bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-P08-6: ESTIMATION OF TOTAL CARDIOVASCULAR RISK AMONG THE RURAL POPULATION OF BANGLADESH USING 2019 WHO CVD RISK PREDICTION NON-LABORATORY-BASED CHARTS
Authors: Mamun Mohd Abdullah Al , Bhuiyan Mahfuzur Rahman , Sultana Sharmin , Akhter Jubaida , Jubayer Shamim , Nabi Md Noor , Sobhan Sheikh Mohammad Mahbubus , Alim Abdul , Milon Sarowar Uddin , Amin Mohammad Robed , Choudhury Sohel Reza
Published: January 2023

Objective:

Cardiovascular disease (CVD) is the leading cause of death globally, require immediate intervention. Package of Essential Noncommunicable diseases (PEN) intervention implemented by World Health Organization in primary care of low resource setting enables healthcare workers to tailor care for patients according to their risk level, thus decrease the health care cost as well as workload of health facility. The objective of this study was to estimate the distribution of 10-year CVD risk among rural Bangladeshi adults aged > 40 years by using the 2019 WHO CVD risk prediction non-laboratory-based charts.

Design and Methods:

Cross-sectional, population-based study. We estimated total CVD risk using 2019 WHO CVD risk prediction non-laboratory-based charts and categorized as very low (< 5%), low (5- < 10%), moderate (10- < 20%), high (20- < 30%) and very high risk (> 30%). Participants were selected from four rural areas of two administrative districts of Bangladesh. Participants age, gender, smoking status, blood pressure, height and weight for calculation of body mass index were recorded. Participants with hypertension and moderate and high CVD risk score were referred to respective primary health care facility for further assessment and management.

Results:

Total of 1234 participants (male 397, female 837) were included in this study. Mean age of the participants was 54.0 years. Among the respondents 42.9%, 33.5%, 18.9% and 4.7% were in the age group of 40 to 50, 51 to 60, 61 to 70 and > 70 years respectively. Among the participants 11.9% were current smoker (men 37.1% and women 0.1%). The mean systolic and diastolic blood pressure of the participants was 134.14 and 85.03 mm of Hg respectively. The prevalence hypertension was 62%. The prevalence of hypertension was much higher among the female participants (men 53.0% and women 66.2%). Three fourth (77.6%) of the participants had CVD risk score of very low and low below (< 10%) and none had CVD score of very high risk (> 30) and one fifth (21.3%) had moderate and high CVD risk score. Among the participants with very low (< 5%), low (5–10%), moderate (10–20%) and high (20–30%) CVD risk score had 20.6%, 38.3%, 57.1% and 95.2% high blood pressure respectively.

Conclusion:

High prevalence of hypertension may be the main contributor of CVD score in this selected rural adult population of Bangladesh. This population require an early intervention with priority to hypertension management at community level to prevent the epidemic of the cardiovascular events.
PS-P09-4: OBESITY AND ITS ASSOCIATION WITH HIGH SENSITIVITY C-REACTIVE PROTEIN AS AN INFLAMMATION MARKER AND THE RISK OF PREHYPERTENSION AMONG ADULTS
Authors: susetyowati susetyowati , faza Farah
Published: January 2023

Objective:

It has been reported that obesity could trigger the elevation of serum high sensitivity C-reactive protein (hsCRP) and abnormal lipid metabolism, manifesting in the progression of metabolic diseases (hypertension, cardiovascular diseases, and type 2 diabetes). Regarding the high prevalence of obesity both in developed and developing countries, assessing hsCRP as an inflammation marker is essential to prevent the high risk of the diseases. We aim to assess the association between obesity with hsCRP and prehypertension among adults.

Design and method:

A cross-sectional study was conducted from July to September 2021 in urban and rural areas. A total of 109 healthy adults were involved with inclusion criteria: aged 19 to 64 years, did not have pregnancy or breastfeeding for women, and did not have any metabolic disease histories. The data was collected by trained enumerators and blood samples were taken by a trained phlebotomist, including socio-demographic, body mass index (BMI), waist circumference (WC), blood pressure, and hs-CRP. A BMI of 30.00 kg/m2 and above was categorized as obesity. A waist circumference of 88 cm above (female) and 102 cm above (male) was categorized as central obesity. A blood pressure of 120 to 139 mmHg (systolic) or 80 to 89 mmHg (diastolic) was classified as prehypertension. The hsCRP of above 3.0 mg/L was classified as a high level.

Results:

52.3% of the subjects were female, and 60.6% of them were living in urban. As 68.8% were obese, 78% were prehypertension, and 30.3% had high hsCRP. There was no association between obesity (BMI) with hsCRP (p > 0.05) yet central obesity (WC) was significantly associated with hsCRP (p = 0.028, PR = 2.8, 95% CI 1.1–6.9). Being female increases by 3.5 higher risk of prehypertension than male (p = 0.015, 95% CI 1.3–9.8) while age was not a risk factor for prehypertension. The nutritional status, determined by BMI and WC, and hsCRP were not significant risk factors for prehypertension, even after being adjusted with covariates.

Conclusion:

Adults with central obesity increased by 2.8 greater risks of high-level hsCRP than normal. Nutritional status and hsCRP were not the risk factors for prehypertension, even after being adjusted with covariates. Comprehensive nutrition intervention, including personalized nutrition and creating a healthier environment, is needed to encourage adults in improving their healthy habits and preventing negative health outcomes.
PS-P10-2: NON-LINEAR RELATIONSHIP BETWEEN CKD PROGRESSION AND SYSTOLIC AND DIASTOLIC BLOOD PRESSURE; IKI EPIDEMIOLOGICAL STUDY OF ATHEROSCLEROSIS AND CKD (ISSA-CKD)
Authors: Maeda Toshiki , Nishi Takumi , Shinohara Yukiko , Abe Makiko , Kawazoe Miki , Satoh Atsushi , Takahashi Koji , Tada Kazuhiro , Itoh Kenji , Yasuno Tetsuhiko , Yoshimura Chikara , Mukobara Shigeaki , Masutani Kosuke , Arima Hisatomi
Published: January 2023

Objectives:

The aim of the study is to assess the non-linear relationship between systolic and diastolic blood pressure and chronic kidney disease (CKD) progression.

