bluuebunny/crossref_metadata_2025 huggingface dataset:
S-43-3: INTRAUTERINE GROWTH RESTRICTION CAUSES AN ALTERATION IN KIDNEY GENE EXPRESSION
Authors: Intapad Suttira
Published: January 2023

High blood pressure (BP) and kidney disease are the leading cause of death in the world population. Experimental and epidemiological studies indicate that the fetal environment is critical in determining adult cardiovascular (CV)-renal outcome. It is known that intrauterine growth restriction (IUGR) or low birth weight (LBW) induces an increased risk of hypertension and kidney disease in later life. Placental insufficiency is the common cause of IUGR. Low birth weight is a significant public health problem globally and is associated with short- and long-term consequences. About 15–20% of all births worldwide are LBW, representing more than 20 million births a year. Clinical studies indicate that birth weight is positively associated with glomerular filtration rate (GFR) and negatively associated with BP. Also, animal models of IUGR exhibit a higher susceptibility to ANGII induced high BP and kidney damage in response to acute ischemic reperfusion injury. Thus, these data suggest that IUGR programs greater risk of hypertension and renal dysfunction. However, the exact mechanisms linking an adverse fetal environment with a later increased risk of these diseases are unclear.

Objective:

This study aims to evaluate the global genetic change in the kidney of the animal model of IUGR.

Design:

female C57Bl/6J were mated with male C57bl/6J. Upon confirming the pregnancy by sperm plug (day 0 of gestation), the pregnant animal will be undergone reduced uterine perfusion surgery (RUP) or shame surgery at day 13 of gestation. The offspring of RUP mom will be labeled as IUGR, and from the sham will be labeled as control. The offspring will be used for blood pressure measurement using radio-telemetry and kidney microarray analysis when they reach 24 weeks.

Results:

Th IUGR offspring significantly has an increase in blood pressure compared to the control. The kidneys of male IUGR have 6529 gene upregulation compared to male control. The make IUGR also has 5713 genes dow-regulation as compared to same-sex control. The female IUGR has 1635 genes upregulated and 1513 genes downregulated compared to the kidney from the female control group.

Conclusion:

the complication during pregnancy, such as reduced uterine perfusion, which is commonly found in preeclampsia programs, alters gene expression in the kidneys of their offspring. This finding suggests that IUGR causes the gene alteration in the kidneys, which is the primary organ in controlling the blood pressure of the offspring, and may lead to the development of hypertension and kidney disease.
S-46-6: COMPARING OFFICE, CENTRAL, HOME AND AMBULATORY BLOOD PRESSURE IN PREDICTING LEFT VENTRICULAR MASS
Authors: Aparicio Lucas Sebastian , Peuchot Verónica Andrea , Giunta Diego Hernan , Martinez Rocio , Barochiner Jessica
Published: January 2023

The blood pressure measurement method that more accurately predicts a left ventricular mass is controversial, and the evidence suggesting superiority of central over brachial measurements is contradictory. The aim of this study was to compare the relationship between the different clinic and out-of-clinic blood pressure measurements methods with left ventricular mass in patients who attended a specialised hypertension centre for a central blood pressure measurement. An analysis was performed on the correlations between left ventricular mass and central and brachial blood pressure measurements made in the clinic, and home, as well as 24-h systolic blood pressure measurements. A linear regression analysis was then performed to assess the independent relationship of each blood pressure measurement with left ventricular mass. The results on 824 treated and 123 untreated patients showed no significant differences between correlations, although home readings tended to have the best correlations. In regression adjusted models, for each 10 mmHg increase in systolic home blood pressure the left ventricular mass increased 10 g/m2 (95% CI; 3.7–27, P = .01, adjR2 0.38), and for 24-h ambulatory systolic blood pressure it increased 2.3 g/m2 (95% CI 0.76–3.9, P < .01, adjR2 0.15) in treated and untreated patients, respectively. The association of systolic blood pressure with left ventricular mass was better explained by home and 24-h ambulatory monitoring than to clinic-based measurements in treated and untreated patients, respectively. In the clinic, however, the central measurement was not superior to brachial blood pressure.
S-48-4: PHYSICAL FRAILTY IN HYPERTENSION MANAGEMENT
Authors: Yamamoto Koichi
Published: January 2023

The significance of hypertension management in older individual is greatly influenced by factors other than chronological age, as they have diverse physical, mental, and social backgrounds. Particularly, differences in physical function, between independence, frailty and dependence, have a great impact on antihypertensive therapy in the older population. Recent clinical trials support the significance of active antihypertensive therapy in the independent elderly, and inadequate blood pressure control in the older patients is one of the challenges in the practice of hypertension. On the other hand, there is a lack of evidence to positively support the significance of antihypertensive therapy for the older people who require nursing care, and some observational studies suggest that antihypertensive therapy is actually detrimental. Physical frailty between independence and the need for nursing care, is suggested to be the tipping point at which the significance of antihypertensive therapy changes, and observational studies have shown that the relationship between blood pressure and prognosis changes with the degree of frailty. In the practice of hypertension treatment in the older patients, it is important to understand such changes in the significance of antihypertensive therapy according to physical function. There are still issues to be addressed in practicing antihypertensive therapy with an awareness of the concept of frailty. For example, the Guidelines for the treatment of hypertension recommend that antihypertensive therapy for older patients with frailty be determined on an individual basis, but it is currently not easy to understand the basis to support such a decision. It is important to elucidate the factors that influence the association between blood pressure control and prognosis in frail hypertensive patients. Conversely, given the association between the significance of antihypertensive therapy and physical function, the preservation of physical function is a key to maintain the significance of antihypertensive therapy. In particular, as it is important to maintain or improve physical function in frail older patients, a future challenge is required to clarify what kind of assessment and antihypertensive treatment is optimal for this purpose. The future challenges to improve the management of hypertension in frail patients in the perspectives of geriatric medicine will also be presented.
S-53-6: ANALYSIS OF BP SCREENING IN PAKISTAN (MMM EXPERIENCE)
Authors: Ishaq Mohammad
Published: January 2023

