bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-BPP06-7: ASSOCIATION BETWEEN SALT INTAKE AND BLOOD PRESSURE IN COMMUNITY-DWELLING OLDER PEOPLE: THE SONIC STUDY
Authors: Yoshida Hiroko , Kabayama Mai , Godai Kayo , Akasaka ken , Yamamoto Kouichi , Ikebe Kazunori , Yasumoto Saori , Gondo Yasuyuki , Rakugi Hiromi , Kamide Kei 
Published: January 2023

Objective:
It is well known that excessive salt intake is associated with hypertension (HT) and salt intake reduction lowers blood pressure. However, the knowledge of salt intake and blood pressure in the older people is not sufficient. This study aimed to clarify the relationship between salt intake and blood pressure among community-dwelling Japanese older people.

Design and method:
This study was cross-sectional design based on a prospective cohort study called the SONIC (Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians) study. We used data collected from 2010 to 2012. The dependent variable was the blood pressure at the venue and the independent variable was salt intake.
Salt intake was calculated using the brief-type self-administered diet history questionnaire (BDHQ). After adjustment for energy using the residual method, Salt intake was classified into quartiles. Blood pressure values for each quartile were compared by Jonckheere-Terpstra test.

Results:
The number of participants was 2,163 (female: 53.3%). Persons who may have over- or under-reporting nutrition and had no blood pressure data was excluded. Participants of 70 ± 1 years old were 947 (HT: 50.2%), 80 ± 1 years old were 951 (HT: 63.9%), 90 ± 1 years old were 265 (HT: 50.6%).
There was no clear difference of systolic blood pressure among the four quartiles of salt intake. Participants taking angiotensin II receptor blocker (ARB) were 448, and mean systolic blood pressure in the four quartiles of salt intake were Q1:142.1 ± 17.7mmHg, Q2: 145.2 ± 17.3, Q3: 146.1 ± 17.2, and Q4: 147.8 ± 18.8. There was a stepwise increase in systolic blood pressure with increasing salt intake quartile (p = 0.018 for trend).

Conclusions:
For the elderly taking ARBs, salt reduction was shown to improve blood pressure control, but for the other elderly, no effect of salt intake was observed. Further studies are needed to examine including other factors what affects blood pressure for older population.
PS-BPR01-1: SUCCESSFUL TREATMENT WITH ESAXERENONE IN A PREGNANT WOMAN WITH PRIMARY ALDOSTERONISM AND SUPERIMPOSED PREECLAMPSIA
Authors: Yamashita Kaoru , Morimoto Satoshi , Inoue Yuko , Hirata Kiyotaka , Kimura Shihori , Seki Yasufumi , Bokuda Kanako , Watanabe Daisuke , Ichihara Atsuhiro 
Published: January 2023

Background:
During pregnancy, there is no established treatment for idiopathic hyperaldosteronism (IHA), the most common form of primary aldosteronism (PA) due to bilateral adrenal hyperplasia. Here, we report the case of a pregnant patient with IHA who was successfully treated with esaxerenone, a non-steroidal mineralocorticoid receptor (MR) antagonist.

Case:
A 39-year-old woman was referred to our outpatient clinic for hypertension with high plasma aldosterone concentration (PAC). Her PAC was 204 pg/mL (radioimmunoassay) and plasma renin activity was 1.2 ng/mL/h at the time of referral. She was diagnosed with PA since the saline-loading test for PA was positive. She had no hypokalemia and computed tomography scans showed no adrenal tumors. Adrenal vein sampling indicated overproduction of aldosterone in both adrenal glands leading to the diagnosis of IHA. She was commenced on nifedipine controlled release (CR) 20 mg daily because she desired to be pregnant. After one year, she became pregnant. Her blood pressure was well controlled until 34 weeks of gestation when her home blood pressure became elevated up to 140/90 mmHg. Although the dose of nifedipine CR was increased to 80 mg daily, her blood pressure increased to 151/97 mmHg and urinary test showed proteinuria of 2 + in 35 weeks of gestation. She was diagnosed with superimposed preeclampsia (SPE) and additionally treated with esaxerenone. Her blood pressure decreased to 120–140/98–100 mmHg and the proteinuria improved to +/-. A successful cesarean section at 37 weeks resulted in the delivery of a healthy baby boy. Esaxerenone was discontinued 2 weeks after delivery, because she was eager to breast-feed the baby and no safety data of esaxerenone in breast-feeding woman was available. Her blood pressure has been well controlled by nifedipine CR 80 mg daily even after 100 days of postpartum.

