bluuebunny/crossref_metadata_2025_split huggingface dataset:
O70 INVOLVEMENT OF MICRORNAs-146a-5P, -155-5P, AND -29b-5P IN CARDIAC REMODELLING AND DYSFUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Mkhize Siluleko , Manilall Ashmeetha , Gunter Sule , Mokotedi Lebogang , Millen Aletta AM , Nthlane Refentshe , Michel Frederic S 
Published: September 2024

Background:
MicroRNAs have been implicated in the pathogenesis of cardiovascular disease. However, the contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology.

Aim:
We investigated the role of miR-146a-5p, -155-5p, and -29b-5p in the development of cardiac hypertrophy and dysfunction in male and female spontaneously hypertensive rats (SHR).

Methods:
Seven (7)-month-old SHR (n=7 male, n=10 female), and age- and sex-matched normotensive Wistar Kyoto rats (WKY, n=7 male, n=9 female) were used for the study. Cardiac geometry and function were determined from echocardiography. Plasma levels of inflammatory markers were measured by ELISA. Collagen fraction area was determined from histological sections of the left ventricle (LV). MicroRNA, and mRNA expression of target genes was determined in the LV by RT-qPCR. Group differences were ascertained from 2-way ANOVA. Associations were determined from pearson's correlation.

Results:
In SHR, normalised heart and LV masses, LVPWTd, RWT, E, A, E/e’, and collagen fraction area were significantly greater compared to WKY. MidFS, e’, and a’ were significantly lower in SHR versus WKY. Female rats exhibited significantly greater LV mRNA expression of Lox1, Col1a/Col3a ratio, and plasma levels of CRP, IL-6, and TNF-α compared to males. MiR-29b-5p showed similar expression levels across experimental groups. MiR-146a-5p was upregulated in SHR and exhibited positive associations with BP, normalised heart and LV masses, RWT, collagen fraction area, and E/e’ ratio, but negative associations with e’. Conversely, miR-155-5p was downregulated in females and only positively associated with absolute heart, LV, kidney masses, and stroke volume.

Conclusion:
Upregulation of miR-146a-5p was associated with indices of concentric LVH, diastolic dysfunction, reactive fibrosis, and may be involved in the hypertensive-induced LV remodelling; whereas, changes in expression of miR-155-5p may be involved with a cardiac phenotype related to sexual dimorphism.
O72 ASSOCIATION BETWEEN CUMULATIVE BLOOD PRESSURE AND RISK OF GASTEROINTESTINAL CANCER
Authors: Liu Qian , Si Fei , Wu Yuntao , Yu Jing 
Published: September 2024

Objective:
We aimed to examine the association between cumulative blood pressure (cumBP) and risk of gastrointestinal cancer.

Methods:
The Kailuan study is a prospective cohort study based on community. CumBP (mmHg year) was calculated as follows: cumBP = [(BP1 + BP2)/2 time1-2] + [(BP2 + BP3)/2 time2-3]. All participants were into four groups according to the quartiles of cumBP. The association between quartiles of cumBP or duration of hypertension and gastrointestinal cancer was assessed by the Cox proportional hazards models (hazard ratios [HRs], 95%confidence intervals [CI]).

Results:
During the median follow-up time of 11 years, a total of 624 (0.95%) participants gastrointestinal cancer occurred among 65,734 participants. The Kaplan-Meier curves showed that higher quartiles on cumulative systolic blood pressure (cumSBP), cumulative diastolic blood pressure (cumDBP) and cumulative pulse pressure (cumPP) or duration of hypertension are strongly associated with an increased risk of gastrointestinal cancer. After adjusting for covariables, compared with the lowest quartile of cumSBP, cumDBP and cumPP, the HRs (95%CI) of gastrointestinal cancer in highest quartiles were 1.96 (1.44-2.67), 1.29 (0.98-1.71), and 2.18 (1.62-2.92), respectively. Furthermore, compared to those with hypertension unexposed, participants with a 6 years exposure duration of hypertension had 1.37-fold higher risk of gastrointestinal cancer.