Pakistan Hypertension League, under the banner of MMM, conducted a cross-sectional survey by involving all of its 14 regional chapters, throughout Pakistan. More than 150 volunteers were selected to conduct this survey with the help of pharmaceutical industry and were trained at PHL regional chapters. Screening camps were arranged in the month of May, at public places, hospitals and various institutions to allow general public to be screened for their BPs after taking their informed consent. MMM pre piloted data tool was used to record the demographic data including age and gender. Blood pressure of every individual was recorded in sitting position by using an OMRON digital BP apparatus. A subject was classified as having hypertension if the BP reading of >140/90mmHg or in those taking medication for high BP. All data were coded and analyzed by the MMM statistics team.

We present the screening results from three consecutive years (2017,18,19).A total of 37328 individuals screened of which 21270 (66.32%) were male and 16058 (33.8%) females. Mean age was 45.1 years. Mean systolic and diastolic B.P were 128.7 by 82.7 mmHg. A total of 21270 (55.3%) were found to be hypertensive.

Further analysis of largest data from 2018, screened 25076, out of which 14726 (58.7%) were hypertensive. Out of them 11681 (79.3%) were aware and 10759 (73.1%) were taking antihypertensives. Only 47.3% of those on medications had controlled BP, while only 34.5% of screened had their BP controlled less than or equal to 140/90 mmHg. Those who never had their BP checked were 26.3%. Diabetes Mellites was the commonest co-morbidity 29.2%, followed by previous MI and Stroke 12.9% and 12.4% respectively. In summary the prevalence of High BP in Pakistan was very high compared to other countries in the region. This data for logistic purposes belongs to urban & semi urban population. More surveys are required including rural communities.
S-54-1: SUBSTITUTING THE WORLDS SALT SUPPLY
Authors: Neal Bruce
Published: January 2023

The adverse effects of excess dietary sodium intake on blood pressure levels are well-established. On average the world eats dietary sodium, mostly in the form of salt, at twice the level recommended by the World Health Organization and five times the level consumed during a million years of hominid evolution. At the same time, average dietary potassium intake is below recommended intake levels in many populations, and inadequate potassium intake is also associated with high blood pressure.

Potassium-enriched salt substitute, in which some of the sodium chloride is replaced with potassium chloride, was first showed to lower blood pressure more than a decade ago. Most recently, in 2021, the Salt Substitute and Stroke Study showed that potassium-enriched salt can also reduce the risks of stroke (rate ratio 14%; p = 0.006), major cardiovascular events (13%; p < 0.001) and premature death (12%; p < 0.001). This large-scale randomised trial done amongst 21,000 individuals followed for 5 years also showed that these benefits were achieved without harm, and in particular, with no evidence of hyperkalemia (rate ratio 1.04; p = 0.76).

Potassium-enriched salts are a pragmatic means of reducing dietary sodium intake and supplementing dietary potassium intake in parallel. Unlike many other sodium reduction strategies, they are easy to implement because potassium-enriched salt can be used in just the same way as regular salt. This provided for excellent adherence in the Salt Substitute and Stroke Study, with 93% of participants still using the salt substitute at the end of the study.

The potential health gains from a switch to potassium-enriched salt are very large. Modelling done for China indicates that about 1 million strokes and heart attacks could be prevented each year if the switch was made nationwide. Several million more events might be averted if implementation was global. Another key feature of potassium-enriched salt is that it can be provided at low cost. While on average about twice as expensive as regular salt, potassium-enriched salt has a median price of less than $3 per kilogram in low- and middle-income countries.

Over the last 50 years, the fight against iodine deficiency disorders has seen the global salt supply switched from salt to iodized salt. It is now time to make a second switch from iodized salt to iodized and potassium-enriched salt to also prevent blood pressure related diseases.
S-57-1: GUIDELINES FOR GUT MICROBIOTA STUDIES IN EXPERIMENTAL AND CLINICAL HYPERTENSION
Authors: Marques Francine Z
Published: January 2023

