bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-BPP02-7: DEFINING THE OPTIMAL CUT-OFF POINTS OF BLOOD PRESSURE COMPONENTS TO PREDICT THE PROGRESSION OF CHRONIC KIDNEY DISEASE IN TOYOOKA CITY
Authors: Kishimoto Ichiro
Published: January 2023

Objective:

Early control of blood pressure is critical to delaying the progression of chronic kidney disease (CKD) and preventing future cardiovascular events and mortality. The primary objective of the study is to assess the optimal cut-off points of blood pressure components for predicting the worsening of proteinuria or renal function.

Design and method:

Retrospective longitudinal data from 2013–2017 specific health surveys among participants of National Health Insurance in Toyooka City were analyzed (n = 5,169 at baseline). Association of blood pressure at baseline and worsening of dip-stick proteinuria or estimated glomerular filtration rate (eGFR) during follow-up were determined with Cox proportional hazard analysis. The optimal cut-off points were determined with time-dependent receiver operating characteristic curves (ROC).

Results:

Survival analysis revealed that worsening of proteinuria during follow-up was significantly associated with baseline systolic and diastolic blood pressure levels independently of age, gender, or HbA1c levels. Time-dependent ROC curves for detecting worsening of proteinuria during follow-up revealed that the optimal cut-off points of systolic and diastolic blood pressure were 126 mmHg (sensitivity 0.62, specificity 0.45) and 81 mmHg (sensitivity 0.38, specificity 0.70), respectively. When the whole population was categorized with the systolic blood pressure levels of < 126, 126–139, or > = 140 mmHg, the age, gender, and HbA1c-adjusted risks for worsening proteinuria in the highest and intermediate systolic blood pressure groups were 1.5-fold (p = 0.002) and 1.3-fold (p = 0.014) higher than that in the lowest group, respectively. In addition, the risks for more than a 15%-decrease in eGFR during follow-up in the highest and intermediate groups were 2.0-fold (p < 0.001) and 1.6-fold (p = 0.009) higher than that in the lowest group, respectively. When the whole population was categorized with the diastolic blood pressure levels of < 81, 81–89, or > = 90 mmHg, the risks for worsening proteinuria in the highest and intermediate diastolic blood pressure groups were 1.5-fold (p = 0.004) and 1.2-fold (p = 0.056) higher than that in the lowest group, respectively. Furthermore, the time-dependent ROC curve for detecting more than a 15%-decrease in eGFR during follow-up revealed that the optimal cut-off point of pulse pressure was 52 mmHg (sensitivity 0.48, specificity 0.58). In subjects with a baseline pulse pressure of > = 52 mmHg, the adjusted odds ratio for detecting more than a 15%-decrease in eGFR during follow-up was 1.5-fold higher than in those with a baseline pulse pressure of < 52 mmHg (p = 0.005).

Conclusions:

Data from specific health surveys revealed regional blood pressure-related risks associated with worsening of CKD among participants of National Health Insurance.
PS-BPP03-1: PREDICTIVE ABILITY FOR NEW-ONSET CHRONIC KIDNEY DISEASES BY MACHINE LEARNING ALGORITHM USING HEALTH CHECKUP DATA
Authors: Kawasoe Shin , Kubozono Takuro , Ojima Satoko , Kawabata Takeko , Salim Anwar Armed , Ikeda Yoshiyuki , Miyahara Hironori , Tokushige Koichi , Ohishi Mitsuru
Published: January 2023

Background:

In Japan, many data on relatively healthy individuals exist because specific health checkups are conducted annually for individuals aged 40 and older for the purpose of early detection and intervention of lifestyle-related diseases. Efforts to effectively utilize these data to predict the future development of chronic kidney disease (CKD) are important from the perspective of improving prognosis and quality of life, as well as healthcare economics.

Aim:

We aimed to evaluate the predictive ability of machine learning algorithms for newly developed CKD using health checkup data.

Methods:

We included individuals aged 30–69 years who had a health checkups between April 2008 and March 2018 with baseline (year X) and 5-year (year X + 5) data. CKD was defined as < 60 ml/min/1.73m2, and those with hypertension in year X were excluded. Three different machine learning algorithms, including Random Forest, Logistic Regression, and Neural Network, were evaluated to predict the development of new-onset CKD at year X + 5 from baseline (year X) data, and the AUCs of the ROC curve were used to assess the predictive ability of the models. Explanatory variables included physical measurements, blood pressure and pulse rate, laboratory values, lifestyle-related indicators, and medication history.

Results:

A total of 58,418 participants (age 53.8 ± 10.2 years, male 49.9%) were included in this study. Among them, 3,997 individuals (6.8%) had newly developed hypertension in year X + 5. The indices of predictive ability were as follows: Random Forrest, AUC 0.88, accuracy 0.93, recall 0.99, precision 0.93; Logistic Regression, AUC 0.89, accuracy 0.93, recall 0.99, precision 0.94; Neural Network, AUC 0.89, accuracy 0.93, recall 0.99, precision 0.93. The variables with the highest importance features were baseline creatinine level (0.49), age (0.24), systolic blood pressure (0.07), and anti-hypertensive medication (0.06).

