bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-BPC12-8: ASSOCIATION OF URIC ACID WITH BLOOD PRESSURE LEVEL IN ESSENTIAL HYPERTENSION: DIFFERENCES ACCORDING TO DIPPING PATTERN OF NOCTURNAL BLOOD PRESSURE
Authors: Koike Tsutomu , Tomoda Fumihiro , Ohara Maiko , Yamazaki Hidenori , Kinugawa Koichiro
Published: January 2023

Objective:

In essential hypertensive patients, independent of the degree of hypertension, a non-dipping blood pressure pattern is a risk factor for the development of cardiovascular diseases. Serum uric acid level was demonstrated to be an independent predictor of developing hypertension. The increase of uric acid promotes oxidative stress and inflammation, which then enhances endothelial dysfunction. In this study, the association of serum uric acid with 24 hour average blood pressure level was investigated from differences in patterns of circadian blood pressure in patients with essential hypertensive patients.

Design and method:

In 154 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), 24 hour ambulatory blood pressure monitoring and blood sampling were performed. In blood samples, biochemical parameters including highly sensitive CRP (hsCRP) and nitric oxide metabolites (NOx) were measured. Non-dipper status was defined as a decrease in nocturnal systolic blood pressure < 10 %. The patients were divided into two groups according to their nocturnal systolic blood pressure status: 56 patients with non-dipper status and 98 patients with dipper status.

Results:

24 hour systolic blood pressure was higher in the non-dipper patients than in the dipper group (148 ± 17 vs 139 ± 16 mmHg, p < 0.001), whereas diastolic blood pressure and pulse rate did not differ between the two groups. The non-dipper group was characterized by increased serum uric acid and hsCRP and decreased plasma NOx level compared with the dipper group (6.0 ± 1.7 mg/dL, 0.10 ± 0.15 mg/dL, 41.4 ± 25.3 μmol/L in the non-dipper group vs 5.5 ± 1.5, 0.07 ± 0.11, 50.1 ± 31.3 in the dipper group, p < 0.05, respectively). 24 hour systolic blood pressure correlated positively with serum uric acid and hsCRP and negatively with plasma NOx in the non-dipper group (r = 0.25, 0.32, -0.25, p < 0.05, respectively), but did not so in the dipper group. Furthermore, in the non-dipper group, multiple regression analysis revealed that serum uric acid was an independent determinant for 24 hour systolic blood pressure level together with hsCRP, and plasma NOx (R2 0.25, p < 0.01).

Conclusions:

These data indicate that the elevation of serum uric acid could associate with persistently elevated blood pressure accompanied with micro-inflammation and vascular endothelial dysfunction in essential hypertensive patients with an attenuated nocturnal blood pressure dipping.
PS-BPP01-5: ASSOCIATION BETWEEN LENGTH OF DAILY SIESTA AND BRACHIAL-ANKLE PULSE WAVE VELOCITY (BAPWV): A COMMUNITY-BASED CROSS SECTIONAL STUDY IN NORTH CHINA
Authors: Zhao Xiaolei , Hu Aihua , Cai Qiujing , Dong Liguang , Wang Shuyi , Liu Lisheng , Zhang Xinmin , Wang Chenglong
Published: January 2023

Background:

To date, many studies have proved the association between siesta and cardiovascular events. As the baPWV can assess the degree of atherosclerosis and the arterial stiffness, little is known about the association between siesta and baPWV levels. Thus we used a cross-sectional study to examine the association between siesta and baPWV levels.

Methods:

The baseline examination of 6,566 participants aged > 35 years included interviews, physical examinations, laboratory tests, and electron beam computed tomography. We compared the baseline data in 3 categories of siesta habits: irregular or no siestas; daily short siestas (1 hour or less); and daily long siestas (> 1 hour). Logistic regression models and multiple linear regression were applied to find the association between siesta and baPWV.

Results:

Among all participants, the different siesta groups have a significant difference of the prevalence of several AS degrees (P < 0.001). We also found a similar result in male or female (male P < 0.001, female P < 0.001). Daily long siestas had positive associations with prevalence of several cardiovascular risk factors and measures of subclinical atherosclerosis. Results from model3 (fully adjusted model) showed that long siesta (> 60 min, OR = 1.18, 95%CI: 1.06–1.31, P = 0.002) was associated with more severe level of the baPWV. For age or gender stratification, we found significant differences between non-siesta and > 60 min siesta groups from model3. Multiple linear regression analysis showed a positive relationship be¬tween siesta duration and baPWV (b; = 0.197, P = 0.038).

Conclusions:

Long siesta was associated with increased risk of atherosclerosis. These findings warrant further examination with prospective studies and laboratory investigations.
PS-BPP01-6: IMPACT OF THE DEGREE OF HYPERTENSION ON SUBCLINICAL CORONARY ATHEROSCLEROSIS IN ASYMPTOMATIC INDIVIDUALS
Authors: Park Gyung-Min , Kim Yong-Giun
Published: January 2023

Objective:

This study sought to evaluate the association between degree of hypertension and subclinical coronary atherosclerosis

Design and method:

We analyzed 9,459 asymptomatic individuals (mean age 53.8 ± 8.0 years; 6,126 [64.8%] men) with no prior history of coronary artery disease (CAD) who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. The classification of hypertension was adapted from the American College of Cardiology/American Heart Association 2017 guideline. The degree of subclinical coronary atherosclerosis was evaluated by CCTA, and classified into normal coronary arteries, non-obstructive CAD (diameter stenosis < 50%), and obstructive CAD (diameter stenosis > = 50%).

