bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-P05-4: GLOBAL BURDEN OF ATRIAL FIBRILLATION/ATRIAL FLUTTER DUE TO HYPERTENSION DURING 1990–2019
Authors: Wang Keke , Jin Yaqiong , Wamg Mengxiao , Gao Xueying , Zhang Jie , Lu Jingchao 
Published: January 2023

Objective:
High systolic blood pressure (HSBP) remains the leading risk factor for atrial fibrillation/atrial flutter (AF/AFL) worldwide. However, limited quantitative research has revealed the specific AF/AFL burdens due to HSBP. This study aimed to estimate the global burden of AF/AFL attributable to HSBP by region, sex, and age.

Design and method:
Data on HSBP-related AF/AFL burden was extracted from the 2019 Global Burden of Disease (GBD) study. Numbers and age-standardized rates of deaths, disability-adjusted life years (DALYs) and corresponding estimated annual percentage change (EAPC) were discussed by age, sex, socio-demographic index (SDI) and locations.

Results:
Globally, HSBP-related AF/AFL caused 107,091 deaths and 3,337,876 DALYs in 2019, an increase of 142.5% and 105.9% from 1990, respectively. The corresponding mortality and DALYs rates dropped by 5.8% and 7.7%, respectively. Almost half of the HSBP-related AF/AFL burden was bore by high and high-middle SDI regions and it was experiencing a shift from high and high-middle SDI regions to lower SDI regions. In general, females and elderly people tended to have a higher HSBP attributable AF/AFL burden. In addition, young adults (30–49 years old) experienced an annual increase in global deaths and DALYs rates. V-shaped correlation was detected between SDI and HSBP-related AF/AFL burden.

Conclusions:
HSBP attributable AF/AFL burden has been an incremental public health concern worldwide, with heterogeneities across regions, sexes and ages. Geographically and sexually tailored strategies were required to reduce the burden of hypertension-related AF/AFL.
PS-P05-9: A PROTOCOL OF DIGITAL PROSPECTIVE COHORT STUDY ON HEART FAILURE AND COGNITIVE DECLINE IN URBAN RESIDENTS: THE SUITA STUDY NEXT
Authors: Kokubo Yoshihiro , Kashima Rena , Teramoto Masayuki , Arafa Ahmed , Gao Qi , Sakai Yukie , Nosaka Saya , Maeda Saori , Wada Akane , Yasui Yuka , Kawachi Haruna , Dohi Tomoharu , Matsumoto Chisa , Sheerah Haytham A , Izumi Chisato 
Published: January 2023

Background:
The aging rate in Japan is about 30%, which is the highest worldwide and will continue to increase. The prevalence of heart failure and dementia in Japan increases much more than the nationally known values. There is an urgent need for a drastic solution to this. Multi-employers’ community intervention prevents heart failure and dementia in Western countries, but Japan mainly relies on family care to prevent them. Although heart failure and dementia worsen each other, there are few cohort studies aimed at both at the same time. Also, there are few cohort studies of Japanese heart failure.

Objective:
This study aims to show the evidence of risk factors for heart failure and dementia in urban residents and to build evidence to create a town where multi- employers’ community intervention is possible

Methods:
We recommend that all people aged 65 or older who live in two predetermined (elementary school) districts of Suita City receive a medical examination (6,340 people). We will conduct the following tests accompanying the medical check-up: echocardiography, carotid artery echo, limb blood pressure, Holter electrocardiography, ophthalmic examination (visual acuity, fundus examination, color vision examination, tonometry, optical interference tomography), otolaryngology examination (auditory examination, olfactory test), physical fitness test (grip power, walking test), oral examination (dental prescale, masticatory ability measurement, and repeated saliva swallowing test), cognitive function test, depression test, and health and semi-quantitative food frequency questionnaires. Blood collection will be carried out collectively for research and biobank projects (only for consenters). In addition, we will receive prognosis data (annual medical examination data, medical expenses, long-term care, transfer information, and cause of death) of cohort subjects. We encourage and follow up every three years for people aged 65 and over who live in the same two specific districts. The Institutional Review Board approved this protocol. Informed consent is obtained from all subjects.

