bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-BPB03-5: DEVELOPMENT OF A THERAPEUTIC VACCINE FOR DYSLIPIDEMIA AND RELATED DISEASES TARGETING ANGIOPOIETIN-LIKE PROTEIN 3 (ANGPTL3).
Authors: Fukami Hirotaka , Morinaga Jun , Nakagami Hironori , Kuwabara Takashige , Morishita Ryuichi , Oike Yuichi , Mukoyama Masashi
Published: January 2023

Background:

Dyslipidemia is a major factor in the development and progression of atherosclerotic diseases. Among dyslipidemias, familial hypercholesterolemia (FH) is a genetic disorder affecting approximately 34 million people worldwide, with 300,000 patients in Japan. Since homozygous FH in particular is resistant to existing therapies, there is an urgent need to develop new therapies to reduce the risk of cardiovascular disease (CVD) in patients with FH.

Design and Method:

We focused on angiopoietin-like protein 3 (ANGPTL3) as a novel therapeutic target for dyslipidemia. ANGPTL3 is known to inhibit lipoprotein lipase as well as angiogenesis. Mutations of this gene in humans were reported to have no apparent pathogenic effects and have been reported to reduce triglyceride (TG) and LDL cholesterol (LDL-C) levels in the blood and the risk of developing CVD. We have developed a peptide vaccine that induces anti-ANGPTL3 antibodies and produces a potent therapeutic effect on dyslipidemia. We vaccinated ob/ob mice, an obese mouse model of type 2 diabetes, with a total of three doses of vaccine every two weeks and analyzed the results.

Results:

The vaccine group (n = 12) showed significant reductions in blood TG concentration by 52%, LDL-C concentration by 41%, and small dense LDL-C concentration by 49% compared to the control group (n = 10). In addition, histologically fatty liver was improved, and analysis of TG accumulation in hepatocytes showed a 47% reduction in the vaccine group. Furthermore, vaccination reduced dyslipidemia and atherosclerosis in ApoE function-deficient mice, a model of severe familial hypercholesterolemia. Notability, the vaccine did not induce cytotoxic immunity against the mouse liver and ANGPTL3-producing organs.

Conclusions:

Based on these results, this vaccine is expected to be one of the effective treatments for atherosclerotic diseases.
PS-BPB03-6: COMPOUND A, A GINGER EXTRACT, SIGNIFICANTLY PREVENTS PRESSURE OVERLOAD-INDUCED SYSTOLIC DYSFUNCTION IN MICE
Authors: Hamabe-Horiike Toshihide , Kawase Yuto , Shimizu Kana , Funamoto Masafumi , Sunagawa Yoichi , Katanasaka Yasufumi , Shimizu Satoshi , Komiyama Miki , Hasegawa Koji , Morimoto Tatsuya
Published: January 2023

Introduction:

Cardiac remodeling induced by hypertrophic stresses such as hypertension or myocardial infarction is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Since cardiac remodeling eventually leads to systolic dysfunction or decompensated heart failure (HF), there is urgent necessary for compounds that can effectively suppress both cardiomyocyte hypertrophy and cardiac fibrosis. p300, a transcription coactivator with histone acetyltransferase (HAT) activity, plays an important role in the development of HF and maybe a target for HF therapy. In this study, we used a natural compound library to screen for compounds that suppress cardiomyocyte hypertrophy, cardiac fibrosis, and p300-HAT activity with cultured cardiomyocyte, cardiac fibroblasts, and in vitro, and identified compound A, a ginger extract, as a candidate for HF therapy. The purpose of this study is to investigate the effect of compound A on cultured cardiomyocyte hypertrophy and cardiac fibrosis and on the development of HF in vivo.

Methods & Results:

An in vitro p300-HAT assay was performed using compound A. The results revealed that compound A significantly suppressed the acetylation of histone H3K9. Primary cultured cardiomyocytes prepared from neonatal rats were treated with 1 μM of compound A and then stimulated with phenylephrine (PE) for 48 hrs. The results of immunofluorestaining showed that the compound A significantly suppressed PE-induced increase in the surface area of these cells. Quantitative PCR and western blotting analysis demonstrated that compound A significantly suppressed PE-induced increases in the mRNA levels of hypertrophic response genes such as ANF and BNP and histone H3K9 acetylation. Next, primary cultured cardiac fibroblasts were treated with 1 μM of compound A and then stimulated with transforming growth factor-beta (TGF-β;). The results of measurement of L-proline incorporation showed that the compound A significantly suppressed TGF-β;-induced incorporation. Quantitative PCR and western blotting demonstrated that compound A significantly suppressed TGF-β;-induced mRNA and protein levels of α-smooth muscle actin (α-SMA), and histone H3K9 acetylation. Finally, C57BL/6J mice were subjected to transverse aortic constriction (TAC) surgery and then treated with a daily oral administration of 1 mg/kg of compound A for 8 weeks. Echocardiographic analysis showed that compound A prevented TAC-induced increases in posterior wall thickness and decrease in systolic function. Compound A also suppressed TAC-induced increase in HW/BW ratio and histone H3K9 acetylation.

Conclusion:

Compound A effectively suppressed pressure overload-induced development of HF by inhibiting p300-HAT activity. This non-toxic dietary compound may be effective for HF therapy in humans.
PS-BPB04-5: SELECTIVE ACTIVATION OF GLUTAMATERGIC NEURONS WITHIN THE SFO EVOKES A PRESSOR RESPONSE THAT IS DEPENDENT ON THE PVN
Authors: Acquoy Monique L Van , Nedelkoska Teodora , Burke Peter G R , Hildreth Cara M
Published: January 2023

Objective:

An overactive glutamatergic projection from the subfornical organ (SFO) to the paraventricular nucleus (PVN) is associated with the development of hypertension. Despite this, the functional relationship of this pathway under normotensive conditions remains poorly defined within the literature. Without this knowledge, it remains unknown if a dysfunction of this pathway is the underlying cause of hypertension or rather simply a consequence of the underlying hypertensive disease pathology. As such, the aim of this study is to identify the short-term function of the SFO and PVN pathway under normotensive conditions.