Conclusions:
The higher exposure of cumSBP, cumPP and duration of hypertension are associated with an increased risk of gastrointestinal cancer. Striving to control long-term SBP, PP and hypertension across the life course, and avoiding to develop hypertension by keeping good pathways such as health lifestyles could be of enormous benefit for gastrointestinal cancer risk reduction.
O74 EPOXYEICOSATRIENOIC ACIDS ANALOGUE (EET-A) FOR THE TREATMENT OF CHEMOTHERAPY-INDUCED HEART FAILURE WITH NEPHROTIC SYNDROME
Authors: Gawrys Olga , Škaroupková Petra , Kikerlová Soňa , Vaňourková Zdeňka , Imig John D. , Cervenka Ludek 
Published: September 2024

Background and Objective:
Doxorubicin (DOXO) is still commonly used anthracycline for the treatment of many types of cancers, but its application is burdened with a high risk of cardiotoxicity. The exact mechanisms of DOXO cardiotoxicity are still under investigation. Currently it is believed that the formation of topoisomerase II beta complex with DOXO, together with increased levels of reactive oxygen species (ROS) leads to cardiotoxicity. However, many additional mechanisms can weaken the heart and contribute to HFrEF development. Few years ago, new hypothesis emerged linking the DOXO-cardiotoxicity with the diminished expression of CYP2J2, an isoform of cytochrome P450, which is responsible for epoxyeicosatrienoic acids (EETs) formation. EETs were shown to exhibit vasodilation, decrease inflammation and to promote sodium excretion. Cardiac CYP2J2 overexpression decreased the cardiac injury in DOXO-treated mice. Hence, we decided to test the effectiveness of the EETs analogue (EET-A) in a model of DOXO-induced HFrEF with nephrotic syndrome.

Methods:
DOXO was administered to male Ren-2 transgenic rats (TGR) via five intravenous injections (cumulative dose 10 mg/kg of body weight). The long-term survival (20 weeks) of rats treated with EET-A (10 mg/kg of body weight administered in drinking water) was compared to ACE inhibitor (ACEi). Cardiac function was evaluated by echocardiography, urine and blood were collected for analysis.

Results:
The treatment with EET-A did not improve survival and cardiac function measured by echocardiography, however there was a clear renoprotective effect observed. Albuminuria was significantly lower in the EET-A treated group, when compared to ACEi. Plasma albumin did not change after 4-week treatment with EET-A, whereas in both placebo and ACEi a significant decrease was recorded.

Conclusions:
Despite the lack of improvement of survival, the beneficial effect of EET-A on the kidneys supports its potential for nephrotic syndrome treatment.
Supported by MH CZ - DRO (“Institute for Clinical and Experimental Medicine - IKEM, IN 00023001”)
O82 NUTRITIONAL DEFICIENCIES AND HYPERTENSION: EXPLORING THE ROLE OF POTASSIUM, MAGNESIUM, AND VITAMIN D ACROSS DIVERSE POPULATIONS: A NARRATIVE REVIEW STUDY
Authors: Ahmed Wishah M.nour , Behairy Hind 
Published: September 2024

Background:
Globally, hypertension is a prevalent risk factor for cardiovascular and kidney diseases, and death. It is well recognized that a healthy diet and nutrition are essential for the treatment and control of hypertension.

Objectives:
to identify the role of potassium, magnesium, and vitamin D in blood pressure regulation and to assess the gaps in nutrition and diverse diets regarding hypertension management across the globe.

Methodology:
The Methods of Searching were established on the 10th of April 2024: Scholar chat, Consensus tools for Artificial intelligence searching, and the Use of research databases in PubMed and Google Scholar, and other programs like Grammarly, Endnote, and Quillbot were used.
Results: This study explored the relationship between dietary deficiencies and hypertension, focusing on potassium, magnesium, and vitamin D. It examined research findings across diverse populations. The Key Findings were: that 100% of 46 research studies stated Lower blood pressure is associated with higher dietary potassium intake. Although the evidence for magnesium and vitamin D is not as strong, 6 studies (13%) stated that they reduce systolic blood pressure, 12 studies (26%) stated that Magnesium has an effect but not identified, 10 Studies (22%) stated that Vitamin D decreases blood pressure alone and 3 Studies (7%) stated that Magnesium and vitamin D have no effect concluding that Fruits, and vegetables, and whole grain-rich diets appear to be protective against hypertension. Research Needs: More investigation is required to determine the causal links between individual nutrients—particularly magnesium and vitamin D—and blood pressure. To account for any variances, research should involve a variety of populations.

