bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-P08-9: DEPRESSION IS ASSOCIATED WITH NEW-ONSET DIABETES MELLITUS, BUT NOT HYPERTENSION, IN THE GENERAL POPULATION
Authors: Konno Satoshi , Munakata Masanori
Published: January 2023

Objective:

Epidemiological studies have shown that depression is a risk factor for cardiovascular disease, however, the mechanism underlying this association is yet unclear especially in the general populations. The aim of this study was to evaluate the relationship between depression and new-onset hypertension/diabetes mellitus in the general population.

Design and Method:

Individuals from the general population who participated in a medical check-up both in 2019 and 2020 were enrolled in this study. Fasting blood and urinary samples were taken for biochemical analysis, and depression was assessed by using Self-rating Depression Scale (SDS). Hypertension was defined as blood pressure of more than or equal to 140/90 mmHg or use of anti-hypertensive drugs. Diabetes mellitus was defined as fasting blood glucose of more than or equal to 126 mg/dL or HbA1c of 6.5% or use of anti-diabetic drugs. Multivariate logistic regression models were used to calculate odds ratios for new-onset hypertension and diabetes mellitus in 2020 after adjustment for possible confounding factors.

Results:

Among 550 participants without present hypertension in 2019, 124 developed hypertension in 2020. Similarly, among 890 participants without diabetes mellitus in 2019, 39 developed diabetes in 2020. Multivariate logistic regression analysis showed that severe depression (SDS score of more than or equal to 48) was significantly associated with new-onset diabetes mellitus (odds ratio: 2.558, 95%CI: 1.009–6.487, p = 0.048), but not with new-onset hypertension (odds ratio: 0.943, 95%CI: 0.434–2.051, p = 0.883) after adjustment for potential risk factors.

Conclusions:

In conclusion, severe depression may be a possible predictor of new-onset diabetes mellitus in the general population.
PS-P10-5: PREDICTORS OF HYPERTENSION AMONG APPARENTLY HEALTHY ADULT FILIPINOS IN THE LIFECARE PHILIPPINE COHORT STUDY
Authors: Duya Jose Eduardo De Leon , Punzalan Felix Eduardo R , Sison Olivia T , Llanes Elmer Jasper B , Carandang Nina Castillo , Guamatay Wilbert Allan G , Dominguez Paulette Nacpil , Reganit Paul Ferdinand M , Sy Rody G
Published: January 2023

Hypertension is the most common cardiovascular risk factor in the Philippines being significantly correlated with cardiovascular events when it remains uncontrolled. Early identification of these patients at risk of developing hypertension will prevent early cardiovascular complications. The main objective of this study is to determine the predictors for the development of hypertension among the Philippine LIFECARE participants. This prospective community-based study that included non-hypertensive participants from the LIFECARE Philippine cohort at baseline and was followed up after 5 years. A total of 2,089 non-hypertensive participants were included which comprised of 59% women with an average age of 35 years. Incidence rate of hypertension after 5 year was at 15%. After multiple regression analysis, variables that were correlated with development of hypertension after 5 years were: increasing age, male sex, family history of hypertension, abdominal obesity by waist circumference and pre-hypertension blood pressure levels.
PS-P10-9: INCIDENCE OF DIALYSIS AFTER MASSIVE NATURAL DISASTER DUE TO END-STAGE KIDNEY DISEASE ASSOCIATED WITH HYPERTENSION
Authors: Abe Michiaki
Published: January 2023

Objective:

The relationships between a massive disaster and the development of end-stage kidney disease (ESKD) is still unknown. We investigated the incidence and the causes of dialysis initiation in a city affected by the Great East Japan Earthquake (GEJE).

Design and method:

Single-center, retrospective observational study. All patients who initiated or were treated with dialysis in Kesennuma City Hospital between 2007 and 2021 were enrolled. The year of the dialysis initiation was determined retrospectively based on the initiation date. The causes of ESKD were clinically and conveniently divided into four groups; diabetic nephropathy (DN), hypertensive renal disease (HRD), glomerulonephritis (GN) and others.

Results:

The increasing number of dialysis initiation after GEJE were recognized around after the five years and peaked down after the ten years. The age at dialysis initiation among the four groups and the ratios of the four groups between before and after GEJE were significantly different (p = 0.0142, p = 0.0317). The age at the initiation by HRD was significantly increased than that by DN after GEJE (p = 0.0088), but not the before. The initiation by DN was high both before and after GEJE. No characteristic variation was seen in the initiation by GN. Notably the initiation by HRD was significantly increased around five years after GEJE and returned after the ten years. It looked like the increased initiation cause of HRD was related with GEJE.

Conclusions:

The influences of GEJE on dialysis initiations were sustained for up to 10 years after GEJE, that was probably associated with HRD. This is a first proposal the massive disaster could develop EKSD.
PS-R03-1: A CASE REPORT OF NEUROFIBROMATOSIS TYPE 1 (VON RECKLINGHAUSEN'S DISEASE) WITH HYPERTENSION, ASSOCIATED WITH PHEOCHROMOCYTOMA
Authors: Fujita Megumi
Published: January 2023

