first visit of the ARIC (Atherosclerosis Risk in Communities) Study (1987-1989) within 2 minutes of standing. All participants were followed up for the development of myocardial infarction, heart failure, stroke, fatal coronary heart disease (CHD), any CHD (combination of silent, nonfatal, and fatal CHD or cardiac procedures), and all-cause mortality. Participants were assessed for carotid intimal thickness and plaque during the first visit. Detectable high-sensitivity troponin T (?5 ng/L) and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide; ?100 pg/mL) were determined in blood collected during the second visit (1990-1992). All associations were adjusted for known CVD risk factors. In 9139 participants (57% women; 23% black; mean age, 54±5.7 years), 3% had OH. During follow-up (median, 26 years), OH was associated with myocardial infarction (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.44-2.46), congestive heart failure (HR, 1.65; 95% CI, 1.34-2.04), stroke (HR, 1.83; 95% CI, 1.35-2.48), fatal CHD (HR, 2.77; 95% CI, 1.93-3.98), any CHD (HR, 2.00; 95% CI, 1.64-2.44), and all-cause mortality (HR, 1.68; 95% CI, 1.45-1.95). OH was also associated with carotid intimal thickness (?, 0.05 mm; 95% CI, 0.04-0.07 mm), carotid plaque (odds ratio, 1.51; 95% CI, 1.18-1.93), detectable high-sensitivity troponin T (odds ratio, 1.49; 95% CI, 1.16-1.93), and elevated NT-proBNP (odds ratio, 1.92; 95% CI, 1.48-2.49). CONCLUSIONS:OH identified in community-dwelling middle-aged adults was associated with future CVD events and subclinical CVD. Further research is necessary to establish a causal role for OH in the pathogenesis of CVD.
| S-EPMC6015335 | biostudies-literature
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| S-EPMC8357050 | biostudies-literature
Project description:PurposeIn neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension.MethodsA multicenter ascending-dose trial (range 1-20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety.ResultsThirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6-52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration.ConclusionAmpreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure.Trial registrationNCT02705755 (first posted March 10, 2016).
| S-EPMC8629777 | biostudies-literature
Project description:To examine the association of orthostatic hypotension with incident heart failure (HF) in older adults.Of the 5,273 community-dwelling adults aged 65 years and older free of baseline prevalent HF in the Cardiovascular Health Study, 937 (18%) had orthostatic hypotension, defined as ?20 mmHg drop in systolic or ?10 mmHg drop in diastolic blood pressure from supine to standing position at 3 minutes. Of the 937, 184 (20%) had symptoms of dizziness upon standing and were considered to have symptomatic orthostatic hypotension. Propensity scores for orthostatic hypotension were estimated for each of the 5,273 participants and were used to assemble a cohort of 3,510 participants (883 participants with and 2,627 participants without orthostatic hypotension) who were balanced on 40 baseline characteristics. Cox regression models were used to estimate the association of orthostatic hypotension with centrally adjudicated incident HF and other outcomes during 13 years of follow-up.Participants (n = 3,510) had a mean (±standard deviation) age of 74 (±6) years, 58% were women, and 15% nonwhite. Incident HF occurred in 25% and 21% of matched participants with and without orthostatic hypotension, respectively (hazard ratio, 1.24; 95% confidence interval, 1.06-1.45; p = .007). Among matched participants, hazard ratios for incident HF associated with symptomatic (n = 173) and asymptomatic (n = 710) orthostatic hypotension were 1.57 (95% confidence interval, 1.16-2.11; p = .003) and 1.17 (95% confidence interval, 0.99-1.39; p = .069), respectively.Community-dwelling older adults with orthostatic hypotension have higher independent risk of developing new-onset HF, which appeared to be more pronounced in those with symptomatic orthostatic hypotension.
| S-EPMC4038247 | biostudies-literature
Project description:BackgroundVenlafaxine, a serotonin-norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with adverse blood pressure (BP) effects.MethodsAdults ⩾60 years of age in a current major depressive episode were treated in a protocolized manner with venlafaxine XR; 429 participants were treated for 8-16 weeks with a daily dose up to 300 mg to achieve remission from depression. Cardiac measures included sitting and standing BP and heart rate.ResultsOf participants who were normotensive at baseline, 6.5% were found to have elevated BP during the study (1.9% <225 mg/day; 9.8% ⩾225 mg/day). There was no significant change in mean BP in the overall sample, or in the subgroup treated with doses ⩾225 mg/day. Additionally, 20.1% of the participants who did not have orthostatic hypotension at baseline were found to have orthostatic hypotension (16.8% <225 mg/day; 22.4% ⩾225 mg/day). Participants with new-onset orthostatic hypotension were significantly more likely to fall than the other participants.ConclusionA large proportion of older adults treated with venlafaxine experience orthostatic hypotension, putting them at risk for falls. A smaller proportion experience elevated BP. Older patients prescribed venlafaxine, particularly at high doses, should be advised and counseled about these adverse effects.
| S-EPMC8200287 | biostudies-literature
Project description:PURPOSE OF REVIEW:This article reviews the management of orthostatic hypotension with emphasis on neurogenic orthostatic hypotension. RECENT FINDINGS:Establishing whether the cause of orthostatic hypotension is a pathologic lesion in sympathetic neurons (ie, neurogenic orthostatic hypotension) or secondary to other medical causes (ie, non-neurogenic orthostatic hypotension) can be achieved by measuring blood pressure and heart rate at the bedside. Whereas fludrocortisone has been extensively used as first-line treatment in the past, it is associated with adverse events including renal and cardiac failure and increased risk of all-cause hospitalization. Distinguishing whether neurogenic orthostatic hypotension is caused by central or peripheral dysfunction has therapeutic implications. Patients with peripheral sympathetic denervation respond better to norepinephrine agonists/precursors such as droxidopa, whereas patients with central autonomic dysfunction respond better to norepinephrine reuptake inhibitors. SUMMARY:Management of orthostatic hypotension is aimed at improving quality of life and reducing symptoms rather than at normalizing blood pressure. Nonpharmacologic measures are the key to success. Pharmacologic options include volume expansion with fludrocortisone and sympathetic enhancement with midodrine, droxidopa, and norepinephrine reuptake inhibitors. Neurogenic supine hypertension complicates management of orthostatic hypotension and is primarily ameliorated by avoiding the supine position and sleeping with the head of the bed elevated.
| S-EPMC7339914 | biostudies-literature