bluuebunny/crossref_metadata_2025 huggingface dataset:
S-39-4: PLASMA FROM SARS-COV-2 PATIENTS INDUCES OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION VIA ANGIOTENSIN II TYPE 1 RECEPTOR (AT1R)/P38 MAPK PATHWAY
Authors: Almutlaq Moudhi , Mansour Fatmah A , Alamri Hassan S , Alroqi Fayhan , Barhoumi Tlili
Published: January 2023

Background:

Acute respiratory distress syndrome (ARDS) is a distinctive feature of severe COVID-19 infections that occurs mainly in patients with coexisting health problems, such as hypertension, atherosclerosis, and diabetes. Endothelial dysfunction is a major contributing factor during ARDS development in COVID-19 patients with pre-existing comorbidities.

Objective:

Studying the mechanism by which endothelial activation and dysfunction could provide a therapeutic target for COVID-19 treatment.

Design and method:

The current study measured endothelial dysfunction and oxidative stress by incubating human umbilical vein endothelial cells (HUVECs) with plasma from patients with mild, moderate, severe and extremely severe COVID-19. Using flow cytometry, wound-healing assays and phosphokinase arrays,

Results:

We detected increases in cell apoptosis; reactive oxygen species (ROS) formation; hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular cell adhesion molecule-1 (VCAM-1), and vascular endothelial growth factor receptor-1 (VEGFR-1) expression; viral entry; and inflammatory-related protein activity. We also found an impairment in the wound-healing process. Moreover, we found that AT1R blockade and P38 MAPK inhibition reversed all of these effects, especially in the severe group.

Conclusions:

These findings indicate that AT1R/P38 MAPK-mediated oxidative stress and endothelial dysfunction occur during COVID-19 infection.
S-40-1: INFLAMMATION AND IMMUNITY IN HYPERTENSION
Authors: Schiffrin Ernesto L.
Published: January 2023

Over the past almost 30 years the roles of inflammation and later of specific immune cells in the mechanisms of hypertension have increasingly been demonstrated. Initially it was shown that immune cells infiltrated perivascular tissue in the heart and kidney. Later, the demonstration that macrophages and shortly after T lymphocytes were critical for angiotensin II and DOCA-salt-induced hypertension consolidated the idea that immune mechanisms played a role in cardiovascular and renal injury in hypertension. As well, the anti-inflammatory role of T regulatory lymphocytes, the participation of dendritic cells, of gamma/delta T lymphocytes, of neutrophils through the formation of neutrophil extracellular traps (NETs), has become evident. The role of antigen presentation and intracellular mechanisms leading to activation of innate and adaptive immunity in hypertension have offered additional opportunities for eventually targeting the immune system to control inflammation-mediated damage in hypertension. Interferon-gamma and interleukin-17 appear to be important pro-inflammatory cytokines, whereas interleukin-10 plays an anti-inflammatory role in hypertension. Recent application of single cell RNA sequencing has opened novel vistas of the landscape of immune cells participating in cardiovascular and renal injury in hypertension, which can lead to new therapeutic options to control blood pressure and target organ damage in hypertensive patients.
S-40-6: ACTIVATION OF CATHEPSIN S/CXCL1 AXIS-MEDIATED MACROPHAGE AND TUBULAR CELL CROSSTALK LEADS TO RENAL INFLAMMATION AND FIBROSIS
Authors: Li Xiaodong , He Shun , Lu Yuanyuan , Wang Jiguang , Gao Pingjin
Published: January 2023

Chronic kidney disease (CKD) is a progressive and irreversible pathological feature with no effective therapies in clinic. Persistent inflammation is a key characteristic of CKD that leads to progressive renal fibrosis. Cathepsin S (Cat S) is a cysteine protease contributing to the progression of multiple diseases through modulating inflammation, but its role in the pathogenesis of CKD remains unknown. Here, we found that Cat S was significantly upregulated in renal macrophage during unilateral ureteral obstruction (UUO). Knockout of Cat S attenuated, whereas AAV (adeno-associated virus)-mediated macrophage-specific overexpression of Cat S exacerbated macrophage recruitment, inflammatory factors expression, renal injury and epithelial mesenchymal transition (EMT). Using macrophage depletion, bone marrow transplantation, protein chip and luciferase reporter assays, we determined that macrophage-derived Cat S induced CXCL1 secretion from tubular cells which mediated macrophage recruitment. Immunoprecipitation combined with mass spectrometry identified that Cat S directly bind with Rack1, which disrupted the Rack1-IKK-alpha complex to activate NF-kappaB signaling. Knockdown of CXCL1 attenuated aggravating pathological changes in macrophage-specific overexpression of Cat S mice. Furthermore, therapeutic administration of Cat S inhibitor significantly reversed renal injury in UUO mice. In patients with renal tubulointerstitial lesions, increase expression of plasma and renal Cat S was associated with renal function impairment and fibrosis severity. Our study demonstrated that Cathepsin S/CXCL1 axis mediated interaction between macrophage and tubular cell that contributed to CKD, with translational implications in humans.
S-41-2: ROLE OF TERTIARY LYMPHOID TISSUES IN KIDNEY INFLAMMATION
Authors: Yanagita Motoko
Published: January 2023

