bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-P03-3: PREVALENCE OF HYPERTENSION IN NEPAL: RESULTS OF MAY MEASUREMENT MONTH 2020
Authors: Subedi Narayan , Acharya Pawan , Koirala Sweta , Soti Pabitra Babu , Sharma Sneha , Sapkota Abhisekh , Kafle Simrin , Paudel Kiran , Poudel Santosh , Neupane Dinesh
Published: January 2023

Objective:

To increase public awareness on importance of blood pressure (BP) screening for hypertension prevention and management through a national campaign in Nepal.

Design:

Opportunistic BP screening campaign was carried out among people 18 years or more in the year 2020, following the COVID-19 safety measures. The study used a cross-sectional survey design.

Method:

Systolic and diastolic BP data of the participants were obtained from three consecutive measurements of which second and third measurements were used to estimate the mean. Hypertension was defined as the systolic BP more than or equal to 140 and/or diastolic BP more than or equal to 90 mmHg or currently taking antihypertensive medicine. The screening campaign was conducted in 25 sites of the country. Measurement was done using OMRON automatic monitors. Altogether, 115 volunteer research assistants with public health background used mobilized for data collection. Logistic regression analysis was used to identify the factors associated with hypertension.

Results:

In total, 11,481 people participated in the BP screening campaign of which more than half were females (57%, 6568/11,481). Mean age of the participants was 45 ± 17 years. Mean systolic and diastolic BP were 125.8 ± 18 and 81.6 ± 10.5 respectively. Nearly a third (31.1%, 3592/11,481) of participants were hypertensive of which only 40% (1444/3592) were aware about their hypertension status. However, only about 80% (1146/14444) hypertensive participants were talking medicines. High age-group, high body mass index and smoking were found associated with hypertension adjusting age, sex and body mass index and smoking status of the participants.

Conclusions:

Blood pressure screening campaign provided an important opportunity to identify undiagnosed hypertension and raise awareness on hypertension among the general population. Awareness raising programs at the population and targeted interventions are warranted for prevention and control of hypertension in Nepal among older, overweight, and obese people and smokers.
PS-P03-9: CONTENT AND DELIVERY PREFERENCES FOR INFORMATION TO SUPPORT THE MANAGEMENT OF HIGH BLOOD PRESSURE
Authors: Chapman Niamh , Marques Francine Z , Picone Dean S , Schultz Martin G , Mynard Jonathan P , Climie Rachel ED
Published: January 2023

Blood pressure(BP) management interventions have been shown to be more effective when accompanied by appropriate patient education. As high BP remains poorly controlled, there may be gaps in patient knowledge and education. Therefore, this study aimed to identify specific content and delivery preferences for information to support BP management among Australian adults from the general public. Given that BP management is predominantly undertaken by general practitioners(GPs), information preferences to support BP management were also ascertained from a small sample of Australian GPs.

An online survey of adults was conducted to identify areas of concern for BP management to inform content preferences and preferred format for information delivery. A separate online survey was also delivered to GPs to determine preferred information sources to support BP management. Participants were recruited via social media.

General public participants (n = 465) were mostly female (68%), > 60 years (57%) and 49% were taking BP-lowering medications. The management of BP without medications, and role of lifestyle in BP management were of concern among 30% and 26% of adults respectively. Most adults(73%) preferred to access BP management information from their GP. 57% of GPs (total n = 23) preferred information for supporting BP management to be delivered via one-page summaries.

This study identified that Australian adults would prefer more information about the management of BP without medications and via lifestyle delivered by their GP. This could be achieved by providing GPs with one-page summaries on relevant topics to support patient education and ultimately improve BP management.
PS-P04-6: THE ROLE OF CUMULATIVE MEAN ARTERIAL PRESSURE IN FIRST STROKE EVENTS AMONG ADULTS WITH HYPERTENSION: A 10-YEAR PROSPECTIVE COHORT STUDY
Authors: Wang Dan , Wang Jiaqi , Liu Jiali , Qin Yu , Lou Peian , Zhang Yongqing , Zhang Yuqing , Xiang Quanyong
Published: January 2023

Objective:

Mean arterial pressure (MAP) has been proved to be an independent risk factor for stroke. In this study, we explored whether cumulative exposure of MAP in patients with hypertension is more associated with the occurrence of stroke.

Design and Method:

In this prospective follow-up cohort study of hypertension from June 2010 to May 2020, 9,136 participants without previous stroke at recruitment were included, of whom 492 (5.4%) had a first incident stroke during the study period (418 ischemic strokes and 74 hemorrhagic strokes). The study exposure factor was cumulative MAP, and was quartered from low to high (Q1, Q2, Q3, Q4). We analyzed the risk of first stroke using multivariable adjusted Cox regression models, and used stratified analysis to further explore the risk of stroke in hypertensive patients with different characteristics.

Results:

Increased cumulative MAP in patients with hypertension were associated with risk for ischemic stroke (HR, Q2, 1.23 [95% CI, 0.91–1.67]; Q3, 1.35 [95% CI, 1.01–1.82]; Q4, 1.55 [95% CI, 1.15–2.10]; P = 0.035). furthermore, this trend persisted after stratified analysis in men (HR, Q3, 1.76[1.10–2.82]; Q4, 2.05[1.28–3.28]), aged 60 or above (HR, Q4, 1.63[1.13–2.35]) and higher body mass index (BMI) populations (HR, Q3, 1.48[1.02–2.14]; Q4, 1.59[1.09–2.32]). In contrast, cumulative MAP was not significantly associated with stroke in women, age under 60, and non-obese individuals.

