bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-B02-14: DISCOVERY OF A NEW DRUG FOR PRIMARY ALDOSTERONISM TARGETING THE CYP11B2 AND KCNJ5 MUTANTS
Authors: Otsubo Yuri , Shimada Hiroki , Nakamura Yasuhiro , Yokoyama Atsushi , Sugawara Akira 
Published: January 2023

Primary aldosteronism (PA) is a common cause of secondary hypertension. PA induces damage to cardiovascular and renal blood vessels. Therefore, PA is regarded as a problem because it increases the risk of stroke, cardiomyopathy, kidney disease, etc. Aldosterone-producing adenomas (APA) are one of the major causes of PA, and gene mutations are often identified in tumor cells. KCNJ5 mutation is well known as a gene mutation that causes the loss of ion selectivity in APA. KCNJ5 is an inwardly rectifying potassium channel. KCNJ5 induces sodium ion influx due to mutations in APA. The sodium ion influx induces depolarization, and which overexpresses CYP11B2. CYP11B2 is the rate-determining enzyme for aldosterone synthesis, overexpression of CYP11B2 induces aldosterone overproduction.
Examples of therapeutic drugs for PA and APA include calcium channel blockers, aldosterone antagonist and β;-blockers. However, therapeutic drugs for PA and APA targeting cell membrane depolarization have not been developed yet. We aim to find compounds that suppress CYP11B2 expression by membrane depolarization to develop novel therapeutic drugs for PA and APA. By developing a therapeutic drug that targets depolarization, we hope to establish an effective therapeutic method for APA caused by gene mutations such as KCNJ5 mutation. We performed high-throughput screening (HTS) using Tohoku University Compound Library (6080 compounds). First, we generated H295R-CYP11B2 N-Luc cells in which the luciferase gene is inserted downstream of the CYP11B2 locus. The cells H295R-CYP11B2 N-Luc were stimulated with KCl to cause depolarization, after which candidate compounds were added and HTS was performed by Luc assay. As a result, 101 compounds were selected. Furthermore, 25 of 101 compounds were selected by examining the cytotoxicity and dose response.
Also, 11 of the 25 compounds suppressed CYP11B2 mRNA expression in KCl stimulated H295R cells. Secondary, we generated KCNJ5 mutant cells that expressed the KCNJ5 mutant (L168R) in a Doxycycline-inducible manner. 3 of 11 compounds that suppressed the expression of CYP11B2 mRNA were selected by examination using KCNJ5 mutant cells. After that, 2 of 3 compounds decreased the aldosterone production.
These compounds have a different structure from existing therapeutic drugs such as calcium channel blockers. Since these can be novel therapeutic drugs for PA and APA caused by depolarization such as KCNJ5, we are examing the detailed mechanism of action of the compounds. In addition, we would like to further experiment the effects of the compounds in vivo using hypertensive model mice, Task1 /Task3 double KO mice.
PS-C01-3: ACCURACY OF THE AKTIIA BRACELET IN THE ELDERLY IN DIFFERENT BODY POSITIONS
Authors: Theiler Kenji , Sola Josep , Alexandre Jeremy , Vermare Pascale , Durgnat Virginie , Wuerzner Gregoire 
Published: January 2023

Objective:
Accurate blood pressure (BP) measurement is essential for the correct diagnosis and management of hypertension (HTN) especially in the elderly population, which has the highest prevalence of HTN. Recently cuffless devices have been developed with the hope of facilitating blood pressure measurement. However, validation studies of cuffless are scarce and a universally accepted validation protocol has yet to be published. The objective of the second arm of this study (NCT04027777) was to test the accuracy of the Aktiia bracelet in an elderly population cohort in different body positions.

Design and method:
We recruited 40 patients aged from 65 to 85 years with different blood pressure categories and without diabetes. BP measures from Aktiia Bracelet were compared to reference double auscultatory measurement in various body positions: sitting, standing and lying (including after aerobic physical activity in supine position) on four separate visits distributed over one month.