Kidneys are vulnerable organs, and often fail to repair. In particular, renal damage is prolonged and severe in the elderly, but the mechanism behind this was unknown. Recently, we identified a unique microenvironment orchestrating kidney injury and inflammation. Tertiary lymphoid tissues (TLTs), which mainly consist of lymphocytes and fibroblasts, are formed in the chronic phase after injury in aged kidneys, contributing to prolonged inflammation and delayed regeneration. Resident fibroblasts in the kidney play critical roles in the formation of TLTs by acquiring the abilities to produce retinoic acid and homeostatic chemokines, and to support B cell area formation. Notably, therapeutic strategy targeting TLTs attenuates tubular injury and fibrosis in mouse models. Furthermore, TLTs are found in human kidneys, and the presence of advanced-stage TLTs correlates with the severity of kidney injury and inflammation. Specifically, TLTs are commonly found in protocol biopsies of transplanted kidneys, and advanced-stage TLTs are associated with progressive graft dysfunction. Recently, we identifed TNF superfamily CD153-CD30 signaling between two unique age-dependent lymphocyte subpopulations, senescence-associated T (SAT) cells and age-associated B cells (ABCs), as a driver for TLT expansion, and demonstrated that CD153 or CD30 deficiency resulted in attenuated TLT formation with improved inflammation, fibrosis and renal function. Understanding the mechanism of TLT formation may provide clues for the development of therapeutic agents for slowing kidney disease progression.
S-41-5: NEW INSIGHTS INTO THE OPTIMAL ANTIHYPERTENSIVE THERAPY IN CKD PATIENTS
Authors: Ishimitsu Toshihiko
Published: January 2023

Chronic kidney disease (CKD) is defined as continuous existence of reduced renal function, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, and/or proteinuria including microalbuminuria. CKD patients are not only prone to progress to renal failure but also at high risk for developing cardiovascular diseases (CVD) as the concept of cardio-renal syndrome is assumed. As the cause of CKD, diabetic kidney disease and nephrosclerosis are dominating and their progression is promoted by aging and lifestyle-related diseases (LSD) such as hypertension and diabetes. Therefore, in order to maximally prevent renal failure and CVD in CKD patients, aggressive intervention achieving strict control of LSD starting at its earliest stage is important. Renal function is generally evaluated by eGFR, however, the fundamental aspect of renal function is renal blood flow or renal plasma flow (RPF), and the decrease of RPF is compensated by the increase in filtration fraction yielding the maintenance of GFR value. Accordingly, if eGFR is less than 60, it should be recognized that the extent of renal injury is not mild but moderate or worse. However, the measurement of RPF requires laborious and invasive procedure. Albuminuria may reflect the increase in glomerular capillary pressure (glomerular hypertension) elicited by reduced nephron number but the urinary albumin excretion is highly variable and is not necessarily parallel to the degree of renal injury.

Among LSD, hypertension plays a pivotal role as the risk factor for renal failure and CVD, and the strict blood pressure control targeting < 130/80mmHg is recommended in the guidelines. As antihypertensive agents, renin-angiotensin system inhibitors such as ARB and ACE inhibitors are preferred because of dilating the efferent arterioles resulting in the alleviation of glomerular hypertension and the reduction in albuminuria. Calcium channel blockers have advantage in preserving RPF and GFR by dilating the afferent arterioles. In addition, recent randomized controlled trials have demonstrated that sodium-glucose cotransporter 2 inhibitors retard the GFR decrease in diabetic and non-diabetic CKD patients. Angiotensin receptor neprilysin inhibitor, now used for hypertension, has also been shown to reduce the risks of GFR decrease and worsening of renal function in heart failure patients. Nonsteroidal mineralocorticoid receptor antagonists are expected to provide renoprotective effects such as albuminuria reduction with affordable risk of hyperkalemia.

Thus, in future strategy of antihypertensive therapy for CKD aiming maximum renal and cardiovascular protection, practical evaluation of renal injuries at early stages and incorporation of drugs with new evidence are the key issues.
S-42-7: TELEMEDICINE FOR POST-COVID-19 MANAGEMENT OF HYPERTENSION
Authors: Yatabe Midori
Published: January 2023

The pandemic has led to changes in regulations and reimbursement rules to generally favor telehealth, as well as increased public awareness and acceptance of virtual visits.

In Japan, the adoption of virtual video visits has been slow, largely due to regulations and reimbursement policies. For the whole country, much less than 1% of total outpatient visits has used virtual video visits.

Compared to traditional care, hypertension management using online digital solutions has a potential to improve care access and reduce untreated hypertension population.

Notably, hypertension is one of the best fit conditions to be managed by virtual care among various acute and chronic illnesses because the primary index of treatment is self-measured home blood pressure and effective medications with minimal side effects are available.

However, currently implemented hypertension telemedicine includes different styles of care delivery that needs to be taken into account when discussing remote hypertension management.

According to a report, telephone visits and video visits had lower proportion of visits with recorded blood pressure compared to in-person visits (Ye, JMIR Formative Research, 2022).

An ideal ICT-assisted management likely involves home blood pressure monitoring, team care with interactive lifestyle modification guidance, and audio-video visits.

Post-COVID-19 management of Hypertension can be enriched by combining remote blood pressure monitoring and virtual visits with digital therapeutics and mHealth services promoting lifestyle modifications.

The remaining challenge includes cost considerations and disparities that may arise from economic status, internet availability, and digital service familiarity.