Conclusions:

Increased cumulative MAP is an independent risk factor of ischemic stroke in patients with hypertension. Special attention should also be paid to men, aged 60 or older, or those with a higher BMI.
PS-P05-3: ASPECTS AND DETERMINANTS OF TREATMENT COMPLIANCE AMONG HYPERTENSIVE PATIENTS I THE MAKWALLA HEALTH CARE SERVICES HOSPITALS
Authors: Musango Dennis Anthony , Onyeagala Augustine Anayo
Published: January 2023

Hypertension, a major cardiovascular risk factor, has become a public health problem in developing countries. It affects almost every household of adult population in black Africa, with higher rates in urban areas.(1) Adherence to treatment of chronic conditions such as hypertension is difficult especially when results are not very evident. Poor adherence leads to loss of control of hypertension and later to occurrence of complications. (2), (3) Compliance to hypertension treatment involves not only taking the prescribed drugs but also lifestyle modification. Patients knowledge about hypertension is another important factor for good compliance.(4)
PS-BPB02-2: POLYMORPHISM OF DNA REPAIR GENE IS ASSOCIATED WITH HYPERTENSION-INDUCED LEFT VENTRICULAR HYPERTROPHY - ROLE OF DNA DAMAGE AND CELL SENESCENCE
Authors: Sakai Chiemi , Ishida Mari , Ariyandy Andi , Ishida Takafumi
Published: January 2023

Objective:

Deficiency of X-ray repair cross-complementing protein 3 (XRCC3), a DNA-damage repair molecule, and 241Met variant of XRCC3 are prone to increase endoreduplication, resulting in pathological polyploidy. In this study we investigated the impact of XRCC3 polymorphism on the incidence of hypertension-induced left ventricular hypertrophy (LVH) and underlying mechanisms.

Design and method:

Patients under hemodialysis (n = 77) were genotyped for XRCC3 Thr241Met polymorphism. LVH was determined by echocardiography. To investigate the possible mechanisms for LVH, human XRCC3 cDNA of 241Thr or that of 241Met was introduced into cultured cells. The surface area of the cells was measured and spontaneous DNA double-strand breaks were detected by immunofluorescent study with anti-53BP1 antibody. The mRNA levels of basal and TNF-α-stimulated MCP-1 were quantified by real-time RT PCR. FACS analysis was performed to count the percentage of polyploidy.

Results:

In patients under hemodialysis, XRCC3 241Thr/Met genotype was more frequent in LVH (+) group than in LVH (-) group (42.3% vs. 13.7%, χ2 = 7.85, p = 0.0051). To investigate the possible mechanisms for LVH, following in vitro experiments were performed. The surface area of Chinese hamster ovary cells expressing XRCC3 241Met variant was larger than those expressing 241Thr. The accumulation of spontaneous DNA double-strand breaks (DSBs) was increased in NIH3T3 cells expressing 241Met (3T3–241Met) than those expressing 241Thr (3T3–241Thr). Ionizing radiation-induced cell senescence was significantly enhanced in 3T3–241Met than in 3T3–241Thr. The mRNA levels of basal and TNF-α-stimulated MCP-1 were higher in 3T3–241Met variant than 3T3–241Thr. Finally, FACS analysis revealed that the cell percentage in G2/M phase including polyploidy was significantly increased in 3T3–241Met compared with 3T3–241Thr. In addition, the basal mRNA level of MCP-1 was positively correlated with the cell percentage in G2/M phase and polyploidy.

Conclusion:

The current study suggests that XRCC3 241Met variant increases the risk of LVH via the accumulation of DNA damage, alteration of cell cycle progression, and induction of cell senescence and proinflammatory phenotype.
PS-BPB02-5: INHIBITION OF CALPAIN ALLEVIATES FERROPTOSIS IN DOXORUBICIN-INDUCED CARDIOMYOPATHY
Authors: Chen Zhiwei , Chen Ruizhen
Published: January 2023

Rationale:

Maintaining iron homeostasis is essential for proper cardiac function. Although excessive activation of calpain plays a central role in cardiomyopathy and heart failure via complex mechanisms, the molecular function of calpain in iron homeostasis and cardiomyocyte ferroptosis remains unknown.

Objective:

To characterize the functional role of calpain in mediating cardiac iron homeostasis and heart disease.

Methods and Results:

Doxorubicin-induced cardiotoxicity (DIC) model with C57BL/6 mice was established and confirmed by transthoracic echocardiography examination. The induction of ferroptosis in the DOX-treated murine heart was confirmed by transmission electron microscopy, cardiac malondialdehyde (MDA) level, glutathione (GSH) level and Ptgs2 mRNA expression. We then investigate the role of calpain in DOX-induced cardiomyocytes ferroptosis. Both in vitro and in vivo experiments proved the upregulation of calpain-1 in DIC, which can be partially prevented with Lip-1 or Fer-1 treatment. Knock-down of calpain-1 in cell lines showed noteworthy protection to ferroptosis, while the overexpression of calpain-1sensitized cardiomyocytes to ferroptosis by DIC. Both in vitro and in vivo experiments proved PD150606, a specific inhibitor of calpain, inhibits lipid oxidation and DOX toxicity in DIC through promoting dihydroorotate dehydrogenase (DHODH) level, supporting calpain activation plays a central role in DOX-induced cardiomyocytes ferroptosis. Finally, we found that BAY-2402234, a novel DHODH inhibitor, undermined the protection effect of PD150606 in DIC.