Results:
The average participant's age was 73 ± 6 years with 52.5% female participants. A total of 469 comparison measurements were made, with an overall acceptance rate of 79% (percentage of optical recordings with sufficient quality to be analyzed by the cuffless device). Five participants were excluded either due to failed initialization or to ensure a distribution of blood pressure categories compliant to the requirements of ISO 81060-2. After initialization procedures on day 1, we observed means and standard deviations of differences for systolic BP of 1.23 ± 7.88 mmHg in sitting position, -1.81 ± 11.11 mmHg in the standing and -1.8 ± 9.96 mmHg in the lying position (including after aerobic exercise). Differences for diastolic BP were 0.2 ± 5.55 mmHg, -5.35 ± 7.75 mmHg and -0.94 ± 7.47 mmHg respectively. The acceptance rate for each position was 86%, 69% and 75% respectively. When considering all possible body positions representative of a realistic use of the device, and along the entire monitoring period of one month, systolic and diastolic BP differences were -0.26 ± 9.96 mmHg and -0.75 ± 7.0 mmHg respectively. Figure 1 illustrates the Bland-Altman plots for SBP and DBP for the sitting position.

Conclusions:
This study demonstrates that the Aktiia bracelet can accurately estimate the BP in an elderly population in the sitting position (according to the requirements of ISO 81060-2) and in other body positions representative of a realistic use of the device. The use of more comfortable, non-invasive and non-occlusive BP monitoring may contribute to better diagnosis and treatment of hypertension in the elderly through patient empowerment.
PS-C01-11: ARTERIAL STIFFNESS AND SOCIOECONOMIC STATUS
Authors: Deng Peizhi 
Published: January 2023

Objective:
No study has been examined to synthesize the association between scores composed of multiple indicators and arterial stiffness (AS). We aim to explore whether the socioeconomic scores can influence the AS in a large ongoing cohort.

Design and method:
We analyzed data from the UK Biobank, which prospectively followed up 502,413 participants ranging from 40 to 69 years of age from 2006 to 2010. Education score, income score, and Town send deprivation index were defined as three socioeconomic variables. Arterial stiffness index (ASI) was measured noninvasively from the pulse waveform. Linear regression models were developed to examine associations of socioeconomic background with AS. Restricted cubic spline RCS models were developed to examine dose response relationships. In addition, we also examined effect modifications by sex, age and body mass index.

Results:
This cross sectional study used a target sample of 149,781 UK Biobank participants aged more than 40 years. After full adjustments, in reference to the lowest education score, income score, and Town send deprivation index quartile, those in the highest were associated with higher ASI (beta = 0.306 m/s, 95% CI: 0.253 to 0.359; beta = 0.163 m/s, 95% CI: 0.106 to 0.220; beta = 0.070 m/s, 95% CI: 0.017 to 0.123, respectively). The positive association between 3 socioeconomic scores and ASI was more pronounced among lean and younger adults, and women were more associated with AS in the highest income score quartile.

Conclusion:
Socioeconomic score was associated with an increased prevalence of arterial stiffness, which are influenced by age, sex, and body mass index. Our findings indicate that special attention can be paid to the composite indicators from the evaluation of socioeconomic status in order to prevent the underlying arterial stiffness.
PS-C01-15: EFFECTIVENESS OF MOBILE APP-ASSISTED INTERVENTIONS FOR IMPROVING SALT RELATED BEHAVIOR IN HYPERTENSIVE PATIENTS
Authors: Kim Yong-Jae , Kim Hyun-Sook , Lim Yu-Jin , Park Jong-Ho , Jo Sang-Ho , Kim Eung-Gyu , Kim Eun-Mi , Lee Seung Hee , Kim Won-Ho 
Published: January 2023

Objective:
Current evidence supports that an increased intake of dietary salt was related to an increased prevalence of cardiovascular diseases. Interventions to reduce salt intake are essential to reduce hypertension and its disease burden. The use of mobile health care is becoming increasingly popular in the self-care of chronic diseases such as hypertension.

Design and method:
This study is an open-label intervention study that aims to assess the effect of a mobile application specifically designed to aid in lowering the dietary salt. Participants will be asked to answer a questionnaire regarding their behaviors about salt-related dietary management and knowledge about the control of hypertension. Primary outcomes focus on feasibility measures of implementation and acceptability of the interventions. Secondary outcomes will include changes in blood pressure, dietary salt intake and hypertension-related behaviors. Sodium intake was estimated with the spot urine sodium content using the Kawasaki equation. User instructions for the mobile applications provides sodium content and calories for the dietary intake records made by the participants.