Results:

Subjects were classified into 4 groups: normal (systolic blood pressure [SBP] < 120 mm Hg and diastolic blood pressure [DBP] < 80 mm Hg; n = 2,944), elevated (SBP 120–129 mm Hg and DBP < 80 mm Hg; n = 1,237), stage 1 hypertension (SBP 130–139 mm Hg or DBP 80–89 mm Hg; n = 3,827), and stage 2 hypertension (SBP > = 140 mm Hg or DBP > = 90 mm Hg; n = 1,451). After adjustment for cardiovascular risk factors, the stage 1 hypertension group was significantly associated with non-obstructive CAD (adjusted odds ratio [aOR] 1.384; 95% confidence interval [CI], 1.223–1.567; P < 0.001). Furthermore, the stage 2 hypertension group had a significant association with both non-obstructive CAD (aOR, 1.433; 95% CI, 1.227–1.675; P < 0.001) and obstructive CAD (aOR, 1.463; 95% CI, 1.110–1.928; P = 0.007).

Conclusions:

In this large cross-sectional study, the degree of hypertension was associated with increased risk and severity of subclinical coronary atherosclerosis. These findings suggest the importance for control of blood pressure in asymptomatic individuals.
PS-BPP02-1: EFFECTS OF INCREASED ARTERIAL STIFFNESS ON HEMODYNAMIC RESPONSE DURING AND AFTER SUBMAXIMAL STEP EXERCISE TEST IN MIDDLE-AGED NORMOTENSIVE INDIVIDUALS
Authors: Miyai Nobuyuki , Zhan Yan , Sakaguchi Masato , Terada Kazufumi , Mure Kanae , Utsumi Miyoko , Miyashita Kazuhisa , Arita Mikio
Published: January 2023

Objective:

This study was designed to examine the effects of increased arterial stiffness on hemodynamic response during and after simple step exercise test in middle-aged normotensive individuals.

Design and method:

The study participants consisted of 819 untreated normotensive individuals (aged 54.8 years; 39.6% men) without a history of cardiovascular disease, stroke, and renal disease. The participants underwent a submaximal step exercise test (25 steps/min for 2 min). Brachial arterial blood pressure (BP) and pulse rate were measured at 1-min interval before, during, and after the step exercise test. During the end of exercise (exercise SBP) and 2 min after exercise (recovery SBP) were evaluated. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness using an oscillometric device.

Results:

The mean values of resting SBP, exercise SBP, and recovery SBP were 121 ± 12 mmHg, 153 ± 17 mmHg, and 130 ± 14 mmHg, respectively. The individuals with increased baPWV (> = 1400 cm/s, n = 305) showed significantly higher exercise SBP and recovery SBP than those with normal baPWV (Exercise, 162 ± 16 mmHg vs. 148 ± 16 mmHg, P < 0.001; Recovery, 138 ± 13 mmHg vs. 125 ± 13 mmHg, P < 0.001). The odds ratios for an exaggerated exercise SBP (> = 180 mmHg) and delayed recovery SBP (> = 150 mmHg) in individuals with increased baPWV were 2.7 (95%CI, 1.8–4.9; P = 0.001) and 3.3 (95%CI, 1.8–6.2; P < 0.001) after adjusting for age, gender, body mass index, and resting SBP. When participants were divided according to a combination of exercise SBP and recovery SBP, the baPWV of the subgroup with exaggerated exercise SBP and delayed SBP recovery was higher than that of those with only exaggerated exercise SBP and delayed SBP recovery (Both, 1585 ± 301 cm/s; Exercise, 1505 ± 232 cm/s; Recovery, 1475 ± 160 cm/s).

Conclusion:

Exaggerated BP increase and delayed BP recovery during submaximal step exercise test are associated with increased arterial stiffness in normotensive individuals. Subclinical vascular impairment may influence vascular reactivity to a greater degree than basal tone and could be identified by an abnormal BP response to exercise even before clinical manifestation of hypertension.
PS-BPP02-2: BLOOD PRESSURE VARIABILITY PREDICTS THE DEVELOPMENT OF HYPERTENSION IN NORMOTENSIVE INDIVIDUALS
Authors: Takase Hiroyuki , Machii Masashi , Hayashi Kazusa , Kin Fumihiko , Nakano Suguru , Takayama Shin , Sugiura Tomonori , Dohi Yasuaki
Published: January 2023

Objective:

Hypertension is one of the important risk factors for atherosclerosis leading to cardiovascular diseases. Although several factors have been reported as predictors of new onset of hypertension, the association of blood pressure (BP) variability in normotensive subjects with future development of hypertension is not intensively discussed. We tested the hypothesis that the yearly variability of BP in normotensive subjects predicts new onset of hypertension.

Design and Methods:

Subjects who participated in our annual physical check-up program for 5 years in a row during 2008 and 2013 were screened (screening period) and those under antihypertensive medication or with the average BP for the 5 visits ≧ 140/90 mmHg were excluded. The rest of 2006 participants (male = 1287) were eligible in the present study. Standard deviation (SD) and coefficient of variation (CV) of their systolic BP (SBP) during the 5 consecutive visits were calculated (screening period) and, then, they were followed up for the next 5 years (follow-up period). The onset of hypertension was defined as average BP during the follow-up period ≧ 140/90 mmHg or the use of antihypertensive medications.

Results:

The average, SD, and CV of SBP were 118.7 ± 10.0 mmHg, 7.44 ± 2.98 mmHg, and 6.30 ± 2.54%, respectively. During the follow-up, hypertension developed in 259 subjects, with the incidence being more frequent in male (n = 180, 14.0%) than female subjects (n = 79, 11.0%). In retrospective analysis, the average (128.7 ± 7.7 vs. 117.2 ± 9.5 mmHg, p < 0.001) and SD (8.05 ± 3.48 vs. 7.34 ± 2.89 mmHg, p < 0.001) were higher in subjects with than without future hypertension, whereas CV was not different in the both groups (6.28 ± 2.73 vs. 6.30 ± 2.51%). Non-adjusted odds ratio (OR) (95% confidence interval [CI]) of average, SD and CV for the incident hypertension were 1.169 (1.146–1.193), 1.078 (1.034–1.124) and 0.997 (0.947–1.050), respectively. Multivariate logistic regression analysis adjusted for age, gender, family history of hypertension, frequent alcohol consumption (six or seven times per week), current smoking, body mass index, heart rate, serum creatinine, fasting plasma glucose, LDL-cholesterol, and triglyceride at baseline demonstrated that average (OR [95%CI] = 1.193 [1.138–1.187]) and SD (1.058 [1.014–1.105]), but not CV (0.992 [0.941–1.046]), were associated with new onset hypertension. Similar results were obtained using diastolic BP (data not shown).

