scholarly journals Predictors of the Pressor Response to the Norepinephrine Transporter Inhibitor, Atomoxetine, in Neurogenic Orthostatic Hypotension

Author(s):  
Cyndya A. Shibao ◽  
Jose-Alberto Palma ◽  
Jorge E. Celedonio ◽  
Jose Martinez ◽  
Horacio Kaufmann ◽  
...  

We previously reported that the norepinephrine transporter inhibitor, atomoxetine, improved standing blood pressure and lightheadedness in patients with neurogenic orthostatic hypotension (nOH). The purpose of the present study was to determine the predictors of the pressor response to atomoxetine. Patients with nOH who participated in the clinical trials ( https://www.clinicaltrials.gov ; Unique identifiers: NCT00223691 and NCT01316666) were included in this retrospective analysis. All subjects underwent autonomic function testing, plasma norepinephrine, systolic, diastolic blood pressure, and symptoms assessments, whereas seated and standing, before, and 60 minutes after a single dose of atomoxetine 18 mg. A subset of 25 patients underwent iodine-123–labeled metaiodobenzylguanidine scanning to estimate the degree of cardiac sympathetic denervation. A total of 99 subjects with nOH (67±9 years old, 40 women) participated in the study, 35 with multiple system atrophy, 52 with pure autonomic failure, and 12 with Parkinson disease. The average orthostatic decrease in their systolic blood pressure/diastolic blood pressure was −52±26/−22±15 mm Hg. Supine plasma norepinephrine levels predicted the standing systolic blood pressure (adjusted R 2 was 0.12, F [3,80]=4.66, P =0.007) and diastolic blood pressure (adjusted R 2 was 0.18, F [3, 80]=7.04, P =0.001) in response to atomoxetine. The increase in systolic blood pressure after atomoxetine was associated with the decrease in nOH-related symptoms ( R 2 =0.14, F [1,44]=8.16 P =0.007). In conclusion, plasma norepinephrine was modestly associated with the pressor response to atomoxetine in patients with nOH. Additionally, the improvement in nOH-related symptoms was associated with the increase in the pressor response to atomoxetine.

Author(s):  
Horacio Kaufmann ◽  
Ross Vickery ◽  
Whedy Wang ◽  
Jitendra Kanodia ◽  
Cyndya A. Shibao ◽  
...  

Abstract Purpose In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension. Methods A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety. Results Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration. Conclusion Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure. Trial registration NCT02705755 (first posted March 10, 2016).


Author(s):  
Artaza Gilani ◽  
Raffaele De Caterina ◽  
Olia Papacosta ◽  
Lucy T. Lennon ◽  
Peter H. Whincup ◽  
...  

We have assessed the association between excessive orthostatic changes in blood pressure and risk of incident heart failure (HF) in older, community-dwelling men. This was a prospective cohort study of 3505 men (mean age, 68.5 years), who did not have prevalent HF, myocardial infarction, or stroke. Excessive orthostatic change in blood pressure was defined continuously and categorically as orthostatic hypotension (sitting-to-standing decrease in systolic blood pressure ≥20 mm Hg or diastolic blood pressure ≥10 mm Hg), systolic orthostatic hypertension (increase in systolic blood pressure ≥20 mm Hg, diastolic orthostatic hypertension as diastolic blood pressure ≥10 mm Hg), and orthostatic normotension (neither orthostatic hypotension nor orthostatic hypertension). There was a U-shaped association between orthostatic changes in systolic blood pressure and the risk of incident HF; for diastolic blood pressure, only its fall predicted HF. After adjustment for possible confounders, the hazard ratio (95% CI) for incident HF was 1.65 (1.24–2.18) in men with orthostatic hypotension and 0.90 (0.65–1.24) and 1.88 (1.30–2.73) in men with diastolic and systolic orthostatic hypertension, respectively. Both components of orthostatic hypotension were associated with increased risk, although the systolic component was more predictive than the diastolic component. Both orthostatic hypotension and orthostatic hypertension are associated with risk of incident HF in older men. Our findings suggest that orthostatic hypertension is defined by a rise beyond threshold in systolic blood pressure only. Further prospective studies in diverse cohorts are needed to confirm our findings.