Especially for a patient population whose primary or sole health condition needing medical attention is hypertension, total care with online visits may have advantage over other forms of care, offering convenience, care effectiveness using accurate BP assessment, and good cost profile.

In addition, online hypertension care employing properly-planned data structure can help generate a high-quality real-world dataset which may be used to evaluate the advances in quality of care using technologies.
S-43-1: THE CHANGING EPIDEMIOLOGY OF HYPERTENSION IN CHILDREN AND ADOLESCENTS
Authors: Lurbe Empar
Published: January 2023

Some scientific concepts take time to overcome initial disbelief before they are finally embraced by the research community. One of these concepts is hypertension in children and adolescents. Little was known about childhood hypertension until the early 1980 s, mainly because blood pressure was not commonly measured in pediatric clinical practice. In the few cases blood pressure levels were determined to be abnormal in children, they were considered to be secondary hypertension resulting from an underlying condition. Even though secondary causes of hypertension tend to occur more often in hypertensive children than in adults, its prevalence is only about 1 percent overall, leaving primary hypertension especially in adolescents as the most frequent type.

Even when there are many studies that have assessed the prevalence of hypertension in children and adolescents, scientists have faced difficulties to state this prevalence for three main reasons. To begin with, blood pressure normally changes with increasing age and body size. This makes establishing a fixed cutoff for values of systolic and diastolic blood pressure elevation rather challenging. This difficulty has led to the use of percentiles based on age, sex, and height to define the normal distribution, with a hypertensive level of blood pressure in the 95th percentile or higher. Another obstacle is that there is a variety of different definitions of hypertension used by the three most recent clinical practice guidelines coming from Europe, the United States and Canada. The last challenge is focused on the beat-to-beat blood pressure variability, the definition of hypertension requires that systolic and/or diastolic blood pressure to be persistently higher than the established thresholds on three separate occasions. Many cross-sectional studies with only one single measurement of blood pressure have not been able to define the prevalence of hypertension.

The epidemiology of hypertension in childhood and adolescence can be linked to the worldwide obesity epidemic. Hypertension is more prevalent than before, with primary hypertension being the main type. It is well known that the factors related to primary hypertension can be modified, therefore childhood is a period in which prevention could be effective. If prevention is followed throughout childhood, it could contribute to a healthier young adulthood in the long run. Therefore, primordial prevention is an opportunity not to be missed.
S-44-1: SALTING A BIRD'S TAIL
Authors: Shimosawa Tatsuo
Published: January 2023

It is needless to stress high-salt intake threaten cardiovascular diseases because of inrement of hypertension and social activities to reduce salt intake is beneficial for healthy longetivity. The pathophysiology of salt-induced hypertension has been studied and innapropriate handling of salt in the kidney, vascular reaction to the salt and recently interstitial accumulation of sodium are proposed mechanism.

In addition to raise blood pressure, too much salt may cause systemic effect such as regulation of immune responses. Not all patients are salt-sensitive in terms of blood pressure and we do not know if there are salt-sensitive and resistant in other physiological effect of salt or not. It is required to develop the diagnositic tools to find who is salt-sensitive and tools to keep patients under appropriate salt intake chronically. In this review, I am going to discuss salt-sensitivity, pathological effect of high salt intake and possible markers for salt-sensitive hypertension.
S-44-2: ANTIHYPERTENSIVE EFFECT OF GALANGIN IN RENAL ARTERY STENOSIS-INDUCED HYPERTENSIVE RATS
Authors: Chaihongsa Nisita , Sangartit Weerapon , Rattanakanokchai Siwayu , Bunbupha Sarawoot , Pakdeechote Poungrat , Maneesai Putcharawipa
Published: January 2023

Background:

Galangin is a natural flavonoid found in honey and Alpinia officinarum. Several reports have suggested the anti-mutagenic, antioxidant, anti-proliferative, and apoptotic effects. However, the antihypertensive effect of galangin in renovascular hypertension has not been investigated.

Aims:

This study aims to investigate the effect of galangin on blood pressure and cardiac changes in renovascular hypertension.

Methods:

Male Sprague Dawley rats (180–220 g) were induced hypertension by clipping the left renal artery, 2-kidney-1-clip (2K-1C). After 3 weeks of the induction period, galangin (30 and 60 mg/kg) and losartan (10 mg/kg) were given to the rats for 4 weeks (n = 8/group). Blood pressure and cardiac function were evaluated at the end of the experimental day. The level of angiotensin-converting enzyme (ACE) activity, angiotensin II, and oxidative stress markers were assessed in the plasma and cardiac tissue of rats. The protein expression of angiotensin

II receptor type 1 (AT1R), transforming growth factor-beta 1 (TGF- β 1) and collagen type I (Col I) were determined in cardiac tissue. Statistical analysis was carried out by one-way ANOVA followed by Tukey post hoc test. A p value less than 0.05 was considered statistically significant.

Results:

Hypertension and cardiac dysfunction and hypertrophy were observed in 2K-1C rats compared to the sham-operated rats (p < 0.05). Treatment with galangin (30 and 60 mg/kg) decreased high blood pressure and improved cardiac function as well as alleviated left ventricular hypertrophy in 2K-1C hypertensive rats (p < 0.05). This result was related with the reduction of systemic ACE activity and angiotensin II levels in 2K-1C hypertensive rats that were treated with galangin (p < 0.05). Moreover, the expression of AT1R, TGF- β 1 and Col I in cardiac tissue was modulated by treatment with galangin (p < 0.05).

