Orthostatic Intolerance in Children With Long COVID Utilizing a 10-Minute Passive Standing Test.

Despite there being a wide variety of symptoms reported in pediatric long COVID, one condition that has become increasingly recognized is orthostatic intolerance (OI), which can cause significant morbidity, limiting activities of daily living. This study examines rates of OI in 92 children with long COVID who underwent a bedside passive standing test in a pediatric post-COVID-19 rehabilitation clinic. Seventy-one percent met criteria for an orthostatic condition, including postural orthostatic tachycardia syndrome (POTS), orthostatic tachycardia (OT), classic orthostatic hypotension (OH), delayed OH, and orthostatic hypertension. Our findings suggest that OI is common in pediatric long COVID, necessitating appropriate clinical screening and treatment.

Identification and treatment of midaortic syndrome in an adult patient with orthostatic tachycardia and hypertension: A case report.

Anatomical cardiovascular etiologies are less frequently investigated and identified in cases of orthostatic intolerance, which can have a profound impact on a patient's functional status. Here, we present a 26-year-old female with a recent diagnosis of hyperadrenergic postural orthostatic tachycardia and hypertension who was found to have diminished pedal pulses. Workup revealed an underlying midaortic syndrome that was then surgically corrected with resolution of symptoms. We discuss the epidemiology, presentation, and management of this rare condition, as well as its role in our patient's symptomatology.

Cardiopulmonary deconditioning and plasma volume loss are not sufficient to provoke orthostatic hypertension.

Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.

Association Between Orthostatic Hypertension and Frailty Among Older Patients With Hypertension.

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Orthostatic blood pressure changes do not influence cognitive outcomes following intensive blood pressure control.

BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

Preclinical Orthostatic Abnormalities May Predict Early Increase in Vascular Stiffness in Different Age Groups: A Pilot Study.

Clinical orthostatic hypotension (OH) and hypertension (OHT) are risk factors for arterial hypertension (AH) and cardiovascular diseases (CVD) and are associated with increased vascular stiffness. Preclinical OH and OHT are poorly understood. The main objective was to investigate preclinical orthostatic abnormalities and their association with increased vascular stiffness in different age groups of adults. A specially designed head-up tilt test standardized for hydrostatic column height was used to detect them. Three age groups of clinically healthy subjects were examined. In the group of young adults up to 30 years old, a significant predominance of orthostatic normotension (ONT) and an insignificant number of subjects with preclinical OH and OHT were found. In the age group over 45 years, compared to the group under 30 years, there was a twofold decrease in the proportion of individuals with ONT and a significant increase with preclinical OH and OHT. In all age groups, there was a significant orthostatic increase in vascular stiffness (as measured by the brachial-ankle pulse wave velocity (baPWV), which was recovered to the baseline level when returning to the supine position. Overall, subjects with preclinical OH and OHT had significantly higher baPWV values compared to those with ONT (p = 0.001 and p = 0.002, respectively), with all subjects having vascular stiffness values within normal age-related values.

Orthostatic hypotension and orthostatic hypertension are both associated with lower cognitive function: The S.AGES cohort.

BACKGROUND: Blood pressure (BP) postural changes, both orthostatic hypotension (OHYPO) and orthostatic hypertension (OHYPER) are common in older adults. Few studies have investigated their association with cognition, particularly for OHYPER, an emerging cardiovascular risk factor. We aimed to assess the association between OHYPO, OHYPER and cognition in non-institutionalized older subjects. METHODS: The S.AGES (Sujets ÂGES, Aged Subjects) cohort followed every 6 months for 3 years non-institutionalized subjects aged ≥65 years without dementia at inclusion, in France. OHYPO and OHYPER were respectively defined as a fall or an increase of ≥20 mmHg in systolic BP and/or ≥10 mmHg in diastolic BP after standing from a sitting position. Cognition was assessed using the Mini-Mental State Examination (MMSE). Linear mixed models were used for the analyses. RESULTS: Among the 3170 subjects included (mean age 78 years, 56% women), 209 (6.5%) had OHYPO and 226 (7.1%) had OHYPER at baseline. After adjustment for demographics, cardiovascular risk factors and disease, seated SBP/DBP and BP lowering treatment, mean MMSE was 0.52 point lower in participants with OHYPER compared to those with normal BP postural changes (ß adjusted [95% CI] = -0.52 [-0.96; -0.09], p = 0.02) and 0.50 point lower in participants with OHYPO compared to those with normal BP postural changes (ß adjusted [95% CI] = -0.50 [-0.95; -0.06], p = 0.03). Sensitivity analyses showed a dose-response relationship between OHYPO and cognition. CONCLUSION: Although the absolute differences in MMSE were small, both OHYPO and OHYPER were associated with lower cognition. Orthostatic BP measurements could help identify patients with risk of cognitive impairment. Further studies are needed to assess whether controlling orthostatic BP could be a promising interventional target in preserving cognition among older adults.

