bluuebunny/crossref_metadata_2025 huggingface dataset:
O48 CHRONIC EXPOSURE TO POLLUTED URBAN AIR ALTERS MOUSE SYSTEMIC AND TISSUE-SPECIFIC COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM (RAS)
Authors: Dominici Fernando , Pardo Jorge Narvaez , Freire Agustina , Barrales Benjamin , Buccholz Bruno , Gironacci Mariela , Magnani Natalia , Evelson Pablo
Published: September 2024

Background and Objective:

Chronic exposure to air pollution induces pulmonary, cardiovascular, and renal diseases. In the current study, we investigated the hypothesis that postulates that a dysregulation of the RAS may contribute to these pathologies.

Methods:

Male Balb/C mice were exposed to urban air from Buenos Aires City, in whole-body exposure chambers for 14 weeks. Control animals were exposed to filtered air. The levels of main RAS components including angiotensin-converting enzyme (ACE) and ACE2; AT1, AT2, and Mas receptors (R) were determined in mouse lungs, kidneys, and heart, through western blotting (WB) and RT-qPCR, respectively. The tissue content of cytokine mARN was determined by RT-qPCR. The tissue content of nitrotyrosine and 4-hydroxynonenal (4-HNE) levels, were determined by WB. Circulating angiotensin (Ang) II levels were determined by radioimmunoassay. Systolic blood pressure was measured by the tail-cuff method.

Results:

Exposure to air pollution resulted in a) Increased levels of ACE and AT1R mRNA in the lungs and augmented the abundance markers of inflammation (TNF-α, IL-6, and IL-1β) and oxidative stress (nitrotyrosine and 4-HNE) in this tissue, b) increased levels of MasR mRNA (all analyzed tissues) and MasR protein levels (lungs and heart), c) upregulated mRNA and protein abundance of cardiac and renal AT2Rs, and d) Increased levels of circulating Ang II and e) augmented systolic blood pressure.

Conclusions:

Our findings indicate that chronic exposure to air pollution alters the expression of both tissue and systemic components of the RAS. Since both AT2R and MasRs have been shown to participate in tissue-repair mechanisms, the upregulation of these receptors detected in mouse lungs, heart, and kidney after chronic exposure to polluted urban air could represent a mechanism of tissue protection against damage induced by air pollution.
O51 EXPLORING GENETIC BASIS OF RESISTANT HYPERTENSION IN EUROPEAN AND AFRICAN POPULATIONS
Authors: Lorenzo Oscar , Garcés Dr Carmen , Pérez-Nadador Iris , Fokkens Hannah , Abrahams-October Zainonesa , Sharma Jyoti , Cortés Marcelino , Pello Ana , Tuñon José , Apalata T , Johnson Rabia
Published: September 2024

Background:

Approximately 15% of hypertensive (HTN) patients experience resistant hypertension (RHTN) despite the use of ≥ 3 antihypertensive agents (diuretic and blockers of calcium channels and the renin-angiotensin system) at maximum tolerated doses. Intriguingly, genetic variation and alterations in gene content may contribute to RHTN developing.

Aim:

To comprehend the genetic determinants of RHTN across diverse ethnicities, this study has compared the gene content and presence of single nucleotide variants (SNVs) in RHTN versus controlled-HTN and normotensive participants within European (EU) and South African (SA) populations.

Methods:

Blood-isolated DNA was collected from 6 participants from EU and 15 from SA. Patients were categorized into 3 groups: RHTN (SA; n=5 and EU; n=6), controlled-HTN (n=5), and normotensive (n=5). DNA was used for Whole Exome Sequencing (WES) analysis. Library preparation and exome capture were done using the MGIEasy Universal DNA library prep and exome capture v5 probe set. Mapping was done using GATK, and the variant calling and annotation were performed using with the SIFT tool and R software.

