Reply to: Comment on: Comparison of supine and seated orthostatic hypotension assessments and their association with falls and orthostatic symptoms.
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SUBMITTER: Juraschek SP
PROVIDER: S-EPMC10189164 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Reply to: Comment on: Comparison of supine and seated orthostatic hypotension assessments and their association with falls and orthostatic symptoms.
Juraschek Stephen P SP Appel Lawrence J LJ Lipsitz Lewis A LA Miller Edgar R ER
Journal of the American Geriatrics Society 20221110 2
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Project description:BackgroundOrthostatic hypotension (OH) based on a change from seated-to-standing blood pressure (BP) is often used interchangeably with supine-to-standing BP.MethodsThe Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a randomized trial of vitamin D3 supplementation and fall in adults aged ≥70 years at high risk of falls. OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mmHg, measured at pre-randomization, 3-, 12-, and 24-month visits with each of 2 protocols: seated-to-standing and supine-to-standing. Participants were asked about orthostatic symptoms, and falls were ascertained via daily fall calendar, ad hoc reporting, and scheduled interviews.ResultsAmong 534 participants with 993 paired supine and seated assessments (mean age 76 ± 5 years, 42% women, 18% Black), mean baseline BP was 130 ± 19/68 ± 11 mmHg; 62% had a history of high BP or hypertension. Mean BP increased 3.5 (SE, 0.4)/2.6 (SE, 0.2) mmHg from sitting to standing, but decreased with supine to standing (mean change: -3.7 [SE, 0.5]/-0.8 [SE, 0.3] mmHg; P-value < 0.001). OH was detected in 2.1% (SE, 0.5) of seated versus 15.0% (SE, 1.4) of supine assessments (P < 0.001). While supine and seated OH were not associated with falls (HR: 1.55 [0.95, 2.52] vs 0.69 [0.30, 1.58]), supine systolic OH was associated with higher fall risk (HR: 1.77 [1.02, 3.05]). Supine OH was associated with self-reported fainting, blacking out, seeing spots and room spinning in the prior month (P-values < 0.03), while sitting OH was not associated with any symptoms (P-values ≥ 0.40).ConclusionSupine OH was more frequent, associated with orthostatic symptoms, and potentially more predictive of falls than seated OH.
| S-EPMC9378443 | biostudies-literature
Project description:Orthostatic hypotension (OH) often co-exists with hypertension. As increasing age affects baroreflex sensitivity, it loses its ability to reduce blood pressure when lying down. Therefore, supine hypertension may be an important indicator of baroreflex function. This study examines (i) the association between OH and future falls in community-dwelling older adults and (ii) if these associations persist in those with co-existing OH and baseline hypertension, measured supine and seated. Data from 1500 community-dwelling adults aged ≥65 years from The Irish Longitudinal Study on Ageing (TILDA) were used. Continuous beat-to-beat blood pressure was measured using digital photoplethysmography during an active stand procedure with OH defined as a drop in systolic blood pressure (SBP) ≥20 mmHg and/or ≥10 mm Hg in diastolic blood pressure (DBP) within 3 minutes of standing. OH at 40 seconds (OH40) was used as a marker of impaired early stabilisation and OH sustained over the second minute (sustained OH) was used to indicate a more persistent deficit, similar to traditional OH definitions. Seated and supine hypertension were defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Modified Poisson models were used to estimate relative risk of falls (recurrent, injurious, unexplained) and syncope occurring over four year follow-up. OH40 was independently associated with recurrent (RR = 1.30, 95% CI = 1.02,1.65), injurious (RR = 1.43, 95% CI = 1.13,1.79) and unexplained falls (RR = 1.55, 95% CI = 1.13,2.13). Sustained OH was associated with injurious (RR = 1.55, 95% CI = 1.18,2.05) and unexplained falls (RR = 1.63, 95% CI = 1.06,2.50). OH and co-existing hypertension was associated with all falls outcomes but effect sizes were consistently larger with seated versus supine hypertension. OH, particularly when co-existing with hypertension, was independently associated with increased risk of future falls. Stronger effect sizes were observed with seated versus supine hypertension. This supports previous findings and highlights the importance of assessing orthostatic blood pressure behaviour in older adults at risk of falls and with hypertension. Observed associations may reflect underlying comorbidities, reduced cerebral perfusion or presence of white matter hyperintensities.
