bluuebunny/crossref_metadata_2025_split huggingface dataset:
JS-NG-8: CASE REPORT: POSSIBLE NEW CHANNELOPATHY ASSOCIATED WITH ELEVATED ALDOSTERONE LEVELS
Authors: Iatan Iulia , Mellor Kaitlyn , Khan Nadia 
Published: January 2023

Background:
Potassium channelopathies are associated with prolonged QT cardiac syndrome. New potassium channelopathies in somatic cells, including KCNJ5 mutations, also underlie some forms of primary hyperaldosteronism. We present a first-in-human report of an association between a KCNQ1 loss of function mutation manifesting with life threatening-ventricular tachycardia (VT), severe hypokalemia and presumed hyperaldosteronism.

Case Presentation:
The patient is a 51-year-old Asian woman known for obesity, Wolff-Parkinson-White post ablation, and recurrent syncopal episodes with polymorphic VT due to prolonged QTc, requiring an implantable cardioverter defibrillator. On initial presentation for syncope, spontaneous hypokalemia was discovered at 3.1 mmol/L. She had multiple hospitalizations for torsade storms and persistent hypokalemia resistant to aggressive potassium supplementation until addition of spironolactone. Investigations revealed a suppressed plasma renin activity < 0.05 ng/L/s, serum aldosterone concentration at 302 pmol/L, and an aldosterone to renin ratio (ARR) > 6040. Repeated ARR was > 10980. Confirmatory saline suppression testing or adrenal vein sampling were not performed due to risk of recurrent VT associated with spironolactone cessation. A comprehensive evaluation for the etiology of this patient's clinical presentation revealed a mutation in the KCNQ1 gene type 1.

Literature review:
The voltage-dependent K(+) channel responsible for activating delayed K(+) current is composed of pore-forming KCNQ1 and regulatory KCNE1/3 subunits which loss of function predispose to sustained torsade de pointes. Animal models demonstrate that KCNQ1 and KCNE1 mRNAs are expressed in the zona glomerulosa of adrenal glands where potassium channels directly participate in the control of aldosterone production. Although KCNE3 is not expressed in mouse adrenals, its deletion is thought to cause activation of lymphocytes targeting adrenal glands, leading to hyperaldosteronism. Furthermore, administration of spironolactone to KCNE3 knockout mice ameliorates their QT prolongation and predisposition to VT. There have been no case reports of an association between KCNQ1/E1/E3 loss of function and hyperaldosteronism in humans.

Conclusion:
This raises the question if this mechanism can also be a component of human KCNQ1 and KCNE1/3-linked arrhythmogenesis and hyperaldosteronism. Alternatively, we can further speculate that patients with hyperaldosteronism who develop malignant arrhythmias during hypokalemia are subjects with impaired repolarization reserve as a consequence of variants in genes known to cause long QT syndrome. The variants, leading to subclinical ion channel dysfunction, are typically silent until unmasked by electrolytes abnormalities such as hypokalemia. To our knowledge, this case is a first report of a potentially novel channelopathy associated with hyperaldosteronism in humans. These findings are hypothesis generating and require further investigations.
JS-WHL-ISH-RTSL-2: WHY SHOULD WE WORRY ABOUT SODIUM INTAKE, IF WE INCLUDE A DIURETIC IN THE HYPERTENSION TREATMENT REGIMEN ?
Authors: Lackland Daniel T 
Published: January 2023