Antihypertensive medication class and diastolic orthostatic hypertension in older Caribbean adult patients.

In the Caribbean there is limited data on orthostatic hypertension (OHT) in elderly hypertensive patients with atherosclerotic disease who are at risk for cardiovascular events. The authors examined the association of antihypertensive classes of drugs with diastolic OHT in patients 60 year and older with hypertension and hyperlipidemia attending public primary care facilities. These relationships were evaluated in a cross-sectional study of hypertensive hyperlipidemic older patients (n = 400) to determine orthostatic changes in blood pressure based on seated to standing measurements. OHT was defined as an increase in systolic blood pressure of ≥20 mm Hg and/or increase in diastolic blood pressure of ≥10 mm Hg upon orthostasis at 3 min. Patients were categorized based on their orthostatic blood pressure response: orthostatic normotensive (n = 200) and blood pressure dysregulated (n = 200) of which 168 were diastolic OHT. Multivariable logistic regression models were used to examine associations of antihypertensive classes and diastolic OHT. Renin-angiotensin-aldosterone-system (RAAS) blockers were the most commonly prescribed (79.3%), followed by diuretics (DIUs) (61.6%), dihydropyridine calcium channel blockers (dCCBs) (53.8%), and beta-blockers (BBs) (19.3%). Most normotensive (76.0%) and diastolic OHT (75.0%) patients were prescribed two or more antihypertensive medications. Pharmaceutical prescription of triple combination RAAS blockers + dCCBs + DIUs (OR, 0.55; 95% CI, 0.31-0.99) or RAAS blockers + dCCBs + BBs (OR, 0.23; 95% CI, 0.06-0.92) showed a protective effect of diastolic OHT in analyses adjusted for age, sex, sitting diastolic blood pressure, and comorbidities. Our study suggests prescription of triple combination antihypertensive drugs of RAAS blockers + dCCBs + DIUs or RAAS blockers + dCCBs + BBs may reduce the likelihood of diastolic OHT.

Orthostatic hypertension and major adverse events: a systematic review and meta-analysis.

AIMS: The role of orthostatic hypertension (OHT) in cardiovascular disease (CVD) and mortality is unclear. We aimed to determine if this association exists through a systematic review and meta-analysis. METHODS AND RESULTS: Study inclusion criteria included: (i) any observational/interventional studies of participants aged ≥18 years (ii) that assessed the relationship between OHT and (iii) at least one outcome measure-all-cause mortality (primary outcome), coronary heart disease, heart failure, stroke/cerebrovascular disease, or neurocognitive decline. MEDLINE, EMBASE, Cochrane, clinicaltrials.gov, and PubMed were independently searched by two reviewers (inception-19 April 2022). Critical appraisals were conducted using the Newcastle-Ottawa Scale. Random-effects meta-analysis was performed using a generic inverse variance method, and narrative synthesis or pooled results were presented as an odds or hazards ratio (OR/HR), with 95% confidence interval. Twenty studies (n = 61 669; 47.3% women) were eligible, of which 13 were included in the meta-analysis (n = 55 456; 47.3% women). Median interquartile range (IQR) follow-up for prospective studies was 7.85 (4.12, 10.83) years. Eleven studies were of good quality, eight fair, and one poor. Relative to orthostatic normotension (ONT), systolic OHT (SOHT) was associated with a significant 21% greater risk of all-cause mortality (HR: 1.21, 1.05-1.40), 39% increased risk of CVD mortality based on two studies (HR: 1.39, 1.05-1.84), and near doubled odds of stroke/cerebrovascular disease (OR: 1.94, 1.52-2.48). The lack of association with other outcomes may be due to weak evidence or low statistical power. CONCLUSION: Patients with SOHT may have higher mortality risk relative to those with ONT and increased odds of stroke/cerebrovascular disease. Whether interventions can reduce OHT and improve outcomes should be explored.