Design and Method:

This is a cohort study using annual health check-up data from 2008 to 2018 in Iki City, Nagasaki, Japan. After excluding those who had health check-ups only once or those with the missing value for serum creatinine or urinalysis, a total of 5919 participants were included in the present analysis. The outcome of the present analysis was CKD progression, which was defined as worsening either the glomerular filtration rate stage or albumin creatinine ratio stage according to KDIGO classification at a visit and at the end of follow-up. Non-linear effects of SBP and DBP on the progression of CKD were evaluated by Cox proportional analysis with a restricted cubic spline controlling for confounding factors.

Results:

During a mean follow-up of 4.9 years, 1167(19.7%) CKD progression was observed. As each SBP and DBP were classified into quartiles, there was a linear relationship between SBP and CKD progression (p < 0.001 for trend), on the other hand, there was no linear relationship between DBP and CKD progression (p = 0.534 for trend). For restricted cubic spline, we found a sigmoid curve-like relationship between SBP and CKD progression, in which CKD progression increased in accord with BP increase. For DBP, we found a U-like shape relationship between DBP and CKD progression, in which there was the lowest risk at nearly 70–80 mmHg, and then the risk for CKD progression increased to both lower and higher DBP.

Conclusions:

The findings of the present analysis showed a near-linear trend that higher SBP had a significant relationship with an increase in CKD progression. On the other hand, the relationship between DBP and CKD progression was not linear, and both lower and higher DBP could be related to CKD progression.
PS-P10-6: IDENTIFYING A URINARY PEPTIDOMICS PROFILE FOR HYPERTENSION IN YOUNG ADULTS: THE AFRICAN-PREDICT STUDY
Authors: de Beer Dalene , Mels Catharina MC , Schutte Aletta E , Delles Christian , Samji Sheon M , Mullen William , Mischak Harald , Kruger Ruan
Published: January 2023

Background and Aims:

Hypertension is one of the most important and complex risk factors for cardiovascular diseases. Identifying biomarkers in hypertension may lead to better strategies to understand the development of hypertension. Biomarker discovery through the use of peptidomics may also provide essential information for the prediction and prevention of premature CVD development.

Methods and Results:

We included 78 hypertensive (based on 24-hour ambulatory blood pressure) and 79 normotensive age (20–30-years old), sex and ethnicity (62% black and 48% white) matched participants from the African-PREDICT study. Urinary peptidomics were analysed with capillary electrophoresis time-of-flight mass spectrometry. Hypertension-specific peptide profiles were combined into a single summary multidimensional classifier. When comparing the peptide data between the normotensive and hypertensive groups, 354 peptides were nominally differentially expressed (Wilcoxon p-value less than 0.05). Nonetheless, only three peptides (ID10000 (SHANK1), ID8939 (unsequenced) and ID6841 (unsequenced)) remained significant after rigorous adjustments for multiple comparisons (maxT test) and were more abundant in the hypertensive compared to the normotensive group (all p-value less than 0.001). Furthermore, the 15 nominally most significant peptides (all p-value less than or equal to 0.0013) were combined into a unifying score which differed significantly between the groups (p-value less than 0.001) but had an insufficient prediction capability for hypertension.

Conclusion:

Apart from differential expression of single peptides in hypertensive adults, including ID10000 (SHANK1), no unifying urinary hypertension peptidomics profile was identified with a sufficient prediction capability. Our findings suggest that a downstream multimarker approach cannot reliably represent a complex multifactorial condition such as hypertension.
PS-P10-7: SEVENTY YEARS OF PHEOCHROMOCYTOMAS AND PARAGANGLIOMAS IN ARGENTINA
Authors: Aparicio Lucas S , de Miguel Valeria , Marín Marcos , Paissan Andrea , Sansó Gabriela , Lupi Susana , Barontini Marta
Published: January 2023

In Argentina, data regarding Pheochromocytomas and Paragangliomas (PPGLs) are scarse.

Objective:

to describe demographic, biochemical and genetic characteristics of children and adults with confirmed PPGls.

Design and method:

Observational multicenter study of recruited participants surveyed from a retrospective cross sectional database from january 1953 until January 2022.

Results:

We included 486 patients (58.4% women) from 93 recruiting centers, mean age at diagnosis 38.3, 393 (80.9%) hypertensives, baseline office systolic/diastolic blood pressure 157.8/96.5 mmHg. Of all tumors, 382 (79.6%) were Pheochromocytomas, 67 (13.8%) paragangliomas and 11 (2.3%) mixed. The most prevalent cathecolamin secretion type was noradrenergic (35%), followed by adrenergic (30.6%) and mixed (20.3%). Local recurrence and mestastasis occured in 10% of subjects. The most common symptoms were headache (57%), sweating (57.5%) and palpitations (53.4%). In 147 patients with a genetic syndrome, we found 44 MEN2A, 7 MEN2B, 1 MEN1, 42 Von Hippel Lindau, 11 neurofibromatosis type 1, 32 PGL4, 6 PGL1, 2 MAX, 1 TMEM127, and 1 mosaic EPAS1/HIF2A. We found the genetic variant types in 102 patients.