Conclusions:
This is the first case of a pregnant woman who was successfully treated with esaxerenone despite being an elderly pregnant woman who had been diagnosed with IHA and developed SPE. Further studies are needed to investigate the efficacy and safety of non-steroidal selective MR antagonist in similar pregnant patients with IHA, to establish better treatment strategy for these patients.
PS-BPR01-6: A CASE SERIES OF UNILATERAL PRIMARY ALDOSTERONISM TREATED BY RADIOFREQUENCY ABLATION
Authors: Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Morimoto Ryo , Oguro Sota , Takase Kei , Tanaka Tetsuhiro , Satoh Fumitoshi 
Published: January 2023

Background:
In primary aldosteronism (PA), early and appropriate management based on its subtype is crucial to abolish an enhanced cardiovascular risk. Mineralocorticoid receptor antagonists (MRAs) are the mainstay of PA treatment, while a unilateral adrenalectomy (ADX) has been considered as the gold standard intervention for unilateral PA, mainly caused by an aldosterone-producing adenoma. The laparoscopic ADX is a less-invasive procedure than open surgery, whereas the procedure harbors a perioperative risk associated with general anesthesia. Herein, we report 3 PA cases where we employed radiofrequency ablation (RFA) as an alternate therapy for their aldosterone-producing tumors. In those cases, RFA successfully and safely led to remission of PA with more reduced physical burden, compared with the laparoscopic ADX.

Case presentation:
We performed RFA in 3 unilateral PA cases with aldosterone-producing tumors; Case 1, a 46-year-old man with a right adrenal tumor (14 mm); Case 2, a 65-year-old man with a right adrenal tumor (15 mm); Case 3, a 47-year-old man with a left adrenal tumor (19 mm). At baseline, their blood pressure levels were 124/87, 118/79 and 142/88 mmHg under 1, 2 and 2 antihypertensive agents, respectively. Plasma aldosterone concentrations and renin activity levels were as follows; 29.70, 25.7 and 48.6 ng/dL and 0.5, < 0.2 and < 0.2 ng/mL/hr, respectively. In all cases, we confirmed the presence and localization of PA with confirmatory tests and segmental adrenal venous sampling. Before the RFA procedure, we initiated and titrated MRAs to sufficiently block effects of hyperaldosteronism. Percutaneous RFA was guided by computed tomography under intravenous anesthesia without intubation. Complete tumor ablation was achieved within 1 hour, confirmed by enhanced adrenal imaging. No major complication was observed, and physical activity was almost recovered on the same day. Three months after RFA, all 3 patients showed normotension without any antihypertensives. For biochemical parameters, plasma aldosterone levels decreased to 2.47, < 0.40 and 1.41 ng/dL in Case 1, 2 and 3, respectively, followed by mild restoration of plasma renin activity (1.4, 0.5 and < 0.2 ng/mL/hr, respectively).

Conclusion:
This case series demonstrates that RFA is an alternate treatment for unilateral PA. Based on accurate localization of hyperaldosteronism, RFA could cause necrosis of only an adrenal-producing tumor and spare an ipsilateral adjacent adrenal gland, resulting in remission of PA with minimal physical burden.
PS-B03-2: SGC STIMULATOR, BAY41 8543, FOR THE TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION AND CARDIORENAL SYNDROME
Authors: Gawrys Olga , Skaroupkova Petra , Huskova Zuzana , Honetschlagerova Zuzana , Vanourkova Zdenka , Kikerlova Sona , Melenovsky Vojtech , Cervenka Ludek 
Published: January 2023