Conclusions:

The AUCs of the model predicting the development of CKD after 5 years ranged from 0.88 to 0.89, which were generally superior to previously reported risk models using statistical methods. Baseline creatinine levels, age, and blood pressure were found to contribute significantly to new-onset CKD.
PS-BPP03-3: CARDIOVASCULAR RISK AND METABOLIC CHARACTERIZATION OF METABOLICALLY HEALTHY OBESITY CLASSIFIED BY THE NEWLY PROPOSED DEFINITION: A PROSPECTIVE STUDY
Authors: Wei Dongmei , Marrachelli Vannina Gonzalez , Melgarejo Jesus , Liao ChiaTe , Janssens Stefan , Verhamme Peter , Monleon Daniel , Redon Josep , Aelst Lucas Van , Vanassche Thomas , Zhang ZhenYu
Published: January 2023

Objective:

The varying definition of metabolic health is responsible for the debate about whether metabolically healthy obesity (MHO) is associated with increased cardiovascular risk. An empirically derived definition of metabolic health has been newly proposed to identify individuals with obesity but without excess mortality risk. This study aimed to evaluate the association of MHO classified by the new definition with cardiovascular events and to reveal the metabolic characterization of MHO.

Design and method:

We classified 1331 Flemish people (mean age: 51.3 years; women: 50.3%) by their metabolic health status (systolic blood pressure < 130 mmHg, waist-to-hip ratio < 0.95 for women or 1.03 for men, and absence of antihypertensives and diabetes) and obesity status (body mass index > = 25 kg/m2). Plasma 44 metabolites were measured by nuclear magnetic resonance spectroscopy at baseline. Hazard ratios (HRs), odds ratios, and 95% confidence intervals (95% CI) were calculated using Cox proportional hazard regressions and logistic regressions, accounting for sex, age, sex, smoking, alcohol, and physical activity.

Results:

During 5.6 years of follow-up, 111 cardiovascular events and 33 diabetes incidents occurred. MHO was not associated with cardiovascular events (HR 1.61, 95% CI: 0.49–5.27) compared with metabolically healthy normal weight. The HRs were 3.19 (95% CI: 1.07–9.53) and 3.27 (95% CI: 1.15–9.32) for metabolically unhealthy normal weight and obesity, respectively. Individuals with metabolic health had a lower risk of diabetes (HR: 0.22, 95%CI: 0.06–0.77). Compared with metabolically unhealthy obesity, MHO was associated with eight metabolites, including six with positive association (2-aminobutyrate, 4-aminobutyrate, alanine, leucine, 4-hydroxybutyrate, and acetate) and two with negative association (valerate and lactate). Metabolites positively associated with MHO showed inverse associations with diabetes risk, while metabolites negatively associated with MHO showed positive associations with diabetes risk. The associations of these metabolites with MHO reversed their directions compared with metabolically healthy normal weight. None of the eight metabolites was associated with cardiovascular events.

Conclusion:

This new definition of metabolic health can be replicated to stratify cardiovascular risk for individuals with or without obesity. The metabolic characterization of MHO was not completely ‘healthy’, which might help to identify novel targets for intervention.
PS-BPP05-1: ASSOCIATIONS OF ENVIRONMENTAL TEMPERATURES AND HOME BLOOD PRESSURE: THE MASUDA STUDY
Authors: Kinuta Minako , Hisamatsu Takashi , Fukuda Mari , Taniguchi Kaori , Nakahata Noriko , Kanda Hideyuki
Published: January 2023

Objective:

The prevalence of elevated blood pressure (BP) remains high, with the greatest absolute burden of elevated BP particularly in the East Asian and Pacific regions. Temperature and BP are closely related; however, few studies have examined the association of out-of-office BP with indoor or outdoor temperature. The effect of the difference between indoor and outdoor temperatures on BP also remains unknown. we examined the association of indoor and outdoor temperatures, and their difference with self-measured BP at home.

Design and method:

Using 2-year data on temperature and self-measured home BP in healthy 352 participants (mean age, 49.8 years; 46.0% women) from a population-based cohort. We measured home BP and indoor temperature at the same time in the morning and evening every day. Outdoor temperature at the same time period of the home BP measurements in Masuda City was based on the national data from the Japan Meteorological Agency. A linear mixed model was used for analyzing the association between home BP and indoor or outdoor temperature as fixed effects and each participant as a random effect adjusted for age, sex, smoking status, alcohol drinking, obesity, physical activity, diabetes mellitus, and antihypertensive medication use.

Results:

We observed BP measurements of 82,900 in the morning and of 66,420 in the evening. After adjustment for age, sex, and possible confounders, indoor temperature was inversely associated with systolic and diastolic BP in the morning and evening. A 1 °C increase in the indoor temperature reduced systolic/diastolic BP by 0.37/0.22 mmHg, respectively, in the morning and 0.45/0.30 mmHg, respectively, in the evening (all P-values < 0.001). The magnitude of associations was stronger for indoor than outdoor temperature. Similarly, a 1 °C increase in the indoor temperature above outdoor temperature decreased systolic/diastolic BP by 0.33/0.12 mmHg, respectively, in the morning and 0.45/0.26 mmHg, respectively, in the evening independent of outdoor temperature (all P-values < 0.001).

Conclusions:

Our findings highlight the importance of indoor temperature for influencing home BP levels. The control of indoor temperature is considered an easy approach for the general population to tackle. It is necessary to control the rise in home BP by controlling indoor temperature in order to reduce high BP, possibly leading to reduced mortality and morbidity from CVD.
PS-BPP05-5: HIGH LEVELS OF FATTY LIVER INDEX PREDICT NEW-ONSET HYPERTENSION WITH DYSGLYCEMIA
Authors: Wu Dan , Hirata Aya , Hirata Takumi , Imai Yukiko , Kuwabara Kazuyo , Funamoto Mika , Sugiyama Daisuke , Okamura Tomonori
Published: January 2023

Objective:

To investigate whether the fatty liver index (FLI) predicts the development of hypertension in individuals with and without dysglycemia in the general Japanese population.