The causal role of sodium intake on blood pressure level has been long recognized. While the pathophysiological link between hypertension and cardiovascular, cerebrovascular, and renal disease events are clear, there is evidence that sodium has an independent direct effect on target organs through multiple mechanisms including vascular damage, oxidative stress, hormonal alterations, the immune system and the gut microbiome. Thus, reduction in salt and sodium intake is an important global strategy to reduce disease burden.
Certainly sodium is an essential element for homeostasis, but the levels of consumption far exceed the amount needed for physiological function. Likewise, considerable evidence indicates reduction in sodium consumption is associated with significant reduction in blood pressure in all individuals at the population level. Individual response to sodium intake is variable, but should be considered a risk factor when consumption is excessive. Interventions such as the DASH-sodium (Dietary Approaches to Stop Hypertension) study has clearly demonstrated benefit from sodium reduction.
In nearly all populations acculturated to an industrialized lifestyle, blood pressure increases with age resulting with an increasing hypertension prevalence. Thus, salt intake becomes increasingly relevant at all ages.. Nonetheless the levels of salt consumption that are recommended remain debated. Contributing to the varying study results are the individual differences in salt sensitivity. Therefore, for salt-sensitive risk groups in the population, stricter limits of salt consumption should be implemented, with a specific target to the young before target organ damage. Maximum prevention benefit for reduced sodium consumption should target children. The magnitude of blood pressure lowering achieved with sodium reduction has a dose-response relationship with greater impact in older, non-white, and hypertensive populations.
Many factors contribute to blood pressure and risk reduction with salt consumption leading to unclear and less precise results and conclusions. Individuals with salt-sensitive hypertension and/or low-renin hypertension typically have factors conducive to treatment with a diuretic. As salt-sensitive hypertension is more common in black patients, older adults, patients with more severe hypertension, and patients with co-morbidities, diuretics have been shown to be particularly effective with salt reduction adding additional benefit.
JS-WHL-ISH-LANCET-3: HOW CAN CLINICIANS AND THE PUBLIC DETERMINE WHETHER A BLOOD PRESSURE MEASURING DEVICE IS CLINICALLY VALID?
Authors: Stergiou George S 
Published: January 2023

The global market of blood pressure (BP) measuring devices was estimated at USD 2.1 billion in 2021, and the forecast is to grow at 13.5% per year and reach USD 4.5 billion in 2027. The accuracy of cuff BP monitors needs to be tested using one of the established validation protocols, such as the US AAMI, the UK BHS, the European ESH-IP, or the ISO. In 2018 the AAMI/ESH/ISO Universal Standard (ISO 81060–2:2018) was agreed for global use, and using the previous protocols in not encouraged anymore. Unfortunately, of almost 5,000 BP device models on the market, fewer than 10% have a validation study documenting the measurement accuracy using one of the above-mentioned validation protocols and the results published in a peer-review PubMed journal. Another issue is that an electronic BP monitor which has been successfully validated in adults may not be accurate in some special populations, including children, pregnant women, individuals with very large arms (circumference larger than 42 cm) and patients with arrhythmias (particularly atrial fibrillation). Thus, separate validation is necessary in these populations. Thus, it is essential that healthcare professionals, individuals with hypertension, and the public have access to valid information for which devices are properly validated. In 2003, Eoin OBrien founded the first website providing online updated lists of properly validated BP measuring devices. Several websites are currently available providing lists of validated devices (see Table), of which some are national (devices locally available; website in local language), and others do not have scientific supervision. STRIDE BP is a non-profit organisation founded by 24 distinguished scientists, operating in affiliated with the International Society of Hypertension, the European Society of Hypertension, and the World Hypertension League. STRIDE BP has an online peer-review system for PubMed published validation studies, and applies a review process which is more systematic and strict than that of PubMed journals. Thus, STRIDE BP may reject a device which appears as accurate in a PubMed published validation study. STRIDE BP provides lists of validated devices in 3 languages (English, Spanish, Chinese). List of validated devices are provided for adults, but also separately for children and for pregnant women, for use in the office/clinic, at home, and for 24-hour ambulatory BP monitoring. STRIDE BP also has an online accredited e-learning platform for healthcare professionals, with interactive educational modules for the established BP measurement methods (office, home, ambulatory).
JS-WHL-ISH-LANCET-5: HOW TO ENSURE THE SALE OF CLINICALLY VALIDATED BP DEVICES IN LOW-AND MIDDLE-INCOME COUNTRIES
Authors: Schutte Aletta E 
Published: January 2023

We now know that not only in high-income countries, but also in low- and middle-income countries there is a major challenge in ensuring that BP devices are accurate. When evaluating the global availability of devices online for sale, there was no evidence of validation for 73% of all devices (2486 devices listed on the Medaval database). This global availability may refer largely to high-income countries, but the crux of the challenge is in fact in lower income regions. In fact, more than an estimated 1 billion people with hypertension reside in low- and middle-income countries compared to approximately 350 million in high-income countries based on data from 2010.
A major factor that comes into play in low- and middle-income countries are cost. The health systems of lower income countries are plagued by several challenges, such as managing both infectious and non-communicable diseases. While balancing the management and cost of HIV, COVID-19, malaria and a major rise in obesity and hypertension in an environment with a low physician-to-patient ratio, it is not hard to understand that the cost of a medical device will be a major consideration when deciding on purchasing devices. It has been demonstrated before that non-validated BP devices are cheaper than validated ones in a high-income country, and it is very likely to be the case on lower income regions too. While many clinicians and hospitals may not be aware that the majority of available devices are not validated for accuracy, this may not even be a major consideration in the face of financial challenges. But to ensure better detection, diagnosis and management of hypertension in these settings, perhaps the only intervention to overcome this challenge is to require regulatory approvals of only BP devices that have been validated for accuracy. This is not a simple solution, as effort is required across a range of stakeholders including government regulatory organisations, non-government organisations, manufacturers, researchers, health professionals, and consumers. Only once mandatory validation of BP devices is legislated, the availability of non-validated devices would be stopped.
JS-HR-5: APPROPRIATE BLOOD PRESSURE ASSESSMENT METHODS FOR THE PREVENTION OF HYPERTENSION COMPLICATIONS BY NEW TECHNOLOGIES
Authors: Nozato Yoichi 
Published: January 2023