The patient is a 75-year-old man, who had multiple neurofibromas on the skin since the age 30 and was clinically diagnosed as neurofibromatosis type 1 (von Recklinghausen's disease) at the age 57, although there was no apparent family history. At the age 70, the patient had excerbated hypertension (home blood pressure 160/90 mmHg) and received amlodipine 5 mg/day. At the age 73, a 35 mm left adrenal tumor was incidentally noted on CT performed with an exacerbation of ulcerative colitis. He was diagnosed with left adrenal pheochromocytoma, due to high levels of urinary metanephrine and normetanephrine shown by urinalysis and an accumulation of 123I on the tumor site shown by 123I-MIBG scintigraphy. After adequate alpha blocking, left adrenal resection was performed. Pathology showed that PASS was 2 points, and MIB1 was 2–3%. Recently, two years after the operation, metanephrine and normetanephrine level has not been increased and keeps in normal range. Hypertension has been improved: Office blood pressure is about 130/70 mm Hg, and home blood pressure 120/70 mmHg, taking doxazosin 2 mg /day only, without amlodipine. Neurofibromatosis type 1 is an autosomal dominant genetic disorder caused by NF1 gene abnormality, characterized by cafe Ole spots and multiple neurofibromas. Pheochromocytomas have been clinically identified in 0.1 to 5.7% of patients with von Recklinghausen's disease (J Urol 1999; 162: 1582). When hypertension is observed in patients with neurofibromatosis type 1 (Recklinghausen's disease), it is important to screen for pheochromocytoma.
PS-R03-8: PARATHYROID ADENOMA PRESENTING AS UNEXPLAINED SINUS TACHYCARDIA AND REFRACTORY HYPERTENSION: A CASE REPORT
Authors: Senanayake Solith , Lokuketagoda Kasun , Hettiarachchi Chamath , Herath Jagath , Weerawardena Nethmi
Published: January 2023

Introduction:

Primary hyperparathyroidism (PHPT) and malignancy account for most cases of hypercalcemia in clinical practice. They commonly occur in relation to a solitary parathyroid adenoma, parathyroid hyperplasia, or carcinoma. Majority of patients are asymptomatic, although some present with vague unusual symptoms.

Case:

We report a case of a 50-year-old lady presenting with unexplained resting tachycardia, uncontrolled hypertension and generalised ill-health for one year in the background of complicated type 2 diabetes, dyslipidaemia, and hypertension. She had marginally elevated serum ionized calcium with normal serum phosphate levels in the background of early chronic kidney disease. Intact parathyroid hormone level was elevated with concomitant low levels of vitamin D. Clinical evaluation revealed an anterior neck lump which was ultrasonically suspected as a thyroid enlargement with possibility of a deep-seated parathyroid mass. A sestamibi B scan confirmed the presence of a single parathyroid adenoma. The possibility of Multiple Endocrine Neoplasia (MEN) was ruled out. She underwent a successful partial thyroidectomy with removal of the parathyroid mass. Histology revealed a solitary benign parathyroid adenoma. Following surgery, her calcium levels returned to normal range and her unexplained tachycardia had settled, as well as her general wellbeing. Her blood pressure was controlled with 3 antihypertensive drugs.

Discussion:

Hypercalcemia should be suspected as a rare possibility in the workup of unexplained sinus tachycardia and hypertension, and could be masked with concomitant vitamin D deficiency.
PS-R03-9: PERIODIC PARALYSIS AS A PRESENTATION OF PRIMARY HYPERALDOSTERONISM: A CASE REPORT
Authors: Gulkevych Oksana Volodymyrivna , Mishchenko Larysa Anatoliivna , Matova Olena Oleksandrivna , Logvynenko Alla Oleksiivna
Published: January 2023

Objective:

the typical clinical presentations of patients with primary aldosteronism (PA) include generalized weakness, fatigue, high blood pressure and potassium deficiency. However, onset of PA with periodic paralysis is rare.

Design and method:

herein, we present the case of a 40-year-old, Caucasian women (BMI 25,6 kg/m2) with severe resistance arterial hypertension (BP 200–190/110–120 mmHg while taking antihypertensive drugs: valsartan 320 mg/day, bisoprolol 5 mg, hydrochlorthiasid 12,5 mg, amlodipin 10 mg/day, spironolacton 25 mg/day) and muscle weakness. Over the last 2 years prior to presentation, she had multiple such episodes of generalized weakness and losing the ability to stand up, move limbs, wich typically lasted for few minutes to hours/days and resolved spontaneously. Her blood pressure was uncontroled despite taking antihypertensive drugs. She was hospitalized several times because of these conditions, but there is no data on potassium levels during that period. Due to misdiagnosis, she was operated on twice (discectomy C5-C6, C6-C7 and resection of the right internal carotid artery due to pathological tortuosity), but her condition did not improve.

Results:

At the presentation U waves were registered in the electrocardiography the laboratory examination revealed low plasma potassium level (3,05 mmol/l). Serum TSH, cortisol level were normal. Pasma aldosteron level was 38,6ng/dl (n. 4–31). CT abdomen: adenoma of left adrenal gland. Surgical adrenalectomy was performed. Pathological diagnosis was a bening cortical adenoma.

Outcomes:

Patient's serum potassium level became normalized after surgical removal of adrenal adenoma. Patient's blood pressue is controlled (130/80 mmHg) by taking a fixed combination perindopril 10 mg/indapamid 2,5 mg/amlodipin 10 mg daily and there is no muscle weakness.

Conclusions:

Patients with periodic acute muscles weakness and arterial hypertension should monitor electrolyte levels, especially potassium, and evaluate for primary hyperaldosteronism to avoid delayed diagnosis and treatment.
PS-R04-7: UNSOLVED CASE OF RESISTANT HYPERTENSION: A CHALLENGING ISSUE IN A DEVELOPING COUNTRY
Authors: Tiksnadi Badai Bhatara , Jungjunan Ridho
Published: January 2023

Introduction:

It is difficult to find a definite etiology of resistant hypertension (RH) in developing countries due to limited resources. We present a case report and discuss RH's diagnosis and treatment approaches, which we suspected owing to Obstructive Sleep Apnea (OSA) after extensive assessment, including nuclear imaging and renal arteriography.