Discussion:
We started this cohort study in September 2021. After a three-year baseline survey, a follow-up survey will begin. In a cross-sectional study of the baseline survey, we prepare profile papers on the relationship between the prevalence of heart failure and cognitive decline and prognosis. We are studying multi-layered omics analysis using blood sampling and AI research using a lot of digital data. We will first provide evidence on the prevention of heart failure and dementia among the urban residents in Japan and present materials that contribute to policymaking that can extend healthy life expectancy.
PS-P06-1: REDUCED HEALTHCARE UTILIZATION AMONG PATIENTS WITH CHRONIC DISEASES DURING THE PANDEMIC
Authors: Gamage Anuji Upekshika , Gunasekera Therani , de Silva Amala 
Published: January 2023

Objective:
Public-health strategies resorted to world-wide, to reduce the transmission of COVID-19 impacted the healthcare-utilization of people with pre-existing chronic diseases. We aimed to assess the healthcare utilization, patient-experiences and economic impacts among people with chronic diseases due to COVID-19 pandemic.

Design and Methods:
An online survey was conducted in 2021 involving 449 adults living in the Western-Province of Sri Lanka. Data on participants socio-demographic and economic status, co-morbidities, healthcare utilization, and healthcare-seeking behaviours were collected using a pre-tested questionnaire. The questionnaire link was distributed through social media and by emails. Categorical data were expressed as proportions/percentages with 95% confidence intervals where relevant. Quantitative data, normally distributed, were summarized in terms of mean and standard deviation (SD) and non-normally distributed as the median and interquartile-range (IQR).

Results:
449 respondents completed the survey. Majority (55%) responded that they experienced a negative impact on their main income. 26%(n = 115) mentioned that they had a doctor-diagnosed chronic disease or a disability and of them 72% (n = 83) were on regular medication. Nearly half (n = 55;48%) mentioned that there was a delay in seeking healthcare during the pandemic and 27% (n = 30)reported not having sought treatment during the lockdown period. Of the people with delayed healthcare seeking 25% had hypertension, 16% diabetes, and 12.2% asthma. Considering care seeking pattern among people with chronic illness, it declined in all institutions during the lockdown period. However careseeking in the private sector, only margially declined during the pandemic. Considering care seeking at a government hospital, a drastic drop was observed during the lockdown period (n = 13; = 11.3%). Of the respondents who sought healthcare for chronic illness during the pandemic in lockdown (n = 85; 74%) and no-lock down (n = 107; 93%), a considerable proportion mentioned that clinics were either not functioning on time or not functioning at all. Although the majority agreed that their perceived health despite the chronic illness was good, very good, or excellent, around 38% reported it as fair or poor.

Conclusion:
Health-care utilization among people with a chronic disease reduced due to supply and demand driven factors in healthcare. Efforts are necessary to ensure continuity of care for people with chronic disease to prevent complications. The government needs to invest in resilient health systems to be better equipped to provide uninterrupted care for NCDs in any circumstances. To support this, primary healthcare strengthening and tele-health options should be explored.
PS-R01-5: SACUBITRIL/VALSARTAN IMPROVES HYPERTENSION, NIGHTTIME BLOOD PRESSURE AND HEART FAILURE: A CASE-REPORT
Authors: Takami Takeshi 
Published: January 2023

Objective:
Sacubitril/valsartan, angiotensin receptor blocker (ARB)/neprilysin inhibitor, has been shown to effectively reduce ambulatory 24-h blood pressure in patients with hypertension. Improvements in heart failure have also been reported. This case report highlights the validity of sacubitril/valsartan for the treatment of hypertension, nocturnal blood pressure, and heart failure.

Methods:
A 75-year-old hypertensive male patient with heart failure was prescribed an ARB and a β;-blocker, along with a mineralocorticoid receptor antagonist (MRA) for diuresis. However, his nighttime blood pressure and central blood pressure remained high, and left ventricular ejection fraction (LVEF) remained low, along with persistent elevation of serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) levels.
Hence, we switched the ARB to sacubitril/valsartan. The other drugs were left unchanged. We measured his daytime and nighttime blood pressure by ambulatory blood pressure monitoring (ABPM) before and 6 months after the change of medication. In addition, central systolic blood pressure (cSBP) was measured using an automated tonometry system, LVEF, left ventricular mass index (LVMI), left atrial (LA) diameter and septal ratios of transmitral flow velocity to annular velocity (septal E/e’ ratio) were measured using a Vivid S6 ultrasound system with 3-MHz transducer and serum sample was obtained for NT-pro BNP assessment before and 6 months after the change of medication.

Results:
Brachial blood pressure (154/71 to 132/72 mmHg), nocturnal blood pressure (average value: 136/65 to 121/67 mmHg), and cSBP (154 to 135 mmHg) improved by changing the treatment. Additionally, the riser pattern was improved to the dipper blood pressure pattern by changing the prescription, along with improvements in EF (39.5 to 51.2%), LVMI (127.3 to 119.6 g/m2), LA diameter (40.1 to 37.8 mm) and septal E/e’ ratio (15.1 to 14.5). Further, although serum levels of NT-pro BNP improved with the change of treatment (656 to 325 pg/mL).
Symptoms of heart failure were also reduced from New York Heart Association (NYHA) class 3 to NYHA class 2. There were no noticeable adverse effects after the change.