2019 ◽  
Vol 10 (01) ◽  
pp. 33-44
Author(s):  
N.L.G. Sudaryati ◽  
I P. Sudiartawan ◽  
Dwi Mertha Adnyana

The aim of the study was to determine the effectiveness of giving hydrotherapi foot soak in hypertensive patients. The study was conducted with one group pretestposttest design without a control group by measuring blood pressure (pretest) before being given an intervention in the form of foot soak hydrotherm against 15 people with hypertension in Banjar Sri Mandala, Dauhwaru Village, Jembrana Subregency. Then do the blood pressure measurement again (posttest) after finishing the intervention. After the study was completed, the results showed that before the hydrotherapi foot bath intervention, there were 0% of patients classified as normal, 13.32% in prehypertension category, 60.08% in hypertension category I and 26.60% in hypertension category II. After the intervention was given, there were 13.32% of the patients classified as normal, 66.68% in the prehypertension category, 20.00% in the first category of hypertension and no patients belonging to the second grade hypertension category. There is a decrease of 20-30 mmHg for systolic blood pressure and 0-10 mmHg for diastolic blood pressure after intervention. Based on the results of the study it can be concluded that the hydrotherapi foot bath is effectively used to reduce blood pressure in hypertensive patients in the Banjar Sri Mandala, Dauhwaru Village, Jembrana District.


2016 ◽  
pp. 31-40
Author(s):  
Long Nhon Phan ◽  
Van Minh Huynh ◽  
Thi Kim Nhung Hoang ◽  
Van Nham Truong

Objective: To evaluate the results of treatment achieved blood pressure goal (BP goal) and results of hypertensive patient management. Subjects and methods: A study of 400 hypertensive patient intervention, treatment and management after 2 year. To assess the results of BP target, monitor the use of medicines, the situation of hospitalization and complications of stroke. Results: Treatment: -100% of patients using diuretics and angiotensin-converting enzyme inhibitors (ACEIs), 33% of patients using angiotensin receptor blockers (ARBs), 46.25% of patients using calcium channel blockers (CCBs) and 19.5% of patients using beta-blocker. After 24 months of treatment: 50.5% of patients using 1 antihypertensive drug, 22% of patients using 2 drugs, 20.5% of patients using 3 drugs and 7% of patients taking more than 3 drugs. After 24 months of treatment: 91.75% achieved BP target and 8.25% fail. -Average risk stratification: 97.32% achieved BP target, hight risk stratification: 95.91% and very hight risk stratification: 73.03%. After 24 months of treatment. -Stage 1: 88.48% achieved BP target, stage 2: 92.85% achieved BP target and stage 3: 71.08% achieved BP target. After 24 months of treatment. -Hypertesive results before treatment were: 159.80 ± 20,22mmHg average systolic blood pressure and 82.97 ± 5,82mmHg average diastolic blood pressure. After treatment: average systolic blood pressure 125.38 ± 6,88mmHg and average diastolic blood pressure 79.83 ± 1,79mmHg. No adverse change in the index of tests about lipidemia, liver, kidney, glucomia and no recorded cases of drug side effects. Management of patients: -There were 89% non-medical examinational patients 1 month, 5.25% non-medical examinational patients 2 months, 4.25% non-medical examinational patients 3 months and 1.5% non-medical examinational patients 4 months. There were 93.5% drop pill 1 month, 3.25% drop pill 2 months, 4.25% drop pill 3 months and no patient drop pill over 3 months. In 24 months follow-up, 47% hospitalized inpatients <5 times, 44.5% hospitalized inpatients 5-10 times, 3% hospitalized inpatients 11-15 times, 4.75% hospitalized inpatients from 16-20 times and 0.75% hospitalized inpatients > 20 times. -There were 32.75% hospitalized inpatients for reasons of hypertension and 63.75% hospitalized inpatients for other common diseases. -There were a total of 11592 contacts directly by phone for medical advice, medical reminders and examinational reminders during 24 months of management. -There were 0.5% of patients stroked during 24 months of treatment and management. Conclusion: Treatment by protocol and management by phone directly for medical taking and re-examinational reminders is the best resulted method of achieving blood pressure target and reducing complications of stroke for hypertensive patients. Key word: : blood pressure target; risk stratification; treatment; management; stage; phone.


