Symptoms are an optimal target for orthostatic hypotension screening and management: an argument in favor

Extracellular volume (ECV) predicts mortality in hemodialysis patients, but it is difficult to assess clinically. Peridialytic blood pressure (BP) measurements can help ECV assessment. Orthostatic BP is routinely measured clinically, but its association with ECV is unknown. In a cohort of hypertensive hemodialysis patients, we measured posthemodialysis ECV/weight with bioimpedance spectroscopy and analyzed its association with post-HD orthostatic BP measurements obtained during routine care. Using linear and logistic regression, the primary outcomes were orthostatic BP change and orthostatic hypotension (OH) defined by systolic BP decrease of at least 20 mmHg or diastolic decrease of at least 10 mmHg. Model 1 controlled for sex, age, and diabetes. Model 2 additionally controlled for ultrafiltration rate and antihypertensive medications. We conducted sensitivity analysis using OH definition of systolic BP decrease of at least 30 mmHg. Among 57 participants, mean orthostatic systolic BP change was -7.30 (20) mmHg and mean ECV/weight was 0.24 (0.04) L/kg. Post-HD ECV/weight was not associated with orthostatic systolic BP change (β=8.2, p=0.6). There were 16 participants with and 41 participants without OH. The ECV/weight did not differ between these groups (0.22 [0.04] vs. 0.24 [0.05] L/Kg, p=0.09) and did not predict OH in logistic regression (OR 11, 4.04; 95% CI 0.2-671, 0.03-0.530 in the two models.) In a sensitivity analysis, ECV/weight was lower in the OH group (0.22 [0.03] vs. 0.25 [0.04] L/kg, p=0.005), but this was accompanied by differences in sex and diabetes. Using logistic regression, there was no independent association between ECV/weight with OH. Orthostatic systolic BP change after HD completion is not a reliable indicator of posthemodialysis ECV. When considering other factors associated with orthostatic BP, ECV/weight is not independently associated with OH. Although transient postdialytic differences in intravascular volume may be associated with OH, posthemodialysis OH does not necessarily indicate ECV depletion.

Introduction: The association between orthostatic blood pressure (BP) changes and cognitive function has not been thoroughly investigated. Moreover, whether orthostatic hypotension or hypertension modifies the effects of intensive BP control on cognitive outcomes is unknown. Hypothesis: We hypothesized that orthostatic BP changes were associated with cognitive function and the effects of intensive BP control on cognitive outcomes might be different among individuals with/without orthostatic hypotension or hypertension. Methods: We performed a post hoc analysis of SPRINT MIND, a randomized controlled trial evaluating the effects of intensive vs. standard SBP control on cognitive outcomes in hypertensive patients. The relationships between baseline orthostatic BP changes (defined as baseline standing systolic BP [SBP]–baseline seated SBP) and probable dementia (PD) and mild cognitive impairment (MCI) were analyzed. The competing risk proportional hazards regression and cubic spline regression were used in analysis. Results: A total of 8547 participants (mean [SD] age, 67.9 [9.3] years; 5543 [64.9] men) were included in this analysis. In the crude model, the restricted cubic spline analysis showed L-shaped associations between orthostatic SBP change and new-onset PD and MCI (all P for nonlinearity<0.05). However, these associations all disappeared after adjustment for covariates. Moreover, orthostatic diastolic BP change was not associated with the PD or MCI incidence. Intensive BP control did not alter the risk of PD or MCI in patients with/without orthostatic hypotension or hypertension. Conclusions: Orthostatic BP changes were not associated with the risk of PD or MCI; baseline orthostatic hypotension or hypertension did not influence the effects of intensive BP control on cognitive outcomes. These results are hypothesis-generating and merit further study.