Conclusion:
In our patient, changing from an ARB to sacubitril/valsartan resulted in an improvement in nighttime and central blood pressure, and left ventricular hypertrophy and diastolic function, and to recovery of EF, with a change from heart failure with reduced ejection fraction (HFrEF) to heart failure with preserved ejection fraction (HFpEF). His NT-proBNP levels and heart failure symptoms also improved.
Our experience suggests that sacubitril/valsartan might be useful in patients with heart failure who have nocturnal hypertension.
PS-R02-4: MANAGEMENT OF BLEEDING IN SEVERE TR AND MR WITH CAD UNDERGOING OPEN HEART SUGERY
Authors: Jain Rajesh , Hosseini JS , Shogli Reza 
Published: January 2023

Raising ACT may be led to active bleeding. There are two scenarios

On the other hand, after major causes, use the best treatment in the patient with a history of coagulopathy, and using anticoagulant drugs can typically prevent the same events. Raising ACT may be led to active bleeding. There are 2senarios 1. active bleeding similar to our case.
2. delayed tamponade because this bleeding summed and gathered and cause clotting formation and led to tamponade.
On the other hand, after major causes, use the best treatment in the patient with a history of coagulopathy, and anticoagulant drugs can prevent the same events.

Summary of the report
This is about a specific 68 years old woman diagnosed with severe TR (tricuspid valve disease) and severe MR mitral valve regurgitation. After that, she underwent open-heart surgery, and subsequently, after three hours of needed surgery, she experienced drainage. Alternatively, she had transferred to the operations room, and the very first problem was that she had no dominant surgical site, while her ACT Active Clotting Time was 900. On the other hand, because the case had been treated with aspirin, after the operation, she received protamine; however, protamine, in these cases, shows the rebound feedback, and the complex interaction with the platelet is not successful and robust. For this apparent reason, when the ACT is about 130, one hour after the operation, ACT elevates to 900, and the patient experiences bleeding. Her sternum was kept open out of lacking any operation site. Standard treatment with FFP and Fibrinogen started, and after that, the patient general condition improved, and her sternum was closed the following day. It should be noted that the patient had a pandesal surgery history and also raised ACT history 16 years before the mentioned surgery.
PS-BPB01-6: PROTECTIVE NOX4 EFFECT IN ENDOTHELIAL CELLS INVOLVES ACTIVATION OF TRANSIENT RECEPTOR POTENTIAL MELASTATIN 2 (TRPM2) CATION CHANNEL
Authors: Lopes Rheure Alves , Neves Karla , Harvey Adam , Montezano Augusto , Touyz Rhian M 
Published: January 2023

Objective:
In endothelial cells, Nox4 is the most prevalent isoform and, in contrast to other Noxes, which generate superoxide O2, Nox4 produces mainly H2O2. Low H2O2 levels have been described to lower blood pressure, which suggests that a certain level of reactive oxygen species (ROS) can have protective effects on the cardiovascular system. We demonstrated that TRPM2 is a target of H2O2 in vascular cells. TRPM2 is a redox-sensitive Ca2+ channel and once activated leads to Ca2 influx. Endothelial dysfunction involves a reduction in eNOS activation by Ca2+ and is potentiated in the absence of Nox4. As TRPM2 channel is a H2O2 sensor and regulates Ca2+ entry, we questioned whether protective Nox4 effect in endothelial cells involves the H2O2-TRPM2-Ca2+ axis, with consequent regulation of NO signalling.

Design and Methods:
WT and TTRhRen hypertensive mice were crossed with Nox4 KO mice. Vascular function was measured by wire myograph in resistance arteries. ROS and H2O2 generation were assessed by lucigenin and amplex red, and Ca2+ influx by fluorescence microscopy in rat aortic endothelial cells (RAEC). eNOS activation was assessed by immunoblotting.