Conclusions:

In normotensive subjects, an increase in year-to-year variability as well as average of SBP may be a predictor of the new onset of hypertension. Careful interpretation of year-to-year BP variability is necessary for evaluation of future cardiovascular risk in normotensive individuals.
PS-BPP03-4: METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE (MAFLD) PREDICTS NEW ONSET OF CHRONIC KIDNEY DISEASE BETTER THAN DOES FATTY LIVER OR NAFLD
Authors: Tanaka Marenao , Mori Kazuma , Takahashi Satoko , Higashiura Yukimura , Ohnishi Hirofumi , Hanawa Nagisa , Furuhashi Masato
Published: January 2023

Background:

Possible associations of chronic kidney disease (CKD) with fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) have recently been focused on. Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic abnormalities, has been proposed as a new feature of chronic liver disease. However, the relationship between MAFLD and new onset of CKD has not been fully addressed.

Methods:

We investigated the associations of FL, NAFLD and MAFLD with the development of CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 or positive for urinary protein, over a 10-year period in 28,890 Japanese subjects who received annual health examinations. After exclusion of subjects with no data for abdominal ultrasonography and subjects with CKD at baseline, a total of 13,159 subjects (men/women: 8,581/4,578, mean age: 48 years) were recruited.

Results:

The prevalences of FL, NAFLD and MAFLD were 34.6% (men/women: 45.1%/15.1%), 32.8% (men/women: 42.7%/14.5%) and 32.3% (men/women: 42.4%/13.4%), respectively. During the 10-year follow-up period, 2,163 subjects (men/women: 1,475/688) had new onset of CKD. Multivariable Cox proportional hazard model analyses showed that MAFLD (hazard ratio [95% confidence interval]: 1.12 [1.02–1.26], p = 0.027), but not FL or NAFLD, was an independent risk factor for new onset of CKD after adjustment of age, sex, eGFR, current smoking habit, ischemic heart disease, diabetes mellitus, overweight/obesity, hypertension and dyslipidemia. The addition of MAFLD (continuous net reclassification improvement [NRI]: 0.154, integrated discrimination improvement [IDI]: 0.0024) to traditional risk factors without metabolic abnormalities significantly improved the discriminatory capacity better than did the addition of FL (NRI: 0.138, IDI: 0.0018) or NAFLD (NRI: 0.132, IDI: 0.0017).

Conclusions:

MAFLD is independently associated with new onset of CKD and predicts the risk for development of CKD better than does FL or NAFLD.
PS-BPP04-6: DIASTOLIC BLOOD PRESSURE LEVELS AND CARDIOVASCULAR EVENTS: THE JAPAN EPIDEMIOLOGY COLLABORATION ON OCCUPATIONAL HEALTH STUDY
Authors: Kuwahara Keisuke , Ohkubo Takayoshi , Inoue Yosuke , Kabe Isamu , Dohi Seitaro , Mizoue Tetsuya
Published: January 2023

Objective:

In Japan, data are sparse as to the association of diastolic blood pressure (DBP) within the elevated blood pressure range (i.e., DBP of 80 to 89 mm Hg) with risk of cardiovascular diseases (CVD) in young to middle-aged adults. We examined this association by using prospective data collected in the Japan Epidemiology Collaboration on Occupational Health (JECOH) Study.

Methods:

Participants were 81,876 workers (67,150 men and 14,636 women, aged 20 to 64 years) without taking antihypertensive medication who underwent periodic health checkup in 2011 or 2010 (baseline). Blood pressures categories at baseline were used as exposure. Data on fatal and non-fatal cardiovascular events (ICD10: I21 to I25, I46, I48 to I50, I60 to I69, I71 to I72) that occurred between April 2012 and March 2021 were retrieved from a within-study registry. Multivariable-adjusted hazard ratios according to DBP levels were calculated using Cox regression.

Results:

Over the 9 years of follow-up (0.5 million person years), 319 cardiovascular events (hemorrhage or ischemic stroke [ICD10: I60/I63], 177 cases; myocardial infarction [ICD10: I21], 77 cases) including 74 cardiovascular deaths were documented. Higher levels of DBP were associated with increased risk of cardiovascular events. As compared with DBP of < 80 mm Hg, multivariable adjusted hazard ratios (95% confidence intervals) of cardiovascular events were 1.58 (1.12, 2.22), 2.25 (1.75, 2.91), 2.85 (1.97, 4.11), 2.89 (1.52, 5.48), and 5.60 (2.52, 12.42) for DBP of 80 to 84, 85 to 89, 90 to 99, 100 to 109, and ≧ 110 mm Hg, respectively (P value for trend < 0.001). Risk of CVD mortality was also increased, albeit not significantly, at DBP of 80 to 84 and 85 to 89 mm Hg (19% and 59% increase, respectively).

Conclusion:

The present data from JECOH Study showed that DBP of 80 to 84 mm Hg was associated with a significantly higher risk of cardiovascular events. Our results support the blood pressure classification in the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH2019) for CVD prevention.
PS-BPP06-1: ESTIMATION OF SALT INTAKE AND REMOVAL IN HEMODIALYSIS PATIENTS
Authors: Ishii Takeo , Hagiwara Yasuhiro , Tagawa Hitoshi , Arimura Yoshiriro , Wakui Hiromichi , Matsuyama Yutaka , Tamura Kouichi , Oyama Kunio
Published: January 2023

Background:

Measurement of salt intake is difficult in dialysis patients, and prognosis analysis is insufficient. Recent studies have also reported that excessive salt intake leads to muscle wasting by activating the urea cycle. Hence, the removal of sodium via electrical force may lead to a favorable outcome by preventing urea cycle activation, thereby preserving tissue nutritional status, and avoiding tissue inflammation.