Objective:
Heart failure with reduced ejection fraction (HFrEF) imposes a significant health and socioeconomic burden. The life expectancy and prognosis are particularly dreadful for patients that develop simultaneous renal dysfunction, so called cardiorenal syndrome, hence new treatment strategies are still in a great demand. Recent therapies for HFrEF include targeting the nitric oxide (NO)/ soluble guanylyl cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathway by sGC stimulators. These compounds bind to the heme moiety of the sGC and stimulate the sGC in the absence of NO (NO independent action), but also they sensitize sGC to low levels of endogenous NO by stabilizing NO/sGC binding.

Design and method:
We explored the efficiency of sGC stimulator (BAY41 8543, an analogue of vericiguat) in the animal model of HFrEF with kidney dysfunction. We used ren2 transgenic hypertensive rats (TGR) with aortocaval fistula (ACF), in which HFrEF is due to volume overload. Firstly, we investigated the long term activity of BAY41 given alone (3 mg/kg/day in the food) or combined with an ACE inhibitor (ACEi, Trandolapril, 0.25 mg/kg/day in drinking water) on the survival rate of ACF induced HFrEF in TGR (30 weeks). In separate series of experiments the impact of BAY41 on blood pressure was measured by telemetry. Blood, urine and in the end tissue samples were collected to evaluate the levels of cGMP, albuminuria and the production of nitric oxide during the two week treatment.

Results:
sGC stimulator significantly improved the survival rate of ACF TGR in comparison to untreated animals with ACF. However, BAY41 administered together with ACEi decreased its beneficial activity. The overall survival in BAY41+ACEi treated group was 50%, while in the group which received only ACEi it was still 90% in the end of the observation. Noteworthy, a temporary blood pressure decrease (10 mmHg) was recorded during first few days after sGC stimulator administration, but early on SBP started to rise and by the end it was on the same level as in untreated ACF TGR (127 ± 3 vs 131 ± 6 mmHg, respectively; NS).

Conclusions:
It seems that the NO independent stimulation of sGC is a promising strategy to treat HFrEF with cardiorenal syndrome, however, more caution and additional studies are necessary to enlighten the puzzling decrease in survival rate in the group that received combined treatment with sGC stimulator and ACEi. Perhaps selected dose regimen was not optimal for the combined treatment (e.g. due to hypotension).
PS-B03-12: DIETARY CAPSANTHIN INHIBITS ATHEROSCLEROTIC INFLAMMATION IN APOLIPOPROTEIN E-DEFICIENT MICE
Authors: Joo Hee Kyoung , Kim Sungmin , Lee Yu Ran , Lee Eun-Ok , Jin Hao , Choi Yeon-Hee , Choi Eun Ju , Jeon Byeong Hwa 
Published: January 2023

Objective:
Among carotenoids, capsanthin is a lipophilic red pigment responsible for the red pigmentation of paprika fruits (Capsicum annuum L.) However, its role in atherosclerosis is yet to be fully elucidated. In this study, we investigated the role of dietary capsanthin on vascular inflammation in atherosclerotic mice.

Design and method:
We evaluated the anti-atherosclerotic effects of daily oral administration of capsanthin (0.5 mg/kg of body weight/day) in apolipoprotein E-deficient mice fed a Western-type diet (WD).

Results:
Dietary capsanthin significantly inhibited the WD-induced elevation in the plasma levels of total cholesterol, low-density lipoprotein, and triglyceride in mice. The WD group showed a remarkable increase in oil red O-positive lesions indicating aortic plaque formation in whole and cross-sectional aorta. Interestingly, capsanthin reduced aortic plaque formation and VCAM-1 expression, which is vascular inflammation, in atherosclerotic mice. Furthermore, capsanthin significantly reduced the levels of proinflammatory cytokines and the neutrophil-lymphocyte ratio, a systemic inflammatory marker, in atherosclerotic mice.