Orthostatic hypertension (OHT) is defined as an arbitrary rise in upper (systolic) and/or lower (diastolic) blood pressure readings on standing. We performed a thorough literature search and combined the evidence of impact of OHT on future adverse events, including death, heart attack, heart failure, stroke, falls, and impaired cognition. We found the following:Twenty studies that investigated the association between OHT and future adverse events. Of these, 13 were eligible to be included in the combined evidence (meta-analysis). This formed a total sample of 61 669 participants (47.3% women), of which 55 456 (47.3% women) were included in the meta-analysis.Systolic OHT (SOHT) was associated with a significant 21% increased risk for death from any cause, a 39% greater risk of death due to heart and blood vessel disease and near doubled odds of stroke or brain vessel disease. Furthermore, three of four studies found a significant association between SOHT and impaired cognition. Diastolic OHT was not found to be associated with these outcomes. The lack of association with other outcomes investigated may be due to weak evidence.Eleven studies were of good quality, eight fair, and one poor. Differences in study design, study criteria, and study populations mean that the results need interpreting with caution. Future robust studies can build on this evidence to assess if treatment to reduce OHT would improve future outcomes.

Exaggerated blood pressure elevation in response to orthostatic challenge, a post-acute sequelae of SARS-CoV-2 infection (PASC) after hospitalization.

OBJECTIVE: Post-acute sequelae of SARS-COV-2 (PASC) are emerging as a major health challenge. Orthostatic intolerance secondary to autonomic failure has been found in PASC patients. This study investigated the effect of COVID-19 after recovery on blood pressure (BP) during the orthostatic challenge. RESEARCH DESIGN AND METHODS: Thirty-one out of 45 patients hospitalized due to COVID-19-related pneumonia that developed PASC and did not have hypertension at discharge were studied. They underwent a head-up tilt test (HUTT) at 10.8 ± 1.9 months from discharge. All met the PASC clinical criteria, and an alternative diagnosis did not explain the symptoms. This population was compared with 32 historical asymptomatic healthy controls. RESULTS: Exaggerated orthostatic blood pressure response (EOPR)/orthostatic hypertension (OHT) was detected in 8 out of 23 (34.7 %) patients, representing a significantly increased prevalence (7.67-fold increase p = 0.009) compared to 2 out of 32 (6.4 %) asymptomatic healthy controls matched by age, who underwent HUTT and were not infected with SARS-CoV-2. CONCLUSIONS: This prospective evaluation in patients with PASC revealed abnormal blood pressure rise during the orthostatic challenge, suggesting of autonomic dysfunction in a third of the studied subjects. Our findings support the hypothesis that EOPR/OHT may be a phenotype of neurogenic hypertension. Hypertension in PASC patients may adversely affect the cardiovascular burden in the world.

Consensus statement on the definition of orthostatic hypertension endorsed by the American Autonomic Society and the Japanese Society of Hypertension.

We propose a consensus definition of "an exaggerated orthostatic pressor response" in subjects in whom systolic blood pressure increases ≥20 mmHg when going from the supine to standing posture. This definition can be extended for seated to standing measurements. We reserve the term "orthostatic hypertension" if this pressor response leads to an upright systolic blood pressure ≥140 mmHg. We believe this consensus definition will help in the study of the pathophysiology, clinical impact, and potential treatment of these entities, and the identification of patients that are at greater cardiovascular risk.

Consensus statement on the definition of orthostatic hypertension endorsed by the American Autonomic Society and the Japanese Society of Hypertension.

We propose a consensus definition of "an exaggerated orthostatic pressor response" in subjects in whom systolic blood pressure increases ≥ 20 mmHg when going from supine to standing posture. This definition can be extended for seated to standing measurements. We reserve the term "orthostatic hypertension" for when this pressor response leads to an upright systolic blood pressure ≥ 140 mmHg. We believe this consensus definition will help in the study of the pathophysiology, clinical impact, and potential treatment of these entities, and identification of patients who are at greater cardiovascular risk.