In the last 7 years, we have seen a large body of evidence showing that the gut microbiota, the microorganisms that inhabit the intestine, have a role in experimental and clinical blood pressure (BP) regulation. Robust evidence comes from forward and reverse microbiome experiments, where faecal microbiota transplantation and treatment with specific microorganisms or metabolites they produce show they lead to changes in BP. However, this emerging field has also seen many poorly designed and/or reported studies that led to inconclusive findings. To improve reproducibility, together with co-authors, we have proposed guidelines to improve experimental design, transparency in reporting and data availability (Marques et al., 2019 Hypertension PMID: 31679421; Mirzayi et al., 2021 Nature Medicine PMID: 34789871). In this presentation, we will summarise the recommendations from these guidelines, as well as report on findings in ∼500 samples from hypertensive models where a series of confounder factors have been studied in detail.
AW-AD-2: ASSOCIATION BETWEEN AMBULATORY BLOOD PRESSURE AND RISK OF HOME HYPERTENSION IN A NORMOTENSIVE POPULATION
Authors: Nakayama Shingo , Satoh Michihiro , Metoki Hirohito , Murakami Takahisa , Tatsumi Yukako , Asayama Kei , Hara Azusa , Hirose Takuo , Utsugi Megumi Tsubota , Kikuya Masahiro , Mori Takefumi , Hozawa Atsushi , Imai Yutaka , Ohkubo Takayoshi
Published: January 2023

Objective:

Most of the hypertension management guidelines recommend out-of-office blood pressure (BP) measurement such as self-measured BP at home (home BP) and ambulatory BP monitoring for the accurate diagnosis and management of hypertension. Both out-of-office BP measurements are more useful than office BP as prognostic indicators of cardiovascular risk. However, no prospective study has assessed the longitudinal association between the two types of out-of-office BP measurements. Therefore, we investigated the association between ambulatory BP and the risk of home BP-based hypertension in a normotensive population and whether considering ambulatory BP improves the 10-year prediction model for home hypertension risk, which was developed in the previous study.

Desigh and method:

We followed up 410 participants (83.2% women; age, 53.6 years) without home and ambulatory hypertension in the general population of Ohasama, Japan. The Cox model was used to assess the hazard ratios for home hypertension (home BP ≧135/≧85 mmHg or initiation of antihypertensive treatment). In addition, the predictive ability for home hypertension incidence between the models adjusted for the covariates with 24-h, daytime, or nighttime SBP was examined using Harrell's C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The NRI considers changes in the estimated prediction probabilities that imply a change from one category to another between different models. IDI is defined as the difference between the discrimination slopes of a basic model and an extended model.

Results:

During a mean 14.2-year follow-up, 225 home hypertension incidences occurred. The hazard ratio (95% confidence interval) for home hypertension incidence per 1-standard deviation increase in 24-h systolic BP (SBP) was 1.59 (1.33–1.90) after adjustments for possible confounding factors, including baseline home SBP. Harrell's C-statistic was 0.72 (0.69–0.75) for the basic 10-year risk prediction model, which includes sex, age, BMI, current or ex-smoker status, office SBP, and baseline home SBP. By adding 24-h, daytime, or nighttime SBP to the basic model, continuous NRI and IDI significantly improved although no significant improvement in Harrell's C-statistics was observed.

Conclusions:

Independent of the baseline home SBP, 24-h SBP was associated with the risk of home hypertension in a normotensive population. The prediction model for home hypertension risk was improved by the addition of 24-h SBP to the basic model. It could be useful to measure ambulatory BP for the early detection of home hypertension.
AW-AD-4: RENOPROTECTIVE EFFECTS OF CANAGLIFLOZIN VIA LESSENING HYPERINSULINEMIA IN DIABETIC PATIENTS WITH HEART FAILURE: A POST-HOC ANALYSIS OF THE CANDLE TRIAL
Authors: Yamaguchi Satoshi , Shimabukuro Michio , Tanaka Atsushi , Node Koichi
Published: January 2023

Objective:

The mechanisms by which sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce proteinuria in patients with type 2 diabetes mellitus (T2DM) remain unclarified. We evaluated factors associated with proteinuria regression in patients with T2DM treated with canagliflozin.

Design and method:

This study was a post-hoc analysis of the CANDLE trial (UMIN000017669), which compared the effect of 24 weeks treatment canagliflozin and glimepiride for changes in NT-proBNP in patients with T2DM and chronic heart failure (CHF). Factors associated with regression of proteinuria at 24 weeks were evaluated with multivariate logistic models.

Results:

The rate of regression of proteinuria was higher and that of progression was lower in the canagliflozin versus the glimepiride group. There were no differences in the change in systolic and diastolic blood pressure and eGFR category between groups at baseline. Systolic blood pressure and insulin levels significantly decreased in the canagliflozin group but not in the glimepiride group. Insulin level, HOMA-β, HOMA-IR, and estimated plasma volume were decreased at 24 weeks in the proteinuria regression subclass but not in the proteinuria progression subclass, suggesting that regression of proteinuria is associated with the declines in these values in the canagliflozin group. Systolic and diastolic blood pressure did not change significantly in either the proteinuria progression or regression groups in both the canagliflozin and glimepiride groups. Higher insulin level was solely associated with proteinuria regression in the multivariate logistic regression model.