Results:
Preliminary data from 50 subjects are as follows. Hypertension management behaviors of the subjects changed significantly in all categories. The total score of Confidence changed from 11.67 ± 2.94 points to 12.73 ± 2.25 (p < 0.001), Knowledge from 13.23 ± 2.08 to 14.02 ± 2.32 (p < 0.05), Action from 35.08 ± 7.03 to 39.12 ± 5.85 (p < 001), and Diet from 6.07 ± 2.13 to 7.87 ± 2.26 (p < 001). Significant changes were observed in the BP. The systolic BP decreased from 134.09 ± 11.34 mmHg to 127.27 ± 10.87 mmHg (p < 0.001), and diastolic BP decreased from 80.81 ± 8.19 mmHg to 77.97 ± 8.96(p < 0.05).

Conclusion:
This trial is currently enrolling patients. To date, 226 patients have been enrolled, surpassing the pre-calculated sample size of 220. Results will be available in the winter of 2022. This trial tests the efficacy of dietary intervention through a novel mobile app. If effective, this mobile app based intervention could reduce the health burden of hypertension.
PS-C02-5: HYPERTENSION IS NOT A PREDICTOR OF ATRIAL FIBROSIS IN PATIENTS WITH ATRIAL FIBRILLATION - EVIDENCE FROM ATRIAL BIOPSY
Authors: Takahashi Yuya , Yamaguchi Takanori , Otsubo Toyokazu , Nakashima Kana , Shinzato Kodai , Osako Ryosuke , Shichida Shigeki , Node Koichi 
Published: January 2023

Objective:
Hypertension is considered to promote atrial fibrosis and contribute to the development of atrial fibrillation. The purpose of this study is to investigate the effect of arterial hypertension on atrial fibrosis in patients with atrial fibrillation (AF).

Design and method:
We examined 234 patients (67 ± 12 years old, 72 female genders, 145 non-paroxysmal AF type) who underwent right atrial septum biopsy under the guidance of intracardiac echocardiography and fluoroscopy (Figure A) during catheter ablation for AF. The extent of histological fibrosis (%Fibrosis) was quantified using digital imaging platform based on the Masson trichrome staining (Figure B). Clinical factors possibly associated with %Fibrosis were evaluated using simple and multiple linear regression analysis.

Results:
A total of 132 patients had hypertension. The mean %fibrosis was 7 ± 4% (range 1–20%). There was no significant difference of %Fibrosis in patients with and without hypertension (Figure C). Univariate analyses identified age, female gender, smaller body surface area (BSA), decreased eGFR, non-paroxysmal AF type, larger left atrial volume/BSA, and higher E/e were associated with increase in %Fibrosis. Multivariate analysis showed that only non-paroxysmal AF type and left atrial volume/BSA were identified as significant clinical factors associated with %Fibrosis (Figure D).

Conclusions:
Our data suggest that hypertension is not an independent predictor of atrial histological fibrosis in patients with AF. The mechanism of atrial fibrosis would not be directly related to arterial hypertension contrary to previous hypotheses.
PS-C02-7: ANALYSIS OF ELECTROLYTE CHARACTERISTICS IN PATIENTS WITH PRIMARY ALDOSTERONISM COMPLICATED WITH ARRHYTHMIA
Authors: Long Zhang you , Liang Wei , Wang Ming ming , Chen Rong xin , Si Ni dan , Yu Jing 
Published: January 2023

Background:
primary aldosteronism is important for electrolyte balance in addition to its direct cardiovascular effects. High aldosterone can aggravate electrolyte disorder, resulting in low potassium, low calcium, high sodium, low phosphorus and so on. Electrolyte balance is the basis of maintaining normal electrophysiological activity of cells. Electrolyte disturbance can affect cardiac electrical activity, and then may induce a series of arrhythmias, increase cardiovascular burden, hospitalization rate and mortality rate.

Objective:
To study the electrolyte characteristics of arrhythmia in patients with primary aldosteronism.

Methods:
A retrospective study was performed on 287 patients diagnosed with primary aldosteronism who were admitted to the Department of Cardiology, Second Clinical Hospital of Lanzhou University from January 2018 to May 2021, and they were divided into arrhythmia group (n = 137 cases) and non-arrhythmia group (n = 150 cases) according to whether they had arrhythmia. The electrolyte characteristics of the two groups were compared.

Results:
There were no significant differences in age, gender, basal blood pressure, activity of sitorenin, blood sodium, blood calcium, blood magnesium and blood phosphorus between the two groups (P > 0.05). Compared with the group without arrhythmia, serum potassium in the group with arrhythmia was lower(P < 0.05)., the sitting plasma aldosterone and body mass index (BMI) were higher (P < 0.05), and the detection rate of hypokalemia was higher in patients with arrhythmia (P < 0.0)5). Speatman correlation analysis showed that there was a positive correlation between sitting aldosterone and BMI (R = 0.311, P < 0.05), and a negative correlation between sitting aldosterone and potassium (R = -0.253, P < 0.05).