Conclusions:
Taken together, our data demonstrate that dietary capsanthin plays a protective role against atherosclerosis in hyperlipidemic mice.
PS-B04-9: ELUCIDATING EFFECT OF INHIBITING ALDOSTERONE SYNTHESIS ON HUMAN ADRENOCORTICAL CELLS
Authors: Long Kha Chin , Sukor Norlela , Tan Geok Chin , Murad Nor Azian Abdul , Brown Morris Jonathan , Azizan Elena Aisha 
Published: January 2023

Introduction:
Modern human diet is high in salt. High salt stimulates decrease of aldosterone by down-regulation of aldosterone synthase (encoded by the gene CYP11B2) in the zona glomerulosa (ZG). Aldosterone regulates blood pressure and volume by regulating salt secretion. Interestingly, adult human adrenal ZG is sparse and confined to discrete islets of cells unlike rodent adrenal where the zone encompasses the whole periphery of the adrenal. We therefore hypothesize that ZG cell function change from synthesis to apoptosis/migration mode when aldosterone is not required due to the high salt diet.

Objective:
Herein, we intend to characterise human adrenocortical cells silenced for CYP11B2.

Methods:
We transfected HAC15, a subclone of the H295R human adrenocortical cancer cell line with scrambled siRNA (siScrambled) or siRNA targeting CYP11B2 (siCYP11B2) using the Neon Transfection System. 48-h post-transfection, cell apoptosis rate was assessed using the Pacific Blue Annexin V/SYTOX AADvanced apoptosis kit. The supernatants and cells were harvested for aldosterone and cortisol measurements, and RNA isolation. A representative sample of siCYP11B2 and siScrambled from each independent experiment was selected for RNA-Sequencing (RNAseq). The EZMTT Proliferation Assay was performed on equally seeded HAC15 cells, 72-h post-transfection with either siScrambled or siCYP11B2 using the Lipofectamin 3000 Transfection reagent. Experiments were repeated 3 times independently in triplicates.

Results:
siCYP11B2 transfection limited the production of aldosterone by 69.8% (p = 0.001) and down-regulated the expression of CYP11B2 by 83.0% (p = 0.001). We confirmed that the silencing was specific to CYP11B2 despite the gene being highly homologous to CYP11B1 as there were no significant change on cortisol production and CYP11B1 mRNA expression. RNAseq analysis found 3 genes, CYP11B2, HNRNPA1, and UHMK1, consistently down-regulated in siCYP11B2 by 32%, 65% and 67% respectively. The most enriched pathways among the differentially expressed genes (DEG) were mitophagy and autophagy. No difference in cell apoptosis was seen in siCYP11B2 cells. Instead, an increase in cell proliferation was detected with the EZMTT assay.

Conclusion:
Our findings suggest that silencing of CYP11B2 does not affect apoptosis but does affect cell proliferation. Interestingly, the mitophagy and autophagy pathways were enriched in the DEGs of siCYP11B2 cells.
PS-B09-10: CANAGLIFLOZIN, A SODUIM-GLUCOSE TRANSPORTER 2 INHIBITOR IMPROVES GLUCOCORTICOID-INDUCED CARDIAC AND RENAL LIPID MISHANDLING BY SUPPRESSING LACTATE PRODUCTION IN FEMALE RATS
Authors: Olatunji Lawrence Aderemi 
Published: January 2023