| S-EPMC8158994 | biostudies-literature
Project description:ObjectiveTo test whether the plasma levels of norepinephrine (NE) in patients with neurogenic orthostatic hypotension (nOH) predict their pressor response to droxidopa.MethodsThis was an observational study, which included patients with nOH. All patients had standardized autonomic function testing including determination of venous plasma catecholamine levels drawn through an indwelling catheter while resting supine. This was followed by a droxidopa titration with 100 mg increments in successive days until relief of symptoms, side effects, or the maximum dose of 600 mg was reached. No response was defined as an increase of <10 mm Hg in systolic blood pressure (BP) after 3-minute standing 1 hour after droxidopa administration. Nonlinear regression models were used to determine the relationship between BP response and plasma NE levels.ResultsWe studied 20 patients with nOH due to Parkinson disease, pure autonomic failure, multiple system atrophy, or autoimmune autonomic neuropathies. Their supine plasma NE levels ranged from 44 to 850 pg/mL. Lower supine plasma NE levels were associated with greater pressor effect 1 hour after dose (R2 = 0.49) and higher standing BP (R2 = 0.45). Patients with no pressor response to droxidopa had higher NE levels (382 ± 100 vs 115 ± 20 pg/mL, p = 0.0014). A supine NE level of <219.5 pg/mL had 83% sensitivity and 93% specificity to predict a pressor response (area under the curve = 0.95, p = 0.0023).ConclusionsIn patients with nOH, lower supine resting plasma NE levels are associated with a greater pressor effect of droxidopa treatment. This finding should help identify patients with nOH most likely to respond to standard doses of droxidopa.Classification of evidenceThis study provides Class I evidence that lower supine plasma NE levels accurately identify patients with nOH more likely to have a greater pressor effect from droxidopa.
| S-EPMC6202942 | biostudies-literature
Project description:BackgroundMultiple definitions are used to characterize orthostatic hypotension (OH), but the degree to which these definitions correspond with orthostatic symptoms is unknown.MethodsWe analyzed data from African American Study of Kidney Disease and Hypertension (AASK), a randomized trial of African Americans with hypertension and kidney disease, to characterize the relationship between OH definitions and self-reported syncope, dizziness, or light-headedness. Orthostatic changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), or heart rate (HR) were determined each visit after standing 2:45 minutes. OH was defined using the consensus definition (a drop in SBP ≥20 mm Hg or DBP ≥10 mm Hg) or an often used clinical substitute based on HR (an increase ≥20 bpm).ResultsAmong 1,094 participants (mean age 54.5 ± 10.7 years, 38.9% female), there were 52,636 visits (mean 48/person). Mean resting SBP, DBP, and HR at baseline were 147.7 ± 22.3 mm Hg, 92.2 ± 13.4 mm Hg, and 71.1 ± 11.7 bpm, respectively. While the OH consensus definition was associated with syncope (odds ratio 2.49; 95% confidence interval: 1.13, 5.51), dizziness (1.89; 1.53, 2.33), and light-headedness (1.84; 1.52, 2.23), the clinical HR definition was only associated with dizziness (1.28; 1.07, 1.52). None of the OH components (SBP, DBP, or HR) reflected a natural threshold in the prevalence of symptoms; definitions using each of the 3 components were highly specific (≥96%) with low sensitivity (1-5%).ConclusionsWhile the consensus definition was more strongly associated with symptoms, OH definitions did not reflect natural thresholds in symptoms and were insensitive. This implies that the absence of OH using either consensus or clinical definitions does not exclude orthostatic symptoms, which has implications for evaluating clinical events like falls.Clinical trials registrationTrial Number: NCT01206062 (clinicaltrials.gov).