Conclusion:
Hypokalemia is the characteristic of electrolytes in patients with arrhythmia. In the electrolysis disorder caused by increased aldosterone, hypokalemia is more likely to induce arrhythmia. In addition, patients with primary aldosteronism with higher BMI are more likely to develop arrhythmias, and there may be a certain correlation between BMI and blood potassium, which needs further demonstration.
PS-C02-10: IMPACT OF SARCOPENIA AND ATRIAL FIBRILLATION ON THE INCIDENCE OF HEART FAILURE IN ELDERLY PATIENTS
Authors: Tani Akihiro , Soeki Takeshi , Ozaki Yuji , Aihara Ken-ichi , Sata Masataka 
Published: January 2023

Objective:
Sarcopenia is an age-dependent skeletal muscle disorder that is associated with multiple adverse outcomes including cardiovascular events. Sarcopenia can influence the outcomes of patients with heart failure, myocardial infarctions, and atrial fibrillation (AF). This study aimed to clarify the clinical significance of sarcopenia in the incidence of heart failure in elderly individuals.

Design and method:
A total of 118 elderly participants with cardiovascular risk factors (mean age 76.7 years old) were included in the study. The body composition including the skeletal muscle mass index (SMI), body fat percentage, ratio of extracellular water to the total body water (ECW/TBW), and phase angle were measured using a multifrequency bioelectrical impedance analysis (BIA). Sarcopenia was defined according to the criteria of the Asian Working Group, which involves a low grip strength or slow gait speed and low SMI. Heart failure (HF) was defined according to the Framingham criteria. Statistical associations between those BIA-related parameters and the incidence of HF were evaluated by multiple logistic regression analysis. The threshold for a statistical significance was set at p < 0.05.

Result:
Sarcopenia was observed in 33 subjects (28.0%) and AF was observed in 29 (25.4%) of 118 participants. The ECW/TBW, which reflected cellular edema, was higher in patients with HF than in those without whereas the body fat percentage and phase angle did not differ between the patients with and without HF. Although AF was associated with the incidence of HF and sarcopenia was not associated with it, concomitant sarcopenia and AF, was associated with the incidence of HF than sarcopenia or AF alone. A multiple logistic regression analysis showed that AF accompanied with sarcopenia and ECW/TBW were significantly and positively associated with the incidence of HF independently of the age, gender, and other cardiovascular risk factors.

Conclusion:
In the present study, AF complicated with sarcopenia and cellular edema increased the incidence of HF in elderly individuals with cardiovascular risk factors. The obtained results suggested that the management of sarcopenia and cellular edema is a critical problem for the prevention of HF in elderly patients with AF.
PS-C02-11: ASSOCIATION BETWEEN BROAD P WAVE AND ECHOCARDIOGRAPHIC FINDINGS ON 12-LEAD ECG IN HYPERTENSIVE PATIENTS
Authors: Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi 
Published: January 2023

Background:
Broad P waves have been shown to be associated with the development of atrial fibrillation and cardiovascular events. The relationship between broad P waves, left atrial and left ventricular findings assessed by echocardiography is unclear in hypertensive patients.

Methods:
We enrolled 3952 hypertensive patients in the Coupling study. P waves were measured by 12-lead electrocardiogram and defined broad P as P waves with a maximum P wave width ≧ 140 ms. Left atrial diameter (N = 436) and left ventricular mass index (LVMI, N = 736) were measured by echocardiography. LVH was defined as any LV mass 115 g/m2 in men and 95 g/m2 in women.

Results:
The Broad P group (N = 296) had more men and more history of heart failure than the control group (N = 3656) (men: 71 vs. 49%, p < 0.001; heart failure: 11 vs. 3%, p < 0.001). Office blood pressure levels did not differ significantly in both groups (systolic blood pressure: 136.3 ± 16.6 vs. 134.9 ± 16.2 mmHg, p = 0.15, diastolic blood pressure76.7 ± 10.7 vs. 77.0 ± 10.6 mmHg, p = 0.65). Left atrial diameter (LAD) and LVMI were greater in the broad P group than those in control group (LAD: 39.1 ± 6.3 vs. 35.3 ± 5.4 mm, p < 0.001, LVMI 116 ± 34 vs. 97 ± 22 g/m2, p < 0.001). After adjusting for age and sex, broad P was an independent determinant of LVH (odds ratio 3.40, 95% CI 1.91–6.04, p < 0.001).