Design and Methods:

An optogenetic viral vector (pAAV-CaMKIIa-hChR2 (H134R)-EYFP) was microinjected into the SFO of Lewis rats (n = 5). Three weeks later, rats were anaesthetised and instrumented to record blood pressure and sympathetic nerve activity, administer intravenous drugs and to photo-stimulate glutamatergic SFO neurons.

Results:

Photostimulation of glutamatergic SFO neurons produced a pressor response that was abolished by inhibition of neuronal transmission within the PVN (9 ± 1mmHg vs 3 ± 1mmHg peak change from baseline, baseline vs PVN inhibition, n = 2 rats, 3 replicates per rat). In a separate cohort (n = 3 rats, 5 replicates per rat), we determined if the pressor response elicited was dependant on the sympathetic nervous system and/or the release of the vasoactive hormone vasopressin. Blockade of sympathetic vasomotor outflow attenuated the pressor response by 76%, whereas combined inhibition of sympathetic outflow and vasopressin 1a receptors attenuated the pressor response by 88%. Finally, photostimulation of glutamatergic SFO neurons led to a peak increase in sympathetic nerve activity (n = 2) that was abolished by phenylephrine administration, suggesting that the neuronal circuitry underpinning this response is barosensitive.

Conclusions:

This study demonstrates that the pressor response elicited by glutamatergic SFO neurons is dependent on the PVN and is largely mediated by the sympathetic nervous system via barosensitive neuronal circuitry. Chronic activation of this pathway will be undertaken to determine if an overactivation of this neuronal pathway induces hypertension in normotensive animals.
PS-BPB04-6: PROOF OF BIOLOGICAL ACTIVITY AND EXPLORATION OF EARLY SIGNALING EVENTS OF ANGIOTENSIN-(1–5)
Authors: Silva Igor Maciel Souza , Peluso Antonio Augusto , Jakobsen Lene Andrup , Jensen Pia , Ribeiro Lucas Rodrigues Aguiar , Mortensen Christina , Sumners Colin , Braga Thiago Verano , Larsen Martin Roessel , Steckelings Ulrike Muscha
Published: January 2023

Introduction:

Recombinant human ACE2 increases the circulating levels of angiotensin-(1–5) [Ang-(1–5)], a peptide thus far regarded as biologically inactive. Since ACE2 is a central component of the protective RAS, we hypothesized that Ang-(1–5) is a new biologically active peptide within this hormonal system.

Objective:

To investigate biological activity and signaling mechanisms of Ang-(1–5).

Methods:

In order to show a biological effect and to test whether Ang-(1–5) signals through the AT2-receptor (AT2R), nitric oxide (NO) release was measured by DAF-FM fluorescence in AT2R transfected (AT2R-CHO) or non-transfected (NT-CHO) CHO cells, treated with Ang-(1–5) or C21 (AT2R agonist, positive control) (0.1 nM to 10 μM) for 15 minutes. Vehicle (cell media) treated cells served as negative control. To investigate Ang-(1–5) signaling patterns, human aortic endothelial cells (HAEC) were treated with vehicle or Ang-(1–5) (1 μM) for 1, 3, 5 or 20 minutes. Proteins were harvested, digested and labeled with TMTpro-16plex. Phosphopeptide enrichment was carried out by TiO2. Samples were subjected to LC-MS/MS analysis and the resulting mass spectra were searched against the human SwissProt database.

Results:

Ang-(1–5) induced a concentration-dependent increase in NO production in AT2-CHO cells (Emax: 65.60 ± 14.02%), thus proving its biological activity. Ang-(1–5) had 69% higher efficacy than the established AT2R agonist C21 (Emax: 38.76 ± 10.24%). Ang-(1–5) seems to signal through the AT2R, because effects on NO release were absent in NT-CHO cells. Treatment of HAEC with Ang-(1–5) significantly modified the phosphorylation status of 831 proteins at 1799 residues. The majority of residues (1079) were dephosphorylated while 729 residues were phosphorylated. Changes in protein phosphorylation in response to Ang-(1–5) occurred at all investigated time points, most of them after 20 minutes. Functional bioinformatic analysis revealed a cluster of proteins involved in cell cycle and cell division regulation.

Conclusion:

This study provides evidence that Ang-(1–5) is an endogenous AT2R agonist with high efficacy towards the AT2R. The early signaling phosphorylation pattern resembles those of other protective RAS agonists, such as C21 and Ang-(1–7).
PS-BPB04-9: DEVELOPMENT AND VALIDATION OF NEW METHOD TO MEASURE PLASMA ALDOSTERONE AND RENIN ACTIVITY USING LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETER (LC-MS/MS)
Authors: Hee Daryl Kim Hor , Tan Yi Ting , Aw Tar Choon , Puar Troy
Published: January 2023

Objective:

Measurement of aldosterone, renin, and aldosterone-renin ratio (ARR), are used to diagnose primary aldosteronism (PA). Immunoassays used to measure plasma aldosterone yield higher results compared to tandem mass spectrometry (LC-MS/MS). This can lead to false positive diagnosis of PA, and potential for unnecessary adrenal vein sampling. We report our development and validation of a novel test using LC-MS/MS, with reduced run time, for measurement of plasma aldosterone concentration (PAC) and plasma renin activity (PRA).