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. 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. 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 >20mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20mmHg. 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. Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

Background Intensive blood pressure (BP) control has been proven to reduce the risks of major cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM) (1). Excessive orthostatic BP changes should be fully addressed, given its high prevalence and associations with adverse events among T2DM patients (2-5). However, the benefits of intensive BP control among T2DM patients with significant orthostatic BP changes have been equivocal. Purpose To examine whether orthostatic BP changes modify the efficacy of intensive BP control on CVD outcomes in patients with T2DM. Methods The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) is a 2×2 factorial designed trial that aimed to evaluate the effects of intensive glycemia and BP control on major CVD events among T2DM patients (6). We enrolled participants with at least one record of orthostatic BP values for analysis. The composite CVD outcome in this study comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalized congestive heart failure. Associations between orthostatic BP changes and the composite CVD outcome and all-cause death, respectively, were presented by restricted cubic spline curves based on multivariable Cox models. We examined if the effects of intensive BP control varied across the orthostatic BP change for the composite CVD outcome and all-cause death. Results Among 4330 participants, 877 (20.3%) experienced episodes of orthostatic hypotension (OH) at baseline or during follow-up. There was no significant difference in the proportions of OH participants between the intensive and standard BP arms. U-shaped associations were observed between orthostatic systolic BP changes and the composite CVD outcome, as well as all-cause mortality (Figure 1). In the standard glycemia arm, intensive BP control was significantly associated with a lower risk of composite CVD outcome (HR 0.76, 95%CI 0.59-0.97). There was a beneficial association of intensive BP control with all-cause mortality without statistical significance (HR 0.85, 95%CI 0.56-1.30). The favorable effect of intensive BP control was not influenced by orthostatic BP changes (P for interaction 0.51 for the composite CVD outcome and 0.97 for all-cause mortality) (Figure 2). Beneficial effects of intensive BP control were not observed for participants in the intensive glycemia arm on the composite CVD outcome (HR 0.99, 95%CI 0.76-1.28) and all-cause mortality (HR 1.19, 0.79-1.80). Conclusion Orthostatic BP changes should not be a barrier to intensive BP control for T2DM patients treated with guideline-recommended standard glycemia control.

Using a simple standing-up test in normotensive subjects, we evaluated orthostatic upright postural blood pressure (BP) changes and autonomic nervous function, as well as the relationship between orthostatic BP changes and subclinical markers of atherosclerosis. A total of 515 normotensive subjects aged 35-75 years (58.4±10.0 years) were enrolled. We measured body mass index (BMI), systolic BP (SBP) and diastolic BP (DBP), serum lipids, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hs-CRP), and urinary albumin-to-creatinine ratio. Brachial to ankle pulse wave velocity (baPWV) and carotid mean intima-media thickness (IMT) were measured. Participants underwent a simple standing-up test involving sitting then standing for 2 minutes each, followed again by sitting. To evaluate autonomic fluctuations, we calculated the coefficient of variation of the R-R interval, the ratio of low to high frequency heart rate variability (LF/HF), and the coefficient of component variance of high frequency. SBP and DBP decreased when standing, with a reduction of SBP when changing position of -8.0±10.2mm Hg. Orthostatic hypotension (OH) produced a significantly higher SBP than without OH. The baPWV was significantly higher in OH than in without OH. Stepwise regression analysis adjusted for age, sex, BMI, baseline SBP, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, HbA1c, hs-CRP, IMT, late systolic peak of the pressure wave form (SBP2), and baPWV confirmed that baPWV, SBP2, and triglycerides were independently related to orthostatic BP changes. Multiple regression analyses showed that a decrease in SBP as well as baseline SBP, age, BMI, and fasting glucose were independent determinants of PWV. We have shown that increased arterial stiffness was associated with OH during a standing-up test. Arterial stiffness may contribute to greater BP responses to postural changes from standing.