Conclusion:

Our findings provide compelling evidence that calpain plays a major role in cardiac ferroptosis and subsequent cardiomyopathy, providing a potential treating target in preventing DIC by anti-ferroptosis.
PS-BPB04-1: DNA-APTAMER RAISED AGAINST RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS INHIBITS ATHEROSCLEROSIS
Authors: Terasaki Michishige , Mori Yusaku , Yashima Hironori , Saito Tomomi , Sotokawauchi Ami , Matsui Takanori , Hiromura Munenori , Osaka Naoya , Fukase Ayako , Kawakami Raichi , Shiraga Yoshie , Ohara Makoto , Fukui Tomoyasu , Yamagishi Shoichi
Published: January 2023

Background and Aims:

Interaction of advanced glycation end products (AGEs) with the receptor RAGE could accelerate atherosclerotic plaque formation. However, effect of DNA-aptamer raised against RAGE on atherosclerosis remains unclear. In this study, we aimed to elucidate whether and how RAGE-aptamer could inhibit atherosclrotic lesions and oxidized-LDL uptake of macrophages derived from apolipoprotein E (ApoE)-null mice, a representative animal model of atherosclerosis. We also examined whether RAGE-aptamer could inhibit oxidized-LDL uptake in AGE-exposed mouse peripheral macrophages and human U937 cells.

Materials and Methods:

Seventeen-week-old male ApoE-null mice were subcutaneously infused with RAGE-aptamer (10 pmoL/g/day) or control-aptamer by osmotic pump for 4 weeks. Peritoneal macrophages were extracted from mice at 21 weeks of age just after intraperitoneal injection of thioglycollate broth. The entire aortae and cross-sections of the aortic roots were stained with Oil Red O or MOMA-2 for the assessment of atherosclerotic lesions or macrophage infiltration. Mouse macrophages and human U937 cells were incubated with 100 μg/mL AGE-bovine serum albumin (AGE-BSA) or non-glycated BSA for 24 hours. Then the cells were treated with RAGE-aptamer or control-aptamer for 18 hours. Oxidized-LDL uptake was determined by Dil-oxidized-LDL fluorescent intensity using immunohistochemistry. Quantitative RT-PCR analysis was performed using TaqMan-based probes and SYBR-based primers.

Results:

Atherosclerotic lesions and infiltration of macrophages in the aortae isolated from ApoE-null mice infused subcutaneously with RAGE-aptamer were significantly suppressed compared with control-aptamer-treated mice. Oxidized-LDL uptake, and cyclin-dependent kinase 5 (Cdk5) and CD36 gene expression in macrophages extracted from ApoE-null mice infused with RAGE-aptamer were attenuated in comparison to those from mice infused with control-aptamer. Furthermore, RAGE-aptamer significantly inhibited oxidized-LDL uptake, and Cdk5 and CD36 gene expression in mouse macrophages and human U937 cells compared with those exposed with control-aptamer. Gene expression level of Cdk5 in mouse or human U937 cells was correlated with that of CD36.

Conclusion:

Our present findings suggest that RAGE-aptamer could play a protective role against atherosclerosis through the inhibition of macrophage foam cell formation via Cdk5-CD36 pathway in mice and human, which may be caused by attenuating the harmful effects of AGEs.
PS-BPB05-9: DUAL DELETION OF GUANYLYL CYCLASE-A AND P38 MAPK IN PODOCYTES WITH ALDOSTERONE ADMINISTRATION CAUSES GLOMERULAR INTRACAPILLARY THROMBI
Authors: Sugioka Sayaka , Yamada Hiroyuki , Ishii Akira , Kato Yukiko , Mori Keita P , Ohno Shoko , Handa Takaya , Ikushima Akie , Ishimura Takuya , Tokudome Takeshi , Matsusaka Taiji , Nebreda Angel R , Yanagita Motoko , Yokoi Hideki
Published: January 2023

Objective:

Previously, we demonstrated that uninephrectomized aldosterone-infused, high salt-fed podocyte-specific guanylyl cyclase-A (GC-A) conditional KO (pod-GC-A cKO) mice exhibit glomerular injury and that pharmacological inhibition of p38 MAPK ameliorates podocyte damage. However, the effects of genetic deletion of p38 MAPK in podocytes of pod-GC-A cKO mice have been unknown. By generating podocyte-specific p38 MAPK and GC-A double cKO mice, the study investigated the effects of p38 MAPK deletion in podocytes on glomerular injury with aldosterone and a high salt diet in mice.

Design and method:

We generated p38 MAPK(fl/fl);Nephrin-Cre (pod-p38 MA- PK cKO) mice and p38 MAPK(fl/fl);GC-A(fl/fl);Nephrin-Cre (pod-p38MAPK/GC-A double cKO) mice. For induction of glomerular injury, we treated them with aldosterone and high salt at 2 months of age for 3 weeks without nephrectomy (B-ALDO). In vitro, firstly, we examined human podocytes which p38 MAPK was deleted by Crispr/Cas9 system and GC-A was suppressed by siRNA. Secondly, we used a transwell co-culture system to investigate changes of wild-type human umbilical vein endothelial cells (HUVEC) mRNA in the lower layer culture with immortalized p38 MAPK-null podocytes transfected with si-GC-A in the upper layer.

Results:

Unexpectedly, aldosterone-infused, and high salt-fed (B-ALDO)-treated pod-p38 MAPK/GC-A double cKO mice resulted in significant elevation of serum Cr (0.29 ± 0.04 mg/dL), massive albuminuria (42,0541 ± 8,493 μg/mgCr) and severe foot process effacement in addition to intracapillary fibrin thrombi which indicated endothelial damage. In vitro, knockout of p38 MAPK and suppression of GC-A in human cultured podocytes induced podocyte damage. Deletion of p38 MAPK and inhibition of GC-A in podocytes in the upper layer upregulated TGFB1 and FN1 in the HUVEC in the lower layer, indicating that some humoral factors derived from podocytes could work as cell-to-cell mediators, especially for HUVEC.