Design and method:

The detection and quantification of plasma aldosterone and angiotensin 1 (product for the calculation of renin activity) in the mass spectrometer was based on the multiple reaction monitoring of precursor to fragment ions under negative and positive ionization modes, respectively. Validation of the tests were based on the CLSI (Clinical & Laboratory Standards Institute) guidelines. Concurrent measurement for 190 samples were done on our instrument, and on a commercial lab using LC-MS/MS (Mayo Laboratories, USA) for comparison.

Results:

Our measurements of PAC and PRA was sensitive with a limit of quantification at 3 ng/dL and 0.25 ng/ml/h, respectively, and analytical run times were 6.5 min and 3.5 min, respectively. Both aldosterone and angiotensin 1 calibration curves had excellent linearity in the ranges of 3 - 300 ng/dL and 0.25 - 25 ng/ml/h, respectively, with coefficient of correlation, r2 > 0.994. The intra and inter day accuracy of aldosterone and angiotensin 1 were in the range of 95–110% with CV of < 13%. Reference ranges were established for our local population. Compared with the other LC-MS/MS laboratory, there was good correlation for PAC, r2 = 0.90, 95%CI: 0.86 - 0.92, and PRA, r2 = 0.81, 95% CI: 0.75 - 0.86, using 190 samples. In addition, amongst those with low aldosterone < 6ng/dL, there was good agreement between both labs, with 95 of 122 (77.9%) samples having low aldosterone using both methods, which has been shown to be an ideal threshold to exclude the diagnosis of PA.

Conclusions:

Our laboratory has developed and validated a sensitive and accurate LC-MS/MS test for PAC and PRA with shortened run time, for the diagnosis PA.
PS-BPB05-2: ENDOTHELIN A RECEPTOR BLOCKADE INCREASES RENOPROTECTION IN EXPERIMENTAL MODEL OF CONGESTIVE HEART FAILURE COMBINED WITH CHRONIC KIDNEY DISEASE
Authors: Vaneckova Ivana , Kala Petr , Vanourkova Zdenka , Skaroupkova Petra , Cervenka Ludek
Published: January 2023

Objective:

Congestive heart failure (CHF) represents an extreme burden to the public healthcare worldwide. The incidence and prevalence of chronic kidney disease (CKD) is also increasing and CKD is known as one of the strongest risk factors for the development of CHF. CHF coexists with CKD in approximately half of CHF patients and results in a poor survival rate. The aim of this study was therefore to examine if the addition of endothelin type A (ETA) receptor antagonist atrasentan (5 mg/kg/day) to the angiotensin-converting enzyme inhibitor (ACEi trandolapril; 2 mg/L) will bring additional beneficial effects.

Design and Methods:

CKD was induced by 5/6 renal mass reduction (5/6 NX) at the age of 8 weeks and CHF was elicited by volume overload achieved by the creation of aortocaval fistula (ACF) four weeks later in normotensive Hannover Sprague Dawley rats. The follow-up was 24 weeks after the first intervention (5/6 NX). The treatment regimens were initiated 6 weeks after 5/6 NX and 2 weeks after ACF.

Results:

The final survival in untreated group was 15%. The treatment with ETA receptor antagonist alone or ACEi alone and the combined treatment improved the survival rate to 64%, 71% and 75%, respectively, with no significant difference between the combination and either single treatment regimen. At the end of the study, atrasentan or trandolapril given alone partially reduced albuminuria, but had no effect on albumin/creatinine ratio. In contrast, both parameters were substantially improved by the combined treatment which caused ∼45 % reduction in albuminuria. Moreover, it also reduced markers of renal damage.

Conclusions:

Our results demonstrated that the treatment with ETA receptor antagonist attenuated the mortality related to CKD or CHF and that the addition of ETA receptor antagonist to the standard blockade of renin angiotensin system by ACEi exhibited additional renoprotective actions.
PS-BPB06-1: GLOMERULAR HEMODYNAMIC CHANGES WITH SGLT2 INHIBITION IN TYPE 2 DIABETIC RATS USING IN VIVO IMAGING
Authors: Tatsugawa Rie , Wada Yoshihisa , Kidokoro Kengo , Kashihara Naoki
Published: January 2023

Background and aim:

Clinical trials have shown that sodium-glucose co-transporter 2 inhibitor (SGLT2i) not only reduce the risk of heart failure and cardiovascular events in people with type 2 diabetes, but also inhibit DKD progression. Improvement of glomerular hyperfiltration via tubuloglomerular feedback (TGF) is considered to be one of the possible pathways for renal protection with SGLT2i in DKD. However, the mechanisms responsible for kidney protection, especially in the setting of T2D, remain incompletely understood. In previous work, we established a method for measuring single nephron GFR (SNGFR) in mice using in vivo imaging and found that the adenosine/adenosine A1 receptor (A1aR) pathway is central for tubuloglomerular feedback (TGF) signaling and the pathogenesis of glomerular hyperfiltration in animal models of type 1 diabetes (Kidokoro K. et al. Circulation 2019). The mechanism of development of glomerular hyperfiltration, and improvement of glomerular hyperfiltration by SGLT2i may, however, be different in type 1 vs type 2 diabetes and related DKD. However, the detailed regulatory mechanism of GFR have not yet been elucidated in DKD related to T2D.

Methods:

Zucker lean (ZL) rats and Zucker diabetic fatty (ZDF) rats were used. In the first experiment, SNGFR and diameters of glomerular afferent/efferent arterioles were measured in both groups. Next, we examined the change of SNGFR and diameters of glomerular afferent/efferent arterioles, as well as urinary excretions of glucose and sodium in ZDF after a single-dose administration of SGLT2i (luseogliflozin; 10 mg/kg, gavage) for 120 minutes, which generated the following three groups: SGLT2i group, SGLT2i + adenosine A1 receptor (A1aR) antagonist (8-cyclopentyl-1,3-dipropylxanthine, 1 mg/kg) group, and insulin group.