2017 ◽  
pp. 88-92
Author(s):  
Van Hien Pham ◽  
Huu Vu Quang Nguyen ◽  
Tam Vo

Background: Cardiovascular diseases are the leading cause of death in patients with chronic renal failure. When a patient undergoes dialysis, making AVF or AVG causes cardiovascular events. Understanding the relationship between complications: hypertension, heart failure, AVF or AVG (formation time, position, diameter) helps us monitor, detect, prevent and treatment of complications to limit the risk of death in patients with dialysis. Objective: Relationship between cardiovascular diseases and anatomosis of arteriovenous fistular in patients with regularly hemodialysis at Cho Ray Hospital. Methods: A cross-sectional study was conducted at Cho Ray Hospital from 2015 to 2016. The survey some cardiovascular diseases are done by clinical examination, tests for diagnostic imaging such as X-ray, electrocardiogram and echocardiogram: heart and diameter of anastomosis AVF, AVG. Results: The study population included 303 patients with chronic renal failure who were dialysis. Of which, patients aged 25-45 accounted for the highest proportion (43.9%). The proportion of male and female patients was similar (48.5% and 51.5% respectively). The mean value of systolic blood pressure on patients made AVF, AVG less than 12 months is higher than patients made AVF, AVG over 12 months, and there is negative correlation (r = -0.43) between AVF, AVG and systolic blood pressure (p <0.05). The mean value of diastolic blood pressure on patients made AVF, AVG less than 12 months is lower than patients made AVF, AVG over 12 months, and and there is positive correlation (r = -0.43) between AVF, AVG and diastolic blood pressure (p <0.05) (p <0.05). The prevalence of patients with heart failure made AVF, AVG over 12 months is higher than that of the under 12 months group, there is a negative correlation (r = - 0.43) between AVF, AVG diameter and EF index (p <0.05). Conclusion: It is important to note the diameter of anastomosis AVF, AVG in patients with chronic renal failure dialysis to limit cardiovascular complications, especially heart failure. Key words: Chronic kidney disease, hemodialysis.


2021 ◽  
Vol 10 (7) ◽  
pp. 1426
Author(s):  
Bok-Nam Seo ◽  
Ojin Kwon ◽  
Siwoo Lee ◽  
Ho-Seok Kim ◽  
Kyung-Won Kang ◽  
...  

Postmenopausal women have a higher prevalence of hypertension compared to premenopausal women. Hypertension is a risk factor for cardiovascular diseases, the prevalence of which is ever increasing. This study investigated the effects of long-term acupuncture on lowering the blood pressure of postmenopausal women with prehypertension and stage 1 hypertension. Participants were 122 postmenopausal women aged less than 65 years, diagnosed with prehypertension or stage 1 hypertension (systolic blood pressure 120–159 mmHg or diastolic blood pressure 80–99 mmHg). We used a propensity score-matched design. The experimental group (n = 61) received acupuncture for four weeks every six months over a period of two years. The control group (n = 61) received no intervention. An Analysis of covariance (ANCOVA) was performed for the primary efficacy analysis. Relative risk ratios were used to compare group differences in treatment effects. Acupuncture significantly reduced the participants’ diastolic blood pressure (−9.92 mmHg; p < 0.001) and systolic blood pressure (−10.34 mmHg; p < 0.001) from baseline to follow-up. The results indicate that acupuncture alleviates hypertension in postmenopausal women, reducing their risk of developing cardiovascular diseases and improving their health and quality of life.