Conclusions:

Our results are consistent with other publications from foreign databases. PPGls are rarely diagnosed in Argentina, and the genetic profile is lacking in three fourths of patients.
PS-R03-5: HYPOTENSIVE AND HYPERGLYCEMIC EFFECTS OF DIAZOXIDE IN A CASE OF INSULINOMA
Authors: Yamagishi Toshio
Published: January 2023

Case report:

We report the case of sporadic insulinoma in a 70-year-old female with breast cancer and hypertension treated by irbesartan 100 mg and benidipine 8 mg, who presented with a 1-month history of episodic tremulousness, diaphoresis, increased hunger, confusion and fainting. Initial laboratory investigations showed low blood glucose (21 mg/dL) and high blood insulin (107 μU/mL) levels. The hypoglycemic symptoms were relieved greatly by glucose administration and Whipple's triad for insulinoma was met. An abdominal contrast-enhanced computed tomography scan showed a 12 mm, small, well demarcated, heterogeneously enhancing lesion within the tail of pancreas without dilatation of pancreatic duct. The site also showed a well-defined accumulation of boundaries on PET-CT. Patient was diagnosed with insulinoma. Since Patient did not initially wish to undergo surgery, blood glucose control was performed by taking diazoxide 225 mg, gradually reduced to 50 mg. Before and after taking diazoxide, blood glucose increased from 75 ± 40 mg/dL to 124 ± 35 mg/dL significantly (p < 0.05). On the other hand, blood pressure was significantly reduced from 141 ± 3/78 ± 3 mmHg to 126 ± 3/75 ± 3 mmHg. Benidipine was withdrawn to about 130/80 mmHg. Then, Patient changed her mind and underwent laparoscopic caudal pancreatic resection. Histopathological examination of the pancreatic mass confirmed neuroendocrine tumor (insulinoma). Patient had an uneventful recovery. Blood pressure re-increased above 140/90 mmHg and benidipine was resumed. Although diazoxide suppresses insulin secretion in the pancreas due to its KATP channel opening action and improves hypoglycemic attacks with insulinoma, it also acts on the KATP channel of vascular smooth muscle and show a hypotensive effect. It is important to pay close attention not only to blood glucose but also to blood pressure fluctuations when using diazoxide.
PS-R04-3: A CASE OF RESISTANT HYPERTENSION
Authors: Nakajima Yuya , Irie Junichiro , Nakamura Toshifumi , Kawano Yoshinaga , Ito Arata , Kinouchi Kenichiro , Kobayashi Sakiko , Meguro Shu , Itoh Hiroshi
Published: January 2023

Background:

Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg despite the use of three antihypertensive medications of different classes at the maximally tolerated doses, one of which is a diuretic. It is reported that approximately 10% of patients with hypertension have resistant hypertension, but the optimal management of resistant hypertension remains to be unclear.

Case presentation:

A 56-year-old Japanese woman visited our hospital because she presented high blood pressure of about 170/100 mm Hg even after the treatment by her primary physician. She had hypertension after giving birth at age 26 and her blood pressure was about 170/100 mm Hg. She was suspected of having secondary hypertension and the laboratory and imaging examination were conducted. The functions of the adrenal gland and thyroid were normal, and the renal artery stenosis and chronic kidney disease were excluded. She did not have NSAIDs, oral contraceptives, and herbal products. Although she had been intensively treated for hypertension, she suffered from a brain hemorrhage. Her systolic blood pressure has been still not controlled appropriately by 80 mg of nifedipine, 400 mg of the combination of sacubitril/valsartan, 2.5 mg of esaxerenone, 2 mg of trichlormethiazide, and 9 mg of bisoprolol transdermal patch daily.

Conclusion:

Because patients with resistant hypertension have a higher risk of stroke, kidney disease, and heart failure, the careful examination and intensive treatment are necessary.
PS-R04-4: A CASE OF PHEOCHROMOCYTOMA IN A 17-YEAR-OLD MALE
Authors: Liberato Jessa Mae Daranciang , Punzalan Jemely Metra
Published: January 2023

Background:

Pheochromocytoma is a rare catecholamine secreting tumor arising from the adrenal medulla and produces signs and symptoms due to excessive catecholamine secretion from the tumor. It is a rare cause of secondary hypertension and a delay in recognition and treatment can present serious consequences to the patient.

Case Summary:

We present a case of a 17-year-old male with a history of hypertension for 4 years with episodic headache, palpitations, and sweating. He does not have any history of serious illnesses, hospitalizations, or trauma. He was not on any medications. He has a family history of hypertension. He does not drink alcohol, smoke cigarettes, or do any illicit drugs. Upon arrival to the ER, he was conscious, coherent with BP of 170/140mmHg, PR 111bpm, RR 26cpm, and afebrile.

Laboratory work-up showed proteinuria, elevated BUN and creatinine levels, hyponatremia, hypokalemia, and hypocalcemia. A 2D echocardiography showed left ventricular hypertrophy. The whole abdominal CT scan demonstrated a fairly defined hypodense mass in the left suprarenal measuring 4.8 x 6.4 x 4.7 cm. Pheochromocytoma was confirmed by biochemical tests that showed elevated plasma normetadrenaline and 24-hour urine metanephrine. The patient was initially started on an alpha-adrenergic blocker, Terazosin, and a beta-blocker, Propranolol. Blood pressure was still uncontrolled hence calcium-channel blocker, Nicardipine drip was also given to control the blood pressure. During surgery, they noted the mass to be 8x5 cm invading the superior pole to mid pole and renal hilum hence the patient underwent left open adrenalectomy with left radical nephrectomy. Immediately upon removal of the mass, the patient had a hypotensive episode, which was addressed immediately. The histopathologic finding showed no extension of the mass to the kidneys and it is consistent with pheochromocytoma. Blood pressure control without medication was achieved 13 days post-operatively. The patient is regularly monitored for the recurrence of hypertension due to the increased risk of recurrence. The patient is now living with a solitary kidney hence should also be followed up through.

