Supine Systolic Blood Pressure Research Articles

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.

Neural-Cardiovascular Responses to Orthostasis Following 8-Weeks of Home-Based Lower Leg Heating in Older Women with Hypertension

Background: Hypertension remains a significant health problem for older women (≥60 y). Though effective blood pressure (BP) interventions exist (e.g., exercise, medication), adherence to these options is low. Lower leg heat therapy represents a promising and easily implementable adjuvant treatment that may offer cardioprotective benefits. However, no studies have investigated lower leg heat therapy’s effects on BP and neural-cardiovascular function, let alone in older women with hypertension. Accordingly, we hypothesized that 8-weeks of home-based lower leg heat therapy in older women with hypertension would 1) reduce ambulatory BP and 2) reduce muscle sympathetic nerve activity (MSNA) while augmenting cardiac output and stroke volume during graded head-up tilt (HUT). Methods: Forty older women with hypertension (69 ± 5 y [mean±SD]) were randomized to either heat therapy (INT, 42°C; n = 20) or a thermoneutral control (CON, 35°C; n = 20). Each woman completed 8 wks of at-home sessions (~4/wk; 45 min/session) immersing their legs ~33 cm in a portable spa bath. 24-h ambulatory BP was measured pre- (PRE) and post-intervention (POST). A subset of women (n = 18 for each group) completed supine rest and 5 min of 30° and 60° HUT at each time point, whereby laboratory heart rate, systolic and diastolic BP, MSNA burst frequency and incidence (microneurography), cardiac output (acetylene rebreathing), and stroke volume (cardiac output/heart rate) were measured. Results: Between INT and CON, PRE ambulatory awake systolic BP (140 ± 7 vs. 142 ± 6 mmHg; P = 0.34) and diastolic BP (80 ± 6 vs. 79 ± 6 mmHg; P = 0.51) were not different, nor were PRE supine systolic BP, diastolic BP, or heart rate (all P &gt; 0.05). PRE supine resting MSNA burst frequency (36 ± 13 vs. 33 ± 16 bursts/min), MSNA burst incidence (54 ± 19 vs. 51 ± 22 bursts/100 heartbeats), cardiac output (4.9 ± 0.9 vs. 5.1 ± 1.0 L/min), and stroke volume (72 ± 15 vs. 76 ± 15 mL/beat) were not different between groups (all P &gt; 0.05). From PRE to POST neither ambulatory awake systolic nor diastolic BP differed between groups (all P &gt; 0.05). Despite this, POST laboratory systolic and diastolic BP were greater in INT (both P &lt; 0.05) but not in CON (both P &gt; 0.05) during HUT. POST laboratory heart rate was reduced in INT ( P = 0.025), and trended greater in CON ( P = 0.065) across HUT. Neither MSNA burst frequency nor burst incidence changed during HUT PRE to POST (all P &gt; 0.05). Despite no PRE to POST differences in cardiac output in either group (all P &gt; 0.05), INT had a greater overall POST stroke volume throughout HUT ( P = 0.011), while CON had a reduced stroke volume during 60° HUT ( P = 0.036). Conclusions: Contrary to our hypotheses, 8-weeks of home-based lower leg heat therapy did not improve ambulatory BP or HUT MSNA and cardiac output in older women with hypertension. However, women completing INT appeared to have a greater stroke volume and lower heart rate during HUT. Accordingly, these data suggest that 8-weeks of lower leg heat therapy in older women with hypertension may improve cardiac function during orthostasis without significant changes in sympathetic outflow or ambulatory BP. Supported by the National Institutes of Health (R01AG059314 and F32HL167556). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exercise systolic blood pressure response during cycle ergometry is associated with future hypertension in normotensive individuals.

We aimed to investigate the association between the exercise systolic blood pressure (SBP) response and future hypertension (HTN) in normotensive individuals referred for cycle ergometry, with special regard to reference exercise SBP values and exercise capacity. In this longitudinal cohort study, data from 14 428 exercise tests were cross-linked with Swedish national registries on diagnoses and medications. We excluded individuals with a baseline diagnosis of cardiovascular disease or HTN. The peak exercise SBP (SBPpeak) was recorded and compared with the upper limit of normal (ULN) derived from SBPpeak reference equations incorporating age, sex, resting SBP, and exercise capacity. To evaluate the impact of exercise capacity, three SBP to work rate slopes (SBP/W-slopes) were calculated, relative to either supine or seated SBP at rest or to the first exercise SBP. Adjusted hazard ratios [HRadjusted (95% confidence interval, CI)] for incident HTN during follow-up, in relation to SBP response metrics, were calculated. We included 3895 normotensive individuals (49 ± 14 years, 45% females) with maximal cycle ergometer tests. During follow-up (median 7.5 years), 22% developed HTN. Higher SBPpeak and SBPpeak > ULN were associated with incident HTN [HRadjusted 1.19 (1.14-1.23) per 10 mmHg, and 1.95 (1.54-2.47), respectively]. All three SBP/W-slopes were positively associated with incident HTN, particularly the SBP/W-slope calculated as supine-to-peak SBP [HRadjusted 1.25 (1.19-1.31) per 1 mmHg/10 W]. Both SBPpeak > ULN based on reference values and high SBP/W-slopes were associated with incident HTN in normotensive individuals and should be considered in the evaluation of the cycle ergometry SBP response.