Conclusions:

Genetic dual deletion of p38 MAPK and GC-A in podocytes accelerates both podocyte and endothelium injuries, suggesting that p38 MAPK in podocytes has an essential role in maintaining podocyte-endothelial interactions, especially under diseased conditions.
PS-BPB09-7: ENDOTHELIAL CNP-GC-B SYSTEM PLAYS A PROTECTIVE ROLE IN THE DEVELOPMENT OF PULMONARY HYPERTENSION
Authors: Yanagisawa Hiromu , Nakagawa Yasuaki , Nishikimi Toshio , Kuwahara Kouichirou
Published: January 2023

Background:

Pulmonary hypertension (PH) is a disease with a poor prognosis despite the development of various treatments, and a further therapeutic agent is required. C-type natriuretic peptide (CNP), one of the natriuretic peptide family, affects vasorelaxation and inhibition of vascular remodeling through its receptor guanylyl cyclase-B (GC-B). However, the beneficial effect of CNP on PH is still controversial. In this study, we examined the role of the CNP-GC-B pathway in the pathogenesis of PH.

Methods and Results:

To clarify the effect of the endogenous CNP-GC-B system on PH, we evaluated two types of PH models (monocrotaline pyrrole-induced and hypoxia-induced PH models) by using endothelial cell-specific CNP knockout mice (ecCNP-cKO), endothelial cell-specific GC-B knockout mice (ecGC-B-cKO), and smooth muscle cell-specific CG-B knockout mice (smGC-B-cKO). In both PH models, ecGC-B-cKO and ecCNP-cKO mice exacerbated PH compared to control cre-mice. Besides, mRNA levels of Edn1, IL6 and Ccl2 of the lung were significantly increased in the PH models of these mice. However, PH models of smGC-B-cKO mice showed no significant difference compared to those of control cre-mice. In cultured pulmonary arterial endothelial cells, synthesised CNP significantly attenuated PDGF- or hypoxia-induced increase in mRNA expression of Edn1, IL-6, and Ccl2. Moreover, continuous subcutaneous administration of synthesised CNP by osmotic mini-pump significantly ameliorated PH in PH model mice.

Conclusion:

CNP plays a protective role in the development of PH via endothelial GC-B through inhibiting endothelin-1 and inflammatory signals involvement. These data suggest CNP could be a novel therapeutic agent for PH.
PS-BPB10-2: MOLECULAR INSIGHT INTO SALT-SENSITIVITY; THE ROLE OF ATF3 AND THE GENERATION OF TUBULAR SPECIFIC KO MICE. (1)
Authors: Machida Kosuke , Mouri Satoshi , Maeda Kazuki , Matsumoto Kento , Kino Tabito , Saigo Sae , Uchida Kotaro , Chen Lin , Minegishi Shintaro , Arakawa Kentaro , Sugiyama Michio , Tamura Koichi , Ishigami Tomoaki
Published: January 2023

Objectives:

Current research including ours suggested pivotal roles of expressions of and regulations of tubular ion transporters for developments of sodium sensitivity and hypertension. Orlov et al. demonstrated using rat cardiomyocytes three different genes which are activated according to the elevation of intra-cellular Na ion concentration. (2015) To elucidate detailed biological roles of these genes in tubules, we performed current experiments.

Methods:

We tested expressions of three genes for cDNA from kidneys of Nedd4 2 C2 KO mice using quantitative RT PCR methods. Subsequently, we performed crossbreeding experiments between floxed target gene mice (generous gift from Prof. Kitamura, Tokyo Medical and Dental University) and Ksp-cre mice (Jackson Laboratory), which cre-recombinase expresses specifically along urinary tubules to generate mice with cre+, flox/flox genotype.

Results:

We found expressions of Atf3 are significantly changed due to oral sodium intake and diuretics treatment in Nedd4–2 C2 KO mice. We successfully generated mice with cre+, Atf3 flox/flox mice for current experiments. Under normal salt diet, we could not find any significant differences between cre + and minus mice in terms of systolic blood pressure, water intake, urine volume, urinary sodium excretions, urinary pH, and urinary osmotic pressures using metabolic cage experiments. We found, under high salt intake, gene expressions of both classic renin and tubular alternative renin are significantly suppressed for 30 to 70% in KO mice by quantitative RT PCR and immunohistochemistry imaging.

Conclusions:

Tubular epithelial Atf3 genes are involved in regulations of renin gene expressions in accordance with intracellular Na ion concentrations. Therefore, there are possibilities that tubular specific Atf3 KO mice shows blood pressure change under various salt intake and diuretics treatment.
PS-BPC01-6: DEEP LEARNING IS USEFUL FOR THE PATHOLOGICAL ANALYSES OF HUMAN KIDNEY BIOPSY IMAGES
Authors: Matsui Isao , Matsumoto Ayumi , Imai Atsuhiro , Okushima Hiroki , Katsuma Yusuke , Yasuda Seiichi , Inoue Kazunori , Isaka Yoshitaka
Published: January 2023

Objective:

The kidney plays a pivotal role in the maintenance of blood pressure. Non-neoplastic kidney biopsy images yield a great deal of diagnostic information, however, several studies have shown that there is room for improvement in pathological diagnostic reproducibility. Recently, deep learning has made major breakthroughs in various tasks. Therefore, we tried to analyze human kidney biopsy images using deep learning.

Design and Method:

We analyzed 5002 non-neoplastic kidney biopsy whole slide images (WSIs) obtained from 24 facilities in Japan using deep learning. Images of periodic acid-Schiff stained kidney sections were analyzed.

