Abstract P118: Antihypertensive Treatment Guided By Genetics: Pearl-ht, The Randomized Proof-of-concept Trial Comparing Rostafuroxin With Losartan

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Lorena Citterio ◽  
Giuseppe Bianchi ◽  
Daniele Cusi ◽  
Mara Ferrandi ◽  
Chiara Livia Lanzani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sh2 Domain ◽  
Primary Hypertension ◽  
Chinese Patients ◽  
Gene Variants ◽  
Selective Blockade ◽  
Endogenous Ouabain ◽  
Genes Encoding ◽  
The Difference ◽  
Post Hoc

Primary hypertension contributes to more than 50% of all the worldwide cardiovascular deaths. Current antihypertensive therapy is still targeting the physiological mechanisms regulating blood pressure, but not the “causal” ones. So far, genetic studies have been unable to prove gene causation in human primary hypertension. In this study we compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension (PEARL-HT trial registration: EudraCT: 2010-022073-34, ClinicalTrials.gov: NCT01320397). Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10 -11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in Office Systolic Blood Pressure (OSBP) after two-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis ( LSS and HSD3B1 ), EO transport ( MDR1/ABCB1 ), adducin ( ADD1 and ADD3 ); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6-19.0), P =0.038 and 13.4 (25.4-2.5), P =0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former ( P =0.038); this difference was abolished by rostafuroxin at 10 -11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that the selective blockade of mutant adducin and endogenous ouabain pressor mechanisms by rostafuroxin improves the therapy of primary hypertension in in Caucasians carriers of the related gene variants.

scholarly journals Antihypertensive treatment guided by genetics: PEARL-HT, the randomized proof-of-concept trial comparing rostafuroxin with losartan

2021 ◽  
Author(s):  
Lorena Citterio ◽  
Giuseppe Bianchi ◽  
Giuseppe A. Scioli ◽  
Nicola Glorioso ◽  
Roberto Bigazzi ◽  
...  
Keyword(s):  
Sh2 Domain ◽  
Primary Hypertension ◽  
Chinese Patients ◽  
Group Differences ◽  
Endogenous Ouabain ◽  
Genes Encoding ◽  
H295r Cells ◽  
The Difference ◽  
Post Hoc ◽  
Losartan Treatment

AbstractWe compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10–11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6–19.0), P = 0.038 and 13.4 (25.4–2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10–11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.

High disease activity is associated with higher blood pressure in recent onset rheumatoid arthritis patients, post-hoc analyses of IMPROVED study

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Gegenava ◽  
SA Bergstra ◽  
H Maassen ◽  
CF Allaart
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Pressure ◽  
Disease Activity ◽  
Classification Criteria ◽  
Recent Onset ◽  
American College Of Rheumatology ◽  
Cardiovascular Morbidity And Mortality ◽  
The Difference ◽  
Post Hoc ◽  
Acpa Status