Advances on pathogenesis and clinical diagnosis and treatment of orthostatic hypertension in children / 中国小儿急救医学

Orthostatic hypertension (OHT) is a common type of syncope in children, characterized by a highly complex neural reflex mechanism.It is closely associated with abnormalities in vascular endothelial function, disruptions in the renin-angiotensin-aldosterone system, and reduced or deficient levels of vitamin D. However, the exact pathogenesis of OHT remains unclear.OHT has a relatively high incidence and may be a risk factor for hypertension and cardiovascular diseases in children, significantly impacting their physical and mental health.Nevertheless, the etiology and treatment of OHT are still in the exploratory stage.Therefore, a thorough exploration of OHT is essential.This review provided a brief overview of the pathogenesis and clinical diagnosis and treatment of OHT.

Prevalence of orthostatic hypertension and its association with cerebrovascular diagnoses in patients with suspected TIA and minor stroke.

PURPOSE: We aimed to compare the rate of stroke, transient ischemic attack, and cerebrovascular disease diagnoses across groups of patients based on their orthostatic blood pressure response in a transients ischemic attack clinic setting. MATERIALS AND METHODS: We retrospectively analysed prospectively collected data from 3201 patients referred to a transient ischemic attack (TIA)/minor stroke outpatients clinic. Trained nurses measured supine and standing blood pressure using an automated blood pressure device and the patients were categorized based on their orthostatic blood pressure change into four groups: no orthostatic blood pressure rise, systolic orthostatic hypertension, diastolic orthostatic hypertension, and combined orthostatic hypertension. Then, four stroke physicians, who were unaware of patients' orthostatic BP response, assessed the patients and made diagnoses based on clinical and imaging data. We compared the rate of stroke, TIA, and cerebrovascular disease (either stroke or TIA) diagnoses across the study groups using Pearson's χ2 test. The effect of confounders was adjusted using a multivariate logistic regression analysis. RESULTS: Cerebrovascular disease was significantly less common in patients with combined systolic and diastolic orthostatic hypertension compared to the "no rise" group [OR = 0.56 (95% CI 0.35-0.89]. The odds were even lower among the subgroups of patients with obesity [OR = 0.31 (0.12-0.80)], without history of smoking [OR 0.34 (0.15-0.80)], and without hypertension [OR = 0.42 (95% CI 0.19-0.92)]. We found no significant relationship between orthostatic blood pressure rise with the diagnosis of stroke. However, the odds of TIA were significantly lower in patients with diastolic [OR 0.82 (0.68-0.98)] and combined types of orthostatic hypertension [OR = 0.54 (0.32-0.93)]; especially in patients younger than 65 years [OR = 0.17 (0.04-0.73)] without a history of hypertension [OR = 0.34 (0.13-0.91)], and patients who did not take antihypertensive therapy [OR = 0.35 (0.14-0.86)]. CONCLUSION: Our data suggest that orthostatic hypertension may be a protective factor for TIA among younger and normotensive patients.

Association between orthostatic blood pressure dysregulation and geriatric syndromes: a cross-sectional study.

BACKGROUND: Orthostatic blood pressure dysregulation, including orthostatic hypotension (OH) and orthostatic hypertension (OHT), is common in the elderly. The association between OH and, to a lesser extent, OHT with geriatric syndromes is controversial and little investigated. Our objective was to assess the association between orthostatic blood pressure dysregulation and geriatric syndromes in an ambulatory outpatient population. METHODS: This observational study included all outpatients for whom a one-visit comprehensive geriatric assessment was performed during a year. OH was defined as a decrease of at least 20 mmHg in systolic blood pressure (SBP) and/or 10 mmHg in diastolic blood pressure (DBP) after 1 or 3 min of standing. OHT was defined as an increase of more than 20 mmHg in SBP after 1 or 3 min of standing. Comorbidities, drugs regimen, a history of previous falls, nutritional, frailty, functional and cognitive status were compared between patients with OHT or OH and controls (NOR). RESULTS: Five hundred thirty patients (mean age: 82.9 ± 5.1 years) were included. 19.6% had an OH and 22.3% an OHT. OHT patients were more frequently female, had more diabetes and a lower resting SBP than patients with NOR. OH patients had a higher resting SBP than NOR. After adjusting for age, sex, resting SBP and diabetes, OHT was associated with a low walking speed (OR = 1.332[1.009-1.758]; p = 0.043) and severe cognitive impairment at MMSe score (OR = 1.629[1.070-1.956]; p = 0.016) compared to NOR. Conversely, OH was associated with a lower grip strength (p = 0.016) than NOR. CONCLUSION: OHT and OH are common in elderly but associated with different geriatric phenotypes.