Conclusion:
a diet high in fruits, vegetables, and whole grains appears to protect against hypertension. The cause-and-effect interactions between certain nutrients and blood pressure require further investigation; this is especially the case for magnesium and vitamin D.
O87 CONCORDANCE BETWEEN NOCTURNAL CARDIAC OUTPUT ESTIMATED WITH A NOVEL NON-INVASIVE METHOD USING BRACHIAL OSCILLOMETRIC BLOOD PRESSURE MEASUREMENTS AND ECHOCARDIOGRAPHY
Authors: Fernández-Ruíz Ricardo , Álvarez-Montoya Diego , Jaramillo-Gómez Carlos , Madrid-Muñoz Camilo , Gallo-Villegas Jaime , Aristizábal-Ocampo Dagnovar 
Published: September 2024

Background and Objective:
Nocturnal hypertension, characterized by elevated blood pressure (BP) levels during sleep as measured by 24-hour ambulatory blood pressure monitoring (24-h ABPM), has garnered increasing interest. However, understanding the explanatory mechanisms and non-invasive demonstration of these alterations poses challenges. We developed a non-invasive method to estimate cardiac output (CO) using brachial oscillometric BP measurements based on total arterial compliance (Ct). Yet, the agreement between estimated nocturnal CO and echocardiography-measured CO, considered the gold standard at rest, remains uncertain. This study aims to evaluate the concordance between the two methods.

Methods:
A cross-sectional study was conducted involving 216 adult patients who underwent Doppler echocardiograms and 24-h ABPM, regardless of valvular or cardiac pathology, or medication use, provided they had normal aortic valvular anatomy. Stroke volume was calculated as the product of the cross-sectional area of the aortic annulus and the average velocity of the left ventricular outflow tract. Using nocturnal BP and heart rate measurements from the 24-hour ABPM, along with weight, height, age, and sex, Ct and CO were estimated. Values were compared to determine validity.

Results:
Of the participants, 50.0% were men, with an average age of 54.0±14.0 years. Among them, three had a history of myocardial infarction, nineteen were diabetic, and one hundred thirty-six were hypertensive. CO measured by echocardiography averaged 4.9±1.0 L/min, ranging from 2.8 to 8.1 L/min. The agreement of CO between the new method and Doppler echocardiography was good, with an intraclass correlation coefficient of 0.421 (95%CI 0.305 to 0.525). The mean difference was 0.027±0.977 L/min (95%CI -0.104 to -0.157). Bland-Altman plots demonstrated that the differences between the methods were randomly distributed along the mean difference line (Figure).

Conclusions:
The novel method for estimating nocturnal CO based on Ct using brachial oscillometric BP measurements demonstrate validity across various clinical conditions. Its adoption in clinical settings could simplify the assessment of nocturnal hypertension with 24-h ABPM.
O89 POOLED, LONG-TERM ANALYSIS OF THE GLOBAL SYMPLICITY CLINICAL TRIAL PROGRAM OF RADIOFREQUENCY RENAL DENERVATION FOR THE TREATMENT OF UNCONTROLLED HYPERTENSION
Authors: Mahfoud Felix , Townsend Raymond , Mancia Giuseppe , Kandzari David , Whitbourn Robert , Bhatt Deepak , Bakris George , Kario Kazuomi , Fahy Martin , Böhm Michael 
Published: September 2024

Background/Objective:
The Global Symplicity Clinical program is the largest investigation of radiofrequency renal denervation (RDN) to treat uncontrolled hypertension (HTN) to date. Over 4,000 patients enrolled into Spyral First-in-Man, Global SYMPLICITY Registry DEFINE, and multiple randomized, controlled and sham controlled trials including HTN-Japan, Symplicity HTN-3, SPYRAL HTN-OFF and -ON MED studies. We leveraged the entire Symplicity Global Clinical program dataset to develop a multivariate, patient-level, mixed model assessing (1) long-term BP reductions after RDN, and (2) whether specific patient characteristics correlate with future BP reductions after the procedure.