Case presentation:

A 58-year-old female was referred to Hasan Sadikin General Hospital for RH assessment. Having conducted ambulatory blood pressure monitoring and echocardiography, which suggested hypertensive heart disease, we confirmed the diagnosis of RH in this patient. The patient has a 4-year history of hypertension, accompanied by throbbing headaches and snores. She underwent percutaneous coronary intervention two years ago due to angina. During the physical examination, she was fully alert with a blood pressure of 170/90 mmHg and a heart rate of 62 times/minute, mild exophthalmos, and cardiomegaly. Her renal (including proteinuria), and thyroid function were within normal limits. Echocardiography revealed concentric left ventricular (LV) hypertrophy with normal LV systolic function. An abdominal Computed Tomography indicated pheochromocytoma or adrenal tumor. Metanephrines examination was not feasible due to cost issues. Using metaiodobenzylguanidine scan (Tc-99 and I-131), nuclear imaging failed to establish diagnosis of pheochromocytoma. Renal artery ultrasonography increased the suspicion of renal artery stenosis; however, renal arteriography showed mild renal artery stenosis. We referred the patient to a neurologist for OSA screening, from STOP-Bang questionnaire result indicated that the patient was likely to have OSA. Unfortunately, the diagnosis was inconclusive due to unavailability of polysomnography facility. The unavailability of minoxidil, renal denervation and continuous positive airway pressure (CPAP) hinders the optimal treatment in this patient. The blood pressure target remains unachievable despite Amlodipine 1x10 mg, candesartan 2x16 mg, bisoprolol 1x10 mg, tamsulosin 1x400 mg, spironolactone 1x50 mg, dan isosorbide mononitrate 2x2.5 mg consumption. The unavailability of chromatography-mass spectrometry for evaluation of medication adherence was also a significant limitation.

Conclusion:

This case showed that the blood pressure remains uncontrolled despite six different medications, which may be due to the untreated etiology of secondary hypertension. Furthermore, although extensive examinations have been performed, a definite diagnosis could not be made due to cost/facility issues for other diagnostic approach. To further complicate matters, the evaluation of medication adherence and optimal treatment were not available. Therefore, RH remains a challenging issue in developing countries.
PS-R04-10: MALIGNANT HYPERTENSION AFTER COVD-19 VACCINE INJECTION
Authors: Wakino Shu , Miyakami Shinji , Ueda Sayo , Shibata Eriko , Tamaki Masanori , Hasegawa Kazuhiro
Published: January 2023

Case; 40 y/o male. Clinical course; The patient was transferred to our university hospital because of DOE and severe headache. He had been well and had no history of hypertension or obesity. He had experienced the COVID-19 vaccine injection two week before this visit. After the injection he had been experienced high fever and general fatigue as well as 7 kg of weight loss. On examnation, it was found that he had severe hypertension (190/110 mmHg) and hypertensive optic fundi. On chest X-ray, cardiomegaly and bilateral lung infiltrations was evident and biochemical data indicated renal dysfunction (serum creatinine 2.35 mg/dl), high levels of plasma renin activity (39.1 ng/ml/hour normal; 0.6–3.9) and aldosterone concentration (176 pg/ml normal; 4.0–82.1), and inflammatory changes (CRP = 23 mg/dl). We also found that increased levels of LDH and decreased levels of hemoglobin which indicated hemolytic anemia and thrombotic microangiopathy. After the control of high blood pressure by intravenous administration of Calcium channel blockades, We performed renal biopsy, which had a finding of diffuse findings of onion skin lesion and global glomerular sclerosis compatible with the diagnosis of malignant hypertension. Any secondary etiologies including renal artery disease or collagen disease had not been identified. Seven days after the admission, we started hemodialysis for this patient because of the renal failure was not resolved. We also had startred ACE inhibitors. We stopped the diuretics and minimized the ultrafiltration. Twenty-five days after the admission the patients was withdrawn from dialysis with the urine volume around 2000 ml/day and the serum creatinine concentration 5.29 mg/dl. He was discharged without any aid of dialysis and with small number of anti-hypertensives. Four months after the discharge, his serum creatinine concentration was 3.36 mg/dl and his blood pressure was 139/85 mmHg with the ACE inhibitor and calcium channel blockades. Conclusions; The case suggested that the malignant hypertension might be triggered by COVID-19 vaccine injection, which is of clinical importance.
PS-R05-2: ESAXERENONE AMELIORATES EGFR DETERIORATION AND URINE PROTEIN SECRETION IN DIABETES MELLITUS (DM) NEPHROPATHY: LONG TIME FOLLOW-UP
Authors: Yamazaki Osamu , Yasukawa Minoru , Ochiai Fumika , Morimoto Chikayuki , Asakawa Shinichiro , Nagura Michito , Arai Shigeyuki , Tamura Yoshifuru , Fujigaki Yoshihide , Shibata Shigeru
Published: January 2023

Introduction:

Mineralocorticoid antagonist (MRA) not only reduce cardiovascular event, but also may have the probable renoprotective events, likewise other RAAS inhibitors. Here we experienced that esaxerenone ameliorates eGFR deterioration and urine protein secretion in severe DM nephropathy.

Patient Presentation:

72-years-old, Female. She referred to our hospital in order to investigate DM retinopathy. She already had DM nephropathy (Cr 0.95 mg/dL, eGFR 44.4 mL/min/1.73m2) with severe urine protein (11.2 g/gCre), and eGFR was decreased -10 mL/min/1.73m2 per year. We started esaxerenone with conventional therapy using ARB. After initiation of esaxerenone, eGFR decreasing rate was significantly ameliorated (eGFR: -4 mL/min/1.73m2 per year). In addition, urinary protein levels were decreased by as much as 98% (urinary protein levels after the initiation were 0.25 g/gCre).

Discussion:

Esaxerenone may have the additional renoprotective effect with conventional RAAS therapy. The evidence on renoprotective effects of MRA will be reviewed along with the case presentation.
PS-R05-3: SEVERE GLOMERULAR MICROANGIOPATHY IN A PATIENT WITH NEPHROTIC SYNDROME FOLLOWING TAKAYASU ARTERITIS
Authors: Yamashita Yuya , Kodama Goh , Ito Sakuya , Kaida Yusuke , Taguchi Kensei , Fukami Kei
Published: January 2023

Introduction:

Takayasu arteritis (TA) is a large vessel inflammation that predominantly involves aorta and its main arteries. TA-caused kidney injury is known to be mainly due to renal artery stenosis. However, glomerulonephritis including membranous proliferative glomerulonephritis, focal segmental sclerosis, or crescentic nephritis has been histologically identified in some TA cases.