Results:

WSIs have billions of pixels, and deep neural networks (NNs) cannot accept such a huge image as an input. Therefore, we prepared 88 μm square 6,125,990 patch images (PIs) from the WSIs, and trained NNs with these PIs. We manually selected 259,682 typical PIs from the whole set of PIs, and annotated them into 56 classes. Using these annotated PIs, we trained EfficientNets B0-B7, whose network depth and width are carefully balanced for various input resolutions (224 to 600 pixels), and found that EfficientNetB4 (hereafter referred to CNN_Man) achieved the best F1 score. Using histological parameters obtained from renal biopsy reports made by nephrologists and pathologists at each facility, we confirmed the reliability of CNN_Man-based prediction. We also finely visualized histological features of WSIs based on CNN_Man prediction (Figure). In addition to these supervised histological analyses, we tried to extract disease features in a loosely supervised manner. In this loosely supervised learning, we tried to extract disease-related rather than histology-related glomerular features by training EfficientNetB4 using final diagnosis as true labels. It is noteworthy that the final-diagnosis-based training is not typical supervised learning because each disease class contains patch images with various histological features to varying degrees. We extracted glomerulus-related PIs by using CNN_Man, and then labeled these PIs into 20 final-diagnosis categories. EfficientNetB4 (hereafter CNN_Diag) was trained with the 20 class images in a 5-fold cross-validation manner. Using UMAP, we visualized the final layer parameters of CNN_Diag corresponding to each PI. This approach divided PIs from IgA nephropathy into many clusters, and each cluster reflected blood pressure, renal function, age, etc., even though they were not explicitly given as teacher labels.

Conclusions:

The analysis of kidney biopsy images using deep learning may be useful for the classification of renal diseases based on new perspectives.
PS-BPC02-2: CLINICAL IMPACTS OF ENDOTHELIUM-DEPENDENT FLOW-MEDIATED VASODILATION ASSESSMENT ON PRIMARY ALDOSTERONISM
Authors: Watanabe Daisuke , Morimoto Satoshi , Morishima Noriko , Ichihara Atsuhiro
Published: January 2023

Objective:

Primary aldosteronism (PA) is defined as autonomous aldosterone production from the adrenal glands and represents the most common and treatable cause of hypertension. Also, it is well known that the incidence of cardiovascular morbidity is higher among patients with PA than among those with essential hypertension (EH). Histologically, PA is divided into two major subtypes, aldosterone-producing adenoma (APA) and bilateral idiopathic hyperplasia (IHA). However, the nature of vascular function in PA patients remains to be determined. The aim of this study was to determine the vascular function and investigate the implications of vascular function assessments in the patients with PA.

Design and Method:

All patients were diagnosed with PA according to the guidelines of the Japan Endocrine Society. Flow-mediated dilation (FMD), as an index of endothelial function, and cardio-ankle vascular index (CAVI), as an index of arterial stiffness, were retrospectively compared between 42 patients with APA, 37 patients with IHA, and 42 patients with EH. These values were also compared with background factors, KCNJ5 mutation and clinical outcome in terms of blood pressure reduction after adrenalectomy in the APA group.

Results:

No differences were found among the three groups (APA, IHA and EH) with regard to age, sex, duration of hypertension, body mass index, blood pressure, renal function and hemoglobin A1c. FMD was significantly lower in the APA group (4.8 ± 2.1%) and IHA group (4.1 ± 1.9%) than in the EH group (5.7 ± 2.1%). CAVI did not differ significantly among APA, IHA and EH groups (7.9 ± 1.3, 7.8 ± 1.0, 7.8 ± 1.1, respectively). Although no significant correlations were seen between FMD and background factors (i.e. age, body mass index, renal function, glucose and lipid metabolic parameters, and hormonal data) in the IHA group, FMD correlated negatively with BMI and plasma aldosterone concentration in the APA group (rs = -0.313, rs = -0.342, respectively). No significant difference in FMD (4.8 ± 1.4%, 4.5 ± 2.1%, respectively) or CAVI (8.1 ± 1.8, 8.0 ± 1.1, respectively) was seen between the KCNJ5-mutant group and the wild-type group. A cut-off FMD of 4.3% was selected for complete clinical success after adrenalectomy, offering 78% sensitivity and 80% specificity.

Conclusions:

Patients with PA displayed impaired endothelial function. Complete clinical success after adrenalectomy was associated with preserved endothelial function. This study provides a better understanding of FMD assessment in patients with PA.
PS-BPC02-3: EVALUATION OF VASCULAR FUNCTION FOR PREDICTION OF RENAL PROGNOSIS IN JAPANESE PATIENTS WITH LIFESTYLE-RELATED DISEASES.
Authors: Masuda Shiho , Hara Tomoyo , Yamagami Hiroki , Mitsui Yukari , Kurahashi Kiyoe , Yoshida Sumiko , Otoda Toshiki , Yuasa Tomoyuki , Nakamura Shingen , Kuroda Akio , Endo Itsuro , Matsuhisa Munehide , Abe Masahiro , Aihara Ken ichi
Published: January 2023

Background:

Since chronic kidney disease (CKD) is associated with the development of serious cardiovascular diseases such as stroke, coronary artery disease and heart failure, prevention and early diagnosis of CKD are important clinical issues. Many risk factors including diabetes, hypertension, dyslipidemia, obesity, and cigarette smoking are known to be involved in the development of CKD; however, there is no available biomarker that can predict the progression of CKD at an early stage. Although it has been reported that glomerular endothelial injury causes development of CKD, it remains unclear whether evaluation of vascular endothelial function can predict renal prognosis. Therefore, in the present study, we examined the association between vascular endothelial function and longitudinal eGFR change in patients with lifestyle-related diseases.

Methods:

We retrospectively evaluated 341 Japanese patients (176 males and 165 females; mean age, 63.87 ± 12.02 years) with lifestyle-related diseases in whom baseline vascular function was evaluated by flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV) and in whom 24-month longitudinal eGFR values were recorded after vascular testing at Tokushima University Hospital and Anan Medical Center, Tokushima Japan. The association between values of FMD and eGFR slope and the association between values of baPWV and eGFR slope were statistically analyzed. Statistical significance was set at p < 0.05.