Results:
Blood pressure was significantly increased in TTRhRen (130.3 ± 7.0 mmHg) and TTRhRen/Nox4 KO mice (141.3 ± 18 mmHg) versus control mice (98.1 ± 8.0 mmHg). TTRhRen mice had reduced endothelium-dependent relaxation (Emax: WT 83.5 ± 4.03 vs TTRhRen 59.1 ± 3.5); an effect worsened by Nox4 KO (37.9 ± 5.4), p < 0.05. The TRPM2 activator, ADPR, improved vascular relaxation in TTRhRen/Nox4 KO mice (75.9 ± 7.7); an effect recapitulated by H2O2 (74.2 ± 15.4), p < 0.05. Ang II-induced ROS and H2O2 generation in RAEC, effect reversed by Nox4 siRNA and followed by increased Ca2+ influx (AUC - Ca2+: 20440.3333 ± 1870.9), important in eNOS activation. Ang II-induced Ca2+ influx in endothelial cells was reduced by TRPM2 siRNA, TRPM2 inhibitors (AUC - Ca2+: 8-br-cADPR 15232.2 ± 1052.1; Olaparib 14952.6 ± 843.2 and 2-APB 13270.8333 ± 277.4, p < 0.05) and by Nox4 siRNA and Nox4 inhibitor GKT137831 (AUC - Ca2+: GKT 15067.5 ± 255.6). Ang II-induced eNOS activation (Ser1177) (%: 72.3 ± 24.7) and NO release were blocked by Nox4 and TRPM2 sirNA, GKT137831, PEG-catalase and the TRPM2 inhibitor 8-br-cADPR (p < 0.05).

Conclusions:
We defined a novel molecular pathway in endothelial cells, where Nox4-induced H2O2 production activates PARP/TRPM2 signalling followed by Ca2+ influx, eNOS activation and NO release. The absence of Nox4 impairs Ca2+ homeostasis leading to endothelial dysfunction, an effect exacerbated in hypertension. The protective role of Nox4 corroborates the idea that the use of antioxidants based on the sole evidence that decreased oxidative stress is cardioprotective, it is not effective.
PS-BPB02-7: THE ROLE OF NEUTROPHIL TO LYMPHOCYTE RATIO AS PREDICTIVE BIOMARKER IN ACUTE CORONARY SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Greca Elona , Spicer Alexander James , Gomez Sabas , Marzban Sima , Michel Jack 
Published: January 2023

Introduction:
Current evidence suggests that the the neutrophil/lymphocyte ratio (NLR) is growing as a prognostic marker in patient with cardiovascular disease. It has been reported expanding evidence that involves innate and adaptive immune cell in the pathogenesis of Acute Coronary syndrome (ACS) which indicate the pivotal role of NLR as valuable diagnostic parameter in ACS patient. Purpose: The objective of our meta-analysis is to investigate the association of neutrophil lymphocyte ratio (NLR) for ACS risk and the prognostic utility of NLR in ACS patients.

Method:
We conducted a systematic literature search on various databases such as PubMed, Cochrane and Scopus to identify the relevant articles published until October 2021. Data extracted were pooled using odds ratios (OR) for incidence of ACS and non- ACS patients between high and low NLR. For studies that did not provide these estimates, data were extracted using weighted mean difference (WMD) of NLR for ACS and non-ACS patients. A random effects model was used to conduct this MA. The receiver operating characteristic (ROC) curve was utilized to analyze the prognostic ability of NLR in the ACS patients. Heterogeneity was evaluate using Cochran's Q- and the I 2 − test. GRADE was used to assess the study's quality. The presence of publication bias was evaluated by Egger's test and by visual inspection of the symmetry in funnel plots. Data analysis was conducted using Stata.

Results:
Nine studies met the inclusion criteria with more than 5215 participants. The MA that used OR as effect size was 1.44 (95% CI:1.082–1.92) with low heterogeneity (Chi- square = 6.2; P-value = 0,0012 I2 = 12.8%). The analyze that used WMD as effect size was 1.24 (95% CI: 1.04- 1.43) with high heterogeneity (Chi-square = 102.7; P-value < 0.001 I2 = 95.1%). There was no evidence of publication bias from Egger's test for OR effect size MA and for WMD MA (coefficient = 0.58; P-value = 0.558) and (coefficient = 3.06; P-value = 0.361). The ROC curve shows that AUC (ACS) = 88.8% (95% CI:0.73 – 1). The best cut- off point of the N/L was 4, with a sensitivity of 82.8 % and a specificity of 77.7 %

Conclusion:
The MA that used OR as effect size indicated high NLR was significantly associated with increased risk of ACS. The analyze that used WMD as effect size indicated mean NLR was significantly higher in ACS patients than in non-ACS patients. ROC curve analysis was significant for NLR in diagnosing ACS. Therefore, our results conclude that the NLR effect was strongest on ACS outcome and might also help in early diagnosis of ACS and all this make NLR a predictive biomarker in ACS patient .
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.