bluuebunny/crossref_metadata_2025 huggingface dataset:
S-58-2: CUFFLESS WEARABLE 24-HOUR BLOOD PRESSURE MONIT ORING VERSUS STANDARD AMBULATORY MONITORING
Authors: Tan Isabella , Gnanenthiran Sonali R , Chan Justine , Kyriakoulis Konstantinos G , Schlaich Markus P , Stergiou George S , Schutte Aletta E
Published: January 2023

Objective:

Cuffless wearable blood pressure (BP) monitors have great potential in assessing 24-hour BP without user disturbance for weeks and months. However, it is uncertain whether these devices can accurately track BP changes during usual daily activities and sleep as with standard 24-hour ambulatory BP monitoring (ABPM). We assessed daytime and nighttime BP using a commercially available cuffless wearable BP device versus classic ABPM.

Design and method:

We included 45 individuals (age 58 ± 14 years [mean ± SD], 33% female, 80% hypertensive) in two centres (Perth, Australia; Athens, Greece). Participants used a cuffless wearable BP monitor (Aktiia, Switzerland) continuously for 7–10 days and 24-hour ABPM (MicroLife WatchBP O3, Switzerland) on the first and the last day of cuffless BP monitoring. Daily 24-hour, daytime, and nighttime BP values were averaged across the total study days for the cuffless device and across the two ABPM days.

Results:

The cuffless device reported higher systolic BP for 24-hours by 6.8 mmHg, 95%CI [3.7, 9.7], daytime by 3.8 mmHg [1.0, 6.7], and nighttime by 17.5 mmHg [13.6, 21.4] (all p < 0.01). Cuffless 24-hour diastolic BP was comparable with ABPM (difference 1.2 mmHg, 95%CI [-1.0, 3.5]), as was daytime diastolic BP (-0.8 mmHg [-3.0, 1.3]) (both p. < 27). However, the cuffless device reported higher nighttime diastolic BP by 9.2 mmHg, 95%CI [6.3, 12.2] (p < 0.001). Nighttime dip as measured by the cuffless device, namely systolic BP (-5.1 mmHg, 95%CI [-13.7, 3.6]) and diastolic BP (-3.8 mmHg [-11.6, 4.2]) were substantially less than ABPM (systolic BP dip: -18.0 mmHg [-35.5, -1.2]; diastolic BP dip: -13.8 mmHg [-27.2, -0.8]). The cuffless device identified 44 nighttime non-dippers (defined as a relative dip < 10%) for systolic BP and 42 non-dippers for diastolic BP, compared to 10 non-dippers for both systolic and diastolic BP as identified by ABPM (both comparisons p < 0.001).

Conclusions:

The Aktiia cuffless wearable BP device considerably overestimated average systolic BP compared to classic ABPM and was unable to adequately track diurnal BP variation.
S-58-4: ARE CUFFLESS BLOOD PRESSURE MEASURING DEVICES READY FOR CLINICAL USE?
Authors: Stergiou George S
Published: January 2023

Several cuffless BP measuring devices are currently available on various markets claiming that they provide accurate measurements, and few have some regulatory approval. These technologies may provide numerous BP readings in different settings and activ ities of daily life without using a disturbing cuff. Thus, they have considerable potential to improve the awareness, treatment, and management of hypertension by. The crucial question is whether thjey can provide accurate measurement of BP. Microsoft Research recently published a major engineering paper presenting results of the Aurora Project assessing the accuracy of several PWA and PWA-PAT devices using radial tonometry, photoplethysmography, electrocardiography, and accelerometry signals in 1,125 participants, including younger and older individuals with low or high BP. The overall results were negative. Smaller recent studies also showed negative results. In a recent study, finger PPG waveform analysis and PAT explored during several interventions inducing BP changes the test device had some value in predicting changes in auscultation SBP but not DBP. Another study of a cuff-calibrated wristband device tested against standard 24-h ambulatory BP showed that the cuffless device was unable to track the BP drop during nighttime sleep. In a third study, a cuff-calibrated smartwatch device showed a systematic bias towards the cuff BP at calibration and could not accurately measure BP compared to standard 24-h ambulatory monitoring.

On the other hand, two recent studies showed positive results. The first showed that a cuff-calibrated device could almost perfectly predict average ambulatory BP, and the second showed that a demographics-calibrated device could predict invasive BP. Although the scientific community, patients, and the public are eager to adopt cuffless BP devices in routine use, further research is needed to bring these technologies to primetime. A recent statement by the ESH Working Group on BP Monitoring recommended not to use cuffless BP devices for the diagnosis and management of hypertension. These technologies and devices require further development and proper testing in independent studies. In addition, there is an urgent need for establishing protocols which are specific for validating cuffless devices, as the Universal Standard (AANMI/ESH/ISO) for testing automated cuff devices is not applicable to cuffless devices. Developing such protocols is challenging, and the current ones require further vetting (IEEE 2014 and ISO under development). Thus, fundamental research questions need to be carefully addressed before cuffless BP devices can be recommended for clinical use.
APSH-OP-4: HISTOLOGICAL MEASURES OF STRUCTURAL KIDNEY DAMAGE ARE ASSOCIATED WITH SHORTENING OF KIDNEY TELOMERE LENGTH
Authors: Akinnibosun Olutope Arinola , Eales James , Nguyen Huy , Bogdanski Pawel , Szczechowska Ewa Zukowska , Denniff Matthew , Dromer John , Tomaszewski Maciej , Charchar Fadi
Published: January 2023

Objective:

Telomeres shorten with each cell division and serve as markers of cell senescence. The rate of telomere attrition varies across tissues within the same individual. Telomere attrition and dysfunction has been associated with various disease states. Studies have shown that leukocyte telomere length (LTL) may be predictive of telomere length in other tissues of the body. Several histological changes occur in the kidney before functional impairment becomes evident. It is unclear if telomeres are associated with these early changes. We sought to (i) investigate whether LTL is a proxy of kidney telomere length (KTL), and (ii) estimate the extent to which both measures of biological ageing associate with histological markers of kidney damage.