Results:

Single regression analysis showed that value of FMD was positively associated with eGFR slope in females (p < 0.001) and non-smoking males (p = 0.033) but not in smoking males (p = 0.133). Multiple regression analysis including confounding factors demonstrated that the value of FMD remained a contributor against annual eGFR decline in females (p = 0.002) and non-smoking males (p = 0.046) but not in smoking males (p = 0.266). On the other hand, the value of baPWV had no significant association with eGFR slope regardless of sex and smoking.

Conclusions:

In patients with lifestyle-related diseases, FMD value can be used for prediction of renal prognosis represented by the eGFR slope in females and non-smoking males. Thus, early comprehensive intervention for improving vascular endothelial function might lead to a better renal prognosis in female and non-smoking male patients with lifestyle-related diseases.
PS-BPC03-6: USING A SIMPLE FIXED-RATIO BASED ALGORITHM MINIMIZES VARIABILITY IN OSCILLOMETRIC BLOOD PRESSURE DERIVATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Ringrose Jennifer , Smith Kevan , Jalali Afrooz , Khinda Harsimran , Wirzba Isaac , Ameh Hannah Ehce , Bello Aminu , Braam Branko , Padwal Raj
Published: January 2023

Objective:

Oscillometric device accuracy may be decreased, and variability may be increased, in patients with chronic kidney disease. The objective of this study was to compare three oscillometric algorithms to identify which minimizes oscillometric blood pressure variability in chronic kidney disease.

Design & Methods:

Sixty patients with chronic kidney disease were studied. Thirty were on hemodialysis (HD group) and thirty had stage 3 chronic kidney disease (Stage 3 CKD). Baseline demographics and medical comorbidities were recorded. The mean of 3 readings from the Omron HEM 907XL device was used to provide a control (reference) blood pressure. Three oscillometric waveforms were also collected using a computer-based system, processed, and used to derive blood pressure by each of three algorithms: 1. simple fixed-ratio; 2. initial binning according to mean arterial pressure and then application of different fixed ratios within each bin (binning method); and 3. binning plus linear regression to incorporate the influence of additional oscillometric waveform characteristics (binning regression method). The mean of three blood pressure determinations from each algorithm was calculated and compared to the Omron mean, with variability assessed by calculating the standard deviation of the difference compared to the Omron.

Results:

Mean age in the overall group (± SD) was 65.6 ± 13.7 years (HD 63.4 ± 16.3 years; Stage 3 CKD 65.9 ± 10.7 years), percent female in the overall group was 42% (HD 37%; Stage 3 CKD 47%), and mean arm circumference overall was 31.5 ± 4.7 cm (HD 30.8 ± 4.4 cm; Stage 3 CKD 32.2 ± 5.0 cm. Hypertension was present in 82% of participants (HD 80%; Stage 3 CKD 83%). Mean Omron blood pressure was 136.9 ± 25.4/72.7 ± 15.8 mmHg. Compared to the Omron, the systolic/diastolic results for each algorithm were 134.4 ± 20.5/75.0 ± 12.9 for fixed ratio, 128.5 ± 19.8/71.4 ± 12.0 for binning, and 127.7 ± 18.7/70.2 ± 8.8 for binning regression (Table 1).

Conclusions:

An oscillometric algorithm based on simple fixed-ratio minimized variability in patients with chronic kidney disease. Manufacturers of devices designed for blood pressure measurement in this population should consider incorporating this approach into their algorithm-based blood pressure derivation.
PS-BPC07-4: RENOPROTECTIVE EFFECTS OF SGLT2 INHIBITORS AND RELATED FACTORS IN CHRONIC HEART FAILURE PATIENTS WITH DIABETES
Authors: Horio Takeshi , Yokouchi Go , Matsumoto Naoki , Fukuda Kohei , Yoshimura Ryutaro , Fujiwara Ryosuke , Matsuoka Yujiro , Sakamoto Yuya , Fujimoto Kohei , Kasayuki Noriaki
Published: January 2023

Objective:

Large-scale clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on not only cardiovascular and renal outcomes but also the preservation of renal function in patients with diabetes mellitus and/or chronic kidney disease. However, the effect of SGLT2 inhibitors on renal function in heart failure remains to be fully elucidated. The present study investigated whether SGLT2 inhibitors exert renoprotective effects in chronic heart failure patients with diabetes, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after SGLT2 inhibitor administration. In addition, if SGLT2 inhibitors had a favorable effect on renal function, we examined what cardiac/hemodynamic and noncardiac factors were involved in its effect.

Design and method: Methods:

From 83 outpatients with chronic heart failure and type-2 diabetes mellitus taking both SGLT2 inhibitors and loop diuretics, 50 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of SGLT2 inhibitors were selected. In this longitudinal observational study, eligible patients were retrospectively followed up before and after SGLT2 inhibitor administration. Clinical data such as body weight, blood pressure, heart rate, blood (hematological and biochemical) parameters, echocardiographic parameters, and medical treatment were collected at respective ends of the follow-up periods before and after SGLT2 inhibitor administration. All eGFR values were separately plotted before and after the initiation of treatment with SGLT2 inhibitors along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR.

Results:

The mean follow-up periods before and after SGLT2 inhibitor administration were 2.6 and 1.9 years, respectively. Changing rates of eGFR per year were significantly improved after treatment with SGLT2 inhibitors (mean ± SD, -5.78 ± 7.67 to -0.43 ± 10.81 mL/min/1.73m2/year, p = 0.006). The daily doses of loop diuretics were not altered after SGLT2 inhibitor administration. Body weight decreased and hematocrit and hemoglobin increased by SGLT2 inhibitor administration, but neither change was not associated with the change in eGFR slope before and after SGLT2 inhibitor administration. While, the decrease in inferior vena cava diameter was significantly correlated with the improvement of eGFR decline slope after SGLT2 inhibitor administration (r = -0.428, p = 0.004).

