Classical Orthostatic Hypotension Research Articles

Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden.

Orthostatic hypotension (OH) is more common in the elderly and associated with increased mortality. However, its implications for 85-year-olds are not known. In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH. Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality. OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.

Blood Pressure Response and Symptoms During Active Standing Test Among Hospitalized and Outpatients With Heart Failure: Results From the GRAVITY-HF Prospective Observational Cohort Study

We conducted a multicenter, prospective, observational study to describe the incidence of orthostatic hypotension (OH) and orthostatic hypertension (OHtn) and its association with symptoms at standing and outcomes in patients with heart failure (HF). 321 active standing tests were performed in 87 inpatients during admission, and 316 tests were performed in 208 outpatients during follow-up. Blood pressure (BP) was measured by an automatic device 4 times in the supine position and at 1, 3 and 5 minutes of standing. Patients were queried about symptoms of orthostatic intolerance. The incidence of OH and OHtn was similar in both groups at baseline (classical OH 11%-22%, OHtn 3%-8%, depending on definition and timing). Reproducibility of BP changes with standing was low. Up to 50% of cases with abnormal responses were asymptomatic. Symptoms were variable and occurred mainly during the first minute of standing and had a U-shaped association with BP changes. OH in outpatients with HF was associated with a higher risks of death or readmission due to HF. Patients with HF have variable hemodynamic responses and symptoms during repeated active standing tests. OH might identify outpatients with HF who are at risk of long-term negative outcomes.

The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy.

Multiple system atrophy (MSA) and Parkinson's disease (PD) have similar clinical presentations in their early stages. Orthostatic hypotension (OH) is a common autonomic dysfunction associated with MSA and PD. Heart rate (HR) and systolic blood pressure (SBP) changes are measured in response to the active standing test, which is widely used to screen for cardiovascular autonomic function. Overall, 255 patients (67 MSA, 188 PD) underwent continuous beat-to-beat non-invasive BP monitoring and active standing test. The total standing time was 10 min, and the BP differences between both groups were compared to determine whether the ΔHR/ΔSBP can differentiate both conditions. Classical orthostatic hypotension (COH) (52%) and initial OH (19%) were most common in MSA and PD, respectively. MSA had a higher HR (75.0 ± 9.7 vs. 71.0 ± 10.7, P = 0.008) than PD in the supine position. SBP (135.70 ± 15.68 mmHg vs. 127.31 ± 15.14 mmHg, P = 0.106), diastolic BP (78.45 ± 12.36 mmHg vs. 67.15 ± 13.39 mmHg, P = 0.009) and HR (73.94 ± 8.39 bpm vs. 71.08 ± 13.52 bpm, P = 0.389) at baseline were higher in MSA-COH than in PD-COH. After adjusting for age and disease duration, the ΔHR/ΔSBP-10 min significantly discriminated MSA-COH from PD-COH (P = 0.031). An ΔHR/ΔSBP-10 min of 0.517 showed a sensitivity of 67% and specificity of 84% (AUC = 0.77, 95% CI: 0.63-0.91). The SBP, diastolic BP, and HR were higher in the supine position; however, ΔHR and ΔSBP were lower after standing in MSA patients than in PD patients. The ΔHR/ΔSBP-10 min discriminated between MSA-COH and PD-COH with quiet acceptable accuracy.

Frequency of hemodynamic response to orthostatic stress in heart failure with reduced ejection fraction, associations with clinical blood pressure