Conclusion:

Although it is a rare condition, pheochromocytoma should be considered a differential diagnosis in young patients presenting with unexplained hypertension, headache, and palpitations. A multidisciplinary approach is the best way to achieve success in the management of a patient with pheochromocytoma.
PS-R04-5: A CASE OF SEVERE RENAL FAILURE WITH HYPERTENSIVE EMERGENCY WHO SUCCEEDED IN HEMODIALYSIS WITHDRAWAL BY STRICT CONTROL OF BLOOD PRESSURE
Authors: Kato Naoyuki , Mizumoto Teruhiko , Izumi Yuichiro , Kuwabara Takashige , Mukoyama Masashi
Published: January 2023

Introduction:

Hypertensive emergency is a condition in which progressive and irreversible organ damages occur as a result of extremely elevated blood pressure. Although the prognosis for renal outcomes has been improved by advances in antihypertensive therapy, the cases who result in maintenance dialysis are still not uncommon. We herein report a case of hypertensive emergency who was successfully withdrawn from hemodialysis by intensive treatment.

Case presentation:

A 55-year-old woman, whose systolic blood pressure was 150–160 mmHg constantly for at least 2 years, was seen by her primary care physician due to nocturnal cough and respiratory distress. She exhibited marked hypertension (diastolic blood pressure, 120–130 mmHg) and renal dysfunction (serum creatinine (sCr), 2.76 mg/dL, baseline 0.5 mg/dL). She was diagnosed as hypertensive emergency and was treated with antihypertensive agents immediately. Despite the treatment, her renal function did not improve, so that she was transferred to our hospital for further examination and intensive treatment. While imaging examination revealed a right adrenal tumor, for which primary aldosteronism was suspected, endocrinological examinations showed high plasma aldosterone concentration with high plasma renin activity; therefore it was assumed that the hormonal changes were secondary to hypertensive emergency. Although funduscopic findings were relatively mild (KW-IIb), the condition was considered as accelerated-malignant hypertension caused by essential hypertension. A renal biopsy revealed extensive interstitial damage with onion skin-like lesions, which led to a diagnosis of malignant nephrosclerosis. While continuing strict antihypertensive management including the renin-angiotensin system blockade, hemodialysis was started on day 17 due to progressive renal dysfunction (sCr 9.27 mg/dL). Continuous intensive treatment gradually alleviated renal dysfunction, and hemodialysis was finally withdrawn on day 38. There was no further deterioration seen, and the patient was discharged on day 55. After discharge, her renal function was kept improved and her sCr was 2.5 mg/dL 6 months after the discharge.

Discussion and Conclusion:

Hypertensive emergency may cause irreversible kidney damage without appropriate antihypertensive therapy. In particular, acute tubular damages have been suggested to correlate with both systolic and diastolic blood pressures. Controlling blood pressure appropriately is crucial to protect kidneys against disease progression and even reverse kidney damage upon acute renal failure with hypertensive emergency.
PS-R04-6: A CASE OF MALIGNANT NEPHROSCLEROSIS WITHDREW FROM TEMPORARY HEMODIALYS
Authors: Daikoku Kensuke , Noguchi Yuji , Yamada Gen , Sugiura Akira , Kudo Masataka
Published: January 2023

In the Case of AKI (acute renal injury) due to malignant hypertension, appropriate BP (Blood Pressure) management is important and sometimes requires hemodialysis. Here we report a 49-year-old female patient with malignant hypertension, AKI and acute pulmonary edema. She presented with severe hypertension (BP213/150 mmHg), high serum creatinine level (Cr12.74 mg/dL), congestive heart in chest radiographic findings and nerve head edema (Scheie: H4S3). There were no findings associated with renal artery stenosis. She was diagnosed as AKI due to malignant hypertension. Nicardipine continuous intravenous infusion was carried out for BP control and temporary hemodialysis had begun almost simultaneously. On Day 5 of admission, she had received oral Ca blocker and low dose of ACE inhibitor (temocapril). BP level remained stable thereafter. Nevertheless, oliguric renal failure lasted for several weeks. On Day 10 of admission, we performed renal biopsy and confirmed onion-skin-like intimal thickening and luminal narrowing findings. These were corresponded to malignant nephrosclerosis, not to chronic nephritic syndrome. We continued 2 times per week hemodialysis using the indwelling catheter after discharge. Her daily urinary output increased substantially day by day (over 1000 ml/day) and her serum creatinine level became less and less around Cr 4.0 mg/dL. This case withdrew temporary hemodialysis over a period of five months conclusively. In some cases, renal dysfunction is improved slowly in the long-term course by appropriate BP management. Accordingly, it is necessary to evaluate the possibility whether or not withdrawing from hemodialysis in the cases of AKI due to malignant hypertension.
PS-R05-8: THREE PATIENTS WITH CHRONIC KIDNEY DISEASE WHEREIN ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR WAS EFFECTIVE AGAINST HEART FAILURE AND HIGH BLOOD PRESSURE
Authors: Sato Eiichi , Tanaka Hiroaki , Sato Shohei , Degawa Manaka , Ono Takao , Lu Hongmei , Matsumura Daisuke , Nomura Mayumi , Moriyama Noriaki , Amaha Mayuko , Nakamura Tsukasa
Published: January 2023

Background:

The efficacy and safety of angiotensin receptor neprilysin inhibitor (ARNI) for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 have not been established. This paper reports three cases of low eGFR wherein ARNI was effective against heart failure and high blood pressure. Case: In case 1 (a woman in her 70 s), eculizumab was used to treat chronic kidney disease (CKD) because of an atypical hemolytic uremic syndrome. Surgery was performed for the exacerbation of chronic heart failure due to worsening mitral regurgitation. The postoperative course was stable. However, from the third disease day, her kidney failure exacerbated (eGFR decline from 16 to 10 mL/min/1.73 m2), heart failure flared up again (B-type natriuretic peptide [BNP] elevated from 500 to 1200 pg/mL), hemodialysis was performed, carperitide was added, and the diuretic stage was started. However, the drug could not be discontinued, and ARNI was initiated (50 mg once twice a day). Consequently, the eGFR was recovered (elevated from 10 to 18 mL/min/1.73 m2), the urine output was increased, and the heart failure was recovered (BNP declined from 1200 to 250 pg/mL). In case 2 (a man in his 80 s), CKD exacerbation due to diabetic nephropathy (eGFR of 18 mL/min/1.73 m2) led to heart failure, and hemodialysis therapy and ARNI (50 mg once two times a day) were initiated. Good diuresis became available, and hemodialysis could be withdrawn (BNP declined from 120 to 70 pg/mL, and the bodyweight from 95 to 75 kg). Since then, the urine output has been maintained, and peritoneal dialysis has been initiated and continued. In case 3 (a man in his 70 s), in whom 6 months had elapsed since the initiation of hemodialysis therapy for CKD caused by diabetic nephropathy, the dry weight was appropriate, but the blood pressure tended to increase (from 140/80 to 186/96 mmHg). Moreover, BNP levels had increased (BNP elevation from 70 to 180 pg/mL). When telmisartan 40 mg once a day was changed to ARNI (100 mg once a day) as an antihypertensive agent, the blood pressure was stabilized (from 186/96 to 140/80 mmHg), and the BNP decreased (BNP declined from 180 to 20 pg/mL). No adverse events were observed in all three cases. Discussion: These cases suggest that ARNI not only has diuretic effects but decreases blood pressure and BNP in patients with CKD, including those requiring dialysis. ARNI may be used relatively safely even in patients with reduced kidney function.
PS-B10-6: CAPILLARY-TO-ARTERIOLAR SIGNALLING, INFLAMMATION AND SMALL VESSEL DISEASE OF THE BRAIN
Authors: Evans Lowri Elizabeth , Taylor Jade , Dabertrand Fabrice , Pritchard Harry , Schiessl Ingo , Allan Stuart , Greenstein Adam
Published: January 2023

Objective:

Chronic cerebral inflammation is thought to be a mechanism by which hypertension causes small vessel disease of the brain, leading to dementia. Mouse studies have demonstrated enhanced small resistance artery constriction and neurovascular uncoupling in hypertension. We wished to examine whether acute exposure to the predominant inflammatory driver in hypertension, interleukin-1β; (IL-1β;) could account for this dual vascular deficit.

Design and method:

Pressure myography of freshly isolated mouse posterior cerebellar pial arteries was used to assess contributions of the inwardly rectifying K+ 2.1 (KIR2.1) channel to vasodilation. In order to assess neurovascular coupling from a vascular perspective, we adopted a recently described approach: the Capillary to Parenchymal Arteriole (CaPA) preparation. In the CaPA preparation, penetrating arterioles (< 40ums) with attached capillary branches are isolated and pressurised. The capillary branch and arteriole are independently stimulated via a micropipette and arteriole diameter is recorded. This approach enables the retrograde hyperpolarising signal from the KIR2.1 channel, which propagates against the flow of blood in the brain, to be assessed both in terms of the extent of arteriole vasodilation and the speed of communication (video).

In order to assess the effects of perivascular inflammation on cerebrovascular function, we incubated (in culture medium) small pial arteries with IL-1β; for 24 hours prior to study on a pressure myograph rig. KIR2.1 function was assessed using 10 mM exogenous K+. Cerebral arterioles with attached capillaries were incubated with IL-1β; for 2 hours prior to CaPA study. We then examined the capillary-to-arteriolar signalling mechanism via application of 10 mM K+ to the capillary. We also assessed arteriolar tone and reaction to directly applied K+, NS309 and U46619.

Results:

Preliminary data suggests that sub-acute incubation with exogenous IL-1β; had no effects on the degree of pressure induced constriction of either the pial artery or the arteriole. CaPA preparation showed that the KIR2.1 capillary-to-arteriolar signalling was preserved as well as arteriolar responses to direct K+, NS309 and U46619 following IL-1β; exposure.

Conclusions:

Whilst chronic cerebral inflammation in the setting of hypertension results in cerebrovascular deficits, sub-acute exposure with IL-1β; does not appear to significantly impair cerebral microvascular function. Precisely how chronic exposure to inflammation in hypertension induces neurovascular uncoupling is the subject of ongoing investigation.
PS-B12-7: PERSISTENT REDUCTION IN RENAL RENIN FOLLOWING EARLY TREATMENT OF SPONTANEOUSLY HYPERTENSIVE RATS WITH LOSARTAN
Authors: Harrap Stephen , Suphapimol Vera , Byars Sean , De Vries Nathan , Prestes Priscilla , WilkinsonBerka Jenny , Charchar Fadi
Published: January 2023

Objective:

Abnormalities of renin-angiotensin system (RAS) and renal function have been reported in young spontaneously hypertensive rats (SHR) and blood pressure (BP) can be permanently reset to lower levels after brief early treatment with RAS inhibitors. We sought to determine whether renal renin was affected long-term by early RAS blockade.

Design:

Male SHR were treated via minipump from 10–14 weeks of age with vehicle (Veh, n = 12) or losartan (Los, n = 14, 7.5 mg/kg/d). Four Veh and six Los SHR were culled at 14-weeks and the remaining animals at 20-weeks. To control for effects of low BP another group received hydralazine (HZ, n = 6, 1 mg/kg/d) from 10–20 weeks.