Case description:

A 69-year-old female presented with leg edema and refractory hypertension with nephrotic range proteinuria (17.0 g/gCr). She exhibited > 10 mmHg blood pressure discrepancy between left and right upper limbs and severe aortic regurgitation. Lab test showed high level of C-reactive protein and high erythrocyte sedimentation rate. Contrast-enhanced computed tomography identified wall thickening of the left subclavian artery, which led to the diagnosis of TA. Renal biopsy demonstrated that double basement membrane, enlarged subendothelial space, and mesangiolysis with no immunoglobulin deposition. Although azilsartan 40 mg QD and nifedipine 30 mg BID had been prescribed, systolic blood pressure (sBP) was still > 160 mmHg. Thus, while oral prednisolone was started to suppress TA-induced inflammation, azilsartan was replaced with sacubitril valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), for treating refractory hypertension. After a few weeks, sBP was decreased to 130 mmHg with sacubitril valsartan 200 mg QD and proteinuria was dramatically improved to 0.5 g/gCr.

Discussion:

TA commonly involves the renal artery, leading to stenosis and subsequent ischemic nephropathy. However, no stenosis and occlusion were observed in renal artery of this case. In addition, small vessel inflammation in the kidney such as vessel wall necrosis and immune cells infiltration around arterioles was not found. Serum levels of pro-inflammatory cytokines including vascular endothelial growth factor and interleukin-6, a well-known contributors for progression of TA-related inflammation, were within the normal range. The results indicate that TA-caused hypertension, but not vessel inflammation induced by TA, seems to play a pathological role for development of glomerular microangiopathy in this case. A previous study showed that 70% of TA patients presenting with glomerular lesion has severe hypertension and intimal thickening in renal arterioles was observed more frequently in TA patients presenting with glomerular lesion when compared to those without glomerulonephritis, which supports our hypothesis. In the present case, ARNI significantly reduced sBP which might directly contribute to the improvement of proteinuria. ARNI can be potent to control hypertension more effectively than conventional hypertensive agents in TA patients.
PS-R05-7: MALIGNANT PHASE OF HYPERTENSION IN A PATIENT ON PERITONEAL DIALYSIS
Authors: Vitkauskaite Monika , Maliukeviciute Indre , Rimsevicius Laurynas , Avizienyte Eleonora , Janusaite Marta Monika , Asakiene Egle , Miglinas Marius
Published: January 2023

Background:

Posterior reversible encephalopathy syndrome (PRES) describes a disorder of abrupt onset neurological symptoms due to potentially reversible lesions on brain imaging. Case reports of PRES in PD patients are scarce.

Case presentation:

A 42-year-old male presented to the emergency department (ED) with two weeks of worsening occipital headaches, nausea, vomiting and dizziness. The patient had a background of end-stage renal disease due to primary focal segmental glomerulosclerosis, and resistant hypertension. He had been receiving peritoneal dialysis (PD) for one month; hypertension was treated with torasemide 100 mg/day, perindopril 10 mg/day, amlodipine 10 mg/day, moxonidine 0.6 mg/day, doxazosin 8–16 mg/day. One week earlier, he was brought into ED due to hypertensive crisis (blood pressure (BP) was 190/120 mmHg); intravenous labetolol 20 mg, oral moxonidine 0.4 mg, doxazosin 8 mg were administered; afterwards he was released for outpatient treatment.

On admission, BP was 187/114 mmHg, heart rate - 75 beats/minute, oxygen saturation - 98% on room air, and body temperature - 36.5°C. Laboratory tests revealed severe renal dysfunction (serum creatinine: 1478 mcmol/l, serum urea: 29.1 mmol/l) and normal inflammatory indicators (WBC: 4.51 x 109/l, CRP: 0.65 mg/l) (Table). Head CT showed no obvious intracranial hemorrhage, ischemia, or mass lesion; PRES was suspected. Due to hypervolemia, he was temporarily transferred to hemodialysis. On day 12, fundoscopy revealed flame-shaped hemorrhages, microaneurysms, cotton wool patches in the posterior pole surrounding the optic nerve. On day 14, he was transferred to the intensive care unit (ICU) due to uncontrollable hypertension (BP was 202/129 mmHg) and epileptic seizure; MRI showed bilateral subcortical occipital and frontoparietal hyperintensity with vasogenic edema typical of PRES. BP was decreased to approximately 155/90 mmHg using a combination of anti-hypertensive medication and ultrafiltration. Subsequently he was discharged on day 28. Two months later he underwent cadaveric kidney transplantation. After the transplantation, his BP control improved and he was left with bisoprolol 5 mg/day, amlodipine 10 mg/day, and doxazosine 4 mg/day (office BP one month after the transplantation: 124/90 mmHg, after two months: 135/95 mmHg, after three months: 135/95 mmHg).