Conclusions:

This study demonstrated that long-term treatment with SGLT2 inhibitors ameliorated annual decline in eGFR in Japanese patients with chronic heart failure. The observed renoprotective effect may have been mediated by improved venous congestion.
PS-BPC08-6: CLINICAL AND BIOCHEMICAL OUTCOMES OF PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMA AFTER RADIOFREQUENCY ABLATION THERAPY AT KEIO UNIVERSITY HOSPITAL: 2022 REPORT
Authors: Kozuma Takahide , Kobayashi Sakiko , Nakamura Toshifumi , Kinouchi Kenichiro , Yokota Kenichi , Miyashita Kazutoshi , Kurihara Isao , Takase Kei , Nakatsuka Seishi , Itoh Hiroshi
Published: January 2023

Objectives:

Total adrenalectomy of an affected adrenal gland is the standard therapy of aldosterone-producing adenoma (APA), a curable subtype of primary aldosteronism. However, the APA is occasionally inoperable in cases with bilateral adenomas or high-risk patients under general anesthesia. Computed tomography (CT)-guided radiofrequency ablation (RFA) of the adrenal gland is a less invasive, cortical-sparing therapy, and may become a treatment of choice for such cases. A multicenter clinical trial of RFA was conducted in patients with APA in Japan from 2015 to 2016. To establish its long-term efficacy and safety, the study subjects enrolled in Keio University Hospital have been annually followed up. Following the progress report at ISH 2018, here we update clinical and biochemical outcomes of this cohort of patients 6 years after the RFA treatment.

Methods:

Follow-up medical interviews, blood pressure measurements, blood tests, and urinalysis were done annually. In addition, at least one CT scan was performed since 2018. Data on antihypertensive medication, blood pressure, hormone and electrolyte levels, urinary albumin, and tumor size were collected and analyzed.

Results:

10 cases of APA were treated with RFA between June 2015 and March 2016. As of April 2022, 6 cases were successfully followed up. Of these patients, the aldosterone-to-renin ratio (ARR) remained normalized in 5 cases (83%), albeit above the upper limit in 1 case (17%). In this particular patient, serum potassium level remained normalized and antihypertensive medication was not needed. Antihypertensive medication was needed in 1 case (17%), while urinary albumin levels were improved in all cases. Of note, follow-up CT scan showed that the tumor was undetectable in 1 case (17%), reduced in size in 3 cases (50%) and unchanged in 2 cases (33%). None of the cases have developed adrenal insufficiency since the RFA.

Conclusion:

The follow-up study on APA patients 6-year after the RFA revealed no cases of recurrence. RFA is likely to be effective and safe in patients with APA.
PS-BPC10-3: DETERMINATION OF AORTIC STIFFNESS USING TWO ESTABLISHED ALGORITHMS
Authors: Tairi Amira , Obeid Hasan , Fortier Catherine , Pare Mathilde , Cote Nadege , Philibert Emy , Garneau Charles Antoine , Goupil Remi , Agharazii Mohsen
Published: January 2023

Objectives:

Arterial stiffness is a risk factor for cardiovascular disease. Aortic stiffness is assessed by determination of pulse wave velocity using pulse transit time and the distance between carotid and femoral arteries. Transit time is obtained by using the foot-to-foot method to define the transit time through intersecting tangents algorithm or the point of maximal upstroke during systole (2nd derivative). Millasseau et al have proposed a formula for converting transit time between methods using SphygmoCor (intersecting tangents) and the Complior Analyse (2nd derivative). Based on a mathematical modeling of the proposed formula, there is discrepancy between values of pulse wave velocities, especially in subjects with higher aortic stiffness. The objective is to directly compare the two methods using the same pressure waveforms obtained by the newer generation of Complior Analyse and using Millasseau formula.

Design and Methods:

In a cross-sectional study of heterogeneous subjects, aortic stiffness was assessed by the Complior device which uses 2nd derivative. The pulse waveforms were extracted and used for the analysis by custom MATLAB algorithm for intersecting tangents, and the results were compared to the formula proposed by Millasseau.

Results:

The preliminary results of the first 24 patients (men: 71%; mean age: 61 ± 18 years) show that Millasseau formula underestimates the transit times values by about 19% in comparison with the transit times obtained by the intersecting tangents method using MATLAB software (50 ± 19 ms vs 62 ± 19 ms; P < 0.001). This results in an overestimation of the pulse wave velocities values by about 30% (13.8 ± 3.8 m/s vs 10.6 ± 2.7 m/s; P < 0.001).

Conclusions:

Our preliminary results allow us to conclude that the values of pulse wave velocities obtained with Millasseau formula overestimate values as compared to the values obtained by intersecting tangents method. Increasing the number of subjects will allow us to examine the possibility of a more reliable formula for converting transit times between methods.
PS-BPC10-5: ASSOCIATION BETWEEN KIDNEY FUNCTION AND CIRCULATING EPHA2 IN PATIENTS WITH HYPERTENSION
Authors: Murakoshi Maki , Iwasawa Takumi , Kato Kazunori , Gohda Tomohito , Suzuki Yusuke
Published: January 2023

Objective:

We have previously demonstrated that high circulating levels of progranulin (PGRN) were negatively associated with estimated glomerular filtration rate (eGFR). PGRN binds to Ephrin type-A receptor 2 (EphA2). Recently, it has been reported that circulating EphA2 levels serve as a biomarker of kidney function decline in patients with diabetic kidney disease. Therefore, we investigated its level correlates with traditional renal measures, eGFR and ratio of proteinuria to creatinine (UPCR), in patients with hypertension.

Design and method:

EphA2 ELISA for human serum was developed and validated. The serum levels of EphA2 were measured in 80 patients with hypertension. The subjects were stratified according to the eGFR: normal kidney function (eGFR > 60 mL/min/1.73m2, n = 16), and declined kidney function (CKD; eGFR < 60 mL/min/1.73m2, n = 64).