Design and method:

A total of 3114 participants including 1036 men and 2078 women who received specific health checkups in 2013 were observed until 2018. We defined dysglycemic as impaired fasting glucose (IFG) and diabetes mellitus. The participants were divided into 6 groups based on FLI tertile by sex and whether they had dysglycemia. The data was analyzed using the Cox proportional hazard model to calculate adjusted hazard ratios (HR) for the incident of hypertension. The model was adjusted for age, low-density lipoprotein, high-density lipoprotein, smoking and alcohol drinking, and further adjusted for systolic blood pressure (SBP) at baseline.

Results:

During a five-year follow-up period, a total of 853 of the 3114 participants had new onset hypertension. Using the low FLI group with normoglycemia as a reference, the risk of developing hypertension was significantly elevated in the high FLI group with normoglycemia, after confounders except for SBP, in male and female [HR (95% CI) male: high, 1.52 (1.06–2.17); female: high, 1.86 (1.43–2.42)], and also, in the high FLI group with dysglycemia, the risk was significantly elevated [male: low, 1.11(0.71–1.74); moderate, 1.58(1.05–2.39); high, 2.05(1.43–2.92); female: low, 1.56(0.97–2.49); moderate, 1.06(0.65–1.71); high, 2.98(2.19–4.07)]. After adjusting for SBP, the significance disappeared in high FLI with normoglycemia among male. meanwhile it remained unchanged in high FLI with normoglycemia in female and in high FLI with dysglycemia in male and female, respectively.

Conclusions:

Our study showed that FLI was independently associated with the risk of new-onset hypertension with or without dysglycemia. It suggests high FLI population, even in normoglycemia, should be managed for prevention of hypertension. The risk of developing hypertension was more pronounced in the dysglycemic population with high FLI, which may help predict subjects at high risk of developing hypertension in the dysglycemic population.
PS-BPP06-8: DIETARY SALT INTAKE PREDICTS FUTURE DEVELOPMENT OF METABOLIC SYNDROME IN THE GENERAL POPULATION
Authors: Takase Hiroyuki , Hayashi Kazusa , Kin Fumihiko , Nakano Suguru , Machii Masashi , Takayama Shin , Sugiura Tomonori , Dohi Yasuaki
Published: January 2023

Objective:

Dietary salt consumption is one of the most important modifiable factors in our lifestyle and restriction of dietary salt results in the reduction of blood pressure in previous studies. Excessive salt intake causes cardiovascular diseases independently of its effects on blood pressure. Since metabolic syndrome also increases a risk of cardiovascular disease, there may be some association between salt intake and metabolic syndrome. Therefore, we investigated a possible relationship between salt intake and future development of metabolic syndrome in the general population.

Design and Methods:

Consecutive 12,256 subjects without metabolic syndrome (male = 7,053, 52.1 ± 12.3 year-old) who visited our hospital for an annual physical check-up from April 2010 to March 2018 were enrolled. After baseline examination, subjects were followed up until March 2019 (median 1,582 days) with the endpoint being the development of metabolic syndrome. Metabolic syndrome was diagnosed according to the Japanese criteria (2005). Individual salt intake was estimated using a spot urine by a previously reported Tanaka method.

Results:

Salt intake was 8.7 ± 1.9 and 8.4 ± 1.8 g/day in male and female subjects, respectively, at baseline. During the follow-up period, 1,669 subjects developed metabolic syndrome (29.9 per 1,000 person-year) with the incidence being more frequent in male than female subjects (41.8 vs. 14.2 per 1,000 person-year). Non-adjusted hazard ratio (HR) (95% confidence interval [CI]) of salt intake for the development of metabolic syndrome was 1.192 (1.164–1.221). Kaplan-Meier analysis where subjects were divided into gender-specific quartiles according to the baseline salt intake revealed that the incidence of metabolic syndrome were increased across the quartiles (19.5, 24.2, 33.1, and 43.9 per 1,000 person-years; logrank p < 0.001). Multivariate Cox proportional hazard analysis adjusted for age, gender, body mass index, systolic blood pressure, heart rate, serum creatinine, uric acid, fasting plasma glucose, low-density lipoprotein cholesterol, triglyceride, hemoglobin and current smoking habit at baseline revealed that salt intake predicted the new onset of metabolic syndrome (HR:1.055, 95%CI:1.028–1.082).

Conclusions:

Excessive salt intake is significantly associated with the new development of metabolic syndrome in the general population. The results suggest that salt restriction prevents cardiovascular diseases through the prevention of not only hypertension but also metabolic syndrome.
PS-BPP06-9: ASSOCIATIONS BETWEEN SERUM AND DIETARY OMEGA-3 FATTY ACID AND COGNITIVE FUNCTION IN A POPULATION OF COMMUNITY-DWELLING JAPANESE. TANUSHIMARU STUDY
Authors: Fukami Ako , Adachi Hisashi , Enomoto Mika , Morikawa Nagisa , Nohara Yume , Sakaue Akiko , Yamamoto Maki , Sato Hiromi , Fukumoto Yoshihiro
Published: January 2023

Objective:

Previous studies indicate that dietary omega-3 polyunsaturated fatty acids (PUFA) are modifiable risk factors for CVD and cognitive decline. This study aimed to investigate the association between serum and dietary omega-3 PUFA and cognitive function were measured in a general population.

Design and method:

A total of 976 residents (381 males, 595 females, mean age 62.6 years) underwent a physical examination, a nutrition survey and the mini-mental state examination as an evaluation of cognitive function in 2009 and followed up in 2018.

Results:

The serum omega-3/omega-6 ratio were significantly associated with age (p < 0.0001), sex (male, p < 0.0001), MMSE (p < 0.0001), LDL-c (inversely, p < 0.01), and salt intake (p < 0.05), using by multiple stepwise regression analysis.