Abstract Funding Acknowledgements Type of funding sources: None. Background Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high prevalence of cardiovascular morbidity and mortality. Purpose: purpose of our project was to investigate the association between disease activity and systolic and diastolic blood pressure (SBP, DBP) in patients with recent-onset rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) who were treated to target disease activity score (DAS)<1.6 in the IMPROVED study. Methods: The associations between disease activity and SBP/DBP were tested for 610 patients (364 RA, 246 UA), cross-sectionally and over time. GEE analyses were performed with both SBP and DBP as outcome measures and disease activity categories (DAS<1.6;>1.6 but ≤2.4; >2.4), CRP level, treatment arms or the number of visits on a certain drug as potential predictors in separate analyses. Separate analyses tested potential contributions of gender, anti-cyclic citrullinated peptide antibodies (ACPA) status, and fulfilling the 2010 ACR/EULAR (American college of rheumatology/ European league against rheumatism) classification criteria. In addition association of BP with various levels of disease activity was tested with T-test. Results: At the baseline mean (SD) SBP was 133 (20) and DBP mean (SD) was 80 (10).  SBP > 140mm Hg was observed in 40% of patients and DBP > 90 mm Hg  in 21% of patients. SBP and DBP statistically significantly decreased during 5 years follow up (mainly during year 1), but the difference in mm Hg was small. Estimates from GEE analysis showed that patients with high DAS >2.4 (HDAS) had a statistically significantly higher SBP (average 3 mm Hg higher, 95% CI 1.7; 4.2, p < 0.01), than the patients in with DAS ≤2.4. ANOVA analyses showed a statistically significant association between SBP and DAS. In addition, post hoc analyses showed that patients with HDAS had a statistically significantly higher  SBP (mean (SD) 132 (19) than the patients with DAS < 1.6 (remission) (mean (SD) 129 (20), p < 0.01), and patients in LDAS but DAS≥1.6 had a statistically significantly higher SBP (mean (SD) 131 (19) than the patients in remission (mean (SD)  129 (20), p = 0.02) (Figure 1), whereas no association was found between DAS category and DBP. Gender, ACPA status or fulfilling the 2010 classification criteria did not influence the relation between DAS and blood pressure. Conclusions: In patients with RA or UA, a higher DAS is associated with higher blood pressure, but the clinical impact is unclear. Abstract Figure 1

scholarly journals A Comparison of the Incidence and Nature of Cardiac Dysrhythmias Occurring during Enflurane and Isoflurane Anaesthesia for Dental Surgery

1987 ◽  
Vol 15 (2) ◽  
pp. 179-184 ◽  
Author(s):  
M. R. C. Rodrigo ◽  
T. M. Moles ◽  
P. K. Lee
Keyword(s):  
Blood Pressure ◽  
Sinus Tachycardia ◽  
Third Molar ◽  
Chinese Patients ◽  
Dental Surgery ◽  
Cardiac Dysrhythmias ◽  
Life Threatening ◽  
The Difference ◽  
Clinically Significant ◽  
Ventricular Ectopics

The incidence and nature of dysrhythmias with equipotent concentrations of enflurane and isoflurane during dental surgery were compared. Seventy-six Chinese patients between 17–30 years, of ASA Grade I, randomly received either enflurane or isoflurane with N2O and O2 for spontaneous ventilation during third molar extractions. The cardiac rhythm and the blood pressure were continuously monitored during the procedure. The incidence of dysrhythmias with both enflurane and isoflurane was low and the difference not statistically significant. During surgery one patient exhibited unifocal ventricular ectopics with isoflurane. Sinus tachycardia was common with both agents. No life-threatening dysrhythmias were seen with either agent and no clinically significant lowering of blood pressure occurred in association with the exhibited dysrhythmias. In this Chinese population, as in other studies, the incidence of dysrhythmias with both agents was low thus showing no difference between the races.

Abstract WP58: Admission Blood Pressure and Infarct Volume in Patients With Large Vessel Occlusions. Insights From the ASTER Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mohammad Anadani ◽  
Bertrand Lapergue ◽  
Michel Piotin ◽  
Maéva Kyheng ◽  
Julien Labreuche ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diffusion Weighted Imaging ◽  
Mechanical Thrombectomy ◽  
Infarct Volume ◽  
Significant Negative Correlation ◽  
Functional Independence ◽  
Post Hoc Analysis ◽  
Post Procedure ◽  
The Difference ◽  
Post Hoc