Methods:
Repeated BP measurements from each patient in the Global Symplicity Clinical program were analyzed using linear mixed models fitted with 24-h ambulatory systolic (S)BP and office SBP as outcome variables. Baseline SBP, baseline number of antihypertensive (AH) medications, and AH medications over time were included as fixed effects. Additional patient characteristics were included as potential significant fixed effects. To account for multiple BP measurements per patient and multiple studies, nested random effects were included using an auto-regressive correlation structure.

Results:
Data from 4156 patients treated with either the first-generation Symplicity Flex or the next-generation Symplicity Spyral catheter. Estimated, office and 24-h ambulatory SBP changes through 36 months, after adjusting for AH medication effects, were biphasic with a steep reduction after RDN through the first 6 months (Figure), followed by a steady reduction in SBP afterward through 36 months. Higher baseline SBP was correlated with greater BP reductions. AF history (-3.7 mmHg compared to no AF, p=0.0048) and increasing eGFR at baseline (-0.039 mmHg for every 1 ml/min increase in baseline eGFR, p=0.040) significantly correlated with lower 24-h ambulatory SBP.

Conclusion:
This is the most comprehensive analysis of radiofrequency RDN to date. Higher baseline SBP was strongly correlated with greater BP reductions. The results demonstrate the durability of RDN as an adjunctive therapy to treat HTN. Prospective studies need to validate whether certain patient characteristics are associated with improved response to RDN.
O91 SIGNIFICANT NIGHTTIME BLOOD PRESSURE REDUCTIONS FOLLOWING RENAL DENERVATION IN PATIENTS WITH UNCONTROLLED HYPERTENSION: POOLED ANALYSIS FROM THE SPYRAL HTN TRIALS
Authors: Kario Kazuomi , Mahfoud Felix , Townsend Raymond R. , Kandzari David E , Weber Michael A , Schmieder Roland E , Tsioufis Konstantinos , Fahy Martin , Böhm MD Michael 
Published: September 2024

Objective:
Elevated nighttime systolic blood pressure (SBP) is more strongly associated with risk for cardiovascular events than daytime or office SBP. We assessed whether radiofrequency renal denervation (RF RDN) reduces nighttime SBP, in addition to other times of the day.

Design and Method:
We pooled data from patients with uncontrolled hypertension undergoing RF RDN using the latest-generation SpyralTM multi-electrode catheter, from the published, SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-ambulatory SBP were evaluated at baseline and at 12 months. Different time ranges were evaluated including nighttime (1am-6am), morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urinary drug testing, where available, was assessed at baseline and at 12 months.

Results:
Data from 388 patients undergoing RDN were pooled. Patients were 54±10yrs old, 26.8% female, BMI 31.3±6.0, 45.1% with >10yrs diagnosis of hypertension, 7.7% type 2 diabetes, 9.8% obstructive sleep apnea, 47.7% history of smoking. The baseline nighttime SBP was 139±11mmHg, and 92.5% had nocturnal hypertension (BP ≥120/70 mmHg). Patients took 1.0±1.2 antihypertensive drugs with drug burden of 1.6±3.1 at baseline.
12 months after RDN, 30.6% of patients no longer had nocturnal hypertension (p<0.0001). The overall 24-h ambulatory SBP reduced by -11.9±12.4mmHg, nighttime -10.8±15.4mmHg, morning -12.8±20.4mmHg, daytime -12.2±13.6mmHg, and office -17.7±15.4mmHg (Figure). Patients took 1.8±1.1 antihypertensive drugs with drug burden of 2.9±3.0 at 12 months. Results from 24 months, not currently available, will also be presented.