BackgroundAlthough recent studies have indicated that both orthostatic hypotension and orthostatic hypertension independently predict cardiovascular events, the underlying mechanisms are still controversial. The aim of the study was to investigate the relationships between orthostatic changes and organ damage in subjects over 60 years old.MethodsThis is a prospective observational cohort study. One thousand nine hundred and ninety-seven subjects over 60 years old were enrolled. Participants were grouped according to whether they had a drop ≥ 20 mmHg in systolic or ≥ 10 mmHg in diastolic BP (orthostatic hypotension), an increase in mean orthostatic systolic blood pressure ≥ 20 mm Hg (orthostatic hypertension), or normal changes within 3 min of orthostatism. Multiple regression modeling was used to investigate the relationship between orthostatic hypotension, orthostatic hypertension and subclinical organ damage with adjustment for confounders.ResultsOrthostatic hypotension and orthostatic hypertension were found in 461 (23.1%) and 189 (9.5%) participants, respectively. Measurement of carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (baPWV), clearance of creatinine, and microalbuminuria were associated with orthostatic hypotension; measurement of IMT and baPWV were associated with orthostatic hypertension in a cruse model. After adjustment, IMT [odds ratio (OR), 95% confidence interval (CI) per one-SD increment: 1.385, 1.052–1.823; P = 0.02], baPWV (OR = 1.627, 95% CI: 1.041–2.544; P = 0.033) and microalbuminuria (OR = 1.401, 95% CI: 1.002–1.958; P = 0.049) were still associated with orthostatic hypotension, while orthostatic hypertension was only associated with IMT (OR = 1.730, 95% CI: 1.143–2.618; P = 0.009).ConclusionsOrthostatic hypotension seems to be independently correlated with increased carotid atherosclerosis, arterial stiffness and renal damage in subjects over 60 years old. Orthostatic hypertension correlates with carotid atherosclerosis only.

Background and Aims There have been no studies which explored the relationship between orthostatic blood pressure (BP) change and incident chronic kidney disease (CKD) in Asian population. Method We reviewed the data of 7,461 non-CKD adults aged 40-69 years who participated in Ansung_Ansan Cohort, a prospective community-based cohort study. BP was measured on supine position and 2 minute–upright position, and the difference was defined as orthostatic BP change. Incident CKD was defined as the first event to be estimated glomerular filtration rate < 60 ml/min/1.73 m2, which was confirmed at least 2 or more times thereafter. Results Of 7,461, orthostatic diastolic BP change was not associated with incident CKD in multivariate Cox proportional-hazard regression model. However, per 1 mmHg increase of orthostatic systolic BP was associated with decreased hazard of incident CKD: hazard ratio 0.988 and 95% confidence interval (0.982-0.994, P <0.001). In penalized spline curve analysis, we identified L-shaped relationship between orthostatic systolic BP change and incident CKD, with the threshold of - 2.4 mmHg. In subgroup analysis, the relationship between orthostatic systolic BP change and incident CKD was evident, particularly in participants without central obesity and reduced high density lipoprotein cholesterol and those with increased white blood cells. Conclusion Orthostatic SBP change was independently associated with incident CKD development. Future studies need to be followed to confirm the results.

Time in range, as an emerging metric of glycemic control, is associated with orthostatic blood pressure changes in type 2 diabetes

Identifying biomarkers that reflect disease progression in Parkinson's disease (PD) is of substantial clinical relevance. Accumulating evidence suggests a potential link between orthostatic hypotension and disease progression in PD. However, prior studies have largely relied on single baseline assessments, thereby overlooking longitudinal fluctuations in orthostatic blood pressure changes. This study aimed to identify distinct longitudinal trajectories of orthostatic systolic blood pressure change (∆SBP) and to investigate their associations with disease progression in PD. A total of 1,081 PD patients were included from two independent cohorts. Latent class trajectory model was applied to delineate longitudinal ∆SBP trajectories. Cox proportional hazards models and linear mixed-effects models were used to evaluate the associations between ∆SBP trajectories and clinical progression. Two latent class of ∆SBP trajectories were identified: a low-stable trajectory and an increasing trajectory. Compared with the low-stable class, patients in the increasing ∆SBP trajectory exhibited a higher risk of developing cognitive impairment, along with faster decline in visuospatial, attentional, and executive functions. They also showed more severe motor symptoms and rapid eye movement sleep behavior disorder, as well as accelerated progression of autonomic dysfunction and impairment in activities of daily living. An increasing ∆SBP trajectory was associated with a more pronounced progression across multiple clinical domains in PD, suggesting that longitudinal orthostatic blood pressure patterns may represent a clinically relevant dimension of disease heterogeneity.