Conclusions:

This is to the best of our knowledge the fifth report of PRES in an adult patient undergoing PD, and the first presenting a PD patient with history of PRES whose hypertension control improved after kidney transplantation. It is likely that the cause of described PRES episode was multifactorial, originating from the complications of ESRD, hypertension and poor compliance with PD.
PS-B10-8: BLOCKADE OF AT1 RECEPTORS RESTORE P2/P1 WITHOUT CHANGING INTRACRANIAL PRESSURE IN RENOVASCULAR HYPERTENSIVE RATS WITH 0.3 M NACL AD LIBITUM
Authors: Lucera Gabriela Maria , Pontes Roberto Braz , Fernandes Marcos Vinicius , Frigieri Gustavo , Andrade Rodrigo , Colombari Eduardo , Menani Jose Vanderlei , Colombari Debora Simoes
Published: January 2023

Objective:

Renovascular hypertension is characterized by activation of the renin angiotensin aldosterone system, elevated sympathetic nerve activity and sodium appetite behavior. The association of increased sodium intake and hypertension can worsen the injury to end organs. We tested the effects of AT1 receptors blockade (losartan, 10 mg/kg iv) on mean arterial pressure (MAP), intracranial pressure (ICP) and P2/P1 ratio (index of brain compliance) in 2K1C rats with 0.3 M NaCl ad libitum. Design and Methods: Male Holtzman rats (150 tp 180 g) with water and food ad libitum received a silver clip around the left renal artery to induce 2K1C or no clip (SHAM surgery) resulting 3 groups: SHAM (n = 9), 2K1C (n = 9) and 2K1C/Na (n = 7), which had an additional bottle of 0.3 M NaCl ad libitum. Six weeks after the renal surgery, MAP and ICP were recorded under urethane anesthesia (1.2 g/kg iv) and the P2/P1 was calculated offline from the waveform. Saline (0.2 ml/rat) was used as control injection before losartan.

Results:

In SHAM rats, ICP and P2/P1 were not changed by losartan (7.8 ± 1.1 and 0.88 ± 0.02; vs. saline: 7.9 ± 1.1 and 0.83 ± 0.01 mmHg, respectively), while MAP was decreased (104 ± 5, vs. saline: 120 ± 3 mmHg, p < 0.05). In 2K1C, MAP, ICP and P2/P1 values were greater than SHAM (respectively, 196 ± 6, 14.7 ± 2.7 and 1.1 ± 0.03 mmHg, vs. SHAM; p < 0.05) and all of them were decreased by losartan pre-treatment (137 ± 6, 8.6 ± 1.3 and 0.87 ± 0.05 mmHg, vs. saline, respectively). In 2K1C-Na MAP and P2/P1 were greater than in SHAM (186 ± 7 and 1.15 ± 0.06 mmHg, vs sham p < 0.05) and were decreased by losartan (162 ± 8 and 0.87 ± 0.02 mmHg, vs. saline; p < 0.05), although the decrease in MAP after losartan was lesser than the observed in 2K1C rats (p < 0.05). In 2K1C-Na rats, ICP was not different from SHAM (10.8 ± 1.2, vs. SHAM: 7.8 ± 1.1 mmHg, p > 0.05) and losartan had no effect on ICP (10.3 ± 1.7, vs. saline: 10.8 ± 1.2 mmHg, p > 0.05).

Conclusion:

Even without a change in ICP, AT1 blockade in 2K1C-Na was effective in restoring P2/P1 ratio, suggesting a beneficial effect on brain compliance in this situation.
PS-B10-10: MRI CEREBROVASCULAR CHARACTERIZATION IN A MOUSE MODEL OF HYPERTENSION-INDUCED BRAIN INJURY
Authors: Carnevale Lorenzo , Carnevale Raimondo , Mastroiacovo Francesco , Perrotta Marialuisa , Carnevale Daniela , Lembo Giuseppe
Published: January 2023

Hypertension has been recognized as the main modifiable risk factor for vascular cognitive impairment (VCI), dementias and neurodegenerative pathologies as Alzheimer Disease (AD). As we previously demonstrated, Transverse aortic constriction (TAC) is a relevant mouse model of cerebral injury and cognitive impairment induced by vascular factors. In this work we characterize the effect of TAC procedure on cerebral injury leveraging Magnetic Resonance Imaging (MRI), and investigate the relationship between the alterations found by MRI and histological, cognitive and cardiac parameters of injury, to establish a framework of translational imaging biomarkers to be applied in human.

We subjected C57Bl/6J to TAC procedure, inducing severe cerebral hypertension. Thereafter, the brain injury was characterized by macro and microstructural MRI; cerebral blood flow (CBF) was analyzed by perfusion MRI. All neuroimaging scans were performed on a small-animal dedicated 7 Tesla MRI. The cognitive phenotype was characterized by Morris Water Maze (MWM) and Novel Object Recognition (NOR), while cardiac and carotid remodeling was assessed by ultrasound imaging. Finally, brains were analyzed for histological alterations in terms of microvascular density and integrity.

Structural MRI showed white matter microstructural degradation in the left Fimbria of TAC mice, evidenced by a reduction of Fractional Anisotropy, Mean Diffusivity and Radial Diffusiity, coupled with bilateral hypothalamic enlargement (Figure A). Hemodynamic alterations resulted in reduced global, cortical and hypothalamic CBF (Figure B). The histological microvascular analysis evidenced capillary rarefaction, reduced capillary-pericyte coverage and Blood-Brain Barrier leakiness in the neocortex (Figure C). Finally, we evaluated whether cerebral MRI parameters of injury were correlated with cardiac, carotid and cognitive alterations: CBF was significantly correlated with mouse performance at Probe trial of MWM test and correlated to cardiac remodeling and diastolic dysfunction. Diastolic disfunction was correlated also to hypothalamic swelling, and cardiac remodeling was significantly correlated to microstructural alterations in the fimbria. Finally, CBF was correlated to bilateral carotid remodeling.

In conclusion we have developed a mouse model of hypertension-induced brain damage that recapitulates typical traits of the human pathology and a pipeline of analysis that will ease allow to appreciate findings resulting from novel molecular targeting of the brain and translate them from bench to bedside.