The dietary intake of proteins from fish (p < 0.0001), trace elements, (p < 0.01), vitamin D, B6, B12 (p < 0.0001), and salt (p < 0.0001) showed dose dependent relationships with the serum omega-3/omega-6 ratio using analysis of covariance.

Subjects were divided into 4 groups according to their progression of cognitive decline in 10 years. Serum omega-3 levels of group with normal cognitive function (NC) were significantly higher than those of group with cognitive decline (CD) (p < 0.05). However, dietary intakes of omega-3 and omega-6 PUFA were not significant. Interestingly, salt intakes in group with CD were higher than those in group with NC (p < 0.05). The logistic regression analysis revealed that salt intakes was associated with cognitive decline 10 years later after adjustments for confounding factors (odds ratio, 1.1; 95% C.I., 1.01–1.13; p = 0.01)

Conclusion:

The present study demonstrated that omega-3 PUFA may preserve a cognitive function and excessive intakes of salt may have an adverse effect on cognitive function.
PS-BPR01-2: PHEOCHROMOCYTOMA WITH HYPERALDOSTERONISM-LINKED MUTATIONS IN THE POTASSIUM CHANNEL KCNJ5
Authors: Mai Xurong , Kometani Mitsuhiro , Kato Toshiaki , Mori Shunsuke , Aono Daisuke , Konishi Seigo , Karashima Shigehiro , Takeda Yoshiyu , Yoneda Mau , Furukawa Kenji , Yoneda Takashi
Published: January 2023

Context:

Recent advances in genetic analysis techniques have led to the genetic analysis of adrenal tumors with hormone excess. In pheochromocytomas, many genetic abnormalities have been identified. Furthermore, several causative genes have been also reported in primary aldosteronism. We performed a comprehensive genetic analysis of functional adrenal tumors using next-generation sequencing. We report here a case of pheochromocytoma with KCNJ5 gene abnormality, which is considered to be specific for primary aldosteronism.

Case:

A 53-year-old woman with high blood pressure since age 48, excessive sweating and weight loss since age 52, and left ventricular hypertension noted on electrocardiogram during a medical checkup presented to her previous physician. A computed tomography scan of the abdomen showed a right adrenal tumor 30 mm in diameter, and an urinary test showed high levels of urinary metanephrine and normetanephrine (1.42 mg/day) and I-123 MIBG scintigraphy showed an accumulation at the tumor. Plasma renin activity was 0.2 ng/mL/hr, plasma aldosterone concentration was 73.9 pg/mL, and a positive captopril challenge test was performed. Adrenal scintigraphy using 131 I-adosterol showed bilateral adrenal accumulation, suggesting bilateral lesions. Laparoscopic right adrenalectomy was performed for pheochromocytoma. Histology showed focal proliferation of enlarged medullary-like cells and calcification of the adjacent adrenal tissue. The tumor tissue was positive for KCNJ5 gene mutation. A postoperative captopril challenge test was performed again, which was negative.

Conclusion:

KCNJ5 gene abnormality is considered specific for primary aldosteronism, but was also found in pheochromocytoma. However, the contribution of KCNJ5 gene abnormality to catecholamine production is not yet elucidated. This is a case of pheochromocytoma in which coexistence of primary aldosteronism is also suspected based on the captopril challenge test and imaging findings, and the finding of a gene mutation associated with primary aldosteronism in such a case is very interesting and will warrant further investigation.
PS-BPR01-5: DOPAMINE-SECRETING PHEOCHROMOCYTOMA: AN OVERLOOKED CAUSE OF INCIDENTALLY DISCOVERED ADRENAL TUMOR AND NORMAL BLOOD PRESSURE
Authors: Miyamoto Shotaro , Yoshida Yuichi , Ozeki Yoshinori , Okamoto Mitsuhiro , Gotoh Koro , Masaki Takayuki , Nishida Haruto , Shibuya Tadamasa , Shin Toshitaka , Daa Tsutomu , Mimata Hiromitsu , Kimura Noriko , Shibata Hirotaka
Published: January 2023

A 64-year-old woman with a history of chronic thyroiditis and no family history of endocrine disease was incidentally determined to have a left retroperitoneal mass on abdominal ultrasonography. A subsequent abdominal computed tomography (CT) scan revealed a 5.6 × 5.1 × 10.6 cm left adrenal tumor (10–50 Hounsfield Units of CT attenuation value), which showed marginal irregularity and an internal cystic structure [Figure 1A]. She was admitted to our hospital for further investigation of a suspected adrenocortical carcinoma. On admission, she was normotensive and had no symptoms of catecholamine excess. The 24-hour urine catecholamine level showed normal norepinephrine (122.9 ug/day), epinephrine (24.3 ug/day), whereas markedly elevated dopamine (148,212.4 ug/day). 123I-MIBG scintigraphy revealed tumor uptake. After alpha-blockade as preoperative management, she successfully underwent laparoscopic left adrenalectomy and was finally diagnosed with an exclusively dopamine-secreting pheochromocytoma. The tumor was histologically comprised of small polygonal cells with high cellularity and was immunohistochemically positive for all three catecholamine synthesizing enzymes: tyrosine hydroxylase (very weak), dopamine beta-hydroxylase (heterogeneous), and phenylethanolamine N-methyltransferase (very weak). Electron microscopy revealed very few catecholamine-containing small vesicles with a few organelles, which reflected immature cells. No biochemical or imaging evidence of recurrence or metastasis was evident 1 year after the surgery. To our knowledge, this is the first case of an exclusively dopamine-secreting pheochromocytoma in which immunostaining of catecholamine synthetic enzymes and electron microscopy of tumor tissues were performed together to identify the mechanism underlying a dopamine-secreting PPGL. The purpose of this report was to identify the mechanism underlying a dopamine-secreting pheochromocytoma from the histopathological findings. We also discuss the reasons for the lack of catecholamine excess symptoms, whether preoperative management of alpha-blockade is needed, and the association between the prognosis and genetic mutation with an extensive literature review.