Prospective association of occupational and leisure-time physical activity with orthostatic blood pressure changes in older adults

Orthostatic hypotension (OH) is common in older people. We examined the influence of self-reported occupational-related physical activity (PA) and leisure-time physical exercise (PE) on orthostatic response in a sample of older people over a 2 year period. Supine and orthostatic systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were assessed in response to Active Stand (AS) test in 205 older subjects (> 60 years old) at baseline and 2-year follow-up. OH was found in 24 subjects (11.71%) at baseline and 20 subjects (9.76%) after 2 years, with a significant degree of variability in the occurrence of OH after 2 years. Twenty-two subjects who had OH at baseline were free of it after 2 years, two subjects had persistent OH at baseline and after 2 years. After 2 years, adults with occupational PA showed no significant decrease of blood pressure in response to AS test, while lack of undertaking an occupation-related PA was significantly related with a greater decrease in sBP and mBP in response to AS testing in the 1st min. Occupation-related PA and leisure-time-related PE were related to an increase in the response of BP on AS in change between baseline and after 2 years. High between-subjects variance in OH over 2 years was noted. Occupations that involved continuous physical activity and leisure-time physical exercise in middle age were both protective for BP decline on orthostatic stress test within 2 years.

Relationship of blood pressure measured in the calf with arm blood pressure and arterial stiffness: a general population study.

Leg blood pressure (BP) measurement is needed when arm BP evaluation is not feasible, and calf BP, especially when measured in standing position, may have greater association with cardiovascular remodeling than arm BP. This study evaluated the relationship between calf and arm BP, and investigated whether calf BP would be superior to arm BP in predicting increased arterial stiffness [pulse wave velocity (PWV) > 10 m/s]. We evaluated clinical and laboratory characteristics, BP measurements, and PWV in 1397 individuals resident in Baependi, Brazil, between 2017 and 2019. Arm BP was measured in the seated and supine positions while calf BP was measured in supine and standing positions using digital oscillometric devices. Carotid-femoral PWV was measured using a noninvasive mechanotransducer. The sample had 62.7% females, age = 48.1 ± 15.4 years and 8.4% with PWV >10 m/s. Results of linear regression analysis showed that BP values of 140/90 mmHg measured in the arm in supine and seated position were equivalent to calf supine BP values of 164/81 mmHg and 166/78 mmHg and calf standing BP values of 217/137 mmHg and 221/137 mmHg, respectively. Calf-arm BP differences were associated with age, glomerular filtration rate, body mass index, smoking, low-density lipoprotein-cholesterol, diabetes and height. Furthermore, stepwise logistic regression analysis revealed that arm supine systolic BP, but not calf BP measurements, was independently associated with increased arterial stiffness. Thresholds of ≈165/80 mmHg and ≈220/135 mmHg could be used for diagnosing hypertension when only calf measurements in supine and standing positions, respectively, are available. Conversely, calf BP was not superior to arm BP in predicting increased arterial stiffness.

What is the prevalence of orthostatic hypotension in an Australasian emergency department population?

Orthostatic hypotension (OH) is associated with increased morbidity and there is limited research on the prevalence in the Australian ED population. The aim was to determine the prevalence of OH in an Australian ED population. Secondary outcomes included any associations of OH with symptoms, presenting complaints, patient demographics, or hospital admission, and the timing of OH findings. Patients presenting to a regional Australasian ED underwent orthostatic measurements at 1, 3 and 5 min of standing following 5 min of supine bed rest. OH was defined as a drop in systolic and/or diastolic blood pressure by ≥20 and ≥10 mmHg, respectively. Of the 312 patients who were enrolled in the study, 69 (22.1%, 95% confidence interval 17.7-27.2%) had OH and 76.8% of cases were detected after 3 min of standing. There was evidence of difference in the prevalence of OH with age (P < 0.001). Similarly, there was evidence of a difference in supine systolic and diastolic blood pressure measurements (P = 0.012 and P < 0.001, respectively) between orthostatic and normotensive subjects. No association was found with OH and hospital admission, presenting complaints or comorbid medical illnesses. In this single Australian ED population, there was a high prevalence of OH (22.1%) with most cases detected within 3 min of standing. A higher-powered study across multiple sites would better substantiate these findings.