Background: Higher systolic blood pressure (SBP) has been shown to be associated with worse outcome after mechanical thrombectomy. However, it is still unknown if higher admission SBP is just an epiphenomenon of higher infarct volume leading to the worse outcome or if the SBP association with the outcome is independent of infarct volume. In this study, we aimed to study the correlation between admission SBP and both admission infarct volume and 24 change in infarct volume. Methods: This is a post hoc analysis of the ASTER randomized trial. Cuff admission SBP was measured on presentation prior to thrombectomy. Diffusion-weighted imaging (DWI) infarct volume was measured on admission and at 24-hours post-procedure. Delta volume was measured by calculating the difference between the admission and 24-hour DWI lesions. Results: A total of 126 patients (mean age was 68.9 ± 14.8 years, median NIHSS was 17 (IQR, 11 to 20), 66% received tPA and 87% achieved mTICI 2b-3 at the end of the procedure) had MRI on admission and were included in this study. There was weak and not statistically significant negative correlation between admission SBP and infarct volume (R=-0.15; P=0.08). We did not find any correlation between admission SBP and 24 hours delta infarct volume. On generalized logistic regression analysis adjusting for infarct volume, SBP was associated with 90-day functional independence (modified Rankin Scale <3) (OR,0.84; 95% CI, 0.70-0.99; p=0.049). Conclusion: We did not find a significant correlation between infarct volume on admission and admission SBP. Moreover, the association between admission SBP and functional outcome was independent of infarct volume.

scholarly journals Difference In The Lower Blood Pressure Of Primary Hypertension Patients Participating In Prolanis And Non Prolanis In The Cipayung District Health Center

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Alviani Latifah Fuat ◽  
Fajar Susanti ◽  
Erlin Ifadah
Keyword(s):  
Blood Pressure ◽  
Health Center ◽  
Blood Pressure Reduction ◽  
Primary Hypertension ◽  
Pressure Reduction ◽  
District Health ◽  
Comparison Research ◽  
Study Population ◽  
The Difference ◽  
The Government

Changes in human development at this time greatly affect lifestyles it is a cause of an increase in non- communicable diseases (PTM) one of which is hypertension. Hypertension control has been pursued by the government by implementing a chronic disease prevention program (PROLANIS) through collaboration with BPJS. This study aims to determine the difference in blood pressure reduction in primary hypertension patients who follow prolanis and non prolanis in the Cipayung District Health Center. Pre-experimental research design with static group comparison research. The study population was primary hypertension patients who followed prolanis and non prolanis in the Cipayung District Health Center. Samples were taken by purposive sampling and found 40 people. The collected data is tested statistically by T-test. The results of the study of primary hypertension patients who follow Prolanis have better blood pressure. Statistical test results showed there were differences in blood pressure reduction in primary hypertension patients who followed prolanis and non prolanis (p = 0,000, p <0.05). Nurses provide education to primary hypertension patients who have not yet joined the program to participate in the PROLANIS program.Keyword: Hypertension, Blood Pressure, PROLANIS

scholarly journals Psychosocial aspects, body composition and hemodynamics parameters in Scouts.

2020 ◽  
pp. 1-5
Author(s):  
Patrícia Espíndola Mota Venâncio ◽  
Mário Henrique Fernandes ◽  
Viviane Soares ◽  
Iransé Oliveira-Silva ◽  
Deise Aparecida de Almeida Pires-Oliveira ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Children And Adolescents ◽  
Categorical Variables ◽  
Anxiety And Depression ◽  
Physical Situation ◽  
Boy Scouts ◽  
Chi Square ◽  
The Difference ◽  
Post Hoc ◽  
Anxiety Depression

Background: In order for the activities carried out by the boy scouts to achieve the objectives foreseen in their planning, it is important to have concrete data on the physical situation of children and adolescents, such as blood pressure, knowledge of how children are related to their degree of stress, anxiety and depression. Objectives: To identify blood pressure, Body mass index (BMI), and scores of stress, anxiety and depression in boy scouts from 7 to 17 years of age from the Bernardo Sayão Scout Group of the city of Anápolis in Goiás. Material and method: Adolescents from 7 to 17 years of age of both genders. BMI data were collected and a stress, anxiety and depression questionnaire was applied and blood pressure was measured. The normality of the data was verified with the Shapiro-Wilk test. The difference between the three groups was verified by the Dunusk’s post-hoc Kruskall-Wallis test. The categorical variables were analyzed by the Chi-square and the Spearman correlation coefficient verified the relationship between age and the variables Systolic Blood Pressure (SBP), Dyastolic Blood Pressure (DBP), BMI, anxiety, depression and stress. Results: The SBP of the participants in the “little wolf” category was inferior when compared to the scouts (p <0.001) and senior (p = 0.004), and the same happened with the PAD (little wolf x scout, p = 0.03 and little wolf x senior, P = 0.005). An association was found between BMI and sections. Most of the juniors, scouts and seniors were underweight. Among scouts children and adolescents there was a significant association with stress. In the category of the “little wolf” was found 53.60% of the children with very intense stress. The correlation between the variables SBP, DBP, BMI, anxiety, depression and stress with the age of children and adolescents. Age correlated negatively with anxiety, depression, and stress. Thus, as children are younger increases the degree of anxiety, depression and stress. Conclusion: The little wolf category had better BP results than the other categories, but they had higher levels of stress, depression and greater anxiety.