JOURNAL/jhype/04.03/00004872-202301001-00862/figure1/v/2023-10-24T163949Z/r/image-jpeg
PS-BPR02-2: ECULIZUMAB FOR RESCUE OF THROMBOTIC MICROANGIOPATHY IN MALIGNANT HYPERTENSION ASSOCIATED WITH MCTD
Authors: Date Ryosuke , Kajiwara Kengo , Johno Takamitsu , Ko Takehiro , Nakamura Tomofumi , Tomita Masao , Mizumoto Teruhiko , Kakizoe Yutaka , Izumi Yuichiro , Kuwabara Takashige , Adachi Masataka , Mukoyama Masashi
Published: January 2023

Introduction:

Eculizumab is effective in atypical hemolytic uremic syndrome (aHUS) caused by complement abnormalities, but its effect on secondary thrombotic microangiopathy (TMA) is obscure. We here report a case of TMA associated with malignant hypertension, who was successfully treated with an ACE inhibitor, plasma exchange and eculizumab.

Case report:

The patient was a 40-year-old woman presenting with severe blood pressure elevation (BP 240/140 mmHg), nausea, fatigue, headache, and visual disturbances. She had a history of systematic lupus erythematosus (SLE) and had been stable by the treatment with 5 mg/day of prednisolone and 2 mg/day of tacrolimus for a long period. This time, she exhibited Raynaud's phenomenon, mild skin lesions, and heliotrope eruption on the eyelids, together with positive anti-U1-RNP antibodies. She was diagnosed with mixed connective tissue disease (MCTD), instead of SLE. Acute kidney injury (serum creatinine, 3.24 mg/dL), anemia (hemoglobin, 8.8 g/dL) and thrombocytopenia (platelets, 137,000/μL) were observed. LDH was elevated at 780 IU/L. The haptoglobin level was decreased to less than detection sensitivity and schistocytes were observed in her peripheral blood. The plasma renin activity was beyond the highest limit. On head MRI, posterior reversible encephalopathy syndrome (PRES) was suggested. A renal biopsy was performed, and a histological diagnosis of malignant hypertensive arteriolosclerosis was obtained. Based on these findings, she was diagnosed as accelerated malignant hypertension, possibly due to TMA with a background of MCTD. She was initially treated with nicardipine, enalapril and aliskiren, but this treatment failed to ameliorate the progression of kidney injury and TMA. Therefore, plasma exchange therapy was performed three days in a row, and then hemodialysis and administration of eculizumab were introduced. After weekly induction dose (900 mg once a week) was given four times, administration of 900–1200 mg of eculizumab every 2 weeks were continued. As the treatment was continued, her renal function was improved gradually. Fifteen months after her onset of AKI and TMA, the patient was withdrawn from dialysis and eculizumab therapy.

Conclusion:

A body of evidence is growing that activation of the complement system may be involved in scleroderma renal crisis. However, the efficacy of eculizumab in TMA, except for aHUS, remains controversial. Our case suggest a possible efficacy of eculizumab along with plasma exchange, as the treatment of malignant hypertension due to scleroderma that was caused by MCTD.
PS-BPR02-3: NOVEL PULSE WAVEFORM INDEX OBTAINED BY ABPM DEVICE COULD ESTIMATE CARDIAC FUNCTION IN A PATIENT WITH FULMINANT MYOCARDITIS
Authors: Narita Keisuke , Kario Kazuomi
Published: January 2023

Introduction:

In this case report regarding a patient with fulminant myocarditis who underwent mechanical hemodynamic support including extracorporeal membrane oxygenation (ECMO), our developed novel hemodynamic index calculated from pulse waveform obtained by ambulatory blood pressure monitoring (ABPM) device was useful for estimation of the improvement of cardiac function. We obtained volumetric pulse waveform from diastolic phase of BP measurement by our recently developed device, a Multisensor-ABPM device (TM-2441, A&D Co., Tokyo). This pulse waveform is divided into ejection wave and reflex wave. The area of the ejection part is square forward pulse wave (Sf), which is related with cardiac ejection volume. Second, amplitude measured pulse wave (Am) of the pulse waveform is a parameter defined by central artery compliance, peripheral artery properties, and cuff compliance. We then calculated Sf/Am as follows: Sf was divided by Am to eliminate the effect of arterial and cuff compliance from the area of the ejection wave, which would indicate left ventricular ejective function.

Case report:

A 43-year-old Asian female presented dyspnea and fever and developed cardiogenic shock. She was transferred from the primary hospital to our intensive care unit. Laboratory test and chest x-ray revealed elevated c-reactive protein, creatine kinase MB, and N-terminal-pro-brain natriuretic peptide and pulmonary edema. Electrocardiogram showed an ST-elevation and there was no stenosis in coronary artery on cardiac catheter examination. Based on these findings, she was diagnosed as viral myocarditis. Her echocardiographic left ventricular ejection fraction (LVEF) decreased less than 20% and hemodynamics were disrupted. Then, she was urgently initiated mechanical support including management of ECMO and intraaortic balloon pumping (IABP). During six-days initiating these mechanical supports, her cardiac function was improved, i.e., LVEF was improved from 6% (almost akinesis) to 64%, and she was able to withdraw from ECMO. We prospectively assessed the changes in the cuff waveform index Sf/Am from during the management of ECMO and IABP. The values of Sf/Am increased in parallel with the improved of LVEF (Figure).