Additionally, galangin showed anti-oxidative effects as it reduced the production of superoxide and malondialdehyde levels in cardiac tissue of rats (p < 0.05).

Conclusion:

Galangin exhibited an antihypertensive effect and alleviated cardiac alteration in renovascular hypertensive rats. The underlying mechanism might be related to its inhibitory effects on renin-angiotensin system and anti-oxidative properties renal artery stenosis-induced hypertensive rats. Furthermore, the beneficial effect of galangin on heart might mediate the suppression of AT1R, TGF- β 1 and Col I pathway.
S-45-2: THE EVALUATION OF LEFT VENTRICULAR GEOMETRY AND LEFT VENTRICULAR EJECTION FRACTION BETWEEN CANCER PATIENTS BEFORE AND AFTER CHEMOTHERAPY
Authors: Karunawan Niyata Hananta , Jusuf Iin Irnawati , Tonang Alvin , Wahab Zulfahmi , Rachmandita Rheno , Pandeiro William Alfred Lapian
Published: January 2023

Objection:

This study aimed to compare the left ventricular (LV) geometry and left ventricular ejection fraction (LVEF) before and after chemotherapy in Cancer Patients

Methods:

This study was a cohort retrospective study design, the study compared the LV geometry and LVEF at baseline and 2-months after anthracyclines administration in cancer patients. Subject participants were aged more than 18 and received doxorubicin for the treatment of cancer at Dr Adhyatma MPH Tugurejo General Hospital from January until May 2022. Two-dimensional (2D) transthoracic echocardiographic (TTE) was performed to assess mass index (LVMI), mass (LVM), relative wall thickness (RWT), end-diastolic diameter (LVEDD), end-systolic diameter (LVESD), interventricular septal end-diastole (IVSd), posterior wall end-diastole (PWd) of the left ventricle at two-time points. The primary outcome of the study was LV Geometry and LVEF follow up after 2 months of doxorubicin therapy. The Data were analyzed univariate and bivariate followed by the chi-square test and paired T-test.

Results:

The Data of 72 cancer patients were dominated by females (87%) and a mean age of 51.19 ± 9.83 years old. Subject included patients with breast cancer (83.3%), non-Hodgkin's lymphoma (13,9%), and sarcomas (2,8%). After a 2-months period, the left ventricular ejection fraction (LVEF) decreased significantly from 70.98 ± 7.97 % to 66.70 ± 8.24 % (p < 0.001). Relative wall thickness (RWT) decreased significantly from 0.39 ± 0.12 to 0.35 ± 0.08 (p: 0.006), and left ventricular end-systolic diameter (LVESD) increased significantly from 25.41 ± 4.35 mm to 27.73 ± 4.58 mm (p < 0.001). LVMI (84.86 ± 28.99 g/m(2) to 80.16 ± 26.58 g/m(2)), LVM (131.75 ± 50.33 g to 126.00 ± 45.34 g), LVEDD (43.06 ± 5.06 mm to 43.98 ± 4.58 mm), IVSd (8.98 ± 2.25 mm to 8.43 ± 2.14 mm) and PWd (8.26 ± 2.30 mm to 7.75 ± 1.42 mm) did not change significantly (p > 0.05). Higher blood pressure was associated with post-cancer therapy.

Conclusion:

The effects of doxorubicin administration after two months were a lower LVEF, a lower RWT and a higher LVESD compared to before cancer therapy.
S-47-1: THE POTENTIAL OF AI IN HYPERTENSION TREATMENT
Authors: Okuno Yasushi
Published: January 2023

Deep learning, which has been the driving force behind AI in recent years, has been shown in various research reports to be as powerful as or more powerful than humans in the medical field. Specifically, deep learning techniques are being applied to images, time series data, biomolecular information, and natural language for medical images, clinical values, genomic information, and medical records in electronic medical records, respectively. In particular, AI for recognizing and diagnosing medical images has been shown to have high accuracy in various diseases including cancer, and it is expected that various types of AI for image diagnosis will be put to practical use in the medical field within the next five years. In addition to highly accurate diagnostic imaging, the benefits of AI for medicine include genomic diagnosis, decision support to reduce the burden on medical professionals, correction of regional disparities in medicine through AI, and self-medication by patients themselves using AI. Furthermore, AI is expected to make it possible to do things that are difficult to do with human knowledge and experience, such as predicting the future of a patient's medical condition, suggesting the best treatment for each individual, and quickly and appropriately extracting medical significant information from a large amount of medical knowledge around the world.

As an application of AI and data science to the healthcare domain, we have worked on big data analysis of the Iwaki health checkup cohort in Hirosaki City, Japan and successfully developed AI to predict the early onset of 11 diseases, including hypertension, from the health checkup data. In addition to predicting disease onset, we have also developed an AI that estimates intervention points and proposes optimal plans to improve health and prevent disease onset. In this presentation, I would like to introduce the potential of big data and AI in hypertension by illustrating these our research.
S-47-6: BIG DATA AND REAL-WORLD DATA FOR HYPERTENSION MANAGEMENT IN THE ERA OF DIGITAL HEALTH
Authors: Okada Mihoko
Published: January 2023

There has been an increasing number of research papers on hypertension studies using healthcare big data. Real-world data (RWD) is a term used for observational studies in a way that appears similar to big data, and is considered as the data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources including EHRs, claims and billing activities, product and disease registries, patient-generated data in home-use settings, data gathered from other sources that can inform on health status such as mobile devices, as described by the U.S. FDA. For the purpose of this presentation, the term RWD will be used regardless of big data or not, unless a distinction between big data and RWD is necessary.