Results:

Validation of the in-house EphA2 ELISA showed good recovery and linearity and no cross-reactivity with other Eph receptors. The levels of EphA2 were significantly higher in CKD group compared to normal kidney function group, and correlated significantly with eGFR (r = -0.83) and UPCR (r = 0.61).

Conclusions:

The high circulating EphA2 level has potential application as a clinical biomarker for presence of CKD in patients with hypertension.
PS-BPC11-3: INVESTIGATION OF THE EFFECT OF VISCERAL FAT ON THE CHRONIC KIDNEY DISEASE DEVELOPMENT AND PROGRESSION IN MEDICAL CHECKUP PARTICIPANTS
Authors: Miyasato Yoshikazu , Oba Koji , Masuda Izuru , Mukoyama Masashi
Published: January 2023

Objective:

Many factors including obesity were reported as risk factors for development and progression of chronic kidney disease (CKD). However, there is a possibility that the effects of risk factors on the progression of renal dysfunction in CKD patients and the development of CKD are different. We aimed to evaluate the relationships of visceral fat area (VFA) and changes in kidney function in medical checkup participants stratified by the presence of CKD for investigation of the effect of visceral fat on CKD development and progression.

Design and method:

Study design: Retrospective cohort study. Setting: Routine medical checkups at two medical examination centers in Takeda Hospital Group. Participants: Subjects who underwent VFA measurements during medical checkups in 2012. The follow-up period was from April 2012 to March 2018. Exposures: VFA (≧ 100 cm2). Main outcomes: Changes in estimated glomerular filtration rate (eGFRcr). Statistical analysis: The relationships between VFA and eGFRcr were evaluated using a linear mixed effects model in the participants stratified by the presence of CKD. We defined CKD as eGFR < 60 mL/min/1.73 m2 in this study.

Results:

Analysis was performed on total 2,753 subjects (age [mean ± SD] 50.3 ± 10.0 years). The non-CKD group was composed of 2,516 subjects (age 49.5 ± 9.67 years, 1,277 men, 1,239 women), and the CKD group was composed of 237 subjects (age 59.5 ± 8.48 years, 142 men, 95 women). In the total subjects the VFA ? 100 cm2 group exhibited a larger annual difference in eGFRcr compared to the < 100 cm2 group (-0.24 mL/min/1.73 m2, p = 0.03). Although the difference of annual eGFRcr change in the non-CKD group was not statistically significant, VFA? 100 cm2 was associated with larger annual declines in eGFRcr in both CKD and non-CKD groups as compared to VFA < 100 cm2 (-0.64 mL/min/1.73 m2, p = 0.01, and -0.20 mL/min/1.73 m2, p = 0.10).

Conclusions:

In the CKD group VFA ≧ 100 cm2 was significantly associated with a greater annual decline in eGFRcr. This significant difference of eGFRcr decline in the CKD group suggests the effect of visceral fat as a modifiable risk factor for CKD progression.
PS-BPC12-4: HYPERTENSION IN CAMEROONIAN RURAL AND URBAN PYGMIES AND BANTUS OF THE SOUTHERN REGION
Authors: Hako Yves , Bika Claude , Okala Cecile , Dissongo Jean II , Degaute Jean Paul , Kabangu Jean Rene Mbuyamba , Van de Borne Philippe , Lemogoum Daniel
Published: January 2023

Objective:

To determine the prevalence of hypertension and associated risk factors among rural and urban pygmy and Bantu dwellers of southern Cameroon

Design and Methods:

In this cross-sectional cluster sampling survey, we examined 100 traditional pygmies (TP) living in equatorial forest in Kavabousse village under hunter-gatherer subsistence mode, 100 traditional Bantus (TB) living in Bidjouka village closed to Kavabousse (rural area); and 100 contemporary pygmies (CP) and 100 contemporary Bantus (CB) both living in the same urban environment in Kribi city. Trained observers recorded in each participant lifestyle and socio-demographic data, and clinical parameters. Brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in triplicate using an automatic sphygmomanometer (Omron 705 CP). Hypertension was defined as SBP/DBP > or = 140/90 mmHg.

Results:

As compared to Bantus, Pygmies were younger (38 ± 16 vs 45 ± 17 years, p = 0.0001), with lower body mass index (22.7 ± 3.3 vs 24.9 ± 4.6, p < 0.0001). Age-adjusted SBP and DBP were lower in Pygmies than in Bantus (p < 0.0001), however within group SBP and DBP were similar among rural and urban individuals. Age-adjusted prevalence of hypertension was lower in pygmies than Bantus globally (7.5% vs 21.5% p = 0.0001), and in rural and urban areas: 4% vs 19% and 11% vs 24 %, respectively, both p < 0.01). In pygmies taken separately, the age-adjusted prevalence of hypertension was lower in TP than in CP (4% vs 11%). In the whole study population, multivariate logistic regression analysis revealed that hypertension was independently associated with urban area (OR = 2.15, 95%CI: 1.14–4.05), Bantu status (OR = 2.17, 95%CI: 1.09–4.34), age > or = 50 years (OR = 2.15, 95%CI: 1.14–4.05), and abdominal obesity (OR = 0.20 95%CI: 0.09–0.46) (all p < 0.05). In pygmies taken separately, multivariate logistic regression analysis shown that age > or = 50 years (OR = 3.83, CI95%: 1.33–11.36) and urban area (OR = 3.33, CI95%: 1.04–11.11) (both p < 0.05) were independent determinants of hypertension.

Conclusion:

This study reveals that hunter-gatherer lifestyle is associated with lower prevalence of hypertension as illustrated in TP. Hypertension is more common in Bantus and CP, and is largely attributable to their westernized lifestyle and the growing urbanization of rural area.