Results:

PCA analysis and minimum spanning network showed significant genetic diversity between EU and SA populations. WES identified 16 common genes, with 207 and 220 genes associated to RHTN in EU and SA, respectively. These genes were involved in cardiac electrical conduction (K+/Ca++ channels) and lipid storage (HDL deficiency). In addition, SNV within pharmacogenes in SA (CYP2D6, CYP3A5, APOE) and EU (ADD1) cohorts alongside genes linked to disease susceptibility (RyR1 and PPP1CA) were also identified. RyR1 and PPP1CA are both implicated in HTN development through their roles in calcium signaling and vascular smooth muscle cell function. Noteworthy, two SNVs, rs121918006 and rs61732908, within RyR1 were previously linked to HTN.

Conclusions:

The large genetic differences observed between EU and SA subjects highlight the diverse genetic landscape surrounding RHTN. Notably, specific genes and their related SNV that associated to cardiac calcium channels and lipid storage could show potential targets for personalized therapeutic intervention.

Scientific Session 15: Exploring Novel Therapeutic Approaches to Kidney Disease
O57 NOCTURNAL BLOOD PRESSURE FLUCTUATION AND DIPPING PATTERNS IN PATIENTS WITH SEVERE OBSTRUCTIVE SLEEP APNOEA
Authors: Patzak Andreas , Bothe Tomas Lucca , Küchler Gert
Published: September 2024

Background and Objective:

Nighttime blood pressure (BP) is important for diagnosis of hypertension and for cardiovascular risk stratification. Remarkably, a reverse dipping pattern is a strong and independent predictor of overall mortality and major adverse cardiovascular events. Therefore, the further clarification of the underlying mechanisms of non- and reverse dipping is crucial to improve the treatment of patients with nighttime hypertension.

Methods:

We investigated 97 patients with suspected obstructive sleep apnoea (OSA, AHI >30) using standard polysomnography and continuous BP measurement based on the pulse-transit-time method (SOMNOscreen Plus®, SOMNOmedics). Frequency and amplitude of fluctuations in systolic BP following sleep disturbances (OSA) were investigated.

Results:

Apnoeic events went along with transient increases of BP. In some cases, systolic BP did not reach the value before the apnoea but increased over time. We defined elevations of the systolic BP baseline by >10 mmHg with a duration of >10 min as BP superpositions. The superposition periods were also characterized by increased BP amplitudes with peak values of BP up to 220 mmHg. Superposition occurred in 48 patients. Further, 65% of the OSA patients were identified as non-dippers. However, nearly all the patients with superposition (98%) were identified to have non-dipper or reverse dipper patterns.

Conclusions:

Our study strongly suggests that non-dipping and reverse dipping in patients with severe OSA are causally linked to OSA related BP fluctuations. Further, continuous elevations in SBP baseline (superpositions) result in extreme BP values. This behaviour with high BP peaks may be contributing to the increased mortality in patients with reverse dipping. Therefore, identification and adequate treatment of patients with reverse dipping reduces the cardiovascular risk and may prolong their life.
O59 INFLUENCE OF CIRCADIAN BLOOD PRESSURE PATTERN ON RIGHT VENTRICULAR STRUCTURE AND FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSIION
Authors: Rekhviashvili Ann , Kvitsiani Arsen , Paposhvili Kakha
Published: September 2024

Background and Objective:

It is well proven, that arterial hypertension affects left side of the heart and causes its remodeling and functional changes. Since heart works as a unit and has ventricular interdependence, aim of the study was to assess influence of hypertension and circadian blood pressure (BP) profile on a right ventricular structure and function.

Methods:

75 hypertensive patients (57.13±7.27 y/o) and 25 normotensive control subjects (57.56±7.55 y/o) were involved in a study. All of them were males without history of coronary artery disease, cerebrovascular or peripheral artery disease, obstructive lung disease, significant valvular heart disease or heart failure. All of them were either lifetime nonsmokers, or stopped smoking more than 5 years. All the patients underwent to 24-hour ambulatory BP monitoring and heart ultrasound with tissue doppler imaging.