In the era of Digital Health, recent hypertension management research shows a prominent trend towards the use of mobile technology that enables self-management of hypertension. By digital health, we mean eHealth and mHealth collectively. We have conducted literature search on digital health studies that targeted hypertension management using PubMed. There are many studies on mHealth for improving lifestyle where smartphone is considered a convenient tool to aid in the treatment of hypertension through the use of apps targeting self-management behavior for blood pressure control. In some studies, data obtained from the apps are combined with clinical data or linked to existing databases for cohort studies. Other studies focus on the use of mHealth technologies for medication adherence, improved communication between clinicians and patients, and or education to patients and to their family. Studies have shown potential of digital interventions in self-management, changing the behavior of people with chronic conditions, with discussions of the feasibility, acceptability, and effectiveness. Effectiveness of digital interventions has been assessed in many trials although most of the studies are small scale. There are also some studies on digital therapeutics (DTx) and their trials for hypertension, where DTx are digital health tools for therapeutic interventions.

In this presentation, we provide an overview of on-going efforts to obtain evidence to determine the overall effect of digital health technology on blood pressure control, medication adherence, and lifestyle changes for people with hypertension. Then we discuss barriers to and enablers of adoption of technology-based interventions, and need of more large-scale well-designed epidemiological research.
S-48-2: ENERGY EXPENDITURE OF OLDER PATIENTS WITH TYPE 2 DIABETES AND HOW IT RELATES TO FRAILTY
Authors: Kastukawa Fuminori
Published: January 2023

Because of the increased anabolic threshold for skeletal muscle synthesis (anabolic threshold), a multicomponent exercise program with an emphasis on resistance training has been recommended for older subjects with frailty risk. However, increasing energy expenditure with physical activity might be also helpful for increasing nutritional intakes and thereby reducing sarcopenia risk.

We have evaluated energy expenditure in older subject with type 2 diabetes (T2DM), which is associated with an increased risk of sarcopenia. Total energy expenditure (TEE) showed no difference between patients with T2DM and non-diabetic controls. However, wide variations in PAL (i.e. TEE/basal metabolic rate) were found, and difference in TEE between the highest and lowest PAL tertile was ∼500 kcal/d, and estimated daily protein intake for the highest and lowest PAL was 1.53 and 1.20 g/kg, respectively.

Non-basal energy expenditure showed weak but statistically significant correlations with fat free mass, grip power, and phase angle, and related to reduced sedentary time and increased moderate intensity locomotive physical activity. Longitudinal studies are further needed to evaluate the role of PA energy expenditure for reduced risk of frailty and sarcopenia.
S-49-3: THE ASSOCIATION BETWEEN CALF CIRCUMFERENCE AND MID-UPPER ARM CIRCUMFERENCE AND PREVALENCE OF HYPERTENSION: FINDINGS FROM THE PURE CHINA STUDY
Authors: Lang Xinyue , Li Wei
Published: January 2023

Objective:

To investigate the association of calf circumference (CC), mid-upper arm circumference (MUAC) and their derivative indexes (waist-to-arm and waist-to-calf circumference ratio) with prevalence of hypertension.

Methods:

A total of 47,677 individuals aged 35–70 years with measurement of CC, MUAC and blood pressure were available for analysis. CC and MUAC were measured under standardized training. The association of CC and MUAC with hypertension were tested in logistic regression analyses and reported as odds ratio (OR) with 95% CI. Subgroup analysis for BMI was conducted.

Results:

CC and MUAC were positively correlated with hypertension in the crude model. When adjusted for the BMI and waist, larger CC and MUAC were associated with a lower hypertension prevalence rate. It was stable after adjusted for demographic characteristics, lifestyle behaviors and health status [OR of 0.96(0.91, 1.03), 0.90(0.83, 0.97), and 0.85(0.80, 0.90) for Q2, Q3, and Q4 for CC, P for trend < 0.05, respectively; OR of 1.00(0.94, 1.07), 0.94(0.88, 1.00), and 0.82(0.76, 0.88) for Q2, Q3, and Q4 for MUAC, P for trend < 0.05, respectively]. Larger waist-to-arm and waist-to-calf circumference ratios were correlated with a higher risk of hypertension. For the overweight (BMI 24–28 kg/m2) group, as the CC or MUAC increased, a significant trend for a lower prevalence of hypertension was observed [OR of 0.87(0.77, 0.98), 0.84(0.75, 0.95), and 0.79(0.69, 0.90) for Q2, Q3, and Q4 for CC, P for trend < 0.05, respectively; OR of 0.86(0.76, 0.97), 0.77(0.69, 0.87), and 0.71(0.63, 0.80) for Q2, Q3, and Q4 for MUAC, P for trend < 0.05, respectively].
S-50-1: INCREASED FIBROBLAST GROWTH FACTOR-21 IN CHRONIC KIDNEY DISEASE IS A TRADE-OFF BETWEEN SURVIVAL BENEFIT AND BLOOD PRESSURE DYSREGULATION
Authors: Kuro-o Makoto
Published: January 2023