Conclusion:

In patients with T2DM and CHF, regression of proteinuria with canagliflozin treatment was associated with the pre-treatment insulin level. These results suggest new mechanistic intuitions into the beneficial effects of canagliflozin on renal outcomes and warrant discussion for selecting preferred patient profiles, including pre-treatment insulin levels.
AW-NI-6: MINERALOCORTICOID RECEPTOR ACTIVATION LEADS TO HIGH BLOOD PRESSURE DUE TO BODY POTASSIUM AND WATER LOSS
Authors: Minegishi Shintaro , Morisawa Norihiko , Kitada Kento , Wild Johannes , Keat Yam Wan , Han Hong Yu , Marton Adriana , Minegishi Kaoru , Tiing Lim Tzy , Ishigami Tomoaki , Tamura Kouichi , Nishiyama Akira , Kovalik Jean Paul , Titze Jens
Published: January 2023

Objective:

Mineralocorticoid receptor (MR) activation is known to reduce renal Na+ elimination and increase body fluid, resulting in arterial hypertension. We have reported earlier that high salt intake, chronic renal failure and psoriasis occur blood pressure increases initiated by body water loss. Here we tested the hypothesis that DOCA treatment induces a similar adaptive water conservation response that also causes arterial hypertension.

Design and method:

Male C57BL/6J mice on the low-salt diet (<0.1% NaCl) were divided into four groups: tap water (control), tap water with subcutaneous 25 mg DOCA (DOCA), 1% NaCl water with DOCA (DOCA salt), 1.44% NaHCO3 water with DOCA (DOCA NaBic). We performed continuous metabolic cage studies. Na+, K+, and water were measured in mice tissue by desiccation and consecutive dry ashing. Blood pressure was measured by telemetry. We also studied body composition, glucocorticoid-receptor (GR) protein/chromatin interaction, skin blood flow perfusion and renal vascular resistance. Metabolome and key enzyme activities of energy production in kidney, skeletal muscle and in liver were compared between four groups.

Results:

Compared to control mice, DOCA mice showed increased urine volume, lower urine osmolality and increased blood pressure. DOCA salt developed arterial hypertension within 3 days of the experiment (P < 0.001, Fig. 1A). In DOCA salt mice, K+ and water loss occurs in the initiation phase of arterial hypertension (Fig. 1B), indicating solute and water loss from the intracellular space. Further water loss was then prevented by secondary Na+ accumulation, indicating that the initial MR-driven dehydration reverted back to normal body fluid level by means of Na+ accumulation. Additional physiological adaptation to DOCA salt-driven body water loss included increased vascular resistance (Fig. 1C) and catabolic amino acid breakdown (Fig. 1D). DOCA NaBic mice showed similar massive primary K+ loss and secondary Na+ retention, but no arterial hypertension occurred (Fig. 1A). While DOCA salt decreased skin blood flow, DOCA NaBic increased it (Fig. 1C). DOCA salt mice showed renal glutamine catabolism as well as muscle protein catabolism (Fig. 1D). This catabolic state was coupled with glucocorticoid receptor binding in skeletal muscle.

Conclusions:

DOCA salt leads to pronounced initial K+ and water loss with hypertension. Na+ retention occurs only secondarily and is a compensatory response that reverts initial body water loss back to normal body water levels. Additional NaBic feeding reveals that the blood pressure level in mice with MR activation is determined by changes in blood flow independent of body Na+ or water content.
JS-IC: AGREEMENT REGARDING OVERCOMING HYPERTENSION IN THE ASIAN HYPERTENSION SOCIETY NETWORK 2022
Authors: JSH International Committee
Published: January 2023

Within Asia, religions and cultures differ, and economic development differs from region to region. However, despite this diversity, things will not progress efficiently or in a certain direction unless certain rules are in place. The global burden of hypertension has already been acknowledged. The reduction in blood pressure significantly reduces cardiovascular morbidity and mortality. Half of the world's population is concentrated in Asia, and this proportion is expected to continue to increase. As the population ages, the number of people suffering from hypertension is also expected to increase. It is critical to address hypertension in Asia. To do so, it is necessary to establish a common direction for the control of hypertension within the Asian region.

Since last year, Japanese Society of Hypertension has performed meeting and discussion with 14 Asian countries/regions to conquer hypertension in Asia. In this session, we will present the agreement to overcome hypertension in Asian population, and representatives from each country/region will make comments. In addition, this agreement will be published in Hypertension Research on the same day.
JS-WHL-ISH-RTSL-3: IS THE CURRENT RECOMMENDATION BY GUIDELINES FOR HYPERTENSION TO KEEP DAILY SODIUM INTAKE BELOW 5 G (SODIUM 2300 MG) REALISTIC?
Authors: Whelton Paul Kieran
Published: January 2023

The human kidney has an exquisite ability to regulate sodium. Absent kidney disease or drugs that interfere with sodium transport, humans require little dietary sodium for physiological function. Most natural foods are low in sodium content. Generally, higher sodium intakes result from the consumption of processed foods or foods that contain excess sodium that has been added during food preparation.

Policy recommendations for dietary sodium reduction are in place in almost 100 countries but the specifics of what is recommended and the approaches to implementation of the recommendations vary substantially. Daily sodium intake targets vary from about 1,200 to 2,400 mgs/day. A recent treatment trials dose-response meta-analysis identified a direct linear relationship between sodium intake and blood pressure (BP), suggesting that any reduction in dietary sodium intake is beneficial for BP lowering.

Feeding studies have demonstrated a capacity to substantially reduce sodium intake. This approach can be applied in commercial programs but has only modest generalizability as a clinical or public health approach. Feeding studies do, however, underscore the value of policies aimed at reducing the addition of sodium during food processing and food preparation. Large behavior-change trials with relatively long periods of follow-up have documented 20–30% reductions in sodium intake. Sodium intake reductions of 10–20% have been achieved in national programs, with the degree of success depending on the level of rigor for implementation of sodium reduction strategies.