Results:

Hypertensive patients with dipper circadian BP profile had higher TAPSE (19±1.586 vs 17.708±2.857; P<0.05), higher right ventricular ejection fraction (55.103±4.597 vs 47.829±14.605; P<0,005) and lower right ventricular outflow tract diameter (29.985±3.932 vs 32.639±3.510; P<0/05). None of the echo parameters were different between normotensive subjects with different circadian BP pattern. Trans tricuspid valve early diastolic (E) and late diastolic (A) peak velocities were significantly lower in hypertensive patients (1.416±0.130 vs 0.897±1.49; P<0.005). Hence, non-dipper hypertensives had significantly lower tricuspid E/A ratio in comparison with dippers (0.812±0.094 vs 1.048±0.101; P<0.00001). Interventricular septum and posterior wall diameters were higher in non-dipper hypertensives (1.134±0.131 vs. 1.322±0.138; P<0.00001 and 1.072±0.175 vs. 1.254±0.135; P<0.001; respectively).

Conclusion:

Study data show increased interdependence between two ventricles. Patients with arterial hypertension have systole-diastolic dysfunction, which especially well is present in patients with non-dipper circadian BP profile.
O62 DEGREE OF HYPERTENSION CONTROL IN ABORIGINAL AND NON-ABORIGINE POPULATIONS OF A CITY IN NORTHERN ARGENTINE
Authors: Romano José René , YEGROS Olga , Fernandez Anair , Gomez Osmar A. Acosta , Eileen Ynfante Maira , Marañon Rodrigo O.
Published: September 2024

High blood pressure is a widely prevalent pathology in the province of Formosa, 52% according to the latest Argentine national survey 2019, so we do not have current data, it was decided to carry out a survey that evaluates blood pressure, arterial stiffness and peripheral resistance. To evaluate how these variables are presented in 2 populations of our city, one of the general population and the other of an indigenous ethnic group of the province called Toba that lives in a neighborhood of this city.

Materials and methods:

data collection was carried out on patients in 3 institutions, all of which were public, with a prior diagnosis of the disease made by a health professional, in the Central Hospital of Formosa, the interdistrict hospital Evita, and the center of primary care in the Nam Qom neighborhood of Formosa. during a period of 1 month The pressure was taken by validated blood pressure monitors as well as central aortic pressure and peripheral resistance. by a Tel O Graph brand team. The data were analyzed Statistix 10.0.

Results:

80 patients, 20 from the ethnic group and 20 from the general population, 62% women, age was 52 years in the general hospital (hg) and 54 in the health center (cs), systolic blood pressure was 129 1/2 and 82 1/2 diastolic, in cs 121 and 83. The central aortic velocity was 7.76 on average and the peripheral resistance 18.62 in the hc - in the cs 6.54 and 18.6. smoking habit, 45 and 25% respectively.

The control was 87% in the BP in the hc and 75% in the cs population.

Conclusions:

Differences were found: a lower prevalence of uncontrolled hypertension than in the general population and in terms of VOP and peripheral resistance we were able to find a difference in favor of the CS population, and also in the degree of control of hypertensive patients in the same trend.
O67 URINARY PROTEOMIC PROFILING REVEALS MOLECULAR CUES UNDERLYING HIGHER HYPERTENSION SUSCEPTIBILITY IN BLACKS THAN WHITES
Authors: An Dewei , Martens Dries , Mokwatsi Gontse , Yu Yu-Ling , Chori Babangida , Latosinska Agnieszka , Mayer Gert , Kruger Ruan , Mels Catharina , Delles Christian , Stolarz-Skrzypek Katarzyna , Nawrot Tim , Li Yan , Mischak Harald , Staessen Jan
Published: September 2024

Background and Objective:

Compared with Whites, Blacks are more prone to hypertension and salt-sensitivity. The objective was to investigate whether sequenced urinary peptide fragments derived from proteins with a key role in cardiovascular or renal structure or function have different levels in sub-Saharan Blacks compared with Whites.