Circulating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on the suprachiasmatic nucleus in hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. CKD was introduced to mice by uninephrectomy followed by high phosphate diet feeding for 6 weeks. FGF21-deficient CKD mice died earlier than wild-type CKD mice. Paradoxically, FGF21-deficeint CKD mice escaped several complications observed in wild-type CKD mice. Wild-type CKD mice exhibited increased variability of systolic blood pressure due to augmentation of blood pressure elevating response during physical activity. The blood pressure dysregulation in wild-type CKD mice was associated with activation of sympathetic nervous activity and suppression of parasympathetic nervous activity during physical activity, and an increase in serum noradrenalin and corticosterone levels. These CKD complications observed in wild-type mice were absent in FGF21-deficeint CKD mice but recapitulated in wild-type non-CKD mice overexpressing FGF21 by administration of an FGF21-expressing adeno-associated virus vector. These findings indicate that FGF21 is necessary and sufficient to induce blood pressure dysregulation. We conclude that increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis.
S-51-1: SYMPATHETIC REGULATION OF SALT SENSITIVITY
Authors: Wainford Richard
Published: January 2023

This presentation will cover recent advances relating the role of the sympathetic nervous system in the regulation of the salt sensitivity of blood pressure. Recent studies from our laboratory have elucidated the previously unknown role of PVN specific Galphai2 signal transduction in the prevention of the development of the salt sensitivity of blood pressure. We will discuss these findings and their potential translational relevance. Highlighting the role(s) of the renal sympathetic nerves in the modulation of sodium reabsorption and long-term blood pressure regulation we will highlight recent advances in the role(s) of the afferent renal nerves in the salt sensitivity of blood pressure and how increased renal sympathetic outflow influences the expression and activity of the renal sodium chloride cotransporter.
S-52-2: PARAMETERS INDICATING HYPERTENSION PREVALENCE IN THREE-YEAR FOLLOW-UP STUDY OF INDIVIDUALS WITH HIGH NORMAL BLOOD PRESSURE
Authors: Kalos Theodoros , Dimitriadis Kyriakos , Andrikou Ioannis , Manta Eleni , Fragoulis Christos , Konstantinidis Dimitris , Tatakis Fotis , Leontsinis Ioannis , Matzouranis Emmanouil , Kariori Maria , Sotiris Drogaris , Polyzos Dimitris , Filippou Christina , Tsioufis Kostas
Published: January 2023

Objective:

Assess the relation of blood pressure response to treadmill exercise test in subjects with high normal blood pressure (BP) while sympathetic overactivity assessed by muscle sympathetic nerve activity (MSNA) and arterial stiffening are linked with development of hypertension (HTN).

Design and method:

100 consecutive subjects with high normal BP according ESC guidelines (systolic BP = 130 to 139mmHg and/or diastolic BP = 85 to 89mmHg), underwent a negative for ischemia treadmill exercise test (Bruce protocol). Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). Sympathetic drive was assessed by (MSNA). A new index the SBP/MET-slope ((peakSBP minus restingSBP)/(peakMET minus 1)) was used. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advise to lower their BP. Endpoint was development of HTN either with OffBP or ABPM. Then they divided into Group I those who developed HTN and Group II without HTN.

Results:

From 100 subjects (54 ± 8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg) 40 developed HTN (Group I) and 50 developed HRE (BP > 210mmHg in men and > 190mmHg in women). Group I vs II had higher HRE (75%vs13%, p = 0.026) with intermediate stage intervals of 3 min (160vs147mmHg, p = 0.068) and 6 min (181vs164mmHg, p = 0.035). The SBP/MET-slope in Group I was increased in all stages till peak exercise independently of sex type (stage1: 6.25vs4.25, stage2: 7.6vs5.3, peak: 7.22vs5.1, p = 0.035). Their exercise capacity was reduced (10vs11.5METs, p = 0.05) as their maximum exercise heart rate (154vs164, p = 0.001). They demonstrated higher levels of PWV (8.35vs7.5m/sec, p = 0.043) and MSNA levels (37vs31 bursts, p = 0.04) both correlated with development of hypertension (p = 0.002), while did not differ regarding their metabolic profile at the followup. The correlation Echocardiographicly LVMI did not differ, but LVEDD (47vs45 mm, p = 0.02), E/A ratio of mitral valve inflow (0.92vs1.05, p = 0.034) and left atrium diameter (3.8vs3.6 mm p < 0.1) were statistically significant. At their initial ECG had shorter P wave duration (101.3vs93.2, p = 0.013) and QRS duration (93.4vs85.7, p = 0.006). In ABPM they demonstrated higher night systolic BP (116vs112mmHg, p < 0.04).