Blood pressure (BP) values can vary and fluctuate widely depending on the method and the environment of BP measurement. Appropriate measurement and interpretation of BP values enable us to make an accurate diagnosis and treatment of hypertension. The BP measuring approach is shifting from traditional methods (office BP, ambulatory and home BP monitoring) to wearable devices and technology. Self-measured BP as well as BP measured by wearable devices gives us frequent BP values, which allows us to detect high risk population and to reduce cardiovascular risks.
In this session, we will introduce the latest papers on “Hypertension management and device” in the “Hypertension Research up-to-date 2021. ∼ Current topics of hypertension journals.∼” This session will also introduce the significance of blood pressure measurement and the latest blood pressure measurement technologies.
JS-HR-9: A NEW ERA OF PROGRESS IN PRIMARY ALDOSTERONISM TREATMENT, A NEW ALDOSTERONE ASSAY, AND A CLINICAL PRACTICE GUIDELINE
Authors: Yoshida Yuichi , Shibata Hirotaka 
Published: January 2023

Primary aldosteronism (PA), one of the mineralocorticoid receptor (MR)-associated hypertension, is a highly prevalent secondary hypertension that accounts for 5–15% of all hypertension and is a severe hypertension that is prone to cerebrovascular and cardiovascular disease. Therefore, it is expected that the pathophysiology and treatment strategies for PA will be elucidated. In recent years, the major changes in PA have been in treatment and diagnosis in Japan.
Bilateral or non-surgical unilateral PA is treated with mineralocorticoid receptor antagonist (MRA). Esaxerenone, a non-steroidal MRA, is now widely used in Japan for hypertension including PA. It has been reported that add-on treatment using esaxerenone with maximal tolerable doses of a renin-angiotensin system inhibitor reduced the urinary albumin creatinine ratio in patients with type 2 diabetes mellitus (ESAX-DN), suggesting a renoprotective effect against diabetic nephropathy. Several clinical studies of another non-steroidal MRA, finerenone(FIDELIO-DKD, FIGARO-DKD, and FIDELITY), have shown its renoprotective effect against diabetic nephropathy as well as cardiovascular events, particularly hospitalization for heart failure in patients with type 2 diabetes and chronic kidney disease. Although there are no reports of clinical studies on finerenone for PA, finerenone may be used in the future for type 2 diabetes patients with PA, as obesity, glucose intolerance, and sleep apnea are common complications in patients with PA. Secondly, radiofrequency ablation of macroscopic adrenal tumors has been reported as an alternative treatment for PA to lower blood pressure and plasma aldosterone levels. This treatment has been covered by health insurance providers in Japan since April 2022, but long-term outcomes need to be validated.
In diagnosis, serum and urine aldosterone has been measured in Japan since early 2021 by the two-step sandwich chemiluminescent enzyme immunoassay (CLEIA) method. This new CLEIA method correlates well with LC-MS/MS values and is expected to be more accurate. As CLEIA serum aldosterone levels are lower than those measured with a previous radioimmunoassay, the Japan Endocrine Society issued the 2021 Primary Aldosteronism Clinical Guidelines, which included a provisional positive value for the diagnosis of PA. More than ever, the diagnosis of PA needs to be carefully considered. This CLEIA method is currently available only in Japan.
This presentation will cover the latest treatments, diagnostic procedures, and other hot topics in PA as described above.
RAG-AMERICAS-4: THE FUTURE OF HYPERTENSION RESEARCH: PRECISION MEDICINE
Authors: Aristizabal Dagnovar 
Published: January 2023