Aim. To assess hemodynamic response to active standing test (AST) with beat-to-beat blood pressure (BP) monitoring, their association with office BP and symptoms of orthostatic intolerance in patients with heart failure (HF).Material and methods. Outpatient HF patients with documented left ventricular ejection fraction <40%, followed up in a HF center and receiving optimal medical therapy, underwent AST with beat-to-beat non-invasive BP monitoring.Hemodynamic response was assessed according to the European Federation of Autonomic Societies criteria.Results. The study included 87 patients (mean age, 57±10 years; men, 76%). Normal hemodynamic response to orthostatic stress was observed in 36 (41,4%) patients. Pathological response prevailed during the first minute of orthostatic stress — initial orthostatic hypotension (OH) (n=29, 33,3%) and delayed BP recovery (n=18, 20,7%). Classical OH was detected in 4 (4,6%) patients. There was no orthostatic hypertension, defined as an increase in systolic BP (SBP) ≥20 mm Hg. According to office BP, hypotension was observed in 19 (21,8%) patients (SBP <90 mm Hg in 4 patients and 90-100 mm Hg in 15), hypertension (SBP >140 mm Hg) in 11 (12,6%) patients. Pathological response to orthostatic stress were more often observed in office SBP >140 mm Hg compared to SBP ≤140 mmHg (90,9% and 53,9%, p=0,020).Orthostatic intolerance was noted in 43 (49,4%) patients and were not associated with the level of office SBP (p=0,398) or pathological responses to orthostatic stress (p=0,758 for initial OH and p=0,248 for delayed BP recovery).Conclusion. The pathological hemodynamic response in AST with beat-to-beat BP monitoring in ambulatory patients with HF is most often represented by initial OH and delayed BP recovery associated with office SBP >140 mmHg. The frequency of symptoms of orthostatic intolerance did not differ between groups depending on the presence of an inadequate response to orthostatic stress.

New hemodynamic criteria to separate classical orthostatic hypotension from vasovagal syncope.

ObjectiveTo define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT).MethodsInclusion criteria for VVS were a history of VVS and tilt‐induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, “convex,” or decelerated, “concave”; (2) the time from head‐up tilt to when BP reached one‐half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations.ResultsWe included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19–98 sec) than in VVS (median 1571 sec, IQR 1381–1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%.InterpretationThese new hemodynamic criteria reliably differentiate cOH from VVS.

Delayed orthostatic hypotension in Parkinson\u2019s disease

Orthostatic hypotension (OH) is relatively common in the early stage of Parkinson’s disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.

Clinical and neuroendocrinological characteristics of delayed orthostatic hypotension in Parkinson's disease.

Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and neuroendocrinological characteristics of DOH in patients with Parkinson's disease (PD). A total of 132 patients with newly diagnosed PD were enrolled. Baseline clinical characteristics, including olfactory function, and changes in norepinephrine (NE) and vasopressin (ADH) concentrations during the head-up tilt test (HUT), were examined. Fifty-five patients (42%) had classical orthostatic hypotension (COH), and 19 patients (14%) had DOH. Patients with COH and DOH tended to have more severe hyposmia than patients without OH. A multivariate linear regression model showed that hyposmia was associated with DOH and COH. The increase of heart rate against the fall in blood pressure was significantly lower in patients with COH and DOH than those without OH. The NE levels at supine rest and after upright tilting were lower in the COH group than in the PD without OH and DOH groups. The levels of ADH were higher in the DOH group than in the COH group at supine rest and higher than in the PD without OH group after upright tilting. There was no significant difference in the cardiac 123I-MIBG scintigraphy between the COH and DOH groups. Compared with patients without OH, patients with DOH had severe hyposmia. Relatively preserved peripheral sympathetic nervous system function in patients with DOH suggests that DOH might be an early and milder form of OH in PD.

Validation of the new index of baroreflex function to identify neurogenic orthostatic hypotension.

According to expert opinion, orthostatic hypotension (OH) associated to a change in heart rate (ΔHR) less than 15bpm suggests neurogenic OH (NOH). Recently, the ratio between HR and systolic blood pressure changes at 3min of tilt test (ΔHR/ΔSBP) has been proposed as a better index than the ΔHR cut-off of 17bpm. Our aim was to validate these indexes based on HR in an independent cohort of patients who performed cardiovascular reflex tests according to standardized procedures at our Institution. We applied the HR indexes to all cardiovascular reflex tests that fulfilled the following criteria: (1) presence of classical OH at tilt test, (2) reliable Valsalva manoeuvre (VM), (3) absence of heart disease. We classified OH according to VM (absence of overshoot=NOH), and verified how many were correctly identified by ΔHR/ΔSBP (≤0.49 neurogenic) and ΔHR (≤17 and ≤15 neurogenic). We identified 369 tests with OH. Based on VM, 335 were NOH. The ΔHR/ΔSBP≤0.49 identified NOH with a sensitivity of 91% and a specificity of 59%, the ΔHR≤17bpm with 88% sensitivity and 38% specificity, and the ΔHR≤15bpm with 84% sensitivity and 50% specificity. In our cohort, the ΔHR/ΔSBP ratio had a good sensitivity but a limited specificity to identify NOH. This easily applicable test may represent a valuable screening tool in a clinical setting to identify patients who need further detailed autonomic testing to confirm the neurogenic origin of OH.