JOURNAL/jhype/04.03/00004872-202301001-01152/figure1/v/2023-10-24T163949Z/r/image-jpeg
PS-B11-3: THE ROLE OF INTESTINAL NAMPT-MEDIATED NAD+ BIOSYNTHESIS IN WHOLE-BODY ENERGY AND GLUCOSE METABOLISM
Authors: Yamaguchi Shintaro , Nagahisa Taichi , Kosugi Shotaro , Nishioka Ken , Watanabe Yasuhiro , Homma Koichiro , Miyashita Kazutoshi , Irie Junichiro , Yoshino Jun , Itoh Hiroshi
Published: January 2023

The purpose of the present study was to test our hypothesis that intestinal nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide (NAD+) biosynthesis plays a pivotal role in whole-body energy and glucose metabolism. To this end, we generated a new mouse model, namely intestinal epithelial cell-specific Nampt knockout (INKO) mice. Under regular chow diet, deletion of intestinal epithelial NAMPT did not affect body weight gain, food intake, or whole-body energy expenditure, suggesting that intestinal epithelial NAMPT deficiency had no significant impacts on overall energy intake or expenditure. However, INKO mice displayed reduced early-phase insulin secretion and postprandial hyperglycemia, at least partly due to diminished glucagon-like peptide-1 (GLP-1) production. In addition, we found that diet-induced obese mice had impaired intestinal NAMPT-mediated NAD+ biosynthesis, associated with impaired GLP-1 production and whole-body glucose metabolism, similar to the INKO mice. Finally, administration of a key NAD+ intermediate, nicotinamide mononucleotide, to INKO and diet-induced obese mice, restored ileal NAD+ levels and obesity-associated metabolic derangements, manifested by an impairment in GLP-1 production as well as postprandial hyperglycemia. Taken together, our study provides a new understanding of the role of intestinal NAMPT-mediated NAD+ biosynthesis in energy and glucose metabolism, and therapeutic insights into intestinal NAD+ biology related to obesity-associated dysregulation of GLP-1 production and postprandial hyperglycemia (Nagahisa, Yamaguchi et al. Endocrinology. 2022). A future study using INKO mice to investigate if diminished GLP-1 production is involved in obesity-associated hypertension is warranted.
PS-B11-10: IRON DEFICIENCY AFFECTS CARDIAC FUNCTION BUT HAS NO EFFECT ON BLOOD PRESSURE IN MICE WITH METABOLIC SYNDROME
Authors: Naito Yoshiro , Yasumura Seiki , Tahara Saki , Asakura Masanori , Tsujino Takeshi , Ishihara Masaharu
Published: January 2023

Objective:

Metabolic syndrome is a serious problem concerning public health, increasing the risk of cardiovascular diseases. Some epidemiological studies have reported that iron overload is associated with metabolic syndrome; however, it remains unknown whether iron deficiency affects the pathogenesis of metabolic syndrome. Therefore, in this study, we investigated the impact of dietary iron deficiency in genetically obese KKAy mice, a model of human metabolic syndrome.

Methods:

Four-week-old male KKAy mice and control C57BL/6J mice (wild-type mice, WT) were fed a normal or an iron-restricted diet, and the impact of dietary iron deficiency was investigated 12 weeks after diet initiation.

Results:

Compared with WT mice, systolic blood pressure presented an increasing trend in KKAy mice; however, the difference was not statistically significant between the two groups, and this trend did not change after iron restriction. Notably, some KKAy mice died following iron restriction, while no deaths were recorded in WT mice. Of interest, obese KKAy mice exhibited cardiac hypertrophy and cardiac dysfunction, thereby developing heart failure with pulmonary congestion after iron restriction.

Conclusions:

These results indicate that iron deficiency affects cardiac function in metabolic syndrome.
PS-B12-11: FUNCTIONAL VERSATILITY OF (PRO) RENIN RECEPTOR CLARIFIED BY STRUCTURAL AND EVOLUTIONARY ANALYSES
Authors: Sugihara Daiki , Matsuyama Makoto , Nakagawa Chiharu , Nabi AHM Nurun , Nakagawa Tsutomu , Nishiyama Akira , Suzuki Fumiaki , Ebihara Akio
Published: January 2023

Objective:

(Pro)renin receptor [(P)RR] is a single-span membrane protein originally identified as a regulator of the renin-angiotensin-aldosterone system. (P)RR reportedly exerts various functions, including an accessory protein of vacuolar ATPase complex and a component of Wnt receptor complex. The soluble form of (P)RR [s(P)RR] which comprises of most of extracellular domain (ECD) exerts an antidiuretic action. although the versatile functions should be mediated through the interactions between (p)rr ecd and its respective binding partners, the one-to-many bindings has not been fully explained. Here we investigated the binding mode of this receptor by structural and evolutionary analyses using three-dimensional structural models of (P)RR, which were predicted by the AlphaFold2 (AF2) program, a machine learning-based algorithm capable of predicting protein structure to near experimental accuracy.

Design and method:

Monoclonal antibodies against (P)RR reduce the Wnt/beta-catenin-dependent development of pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer. Antibodies against two (P)RR regions (residues 47–60 and 200–213) located in ECD reduce the proliferation of human PDAC cells in vitro. The spatial distribution of the two regions was examined using human (P)RR AF2 structural models (monomer and dimer). The evolutionary conservation profile and hydrophobicity were mapped on the models.

Results:

The dimer structure predicted by AF2 shows that (P)RR homodimerizes via ECD, which explains the experimentally proven dimer formation. The 47–60 and 200–213 regions of (P)RR formed a continuous surface patch on the structural model, which comprised evolutionarily conserved hydrophobic residues. The dimer model revealed the presence of two hand-like grooves, with 47–60 and 200–213 regions as its palm and 270–296 region (intrinsically disordered region, IDR) as its fingers.