An extensive, albeit contrasting literature has suggested a possible role for orthostatic hypotension as a risk factor for cardiovascular (CVD) and non-CVD mortality, while no data are available for orthostatic hypertension. We investigated whether orthostatic changes in blood pressure (BP) were associated with any increased risk of all-cause, CVD or non-CVD mortality in a group of elderly people. Two thousand seven hundred and eighty six community-dwelling older participants were followed for 4.4 years. Participants were grouped according to whether they had a drop ≤20 mm Hg in systolic, or ≤10 mm Hg in diastolic BP (orthostatic hypotension), an increase in mean orthostatic systolic BP ≥20 (orthostatic hypertension), or normal changes within 3 minutes of orthostatism. During follow-up, 640 subjects died, 208 of them for CVD-related reasons. Adjusted Cox's regression analysis revealed that, compared with normal changes, orthostatic hypertension was associated with higher all-cause (HR = 1.23; 95% CI: 1.02-1.39) and CVD-related mortality (HR = 1.41; 95% CI: 1.08-1.74), while orthostatic hypotension was only associated with a higher non-CVD mortality (HR = 1.19; 95% CI: 1.01-1.60). Orthostatic hypertension emerged as a predictor of all-cause mortality for: participants over 75 years old; participants with a BMI below 25 kg/m2; participants with no CVD or disabilities; and those taking less than three medications. Orthostatic hypertension also predicted CVD-related mortality in individuals with no hypertension, heart failure, coronary artery disease, or atrial fibrillation. Orthostatic hypertension and hypotension both seem to be relevant risk factors for mortality in the elderly, orthostatic hypertension correlating with all-cause and CVD-related mortality and orthostatic hypotension with non-CVD mortality.

Although orthostatic hypotension (OH) and orthostatic hypertension (OHT) can independently predict cardiovascular events, the underlying mechanisms remain controversial. Our study aimed to examine the relationships between orthostatic blood pressure (BP) changes and arterial stiffness. In this cross-sectional analysis, 1820 participants were divided into three groups according to BP changes within 3 min of orthostatism: the OH group had a decrease of >20 mmHg in SBP or >10 mmHg in DBP, the OHT group had an increase of ≥20 mmHg in SBP, and the orthostatic normotensive (ONT) group had normal changes. Arterial stiffness was assessed by measuring the carotid-femoral pulse wave velocity (cfPWV). OH and OHT were observed in 257 (14.1%) and 62 (3.4%) participants, respectively. Subjects in the OH group were significantly older, were more likely to have hypertension and diabetes, and had higher cfPWV than those in the ONT group ( P < 0.05); however, no differences were found between the ONT and OHT groups. Stepwise multiple regression analysis of the subgroups stratified by hypertension and diabetes revealed that age was related to increased cfPWV in all stratifications, and the change in SBP was significantly positively correlated with cfPWV in hypertensive subjects; however, this association was not observed in nonhypertensive subjects. We found that arterial stiffness was closely related to OH but not to OHT. In addition to expanding current knowledge of the relationship between orthostatic BP changes and arterial stiffness, our study underlines the importance of age, SBP changes, and hypertension in evaluating arterial stiffness.