Collectively, experience indicates that reducing sodium intake is challenging, especially over prolonged periods of follow-up. However, it can be achieved in both the clinical and public health setting, and even modest reductions in sodium intake result in important health benefits.
JS-MT-1: MAINTAINING AN ACTIVE RESEARCH CAREER DURING COVID-19 LOCKDOWNS
Authors: Lankadeva Yugeesh R
Published: January 2023

Maintaining an active medical research career is a multifaceted undertaking, and many challenges arise, even under normal circumstances. Therefore, the Australian government mandated COVID19 lockdowns and worksite restrictions from 2020 2021 inflicted an additional layer of complexity to an already complicated career for most researchers. A critical issue I faced during these COVID19 lockdowns was to establish whether our research focus was considered an essential service during a period of time when the public health advice was to restrict the movement of research staff and students by enacting new laws to ensure they stay at home. My research team members were also rightfully worried about contracting COVID19 during a period when a viable vaccine was not available. In this presentation, I will be covering some of the adaptive changes I implemented during the COVID19 lockdowns to ensure the continuity of our research program, which includes: 1) Proactive engagement with our medical institute and university COVID-19 taskforces to formulate a joint vision of which research areas should be prioritised during these lockdowns in pursuit of both treatments and vaccines; 2) Continuous communication with my research team to encourage, motivate and energise staff and students to allow them to contribute to the research program meaningfully; 3) Provide flexible working hours for research team members to work within the confinements of a reduced worksite footprint with an appreciation for social distancing; and 4) Contingency planning to ensure if one research team member contracts COVID-19, there are others with the cross-functional skillset to take over their responsibilities. Taking such steps ensured the rapid development of a new treatment regime that was showing impressive results in reversing multi-organ dysfunction in another clinically challenging area in intensive care units (sepsis). Following the preclinical assessment of safety and efficacy of this new treatment regime, we were able to compassionately treat a critically ill COVID19 patient receiving intensive care at Austin Health. In a short period of time, we saw improved regulation of blood pressure, arterial blood oxygen levels and kidney function. The patient was able to be taken off machine ventilation 12 days after starting sodium ascorbate treatment and discharged from hospital without any complications 22 days later. This research has now informed the design and commencement of multi-centre randomised controlled clinical trials at four hospital intensive care units in Australia.
JS-HR-2: HYPERTENSION MANAGEMENT IN CKD: UPDATE FOR BETTER CARDIO-RENAL OUTCOMES
Authors: Masuda Takahiro , Nagata Daisuke
Published: January 2023

Hypertension in CKD patients is a risk factor for end-stage renal disease, cardiovascular events, and mortality. Thus, the prevention and appropriate management of hypertension in these patients are essential strategies for better cardio-renal outcomes. Recently, novel risk factors for hypertension have been reported. Circulating fibroblast growth factor 21, an endocrine hormone mainly secreted by the liver, is associated with elevated blood pressure (BP) and/or aortic stiffness with renal dysfunction. Furthermore, several promising prognostic markers for cardio-renal outcomes have been suggested. A higher urinary sodium-to-potassium ratio was independently associated with poor renal outcomes in CKD patients. Higher albumin-to-creatinine ratios significantly increased the risk of first stroke or first ischemic stroke. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and mineralocorticoid receptor (MR) blockers are promising treatment options for better cardio-renal outcomes. The clinical use of SGLT2is has recently expanded to non-diabetic patients with CKD and heart failure as well as diabetic patients. SGLT2is have an antihypertensive effect, and the degree of BP change in patients undergoing SGLT2i therapy depends on the baseline BP; a larger reduction is observed in patients with higher baseline BP, and a minor reduction or slight increase is observed in patients with lower baseline BP. These BP regulation mechanisms may partially depend on body fluid homeostasis by SGLT2is. SGLT2is ameliorate fluid retention through osmotic diuresis and natriuresis, but are also associated with a low rate of hypovolemia, which is evident by the compensatory upregulation of renin and vasopressin levels. These fluid homeostatic mechanisms exerted by SGLT2is may contribute to the stabilization of BP and better cardio-renal outcomes. MR blockers are used in the treatment of essential hypertension and hyperaldosteronism. Recently, a new MR antagonist, finerenone, has been launched as a treatment for CKD with type 2 diabetes. In the FIDELIO-DKD study, finerenone significantly reduced the risk of kidney and cardiovascular events in CKD and type 2 diabetes.
JS-HR-8: PROGRESS OF OBESITY/DIABETES IN AREA OF HYPERTENSION RESEARCH 2021
Authors: Tanaka Atsushi , Node Koichi
Published: January 2023