| S-EPMC5946838 | biostudies-literature
Project description:ObjectiveWe sought to test the hypothesis that technology could predict the risk of falls in Parkinson's disease (PD) patients with orthostatic hypotension (OH) with greater accuracy than in-clinic assessment.MethodsTwenty-six consecutive PD patients with OH underwent clinical (including home-like assessments of activities of daily living) and kinematic evaluations of balance and gait as well as beat-to-beat blood pressure (BP) monitoring to estimate their association with the risk of falls. Fall frequency was captured by a diary collected prospectively over 6 months. When applicable, the sensitivity, specificity, and diagnostic accuracy were measured using the area under the receiver operating characteristics curve (AUC). Additional in-clinic assessments included the OH Symptom Assessment (OHSA), the OH Daily Activity Score (OHDAS), and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS).ResultsThe prevalence of falls was 53.8% over six months. There was no association between the risk of falls and test of gait and postural stability (p ≥ 0.22) or home-like activities of daily living (p > 0.08). Conversely, kinematic data (waist sway during time-up-and-go, jerkiness, and centroidal frequency during postural sway with eyes-opened) predicted the risk of falls with high sensitivity and specificity (> 80%; AUC ≥ 0.81). There was a trend for higher risk of falls in patients with orthostatic mean arterial pressure ≤ 75 mmHg.ConclusionsKinematic but not clinical measures predicted falls in PD patients with OH. Orthostatic mean arterial pressure ≤ 75 mmHg may represent a hemodynamic threshold below which falls become more prevalent, supporting the aggressive deployment of corrective measures.
| S-EPMC7914136 | biostudies-literature
Project description:BackgroundSupine hypertension affects most patients with orthostatic hypotension (OH) due to autonomic failure, but it is often untreated for fear of worsening OH. We hypothesized that increasing intrathoracic pressure with continuous positive airway pressure (CPAP) had a Valsalva-like blood-pressure-lowering effect that could be used to treat nocturnal supine hypertension in these patients, while reducing nocturnal pressure diuresis and improving daytime OH.MethodsIn Protocol 1, we determined the acute hemodynamic effects of increasing levels of CPAP (0, 4, 8, 12, and 16 cm H2O, 3 minutes each) in 26 patients with autonomic failure and supine hypertension studied while awake and supine. In Protocol 2 (n=11), we compared the effects of overnight therapy with CPAP (8-12 cm H2O for 8 hours) versus placebo on nocturnal supine hypertension, nocturnal diuresis and daytime OH in a 2-night crossover study.ResultsIn Protocol 1, acute CPAP (4-16 cm H2O) decreased systolic blood pressure in a dose-dependent manner (maximal drop 22±4 mmHg with CPAP 16) due to reductions in stroke volume (-16+3%) and cardiac output (-14±3%). Systemic vascular resistance and heart rate remained unchanged. In Protocol 2, overnight CPAP lowered nighttime systolic blood pressure (maximal change -23±5 versus placebo -1±7 mmHg; P=0.023) and was associated with lower nighttime diuresis (609±84 versus placebo 1004±160 mL; P=0.004) and improved morning orthostatic tolerance (AUC upright SBP 642±121 versus placebo 410±109 mmHg*min; P=0.014).ConclusionsCPAP is a novel nonpharmacologic approach to treat the supine hypertension of autonomic failure while improving nocturia and daytime OH.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT03312556.
| S-EPMC10128890 | biostudies-literature
Project description:Familial dysautonomia is an inherited autonomic disorder with afferent baroreflex failure. We questioned why despite low blood pressure standing, surprisingly few familial dysautonomia patients complain of symptomatic hypotension or have syncope. Using transcranial Doppler ultrasonography of the middle cerebral artery, we measured flow velocity (mean, peak systolic, and diastolic), area under the curve, pulsatility index, and height of the dictrotic notch in 25 patients with familial dysautonomia and 15 controls. In patients, changing from sitting to a standing position, decreased BP from 124 ± 4/64 ± 3 to 82 ± 3/37 ± 2 mmHg (p < 0.0001, for both). Despite low BP, all patients denied orthostatic symptoms. Middle cerebral artery velocity fell minimally, and the magnitude of the reductions were similar to those observed in healthy controls, in whom BP upright did not fall. While standing, patients had a greater fall in cerebrovascular resistance (p < 0.0001), an increase in pulsatility (p < 0.0001), and a deepening of the dicrotic notch (p = 0.0010), findings all consistent with low cerebrovascular resistance. No significant changes occurred in controls. Patients born with baroreflex deafferentation retain the ability to buffer wide fluctuations in BP and auto-regulate cerebral blood flow. This explains how they can tolerate extremely low BPs standing that would otherwise induce syncope.