The Effects of a Caffeine Placebo and Experimenter Expectation on Blood Pressure, Heart Rate, Well-Being, and Cognitive Performance

2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cognitive Task ◽  
Well Being ◽  
Control Group ◽  
Double Blind ◽  
Main Effect ◽  
The Difference ◽  
Being There ◽  
To Receive

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.

PENGARUH TERAPI TERTAWA TERHADAP PENURUNAN TEKANAN DARAH LANSIA DI UPT PANTI WREDHA BUDHI DHARMA YOGYAKARTA

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Niken Setyaningrum ◽  
Andri Setyorini ◽  
Fachruddin Tri Fitrianta
Keyword(s):  
Blood Pressure ◽  
Data Analysis ◽  
The Elderly ◽  
Control Group ◽  
Group Comparison ◽  
Control Blood Pressure ◽  
Men And Women ◽  
Treatment Of Hypertension ◽  
Before And After ◽  
The Difference

ABSTRACTBackground: Hypertension is one of the most common diseases, because this disease is suffered byboth men and women, as well as adults and young people. Treatment of hypertension does not onlyrely on medications from the doctor or regulate diet alone, but it is also important to make our bodyalways relaxed. Laughter can help to control blood pressure by reducing endocrine stress andcreating a relaxed condition to deal with relaxation.Objective: The general objective of the study was to determine the effect of laughter therapy ondecreasing elderly blood pressure in UPT Panti Wredha Budhi Dharma Yogyakarta.Methods: The design used in this study is a pre-experimental design study with one group pre-posttestresearch design where there is no control group (comparison). The population in this study wereelderly aged over> 60 years at 55 UPT Panti Wredha Budhi Dharma Yogyakarta. The method oftaking in this study uses total sampling. The sample in this study were 55 elderly. Data analysis wasused to determine the difference in blood pressure before and after laughing therapy with a ratio datascale that was using Pairs T-TestResult: There is an effect of laughing therapy on blood pressure in the elderly at UPT Panti WredhaBudhi Dharma Yogyakarta marked with a significant value of 0.000 (P <0.05)

The Randomized Clinical Trial of Pentoxifylline for Reduction of Blood Pressure in Patients with Primary Hypertension

2020 ◽  
Vol 26 (3) ◽  
pp. 279-286
Author(s):  
Hossein Namdar ◽  
Sajad Khiali ◽  
Naser Khezerlou Aghdam ◽  
Afshin Gharekhani ◽  
Taher Entezari-Maleki
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Primary Hypertension

Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-Acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-Analysis of the COPE Trial

2020 ◽  
Vol 16 ◽  
Author(s):  
Seiji Umemoto ◽  
Toshio Ogihara ◽  
Masunori Matsuzaki ◽  
Hiromi Rakugi ◽  
Kazuyuki Shimada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Rank Test ◽  
Vascular Events ◽  
Treatment Groups ◽  
Β Blocker ◽  
The Difference ◽  
Long Acting

Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events) three benidipine (a calcium channel blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional angiotensin receptor blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events p=0.92 renal events p=0.16 log-rank test. Conclusions: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there is no enough these events to compare the difference in the three treatment groups.

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