Conclusions:
In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. RF RDN achieved clinically meaningful reductions throughout the 24-hr circadian cycle including the nighttime SBP, when CV risk is highest. RF RDN, in addition to pharmacotherapy, may help to reduce this risk.
O92 EFFICACY AND SAFETY OF LOW-DOSE ANTIHYPERTENSIVE COMBINATION DRUGS INCLUDING AMLODIPINE, TELMISARTAN, AND CHLORTHALIDONE: A MULTICENTER, RANDOMIZED, DOUBLE-BLINDED, PARALLEL, PHASE II CLINICAL TRIAL
Authors: Park Chang Gyu , Ahn Jeong Cheon , Han Seung Hwan , Kim Moo Hyun , Hong Seung Pyo , Shin Jinho , Sung Jung Hoon , Sohn Il Suk , Cho Eun Joo , Kim Seok Yeon 
Published: September 2024

Background and Objective:
Although single pill high-dose triple antihypertensive combinations are already available on South Korea, there are no reports evaluating the efficacy and safety of the low-dose combination of amlodipine, telmisartan, and chlorthalidone. The aim of this clinical trial was to assess the efficacy and safety of low-dose combination drug containing telmisartan (20 mg), amlodipine (2.5 mg), and chlorthalidone (6.25 mg).

Methods:
This study was a randomized, double-blinded, parallel, multicenter, phase II clinical trial. In total, 221 subjects from 21 clinical trial sites in South Korea were randomly assigned to groups 1 (AD-209; telmisartan 20 mg/amlodipine 2.5 mg/chlorthalidone 6.25 mg), 2 (AD-209-1A; telmisartan 20 mg/amlodipine 2.5 mg), 3 (AD-209-1B; amlodipine 2.5 mg/chlorthalidone 6.25 mg), and 4 (AD-209-1C; telmisartan 20 mg/chlorthalidone 6.25 mg) in a 1:1:1:1 ratio, and the treatments lasted 8 weeks. After the initial drug administration, the subjects visited the clinical trial sites at weeks 4 and 8 to evaluate drug efficacy and safety.

Results:
In patients with mild-moderate hypertension, the mean change in MSSBP from baseline to week 8 between group 1 and groups 2, 3, and 4 was -5.93, -8.69, and -1.51 mmHg, respectively. The blood pressure of the subjects in group 1 was significantly lower than that of those in groups 2 and 3. It was also lower than that of subjects in group 4 although this difference was not significant. Among the 221 subjects enrolled, 20 (9.05%) experienced 25 treatment-emergent adverse events (TEAEs); of these, 14 (6.33%) experienced 17 adverse drug reactions (ADRs). No significant differences in the TEAE or ADR incidence rates were found between group 1 and groups 2, 3, and 4.

Conclusions:
AD-209 (telmisartan 20 mg/amlodipine 2.5 mg/chlorthalidone 6.25 mg), a low-dose triple combination drug, demonstrated a higher blood pressure lowering effect than the corresponding a low-dose dual combination drugs in patients with essential hypertension. Its safety was similar to that of the dual-combination drugs.
O94 MOST EFFECTIVE EXERCISE INTERVENTIONS FOR REDUCING SHORT-TERM BLOOD PRESSURE VARIABILITY: A META-ANALYSIS
Authors: Hao Ziyu , Tran Joshua YS , Yiu Karen KL , Tsoi Kelvin Kf 
Published: September 2024

Objective:
Blood pressure variability (BPV) is a risk factor for cardiovascular disease. Growing evidence suggests that exercise plays a critical role in reducing BPV. Hence, this study aimed to examine the specific types of exercise that are most effective in reducing BPV.

Design and Method:
A literature search was conducted across electronic databases including MEDLINE, Embase, and PsycINFO from their inception to February 2024. The assessment of short-term BPV involved the utilization of diverse equations, such as standard deviations, coefficient of variation, and average real variability, as reported in the included studies. Regarding the heterogeneity arising from the varied calculation methods, standardized mean differences were employed. The heterogeneity was carried out using the I2 statistic, with a fixed-effect Mantel-Haenszel model applied in cases where I2 < 50%, and a random-effect model employed when I2 > 50%.