Abstract P413: Association Between Supine Hypertension And Autonomic Impairment In Patients With Autonomic Failure

Autonomic failure is characterized by an inability to regulate blood pressure (BP). The dominant clinical manifestation of these patients is orthostatic hypotension (OH). However, at least half of them also have supine hypertension, which can arise de novo or due to worsening of preexisting essential hypertension. We hypothesized that, regardless of the cause of hypertension, the loss of baroreflex buffering capacity in these patients contributes to the severity of their hypertension. Thus, we tested whether supine hypertension reflects the severity of autonomic impairment (i.e., reduced BP buffering capacity) in a retrospective cohort of 307 patients (66±1 yr, 183 males, BMI 26.1±0.3) with a diagnosis of neurogenic OH due to multiple system atrophy (MSA, n=95) or peripheral autonomic failure (pAF, n=212). Autonomic impairment was assessed by standard autonomic testing (posture test, Valsalva maneuver [VM], and sinus arrhythmia [SA] ratio) performed off pressor and antihypertensive medications. The association between supine systolic BP (SBP; median [interquartile range, IQR], 146 [130-168] mmHg) and autonomic testing was assessed using multiple regression analyses. After adjusting for age, sex, BMI, and type of autonomic failure (MSA vs. pAF), we found that supine SBP was positively related to age (β=0.33; P=0.034), the severity of OH (the drop in SBP on standing; β= -0.48, P&lt;0.001), and indices of severity of autonomic impairment, including the lack of adequate compensatory increase in heart rate in the setting of OH (ΔHR/ΔSBP, β=-15.43, P=0.044), and lack of recovery of SBP during late phase 2 of the Valsalva maneuver (β=-0.31; P&lt;0.001; model R 2 =0.55, P&lt;0.001). VM and SA ratios were not related to supine hypertension. In conclusion, we postulate that the magnitude of supine hypertension correlates with the severity of autonomic impairment and that both OH and supine hypertension reflect the inability of autonomic failure to regulate blood pressure.

Abstract 071: Seated And Supine Blood Pressure And Risk Of Cardiovascular Disease And Mortality From The Atherosclerosis Risk In Communities Study

Background: Hypertension (HTN) while asleep is strongly associated with cardiovascular disease (CVD) and death. Whether HTN while supine in clinic is a risk factor for CVD independent of seated BP remains unknown. Objectives: To determine the relationship between supine HTN and adverse CVD. Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured supine and seated BP during visit 1 (1987-1989). Supine HTN was defined as a supine systolic BP (SBP) ≥130 or diastolic BP (DBP) ≥80 mm Hg and seated HTN was defined as a seated SBP ≥130 or DBP ≥80mm Hg. We excluded participants with a history of coronary heart disease (CHD), heart failure, or stroke and examined the association of supine HTN with incident CHD, heart failure, stroke, fatal CHD, and all-cause mortality using Cox models adjusted for seated HTN and CVD risk factors. Analyses were repeated in strata of HTN treatment. Results: Of 11,369 participants (56% female, 25% Black, mean age [53.9±5.7 years]), 16% of those without seated HTN had supine HTN, while 74% of those with seated HTN had supine HTN. Over a median of 25-28 years of follow-up, despite adjustment for seated HTN, supine HTN was associated with incident CHD (HR 1.60; 95% CI: 1.45, 1.76), heart failure (1.83; 1.68,2.01), stroke (1.86; 1.63, 2.13), fatal CHD (2.18; 1.84, 2.59), and all-cause mortality (1.43; 1.35,1.52). Results did not differ by HTN medication use ( P -interactions &gt;0.05). Participants with supine HTN alone, had a risk similar to HTN in both positions ( Figure ). Conclusion: Participants with supine HTN had a significantly higher risk of adverse CVD events independent of seated HTN. Supine HTN screening should be further evaluated in a clinical trial.