Objective This study aimed to investigate the association between arterial stiffness and orthostatic hypotension (OH) and orthostatic blood pressure (BP) changes among Tibetans living at high altitude. Methods A total of 630 high-altitude Tibetans were included (56.53 ± 10.16 years; 246 men). Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). OH was defined as a decrease in systolic BP (SBP) >20 mmHg or a decrease in diastolic BP (DBP) >10 mmHg after 1 min or 3 min of moving from supine to standing position. Results The prevalence of OH in this population was 6.3%. Compared with subjects without OH, the subjects with OH had a higher baPWV (P < 0.001). Multiple logistical regression found that baPWV was significantly associated with the occurrence of OH (OR 1.147, CI 95% 1.028–1.280, P = 0.014). Spearman correlation analysis showed that baPWV was negatively associated with orthostatic changes in SBP and DBP(r = −0.256, P < 0.001 and r = −0.194, P < 0.001, respectively). Further multiple stepwise linear regression analysis showed that baPWV was independently correlated with orthostatic BP changes (SBP: β = −0.599, P < 0.001; DBP: β = −0.333, P < 0.001). Moreover, increased baPWV was correlated with attenuation of orthostatic heart rate changes. No significant association was observed between hematocrit or hemoglobin concentration and OH. Conclusion BaPWV was significantly associated with the occurrence of OH and orthostatic changes in the SBP and DBP, which suggests that arterial stiffness may be a potential mechanism of impaired hemodynamic response to orthostatic challenges among high-altitude Tibetans.

Background/Introduction The autonomic nervous system plays a crucial role in orthostatic blood pressure (BP) changes, including orthostatic hypotension (OH) and lesser-known orthostatic hypertension (OHT). The orthostatic normal response (ON) occurs when cardiovascular (CV) mechanisms compensate for reduced venous return upon standing. However, circulatory disruptions due to CV autonomic dysfunction, often seen in cancer, can lead to various forms of orthostatic intolerance. OH is linked to worse prognosis, though little is known about its prevalence in cancer patients. OHT, likely caused by sympathetic activation, may herald, like OH, an increased risk of many cardiovascular diseases (CVDs). Purpose Our study aimed to determine the prevalence of different types of orthostatic reactions in cancer patients compared to cancer-free population. Methods A total of 400 patients (221 females and 179 males, mean age 63.7 ± 10.4 years) were recruited. Group I (n = 220) included hospitalized patients with active treated cancer (chemotherapy, radiotherapy), group II (n = 180) patients hospitalized for other reasons but with no cancer diagnosis. Patients with significant anaemia requiring blood transfusion, diarrhea or after recent surgical procedures were excluded. The collected data included demographic and medical history, type of cancer, comorbidities, used drugs, and orthostatic BP changes. OH was defined as BP decrease on standing ≥ 20 mmHg for systolic or ≥ 10 mmHg for diastolic BP in 1 or 3 minute; or systolic BP decrease &amp;lt; 90 mmHg. OHT was defined as BP increase on standing ≥ 20 mmHg for systolic or ≥ 10 mmHg for diastolic BP in 1 or 3 min; or systolic BP increase &amp;gt; 140 mmHg. In the absence of the above diagnostic criteria, measurements were categorized as ON. Results ON in total studied population was observed in 202 patients (50.5%), OH in 88 patients (22.0%), and OHT in 110 patients (27.5%). In cancer patients compared to non-cancer population we have observed higher rate of abnormal orthostatic reactions, driven mainly by higher prevalence of OH. Instead, OHT occurred at a similar level in both groups (53/220; 24.1% in group I vs 57/180; 31.7% in group II). In the analysis of the different types of cancer, we noticed that OHT was significantly more frequent in patients with male genitourinary cancers (n = 9/21; 42.9%), compared to other groups of malignancies. Conclusions Cancer patients are characterized by a higher risk of orthostatic BP intolerances, especially OH. The prevalence of OHT differs with respect to the type of cancer, being the highest among patients with prostate cancer, who frequently have CVDs. Screening and monitoring of orthostatic changes in BP may improve the care of cancer patients. This might lead to the recommendation of routine orthostatic challenge tests for this population.