Methods:

This individual-participant meta-analysis included individuals enrolled in African-PREDICT (476 Blacks and 483 Whites), FLEMENGHO (720 Whites), PROVALID-Austria (467 Whites) and UPRIGHT-HTM (106 Nigerian Blacks and 61 Polish and Slovenian Whites). Urinary peptides were quantified by capillary electrophoresis combined with mass spectrometry.

Results:

Among 2313 participants (49.7% women), median age was 40.9 years. Of 513 urinary peptides with 70% prevalence, 300 had Bonferroni-corrected significantly different levels among Black and White South Africans sharing the same environment. Analyses contrasting 582 Blacks vs 1731 Whites, sub-Saharan Blacks (582) vs European Whites (1248) replicated the findings. Combining these results with information from public databases, we identified COL4A1, COL4A2, CD99, FAT1, FGA, FXYD2, MGP, MYOCD, PCDH7, PROC, and UMOD as most likely candidates underlying the different susceptibility to hypertension and salt sensitivity between Blacks and Whites. The most relevant enriched pathways were related to hemostasis, platelet activity, collagens and biology of the extracellular matrix, and protein digestion and absorption. Disease Ontology terms comprised small-vessel disease and coronary and macrovascular atherosclerotic disease.

Conclusions:

MGP and MYOCD being involved in cardiovascular function, FGA in clot formation, FYXD2 and UMOD in salt homeostasis, and COL4A1 and COL4A2 as major component of the glomerular basement membrane are proteins deserving further exploration in molecular and human studies as potential targets for intervention to reduce the excess hypertension risk and associated complications in Blacks.
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.
O101 THE ANGIOTENSIN II TYPE 1 RECEPTOR-BIASED AGONIST REDUCES BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS AND RESTORES VENTRICULAR HYPERTROPHY BY AFFECTING THE CONNEXIN 43 PATHWAY
Authors: Fan Xin , MA Jie , Yu Jing
Published: September 2024

Purpose:

Hypertension is one of the common causes of cardiovascular diseases. Long-term hypertension can lead to structural and functional impairment of the heart. Therefore, active treatment of hypertension is highly significant in preventing target organ damage. Angiotensin II (AngII) plays a crucial role in hypertension-induced cardiac hypertrophy. Reportedly, TRV027, an AngII type 1 receptor (AT1R) biased agonist, can competitively bind to AT1R and inhibit the AngII-induced damage. Whether TRV027 could lower blood pressure and treat hypertensive cardiac hypertrophy remains unknown.

Methods:

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were selected, and some of the SHRs were administered with TRV027. H9C2 cells were utilized for in vitro study to explore the underlying mechanism of TRV027. A multidisciplinary approach combining pathology and molecular techniques was used to explore the role and mechanism of TRV027 in reducing blood pressure and restoring ventricular hypertrophy.

Results:

Our studies revealed that TRV027 reduced blood pressure and restored hypertension-induced ventricular hypertrophy in SHRs. Moreover, the modulated expression of Connexin43 (Cx43) and phosphorylation of the MAPK/ERK pathway were normalized by TRV027. After the inhibition of Cx43 expression, cardiomyocytes recovered from hypertrophy and damage, followed by the modulation of phosphorylation of the MAPK/ERK pathway.