Delayed orthostatic hypotension.

Delayed orthostatic hypotension is a fall in blood pressure beyond 3min of standing or upright tilt table testing. The prevalence, clinical features and pathophysiology are reviewed. To date, there is little data to support a standardized or recommended treatment. However, the 10-year mortality rates of individuals with delayed orthostatic hypotension are approximately 50%. Despite the fact that delayed orthostatic hypotension carries the same symptoms, risks and high mortality rate as classical orthostatic hypotension, but is under-recognized. The frequency with which delayed orthostatic hypotension develops into classical orthostatic hypotension, the high associated mortality rates and risk of development of the neurodegenerative disorders classified as alpha-synucleinopathies underscores the need for further study of this condition.

Classical and Delayed Orthostatic Hypotension in Patients With Unexplained Syncope and Severe Orthostatic Intolerance.

Background: Orthostatic hypotension (OH) is a major sign of cardiovascular autonomic failure leading to orthostatic intolerance and syncope. Orthostatic hypotension is traditionally divided into classical OH (cOH) and delayed OH (dOH), but the differences between the two variants are not well-studied. We performed a systematic clinical and neuroendocrine characterization of OH patients in a tertiary syncope unit.Methods: Among 2,167 consecutive patients (1,316 women, 60.7%; age, 52.6 ± 21.0 years) evaluated for unexplained syncope and severe orthostatic intolerance with standardized cardiovascular autonomic tests including head-up tilt (HUT), we identified those with a definitive diagnosis of cOH and dOH. We analyzed patients' history, clinical characteristics, hemodynamic variables, and plasma levels of epinephrine, norepinephrine, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1, mid-regional-fragment of pro-atrial-natriuretic-peptide and pro-adrenomedullin in the supine position and at 3-min HUT.Results: We identified 248 cOH and 336 dOH patients (27% of the entire cohort); 111 cOH and 152 dOH had blood samples collected in the supine position and at 3-min HUT. Compared with dOH, cOH patients were older (68 vs. 60 years, p < 0.001), more often male (56.9 vs. 39.6%, p < 0.001), had higher systolic blood pressure (141 vs. 137 mmHg, p = 0.05), had lower estimated glomerular filtration rate (73 vs. 80 ml/min/1.73 m2, p = 0.003), more often pathologic Valsalva maneuver (86 vs. 49 patients, p < 0.001), pacemaker-treated arrhythmia (5 vs. 2%, p = 0.04), Parkinson's disease (5 vs. 1%, p = 0.008) and reported less palpitations before syncope (16 vs. 29%, p = 0.001). Supine and standing levels of CT-proAVP were higher in cOH (p = 0.022 and p < 0.001, respectively), whereas standing norepinephrine was higher in dOH (p = 0.001). After 3-min HUT, increases in epinephrine (p < 0.001) and CT-proAVP (p = 0.001) were greater in cOH, whereas norepinephrine increased more in dOH (p = 0.045).Conclusions: One-quarter of patients with unexplained syncope and severe orthostatic intolerance present orthostatic hypotension. Classical OH patients are older, more often have supine hypertension, pathologic Valsalva maneuver, Parkinson's disease, pacemaker-treated arrhythmia, and lower glomerular filtration rate. Classical OH is associated with increased vasopressin and epinephrine during HUT, but blunted increase in norepinephrine.