| S-EPMC5531340 | biostudies-literature
Project description:Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure (dtDBP) between supine and standing, and OH is associated with a failure of the cardiovascular reflex to maintain blood pressure on standing from a supine position. To understand the underlying genetic factors for OH traits (OH, dtSBP, and dtDBP), genome-wide association studies (GWASs) using 333,651 single nucleotide polymorphisms (SNPs) were conducted separately for two population-based cohorts, Ansung (n = 3,173) and Ansan (n = 3,255). We identified 8 SNPs (5 SNPs for dtSBP and 3 SNPs for dtDBP) that were repeatedly associated in both the Ansung and Ansan cohorts and had p-values of <1 × 10(-5) in the meta-analysis. Unfortunately, the SNPs of the OH case control GWAS did not pass our p-value criteria. Four of 8 SNPs were located in the intergenic region of chromosome 2, and the nearest gene (CTNNA2) was located at 1 Mb of distance. CTNNA2 is a linker between cadherin adhesion receptors and the actin cytoskeleton and is essential for stabilizing dendritic spines in rodent hippocampal neurons. Although there is no report about the function in blood pressure regulation, hippocampal neurons interact primarily with the autonomic nervous system and might be related to OH. The remaining SNPs, rs7098785 of dtSBP trait and rs6892553, rs16887217, and rs4959677 of dtDBP trait were located in the PIK3AP1 intron, ACTBL2-3' flanking, STAR intron, and intergenic region, respectively, but there was no clear functional link to blood pressure regulation.
| S-EPMC3794085 | biostudies-literature
Project description:ObjectivesDroxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo.MethodsStudy NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups.ResultsA total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients.ConclusionsTreatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed.
| S-EPMC5028156 | biostudies-literature
Project description:Hypertension treatment has been implicated in falls, syncope, and orthostatic hypotension (OH), common events among older adults. Whether the choice of antihypertensive agent influences the risk of falls, syncope, and OH in older adults is unknown. ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) was a randomized clinical trial that compared the effects of hypertension first-step therapy on fatal coronary heart disease or nonfatal myocardial infarction (1994-2002). In a subpopulation of ALLHAT participants, age 65 years and older, we determined the relative risk of falls, syncope, OH, or a composite based on Centers for Medicare and Medicaid Services and Veterans Affairs claims, using Cox regression. We also determined the adjusted association of self-reported atenolol use (ascertained at the 1-month visit for indications other than hypertension) on outcomes in Cox models adjusted for age, sex, and race. Among 23 964 participants (mean age 69.8±6.8 years, 45% women, 31% non-Hispanic black) followed for a mean of 4.9 years, we identified 267 falls, 755 syncopes, 249 OH, and 1157 composite claims. There were no significant differences in the cumulative incidences of events across randomized drug assignments. However, amlodipine increased risk of falls during the first year of follow-up compared with chlorthalidone (hazard ratio [95% CI]: 2.24 [1.06-4.74]; P=0.03) or lisinopril (hazard ratio [95% CI]: 2.61 [1.03-6.72]; P=0.04). Atenolol use (N=928) was not associated with any of the 3 individual or composite claims. In older adults, the choice of antihypertensive agent had no effect on risk of fall, syncope, or OH long-term. However, amlodipine increased risk of falls within 1 year of initiation. These short-term findings require confirmation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.
| S-EPMC6739183 | biostudies-literature