Evidence exist that lactate production has pathophysiological implications in the development of hyperinsulinemia-linked cardiac and renal dysfunctions. The cardio-renal protective effects of sodium-glucose co-transporter-2 inhibitor (SGLT2i) has not been associated with lactate production. The study therefore sought to test the hypothesis that SGLT2i would ameliorate insulin resistance and cardiorenal lipid mishandling by suppressing lactate production. Wistar female rats weighing between 140 and 160 g were randomly allotted into control, DEX and DEX+CANA groups (6 rats per group). The groups received (p.o.) vehicle (distilled water), dexamethasone (0.2 mg/kg) and and a combination of Dex with a SGLT2i (Canagliflozin; 10.0 mg/kg), respectively for a period of 6 days.
Data showed that DEX exposure led to hyperinsulinemia, insulin resistance, elevated atherogenic plasma lipid index, accumulation of cardiac and renal triglyceride, free fatty acid, and increased lipid peroxidation in the hearts and kidneys as well as enhanced lactate production. However, the induced alterations by DEX were ameliorated by SGLT2i, CANA.
Collectively, the present results demonstrate that glucocorticoid-linked hyperinsulinemia-mediated lipid mishandling in the heart and kidney is ameliorated by CANA, a SGLT2i. The implication of the findings of the study is that SGLT2i could reduce lipid accumulation in the hearts and kidneys, at least, by suppression of the lactate production
PS-C17-6: MATERNAL ENDOTHELIAL MITOCHONDRIAL DYSFUNCTION IN GESTATIONAL DIABETES MELLITUS
Authors: Reyes Agafe , Kereliuk Stephanie , Xiao Fengxia , Dolinsky Vernon , Burger Dylan 
Published: January 2023

Objective:
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, and short and long-term maternal and neonatal cardiovascular risks. Our laboratory has shown that elevated levels of endothelial extracellular vesicles (EVs) in pregnant women is predictive of adverse pregnancy outcomes in type 1 diabetes. However, this matter has not been explored in GDM. We therefore investigated the impact of GDM on maternal vascular health, focusing on the mitochondria.

Design and method:
We determined the mitochondrial protein expression altered by GDM in rat kidneys by Western blot analysis. We examined the levels of circulating endothelial EVs and EV mitochondrial DNA (mtDNA) from rat plasma samples via flow cytometry and quantitative real-time PCR, respectively. We assessed the effects of high glucose exposure for 48 hours on endothelial mitochondrial function in human umbilical vein endothelial cells (HUVECs).

Results:
In a rat model of diet-induced GDM (Pereira, 2015 J Physiol), we observed significant decreases in expression of oxidative phosphorylation Complexes I (p < 0.05) and II (p < 0.01) in kidneys. We also observed a three-fold increase in late gestational levels of circulating endothelial EVs in GDM rats (p < 0.01) as well as increases in levels of EV-associated mtDNA, COX2 (p < 0.05) and ND2 (p < 0.01), suggesting mitochondrial dysfunction. In cultured HUVECs exposed to high glucose for 48 hours, we observed a significant decrease in Complex II expression (p < 0.01) and five-fold increases in EV mtDNA levels. This effect persisted even after removing high glucose exposure for 24 hours.

Conclusion:
These data show maternal endothelial dysfunction in GDM, accompanied by mitochondrial dysfunction and increased endothelial EV release. These findings suggest that endothelial mitochondrial health may represent a novel approach to reduce risks associated with GDM.
PS-C18-4: HIGH BODY MASS INDEX IS A RISK FACTOR FOR TRANSITION TO HEMODIALYSIS OR HYBRID THERAPY AND PERITONEAL DIALYSIS-RELATED INFECTION
Authors: Hama Eriko Yoshida , Uchiyama Kiyotaka , Nagasaka Tomoki , Kusahana Ei , Nakayama Takashin , Yasuda Itaru , Morimoto Kohkichi , Washida Naoki , Hayashi Kaori , Itoh Hiroshi 
Published: January 2023

Objective:
Obesity may negatively impact clinical outcomes of peritoneal dialysis (PD) patients. However, obesity is defined differently in Japan, and its impact on PD-related outcomes remains unclear. In current study, we aimed to examine the association of high body mass index (BMI) with the complete hemodialysis (HD) transfer, transition to HD and PD/HD hybrid therapy, peritonitis, catheter exit-site and tunnel infection (ESI/TI), and heart failure-related hospitalization.

Design and method:
This retrospective cohort study included 120 patients who underwent PD catheter insertion between January 2008 and June 2018. BMI ≧ 25 kg/m2, which was calculated from the height (m) and body weight (kg) at the time of PD catheter insertion, was defined as high BMI. Patients who develop solute retention or fluid overload with PD alone could choose to transfer first to PD/HD hybrid therapy, wherein patients usually undergo PD 5–6 days a week along with once-weekly HD, instead of directly transferring to HD alone. Association between high BMI and outcomes were analyzed by the log-rank test and the Cox proportional hazards models.