Conclusion:

In subjects with high normal BP, MSNA identifies a state of increased sympathetic overdrive, PWV demonstrates arterial stiffening and exercise testing provides a prognostic value as a hypertension screening tool acknowledging a state of increased systemic vascular resistance progressing to development of hypertension.
S-52-3: ROLE OF NOVEL ECHOCARDIOGRAPHIC METHODS TO DETECT EARLY MYOCARDIAL DYSFUNCTION IN WOMEN WITH PREECLAMPSIA
Authors: Hristova Krasimira Atanasova , Tselov Nikolay , Marinov Rumen , Stamenov Georgi , Chacheva Kristina , Michova Marina , Georgiev Daniel , Panayotova Jeni , Persenska Sanina , Dimova Neli , Racheva Anelia
Published: January 2023

Normal pregnancy is associated with reversible changes in both systolic and diastolic mechanics, consistent with an increase in preload and decrease in afterload and systemic vascular resistance. The aim of the study is to evaluate left ventricular cardiac mechanics via speckle tracking echocardiography in a population of pregnant women with per partum cardiomyopathy and preeclampsia(PE) after invitro fertilization (IVF) during different stages of pregnancy.

The study population included 525 pregnant women with PE, after IVF, 100 of them with multiple pregnancy (46.5 ± 3 years) and 30 healthy nonpregnant women (33 ± 4years).Apical and basal short axis and apical view for three, two and four chamber for 2D images were acquired (65 ± 7 frames/s) during the first, second and third trimester of the pregnancy, as well as up to two months post partum. The curves of longitudinal(GLS), circumferential(GCS), radial strain(GRS) and LVT /LVUR were extracted using a commercial software.

Results:

Peak LVT and LVUR increased significantly in the 3rd trimester in both pregnancy groups (13.48 ± 2.90°,13.12 ± 3.30?,16.83 ± 3.61?,P < 0.001; and -111.52 ± 23.54°/sec,-107.40 ± 26.58?/sec,-144.30 ± 45.14?/sec, P < 0.001; in the 1st, 2nd, and 3rd trimester, respectively.The pregnants with twins have the highest value for LVT and LVUR compare with other pregnants (p < 0.01), but in the last trimester, the time to peak LVUR is prolonged. An independent correlation was found between the change in LVT and LV end-systolic volume in 1st and 3rd trimester (r = 0,56). Peak LVUR at the 3rd trimester correlated significantly with LV end-diastolic volume. Multiple regression analysis indicates that only systolic blood pressure (r = 0.394, P = 0.005) was an independent predictor for increased LV torsion. Arterial hypertension (AH) and prevalence of preeclampsia (PE) are more often in IVF group. Longitudinal strain decreased significantly (p < 0.001) during 3th trimester in women with AH and PE. Global longitudinal strain measures of the LV were non-significantly different between the different groups in first and second trimester (GLS-20.6 ± 3,14 vs.-19,29 ± 2,17).There are not found significant differences for GCS and GRS during pregnancy.

Conclusions:

During pregnancy LV twist and peak untwisting rate increase in the 3rd trimester and correlate with end-systolic and end-diastolic volume, respectively. Blood pressure and condition of multiple pregnancy are independently associated with increased torsion during pregnancy and may predict the new onset heart failure and perinatal cardiomyopathy. Global longitudinal strain is the main predictor of new onset peripartum cardiomyopathy
S-54-2: ROLE OF THE THIAZIDE-SENSITIVE NA+:CL- COTRANSPORTER IN THE BLOOD PRESSURE-LOWERING EFFECT OF POTASSIUM RICH DIETS.
Authors: Castaneda-Bueno Maria
Published: January 2023

Evidence supports that a negative correlation exists between dietary potassium consumption and blood pressure levels in the population. It has also been well documented that increasing dietary potassium consumption, increases urinary sodium excretion. The molecular mechanisms that contribute to this latter phenomenon are under investigation. Recent evidence suggests that the thiazide-sensitive Na+:Cl- cotransporter, NCC, may play a key role in this regard. For instance, in mouse models, variations in blood pressure and natriuresis observed in response to altered potassium intake are significantly blunted in NCC deficient mice.

NCC activity indirectly modulates urinary potassium excretion and NCC activity is tightly regulated in response to subtle alterations in plasma potassium concentration that occur in response to dietary potassium consumption changes. The molecular mechanisms that mediate this modulation are complex and their characterization has significantly advanced in recent years. Such mechanisms will be discussed in the presentation. The most recent advances will be highlighted.
S-54-3: PREDICTION AND PREVENTION OF THE ONSET OF HYPERTENSION FROM THE VIEWPOINT OF ESTIMATED 24-HOUR SALT EXCRETION AND PHYSICAL FITNESS TEST
Authors: Kato Kiminori , Ishigami Tomoaki , Sone Hirohito
Published: January 2023

Objective:

Both dietary salt and physical activity contribute substantially to development and progression of blood pressure elevation. Earlier detection of blood pressure change by daily simple procedures are effective for health promotion less expensively. We performed both longitudinal and cross-sectional observations for the subjects with annual comprehensive health checkup to test relationships among daily salt intake, physical activity, and blood pressure elevation. Methods: We performed following three observations. A)Body weights, interviewed salt intakes (i-NaCl), and estimated salt intakes (e-NaCl) for single spot urine (Tanaka formula) were measured and compared to blood pressure change monthly for one year in total 17,794 participants. B) To test significance of shared e-NaCl information to health promotions, we shared e-NaCl to total 98,908 participants individually and, subsequently, annual-mean e-NaCl was compared for 5 years. C) To test significance of physical activity for blood pressure elevations, we performed 5-year follow up study for total 22,972 participants to examine the onset of hypertension and physical activity as followings; duration of single-leg balance with eyes closed (sec), grip strength (kg), forward bending (cm), whole body reaction time (msec), vertical jump distance (cm), and supine leg-up (sec), respectively.