Methods:

At 14- and 20-weeks systolic BP was measured, and kidneys collected. Three micrometer paraffin sections of renal cortices were counterstained with hematoxylin for renin immunolabelling, assessed for each animal as the percentage of labelling in 200 glomeruli which displayed the afferent arteriole entering the glomerulus.

Results:

At 14-weeks the systolic BP (mean ± SEM) was significantly (P < 0.001 by ANOVA) lower in both the Los (145 ± 7 mmHg) and HZ (153 ± 7 mmHg) SHR compared with Veh (206 ± 6 mmHg). At 20-weeks, the same pattern persisted (Los: 187 ± 6 mmHg; HZ: (155 ± 4 mmHg; Veh: 220 ± 6 mmHg) (P < 0.001 by ANOVA). Renal renin immunolabelling increased dramatically during treatment at 14-weeks (44.8 ± 1.1%) compared with Veh (10.5 ± 1.7%) (P < 0.0001 by ANOVA). However, at 20-weeks renal renin was significantly lower in Los (7.7 ± 0.9%) (P < 0.05 by ANOVA) compared with Veh (11.9 ± 1.2%), while renal renin was significantly higher in HZ kidneys (18.0 ± 1.0%) than both Los and Veh kidneys (P < 0.01 by ANOVA).

Conclusions:

The persistently low BP in SHR following brief early treatment with losartan is associated with reduced renal renin. Normally one would expect activation of the renal RAS with lower BP, as observed with the hydralazine-treated SHR. These results suggest that long-term reduction in renal renin following brief early RAS blockade in SHR might cause the persistently reduced BP seen in these animals.
PS-B12-10: CLASSIC CARDIOVASCULAR PROTECTIVE SIGNALING IN ANGIOTENSIN II-INDUCED NOVEL PREECLAMPSIA RAT MODEL
Authors: Cui Huixing , Jin Li Yuan , Liu Jun Xian , Zhang Yin Hua
Published: January 2023

Angiotensin II (Ang II)-induces vasoconstriction, in vivo perfusion has been shown to induce preeclampsia (PE) in pregnant rats. In this study, we aimed to examine the protein and mRNA expressions of endothelial and neuronal NOS (eNOS, nNOS) as well as angiotensin II type 2 receptor (AT2R) in normal pregnant and Ang II-induced PE rats.

Pregnant (8 weeks) and non-pregnant SD rats (8 weeks, GD-8) were infused with Ang II via an osmotic minipump (1 ug/kg/min), and the rats (GD-21) were sacrificed 13 days later. Pregnant and non-pregnant rats without Ang II were taken as sham controls. The fetal weight, crown-rump length and placental weight of PE rats were significantly lower compared to those without Ang II infusion. Immunohistochemistry results showed an approximately 30% increase in glomerular volume, suggesting morphological changes in the kidney and Ang II infusion exhibits a PE phenotype. Ang II infusion did not affect AT2R, AT1R and nNOS protein or mRNA expression in the uterus of non-pregnant or pregnant rats. However, eNOS mRNA expression was reduced in PE rats (p < 0.0001) although protein expression was not affected by Ang II infusion. However, in the placenta, AT1R and AT2R protein expression were not different in PE, but AT2R mRNA was decreased (p < 0.0001). eNOS protein was only expressed in fetal vascular endothelial cells, and eNOS protein expression was higher in PE rats (P = 0.001) but eNOS mRNA was decreased (p = 0.0096). Notably, strong nNOS expression was observed in placental trophoblast cell groups of sham and PE rats, and both mRNA and protein expression of nNOS was decreased in placental lysates of Ang II rats (respectively p = 0.0287 and p < 0.0001).

These results demonstrate that we have recapitulated the PE model of Ang II infusion in rats. The expression of nNOS was reduced, and the localization of nNOS in the trophoblast suggested a new functional remodeling in the fetal vasculature.

In the placenta, decreased expression of AT2R and nNOS may be a novel mechanism of impaired fetal development.
PS-C28-8: CILOSTAZOL CONTRIBUTES TO RISK REDUCTION OF STROKE RECURRENCE WITHOUT LOWERING BLOOD PRESSURE: RESULTS FROM CSPS.COM
Authors: Miwa Kaori , Saita Ryotaro , Omae Katsuhiro , Koga Masatoshi , Yamaguchi Takenori , Toyoda Kazunori
Published: January 2023

Background:

The Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com) found that the dual therapy with cilostazol plus aspirin or clopidogrel reduced the risks of recurrent ischemic stroke compared with monotherapy with aspirin or clopidogrel alone in patients with non-cardioembolic ischemic stroke. As its putative mechanisms, cilostazol can serve a role in the inhibition of angiotensin 2-induced endothelial cell apoptosis and vasodilation, which may yield lower systolic blood pressure (SBP). We aimed to determine to what extent the effect on ischemic stroke recurrence was mediated through blood pressure reduction due to cilostazol.

Methods:

In a post hoc analysis of CSPS.com, we defined change in SBP as the change in SBP at the last visit compared with baseline and treated it as a time-dependent mediator. We performed causal mediation analyses to separate the overall effects of the cilostazol on the first recurrence of the symptomatic ischemic stroke into indirect effects (mediated by change in SBP on cilostazol) and direct effects (mediated through pathways other than change in SBP on cilostazol). The effects were summarized by cumulative hazard rate difference.

Results:

In the ITT population, ischemic stroke recurred in 29 (3%) of 932 patients on dual therapy and 64 (7%) of 947 patients on monotherapy during a median 1.4-year follow-up. The estimates for effect of SBP (per 1mmHg increase) on the stroke recurrence at 24-months follow-up was 0.0007 (95% confidence interval [95% CI] 0.00018 to 0.0013). The effect estimates for direct effect and indirect effect of the cilostazol on the stroke recurrence at the same follow-up were -0.045 (95% CI, -0.071 to -0.015) and -0.0007 (95% CI, -0.0023 to 0.00053), respectively. The results of the adjusted model with age were similar.