Conclusions:
Broad P waves in hypertensive patients were independently associated with left ventricular hypertrophy and left atrial diameter.
PS-C04-7: REPRODUCIBILITY OF CAROTID TONOMETER AND FEMORAL CUFF-BASED PULSE WAVE VELOCITY: INTERACTION WITH OPERATOR SKILL
Authors: Cox James R , Tan Isabella , Avolio Alberto P , Butlin Mark 
Published: January 2023

Objective:
Large artery stiffness is strongly correlated with cardiovascular outcomes. The stiffness of the artery can be measured non-invasively using carotid-femoral pulse wave velocity (cfPWV). Originally cfPWV assessment was performed by ECG-gated applanation tonometry at the carotid and femoral site. High quality applanation tonometry is a learned skill. To increase ease of use, many commercial devices now use a pneumatic cuff for femoral pulse acquisition but still retain tonometry-based carotid pulse acquisition. Lack of clinical uptake of cfPWV may be due to perceived poor repeatability, especially where a learned skill is required. This study aimed to quantify how many measurements a skilled and unskilled operator are required to take to obtain an acceptable cfPWV measurement.

Design and method:
Supine cfPWV measurements (SphygmoCor XCEL, AtCor, Sydney) was measured in healthy participants (n = 15, age 30 ± 15 years, 12 female) by both an inexperienced and experienced operator 10 times in each participant. True cfPWV was taken as the average of twenty cfPWV measurements (regression to the mean). The time required to perform the cfPWV assessment by an experienced operator was additionally recorded in a separate set of participants referred to the clinic. Data analysis was performed using regression analysis and Bland-Altman plots.

Results:
The first cfPWV measurement made by both operators (experienced and inexperienced) resided within ± 0.36 m/s (cut off for a 10% increased risk of cardiovascular events) of the true cfPWV in 87% (n = 13) of individuals. The average of the first two cfPWV measurements fell within ± 0.36 m/s of true cfPWV for all participants for the experienced operator and 93% of participants for the inexperienced operator (Figure). Distance measurements were not significantly different between operators (p = 0.14). The total time required to perform a full cfPWV assessment (one distance measurement and two cfPWV measurements), on average, was 238 ± 79 seconds (3 minutes and 58 seconds).

Conclusion:
Irrespective of operator experience an accurate measurement of cfPWV can be obtained by averaging two measurements. These results suggest that cfPWV measurement error should not necessarily be a contributing factor to the limited clinical uptake of cfPWV. The measurement does take considerable time, and this may be a barrier of uptake, along with perceived clinical applicability of arterial stiffness measurement.
PS-C05-1: INCIDENCE OF VERY REDUCED LEFT VENTRICULAR EJECTION FRACTION DURING LONG-TERM FOLLOW-UP AFTER ACUTE MYOCARDIAL INFARCTION: IMPACT FOR MID-TERM OUTCOMES
Authors: Yoshioka Goro , Tanaka Atsuhi , Taguri Akina , Natsuaki Masahiro , Shibata Yoshisato , Node Koichi 
Published: January 2023

Background:
For survivors of myocardial infarction (MI), very reduced left ventricular ejection fraction (LVEF) in acute-phase (within hospitalization) occurred about 5% of patients and that was well known as risk factor of cardiac death. Therefore, very reduced LVEF was one of the criteria for Implantable cardioverter defibrillator. However, the very reduced LVEF in chronic-phase were received limited study.

Method:
We evaluated 2241 consecutive patients with acute MI who received follow-up echocardiography at chronic-phase (after 6-month). Primary outcome was incidence of very reduced LVEF at chronic-phase. Very reduced LVEF was defined LVEF (modified simpson) < 35%. Secondary outcome was cardiac death.

Result:
During follow up (median 1471 days), very reduced LVEF occurred 9.7% patient. As shown in Kaplan-meier curve, very reduced LVEF occurred 9.3% of patients per 10-year. According to figure, these patients revealed high rate of cardiac death. Even if LVEF at acute-phase exceeded 35%, cardiac death rate of these patients was 9.7%.

Conclusions:
Very reduced LVEF at chronic-phase occurred 9.3% per 10-year in MI survivors. Regardless of LVEF at acute-phase, very reduced LVEF at chronic-phase associated with cardiac death.