Results:

A) Only e-NaCl was found to have a strong correlation with the monthly mean systolic blood pressure as shown in a figure. B) By sharing e-NaCl information with participants, annual mean of e-NaCl decreased significantly from 9.22 g/day (male) and 8.79 g/day (female) in 2012 to 9.03 g/day (male) and 8.63 g/day (female) in 2017. C) Even when adjusted for gender, age, BMI, systolic and diastolic blood pressure of first year, single-leg balance with eyes closed and forward bending were significantly associated with the onset of hypertension.

Conclusion:

Since e-NaCl is affected by salt excretion due to sweating, it was presumed that the amount of salt to be excreted in urine correlated well with seasonal changes in blood pressure. In addition, e-NaCl measurement is a good tool that can be used for health guidance to examinees for their life style promotion. It was found that flexibility and a sense of equilibrium are related to the onset of blood pressure.
S-55-2: ROLE OF AVS IN PA SUBTYPING-NOT THE PUREST GOLD STANDARD
Authors: Turcu Adina
Published: January 2023

Primary aldosteronism (PA) has been traditionally grouped into unilateral aldosterone producing adenomas (APA) and bilateral forms. PA subtyping still relies on adrenal vein sampling (AVS), which is invasive, costly, and scantly available. This session will focus on the evolution of steroid profiling by mass spectrometry as a non-invasive tool for PA subtyping.
S-55-4: HISTOPATHOLOGY-GENOTYPE CORRELATION OF ALDOSTERONE- PRODUCING ADENOMAS
Authors: Azizan Elena Aisha
Published: January 2023

Primary aldosteronism (PA) is a vastly underdiagnosed (<1 in 500) cause of secondary hypertension in which aldosterone production is inappropriately high relative to suppressed plasma renin levels. This is of major concern as untreated patients are at increased risk for cardiovascular diseases, stroke, and other comorbidities even when compared to matched essential hypertension patients. PA is commonly caused sporadically by aldosterone producing adenomas (APAs) that harbors somatic mutations in aldosterone driver genes. It can account for up to 5 to 10% of hypertensive cases or up to 10 to 20% of resistant hypertensive cases. The current recommended treatment for APAs when only affecting one adrenal is a unilateral adrenalectomy. This has allowed the excised tissue to be extensively studied and characterized. Interestingly APAs have been found to occur with a spectrum of cell morphology and clinical phenotype. This heterogeneity seem to have a genetic basis. KCNJ5 mutant APAs, the most common genotype of APAs, have zona fasciculata (ZF) like cell morphology & secrete hybrid steroids. They commonly are large and frequently occur among young females and Oriental patients. Whereas CACNA1D mutant APAs are smaller, more zona glomerulosa (ZG) like (i.e. more compact than ZF), and more common in Black patients. To note, CACNA1D is also the most common aldosterone driver mutations in aldosterone producing micronodules and elderly patients, followed by aldosterone driver mutations in ATP1A1 and ATP2B3. CTNNB1 mutant APAs that also harbor GNA11/GNAQ mutations have cells that seem to dedifferentiate towards the adrenal-gonadal precursor cell type as they express the LH/HCG receptor ten fold more than other mutant APAs or even CTNNB1 mutant only APAs. This would explain why patients with the double mutations often present at times of high LH/HCG. These distinct genotype specific phenotypes could be used to facilitate screening and diagnosis of PA. For example, hybrid steroid measurements could be used for screening of KCNJ5 mutant APAs; or onset of hypertension in the first trimester (the period of peak HCG secretion), compared to pregnancy associated hypertension in later trimesters, should prompt consideration for a double mutant APA. Moreover, identification of these somatic mutations has already led to potential therapeutic treatments. For example, chemical screens have identified macrolides that selectively inhibit mutant KCNJ5. Thus, histopathology genotype correlation of APAs have provided new opportunities for the screening, diagnosis, management, and treatment of PA. Further elucidations of the cellular mechanisms associated with each correlation will help to identify the pathological and physiological pathways, and thus novel therapeutic targets.
S-56-1: CLINICAL TRIALS OF TELEMONITORING TO SUPPORT THE MANAGEMENT OF HYPERTENSION IN PRIMARY CARE AND PREGNANCY
Authors: McManus Richard J
Published: January 2023

This talk will review the evidence of telemonitoring in the remote management of hypertension both in primary care and in pregnancy. It will start by introducing the issues around why current hypertension management is sub-optimal. It will review the evidence that self-monitoring of hypertension, linked to electronic can assist both clinicians and their patients in the management of hypertension. It will review the impact on blood pressure of different types of intervention, concentrating on telemonitoring. It will consider the pros and cons of including patients in their own management, including self-management. The pregnancy section will review the translation of lessons learnt in the wider field into the care of pregnancy hypertension and summarise the results of recent clinical trials and linked studies.

The lecture will be illustrated with examples from the literature including from the TASMIN trials, HOME-BP and the recently published BUMP trials. The use of trial data linked to clinical epidemiology will be used to show how such results can inform daily practice.

The session will end with consideration of how such evidence is now being implemented into daily practice and consideration of how this has allowed remote care to be maintained during the pandemic.