Conclusions:

Although it was shown that change of SBP was associated with an increased risk of stroke recurrence, there was no evidence that change in SBP mediated the association between cilostazol and ischemic stroke recurrence, indicating that cilostazol contributed to risk reduction of stroke recurrence without through change in SBP.
PS-C29-4: EVALUATION OF HYPERTENSION COMPLICATIONS AFTER THE START OF WEIGHT MANAGEMENT THERAPY IN OBESITY
Authors: Goto Nobuko , Kita Motoko , Irie Junichiro , Itoh Hiroshi
Published: January 2023

Objective:

We evaluated 86 patients who attended the obesity outpatient clinic continuously for 3 years from their first visit. The assessment items were weight progress and hypertensive complications during this period.

Design and method:

For patients with body mass index (BMI) less than 35, weight loss of 3% or more was considered successful weight loss; for BMI 35 and above, weight loss of 5% or more was considered successful weight loss. The group that regained weight less than 25% of the weight lost after successful weight loss was defined as the weight loss maintenance group. The group that regained weight more than 25% of the weight lost was defined as the weight loss regain group. The group that gained weight less than 3% of BMI < 35 and less than 5% of BMI 35 or greater was defined as the maintenance group. The group with greater weight gain than 3% of BMI < 35 and 5% of BMI 35 or greater without successful weight loss was defined as the gradual weight gain group.

Results:

Patients with an ambulatory blood pressure of 140/90 mmHg or higher or those taking antihypertensive medication were considered to have a hypertension complication. At the initial visit, the percentage of patients with hypertension was 65% in the weight loss maintenance group, 57% in the weight loss regain group, 65% in the maintenance group, and 63% in the gradual weight gain group, with no apparent difference.

Conclusion:

In this report, we describe the status of hypertension complications in the four groups at 6 months, 1 year, 2 years, and 3 years after the start of weight management therapy in obesity.
PS-C29-5: PULMONARY HYPERTENSION AND RIGHT VENTRICULAR REMODELING IN OBSTRUCTIVE SLEEP APNEA
Authors: Takada Yoichiro , Shiina Kazuki , Takahashi Takamichi , Nakano Hiroki , Fujii Masatsune , Matsumoto Chisa , Chikamori Taishiro , Tomiyama Hirofumi
Published: January 2023

Background and Objective:

Acute pulmonary artery (PA) pressure changes during sleep have been extensively reported in obstructive sleep apnea (OSA). However, the role of OSA as an independent risk factor for the day-time pulmonary hypertension (PH) is not well known. The present study was conducted to examine whether OSA is associated with PH and right ventricular (RV) remodeling.

Methods:

423 OSA patients without chronic obstructive pulmonary disease or left ventricular dysfunction {age: 55 ± 13 years old, mean apnea-hypopnea index (AHI): 41 ± 22 /h} were enrolled in this study. All patients were performed polysomnography, echocardiography and spirometry. Pulmonary artery systolic pressure (PASP) was determined by continuous-wave Doppler using the simplified Bernoulli equation. For this study, PH was defined as an estimated PASP of greater than 30 mmHg. Patients were divided into two groups: mild-moderate OSA group (n = 153) (AHI = 5–30 /h) and severe OSA group (n = 270)(AHI over 30/h).

Results:

The prevalence of PH among all OSA patients was 19%. No significant differences were found in PASP, tricuspid annular velocity and tricuspid annular plane systolic excursion (TAPSE) between mild-moderate OSA group and severe OSA group. However, RV diastolic diameter (28.7 ± 3.4 vs 27.7 ± 3.0 mm, respectively, P < 0.01) and main PA diameter (26.2 ± 3.7 vs 24.8 ± 3.9 mm, respectively, P < 0.05) were significantly higher in severe OSA group than those in mild-moderate OSA group.

Conclusions:

The severity of OSA was significantly associated with RV and PA diameters independently PASP. These results suggested that OSA may directly affects RV and PA remodeling independently PH.
PS-C29-8: EFFECT OF WEIGHT GAIN ON ARTERIAL STIFFNESS AND PRESSURE WAVE REFLECTION: A 9-YEAR LONGITUDINAL STUDY
Authors: Fujii Masatsune , Tomiyama Hirofumi , Takahashi Takamichi , Nakano Hiroki , Matsumoto Chisa , Shiina Kazuki , Chikamori Taishiro , Yamashina Akira
Published: January 2023

Background and Aim:

Obesity is a causal factor for conventional risk factors for cardiovascular disease (CVD), and these risk factors affect increased arterial stiffness and also abnormal pressure wave reflection in arterial tree. Even so, because of the potent direct influences of these risk factors on arterial stiffness and pressure wave reflection, the direct effect of obesity on these vascular abnormalities has been still controversial. Then, the present study examined the effect of weight gain on those vascular abnormalities.

Methods and Results:

In 4016 middle-aged (43 ± 9 years) healthy Japanese men without CVD at the study baseline, body weight, risk factors for CVD, brachial-ankle pulse wave velocity (baPWV), and radial augmentation index (rAI) were measured at the baseline and end of study period (mean duration of follow-up was 6.3 years). The study subjects were divided into 3 groups by the change of BMI during the study period. While the change of baPWV in the highest tertile range of increase in BMI (57 ± 138 cm/sec) was larger than that in the lowest tertile range of increase in BMI (46 ± 136 cm/sec)(P < 0.05), these differences were not significant after the adjustment of changes of blood pressure. In addition, the change of rAI was similar between both groups.