Subject method:

A cohort of 6,883 maintenance dialysis patients was followed up for 3 years. The salt intake removal (SALT i/r) was estimated, using the formula previously reported by Watson and Ramdeen, and was classified into five groups. Statistical analysis: Cox hazard analysis, cubic spline curve for outcomes, and generalized estimation equation (GEE) were used.

Results:

A total of 1,209 deaths were reported. The average baseline value of SALT i/r was 7.74 g. In the multivariate Cox hazard analysis, SALT i/r showed no correlation with all cause mortality but had significant correlation with CVD events; hazard ratio (HR) 1.02 (95% CI: 1.005 1.036). The cubic spline curves indicated that SALT i/r levels above 6.0 g decreased the risk of all cause mortality but increased the risk for CVD events and heart failure. GEE analysis suggested that baseline SALT i/r values correlated positively with time dependent serum creatinine (Cr) and CGR%. Additionally, SALT i/r values from the previous month also correlated positively with current serum Cr and CGR%.

Discussion:

Although a Kaplan Meier curve indicated that lower baseline salt intake caused more deaths, this may be attributed to age or malnutrition. Multivariate Cox hazard analysis showed that salt intake does not predict all cause mortality but has a positive correlation with new onset heart failure. We also described the nonlinear relationship between salt intake and risk of all cause mortality/CVD events by using cubic spline curves. This suggested that salt intake above 6 g decreased the risk of all cause mortality while increasing the risk of CVD events. In GEE, there was a significant correlation between previously measured high SALT i/r and current increase in muscle mass. Thus, we hypothesize that salt removal by dialysis without involvement of the urea cycle causally leads to muscle preservation.

Conclusion:

In this large cohort, estimated SALT i/r had a significant correlation with prognosis. We found that salt retention induces heart failure in dialysis patients. However, salt removal by dialysis may causally preserve tissue nutritional status.
PS-BPP06-5: PREVALENCE AND DETERMINANTS OF HYPERTENSION AMONG ADULTS: A CROSS SECTIONAL SURVEY OF ONE TRIBAL AREA IN BANGLADESH
Authors: Majumder Abdullah Al Shafi , Ghosh Rajib , Reza Md Alimur
Published: January 2023

Introduction:

The prevalence of hypertension gradually has become a serious public health threat globally as it is a very pertinent risk factor for non communicable diseases. The prevalence of non communicable diseases is not well known in tribal areas of Bangladesh. Lifestyle and food habits are quite different from majority of population living in plain lands (recognized as Bengali). Though data are available regarding the latter, data on the tribal population is scanty. Purpose: This study was aimed to assess the prevalence and risk factors of hypertension in a tribal area in Bangladesh.

Materials and Methods:

We conducted a cross sectional study of 637 men and women aged 18 years or more located in Rowangchhari THC of Bandarban, a hilly district of Bangladesh. We collected data on demographics, behavioral factors, physical measurements and health history. Data collection was done using a pretested questionnaire and clinical examination. Prevalence and 95% confidence interval were estimated for hypertension. SPSS version 25.0 was used. A value of P less than 0.05 was considered statistically significant.

Results:

Among all 637 participants, 52% patients were male and mean age was 35.4 plus/minus 13.4 years. Almost 78% participants were from different tribal community (e.g. Marma, Tonchonga, Bom, Tripura, Chakma etc.). Hypertension prevalence was 28.9% (95% CI 25.4 to 32.6) and was significantly higher among male than female (33.1% vs 24.3%; p value is 0.014). The highest prevalence of hypertension was observed among aged 60 years or more at 41.3%. Hypertension was higher among Bengali (33.6%) than tribal population (28.1%), but not statistically significant. Determinants of hypertension included male gender, older age, higher income, nature of job, increasing body mass index and waist circumference. More than 85% of the participants has knowledge of harmful effect of Hypertension (86.9%) and smoking (91.2%).

Conclusion:

Our study suggests that the prevalence of hypertension is significant among the population living in tribal area. Specific interventions should be developed to inform adults of the necessary lifestyle changes and the importance of early screening, awareness campaigns for early health seeking and improvement in health access.
PS-BPR01-9: A CASE OF CYCLIC CUSHING'S SYNDROME DIAGNOSED WITH HYPERTENSION AND LEG EDEMA
Authors: Hayakawa Eri , Tomino Yuki , Chonabayashi Minami , Sugiyama Toru
Published: January 2023

Background:

Cushing's syndrome (CS) is associated with hypertension in approximately 80% of cases, which contributes to the increased mortality risk. Few cases of intermittent hypertension due to cyclic CS(CCS) have been reported. Case presentation: A 66-year-old woman with no specific medical history was referred to our hospital for evaluation of hypertension and leg edema. The Cardiovascular examination showed no abnormality in her cardiac function. Laboratory findings revealed hypokalemia, hyperglycemia, and metabolic alkalosis. She was tentatively initiated on calcium channel blocker (CCB) and insulin therapy. The endocrine examination revealed elevated ACTH and cortisol without circadian variation, which responded to neither the 8 mg dexamethasone suppression test nor CRH stimulation, leading to the diagnosis of ACTH-dependent CS. CT, FDG/PET CT, and Octreotide scan showed no obvious lesion other than bilateral adrenal enlargement. Enhanced MRI showed a normal pituitary gland with neither adenoma nor pituitary stalk deviation/tilt. Since the etiology of CS was not confirmed, metyrapone administration was initiated as symptomatic treatment. Her serum ACTH and cortisol fell rapidly after the initiation of metyrapone, and her blood pressure (BP) and blood glucose levels improved accordingly, even without the use of CCB and insulin. Since both ACTH and cortisol became normalized after discharge, metyrapone was tapered off after 4 months. Furthermore, CT showed normalization of the adrenal enlargement. For the next two months, her ACTH and cortisol remained within the normal limits, and her BP, serum potassium and blood glucose were well controlled. However, she visited our hospital because of re-elevated BP thereafter and was found to have re-elevated ACTH and cortisol with bilateral adrenal enlargement as well as re-decreased serum potassium. Since her BP and serum potassium levels were not controlled well even after she resumed taking metyrapone, the dose of metyrapone was increased, spironolactone was added, and CCB was resumed. Another two months later, her ACTH and cortisol normalized without metyrapone again, and her BP was well-controlled accordingly. This cyclical course of ACTH/cortisol elevation strongly suggested CCS. Conclusion: CCS is a clinical syndrome that exhibits a periodic or irregular increasing pattern in cortisol, which is a rare type of CS. Confirmation of CCS diagnosis is only possible during periods of relapse. In the present case, elevated BP was an indicator of hormonal fluctuations that could be appropriately treated. We report here a case of CCS that was diagnosed because of a good correlation between BP and hormone levels.
PS-BPR02-7: SACUBITRIL VALSARTAN FOR REFRACTORY HYPERTENSION CAUSED BY PRIMARY ALDOSTERONISM: A CASE SERIES
Authors: Yamashita Tomohisa , Akazawa Chikako , Osanami Arata , Yano Toshiyuki , Saito Shigeyuki
Published: January 2023