26 Initial Orthostatic Hypotension in Older Persons: Results from the Malaysian Elders Longitudinal Research Study

Abstract Objectives Initial orthostatic hypotension (IOH) is defined as a reduction in systolic or diastolic blood pressure (1) of 40 mmHg or 20 mmHg or greater within 15 seconds of standing. However, little is known about the characteristics of individuals with IOH and its relevance in the older population. The present study aimed to determine factors associated with IOH and classical orthostatic hypotension (COH) and their relationship with physical, functional and cognitive performance. Design Cross-sectional observational study. Setting and Participants Individuals aged ≥55 years were recruited through the Malaysian Elders Longitudinal Research (MELoR) study and continuous non-invasive BP was monitored over five minutes of supine rest and three minutes of standing. Measures Physical performance was measured using timed up and go, functional reach (FR), hand grip (HG) and Lawton’s functional ability scale; cognition was measured with Montreal Cognitive Assessment (MoCA). BP response to standing was categorized as non-OH, COH, IOH or COH and IOH Results 1245 participants were recruited, 623 (50%) had COH, 165 (13%) had IOH and 145 (12%) met the criteria for COH and IOH. COH was associated with increasing age, hypertension, transient ischemic attacks, diabetes mellitus, anti-hypertensive medications and reduced functional reach compared to individuals without COH. IOH was associated with younger age, normo-tension, and the absence of cerebrovascular disease or diabetes. Individuals with IOH had significantly better TUG, FR and HG scores compared to individuals without IOH. Conclusions This study suggests that IOH is associated with better physical performance. Further research is now required to fully elucidate the clinical relevance of IOH and its relationship to COH, as well as determine appropriate clinical cut-offs.

Orthostatic blood pressure changes and physical, functional and cognitive performance: the MELoR study.

Consensus definitions currently define initial orthostatic hypotension (IOH) as ≥40mmHg systolic (SBP) or ≥20mmHg in diastolic blood pressure (DBP) reductions within 15s of standing, while classical orthostatic hypotension (COH) is defined as a sustained reduction ≥20mmHg SBP or ≥10mmHg SBP within 3 min of standing. The clinical relevance of the aforementioned criteria remains unclear. The present study aimed to determine factors influencing postural blood pressure changes and their relationship with physical, functional and cognitive performance in older adults. Individuals aged ≥55 years were recruited through the Malaysian Elders Longitudinal Research (MELoR) study and continuous non-invasive BP was monitored over 5min of supine rest and 3min of standing. Physical performance was measured using the timed-up-and-go test, functional reach, handgrip and Lawton's functional ability scale. Cognition was measured with the Montreal Cognitive Assessment. Participants were categorized according to BP responses into four categories according to changes in SBP/DBP reductions from supine to standing: <20/10 mmHg within 3 min (no OH), ≥20/10 mmHg from 15s to 3 min (COH), ≥40/20 mmHg within 15s and ≥20/10 mmHg from 15s to 3 min (COH + IOH) and ≥40/20 mmHg within 15s and <20/10 mmHg within 3 min (IOH). A total of 1245 participants were recruited, COH + IOH 623 (50%), IOH 165 (13%) and COH 145 (12%). Differences between groups existed in age, gender, hypertension, diabetes, use of alpha-blocker and/or beta-blocker, ACE-inhibitors, diuretics, biguanides, and baseline systolic BP. In univariate analyses, differences between groups were present in physical performance and cognition. Multivariate comparisons revealed better physical performance in IOH compared to no OH, better physical and cognitive performance in COH + IOH compared to no OH, and cognition in COH than no OH. Our findings suggest that older adults who fulfil current consensus definitions for IOH had better physical performance and cognitive scores. This indicates that an initial postural BP drop in people aged ≥55 years may not necessarily be associated with increased frailty, as suggested by previously published literature.

Orthostatic reactions and cognitive dysfunctions in elderly and senile patients with arterial hypertension

Aim. To study the relationship of orthostatic hypotensive reactions (OHR), detected using active (AOT) and passive orthostatic tests (POT) with the state of cognitive functions in patients with arterial hypertension (AH) in older age groups. Materials and methods. 75 patients with hypertension I-III stage were examined (67±5 years). Patients received regular antihypertensive therapy, excluding medication on the day of the study. The study of the OHR was carried out using a 5-minute AOT and 5-minute POT with a minute-by-minute measurement of blood pressure on the shoulder using the oscillometric method and continuous non-invasive measurement of systolic (SBP) and diastolic (DBP) blood pressure in the finger artery by a photocompensation method (Task Force Monitor, CNSystems, Austria). The presence or absence of classical orthostatic hypotension (COH) and initial orthostatic hypotension (IOH) was assessed according to the criteria of the European Society of Cardiology (ESC-2018). The study of cognitive functions was carried out using a brief study of the mental state (Mini-Mental State Examination - MMSE), the clock drawing test and the Münstenberg test. The analysis was performed using Statistica 6.0. Data from sets with normal distribution were compared using student's t-test, Mann-Whitney test was used when comparing data with a distribution different from the normal one. To compare the groups on qualitative characteristics used Fisher's exact test. Results. In 23 (31%) patients, different types of OHR were identified, of them, 9 (12%) had isolated IOH, 14 (19%) had COH, among which 7 patients had a combination of COH+IOH). The revealed COH was neurogenic in all patients. The test result for drawing clocks in patients with OHR was significantly worse compared with patients without OHR (7.5±1.5 vs 8.4±0.8, p0.05; MMSE test: 25.7±2.3 vs 26.9±1.2, p&gt;0.05 respectively). Conclusion. OHR was detected in 31% of patients with AH in older age groups. The most pronounced decrease in cognitive functions was observed in patients with hypertension with COH.