Delirium and abnormal autonomic nervous system response to head-up tilt testing.

BACKGROUND: Delirium is a common condition with poorly understood pathophysiology. Various theories have been proposed including that delirious patients have reduced cerebral blood flow. We hypothesised that patients with delirium could have abnormal autonomic nervous system function, as assessed by tilt table testing, which would explain the alteration in blood flow. METHODS: A prospective cohort study of medical inpatients aged 65 years and older was undertaken. Delirium was assessed using DRS-R98 and DSM-IV criteria. Beat-to-beat blood pressure (BP) was recorded during tilt testing. Differences in BP changes between the two groups (those with delirium and those without) were explored. The association between severity of delirium and magnitude of BP changes was also examined. RESULTS: 64 participants were recruited during hospitalisation. 29 completed follow-up Head-Up Tilt testing. The mean age of participants was 80.8 years (SD 6.2 years). The control group (n = 12) had a median decrease in systolic BP of 17.5 mmHg (IQR 20.75). The delirium group (n = 17) had a median decrease in systolic BP of 1 mmHg (IQR 38.5), p = 0.04. As delirium severity scores increased, systolic BP change during tilting also increased (rs = 0.42, p = 0.03). CONCLUSION: Participants in the delirium group showed different BP responses to tilt test which may represent abnormal sympathetic response. This would be consistent with other features of delirium such as treatment response to centrally acting alpha-2 blockers. Equity of access to research for older, frail and delirious cohorts is essential but feasibility and acceptability needs to be optimised and factored into study design.

Postural changes in blood pressure among patients with diabetes attending a referral hospital in southwestern Uganda: a cross-sectional study.

BACKGROUND: Orthostatic hypotension (OH) and orthostatic hypertension (OHT) are often unrecognized in clinical care for diabetic individuals, yet they are associated with increased risk for adverse cardiovascular outcomes. We aimed to determine the prevalence of the abnormal orthostatic blood pressure (BP) responses, and associated factors among diabetic individuals in ambulatory care for diabetes in southwestern Uganda. METHODS: We conducted a cross-sectional study among diabetic individuals aged 18-65 years at Mbarara Regional Referral Hospital, southwestern Uganda from November 2018 to April 2019. We obtained demographic and clinical data including a detailed medical history, and glycemic profile. BP measurements were taken in supine position and within 3 min of standing. We defined OH in participants with either ≥ 20 mmHg drop in systolic BP (SBP) or ≥ 10 mmHg drop in diastolic BP (DBP) after assuming an upright position. OHT was defined in participants with either a ≥ 20 mmHg rise in SBP, or ≥ 10 mmHg rise in DBP after assuming an upright position. Multivariate logistic regression was used to identify factors associated with OH and OHT. RESULTS: We enrolled 299 participants, with a mean age of 50 years (SD ± 9.8), and mean HbA1c of 9.7% (SD ± 2.6); 70% were female. Of the 299 participants, 52 (17.4%; 95% CI 13.3-22.2%) met the definition of OH and 43 (14.4%; 95% CI 10.6-18.9%) were classified as having OHT. In multivariable models, factors associated with diabetic OH were older age (OR = 2.40 for 51-65 years vs 18-50 years, 95% CI 1.02-5.67, P = 0.046), diabetic retinopathy (OR = 2.51; 95% CI 1.14-5.53, P = 0.022), higher resting SBP ≥ 140 mmHg (OR = 3.14; 95% CI 1.31-8.7.56, P = 0.011), and history of palpitations (OR = 2.31; 95% CI 1.08-4.92, P = 0.031). Self-report of palpitations (OR = 3.14; 95% CI 1.42-6.95, P = 0.005), and higher resting SBP ≥ 140 mmHg (OR = 22.01; 95% CI 1.10-4.42, P = 0.043) were associated with OHT. CONCLUSION: OH and OHT are common among diabetic individuals in ambulatory diabetes care in southwestern Uganda. Orthostatic BP measurements should be considered as part of routine physical examination to improve detection of OH and OHT, especially among older diabetics with complications of the disease. Future studies to assess the health and prognostic implications of OH and OHT among diabetics in the region are warranted.