Introduction:

Primary aldosteronism (PA) is the disease characterized by inappropriately elevated autonomous adrenal aldosterone secretion, leading to the development of refractory hypertension. Patients with PA show higher nighttime blood pressure (BP) and lower nocturnal BP decline than those with essential hypertension. Angiotensin receptor neprilysin inhibitors (ARNIs) are a new class of cardiovascular agents characterized by their dual action on the renin angiotensin system and the natriuretic peptide system. Atrial natriuretic peptide has been shown to inhibit basal aldosterone secretion from adrenal cells in vitro.

Case Presentation:

A man in his 50 s was referred to our hospital due to vision loss and diagnosed with hypertensive retinopathy. His serum potassium level was below 3.5 mEq/L. A captopril test confirmed the diagnosis of PA, though a CT image revealed no adrenal adenoma. According to his discretion, medical treatment including a mineralocorticoid receptor antagonist, a calcium channel blocker, an angiotensin receptor blocker (ARB), an angiotensin converting enzyme inhibitor (ACEI), an alpha blocker and a beta blocker, were commenced. However, the result of ambulatory bloop pressure monitoring (ABPM) revealed his mean BP of 143/91 mmHg and his mean nighttime BP of 148/89 mmHg, indicating riser pattern. Switching from an ACEI, imidapril (10 mg per day), and an ARB, azilsartan (40 mg per day), to sacubitril/valsartan (200 mg per day) decreased his mean BP to 138/89 mmHg. Furthermore, his mean nighttime BP decreased to 122/79 mmHg, indicating that his nocturnal hypertension was improved by sacubitril/valsartan. Similar favorable effects of Sacubitril/valsartan on BP were found in three other patients with refractory hypertension caused by PA.

Discussion:

ARNIs are an appropriate treatment option for refractory hypertension caused by PA.
PS-B05-6: FABRY DISEASE MOUSE IS RESISTANT TO HIGH-SALT DIET-INDUCED HYPERTENSION PROBABLY VIA DYSFUNCTIONAL SODIUM TRANSPORTS AND AQUAPORIN 2
Authors: Chung Sungjin , Son Mina , Park Junkyu , Jo Wonji , Koh Eun Sil
Published: January 2023

Background:

Fabry disease is a rare X-linked lysosomal storage disorder resulting from an error in glycosphingolipid metabolism caused by the GLA gene mutation. Patients with Fabry disease often have near normal or even low systemic blood pressure although the mechanism underlying such observed finding remains unexplained. This study examined whether a high salt intake could affect transport of sodium and water and induce hypertension in mice with Fabry disease.

Methods:

Fabry disease model mice (B6;129-Glatm1Kul/J) and wild-type (WT) mice received 8% or normal NaCl salt diet for 2 weeks.

Results:

A high-salt diet for 2 weeks generated higher blood pressure in WT mice but not in Fabry disease mice. Free water clearance (FWC) and electrolyte free water clearance (EFWC) in groups fed with a high salt diet were lower than those in groups fed with a normal salt diet. Both high salt-fed WT and Fabry disease mice had decreased gamma-subunit of epithelial Na channel (ENaC) compared with normal salt-fed groups. In Fabry disease mice fed a high-salt diet, there was an decrease in renal expressions of Na+/H+ exchanger isoform 3 (NHE3) and Na+-Cl- cotransporter (NCC) compared with WT mice fed a high-salt diet. Although renal expression of vasopressin V2 receptor (V2R) was upregulated in Fabry mice fed with a high salt diet, renal aquaporin 2 (AQP2) level failed to increase up to the level in WT mice fed with a high salt diet.

Conclusion:

These findings suggest that the decreased expression of NHE3 and NCC and impaired response of AQP2 in kidneys of Fabry disease to a salt load could be one of mechanisms by which Fabry disease could have resistance to the development of hypertension.
PS-B05-10: DIABETES MELLITUS AGGRAVATES BEHAVIORAL DEFICIT AND INCREASES SITE-SPECIFIC PHOSPHORYLATION OF TAU PROTEIN IN ALZHEIMER'S DISEASE MOUSE MODEL
Authors: Ito Yuki , Takeda Shuko , Nakajima Tsuneo , Oyama Akane , Takeshita Hikari , Miki Kunihiro , Takami Yoichi , Takeya Yasushi , Shimamura Munehisa , Rakugi Hiromi , Morishita Ryuichi
Published: January 2023

Objective:

Numerous epidemiological studies have demonstrated that vascular risk factors including diabetes mellitus (DM) increase the risk of developing Alzheimer's disease (AD). However, the mechanisms underlying the pathological relationship between DM and AD remain largely unknown. Tau is a microtubule-associated protein that is predominantly expressed in the axons of neurons. More than 80 residues of tau can be potentially phosphorylated. Accumulation of hyperphosphorylated tau protein plays a role in neurodegeneration and cognitive impairment in patients with AD. Here, we developed a unique diabetic AD mouse model and analyzed behavioral phenotypes and biochemical changes occurring in the brain to investigate the impact of DM on tau pathology.