Results:

SNGFR, afferent and efferent arteriole diameter were significantly increased in ZDF compared to ZL, with greater afferent vs. efferent dilatation. SGLT2i treatment resulted in correction of afferent arteriole vasodilation, with post-SGLT2i diameter that was comparable to baseline levels (p > 0.05). Post-SGLT2i SNGFR was also similar compared to baseline levels. Changes in efferent arteriole diameter were not significant. The inhibitory effect on hyperfiltration by SGLT2i was abolished by the concomitant use of an A1aR antagonist. In contrast, urinary sodium and urinary glucose in SGLT2 inhibitor group increased significantly regardless of adenosine A1 receptor antagonist use. In response to SGLT2i, urinary adenosine and PGE2 increased significantly (p > 0.05), while urine NOx did not change.

Conclusion:

Regulation of afferent arteriolar tone with SGLT2i is dependent on adenosine/ A1aR signaling an experimental model of T2D related hyperfiltration, regardless of ARB use.
PS-BPB08-6: REGULATORY MECHANISM OF GLOMERULAR FILTRATION RATE BY THE KEAP1/NRF2 PATHWAY
Authors: Kidokoro Kengo , Kadoya Hiroyuki , Kashihara Naoki
Published: January 2023

The activation of the Kelch like ECH associated protein 1 (Keap1)/nuclear factor (erythroid derived 2) like 2 (Nrf2) pathway increases glomerular filtration rate (GFR) in patients with type 2 diabetes and chronic kidney disease. However, the mechanisms whereby the Keap1/Nrf2 pathway regulates GFR are unknown. C57BL/6 mice (WT), Nrf2 deficient mice, and Nrf2 activated Keap1 knockdown mice were compared, and RTA dh404 (CDDO dhTFEA) was used as a Nrf2 activator. Glomerular hemodynamics and the permeability of glomeruli to macromolecules were evaluated using laser Doppler techniques and in vivo imaging. Calcium influx and the rearrangement of the actin cytoskeleton in response to angiotensin II, H2O2, the Nrf2 activator dh404, and transient receptor potential cation channel, subfamily C (TRPC) channel inhibitors were evaluated in podocytes. Finally, the effects of a TRPC6 inhibitor on GFR were investigated in vivo. Pharmacological and genetic Keap1/Nrf2 activation increased renal blood flow (p < 0.05), glomerular volume (p < 0.05), and GFR (p < 0.05), but did not alter afferent or efferent arteriolar diameter or glomerular permeability. Calcium influx into podocytes through TRPC channels in response to angiotensin II or H2O2 was suppressed by Keap1/Nrf2 activation. TRPC inhibitors and dh404 reduced the activation of the small GTPase(RhoA)/Rho associated kinase 1/LIM domain kinase 1/cofilin pathway and the subsequent actin rearrangement induced by angiotensin II or H2O2. Treatment with a TRPC6 inhibitor increased single nephron GFR in WT mice. In conclusion, the Keap1/Nrf2 pathway regulates GFR through changes in ultrafiltration via intracellular calcium signaling and cellular contractility, mediated through TRPC activity, in glomerular cells.
PS-BPB10-4: CREATION AND CHARACTERIZATION OF THE UBIQUITIN LIGASE KLHL3-S433A KNOCK-IN MICE
Authors: Ishizawa Kenichi , Kaseda Ken , Yamazaki Osamu , Shibata Shigeru
Published: January 2023

Background and aim:

Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure and electrolyte homeostasis. Mutation and inactivation of KLHL3 are known to cause hypertension and hyperkalemia mainly due to the impaired with-no-lysine (WNK) degradation and increased Na-Cl cotransporter (NCC) activity in the kidney. Previously, we have reported that angiotensin II (Shibata et al. PNAS 2014), potassium deficiency, and impaired glucose tolerance (Ishizawa et al. BBRC 2016 and JASN2019) can inactivate KLHL3 by altering phosphorylation at S433 in the Kelch-domain. We and others have also shown that decreased KLHL3 expression is also involved in the pathology of hypertension and hyperkalemia. The current study was designed to demonstrate the physiological importance of S433 in KLHL3 function in vivo in mice.

Method:

Using CRISPR/Cas9, S433 of KLHL3 was substituted to alanine in C57BL/6 mice (KLHL3-S433A Knock in mice: KI). Creation of KI was confirmed by DNA sequencing and RFLP analysis. Blood pressure was evaluated by telemetry, and blood gas was analyzed by iSTAT. Levels of KLHL3, WNK1/4, and NCC in the kidney were determined by Western blot analysis. Gene expression of KLHL3, WNK1 and WNK4 was evaluated by real time RT-PCR.

Results:

On a normal salt diet, blood pressure levels were similar between WT and KI; however, KI mice showed significant increase in response to a high salt diet compared with WT on the same diet. KI mice showed a significant increase in plasma potassium levels and a significant decrease in bicarbonate levels already at baseline, confirming that S433 in KLHL3 is also critical in regulating potassium and acid/base homeostasis. Urinalysis indicated that the increase in plasma potassium levels is mainly attributable to the decreased potassium excretion. Of interest, we found that total KLHL3 abundance was drastically reduced by Western blot analysis, which was accompanied by the increase in KS-WNK1 and WNK4 and an increase in NCC both. Real time RT-PCR showed that gene expression of Klhl3, as well as those of Wnk1 and Wnk4, was unchanged, indicating that S433A substitution promotes degradation of KLHL3, leading to hyperkalemia and increased salt sensitivity.