Conclusion:

This case report highlighted that the novel cuff pulse waveform index Sf/Am obtained by the recent our developed Multisensor-ABPM device was useful for estimation of cardiac function in a patient with fulminant myocarditis who had severe cardiac dysfunction and were needed full mechanical support including ECMO. This case indicated that BP measurement device using the cuff-oscillometric method is useful for evaluation of cardiac function even in intensive care settings.
PS-BPR02-6: NOT FOR THE FAINT OF HEART: A CASE REPORT OF BRADYCARDIA INDUCED HYPERTENSION
Authors: Mellor Kaitlyn , Khan Nadia , Iatan Iulia , Tran Karen
Published: January 2023

Background:

Bradycardia is an underreported and often overlooked contributor to resistant hypertension. We present a case of refractory hypertension and bradycardia with atrial fibrillation and marked improvement in BP control following pacemaker implantation.

Case Presentation:

A 66-year-old asymptomatic Chinese male with a past history of hypertension with unilateral adrenalectomy (no hyperaldosteronism), remote myocardial infarction, treated obstructive sleep apnea, and type 2 diabetes presented with gradually increasing blood pressure (BP) and decreasing heart rate (HR). From 2019 to 2020, his 24-hour ambulatory BP average increased from 140/49 mmHg to 188/66 mmHg with a decrease in HR from 55 to 43 bpm; there was no significant nocturnal dipping. Home and office BPs were similar. Daily medications included candesartan 64 mg, amlodipine 20 mg, chlorthalidone 50 mg, spironolactone 50 mg, doxazosin 8 mg, hydralazine 300 mg, nitropatch 0.8 mg/hour, and kayexalate for persistent hyperkalemia.

Medication adherence was confirmed by a pharmacy database review. Secondary hypertension workup was negative for Cushing's Disease, pheochromocytoma, and renal artery stenosis. Plasma aldosterone was undetectable and plasma renin activity was 1.95 (normal 0.10–1.10ng/L/s) while taking the above medications. Serial 24-hour Holter monitors captured sinus bradycardia without pauses. Echocardiogram revealed concentric left ventricular (LV) hypertrophy, left atrial enlargement, and LV ejection fraction of 55%. Subsequent 2-week Holter monitoring revealed atrial fibrillation with average HR of 44 bpm and multiple prolonged ventricular pauses (longest 5.1 seconds). Following pacemaker insertion, BP normalized to an average of 130/80 mmHg with only 3 agents.

Conclusion:

There is a paucity of literature on severe bradycardia resulting in resistant hypertension; the English language PubMed database documents 3 reported cases. Severe bradycardia may impair cerebral and renal blood flow, increase LV filling pressures through prolonged diastole causing greater ventricular stretch and increased force of contraction, and may alter arterial stiffness. This case demonstrates a rare but important phenomenon of refractory hypertension and bradycardia with marked improvement in BP control following pacemaker insertion. It is important that physicians are aware of this potential phenomenon when evaluating patients with resistant hypertension and bradycardia.
PS-BPR02-8: THE EFFECTS OF AN ORAL FUNCTION IMPROVEMENT PROGRAM INVOLVING CHEWY KELP TEXTURE FOR LOCAL ELDERLY JAPANESE PEOPLE: A PILOT STUDY
Authors: Kawamura Atsuko , Araki Hinano , Shiragami Aya , Tsubota Mako , Yonemura Reiko , Nagata Chizuru , Tsutsumi Masae
Published: January 2023

Objective:

The purpose of this study is to verify the efficacy and sustainability of an oral function improvement program involving chewy kelp texture in nutrition designed specifically for an elderly Japanese population.

Study Design:

A small pilot study

Method:

We developed a chewy kelp nutritional formula through the collaboration of geriatric nursing specialists and the professional staff of a seaweed processing company. The program to improve oral function consisted of a) salivary gland massage and swallowing exercises three times daily before each meal, followed by b) training to chew and eat chewy kelp. The program was conducted for two weeks, and such vital signs as blood pressure (BP), pulse, saliva secretion (relative value of average oral water content), tongue pressure, and occlusal force (glucose elution amount) were measured before and after the intervention.

Results:

10 participants (4 male / 6 female: mean age 74.7 ± 5.4 years) enrolled. The program implementation rate of the participants was 93.6%. Measurements before and after the intervention included mean systolic BP (before, after, p) (138.0 ± 20.0, 131.0 ± 16.4 mmHg, p = .177), mean diastolic BP (79.6 ± 12.6, 73.2 ± 6.6 mmHg, p = .075), mean pulse (75.7 ± 11.0, 74.1 ± 10.8 times / min., p = .577), average oral mucosal moisture relative value (28.2 ± 4.9, 25.9 ± 3.3, p = .160), mean tongue pressure (29.6 ± 6.7, 32.3 ± 7.1 kPa, p = .213), and occlusal force (199.7 ± 78.9, 183.2 ± 42.7 mg / dL, p = .254). Among the participants, in one case in which occlusal function had significantly reduced, both mean systolic and diastolic BP decreased, and both tongue pressure and occlusal force increased.