The Association between Diabetic Retinopathy and Cardiovascular Autonomic Neuropathy in People with Type 2 Diabetes

Abstract Background Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus, which is strongly associated with increased risk of cardiovascular mortality. The aim of the present work is to study the prevalence of CAN in diabetic subjects with retinopathy Methods Ninety subjects participated in the study. They were classified into three groups (Group I: 30 (T2DM) patients with diabetic retinopathy, Group II: 30 (T2DM) patients without retinopathy, Group III: 30 non diabetic volunteers). All patients were evaluated for detection of CAN (Basal Heart Rate, Supine and erect systolic blood pressure variation, Tilt Table Test), diabetes-related micro vascular complications (retinopathy), micro albuminuria (A/C Ratio). Results The prevalence of CAN (using tilt table test) is significantly higher (P = 0.004) in Group I compared to Group II and III. The percentage of positive tilt table test in Group I (43.33%), while in Group II (10%). In Group I, CAN prevalence is higher in proliferative diabetic retinopathy (PDR) compared to non-proliferative diabetic retinopathy (NPDR) (P = 0.007). Logistic regression analysis demonstrated that in T2DM, the odds [OR (95% confidence intervals)] of CAN increased with diabetes duration [4.99 (1.46-17.09)], A/C Ratio [9.99(2.41-41.36)]. Conclusion This study indicated that DR and micro albuminuria could predict CAN. The results suggest that fundus photography and clinical assessment (A/C RATIO) may be an alternative to autonomic function testing when Tilt Table Test is unavailable

Enrolling patients in Cardiac Amyloid Reaching for Extended Survival (CARES) trials: Two placebo-controlled, double-blind, randomized, international phase 3 trials assessing CAEL-101 in patients with Mayo stage IIIa or stage IIIb AL amyloidosis.

TPS8071 Background: Light-chain (AL) amyloidosis is a rare, progressive, systemic disorder caused by plasma cell dyscrasia (PCD). Amyloid fibrils deposit in organs leading to progressive organ damage and death. Prognosis is poor for patients with cardiac involvement. Median survival is 24 and 4 months for patients in Mayo Stages IIIa and IIIb (based on the 2013 European Modification of the Mayo 2004 staging criteria), respectively. The standard of care (SoC) is anti-PCD therapy to suppress amyloid fibril generation. As yet, there are no therapies that remove deposited fibrils. CAEL-101 is a monoclonal antibody that binds to amyloid fibrils and may facilitate their systemic removal, improve organ function, and patient survival. These ongoing trials will evaluate the efficacy and safety of CAEL-101 as first-in-class treatment to reduce amyloid burden in patients with cardiac AL amyloidosis. Notably, 301 (Mayo Stage IIIb) is the first randomized, placebo-controlled efficacy clinical trial to formally assess the effects of a pharmacological in this severely ill population. Because the median expected survival for Mayo Stage IIIb patients is far shorter than for Mayo Stage IIIa patients, the resulting sample size required for the Mayo Stage IIIb study is less than for the Mayo Stage IIIa study. The objective of these trials is to evaluate the efficacy and safety of CAEL-101 when administered concurrently with SoC anti-PCD therapy in treatment-naïve patients with cardiac AL amyloidosis in Mayo Stages IIIb (NCT04504825; 301) or IIIa (NCT04512235; 302). Methods: These international, multicenter, double-blind, randomized, phase 3 trials, initiated in 2020, are enrolling patients at &gt; 100 sites in &gt; 20 countries. Newly diagnosed adults with AL amyloidosis stage IIIb or IIIa measurable hematologic disease, and histopathological diagnosis of amyloidosis with cardiac involvement are eligible. Patients with other forms of amyloidosis, symptomatic orthostatic hypotension, or supine systolic blood pressure &lt; 90 mm Hg are ineligible. Patients in Mayo Stages IIIb (N = 124) and IIIa (N = 267) are being randomized 2:1 to receive once-weekly IV infusions of CAEL-101 (1000 mg/m2) or placebo for 4 weeks, followed by maintenance dosing every 2 weeks. In these event-driven studies, treatment will continue to a minimum of 101 and 79 events for 301 and 302, respectively. Patients will receive concurrent institutional SoC anti-PCD therapy at the discretion of the investigator. Overall survival (primary endpoint) will be analyzed via time-to-event log-rank statistics. Secondary endpoints include functional outcomes, quality of life, and echocardiography. Clinical trial information: NCT04504825 , NCT04512235 .

Concomitantly higher resting arterial blood pressure and transduction of sympathetic neural activity in human obesity without hypertension.