Outline:
Medicine is transitioning from the traditional reactive care based on symptoms, diagnosis and treatment to a system that targets the disease before it occurs and when disease is present, then treats it in a personalized manner.
Chronic diseases such as arterial hypertension are suitable for precision medicine since patients with the same blood pressure (BP) values differ from one another, for instance, in terms of arterial hemodynamics and therefore, respond differently to the same treatment.
From an epidemiological perspective, BP lowering is broadly effective, requiring little or even no information about individuals. The success of public health interventions that do not involve personalized medicine raises the question to what extent will personalizing the treatment of hypertension impact the health of patients.
In general, there is a trade-off between simplicity of one-drug for most hypertensive patients and the addition of more information about individuals for personalized clinical decision-making. More precise treatment strategies create the most value for patients in whom simple strategies with low information is ineffective. A usual clinical scenario is resistant hypertension.
Our research has shown that when hypertension subtypes are considered, BP reduction with current antihypertensive medications considerably differs. Both systolic and diastolic hypertensives exhibit the best antihypertensive response to vasodilators while insolated forms of systolic or diastolic hypertension respond much less to this kind of first line treatment of hypertension.
A new taxonomy based on patient's clinical information, BP subtypes, genetic and epigenetic factors will identify hypertensive phenotypes beyond classical BP based approach, which will lead to a more precise and effective hypertension treatment.
PS-B01-2: ASSOCIATION BETWEEN IMPAIRED METABOLIC FUNCTION AND VASCULAR DYSFUNCTION IN METABOLIC SYNDROME
Authors: Ameer Omar Z , Salman Ibrahim M 
Published: January 2023

Objectives:
Metabolic syndrome is a leading cause for vascular dysfunction and cardiovascular diseases. We have previously shown that vascular functional responses in metabolic syndrome exhibit exaggerated vasocontractility and impaired endothelium-dependent relaxation. However, it remains unclear if a correlation between vascular abnormalities and metabolic disturbances exists. Accordingly, we aimed to explore the association between vascular dysfunction and changes in metabolic parameters in a rodent model of metabolic syndrome, the high fat diet (HFD)-streptozotocin (STZ)-induced diabetes mellitus rat (HFD-D).

Design and method:
Five weeks old male Wistar albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. On week 6, 40 mg/kg STZ and saline were injected intraperitoneally into the HFD and control groups, respectively. At the end of the treatment, metabolic data were collected then rats were euthanized for blood and kidney collection and to measure maximal vasoconstrictor and vasodilator responses of the abdominal aortic rings. Recorded measures also included fasting blood glucose (FBG), plasma total cholesterol (TC), plasma triglyceride (TG), plasma high density lipoprotein (HDL), plasma creatinine (Cr), urinary protein: urinary creatinine (UPC) and kidney index (KI).

Results:
HFD-D rats had higher FBG, TG, Cr, UPC, and KI compared with controls. HDL was lower in HFD-D while TC remained unchanged. Maximal vasoconstriction to norepinephrine (NE Rmax) was greater in the HFD group compared with controls. Maximal endothelium-dependent vasorelaxation to acetylcholine (ACh Rmax) was blunted in the HFD group relative to controls. A positive correlation between NE Rmax and FBG was found, whereas ACh Rmax was negatively correlated with FBG, KI, UPC and TG.

Conclusions:
Impaired glucose metabolism, lipid profile and renal function are likely key contributors to vascular dysfunction in metabolic syndrome; however, further mechanistic investigations are required to verify these assumptions.
PS-B01-10: ULTRASTRUCTURAL CHANGES IN SYSTEMIC RESISTANCE ARTERIES OF HYPERTENSIVE AND NORMOTENSIVE WOMEN WITH UTERINE FIBROIDS
Authors: Brewster Lizzy M , Taherzadeh Zhila , van Montfrans Gert A 
Published: January 2023

Background:
Uterine fibroids, the most common benign neoplasm in women, are associated with hypertension, but the nature of this association is not known. To assess a possible shared pathology of smooth muscle, we studied the ultrastructure of systemic resistance arteries of women with fibroids.

Methods:
Resistance-sized arteries (200 to 400 micrometer) were harvested from omental samples obtained during fibroid surgery. Transmission electron microscopic images were taken at different magnifications and locations of the vessel wall to assess qualitative and morphological characteristics.