Conclusion:

The high implementation rate indicated the potential sustainability of this program. Nevertheless, this study had certain limitations. First, the number of participants in the pilot study was small, falling short of the customary statistical sample size. In addition, because the implementation period was limited, any long-term effects of the program were not yet possible to show. Among preliminary findings of the study, for participants with impaired occlusal function, oral function may be improved and BP stabilized. Since periodontal disease is highly associated with cardiovascular disease and such side effects of hypertension drugs as increased thirst, it can be expected that longer trials of this program may see increased saliva production and improved oral function in participants.
PS-BPR02-10: SYMPATHETIC NERVE TONE AND THE INDOOR ENVIRONMENT IN A HIGHLY INSULATED AND AIRTIGHT MODEL HOUSE DURING THE COLD WINTER SEASON
Authors: Nakagami Hironori , Takahashi Sho Adnas , Sawada Katsutoshi , Kobayashi Nobutoshi , Akiyama Hiroshi , Otsuka Hiroki , Iwamae Atsushi , Yamada Hidekazu
Published: January 2023

While evidence for lifestyle modification such as salt reduction, weight loss, exercise, sobriety, and smoking cessation has accumulated for perfect blood pressure control, there is a lack of evidence on blood pressure fluctuations due to housing environments such as thermal protection and heating. In particular, blood pressure fluctuation due to the difference in room temperature between the living room and the dressing room, toilet, and bedroom is known to be a major risk during the winter season. Therefore, this study focused on the autonomic nervous system as one of the factors causing blood pressure fluctuations, and compared the fluctuations when the same subjects spent two days each at home and in a highly insulated, airtight model house.

JOURNAL/jhype/04.03/00004872-202301001-00877/figure1/v/2023-10-24T163949Z/r/image-jpeg

Subjects were 6 males and 5 females with 20–70 years old. Autonomic activity was measured and calculated using portable electrocardiography (Heartnote: JSR corporation, Tokyo) for the 8 subjects for whom it was possible to measure heart rate, CVRR (Coefficient of variation of R-R interval) and LF(low frequency)/HF(high frequency) ratio. An sympathetic hyperactivation was defined to show more than +2SD for distribution within an individual in LF/HF calculated every 10 seconds. The salivary amylase was measured at several times per day. The indoor environment temperatures were recorded by installing data loggers equipped with temperature sensors in various rooms and taking continuous measurements at 10-min intervals.

In the model house, room temperatures were kept constant at 18°C or more. However, in the home, there were large temperature differences between rooms, and in one case, a room temperature in the bedroom was recorded at 6.3°C.

In the overall analysis of heart rate and CVRR, there were large individual differences in both absolute values and diurnal variations, and no obvious differences by housing environment. In a detailed analysis focusing on early morning (2 hours after waking), two subjects showed excessive sympathetic activation in the early morning at home, but not in the model house. There was no correlation between this change and salivary amylase.

In terms of sleep quality, there were no differences by housing environment.

This case of early morning sympathetic activation in a residential setting suggests the importance of the residential setting in the management of early morning hypertension.
PS-BPR03-1: DIAGNOSIS OF MONOCLONAL IMMUNOTACTOID GLOMERULOPATHY WITH POSITIVE LAMBDA CHAIN BY IMMUNOELECTRON MICROSCOPY
Authors: Sugita Erina , Sonoda Homare , Ryuzaki Masaki , Hashiguchi Akinori , Tokuyama Hirobumi , Wakino Shu , Hayashi Kaori , Kanda Takeshi , Itoh Hiroshi
Published: January 2023

We report a case of a 73 year old man who developed immunotactoid glomerulopathy (ITG). ITG is a rare disease characterized by proliferative glomerulonephritis and capillary wall deposits with a 10 to 60 nm diameter microtubular substructure. Recent reviews recommend distinguishing monoclonal ITG from polyclonal ITG because monoclonal ITG is associated with a higher incidence of hematological disorders and better responsiveness to clone-directed therapy and renal prognosis.

In monoclonal ITG, immunofluorescence analysis typically exhibits IgG with light chain restriction, most often kappa chain restriction. This is the first reported case of a monoclonal ITG, positive only for the lambda chain detected by immunoelectron microscopy. At 6 months after his renal biopsy, the IgG lambda chain was detected in the serum and urine, reflecting possible monoclonality. We would like to present the usefulness of immunoelectron microscopy using biopsy samples as well as protein electrophoresis/ immunofixation using serum and urine samples to diagnose monoclonal ITG, even when routine immunofluorescence shows negative or nonspecific findings.

Conclusions:

It is important to distinguish monoclonal ITG from polyclonal ITG. Immunoelectron microscopy is useful as a salvage technique to diagnose monoclonal ITG.
PS-BPR03-8: MALIGNANT HYPERTENSION WITH ACUTE KIDNEY INJURY AND THROMBOTIC MICROANGIOPATHY SUCCESSFULLY TREATED WITH ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR
Authors: Hishida Erika , Imai Toshimi , Nagata Daisuke
Published: January 2023

Background:

Malignant hypertension is a disease characterized by severe hypertension and multi-organ damage. Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor (ARNi), has already demonstrated the superiority of reducing blood pressure versus olmesartan in patients with hypertension. ARNi has also been shown to improve cardiac biomarkers, cardiac remodeling, and prognosis in patients with heart failure, and a new AHA/ACC/HFSA guideline (2022) redefined to recommend ARNi as first-line renin-angiotensin-system inhibitors (class 1a) in patients with HFrEF (heart failure with reduced ejection fraction). However, the evidence about the efficacy and safety of ARNi in end-stage renal disease (ESRD) patients undergoing hemodialysis has been limited.