Morning blood pressure surge is associated independently with orthostatic hypotension in hypertensive patients under treatment.

Morning blood pressure surge (MBPS) and orthostatic hypotension (OH) play a role in the occurrence of cardiovascular events. We aimed to investigate the association between MBPS and OH in hypertensive patients under treatment. We prospectively included 297 patients (mean age: 53.8±10.7 years, male/female: 101/196) with essential hypertension. Tilt table testing was performed for the diagnosis of OH. OH was classified into three groups as initial OH (0-15 s), classical OH (15 s to 3 min), and delayed OH (3-30 min). Patients were categorized into two main groups: patient with OH or without OH. We used sleep-through MBPS. The MBPS was calculated as the difference between the average blood pressure (BP) during the 2 h after awakening and the lowest night-time BP. We detected initial OH in two patients, classic OH in seven patients, delayed OH in 20 patients, and delayed OH with syncope in two patients. MBPS, thiazide diuretic, and α-blocker treatments were found to be associated independently with the occurrence of OH. Every 10 mmHg increase in MBPS was found to increase the rate of development of OH by 29.6%. The cut-off value of MBPS obtained by the receiver operator characteristic curve analysis was 35 mmHg for the prediction of OH occurrence (sensitivity: 58.0%, specificity: 68.0%). The area under the curve was 0.657 (95% confidence interval: 0.553-0.771, P=0.004). OH is a major problem in hypertensive patients. Increased MBPS, which can be detected easily by 24-h ambulatory BP monitor, predicts the occurrence of OH independently.

State of the art for diagnosis and treatment of orthostatic hypotension

This paper presents state of the art of the problem of diagnosis and treatment of orthostatic hypotension (OH). It focuses on the developed algorithms for diagnostics of classical orthostatic hypotension (COH), initial orthostatic hypotension (IOH) and delayed orthostatic hypotension (DOH). It describes the necessary methods for the differential diagnosis of the OH causes. Comparative analysis of the European Society of Cardiology and American College of Cardiology/American Heart Association/Society of Cardiac Rhythm was performed. The treatment options for different groups of patients with orthostatic hypotension are described.

Different patterns of orthostatic hypotension in older patients with unexplained falls or syncope: orthostatic hypotension patterns in older people.

To evaluate different patterns of orthostatic hypotension (OH) and its relation to mortality in older patients with unexplained falls or syncope. This is an observational cohort study in consecutive patients aged ≥ 65years with unexplained falls or syncope at a Fall Syncope day clinic November 2011 until May 2016. OH is defined as a decrease in systolic blood pressure (BP) ≥ 20mmHg and/or in diastolic BP ≥ 10mmHg during standing test. Main outcomes are the baseline characteristics and prevalence of patients with classical OH (decrease BP until 3min), delayed OH (decrease of BP from 5 to 10min) and continuous OH (decrease of BP for 10min). Secondary outcome is the relation between different OH patterns and mortality. Of 374 patients with a mean age of 80year (SD 6.6), 56% of the patients had OH: 16% had classical OH, 8% delayed OH, 32% had continuous OH and 44% had no OH. Patients with continuous OH and patients with delayed OH tended to have a higher mortality compared to patients with classical OH, 14 vs. 5% (P = 0.07) and 17 vs. 5% (P = 0.06). This possible relation between OH patterns and mortality could not be confirmed in multivariate analysis. In these very old patients, there are various patterns of decline in standing BP. Delayed and continuous OH will be missed if BP is measured only for 3min during standing. This is important because patients with continuous OH and delayed OH might have a relation with mortality. Our results encourage additional studies investigating the relation between different OH patterns and mortality.

