Dataset Information

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.

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 ConclusionOrthostatic hypotension indicates an increased risk of dementia and cognitive decline. SOH may also be considered a risk factor, at least in older hypertensive adults. Questions remain regarding the mechanisms and whether interventions to reduce impact of OH could protect cognition.

SUBMITTER: Peters R

PROVIDER: S-EPMC6122132 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

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.

Peters Ruth R Anstey Kaarin J KJ Booth Andrew A Beckett Nigel N Warwick Jane J Antikainen Riitta R Rockwood Kenneth K Peters Jean J Bulpitt Christopher J CJ

European heart journal 20180901 33

<h4>Aims</h4>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.<h4>Method and results</h4>Participants aged ≥80 years, with hypertension, were from the Hypertension in the Ver ...[more]

PMID: 30052878

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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.

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.

Project description:Although orthostatic hypotension (OH) is a well-recognized manifestation of neuropathy and hypovolemia, its contribution to cardiovascular disease (CVD) risk is controversial. 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 (β, 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). 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.

Dataset Information

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.

Aims

Method and results

Publications

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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