Presentation:

A 23-year-old man with no prior medical history was admitted to the previous hospital with severe hypertension (blood pressure 224/159 mmHg) associated with acute kidney injury (BUN 228.5 mg/dl, serum creatinine 25.50 mg/dl) and was referred to our hospital with the initiation of hemodialysis. He was also complicated with hypertensive heart failure with a preserved ejection fraction (NT-proBNP 172113 pg/ml). Blood test results also revealed thrombocytopenia (platelet 11.9 x 103/μL), hemolytic anemia (hemoglobin 7.4 g/dl, LDH 1076 U/L, haptoglobin < 10 mg/dl), and schistocyte on the blood smear, which was suggestive of thrombotic microangiopathy. His blood cell counts and serum LDH levels improved after antihypertensive treatment. Secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma, and renal artery stenosis, was deniable by further examination. The elevated levels of renin (65.5 ng/ml/hr) and aldosterone (685 pg/ml) were consistent with malignant hypertension. Serum antibody tests for screening of autoimmune disease were all negative. Renal biopsy revealed findings of malignant nephrosclerosis: glomerular collapse, glomerulosclerosis, endothelial swelling, and media thickening of the arteries. Oliguria recovered during the clinical course; however, his renal function did not fully recover. An arterio-venous fistula was created, and maintenance hemodialysis two times per week was continued during hospitalization. Even though his dry weight was adjusted to normal by repeated dialysis, his blood pressure was poorly controlled to systolic blood pressure of 160–170 mmHg by calcium channel blockers, angiotensin II receptor blocker (ARB), and alpha/beta-blockers. After switching from ARB to ARNi by increasing the dose to a maximum of 400 mg, his systolic blood pressure improved to 130–140 mmHg and was stable throughout the day, assessed by ambulatory blood pressure monitoring.

Conclusion:

Through our experience, it is conceivable that ARNi may be helpful in the settings of resistant hypertension in ESRD patients undergoing hemodialysis.
PS-BPR03-10: A CASE OF A WOMAN WITH IGA NEPHROPATHY PRESENTING DURING PREGNANCY
Authors: Yasuda Marie , Kanda Takeshi , Mito Asako , Arata Naoko , Itou Hiroshi
Published: January 2023

Background:

Pregnancy has an influence on autoimmune diseases course and many autoimmune diseases go into remission during pregnancy. The details of the autoimmune mechanism of IgA nephropathy have not been elucidated. The disease activity of IgA nephropathy commonly is stable during pregnancy, however, IgA nephropathy is at high risk of pregnancy complications even if renal function is preserved, and prevention of pregnancy complications are important in pregnant woman with IgA nephropathy.

Case:

A 29 year-old woman, gravida 2, para 0, no history of abnormal urine analysis before pregnancy, presented preeclampsia at 32 weeks pregnancy, and an emergency cesarean section was performed at 32 weeks and 5 days pregnancy. After delivery, microscopic hematuria persisted. Renal biopsy was performed 1 year and 9 months after delivery, and IgA nephropathy was diagnosed. Tonsillectomy was performed for IgA nephropathy, and the patient's renal function did not deteriorate during the follow-up period. In the second pregnancy, low-dose-aspirin was administered from the first trimester, and full term infants delivered without any pregnancy complications.

Conclusion:

IgA nephropathy can become apparent in pregnancy. Postpartum evaluation of urinalysis is important for the early detection of the primary renal disease. In pregnant woman with IgA nephropathy, stabilization of the disease state and administration of low-dose aspirin are very important for outcome of pregnancy and maternal renal prognosis.
PS-B03-5: HIGH-DOSES OF LOSARTAN RATHER ENHANCE CATECHOLAMINE SECRETION FROM THE PERFUSED ADRENAL GLAND
Authors: Koh Young Youp , Cho Byung Ryul , Lim Dong Yoon
Published: January 2023

Objective:

Previously, we have found that Losartan (5∼50 μM), an AT1 receptor blocker, dose-dependently inhibits secretion of catecholamines (CA) evoked by cholinergic and angiotensin II (Ang II) receptor stimulation from the perfused rat adrenal medulla. The aim of the present study was to examine the characteristic effects of high-dose losartan on the CA secretion from the isolated perfused rat adrenal gland, and also to establish its mechanism of action.

Design and Methods:

The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer.

Results:

The perfusion of high-dose losartan (150 ∼ 600 μM) into an adrenal vein for 90 min resulted in great increases in CA secretions evoked by acetylcholine in a dose-dependent fashion. Also, losartan (300 μM) enhanced the CA release evoked by Ang II, high K+ and DMPP (a selective nicotinic receptor agonist), McN-A-343 (a selective muscarinic M1 receptor agonist). Also, in the presence of losartan (300 μM), the CA secretory responses to veratridine (a selective Na+ channel activator), Bay-K-8644 (a Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly potentiated, respectively. The facilitatory CA-releasing effect of Ach evoked by high-dose losartan (300 μM) was time-dependently depressed by pretreatment with nifedipine (Ca2+ channel blocker), while not by pretreatment with sodium nitroprusside (an NO donor). High-dose olmesartan (150 ∼ 600 μM), one of ARBs, also potentiated Ach-evoked CA release in time-dependent fashion. However, in the simultaneous presence of losartan (300 μM) and CGP42112 (an AT2 receptor agonist), the facilitatory responses of losartan on the CA secretion evoked by ACh were rather significantly reduced in comparison with that of losartan-treatment alone. Conclusion: Conclusively, these results demonstrate that high-dose losartan can potentiate the adrenomedullary CA secretion in a calcium-dependent fashion. It seems that this facilitatory effect of high-dose losartan may be mediated by activation of the Ca2+ influx through L-type Ca2+ channels into adrenomedullary cells without inhibition of NO synthesis, which seems to be relevant to AT2 receptor blockade. It also suggests that high-dose ARBs may be a risk factor in causing hypertensive response.