Central (abdominal) obesity is associated with elevated adrenergic activity and arterial blood pressure (BP). Therefore, we tested the hypothesis that transduction of spontaneous muscle sympathetic nerve activity (MSNA) to BP, that is, sympathetic transduction, is augmented in abdominal obesity (increased waist circumference) and positively related to prevailing BP. Young/middle-aged obese (32 ± 7 years; BMI: 36 ± 5 kg/m2, n = 14) and nonobese (29 ± 10 years; BMI: 23 ± 4 kg/m2, n = 14) without hypertension (24-h ambulatory average BP < 130/80 mmHg) were included. MSNA (microneurography) and beat-to-beat BP (finger cuff) were measured continuously and the increase in mean arterial pressure (MAP) during 15 cardiac cycles following MSNA bursts of different patterns (single, multiples) and amplitude (quartiles) was signal-averaged over a 10 min baseline period. MSNA burst frequency was not significantly higher in obese vs. nonobese (21 ± 3 vs. 17 ± 3 bursts/min, P = 0.34). However, resting supine BP was significantly higher in obese compared with nonobese (systolic: 127 ± 3 vs. 114 ± 3; diastolic: 76 ± 2 vs. 64 ± 1 mmHg, both P < 0.01). Importantly, obese showed greater increases in MAP following multiple MSNA bursts (P = 0.02) and MSNA bursts of higher amplitude (P = 0.02), but not single MSNA bursts (P = 0.24), compared with nonobese when adjusting for MSNA burst frequency. The increase in MAP following higher amplitude bursts among all participants was associated with higher resting supine systolic (R = 0.48; P = 0.01) and diastolic (R = 0.48; P = 0.01) BP when controlling for MSNA burst frequency, but not when also controlling for waist circumference (P > 0.05). In contrast, sympathetic transduction was not correlated with 24-h ambulatory average BP. Sympathetic transduction to BP is augmented in abdominal obesity and positively related to higher resting supine BP but not 24-h ambulatory average BP.

Risk factor analysis and clinical decision tree model construction for diabetic retinopathy in Western China.

Diabetic retinopathy (DR) is the driving force of blindness in patients with type 2 diabetes mellitus (T2DM). DR has a high prevalence and lacks effective therapeutic strategies, underscoring the need for early prevention and treatment. Yunnan province, located in the southwest plateau of China, has a high pre-valence of DR and an underdeveloped economy. To build a clinical prediction model that will enable early prevention and treatment of DR. In this cross-sectional study, 1654 Han population with T2DM were divided into groups without (n = 826) and with DR (n = 828) based on fundus photography. The DR group was further subdivided into non-proliferative DR (n = 403) and proliferative DR (n = 425) groups. A univariate analysis and logistic regression analysis were conducted and a clinical decision tree model was constructed. Diabetes duration ≥ 10 years, female sex, standing- or supine systolic blood pressure (SBP) ≥ 140 mmHg, and cholesterol ≥ 6.22 mmol/L were risk factors for DR in logistic regression analysis (odds ratio = 2.118, 1.520, 1.417, 1.881, and 1.591, respectively). A greater severity of chronic kidney disease (CKD) or hemoglobin A 1c increased the risk of DR in patients with T2DM. In the decision tree model, diabetes duration was the primary risk factor affecting the occurrence of DR in patients with T2DM, followed by CKD stage, supine SBP, standing SBP, and body mass index (BMI). DR classification outcomes were obtained by evaluating standing SBP or BMI according to the CKD stage for diabetes duration < 10 years and by evaluating CKD stage according to the supine SBP for diabetes duration ≥ 10 years. Based on the simple and intuitive decision tree model constructed in this study, DR classification outcomes were easily obtained by evaluating diabetes duration, CKD stage, supine or standing SBP, and BMI.

Cardiovascular concentration-effect relationships of amodiaquine and its metabolite desethylamodiaquine: Clinical and preclinical studies.