Conclusions:

Weight gain may affect increase in arterial stiffness rather than abnormal pressure wave reflection, and this effect may be mediated by increase in blood pressure related to weight gain rather than the direct effect of weight gain.
PS-C29-11: IMPACT OF UNDERWEIGHT, OVERWEIGHT, AND OBESITY ON ENDOTHELIAL FUNCTION: FMD-JAPAN REGISTRY
Authors: Kajikawa Masato , Maruhashi Tatsuya , Kishimoto Shinji , Harada Takahiro , Hashimoto Yu , Mizobuchi Aya , Han Yiming , Yusoff Farina Mohamad , Nakashima Ayumu , Higashi Yukihito
Published: January 2023

Background:

The association of body weight with cardiovascular outcomes is still controversial. The aim of this study was to evaluate the association between body mass index (BMI) and endothelial function.

Methods:

We evaluated endothelial function by measuring flow-mediated vasodilation (FMD) in 7682 men. All participants were divided into four groups by BMI: underweight (< 18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight (25.0 to 29.9 kg/m2), and obesity (≧ 30.0 kg/m2). We evaluated the cross-sectional associations between endothelial function and BMI.

Results:

After adjustment for various confounders, overweight (OR: 1.30, 95% CI: 1.14–1.47; P < 0.001) and obesity (OR: 1.40, 95% CI: 1.09–1.80; P = 0.009) were associated with endothelial dysfunction. In 5571 younger adults (< 60 years), overweight (OR: 1.34, 95% CI: 1.16–1.55; P < 0.001) and obesity (OR: 1.37, 95% CI: 1.04–1.81; P = 0.03) were associated with endothelial dysfunction, and underweight (OR: 0.56, 95% CI: 0.35–0.89; P = 0.01) was associated with a reduced risk of endothelial dysfunction. In 2111 older adults (≧ 60 years), underweight (OR: 2.16, 95% CI: 1.22–3.80; P = 0.008) was associated with endothelial dysfunction, and overweight and obesity were not associated with endothelial dysfunction.

Conclusions:

Endothelial function was impaired in the overweight and obesity groups compared with that in the normal weight group. The risk for endothelial dysfunction was higher in obese younger adults than in obese older adults. The association of BMI with endothelial function may be different in young and elderly men.
PS-C29-12: EFFECTS OF WEIGHT LOSS ON THE METABOLIC PROFILE AND CENTRAL HEMODYNAMIC PARAMETERS IN OBESE WITH MODERATE-SEVERE OBSTRUCTIVE SLEEP APNEA
Authors: Cardoso Samanta Mattos , Cunha Michelle Rabello , Klein Márcia Torres , Neves Mário Fritsch
Published: January 2023

Introduction:

Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. The presence of OSA and obesity may have synergistic effects on the progression of cardiovascular disease.

Objective:

To evaluate the effect of weight loss on vascular disease in obese patients with moderate or severe OSA.

Design and method:

Individuals of both sexes, aged 40 to 70 years, body mass index (BMI) > = 30 and < 40 kg/m2, were submitted to nutritional intervention for 16 weeks with restriction of 800 kcal/day, and assessment of central parameters by oscillometry (Mobil O Graph). The sleep study was conducted using a portable home device (WatchPAT).

Results:

Patients (n = 60) were divided into two groups based on the apnea hypopnea index (AHI): absent mild (AM) group (AHI < 15 events/h, n = 23) with BMI = 35 ± 3 kg/m2 and moderate severe (MS) group (AHI > = 15 events/h, n = 37) with BMI = 34 ± 3 kg/m2. After the intervention, weight loss was similar in both groups (4.80 vs 4.18 kg). Cardiovascular risk was significantly reduced in the AM group [4.7 (3.2;7.4) vs 4.1 (2.7;6.1) %, p = 0.039] and the MS group [8.0 (5.0;15.0) vs 6.7 (4.6;15.0) %, p = 0.003] after intervention. Both groups also showed a significant reduction in BMI, insulin and C-reactive protein. Only the MS group presented a significant decrease in HOMA-beta [227 (147;317) vs 193 (156;278), p = 0.033], uric acid [5.3 (3.9;6.3) vs 5.1 (3.7;6.0) mg/dl, p = 0.042] and vascular age [54 ± 9 vs 52 ± 9 years, p = 0.010]. The AHI decreased in the MS group [26 (18;34) vs 20 (12;25) events/h, p = 0.007] and increased in the AM group [8 (5;11) vs 11 (7;15) events/h, p = 0.011]. The MS group showed a significant reduction in the oxygen desaturation index [14 (9;19) vs 9 (6;14) events/h, p =  < 0.001] and in the Epworth sleepiness scale [10 (6;14) vs 8 (4;11) points, p = 0.004]. Central systolic pressure [114 (103;130) vs 110 (102;118) mmHg, p = 0.004] and pulse wave velocity [PWV) (7.7 (7.0;8.5) vs 7.3 (6.7;8.5) m/s, p = 0.015] were also significantly reduced in the MS group.

Conclusion:

Weight loss resulted in more benefits in moderate to severe OSA obese individuals, reducing AHI and improving functional capacity of pancreatic beta cells, with favorable effects on arterial stiffness and central hemodynamics in this population.
PS-C30-1: URINARY ANGIOTENSINOGEN-MELATONIN RATIO IN GESTATIONAL DIABETES AND PREECLAMPSIA
Authors: Valias Gabriela R , Gomes Patricia RG , Amaral Fernanda G , Alnuaimi Saif , Monteiro Daniela , OSullivan Siobhan , Zangaro Renato , Neto Jose Cipolla , Acuna Juan , Baltatu Ovidiu C , Campos Luciana A
Published: January 2023

Objective:

A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications.

Design and Methods:

This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort.

Results:

Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups.

Conclusion:

These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.