Conclusion:

The study confirmed the critical importance of S433 in KLHL3 in controlling the ubiquitin ligase function and electrolyte homeostasis in vivo. It also indicates that the modification of KLHL3-S433 influences the protein abundance without affecting gene transcription.
PS-BPC02-8: EARLY VASCULAR AGING IN HYPERTENSION IS A PREDICTOR OF INCIDENT DIABETES
Authors: Terentes-Printzios Dimitrios , Christopoulou Georgia , Korogiannis Lampros , Ioakeimidis Nikolaos , Aznaouridis Konstantinos , Dima Ioanna , Gardikioti Vasiliki , Oikonomou Dimitrios , Gkini Konstantia P. , Solomou Eirini , Tsioufis Konstantinos , Vlachopoulos Charalambos
Published: January 2023

Objective:

Diabetes is associated with vascular aging and arteriosclerosis. Arterial stiffness can be used to assess vascular aging and is an independent predictor of cardiovascular events and mortality. However, the role of arterial stiffness in the incidence of diabetes and especially in patients under treatment with statins has not been investigated. We sought to investigate the role of carotid-femoral pulse wave velocity (PWV) in the prediction of incident diabetes in hypertensives and hypertensives under treatment with statins.

Design and method:

376 never treated hypertensives (mean age 53 ± 13 years, 175 females) without a known history of diabetes or cardiovascular disease at baseline, were included in the study. Markers of target organ damage [carotid femoral PWV, aortic augmentation index (AIx), and estimated glomerular filtration rate (eGFR)] were evaluated at baseline in all patients. eGFR was estimated using the Cockcroft Gault formula. Hemoglobin A1c (HbA1c) and blood glucose were measured in venous blood samples. Patients were followed up prospectively for the incidence of diabetes as defined by the American Diabetes Association criteria. One hundred and thirty-nine patients received statins during follow up.

Results:

During a median of 13.5 years of follow up, 46 patients (12.2%) patients were diagnosed with diabetes. In multivariable logistic regression analysis, only higher PWV (Odds Ratio [OR] = 1.271, 95% Confidence intervals [CI]: 1.002 to 1.612, P = 0.048) was associated with a higher risk of incident diabetes, which was independent of age, sex, pulse pressure, HbA1c, fasting blood glucose and eGFR (Figure). In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of PWV to discriminate subjects with diabetes. The area under the curve (AUC) and 95% CIs of the ROC curve was AUC = 0.66 (95% CI: 0.58 to 0.74, P = 0.001) for PWV. In the subgroup of patients under treatment with statins, higher PWV (OR = 1.51, 95% CI: 1.09 to 2.11, P = 0.014) was associated with higher risk of incident diabetes, which was independent of the abovementioned confounders. AIx was not associated with the incidence of diabetes.

Conclusions:

Higher arterial stiffness, a marker of early vascular aging, is associated with the incidence of diabetes and also can identify subjects under treatment with statins that are more likely to present with diabetes in the future.
PS-BPC03-2: NIGHTTIME HOME BLOOD PRESSURE WAS ASSOCIATED WITH ADVERSE OUTCOMES IN SUBCLINICAL HEART FAILURE PATIENTS
Authors: Komori Takahiro , Hoshide Satoshi , Kario Kazuomi
Published: January 2023

Objective:

Nighttime blood pressure (BP) has stronger association with target organ damage and cardiovascular outcome than office BP, 24-hr BP, and awake BP in hypertensives. However, clinical significance of nocturnal BP, especially home nocturnal BP, was not established in heart failure (HF) patients. We hypothesized that nighttime home BP was associated with adverse outcome and investigated the association between nighttime home BP and the outcome in subclinical HF patients.

Design and method:

We analyzed 394 patients with NT-proBNP > 125pg/ml from a practitioner-based population with at least one cardiovascular risk factor who underwent home BP monitoring in the Japan Morning Surge-Home Blood Pressure study. Morning, evening and nighttime home BP were measured by validated, automatic, and oscillometric home BP devices, and cardiovascular events were followed up.

Results:

During a mean follow-up of 4.2 years, 43 cardiovascular events occurred. Morning home SBP, evening home SBP and nighttime home SBP were higher in event group than in non-event group (150 ± 23 vs 140 ± 17 mmHg, p = 0.01, 142 ± 22 vs 131 ± 16 mmHg, p < 0.01, 133 ± 22 vs 125 ± 17 mmHg, p < 0.01, respectively). In multivariate Cox regression analysis adjusting for significant variables, average of evening home SBP, and nighttime home SBP were significant predictors of the outcome (HR 1.02, 95%CI: 1.01–1.04, p = 0.01, HR 1.02, 95%CI: 1.01–1.04, p = 0.03, respectively). When nighttime home SBP of 120mmHg was used as cutoff, nighttime home SBP > 120mmHg was significantly associated with the outcome (HR 2.46, 95%CI 1.06–5.68, p = 0.04).

Conclusions:

Elevated nighttime home BP was significant predictor of cardiovascular outcomes in subclinical HF patients.
PS-BPC03-4: DIAGNOSTIC AGREEMENT OF MASKED UNCONTROLLED HYPERTENSION DETECTED BY AMBULATORY BP AND HOME BP MEASURED BY AN ALL-IN-ONE BP MONITORING DEVICE
Authors: Tomitani Naoko , Hoshide Satoshi , Kario Kazuomi
Published: January 2023

Objectives:

Masked hypertension is a phenomenon in which office blood pressure (BP) is in the controlled BP range while out-of-office BP measured by ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) is in the uncontrolled BP range. Out-of-office BP control status may differ if defined by different BP indexes or measured under different conditions (resting or ambulatory), over different time-windows, or with different devices. This study aims to investigate the diagnostic agreement of masked uncontrolled hypertension (MUHT) detected by ABPM indexes (ABPM-MUHT) and HBPM indexes (HBPM-MUHT) using the same all-in-one device.