Amodiaquine is a 4-aminoquinoline used extensively for the treatment and prevention of malaria. Orally administered amodiaquine is largely converted to the active metabolite desethylamodiaquine. Amodiaquine can cause bradycardia, hypotension, and electrocardiograph QT interval prolongation, but the relationship of these changes to drug concentrations is not well characterized. We conducted a secondary analysis of a pharmacokinetic study of the cardiac safety of amodiaquine (10mg base/kg/day over 3days) in 54 Kenyan adults (≥18 years) with uncomplicated malaria. Nonlinear mixed effects modelling was used to assess amodiaquine and desethylamodiaquine concentration-effect relationships for vital sign (pulse rate, blood pressure) and electrocardiograph interval (QT, QRS, PR) outcomes. We also measured the spontaneous beating heart rate after cumulative dosing of amodiaquine and desethylamodiaquine in isolated mouse atrial preparations. Amodiaquine and desethylamodiaquine caused concentration-dependent mean decreases in pulse rate (1.9 beats/min per 100 nmol/L; 95% confidence interval: 1.5-2.4), supine systolic blood pressure (1.7mmHg per 100 nmol/L; 1.2-2.1), erect systolic blood pressure (1.5mmHg per 100 nmol/L; 1.0-2.0) and erect diastolic blood pressure (1.4mmHg per 100 nmol/L; 1.0-1.7). The mean QT interval prolongation was 1.4 ms per 100 nmol/L irrespective of correction factor after adjustment for residual heart rate dependency. There was no significant effect of drug concentration on postural change in blood pressure or PR and QRS intervals. In mouse atria, the spontaneous beating rate was significantly reduced by amodiaquine (n= 6) and desethylamodiaquine (n= 8) at 3μmol/L (amodiaquine: 10±2%; desethylamodiaquine: 12 ±3%) and 10μmol/L (amodiaquine: 50 ±7%; desethylamodiaquine: 46 ±6%) concentrations with no significant difference in potency between the 2 compounds. Amodiaquine and desethylamodiaquine have concentration-dependent effects on heart rate, blood pressure, and ventricular repolarization.

Abstract 15714: Association of Obesity With Orthostatic Hypertension

Introduction: Orthostatic hypertension (OHT) is variably defined, poorly understood, multifactorial but may contribute to target organ damage. Increase systolic blood pressure (SBP) over 10 mmHg from supine to standing may identify OHT with increased baseline sympathetic nervous system (SNS) and renin angiotensin aldosterone system (RAAS) activation. Diabetes, advanced age, and neurological disorders appear to predispose to OHT and this has not been characterized in obese patients. Hypothesis: RAAS and SNS activation is well recognized in obesity. Routine orthostatic BP measurement in obese patients may identify OHT. Methods: Between 5.2021 to 5.2022, we screened obese patients presenting to University of Missouri -Columbia cardiology clinic for OHT. Supine BP was obtained after 5 minutes of rest and standing BP measured 3 minutes after standing. BMI was estimated from height and weight obtained routinely during same clinic visit. Risk factors were estimated from medical records. Results: OHT was identified in 30 patients (Males 7, females 23) with average age 55.1 ± 17.6 years. Weight was 128.6 ± 27.4 kg, BMI 47.9 ± 9.9 kg/m 2 . Supine systolic and diastolic BP were 131.9 ± 15.9 and 78.3 ± 8.4 mmHg. On standing, systolic and diastolic BP increased to 155.7 ± 19.5 and 92.5 ± 13.1 mmHg. Standing resulted in systolic and diastolic BP increase of 23.8 and 14.2 mmHg, respectively. Hypertension (n= 23, 77%), depression (15, 50%) diabetes (12, 40%), asthma (9, 30%), sleep apnea (12, 40%), heart failure (7, 23%), anxiety - post traumatic stress disorder (5, 17%), chronic obstructive lung disease (3, 10%) and atrial fibrillation (3, 10%) were common associations. Acute increase in BP may contribute to palpitation and dyspnea on standing reported in 5 (17%) of the OHT patients. Conclusions: Orthostatic hypertension is prevalent in obese patients and underdiagnosed during clinic visits. Severe obesity predisposes especially women to significant standing blood pressure increase that may cause symptoms and target organ damage. Routine Orthostatic BP Screening during clinic visits especially in obese patients is required to identify orthostatic hypertension, to optimize outcomes with appropriate lifestyle interventions and medications.

Abstract P007: Timing Of Orthostatic Hypotension And Its Relationship With Falls In Older Adults

Background: There is inconsistent evidence on the optimal time after standing to assess orthostatic hypotension (OH). Objectives: To characterize the timing of OH after standing in older adults and the fall risk associated with OH at specific times. Methods: We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You (STURDY). Blood pressure (BP) was measured in the supine position. Participants stood upright and underwent 6 standing BP measurements: 3 (M1-M3) immediately after standing, and 3 (M4-M6) after 3 minutes of standing. OH was defined as a decrease from supine systolic BP (SBP) of 20 or supine diastolic BP (DBP) of 10 mm Hg. We used generalized estimating equations to characterize changes in SBP, DBP, and OH over time. We used Cox models to examine the relationship between OH at each time point and subsequent falls. Results: There were 425 falls among 491 adults with 6,055 BP measurements and a median follow-up of 275 days. SBP/DBP decreased by a mean 9.5/2.6 mm Hg immediately after standing (M1) vs. 2.2/0.9 about 5 minutes after standing (M6). OH was observed in 32% of assessments at M1, and only 16% at M5 and M6 ( Table ). Only OH at M5 (Hazard Ratio = 1.84 [95% confidence interval = 1.17, 2.91]) and M6 (1.85 [1.03, 2.91]) predicted higher fall risk among individual time points. However, average OH from early (M1-3) and late (M4-6) measurements, respectively, also predicted higher fall risk (M1-3 = 1.65 [1.08, 2.52]; M4-6 = 1.73 [1.03, 2.91]). Conclusions: OH was most prevalent immediately after standing, but most informative for fall risk in late and average measurements. Multiple standing BP measurements may improve the clinical assessment of OH.