Obesity/diabetes is a major comorbidity in people with hypertension, and they often share the common pathological backgrounds, such as insulin resistance and vascular failure, and the risk of cardiovascular disease (CVD). Thus, obesity/diabetes is an essential culprit to hamper cardiometabolic health. One of the biggest highlights of recent years in the area or obesity/diabetes has been the remarkable benefits of newer glucose-lowering agents seen in the large-scale clinical trials on cardiorenal outcomes, followed by the relevant clinical guidelines update and the expansion of the clinical application of those agents. In addition, such agents with evidence proved to have common and incidental actions, such as body weight loss and blood pressure reduction, potentially contributing to the better management of risk factors. These evidence and insights have led to new trends in our clinical practice for obesity/diabetes and cardiometabolic syndrome. In this talk, we would like to introduce the progress of obesity/diabetes in area of Hypertension Research 2021 and their clinical perspectives.
JS-HR-10: ADVANCES IN RENAL DENERVATION FOR TREATING HYPERTENSION
Authors: Katsurada Kenichi
Published: January 2023

Excessive activation of sympathetic nervous system is closely related to the onset and progression of hypertension. Renal nerves are composed of sympathetic efferent and sensory afferent nerves. Activation of the efferent renal sympathetic nerves induces renin secretion, sodium absorption, and increased renal vascular resistance, which lead to increased blood pressure (BP) and fluid retention. Afferent renal sensory nerves, which are densely innervated in the renal pelvic wall, project to the cardiovascular center in the brain to modulate sympathetic outflow to the periphery, including the heart, kidneys, and arterioles. Renal denervation (RDN) is a neuromodulation therapy that partially interrupts both the efferent outputs from the brain to the kidney and the afferent inputs from the kidney to the brain and has attracted attention as a novel device therapy for hypertension. In clinical practice, denervation is performed through the lumen of the renal artery using a catheter. Radiofrequency, ultrasound, and alcohol-based RDN devices are being developed as new second-generation devices. A randomized sham-controlled trials using 24-hour ambulatory BP measurement is required for approval of clinical use of RDN. The SPYRAL HTN OFF-MED pivotal trial showed the superiority of RDN using radiofrequency-based catheter compared with a sham procedure to safely lower 24-hour systolic BP in the absence of antihypertensive medications. The RADIANCE-HTN TRIO trials showed the superiority of RDN using ultrasound-based catheter compared with a sham procedure to safely lower daytime BP in patients with resistant hypertension. The REQUIRE trial is the first trial of ultrasound RDN in Asian patients from Japan and South Korea with resistant hypertension.

The study findings were neutral for the primary endpoint, with similar reductions in 24-hour systolic BP in the RDN and sham control groups. Although BP reduction after RDN was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. Japanese Society of Hypertension performed the meta-analysis of nine randomized sham-controlled trials of RDN including these three trials mentioned above. The results showed that RDN significantly reduced a range of office, home and 24-hour BP parameters in patients with resistant, uncontrolled, and drug-naïve hypertension. There were no significant differences in magnitude of BP reduction between radiofrequency-based and ultrasound-based devices. Recently, the efficacy and safety of RDN in the SPYRAL HTN OFF-MED pivotal trial up to 36 months have been reported. In this session, the latest basic and clinical evidence/aspects of RDN will be summarized and discussed, which is about to be introduced into the clinical practice.
RAG-SACA-3: ROLE OF PRIMARY CARE PHYSICIAN TO MANAGE HYPERTENSION IN A LOW-RESOURCE SETTING
Authors: Barua Lingkan
Published: January 2023

Hypertension is a primary care clinical condition that is therefore best detected, managed, and followed at a primary care level by a primary care team led by a physician. However, the delivery of primary care services is not unique in all countries, especially in low- or lower-middle-income countries where primary care physicians used to manage hypertension in low-resource settings (LRS). This presentation will focus on the concept of LRS, a list of potential roles played by a primary care physician, and possible challenges usually face. Usually, the settings where health care systems do not meet the minimum standards set by the World Health Organization or any other quasigovernmental organization are considered LRS. However, there is no explicit definition for LRS. The major roles of a primary care physician in LRS are identification of an individual at high risk for HTN, proper screening, diagnosis with a proper communication strategy to inform about the diagnosis, cost-effective rational treatment with counseling, and finally follow-up. The primary care physician is at the heart of a team-based HTN care in an LRS and will provide supportive supervision to the team to ensure the best outcome: (i) increased patient enrollment, (ii) increased patient treatment rate, (iii) improve BP control rate, (iv) high treatment compliance (v) reduction of drug stock-outs. In LRS, without team-based care and shifting of tasks, it will be very difficult to ensure proper management.

In general, a primary care physician will play a leadership role in a resource-poor setting to successfully implement an HTN management program.
PS-B01-3: IS IT POSSIBLE TO ACCELERATE SENESCENCE IN THE VASCULAR ENDOTHELIAL CELL BY MODULATING SEVERAL MICRORNAS?
Authors: Toyama Kensuke , Spin Joshua M , Tsao Philip S , Mogi Masaki
Published: January 2023

Backgrounds:

Many factors are involved in cellular aging, and senescence induction requires complex regulation of various signaling networks and processes. Specifically, in the area of aging-related vascular cognitive impairment, laboratory-based findings have not yet yielded agents of practical use for clinical settings. One possible reason is that the physiologic elements of aging have been insufficiently considered such as in a drug screening experiments (particular in the vitro-blood brain barrier model). It is difficult to age primary human cerebral vascular endothelial cells for the experiments using standard methods because of their limited ability to survive in vitro. To establish techniques to mimic cellular aging by modulation of microRNAs, we aimed to identify key microRNAs capable of fine-tuning aging-associated genes, and thereby regulating the senescence of vascular endothelial cells.