Design and method:

Tau-tg and WT mice were fed with either normal chow diet (NCD; 12% kcal fat, n = 9) or high-fat diet (HFD; 60% kcal fat, n = 10) from the age of one and a half to nine months. Metabolic parameters and behavioral phenotypes were assessed at eight months of age. Mice were then sacrificed at nine months of age and brains were analyzed histologically and biochemically. A quantitative proteomic analysis of protein phosphorylation was performed using brain extracts of tau-tg mice.

Results:

Tau-tg mice fed with HFD (HFD tau-tg) showed severe obesity and hyperinsulinemia compared with tau-tg mice fed with NCD (NCD tau-tg) (p < 0.01), with slight elevation of plasma glucose levels. HFD tau-tg showed exacerbation of motor impairments and decrement of habituation to novel environment. Histological analysis showed a significant decrease in the number of neurons in HFD tau-tg compared to NCD tau-tg. The amount of aggregated form of phospho-tau (Ser396) was increased in HFD tau-tg brain. Comprehensive phosphoproteomic analysis identified 11 phosphosites of tau significantly hyperphosphorylated in the brain of HFD tau-tg (p < 0.05).

Conclusions:

These results suggest that diabetic conditions such as obesity and hyperinsulinemia with minimal hyperglycemia exacerbate behavioral deficits in AD via hyperphosphorylation of tau protein. We identified specific phosphosites of tau involved in pathological relationship between DM and AD.
PS-B06-4: ADENINE NEPHROPATHY IS ALLEVIATED BY ANTI-INFLAMMATORY PROPERTY OF SODIUM BENZOATE
Authors: Oshima Yoichi , Wakino Shu , Kanda Takeshi , Tajima Takaya , Itoh Tomoaki , Uchiyama Kiyotaka , Yoshimoto Keiko , Sasabe Jumpei , Itoh Hiroshi
Published: January 2023

Background:

D-amino acid oxidase (DAO), a molecule distributed in brain, liver, and kidney in human, oxidases d-amino acids to alpha-keto acids to produce hydrogen peroxides. Sodium benzoate (SB), a known DAO enzyme inhibitor, has anti-inflammatory property, although its effect has not been investigated in chronic kidney disease (CKD).

Methods:

Adenine induced CKD (AdCKD) or 2,8-dihydroxyadenine (2,8-DHA) nephropathy is applied for rodent CKD studies. AdCKD was induced by oral administration of adenine in C57BL/6JJcl mice with or without SB oral administration. AdCKD was also induced in DAO enzyme deficient mice (DAO-/-) and treated with or without SB. Human THP-1 cells and macrophages induced from THP-1 cells by phorbol 12-myristate 13-acetate were stimulated by LPS or TNF-alpha with or without SB to confirm the anti-inflammatory effect of SB.

Results:

AdCKD showed increased serum creatinine and urea nitrogen levels as well as kidney interstitial fibrosis and tubular atrophy score, which were significantly attenuated by the treatment of SB. Survival of AdCKD mice were significantly prolonged by 2.6-fold by SB administration. SB significantly decreased elevated kidney positive F4/80 immunohistochemistry area and renal mRNA level of macrophage markers and inflammatory markers of AdCKD. Human THP-1 cells and macrophages stimulated either by LPS or human TNF-alpha showed increased inflammatory gene mRNA expressions, which were significantly reduced by SB treatment.

Conclusions:

SB significantly ameliorated renal damage in AdCKD by suppressing inflammatory gene expressions and macrophage infiltration.
PS-B06-11: GLUCAGON-LIKE PEPTIDE-1 SUPPRESSES ACTIVATED EFFECTOR MEMORY T CELL SUBSETS IN THE FATTY LIVER INDUCED BY ANTI-CD3-ADNTIBODY ADMINISTRATION IN LEAN MICE
Authors: Itoh Arata , Yuki Kazunari , Irie Junichiro , Itoh Hiroshi
Published: January 2023

Objective:

We previously invented a disease-model of hepatosteatosis, glucose tolerance and hyperlipidemia, typically observed in non-alcoholic fatty liver disease with metabolic syndrome, but without obesity, through activation of CD4-positive lymphocytes by anti-CD3 antibody administration in lean mice. We also showed that this model is CD4 T-cell dependent and glucagon-like-protein-1 receptor agonist reduces cytokine production in the liver with amelioration of fatty liver, hyperglycemia and hyperglycemia in this model. The precise mechanisms, however, remains unclear. We investigated how GLP-1RA targets and suppresses T cells.

Design and Method:

GLP-1R expression on activated T cell subsets in the liver and spleen was analyzed using flow-cytometry one day after administration of anti-CD3 antibody in the female lean Balb/c mice. Purified splenic CD4 T cells were differentiated into Th1, Th2, Th17 or regulatory T cells in-vitro and glp1r gene expression and GLP-1R protein expression were analyzed with real-time PCR and flow-cytometry, respectively.

Results:

anti-CD3 antibodies significantly increased GLP-1R+ CD62L- CD44+ effector-memory CD4 and CD8 T cells in the liver and GLP-1RA protected from increasing number of those CD4 and CD8 T cells in the liver in vivo. Activated and in-vitro induced Th1, Th2, Th17 and regulatory T cell subsets expresses express GLP-1R.

Conclusions:

GLP-1RA targets activated/effector-memory T cell subsets and reduces their proliferation and cytokine production.
PS-B07-5: EXERCISE TRAINING UPREGULATES FATTY ACID B;-OXIDATION WITH INCREASING PGC-1A AND PPARA IN THE KIDNEY OF DAHL SALT-SENSITIVE RATS
Authors: Takahashi Asako Namai , Takahashi Junta , Xu Lusi , Miura Takahiro , Kohzuki Masahiro , Ito Osamu
Published: January 2023

Objective:

Exercise training (Ex) has anti-hypertensive and renal protective effects. Fatty acid metabolism in the kidney is involved in renal damage. In this study, we investigated the effects of the Ex on blood pressure, renal damages, and fatty acid metabolism in Dahl salt-sensitive rats.