Methods:

Medicated hypertension patients enrolled in the Home-Activity ICT-based Japan Ambulatory Blood Pressure Monitoring Prospective (HI-JAMP) Study between 2017 and 2020 consecutively underwent office BP monitoring, 24-h ABPM (with 30-min intervals), and 5-day HBPM (twice each morning and evening) using the same device (TM-2441; A&D Company, Tokyo). Controlled BP ranges for each BP index were as follows: office systolic BP [SBP] < 140 mmHg; morning home, evening home, or morning-evening (ME) average SBP < 135 mmHg; 24-h average SBP < 130 mmHg; daytime SBP < 135 mmHg; and nighttime SBP < 120 mmHg.

Results:

Of 2322 patients (males 53.2%, average age 69.2 ± 11.5 years, average office SBP 132.8 ± 18.8 mmHg), the prevalences of ABPM-MUHT and HBPM-MUHT were 11.0% and 13.9%, respectively, when MUHT was defined only by 24-h average SBP or ME average SBP. Among the 445 patients with any MUHT according to this definition, the diagnostic agreement of MUHT detected by ABPM and HBPM was 29.7%. The prevalences of HBPM-MUHT defined by morning SBP and evening SBP were 22.4% and 11.6%, respectively, and those of ABPM-MUHT defined by daytime SBP and nighttime SBP were 11.8% and 13.8%. When MUHT was defined by any time-window index (ABPM: daytime, nighttime, and 24-h average SBP; HBPM: morning, evening, ME average SBP), the prevalences of ABPM-MUHT and HBPM-MUHT were 19.8% and 25.0%, respectively, and the diagnostic agreement of MUHT detected by ABPM and HBPM in patients with any MUHT (n = 743) increased to 40.1%.

Conclusion:

Even in treated patients with well-controlled office BP, the prevalence of MUHT in the morning and nighttime was high. Assessment of BP control status only by ME average or 24-h average SBP, without considering specific time-windows, might underestimate cardiovascular risk.
PS-BPC04-5: DIFFERENCE BETWEEN MORNING AND EVENING BLOOD PRESSURE AT HOME AND NOCTURNAL HYPOXIA IN THE GENERAL PRACTITIONER-BASED J-HOP STUDY
Authors: Hoshide Satoshi , Kario Kazuomi
Published: January 2023

Objective:

The increase of morning home blood pressure (BP) compared to evening home BP defined as morning minus evening home BP (MEdif) was also associated with target organ damage and cardiovascular prognosis. A majority of previous studies have shown the determinant of MEdif from the point of demographic characteristics, but not from pathophysiological feature.

Methods:

The analysis of this study included participants from the baseline who performed home BP measurements and a portable pulse oximeter during nighttime in the Japan Morning-Home Blood Pressure (J-HOP) study, which is a practitioner-based, prospective, observational cohort study of a large Japanese outpatient population who had home BP measurement with the same validated device.

Results:

In the study of 1053 participants with at least cardiovascular risk, the prevalence of the individuals with 20 mmHg in MEdif was 14.0%. In univariate linear regression analysis, minimum SpO2 (beta = -0.19, P < 0.001) and oxygen desaturation index (beta = 0.06, P = 0.049) was associated with MEdif, but not in mean SpO2 (beta = -0.10, P = 0.496). After adjustment for covariates, only the association between minimum SpO2 and MEave was remained (beta = -0.15, P = 0.002). Dividing the participants into quartiles according to the minimum SpO2, the lowest (Odds ratio [OR], 1.98; 95% confidence interval [CI], 1.13–3.49) and third quartile (OR, 1.76; 95%CI, 1.02–3.04) were significantly determinant of those with ≧ 20 mmHg in MEdif than the top quartile.

Conclusion:

Increased MEdif in the Japanese population with at least one cardiovascular risk. When physicians find increased MEdif, especially greater than or equal to 20 mmHg, the possible impact of nocturnal hypoxia could be accounted.
PS-BPC05-1: HEART RATE VARIABILITY INDICES AS POTENTIAL POST-TRAUMATIC STRESS DISORDER BIOMARKERS
Authors: Cardoso Claudia F , Ohe Natalia T , Bader Yazan , Afify Nariman , Homedi Zahrah Al , Alwedami Salma M , OSullivan Siobhan , Campos Luciana A , Baltatu Ovidiu C
Published: January 2023

Objective:

Psychological distress, such as posttraumatic stress disorder (PTSD), is commonly evaluated using subjective questionnaires, a method prone to self-report bias. The working hypothesis was that levels of autonomic dysfunction determined by heart rate variability (HRV) measures are associated with the severity of PTSD in women following pregnancy loss.

Design and Methods:

This was an observational prospective cohort study with 53 patients enrolled. The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) PTSD scale (PCL-5) was used to assess the severity of PTSD in women after pregnancy loss. The cardiac autonomic function was assessed using HRV measurements during a deep breathing test using an HRV scanner system with wireless ECG enabling real-time data analysis and visualization. HRV measures were: standard deviation (SD) of normal R-R wave intervals [SDNN, ms], square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals [RMSSD, ms], and the number of all R-R intervals in which the change in consecutive normal sinus intervals exceeds 50 milliseconds divided by the total number of R-R intervals measured [pNN50 = (NN50/n-1)x100%] [pNN50%].

Results:

The PCL-5 scores had a statistically significant association with HRV indices (SDNN; RMSSD, and pNN50%). Patients with PTSD had similar mean heart rate values as compared to patients without PTSD (PCL-5), but significantly higher SDNN [median[IQR, interquartile range]: 90.1 (69.1 - 112.1) vs. 52.5 (36.8 - 65.6)], RMSSD [59.4 (37.5 - 74.9) vs. 31.9 (19.3 - 44.0)], and PNN50% values [25.7 (16.4 - 37.7) vs. 10.6 (1.5 - 21.9)]. The SDNN of the deep breathing test HRV was effective at distinguishing between patients with PTSD and those without, with an AUC = 0.83 +/- 0.06 (95 % CI 0.94, p = 0.0001) of the ROC model.