Results:
We obtained resistance arteries of 19 women (9 hypertensive). Vessels of 17 women (8 hypertensive, 4 treated, none controlled) were available for analysis (Table). The arteries of normotensive and hypertensive women showed myocyte-like cells in the intima forming focal neo-intima plaques. In the media, myocytes showed a reduction in contractile fibers and prominent, dilated sarco-endoplasmic reticulum, with elongated mitochondria, and abundant autophagic and extracellular vacuoles. More profound ultrastructural changes were seen in hypertensives. Untreated hypertensives had a significantly higher media-to-lumen ratio than normotensives.

Conclusion:
To our knowledge these are the first data on the ultrastructure of systemic resistance-sized arteries in women with fibroids, showing vascular remodeling in both normotensives and hypertensives, with a shift from a contractile phenotype to a myocyte with prominent organelles involved in biosynthesis (synthetic phenotype). These abnormalities in systemic resistance-sized arteries may indicate that uterine fibroids are a manifestation of underlying systemic pathology affecting smooth muscle, or that fibroids induce systemic effects on the arterial wall, either directly or through factors that increase blood pressure, which needs exploration in further studies.
PS-B01-11: GENERATION OF TRANSGENIC MICE WITH PROXIMAL TUBULE-SPECIFIC OVEREXPRESSION OF ATRAP AND ANALYSIS OF PROXIMAL TUBULE ATRAP IN BLOOD PRESSURE REGULATION
Authors: Yukawa Naoki , Tsukamoto Shunichiro , Miyazawa Tomohito , Okami Naohito , Tanaka Shohei , Urate Shingo , Azushima Kengo , Wakui Hiromichi , Tamura Kouichi 
Published: January 2023

Objective:
Proximal tubule angiotensin II type 1 receptor (AT1R) is involved in blood pressure (BP) regulation (Li XC, et al. Hypertension, 77:1285-1298, 2021). AT1 receptor-associated protein (ATRAP) interacts with AT1R and promotes constitutive internalization of AT1R, to inhibit pathological activation of its downstream signaling (Tamura K, et al. Hypertens Res, 45:32–39, 2022). Endogenous ATRAP is abundantly expressed along kidney tubules in the kidney, and our previous investigations using systemic ATRAP knockout and distal tubule-dominant ATRAP transgenic mice revealed that ATRAP suppressed Ang II-induced hypertension mainly through a distal tubule-mediated mechanism (Wakui H, et al. Hypertension, 61:1203–10, 2013; Ohsawa M, et al. Kidney Int, 86:570–81, 2014). On the other hand, proximal tubule-specific ATRAP knockout mice exhibited similar baseline BP and pressor response to Ang II compared with wild-type mice (Kinguchi S, et al. J Am Heart Assoc, 8(8):e012395, 2019). The present study was performed to investigate the effects of enhancement of proximal tubule ATRAP on Ang II-mediated hypertension, using proximal tubule-specific ATRAP transgenic mice.

Design and method:
[Experiment 1] Using mouse ATRAP cDNA linked to the type II sodium-dependent phosphate cotransporters (NPT2) promoter, we generated transgenic mice (NPT2-Tg mice) with proximal tubule-specific overexpression of ATRAP. ATRAP mRNA expression in the proximal tubule was quantified by a laser capture microdissection and quantitative reverse transcription-polymerase chain reaction analysis.
[Experiment 2] Male NPT2-Tg and wild-type littermate control (LC) mice were divided into Ang II (1000 ng/kg/min) and vehicle groups. BP was measured using a tail-cuff method before and 14 days after treatment, and then mice were sacrificed and their organs were collected.

Results:
[Experiment 1] 5 of 12 lines of ATRAP Tg mice exhibited kidney overexpression of the ATRAP-transgene in comparison with LC mice. Kidney ATRAP expression at the protein level revealed the highest expression level of ATRAP in lines 23, approximately 10-fold higher compared to LC mice. Therefore, we chose line 23 (NPT2-Tg23) for further analysis. ATRAP mRNA expression was increased approximately 9-fold in the proximal tubules of NPT2-Tg23 mice compared with LC mice. On the other hand, ATRAP mRNA expression in the distal tubules was comparable between NPT2-Tg23 and LC mice.
[Experiment 2] We are currently conducting the experiments and will present our findings at this conference.

Conclusions:
We succeeded in generating transgenic mice with proximal tubule-specific overexpression of ATRAP. We plan to present the results of the impact of enhancement of proximal tubular ATRAP on Ang II-dependent hypertension at this conference.