Design and method:

Six-week-old male Dahl salt-sensitive rats were divided into three groups: 1) normal salt diet (NS); 2) high salt diet (HS); 3) HS+Ex. NS or HS groups were fed diet containing 0.6% or 8% NaCl. Treadmill running was performed in HS+Ex group for 8 weeks (5 days/week; 60 min/day at 16–20 m/min, 0% grade). Systolic blood pressure (SBP) was monitored by tail-cuff method. Renal function, histology and the expression of enzymes and regulators for fatty acid metabolism were then assessed.

Results:

HS significantly elevated SBP, and Ex did not change SBP. HS significantly decreased creatinine clearance, and Ex significantly ameliorated creatinine clearance. HS significantly increased urinary protein excretion, and Ex significantly suppressed urinary protein excretion. HS induced glomerular sclerosis, and Ex suppressed them. HS decreased the renal expression of enzymes for fatty acid β;-oxidation including carnitine palmitoyltransferase type I (CPTI) and very long, medium and short-chain acyl-CoA dehydrogenases (CADs) and their transcription factors; peroxisome proliferator-activated receptor α (PPARα) and PPARγ-coactivator-1α (PGC-1α). Ex increased the renal expression of CPTI, CADs, PPARα and PGC-1α.

Conclusions:

Ex improves HS-induced renal damage with fatty acid β;-oxidation with increasing PPARα and PGC-1α in Dahl salt-sensitive rats in a systolic blood pressure-independent manner. These results suggest that Ex may have beneficial effects in HS-induced renal damage.
PS-B07-10: SUPEROXIDE DISMUTASE PROFILE OF LIVER TISSUE IN HYPERURICEMIA RATS AFTER DAILY CONSUMPTION OF COFFEE
Authors: Alfaruqy Maulida Abdillah , Ahsani Dwi Nur , Sudiarto Hilmi Ardian , Yosanto Alfian Novanda
Published: January 2023

Background:

The elevation of serum uric acid may cause metabolic syndrome and increase systemic inflammation also oxidative stress which are the risk factors for liver disease. Recently, coffee as the most popular drink worldwide could promote antioxidant activity due to some anti-inflammatory effects of some polyphenolic compounds such as cafestol, kahweol, and diterpenes. This study aimed to analyze the profile of liver tissue superoxide dismutase (SOD) in hyperuricemia rats after daily consumption of coffee.

Method:

Four groups, each consisting of 6 rats (Rattus norvegicus), respectively were observed as 1) negative control group; 2) positive control group; 3) caffeinated coffee group; 4) decaffeinated coffee group. Hyperuricemia was conditioned by administering high purine intake into the 2nd until 4th group as much as 140 mg/200gr of weight. Coffee, which is caffeinated and decaffeinated was given to the third and the fourth group respectively with doses 144 mg/200gr of weight. SOD of liver tissue was measured after 30 days of treatment.

Result:

In hyperuricemia rats, daily consumption of coffee shows higher liver SOD levels compared to a positive control group. The average (+SD) of liver SOD each group respectively 79.51(+3.06); 32.24(+3.53); 53.28(+4.49); and 68.03(+4.72). Numeric comparative hypothetic test using one-way ANOVA shows the difference mean between each group was statistically significant (95%CI; p < 0.05).

Conclusion:

Daily consumption of both caffeinated and decaffeinated coffee may reduce oxidative stress in liver tissue of hyperuricemia rats.
PS-B08-3: DILATED CARDIOMYOPATHY MOUSE MODEL AGGRAVATES ACUTE KIDNEY INJURY
Authors: Ishimura Takuya , Ishii Akira , Yamada Hiroyuki , Nakagawa Yasuaki , Ohno Shoko , Ikushima Akie , Sugioka Sayaka , Handa Takaya , Kuwahara Koichiro , Yanagita Motoko , Yokoi Hideki
Published: January 2023

Objective:

The relation between cardiac and renal diseases is well known, and the concept of the cardio-renal syndrome has attracted much attention in recent years. However, the molecular mechanism of the cardio-renal syndrome is still unclear. In this study, we used αMHC-dominant negative Neuron-Restrictive Silencer Factor (NRSF) transgenic mice (Tg mice), a mouse model of dilated cardiomyopathy with gradually worsening ejection fraction, to elucidate the pathogenesis of acute kidney injury in the setting of chronic heart failure.

Design and Methods:

Sixteen-week-old Tg and wild-type mice were subjected to unilateral nephrectomy and 45-minute ischemia reperfusion injury (IRI) to the remaining kidney, and then the kidneys and hearts were retrieved 72 hours later. The control group were subjected to unilateral nephrectomy without IRI.

Results:

Heart weights were significantly heavier in Tg mice in both control and IRI-treated groups. In the control group, serum creatinine and blood urea nitrogen were unchanged between wild-type and Tg mice. However, serum creatinine and blood urea nitrogen were significantly elevated in Tg mice compared to wild-type mice in the IRI-treated group, and only IRI-treated Tg mice died within 72 hours after IRI (6/14). Furthermore, mRNA expression of Ccl2 and Lcn2 (NGAL) in the whole kidney was significantly elevated in IRI-treated wild-type mice, and was more upregulated in Tg mice. Periodic acid-Schiff staining showed that tubular injuries, such as dilation of tubules, cast formation and tubular atrophy, were exacerbated in IRI-treated Tg mice. In microarray analysis of IRI-treated kidneys from wild-type and Tg mice, several candidate genes were upregulated in Tg mice.