Conclusions:

In this study, HRV indices as biomarkers of cardiac dysautonomia were found to be significantly related to the severity of PTSD symptoms in women after pregnancy loss.
PS-BPC05-3: THE RELATIONSHIP BETWEEN THE WEIGHT-ADJUSTED-WAIST INDEX AND LEFT VENTRICULAR HYPERTROPHY IN CHINESE HYPERTENSION ADULTS
Authors: Cai Shuang
Published: January 2023

Background:

Left ventricular hypertrophy (LVH) is a major cardiac complication of hypertension. weight-adjusted-waist index (WWI) is a new obesity index that has been found to be positively associated with cardiovascular disease mortality. We aimed to investigate the relationship between the weight-adjusted-waist index and left ventricular hypertrophy in Chinese hypertension adults.

Methods:

The study is a community-based cross-sectional study that included 4715 patients with hypertension and integrated clinical and echocardiographic data. LVH was diagnosed by transthoracic echocardiography in these patients based on a criterion of left ventricular mass index (LVMI) over 49.2 g/m2.7 in men and 46.7 g/m2.7 in women. The independent association between the WWI quartiles and LVH prevalence was analyzed by logistic regression models.

Results:

The prevalence of LVH in the first quartile of WWI (Q1:less than 10.16), second (Q2:10.16∼10.67), the third (Q3:10.68∼11.19), and the highest quartile (Q4:greater or equal to11.20) was 34.1%, 38.4%, 42.4%, 51.5%, respectively. Logistic regression analysis suggested that the WWI was independently correlated with the risk of LVH with adjustment of confounding factors, and increased across the quartile of WWI. Compared to the first quartile of WWI (Q1), the odds ratios (ORs) and their 95% confidence intervals (CIs) for LVH in the increasing quartiles (Q2-Q4) were 1.33(1.08–1.63), 1.50 (1.19–1.89) and 2.28(1.74–2.99), respectively. In stratified analyses, the relationship between WWI and LVH risk persisted.

Conclusions:

The WWI may be an independent risk factor of LVH in Chinese hypertension adults.
PS-BPC05-6: PATIENTS WITH HEART FAILURE ACCOMPANIED BY A HYPERTENSIVE CRISIS HAD A RELATIVELY GOOD PROGNOSIS
Authors: Shin Mi Seung , Won Yoonsun , Yang Tae Il , Kim Joo Han , Lee Joonpyo , Seo Jungduk , Shin Young Hoon
Published: January 2023

Objectives:

Blood pressure (BP) is a prognostic marker of heart failure with reduced ejection fraction (HFrEF). We find hypertensive crisis not uncommon in patients who complain of dyspnea. We aimed to determine the correlation between BP level and time to recovery in patients with HFrEF visiting the emergency department (ED).

Methods:

This observational study included patients aged /> 19 years who visited an ED between 2015 and 2018 for dyspnea. We analyzed the BP, clinical outcomes, and prognosis of 1136 patients with HFrEF, excluding patients with acute myocardial infarction or valvular heart disease, among 2690 patients. Patients were divided into four groups according to their initial BP level based on the ESC/ESH hypertension guideline. The hypertensive crisis was defined as systolic BP /> 180 mmHg and/or diastolic BP /> 110 mmHg, which was equivalent to grade 3 hypertension.

Results:

Among the 1136 patients, 638 (56.2%) were below high normal BP, 236 (20.8%) showed grade 1 hypertension, 169 (14.9%) showed grade 2 hypertension, and 93 (8.2%) showed grade 3 hypertension. The recovery rate of heart failure for 3 years by the group was 21.6%, 32.1%, 38.3%, and 62.7%. The time to recovery was 32.1, 28.3, 15.7, and 7.4 months for each group.

Conclusions:

The hypertensive crisis had a relatively good prognosis in patients with HFrEF when adequate BP control was achieved.
PS-BPC05-8: RELATIONSHIP BETWEEN EXECUTIVE DYSFUNCTION AND READMISSION IN PATIENTS WITH HEART FAILURE
Authors: Kaneko Tetsuya , Kotooka Norihiko , Node koich
Published: January 2023

Objective:

The prevalence of cognitive impairment is high in patients with heart failure and is associated with poor prognosis. Executive dysfunction can influence self-care control and adherence in patients with heart failure. We examined the relationship between executive dysfunction and hospital readmission in patients with heart failure.

Design and Methods:

Patients with heart failure were observed prospectively using a telemonitoring system. Cognitive impairment was evaluated using the Mini-Mental State Examination (MMSE) and executive dysfunction using the Trail Making Test B (TMT-B) at baseline. Cognitive impairment was defined as an MMSE score ≧ 23 points, and executive dysfunction was defined as a TMT-B score ≧ 180 s. We assessed relevant associations using the readmission rate.

Results:

Overall, 37 participants were studied. At a median follow-up of 19.5 months, 15 participants (40.5%) were re-hospitalized for worsening heart failure. Readmission rates for worsening HF were significantly higher in the executive dysfunction group (TMT-B ≧ 180 s) compared to the non-executive dysfunction group (TMT-B < 180 s; log-rank test, p = 0.005). Of the participants with no cognitive impairment (MMSE > 23), 11 had executive dysfunction while 19 did not. Readmission rates for worsening heart failure were higher in participants with cognitive impairment who had executive dysfunction (hazard ratio, 3.72; 95% CI, 0.87–15.8; p = 0.076). Multivariate analysis revealed that executive dysfunction was an independent risk factor for readmission due to heart failure (hazard ratio, 6.26; 95% CI, 1.01–38.4; p = 0.049).