2017 ◽  
Vol 124 (6) ◽  
pp. 1107-1120 ◽  
Author(s):  
Heloyse E. G. Nunes ◽  
Carlos A. S. Alves ◽  
Eliane C. A. Gonçalves ◽  
Diego A. S. Silva

This study aimed to determine which of four selected physical fitness variables, would be most associated with blood pressure changes (systolic and diastolic) in a large sample of adolescents. This was a descriptive and cross-sectional, epidemiological study of 1,117 adolescents aged 14–19 years from southern Brazil. Systolic and diastolic blood pressure were measured by a digital pressure device, and the selected physical fitness variables were body composition (body mass index), flexibility (sit-and-reach test), muscle strength/resistance (manual dynamometer), and aerobic fitness (Modified Canadian Aerobic Fitness Test). Simple and multiple linear regression analyses revealed that aerobic fitness and muscle strength/resistance best explained variations in systolic blood pressure for boys (17.3% and 7.4% of variance) and girls (7.4% of variance). Aerobic fitness, body composition, and muscle strength/resistance are all important indicators of blood pressure control, but aerobic fitness was a stronger predictor of systolic blood pressure in boys and of diastolic blood pressure in both sexes.


1982 ◽  
Vol 50 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Richard J. Roberts ◽  
Theodore C. Weerts

This study was designed to determine if visualization of anger- and fear-provoking scenes produced differential physiological patterns similar to those produced by in vivo manipulations. Normotensive college students were selected on the basis of their responses to newly developed Anger and Fear/Anxiety questionnaires and for their ability to construct arousing scenes during a screening interview. In a 2 × 2 design (intensity × emotion), four scenes (high and low anger, high and low fear) were constructed individually for each of 16 subjects to imagine. Diastolic blood pressure, systolic blood pressure, and heart rate were monitored during visualization of each scene. Change in diastolic blood pressure was significantly greater for high anger than for high fear as predicted. Analysis of change in heart rate and systolic blood pressure showed significant effects for intensity only. These results provide further support for the concept of physiological differentiation in human emotion and suggest the utility of imagery for systematic study of human emotional responding.


2021 ◽  
Vol 10 (13) ◽  
pp. 2824
Author(s):  
Su-Kiat Chua ◽  
Wei-Ting Lai ◽  
Lung-Ching Chen ◽  
Huei-Fong Hung

Background: The management of hypertension remains suboptimal throughout the world. Methods: We performed a random-effects model meta-analysis of randomized controlled trials to determine the effectiveness and safety of sacubitril/valsartan (LCZ696) for the treatment of high arterial pressure. Relevant published articles from PubMed, Cochrane base, and Medline were examined, and the last search date was December 2020. Only published randomized controlled trials and double-blind studies were selected for further analysis. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position, as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were considered as safety outcomes. Results: Ten studies with a total of 5931patients were included for analysis. Compared with placebo, LCZ696 had a significant reduction in msSBP (weight mean difference (WMD) = −6.52 mmHg, 95% confidence interval (CI): −8.57 to −4.47; p < 0.001), msDBP (WMD = −3.32 mmHg, 95% CI: −4.57 to −2.07; p < 0.001), maSBP (WMD = −7.08 mmHg, 95% CI: −10.48 to −3.68; p < 0.001), maDBP (WMD = −3.28 mmHg, 95% CI: −4.55 to −2.02, p < 0.001). In subgroup analysis, only 200 mg and 400 mg LCZ696 showed a significant BP reduction. There was no difference in the AE rate between the LCZ696 and placebo groups (WMD = 1.02, 95% CI: 0.83 to 1.27, p = 0.54). Egger’s test revealed a potential publication bias for msSBP (p = 0.025), but no publication bias for other outcomes. Conclusion: LCZ696 may reduce blood pressure more efficaciously than traditional therapy in hypertensive patients without increasing adverse effects.


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