Methods:

To identify candidate microRNAs, expression microRNA array was performed between control and senescent vascular endothelial cells. Thereafter, bioinformatic analysis was used to select key microRNAs. These candidates were then modulated in vitro using microRNA mimics and inhibitors in vascular endothelial cells, and senescence-associated gene expression patterns were evaluated by qPCR.

Results:

Seventeen microRNAs were significantly increased more than 2-fold in senescent cells. Of those, bioinformatic analysis concluded that miR-181a-5p, miR-30a-5p, miR-30a-3p, miR-100-5p, miR-21-5p, and miR-382-5p were likely associated with regulation of cellular senescence. We evaluated the potential targets of these six microRNAs by comparing them with cell-cycling and apoptosis-related genes from published mRNA transcriptional array data from aged tissues, and found that miR-181a-5p, miR-30a-5p and miR-30a-3p were enriched in overlapping targets compared with the other candidates. When modulating and comparing these microRNAs in vascular endothelial cells with several patterns, we noticed that over-expression of miR-30a-5p, and inhibition of both miR-30a-3p and miR-181a-5p, induce senescence.

Conclusion:

Simultaneous upregulation of miR-30a-5p, and downregulation of both miR-30a-3p and miR-181a-5p, mimic cellular senescence in vascular endothelial cells. This single step induction, as opposed to the time-consuming process of replicative passage senescence, would be useful for mimicking cell senescence vitro model.
PS-B01-5: TISSUE-SPECIFIC REGULATION OF LRG1 EXPRESSION IN MULTIPLE HYPERTENSION MODELS OF MOUSE
Authors: Miyazawa Tomohito , Okami Naohito , Yukawa Naoki , Tsukamoto Shunichiro , Tanaka Shohei , Azushima Kengo , Wakui Hiromichi , Tamura Kouichi
Published: January 2023

Object:

Leucine-rich alpha-2-glycoprotein-1 (LRG1), which is firstly isolated from human plasma, has been reported to be related to several diseases as a biomarker or a pathogenic factor. Serum LRG1 is associated with the prognosis of diabetic nephropathy and cardiovascular diseases, and we previously demonstrated that LRG1 especially plays a pivotal role in the initial development of diabetic nephropathy. In addition, a previous study showed that increased plasma LRG1 levels in patients with type 2 diabetes mellitus was associated with increased systolic blood pressure (BP), arterial stiffness estimated by pulse wave velocity, and decreased endothelium-dependent vasodilation estimated by laser doppler flowmetry. However, the relationship between LRG1 and BP have remained substantially unknown.

With respect to the function of LRG1, LRG1 is expressed in endothelial cells and promotes pathological angiogenesis by modulating TGF-beta signaling. LRG1 switches TGF-beta signaling from the Smad2/3 pathway to the Smad1/5/8 pathway. In addition, the activation of Smad2/3 signaling enhanced endothelial nitric oxide synthase (eNOS) production and promoted endothelium-dependent vasodilation. Suppressing eNOS activity reduces NO levels and leads to endothelial dysfunction and hypertension. Moreover, LRG1 is increased in response to inflammation and oxidative stress in endothelial cells. However, little is known about the relationship between LRG1 in endothelial cells and eNOS.

Based on the previous findings, we hypothesized that LRG1 may inhibit eNOS production by potentially blocking the Smad2/3 pathway, which will promote to form a vicious cycle that progresses vascular endothelial damage and hypertension. As the first step to elucidate this hypothesis, we investigated LRG1 expression in various tissues including vascular endothelium in some hypertension models with endothelial dysfunction.

Design and method:

Male 10–12 weeks-aged C57/BL mice were divided into control and hypertension with endothelial dysfunction. BP was measured using a tail-cuff method during the experiment, and mice were sacrificed and their organs were collected at the end of the experiment. We examined the expression of LRG1, Smad2/3, Smad1/5/8 and NOS in the vascular endothelium, kidney, heart, adipose tissue by PCR, Western blot and immunohistochemical analyses.

Results:

We are currently conducting the experiments and will present our findings at this conference.

Conclusion:

We plan to present the results of tissue-specific regulation of LRG1 expression in some hypertension models of mice at this conference.
PS-B01-8: MALAYSIAN TUALANG HONEY INHIBITS PDGF-INDUCED HUMAN VASCULAR SMOOTH MUSCLE CELLS PROLIFERATION AND MIGRATION
Authors: Azman Ain Nabila Syahira Shamsol , Yong Yoke Keong
Published: January 2023

Introduction and Objective:

Cardiovascular diseases (CVD) are the leading cause of death globally. Atherosclerosis is a common CVD which can lead to the deadliest heart failure. Increasing evidence showed that abnormal vascular smooth muscle cells (VSMC) proliferation and migration constitute the main pathological basis of atherosclerosis. These events are potently stimulated by platelet-derived growth factor (PDGF), causing phenotypic switching of VSMC from a mature, quiescent phenotype to a proliferative, migratory phenotype which is commonly observed in the development of atherosclerosis. Furthermore, study have revealed that PDGF elevates the concentration of reactive oxygen species (ROS) which stimulates VSMC proliferation and migration. Pharmacological treatment for atherosclerosis is often an ongoing, long-term regimen that may have adverse effect to an individual. Thus, alternative therapy based on natural products can potentially be the frontier in atherosclerosis treatment. Interestingly, previous study revealed that Malaysian Tualang Honey (MTH) is capable of protecting vascular endothelial cells from inflammation. However, little is known on the effect of MTH on the PDGF-induced VSMC proliferation and migration. Therefore, the present study aimed to determine the antioxidant, anti-proliferative and anti-migratory effects of MTH in PDGF-induced VSMC.