Conclusion:

TRV027 demonstrates a potential to lower the blood pressure in SHRs and ameliorate hypertension-induced cardiac hypertrophy. While AngII stimulated cardiomyocyte injury by decreasing Cx43 expression and increasing the phosphorylation of the MAPK/ERK pathway, TRV027 repaired the hypertrophy by restoring the expression of the Cx43/MAPK/ERK pathway.
O105 ISOLATED NOCTURNAL HYPERTENSION AND TARGET ORGAN INJURY IN YOUTH
Authors: Hill-Horowitz Taylor , Flynn Joseph , Ferguson Michael , Hanevold Coral , Lande Marc , Meyers Kevin , Mitsnefes Mark , Samuels Joshua , Sethna Christine , Urbina Elaine , Basalely Abby Abby
Published: September 2024

Background and Objective:

New American Heart Association (AHA) recommendations in 2022 for pediatric ambulatory blood pressure monitoring (ABPM) established static blood pressure (BP) cutoffs to define hypertension with an optimal sensitivity-specificity balance to best capture target organ injury (TOI). This increased the prevalence of ABPM hypertension, specifically isolated nocturnal hypertension. We utilized ABPM data from the SHIP-AHOY cohort to describe the epidemiology of INH in youth and to evaluate associations between INH and TOI.

Methods:

We defined INH as wake BP <130/80 mmHg and sleep BP >110/65 mmHg. INH was also evaluated by the 2014 AHA definition: wake BP <95th percentile with sleep BP >95th percentile. Primary outcome was left ventricular hypertrophy (LVH), defined as left ventricular mass index >38.6 g/m2.7. Cardiovascular risk factor (CVRF) scores described the number of risk factors for cardiovascular disease (dyslipidemia, obesity, hypertension by clinic systolic BP, insulin resistance) fro each participant. Logistic regression models assessed the association of INH with LVH, adjusted for age, sex, CVRF score, and ABPM tolerability.

Results:

Of 397 participants, 77 had INH, mostly (62%) due to elevated systolic BPs only. Median age and height were higher in INH than normotension (16.1 v 15.1 years, P=0.022) (height z-score 1.13 v 0.23, P=0.039). Other characteristics did not differ significantly between groups (Table 1). Estimated glomerular filtration rate was lower in INH. Among those with INH, 27% (N=19/71) had LVH, a greater proportion than found with 2014 definitions (21%, N=7/33). Children with INH had 2.61-fold adjusted odds of LVH compared to normotension (95%CI [1.20,5.69], P=0.016).

Conclusions:

Over 20% of the SHIP-AHOY cohort had INH, accounting for >1/3 of hypertension overall. INH was associated with older age and taller height, mostly due to systolic BP. Compared to 2014 guidelines, the 2022 definition of INH captured a higher prevalence of LVH. INH was independently associated with increased odds of LVH. Future studies should follow children with INH longitudinally for potential development of daytime hypertension.

Table 1: Demographic, Anthropomorphic, and Clinical Characteristics of Isolated Nocturnal Hypertension vs Normotension
P010 HYPERTENSION CONTROL CASCADE AMONG OLD AND VERY OLD POPULATION OF NEPAL: A FRAMEWORK TO IMPROVE HYPERTENSION AWARENESS, TREATMENT, AND CONTROL
Authors: Mehata Suresh , Thapa Astha , Mehta Ranju Kumari
Published: September 2024

The older population of Nepal increased from 6% to 10% from 1971 to 2021 census. The prevalence of NCDs increases with the increase in age. This study aimed to assess the prevalence and predictors of hypertension, awareness, treatment and control rate in Nepal.

Nepal demographic and health survey data 2022, a nationally representative survey data was used for this analysis. 1716 (unweighted sample) participants aged 60 years and above were used for this analysis. Multivariate logistic regression was used to assess the predictors (sex, education, place of residence, province and wealth quintile) of hypertension control cascade. All the inferential analysis was carried out considering the cluster sampling design. Sample weight was used to estimate the population statistics. P<0.05 were considered statistically significant.

Study revealed that 44% participants were hypertensive, among them 60% were aware of their status and 45% were under treatment. Among those who were under treatment, 57% respondents blood pressure were under control (Table 1).