Modest association between peak exercise blood pressure and ambulatory hypertension in endurance athletes

Abstract Funding Acknowledgements Type of funding sources: None. Background An exaggerated blood pressure (BP) response to exercise may be an early indicator of hypertension. However, it is common in endurance athletes and the association between systolic blood pressure (SBP) during exercise and hypertension is not well established in this group. Purpose To establish whether there is an association between exercise-induced hypertension (EIH) and clinical hypertension in endurance athletes. Methods 250 current and former endurance athletes (16-80 years, 75% male) performed a maximal exercise test on a cycle ergometer with BP measured every 2 min. Athletes were diagnosed with EIH based on international guidelines (SBP ≥210mmHg males, ≥190mmHg females). The relationship between SBP and workload was determined by linear regression analysis. Office hypertension was identified from either supine SBP ≥140mmHg or diastolic BP ≥90mmHg, or if treated for hypertension. Gold-standard 24-hour ambulatory blood pressure monitoring (ABPM) was performed in a subset of 42 athletes with EIH and 9 athletes with a normotensive response to exercise (NRE). Results On average, peak exercise SBP values were universally high (221±26mmHg in males and 199±21mmHg in females). 71% of athletes (70% of males and 74% of females) met criteria for EIH of which 12% had a peak SBP≥250mmHg. EIH and NRE groups were of similar age, sex, body mass index (BMI) and fitness (Figure 1). The strongest determinant of peak exercise SBP was exercise workload (R=0.78, P&amp;lt;0.001), which remained significant after adjusting for age, sex, BMI and antihypertensive medication (p&amp;lt;0.001) In the full cohort, resting SBP was higher in the EIH group (EIH: 128±13mmHg vs NRE: 122±15mmHg, P=0.006 – Figure 1), however there was a similar prevalence of office hypertension between the EIH (19%) and NRE (15%) groups (P=0.59). This prevalence remained similar (EIH: 13% vs NRE: 10%, P=0.49) after excluding those being treated for hypertension (n=15). In the subset of athletes who underwent 24h ABPM (n=51), there were no diagnoses of clinical hypertension in NRE (n=9, Figure 1). Of the 42 athletes with EIH, a majority (n=32, 76%) were normotensive on ABPM. In the 10 athletes with EIH and hypertension on ABPM, the majority were classified with Grade 1 hypertension (n=5) or daytime hypertension (n=3). Interestingly only two of these athletes would have been identified with office BP measures (see Figure 2). Conclusion EIH is common in endurance athletes and is strongly associated with peak exercise workloads suggesting this may be a reflection of superior cardiovascular fitness. In a small proportion of athletes, EIH may be associated with mild hypertension.

Obesity‐related higher blood pressure is associated with augmented transduction of spontaneous muscle sympathetic nerve activity

Central obesity is associated with elevated adrenergic activity and arterial blood pressure (BP). Therefore, we tested the hypothesis that transduction of spontaneous muscle sympathetic nerve activity (MSNA) to BP, i.e., sympathetic transduction, would be augmented in central obesity (increased waist circumference) and positively related to resting BP. Young/middle‐age obese (n=14) or non‐obese (n=14) adults without hypertension (average ambulatory 24‐hr BP&lt;130/80 mmHg) were included. MSNA (microneurography) and BP (finger cuff) were measured continuously for 10 min (supine) and bursts of MSNA were grouped into quartiles of burst clusters (1, 2, 3, 4+bursts) and burst amplitude. Beat‐to‐beat mean arterial pressure (MAP) was signal‐averaged over 10 cardiac cycles following each burst of MSNA. MSNA burst frequency was similar between obese and non‐obese (21±3vs.17±3 bursts/min, P=0.34). However, supine BP was significantly higher in obese compared with non‐obese (systolic: 127±3vs.114±3; diastolic: 76±2vs.64±1 mmHg, both P&lt;0.01). Importantly, obese showed greater MAP responses to clusters of bursts compared with non‐obese (e.g.,4th quartile: 4.5±0.4vs.3.3±0.4 mmHg, P=0.05), but did not show greater MAP responses to higher burst amplitude (P=0.13). MAP responses to clusters of bursts were positively correlated with systolic BP when controlling for age, sex, and MSNA (R=0.43, P=0.03), but this correlation was abolished when also controlling for BMI (R=0.20, P=0.34). Diastolic BP was only weakly correlated with MAP responses to clusters of bursts (R=0.27, P=0.20). These findings suggest that the pressor response to clustered bursts of MSNA (i.e., sympathetic transduction) is augmented in central obesity and may contribute to the obesity‐related rise in supine systolic BP.