Inflammatory biomarker profiling in classical orthostatic hypotension: Insights from the SYSTEMA cohort

ObjectiveTo investigate the inflammatory biomarker signature associated with classical orthostatic hypotension (OH). MethodsA cross-sectional study including 778 patients with unexplained syncope and/or orthostatic intolerance undergoing head-up tilt test (HUT) and supine blood sampling. Of these, 98 met diagnostic criteria of classical OH and 181 demonstrated normal haemodynamic response during HUT. Blood plasma samples were analysed by antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory and cancer-related human protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by multivariate principal component analysis (PCA), and verification by univariate ANOVA with Bonferroni correction. ResultsPatients with classical OH were older (68 vs. 60years; p<0.001) and more likely to be men (58 vs. 41%; p<0.001). PCA and Bonferroni-adjusted ANOVA identified midkine (MK), immunoglobulin-like transcript 3 (ILT-3), regenerating islet-derived protein 4 (REG-4), and tartrate-resistant acid phosphatase type 5 (TR-AP) as the most robust targeted biomarker signature for OH. In multivariate regression analysis adjusting for age, sex, cardiovascular disease and risk factors, the results remained significant for ILT-3 (p=0.036), MK (p=0.008) and REG-4 (p=0.024), but not for TR-AP. ConclusionsTargeted protein profiling in classical orthostatic hypotension reveals a biomarker signature associated with immunoregulatory functions and vascular inflammation. Circulating levels of midkine, immunoglobulin-like transcript-3, regenerating islet-derived protein-4 are elevated in orthostatic hypotension, suggesting a complex interplay among inflammation, autonomic dysfunction and atherothrombosis.

Do we need to evaluate diastolic blood pressure in patients with suspected orthostatic hypotension?

PurposeThe contribution of diastolic blood pressure measurement to the diagnosis of classical orthostatic hypotension is not known. We aimed to explore the prevalence of isolated systolic and diastolic orthostatic hypotension components in patients with syncope and orthostatic intolerance.MethodsA total of 1520 patients aged >15 years with suspected syncope and/or symptoms of orthostatic intolerance were investigated in a tertiary center using tilt-table testing and continuous non-invasive blood pressure monitoring. Classical orthostatic hypotension was defined as a decline in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg at 3 min of tilt test. The prevalence of upright systolic blood pressure <90 mmHg and its overlap with isolated diastolic orthostatic hypotension was also assessed.ResultsOne hundred eighty-six patients (12.2%) met current diagnostic criteria for classical orthostatic hypotension. Of these, 176 patients (94.6%) met the systolic criterion and 102 patients (54.8%) met the diastolic criterion. Ninety-two patients (49.5%) met both systolic and diastolic criteria, whereas ten patients (5.4%) met the diastolic criterion alone. Of these, three had systolic blood pressure <90 mmHg during tilt test and were diagnosed with orthostatic hypotension on the grounds of low standing blood pressure. Based on patient history and ancillary test results, causes of orthostatic intolerance and syncope other than orthostatic hypotension were present in the remaining seven patients.ConclusionsAn abnormal orthostatic fall in diastolic blood pressure without an abnormal fall in systolic blood pressure is rare among patients with syncope and orthostatic intolerance. Approximately 95% of patients with classical orthostatic hypotension can be identified by systolic criterion alone.

Diagnosing orthostatic hypotension: a narrative review of the evidence.

Orthostatic hypotension (OH) is very common, particularly in older populations. Diagnostic criteria exist but appear to be arbitrary rather than evidence based. This review will visit the evidence for diagnostic strategies for OH. Medline (OvidSP), EMBASE (OvidSP), ISI Web of Science, the Health Technology Assessments Database and the Cochrane Library. A 5-min rest is required before measuring baseline. An active stand with continuous blood pressure (BP) monitoring is preferable to a tilt test to identify initial OH in particular. At least 2 min in the upright position is required. A systolic drop of 20 or a diastolic drop of 10 is supported by the evidence. Reproducibility when testing for OH is poor. Is the active stand preferable to the tilt test to diagnose classical OH? Although continuous BP monitoring increases diagnostic rates, does it improve clinical outcomes? Should symptoms be used to inform diagnosis? Establishing the long-term clinical outcomes for transient drops in BP detected on continuous, non-invasive monitoring. Evaluating the different patterns of BP drop to aid diagnosis and direct treatment.