Conclusions:

Executive dysfunction, as assessed by TMT-B, is associated with an increase of readmission in patients with heart failure. TMT-B may be useful in assessing the risk of readmission in patients with heart failure, as this is difficult to identify with general cognitive assessments.
PS-BPC05-9: MYELOPEROXIDASE PROGNOSTIC ROLE IN HYPERTENSIVE PATIENTS AFTER MYOCARDIAL INFARCTION WITH ST-ELEVATION
Authors: Rodionova Iuliia , Kytya Inna , Kopytsya Mykilay
Published: January 2023

Objectives:

The aim was to study the role of myeloperoxidase (MPO) in left ventricle hypertrophy prognosis in hypertensive patients with ST-elevation myocardial infarction (STEMI) within 12 months.

Design and Methods:

Patients were divided into two groups depending on the level of MPO (median 95.68 ng / ml). Group 1 (with MPO> 95.68 ng/ml) included 48 patients. Group 2 with MPO < 95.68 ng/ml included 48 patients. The level of MPO was determined in all patients on the first day of the disease by enzyme-linked immunosorbent assay using a set of reagents Human MPO Instant ELISA KIT, Invitrogen Austria. The endpoint included left ventricle hypertrophy onset/progression, and was assessed after 12 months of follow up.

Results:

In the analysis of the two groups, it was found that patients in group 2 had significantly higher MPO 159.17 IQR 97.81 to 189.23 compared with the first group 65.77 IQR 48.18 to 94.23 p = 0.039. In univariative logistic analyses MPO showed significant association with LV hypertrophy development, β; = 0.033;p < 0.001. Multivariate logistic analysis revealed the reverse correlation of MPO with the LV remodeling in 12 months follow up β; = 0.010; p = 0.0034.

Conclusion:

The increased level of MPO is a significant predictor for development of left ventricle hypertrophy in hypertensive patients after STEMI in 12 month follow up
PS-BPC06-1: RENIN-ANGIOTENSIN SYSTEM BLOCKER AND THE COVID-19 AGGRAVATION: REPORT BY THE COVID-19 REGISTRY JAPAN
Authors: Yoshihara Fumiki , Ohtsu Hiroshi , Nakai Michikazu , Tsuzuki Shinya , Hayakawa Kayoko , Terada Mari , Matsunaga Nobuaki , Yasuda Satoshi , Ogawa Hisao , Ohmagari Norio
Published: January 2023

Objective:

The role of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the pandemic context of coronavirus disease 2019 (COVID-19) continues to be debated. Patients with hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or chronic obstructive pulmonary disease (COPD), who often use ACEi/ARB, may affect risk of severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population.

Design and method:

This study is an observational study of patients with a positive SARS-CoV-2 test and inpatient treatment at a healthcare facility, using the registry information of COVIREGI-JP. Our primary outcomes were consisting of in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and ICU admission. Out of the 6,055 patients, 1,921 patients with preexisting hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or COPD were enrolled. We also evaluated 1,097 patients with hypertension.

Results:

Factors associated with an increased risk of the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes mellitus. No correlations were observed with ACEi/ARB, cerebro-cardiovascular diseases, or hypertension. Associated factors in male patients were aging, renal impairment, hypertension, and diabetes. In female patients, factors associated with an increased risk were aging, ACEi/ARB, renal impairment, and diabetes, whereas hypertension was associated with a lower risk of the primary outcomes. In patients with hypertension, factors associated with an increased risk of the primary outcomes were aging, male sex, severe renal impairment, and diabetes mellitus, but not ACEi/ARB, cerebro-cardiovascular diseases, or COPD.

Conclusions:

Independent factors for the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes, but not ACEi/ARB, in the COVID-19 patients with preexisting hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease or COPD. Based on this registry data analysis, more detailed data collection and analysis is needed with the cooperation of multiple healthcare facilities.
PS-BPC08-9: A COMPARISON OF THE EFFECTS OF ADRENALECTOMY AND TREATMENT WITH EPLERENONE ON VASCULAR FUNCTION IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMA
Authors: Kishimoto Shinji , Oki Kenji , Maruhashi Tatsuya , Kajikawa Masato , Mizobuchi Aya , Harada Takahiro , Han Yiming , Hashimoto Yu , Yusoff Farina Mohamad , Nakashima Ayumu , Nakano Yukiko , Higashi Yukihito
Published: January 2023

Background:

It is still unclear whether adrenalectomy has more beneficial effects than treatment with a mineralocorticoid receptor antagonist of eplerenone on vascular function in patients with aldosterone-producing adenoma (APA). The purpose of this study was to compare the effects of adrenalectomy and treatment with eplerenone on vascular function in patients with APA.

Methods:

Flow-mediated vasodilation (FMD) as an index of endothelium-dependent vasodilation and nitroglycerine-induced vasodilation (NID) as an index of endothelium-independent vasodilation were measured to assess vascular function before and after 3-month treatment with eplerenone and at 3 months after adrenalectomy in 23 patients with APA.

Results:

FMD and NID after adrenalectomy were significantly higher than those before treatment with eplerenone (5.4 ± 2.6% vs. 2.7 ± 1.9% and 14.8 ± 4.7% vs. 9.6 ± 4.6%, P < 0.01, respectively) and those after treatment with eplerenone (5.4 ± 2.6% vs. 3.1 ± 2.3% and 14.8 ± 4.7% vs. 11.0 ± 5.3%, P < 0.01 and P = 0.03, respectively), while treatment with eplerenone did not alter FMD and NID compared with those before treatment with eplerenone. After adrenalectomy, the increase in FMD and NID were significantly correlated with the decrease in PAC and the decrease in aldosterone-renin ratio. There were no significant relationships between FMD and changes in other parameters or between NID and changes in other parameters.

Conclusions:

Adrenalectomy, but not treatment with eplerenone, improved vascular function in patients with APA. Adrenalectomy may be more effective than treatment with eplerenone for reducing the incidence of future cardiovascular events in patients with APA.