Methodology:

VSMC were treated with increasing concentrations of MTH (0.001–10%) for 24 hours and the cell viability were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were then be treated with non-cytotoxic concentrations of MTH and induced with 20ng/mL PDGF for 72 hours to determine the proliferation rate via MTT assay. The intracellular ROS were measured in these cultured cells by dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Wound healing assay were used to determine the anti-migration activities on PDGF-induced VSMC treated with MTH.

Results:

Our data showed that MTH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to VSMC. Co-culture of the cells with MTH significantly inhibits the proliferation and migration of PDGF-stimulated VSMC in a concentration-dependent manner. Pre-treatment of cells with MTH prior to culturing in 20ng/mL PDGF showed a significant decrease in the production of ROS.

Conclusion:

This study demonstrates that MTH inhibits VSMC proliferation and migration by suppressing the production of ROS which constitute the pharmacological basis of anti-atherosclerotic action. Therefore, MTH potentially can be a promising therapeutic agent in the treatment of atherosclerosis.
PS-B01-9: APATINIB THROUGH ACTIVATING THE RHOA/ROCK SIGNALING PATHWAY TO CAUSE DYSFUNCTION OF VASCULAR SMOOTH MUSCLE CELLS
Authors: wang wenjuan
Published: January 2023

Apatinib is a small molecule TKI that highly selectively binds to and strongly inhibits VEGFR2. Previous studies have shown that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. However, hypertension is one of the main adverse effects of antiangiogenic tumour drugs and affecting the application of the drugs. Previous studies have confirmed that the RhoA/ROCK pathway is involved in the pathogenesis of hypertension. Abnormal cell proliferation and invasion of vascular smooth muscle cells are among the primary causes of cardiovascular disease. In this study, an in vitro experiment was conducted to observe whether apatinib caused dysfunction of MOVAS cells through the RhoA/ROCK signalling pathway and whether it could be improved after Y27632 intervention. Subsequently, cell lines in which the LARG gene, which is involved in the RhoA/ROCK pathway, was knocked out were constructed to observe whether LARG knockdown could improve the proliferation, antiapoptosis, oxidative stress and mitochondrial autophagy of apatinib induced MOVAS cells. To provide a basis for the prevention and treatment of this type of hypertension.
PS-B02-15: LIGHT POLLUTION, OBESITY, AND HYPERTENSION- “LIFESTYLE” RISK FACTORS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT ARRHYTHMIAS. ANTIARRHYTHMIC EFFECT OF OMACOR.
Authors: Sykora Matus , Benova Tamara Egan , Zurmanova Jitka , Knezl Vladimir , Tribulova Narcis , Bacova Barbara Szeiffova
Published: January 2023

Objective:

Light pollution disrupts circadian rhythms that may promote obesity and hypertension, but their association with the susceptibility to malignant cardiac arrhythmias is not well known. We examined whether continuous light as well as a high sucrose diet affect rat heart gene transcripts, miRNAs, or protein expression and hence arrhythmogenesis. In parallel, the benefit of omega-3 (Omacor) supplementation was assessed.

Design and method:

In the first experiment, male and female spontaneously hypertensive (SHR) and normotensive Wistar (WR) rats were housed in 12 h/12 h light/dark cycles or exposed to continuous light at 300 lux for 6 weeks. In the second experiment, aged female WR rats were fed with 30% sucrose for 8 weeks. In both experiments half of the rats were supplemented with Omacor (200 mg /100 g b.w). Susceptibility to electrically-inducible ventricular fibrillation (VF) was assessed in perfused heart.

Results:

Rats exposed to continuous light or fed by sucrose were more vulnerable to develop VF. There was a down-regulation of myocardial connexin-43 (Cx43) along with an increased pro-inflammatory NF-kB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ ATPase transcripts in response to continuous light. Omacor treatment increased the electrical threshold for VF induction associated with attenuation of pro-arrhythmic alterations in myocardial Cx43, NF-kB and iNOS.

Sucrose fed rats exhibited suppression of Cx43 and PKC epsilon signaling, along with upregulation of myocardial PKC delta and miR-30a that is involved in fibrosis. Myocardial miR-1 expression levels involved in the regulation of Cx43 were not affected by the sucrose diet nor Omacor treatment. Antiarrhythmic effects of Omacor supplementation have been shown by attenuation of Cx43, PKC, and miR-30a myocardial abnormalities.

Conclusions:

Findings suggest that light pollution and sucrose diet jeopardize myocardial Cx43-mediated electrical communication, thereby increase susceptibility of the heart to malignant arrhythmias. Adverse effects were alleviated by treatment with Omacor, supporting its potential benefit and the relevance of monitoring the omega-3 index in at-risk human populations.

This research was supported by VEGA 2/0002/20, 2/0158/19, APVV 21-0410, 18-0548, 19-0317, EU ITMS 26230120009