Conclusions:

Considering conformational flexibility of IDR allowing for multiple protein interactions, we propose that the grooves may act as a binding interface with Wnt signaling molecules and antibodies against the grooves probably interfere with the formation of Wnt receptor complex due to steric hindrance and direct competition with the binding interface residues. The hydrophobic nature of the grooves may explain why (P)RR shows one-to-many bindings underpinning its functional versatility. This study provides new insights into the binding mode of (P)RR for the first time. s(P)RR is considered a useful biomarker for diseases, including essential hypertension and cancer. Our findings may help explore a new treatment and biomarker testing of human diseases, and contribute to quality of life in a longevity society.
PS-C28-4: IMPACT OF SYSTOLIC BLOOD PRESSURE ON OUTCOMES IN ACUTE ISCHEMIC STROKE AFTER INTRAVENOUS THROMBOLYSIS: NCVC RT-PA REGISTRY
Authors: Yoshimoto Takeshi , Wada Shinichi , Yoshimura Sohei , Toyoda Kazunori , Ihara Masafumi , Koga Masatoshi
Published: January 2023

Background:

The optimal management of systolic blood pressure (SBP) in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT) remains unclear. We aimed to clarify the association between SBP parameters, including variability and clinical outcomes in AIS patients who received IVT.

Methods:

Data of AIS patients receiving intravenous alteplase at 0.6 mg/kg were extracted from the National Cerebral and Cardiovascular Center (NCVC) rt-PA Registry. SBP was measured seven times at admission and within 24 hours every 4 hours after IVT. SBP variabilities included maximum SBP, minimum SBP, mean SBP, standard deviation, coefficient of variation, and successive variation. Outcomes were defined as modified Rankin Scale score 3–6 at 90 days, representing unfavorable outcome, and symptomatic intracranial hemorrhage (SICH) within 36 hours.

Results:

Among 802 patients (303 women; median age, 76 years; median National Institutes of Health Stroke Scale score, 12), 424 (52.9%) AIS patients had unfavorable outcomes and 16 (2.0%) patients had SICH, respectively. In multivariable analyses, maximum (adjusted odds ratio per 10 mmHg 1.13, 95% confidence interval, 1.04–1.24), minimum (1.27, 1.14–1.42), and mean SBP (1.54, 1.35–1.77) were independently associated with unfavorable outcomes.

Conclusions:

SBP during the initial 24 hours after intravenous low-dose alteplase was associated with unfavorable outcomes.
PS-C28-5: ROLE OF SYMPATHETIC NERVOUS SYSTEM IN ATTENDED AND UNATTENDED BP LEVELS IN ESSENTIAL HYPERTENSION
Authors: Manta Eleni , Andrikou Ioannis , Konstantinidis Dimitrios , Thomopoulos Costas , Dimitriadis Kyriakos , Drogkaris Sotirios , Iliakis Panagiotis , Mantzouranis Emmanouil , Polyzos Dimitrios , Zammanis Ioannis , Tsioufis Konstantinos
Published: January 2023

Objective:

It has been hypothesized that unattended blood pressure (BP) measurement may provide complementary clinical information to conventionally attended BP measurement. The role of sympathetic nervous system activation during attended and unattended BP measurements is largely undetermined.

Design and method:

We studied 161 untreated hypertensive patients undergoing attended and unattended office BP measurements. Patients were divided into two groups - group A, unattended systolic BP greater than the attended systolic BP (n = 79), and group B, unattended systolic BP equal or lower than the attended (n = 82). All participants underwent muscle sympathetic nerve activity (MSNA) estimation by microneurography. Unattended and attended BP measurements were performed with the same device in a random order for each patient on the day of MSNA recording. MSNA levels were compared between the two groups.

Results:

We examined 161 hypertensive patients [54% men, mean age 56 ± 12 years, BMI 29 ± 5 kg/m2, mean attended BP 140 ± 17 / 87 ± 13 mmHg, mean unattended BP 141 ± 20 / 85 ± 12 mmHg]. Group A and group B had statistically significant differences between attended systolic BP (136.7 ± 17.8 vs 143.7 ± 15.7 mmHg respectively, p = 0.009), attended diastolic BP (85.5 ± 14.7 vs 89.7 ± 11.4 mmHg respectively, p = 0.004), unattended systolic BP (145.5 ± 19 vs 135.7 ± 19.9 mmHg respectively, p = 0.002) and unattended diastolic BP (86.9 ± 13 vs 83.2 ± 11.2 mmHg respectively, p = 0.05). However, the two groups did not differ as regards MSNA levels (42.5 ± 10 vs. 41.6 ± 7.8 bursts per minute respectively, p = 0.5). MSNA levels did not correlate to attended and unattended systolic/diastolic BP in both groups.

Conclusions:

In conclusion, sympathetic nervous system activity may not contribute significantly to the differential BP levels during attended or unattended BP measurements.
PS-C28-10: HYPERTENSIVE CARDIOMYOPATHY AS MOST FREQUENT ECHOCARDIOGRAPHIC FINDING IN PATIENTS HOSPITALIZED FOR ISCHEMIC STROKE.
Authors: Zambrano-Medina María Eugenia , Padilla-Pérez Miriam , Lozano-Cabezas Cristobal , Fernández-Guerrero Juan Carlos
Published: January 2023

Objective:

In Spain occurs about 120,000 strokes per year. Initial study usually requires echocardiography to rule out cardioembolic source. We describe most common echocardiographic features in neurological patients and traditional risk factors in them.

Methods:

From August 2020 to August 2021, 502 consecutive Neurology echocardiograms were analysed, collecting data in SPSS for subsequent descriptive and analytical statistical analysis.

Results:

45% were women. Most frequent study reason was ischemic stroke (66%), followed by transient ischemic attack (TIA) (11%), haemorrhagic stroke (2%) and miscellaneous (fever, cardiac enzyme release, dyspnoea, coma) (15%). Highest frequent risk factor was hypertension (HBP) (70%), followed by obesity (51%), dyslipidaemia (46%), diabetes (32%), and kidney failure (15%). Atrial fibrillation (AF) had been documented in 13%, while De novo AF was discovered in an additional 14.5%. Systemic inflammation disorders were present in 19% and hypercoagulability in 9%. 10% had suffered a previous stroke (90% ischemic), and 2.6% TIA.

About treatment 27% had antiaggregation drugs on stroke moment and 12% were anticoagulated (5.6% VKA and 6.6% DOAC).