Results:
The follow-up duration was 46.2 (23.3–75.3) months. Time until transfer to HD and hybrid therapy was significantly shorter in the high BMI group than in the low one, whereas time until transfer to HD was not significantly different between both groups (P < 0.001 and 0.18, respectively). Peritonitis-free and ESI/TI-free survival were significantly shorter in the high BMI group than in the low one (P = 0.006 and 0.03, respectively). After adjusting for age, sex, diabetes mellitus, estimated glomerular filtration rate, BMI ≧ 25 kg/m2 remained as a significant risk factor for transferring to HD and PD/HD hybrid therapy, peritonitis, and ESI/TI (hazard ratio [HR] 2.60, P < 0.001; HR 2.08, P = 0.01; HR 2.64, P = 0.02, respectively).

Conclusions:
High BMI, defined as BMI ≧ 25 kg/m2, is a risk factor for transition to HD and PD/HD hybrid therapy, peritonitis, and ESI/TI. However, high BMI is not associated with early complete HD transfer in Japan, where PD/HD hybrid therapy is commonly used.
PS-C18-5: SEASONAL VARIATION IN PREDIALYSIS SYSTOLIC BLOOD PRESSURE AND CARDIOVASCULAR EVENTS IN JAPANESE MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Uchiyama Kiyotaka , Washida Naoki , Shibagaki Keigo , Yanai Akane , Nakayama Takashin , Takahashi Rina , Morimoto Kohkichi , Itoh Hiroshi 
Published: January 2023

Objective:
Predialysis systolic blood pressure (SBP) in hemodialysis (HD) patients follows a seasonal pattern, peaking during the winter and declining in summer due to changes in ambient temperatures. However, the relationship between seasonal variation in predialysis SBP and clinical outcomes has rarely been studied. We evaluate the association between the seasonal variation in predialysis SBP and clinical outcomes, such as major adverse cardiovascular events (MACEs), in Japanese HD patients.

Design and method:
In this retrospective cohort study, the standard deviation (SD) of each patient's monthly mean predialysis SBP was determined using the data from 47,219 HD sessions in 307 patients over a year (April 2019 to March 2020) at three dialysis clinics, which was defined as the seasonal variation in predialysis SBP. From April 2020 to March 2022, the relationship between seasonal variation in predialysis SBP and clinical outcomes, including MACEs, was investigated. Cardiovascular death, nonfatal myocardial infarction or unstable angina, stroke, heart failure, and other severe cardiovascular events requiring hospitalization were considered examples of MACEs.

Results:
The study included 105 women (34%), with an average age and a median HD vintage of 69.0 ± 12.4 years and 4.1 (2.0–7.7) years, respectively. The monthly mean SBP before dialysis was 8.9 ± 3.6 mmHg. There were 77 MACEs (25%) and 184 all-cause hospitalizations (60%) in this study. A Cox regression analysis adjusted for age, sex, HD duration, Charlson comorbidity index, mean annual predialysis SBP, intradialytic SBP decline, and ultrafiltration rate, revealed that a higher SD of the monthly mean predialysis SBP was significantly associated with an increased risk of MACEs (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.03–1.16). Furthermore, a higher monthly mean predialysis SBP SD was linked to a higher risk of all-cause hospitalization (HR, 1.05; 95% CI, 1.01–1.10). A greater seasonal variation in predialysis SBP was also significantly associated with increased risk of MACEs (HR, 1.08; 95% CI, 1.02–1.16) in the Fine-Gray subdistribution hazards model, considering death and semi-permanent hospitalization due to a decline in Activities of Daily Living as competing risks.

Conclusions:
A higher seasonal variation in predialysis SBP was linked to poorer clinical outcomes, including an increased risk of MACEs and all-cause hospitalization. More research is needed to confirm whether reducing seasonal variations in predialysis SBP improves this prognosis.