The higher prevalence of hypertension was observed among the urban dwellers (49%) compared to rural counterparts (37%) (AOR: 0.65;95%CI:0.52-0.81). By wealth quintile, 55% of the richest quintile population were hypertensive compared to the poorest counterparts (38%) (AOR:1.68;95%CI:1.13-2.50). Study revealed that the dose-response relationship between wealth quintile and hypertension awareness as well as treatment rate. Compared to the poorest, the higher odds of awareness rate were observed among the poor (AOR:2.08(1.19-3.64)), middle quintile (AOR:2.97(1.65-5.36)), richer (AOR:2.50(1.29-4.84)) and richest (AOR:4.05(2.02-8.14)) population. Likewise, compared to the poorest, the higher odds of treatment rate were observed among the poor (AOR:2.47(1.27-4.83)), middle (AOR:2.63(1.41-4.92)), richer (AOR:3.29(1.63-6.65)) and richest (AOR:7.20 (3.43-15.14)) population.

The prevalence of hypertension is high among the Nepalese old population with low awareness, treatment and control rate. The gap between awareness and treatment was 15%. The lowest awareness and treatment rate were observed among rural and poorest population need focused, targeted, tailored intervention through integration of NCDs programming with the primary care.
P012 THE EFFECT OF AGE AND LONG-TERM BLOOD PRESSURE CONTROL ON DIASTOLIC CARDIAC FUNCTION IN MASTERS ATHELETES
Authors: Hedke Nick , Hoffmann Fabian , Hoenemann Jan-Niklas , Moestl Stefan , Rittweger Joern , Tank Jens , Jordan Jens , Reuter Hannes
Published: September 2024

Background & Objectives:

Arterial hypertension and age underlie the risk for diastolic dysfunction and heart failure with preserved ejection fraction. Blood pressure control and physical exercise are known to ameliorate age related cardiac adaptation. Therefore, we assessed diastolic function including left atrial (LA) strains in Masters Athletes as a model for healthy ageing.

Methods:

At the World Masters Athletics Championships 2022 in Tampere, Finland 108 Masters Athletes partook in this field-study. Baseline data included body measures, blood pressure, age, sex and sport disciplines. Transthoracic echocardiography was performed analogous to clinical standards. Additionally, LA reservoir strain (LA-Sr) and conduit strain (LA-Scd) were assessed by speckle tracking.

Results:

Complete data were acquired in 108 (42, 39% female) athletes with a mean age of 62±12 (35-91) years and a body-mass-index of 23,8±2,8 kg/m2. Mean systolic blood pressure was 125±16mmHg, one third (n=36) had values ≥130mmHg. 29 performed endurance, 79 resistance disciplines. LA strain was not influenced by sport discipline nor blood pressure, neither in dichotomization for clinical thresholds nor in linear correlation. Female athletes showed higher LA reservoir and conduit strain (LA-Sr: 29.1±5.3% versus 27±5.5%, p=0.046; LA-Scd: 16.6±6% versus 13.9±5.4%, p=0,018). With increasing age, body-mass-index and left-ventricular-mass-index, LA reservoir and conduit strains declined significantly, independent of blood pressure. In Masters Athletes that did not meet echocardiographic criteria of diastolic dysfunction we found significantly higher LA reservoir and conduit strains than in those with 2 criteria met (LA-Sr 29.8±5.2% versus 25.4±6.6%, p=0.007; LA-Scd -17.3±6% versus -13.4±6.5%, p=0.030).

Conclusion:

In the specialized cohort of Masters Athletes LA reservoir and conduit strain showed the same dependency from age, body-mass-index and left-ventricular-mass-index as other parameters of diastolic function with higher values in females. Furthermore, impaired diastolic function was associated with decreased LA strain. Therefore, assessment of LA strain seems beneficial beyond classical echocardiographic measurements in determining diastolic function in the elderly. Surprisingly, long-term blood pressure control by physical exercise had no effect on LA strains.