In echo images, absence of structural heart disease was the most frequent finding (49%), followed by LA dilatation (48%) and ventricular hypertrophy > 13 mm (34%), both characteristic of hypertensive heart. 5% showed valve disease (more frequent mitral regurgitation) and 5% Cor pulmonale. Cardiomyopathy was found in 3% (Dilated 2.6%). Patent foramen ovale, and aneurysm of the interatrial septum were rare (1% each). Ostium secundum type ASD only one case (0.2%).

In the follow-up 5% had a new event (stroke or TIA) in next 12 months and additional 4.4% evidence of AF was found, this variable being related to left atrial dilatation in statistical analysis.

Conclusions:

In our sample of patients with ischemic stroke the abnormal finding most recurrent was hypertensive heart disease (HBP, LA dilatation, and LVH). LA dilation was related to the development of AF during follow-up, this relationship being statistically significant (p < 0.001) by chi-square test. The percentage of de novo AF discovered in the same stroke episode (14.5%) is noteworthy. The ineffectiveness of antiaggregation (27% took it) and that anticoagulation does not completely eliminate risk either. Presence of structural anomalies such ASD, PFO or thrombus was rare (less than 1%).
PS-C29-9: PROGNOSTIC AND ASSOCIATED FACTORS IN ELDERLY HYPERTENSIVE PATIENTS WITHOUT DIABETES OR CARDIOVASCULAR DISEASES
Authors: Nakamura Satoko
Published: January 2023

Objective:

It is known that metabolic syndrome complicated by hypertension, dyslipidemia, obesity, and glucose metabolism abnormalities increases the risk of atherosclerotic disease synergistically. Therefore, even in elderly hypertensive patients without a history of diabetes mellitus (DM) or cardiovascular diseases (CVD), we examined whether complications such as blood pressure management and metabolic syndrome affect the prognosis.

Design and method:

172 elderly hypertensive patients (76 men, mean age 73 years old) without DM or CVD were conducted. Height, weight, blood pressure, blood test, and urine test at the start of the study were evaluated and risk factors were defined as follows. (1) Poor blood pressure management: systolic blood pressure 150 mm Hg or more or diastolic blood pressure 90 mm Hg or more, (2) dyslipidemia: triglycerides 150 mg / dl or more or HDL cholesterol less than 40 mg / dl, (3) Obesity: BMI (kg / m 2) 25 or more, (4) Glucose metabolism abnormalities: fasting blood glucose 110 mg / dl or more, (5) Hyperuricemia: 6 mg / dl or more of uric acid, (6) Chronic kidney disease: estimated GFR (eGFR) was obtained by the Japanese estimation formula, and eGFR was less than 60 ml / min/1.73 m 2 or proteinuria positive. The incidence of cardiovascular accidents and all-cause deaths during the average observation period of 11 years from the start of observation were investigated, and related factors were examined in the Cox proportional hazard model.

Results:

Risk factors were found in (1) poor blood pressure management 45%, (2) dyslipidemia 38%, (3) obesity 44%, (4) glucose metabolism abnormality 26%, (5) hyperuricemia 38%, and (6) chronic kidney disease 51%, respectively. During the observation period of an average of 11 years, 36 patients developed cardiovascular accidents and 5 died. In a study in a proportional hazards model, chronic kidney disease was involved in the development of cardiovascular accidents. All-cause deaths, on the other hand, involved dyslipidemia and obesity.

Conclusions:

Elderly hypertensive patients without DM and CVD had a high rate of various risk factors, and the risk factors were associated with subsequent cardiovascular prognosis and all-cause death.
PS-C30-3: FEATURES OF THE C-786T NOS3 GENE POLYMORPHISM IN PREGNANT WOMEN WITH PREECLAMPSIA
Authors: Kurbanov Bakhodir
Published: January 2023

Relevance:

Preeclampsia is the multi cause illness. One of the genetic risk factors for the development of preeclampsia may be a polymorphism of the endothelial system genes.

Objective:

to study the C-786T polymorphism of the NOS3 gene in patients with preeclampsia.

Materials and methods:

The study group consisted of 140 pregnant women, of which the main group included 72 patients with preeclampsia, and 68 apparently healthy individuals (control group). The study was conducted in the Tashkent city maternity complex 6. The age of the pregnant women ranged from 19 to 42 years.

The material for the study was DNA samples from a patient with a clinically diagnosed preeclampsia. Statistical processing of the results was carried out using statistical programs “EpiCalc 2000 Version 1.02“.

Results:

The proportion of wild C allele in the subgroup of patients was statistically significantly lower compared to the control (68.6% versus 79.9%, respectively; (p = 0.04; RR = 0.86; OR = 0.55; 95%). On the contrary, the frequency of the unfavorable T allele among patients with severe preeclampsia was significantly higher compared to controls - 31.4% and 20.1%, respectively (p = 0.04). At the same time, the calculated odds ratio for detecting this allele was OR = 1.8, and the relative risk of developing diseases was RR = 1.17 (p = 0.04).

There was a trend towards an increase in the heterozygous C/T genotype in the group of patients with severe preeclampsia, where it was detected with a frequency of 39.5% compared to 27.1% in the control group (p = 0.15; RR = 1.46; OR = 1.76).

The functionally unfavorable T/T genotype was insignificantly more common among patients with severe preeclampsia compared to the control group 11.6% and 6.5%, respectively (p = 0.30; RR = 1.78; OR = 1.88;).

A significant relationship was found between the risk of developing preeclampsia and the carriage of a rare allelic variant of the C-786T polymorphism of the NOS3 gene, associated with a decrease in the synthesis of the NO-synthetase enzyme.

Conclusions:

Thus, the results of our study allow us to conclude that unfavorable genotypic variants of the C-786T polymorphism of the NOS3 gene (associated with vascular endothelial dysfunction) contribute significantly to the mechanism of preeclampsia development.