Durability of the Clinical Benefit of Droxidopa for Neurogenic Orthostatic Hypotension During 12 Weeks of Open-Label Treatment.

IntroductionDroxidopa is approved to treat neurogenic orthostatic hypotension (nOH) symptoms in patients with autonomic failure based on short-term clinical trial data. Additional data on the long-term efficacy of droxidopa are needed. We have evaluated the 12-week efficacy and tolerability of droxidopa in patients with nOH in an open-label period of an ongoing phase 4 study .MethodsPatients received 12 weeks of open-label treatment with an individually optimized droxidopa dose (100–600 mg, 3 times daily) as identified during a preceding titration period. Patient-reported outcomes included the Orthostatic Hypotension Symptom Assessment (OHSA), Orthostatic Hypotension Daily Activity Scale (OHDAS), and clinician- and patient-rated Clinical Global Impression–Severity (CGI-S) scales. Supine blood pressure (BP) and adverse events (AEs) were recorded.ResultsData from 114 patients enrolled into the 12-week open-label period were available for analyses. After 12 weeks of droxidopa treatment, patients reported significant (P < 0.0001) improvements from baseline in OHSA and OHDAS composite and individual item scores and on clinician and patient CGI-S scores. Mean ± SD supine systolic and diastolic BP at week 12 increased by 15.5 ± 22.9 and 7.8 ± 11.7 mmHg from baseline, respectively (P < 0.0001 for both). The most frequently reported AEs were falls (17%), headache (13%), and dizziness (9%); one (0.9%) patient reported an AE of supine hypertension.ConclusionDuring 12 weeks of open-label treatment, droxidopa was associated with significant improvement from baseline in nOH symptoms and activities of daily living. No clinically important changes in supine hypertension or AEs of concern were observed. These results support the efficacy of droxidopa beyond 2 weeks of treatment. Trial RegistrationNCT02586623.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00317-5.

Orthostatic hypotension in kidney transplant recipients

Introduction: Orthostatic hypotension (OH) is associated with increased morbidity and mortality. The prevalence of OH in the general population is 2–26% and is strongly associated with age. The prevalence of OH in kidney transplant recipients (KTRs) is unknown. The study aimed to investigate the prevalence of OH among KTRs and to identify factors associated with this phenomenon. Material and methods: The study was designed as a cross-sectional analysis in KTRs at a routine visit in an outpatient department. Fifty KTRs aged 60 ± 12 years (21 female and 29 male) were investigated. The kidney transplant follow-up was 72 ± 63 months (range 3–243). All subjects underwent an orthostatic test (OT). Clinical and laboratory data were also analyzed. Results: OH was diagnosed in 17 (34%) patients (the OH+ group). KTRs with OH were older (63 ± 9 vs. 54 ± 13; p = 0.01) and were more often diabetic (53% vs. 24%; p = 0.04) than patients without OH. OH+ patients had higher supine systolic blood pressure (152 ± 23 vs. 134 ± 16; p = 0.006) and higher supine pulse rate (75 ± 12 vs. 68 ± 10; p = 0.047). A higher percentage of OH+ patients were taking beta-blockers (94% vs. 70%; p = 0.048) and calcium antagonists (88% vs. 52%; p = 0.01). Pulse rate did not change significantly during the OT in patients with OH, while it increased significantly in patients without OH. Conclusions: Orthostatic hypotension is a common finding among kidney transplant patients, particularly elderly patients with coexisting diabetes. Awareness of such a high prevalence of OH should encourage physicians to perform the orthostatic test in KTRs. Concomitant pulse rate measurement and analysis of current medications may contribute to a better understanding of OH pathogenesis in an individual patient.

Safety and Tolerability of Cael-101 in Combination with Anti-Plasma Cell Dyscrasia Therapy in Patients with AL Amyloidosis: 1-Year Results from an Open-Label Phase 2 Trial

Safety and Tolerability of Cael-101 in Combination with Anti-Plasma Cell Dyscrasia Therapy in Patients with AL Amyloidosis: 1-Year Results from an Open-Label Phase 2 Trial