Objective To observe the incidence of orthostatic hypotension and hypertension in the elderly hypertensive inpatients and investigate the effect of antihypertensive medication on the orthostatic blood pressure changes in the elderly hypertensive inpatients.Methods A total of 185 aged hypertensive inpatients was divided into elderly group(n =126,60～79 years old) and very elderly group(n =59,≥80 years old) according to the age.The orthostatic blood pressure was measured in supine position and after standing.Subjects were divided into 3 subgroups:orthostatic hypotension (OH),orthostatic hypertension (OHT),and orthostatic normotension (ONT) groups according to the standing blood pressure levels.Clinical characteristics of each subgroup were evaluated and analyzed according to the antihypertensive medication.Results Among 185 patients,the OH incidence was 31 (16.76％) cases,the OHT incidence was 23 (12.43 ％) cases,and the ONT incidence was 131 (70.81％) cases.There were 16 (12.70％) patients with OH and 10(7.90％) patients with OHT in elderly group,but 15 (25.42％) patients with OH and 13 (22.03％) patients with ONT in very elderly group.The prevalence of OH and OHT in each elderly group was both higher than elderly group (P ＜ 0.05).Antihypertensive medications such as Calcium channel blockers,angiotensin Ⅱ receptor-blockers,Beta-blockers,diuretics,and angiotensin converting enzyme inhibitors were not significantly different among three subgroups.Conclusions OH and OHT were common in the elderly hypertensive inpatients,especially in the very elderly people.The five-class antihypertensive medication that doctors commonly used at present might be not related to the orthostatic hypotension and hypertension. Key words: Antihypertensive agents/pharmacology; Hypertension; Hypotension,orthostatic; Posture; Aged

To investigate the association of orthostatic hypertension and hypotension with hypertensive target organ damage in middle and old-aged hypertensive patients. This cross-section study was conducted in 4711 hypertensive patients aged 40-75 years old in 7 communities of Xinyang County, Henan Province by a multistage cluster sampling method. All patients received a standardized questionnaire, physical and biochemical examinations, echocardiography, ankle-brachial blood pressure index and orthostatic blood pressure measurement. Orthostatic hypertension was defined as an elevation of systolic blood pressure by 20 mm Hg or more while orthostatic hypotension as a drop of blood pressure by 20/10 mm Hg or more. When an upright posture was assumed. Others not belonging to these two conditions were classified into orthostatic normotension. The prevalence of orthostatic hypertension and hypotension was 16.3% and 23.8% in hypertensive patients. Peripheral artery disease was significantly more frequent in hypertensives with orthostatic hypertension (10.1%) or hypotension (10.7%) than those with orthostatic normotensives (7.4%) (both P<0.05). Patients with orthostatic hypotension had more common left ventricular hypertrophy (53.0% vs 43.2%, P<0.001) and a decreased estimated glomerular filtration rate (38.6% vs 34.4%, P<0.05) than did those with orthostatic normotension. After controlling for age, gender, body mass index and other confounders, orthostatic hypertension was positively associated with peripheral arterial disease (OR 1.39, 95%CI 1.05-1.84) while orthostatic hypotension was significantly associated with peripheral arterial disease (OR 1.45, 95%CI 1.13-1.86) and left ventricular hypertrophy (OR 1.46, 95%CI 1.11-1.84). But no independent association was found between orthostatic hypertension or hypotension and a decreased estimated glomerular filtration rate in hypertensive patients. The adjusted odds ratios (OR) for left ventricular hypertrophy, as predicted by the quintiles of orthostatic systolic blood pressure changes, showed a J-shaped relationship in hypertensive women, and so did peripheral artery disease in untreated hypertensive patients. Hypertensive patients with orthostatic hypertension or hypotension may have an elevated risk of developing target organ damage.