Results:
A total of 8,359 literature records were identified from the electronic databases, 21 articles met the inclusion criteria and were included in this study. Among these, 12 articles were randomized controlled trials (RCTs), 4 were pre-post clinical trials, 2 were cross-sectional studies, and 3 were cohort studies. Among the RCTs, 11 studies focused on short-term blood pressure variability (BPV) as the primary outcome, while the remaining 2 RCTs examined long-term BPV. The collective analysis of 529 participants revealed that exercise interventions resulted in significant improvements in short-term SBPV (standardized mean difference [SMD] [95% CI] = -0.56 [-1.04 to -0.09]) and DBPV (-0.62 [-1.02 to -0.22]). Specifically, resistance exercise demonstrated notable reductions in SBPV (-0.62 [-1.15 to -0.10]), while no significant effects were observed on DBPV (0.04 [-0.54 to 0.62]). Conversely, aerobic exercise exhibited beneficial effects on both SBPV (-0.57 [-1.16 to 0.01]) and DBPV (-0.82 [-1.43 to -0.21]) (Table 1).

Conclusion:
Exercise interventions showed significant improvements in short-term SBPV and DBPV, with resistance exercise specifically reducing SBPV and aerobic exercise benefiting both SBPV and DBPV.
O98 NEW APPROACHES TARGETING THE RENIN-ANGIOTENSIN SYSTEM: BRAIN ACE2 ACTIVATION FOLLOWING BRAIN AMINOPEPTIDASE A BLOCKADE BY FIRIBASTAT IN SALT-DEPENDENT HYPERTENSION
Authors: Hmazzou Réda , Marc Yannick , Flahault Adrien , De Mota Nadia , Llorens-Cortes Catherine 
Published: September 2024

Background and Objective:
In the brain, aminopeptidase A (APA), a membrane-bound zinc metalloprotease, generates angiotensin III from angiotensin II. Brain angiotensin III exerts a tonic stimulatory effect on the control of blood pressure (BP) in hypertensive rats and increases vasopressin release. Blocking brain angiotensin III formation by the APA inhibitor prodrug RB150/firibastat normalizes arterial BP in hypertensive deoxycorticosterone acetate (DOCA)-salt rats. Ang II and Ang III have similar affinities for AT1 receptors and blocking brain AngIII formation by RB150 decreases arterial BP without inducing Ang II accumulation.

Methods:
We therefore hypothesized that another metabolic pathway of brain angiotensin II, such as the conversion of angiotensin II into angiotensin 1-7 (Ang 1-7) by angiotensin-converting enzyme 2 (ACE2) might be activated following brain APA inhibition. To answer this question, we use surgical animal models that could allow us to monitor awake blood pressure responses to intracerebroventricular (icv) injections and measure enzymatic activity.

Results:
We found that the intracerebroventricular administration of RB150/firibastat in conscious DOCA-salt rats both inhibited brain APA activity and induced an increase in brain ACE2 activity. Then, we showed that the decreases in BP and vasopressin release resulting from brain APA inhibition with RB150/firibastat were reduced if ACE2 was concomitantly inhibited by MLN4760, a potent ACE2 inhibitor, or if the Mas receptor (MasR) was blocked by A779, a MasR antagonist.

Conclusions:
Our findings suggest that in the brain, the increase in ACE2 activity resulting from APA inhibition by RB150/firibastat treatment, subsequently increasing Ang 1-7 and activating the MasR while blocking angiotensin III formation, contributes to the antihypertensive effect and the decrease in vasopressin release induced by RB150/firibastat. RB150/firibastat treatment constitutes an interesting therapeutic approach to improve BP control in hypertensive patients by inducing in the brain renin-angiotensin system, hyperactivity of the beneficial ACE2/Ang 1-7/MasR axis while decreasing that of the deleterious APA/Ang II/Ang III/ATI receptor axis.