Conclusions:

In dilated cardiomyopathy model mouse, inflammation and histological changes were aggravated after IRI, suggesting that chronic heart failure augments renal impairment in acute kidney injury.
PS-C17-1: PERIPHERAL MICROVASCULAR DYSFUNCTION IN SUBJECTS WITH TYPE2 DIABETES(T2DM) IN ACCORDANCE WITH ABSENCE OR PRESENCE OF CORONARY ARTERY DISEASE.
Authors: Ueda Tomohiro , Teragawa Hiroki , Oshita Chikage , Fujii Yuichi , Nomura Shuichi
Published: January 2023

Background:

Several studies demonstrated that endothelial function is impaired in patients with T2DM, but no study evaluated vascular parameters in patients with T2DM trough a combined analysis of macro and micro-endothelial function and arterial stiffness indexes. In addition, the difference in vascular parameters between T2DM patients with CAD and without CAD remains unknown. We assessed whether coronary artery disease is associated with impairment of peripheral endothelial function and arterial stiffness indexes in patients with T2DM.

Methods:

We measured vascular function in 219 T2DM subjects (age 68 ± 10 years), including 147 subjects with CAD (CAD group) and 72 subjects without CAD (control group).

Flow mediated vasodilatation (FMD) indicating endothelial function in a conduit artery was measured by ultrasound using a semi-automatic device: UNEXEF18G (UNEX Co. Nagoya, Japan). Reactive hyperemia index (RHI) indicating peripheral endothelial function and Augmentation index (AI) indicating arterial stiffness were measured by peripheral arterial tonometry (EndoPAT 2000). Vascular function tests were measured on the same day.

Results:

RHI and AI was significantly impaired in CAD group (RHI: 2.0 ± 0.7 vs.1.7 ± 0.5 P = 0.012, AI: 30.2 ± 18.1 vs.22.1 ± 19.1 P = 0.043), however FMD had no deference in the two groups. Logistic regression analysis revealed that RHI (odds ratio: 0.44, 95% confidence interval: 0.21–0.94) was an independent predictor for CAD in subjects with T2DM.

Conclusions:

RHI, an acknowledged marker of microcirculatory endothelial function was a more sensitive method in evaluating the risk assessment of CAD in subjects with T2DM.
PS-C17-2: STUDY OF THE ANTIHYPERTENSIVE EFFECTS OF ORAL SEMAGLUTIDE, GLP 1 RECEPTOR AGONIST
Authors: Meguro Shu , Itoh Hiroshi
Published: January 2023

Objective:

Semaglutide, a GLP1 receptor agonist for diabetes mellitus, has been reported to not only improve blood glucose and body weight, but also to lower blood pressure. In this study, we investigated the effects of oral semaglutide on blood pressure.

Methods:

We compared blood pressure, body weight, and HbA1c before, one month after, and three months after semaglutide administration in patients with type 2 diabetes mellitus attending the first author's outpatient clinic who were started on the oral formulation of semaglutide. We selected the patients for study who were administrated oral semaglutide formulations as new additions to previous therapy or conversions from other oral diabetes medications, and those converted from injectable GLP1 receptor agonists were excluded.

Results:

Baseline clinical characteristics of the subjects were 12 (10 men, 2 women), age 57.9 ± 9.8 years, weight 94.9 ± 16.1 kg, blood pressure 147.9 ± 14.3/84.3 ± 6.0 mmHg, HbA1c 7.4 ± 0.6%. Systolic blood pressure was 138.5 ± 11.8 mmHg for 1 month after treatment and 136.6 ± 9.3 mmHg for 3 months after treatment, showing a significant decrease compared to before treatment (p < 0.05). On the other hand, HbA1c and body weight significantly decreased (p < 0.05) to 6.9 ± 0.9% and 92.2 ± 16.6 kg, respectively, after 3 months of treatment, but no significant change was observed after 1 month of treatment. No significant correlation was observed among the changes in HbA1c and body weight and systolic blood pressure at 1 and 3 months.

Conclusions:

Significant reductions in HbA1c, body weight, and systolic blood pressure were observed with the oral formulation of the GLP1 receptor agonist semaglutide. The decrease in systolic blood pressure was preceded by a decrease in HbA1c and body weight.
PS-C17-7: PREVALENCE OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 1 AND TYPE 2 DIABETES MELLITUS AT AMANG RODRIGUEZ MEMORIAL MEDICAL CENTER
Authors: De Guzman Ronnel Vergara
Published: January 2023

Introduction:

Diabetes Mellitus is a global public health challenge with a high epidemiological and economic burden. Its progression may be delayed with correct medications and lifestyle modification. One of the most common microvascular complication and one of the leading causes of preventable blindness is Diabetic Retinopathy.

Methodology:

A descriptive, retrospective, analytical study design was used. All diabetic patients of ARMMC in the OPD from January 2017 to June 2021 were included in this study. All 18-year-old and above with type 1 or type 2 diabetes mellitus and diabetic retinopathy that are seen in ARMMC OPD were included. Excluded are those who have vision loss caused by diseases other than diabetic retinopathy. Charts were reviewed and 107 charts are qualified for the study. All statistical tests will be two tailed test. STATA 13.1 will be used for data analysis.

Results:

Majority of patients are between 47 and 59 years old. Mean age of patients is 53 years old with standard deviation of 11.28. Median is 55 years of age, meaning half of patients are below 55 years old. Almost half of the participants are female with duration diabetes mellitus of more than 5 years, however on review of participants chart, 39.25% had no duration of illness written in the chart. Most of the partici pants are using oral hypoglycemic agents. The result shows the significant associations were found between the duration, insulin use, oral hypoglycemic agent use, and the diabetic retinopathy. The p-values are all 0.00 which are less than 0.05 level of significance.

Conclusion:

This study yielded a prevalence of 1.6% for patients diagnosed with diabetic retinopathy. Majority of diabetic retinopathy patients has type 2 diabetes mellitus with at least 5 years of duration. Most of them are using oral hypoglycemic agents for the main treatment for the diabetes. Age and sex are not associated with diabetic retinopathy.