Design and Methods:

Study group consisted of 200 participants (Female 38% and Male 62%) from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study. Participants had no personal history of primary nephropathy and were eligible for unilateral elective nephrectomy because of sporadic non-invasive renal cancer. Kidney tissue samples were collected from the healthy (unaffected by cancer) pole immediately after nephrectomy and fixed in 10% formalin, then embedded in paraffin blocks. The extent of kidney histological damage was assessed using a semi-quantitative method of kidney slide evaluation. LTL and KTL were quantified using quantitative polymerase chain reaction.

Results:

There was a significant negative correlation between KTL and age (r = -0.287, P < 0.001). The correlation between LTL and age showed directionally consistent, but non-significant pattern (r = -0.135, P = 0.063). Unadjusted and adjusted analysis showed insignificant association between LTL and KTL (r = 0.042, P = 0.575). However, both KTL and LTL correlated with tubular atrophy (r = -0.28, -0.16; P < 0.001, 0.05, respectively). Each increased unit of both KTL and LTL also associated with a decrease of 61.3% and 47.4%, respectively in likelihood of developing tubular atrophy (Table 1). Shorter KTL was associated with increased odds of developing interstitial fibrosis, interstitial inflammation, and Bowmans capsule thickening (Table 1). KTL also associated with percentage of Bowmans capsule thickening (β = -0.214, P = 0.027), percentage of sclerosed glomeruli (β = -0.227, P = 0.017), and Remuzzi score (β = -0.280, P = 0.001). In contrast, LTL did not show an association with any other kidney histology variables, except with tubular atrophy in adjusted analysis.

Conclusions:

LTL shows only a weak association with tubular atrophy and KTL is a much more accurate measure of histologically confirmed structural kidney damage than LTL. LTL cannot be used as a proxy of KTL or the extent of kidney damage.
AW-NI-5: COST-EFFECTIVENESS OF INTENSIVE VERSUS STANDARD BLOOD-PRESSURE CONTROL AMONG HYPERTENSIVE PATIENTS IN TAIWAN: A SIMULATION MODELLING STUDY
Authors: Liao ChiaTe , Toh Han Siong , Wei Dongmei , Melgarejo Jesus , Chang WeiTing , Zhang Zhenyu
Published: January 2023

Objective:

Based on the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial and A Randomized Trial of Intensive versus Standard Blood-Pressure Control (SPRINT) trial, the 2022 Taiwan hypertension guidelines recommend the definition of hypertension as 130/80mmHg and a universal BP target of < 130/80 mmHg. Based on the guidelines, we aimed to analyze the lifetime cost-effectiveness of intensive versus standard blood-pressure control from the perspective of Taiwan national payer.

Design and method:

A simulation model was employed to apply the SPRINT treatment effects for hypertensive patients aged 50–54 and 55–64 years and STEP treatment effects for those aged 65–74 and 75+ years. The medical costs and utility were extracted from national sources or published data to a hypothetical cohort of SPRINT-eligible and STEP-eligible patients in Taiwan. Incremental cost-effectiveness ratio (ICER) against the willing-to-pay threshold at the one-time gross domestic product (GDP) per capita was used to evaluate whether intensive versus standard blood-pressure control was cost-effective.

Results:

Intensive blood-pressure control produced more lifetime medical costs than standard control, i.e., US$39,348–22,978 versus US$20,239–33,414, while intensive treatment also contributed to more quality-adjusted life-year (QALY), i.e., 7.60–16.28 versus 7.37–15.74. ICER values of intensive versus standard treatment were approximate US$10,989 (NT$329,670), US$11,220(NT$336,600), US$11,485(NT$344,550), and US$11,865(NT$355,950) per QALY gained for hypertensive patients aged 50–54, 55–64, 65–74, and 75+ from the perspective of Taiwanese national payer. Simulation results indicated that intensive treatment is very likely to be cost-effective, i.e., all probabilities are greater than 99.8% below the willing-to-pay threshold of US$36,000 (NT$1,080,000).

Conclusions:

In this simulation study, intensive blood-pressure control in the Taiwanese population produced fewer cardiovascular events and acceptable costs per QALY gained, enormously below the willing-to-pay threshold. The cost-effectiveness of intensive blood-pressure control was consistent across different ages, and the advantage was more predominant in younger hypertensive patients.
JS-NG-5: THROMBOTIC MICROANGIOPATHY OR MALIGNANT HYPERTENSION: WHICH COMES FIRST? A CASE REPORT FROM A TERTIARY CARE HOSPITAL
Authors: Vitkauskaite Monika , Macioniene Ernesta , Janusaite Marta Monika , Cerkauskaite Agne , Asakiene Egle , Dobrovolskiene Rasa , Serpytis Mindaugas , Judickas Sarunas , Miglinas Marius
Published: January 2023

A 66-year-old woman with a history of arterial hypertension was admitted to the emergency department (ED) due to disorientation. She reported a severe headache, nausea, vomiting in the evening prior the admission; her blood pressure (BP) when the ambulance arrived was 220/100 mmHg. During admission, BP was 158/91 mmHg, pulse 95 beats/minute, oxygen saturation 88% on room air, body temperature 36.6°C.

The urine examination showed that urine protein was 3+, red blood cell count 10 mg/L. The whole blood cell analysis revealed neutrophilic leukocytosis, thrombocytopenia (Table). There was 1 schistocyte seen in the peripheral blood smear. The serum creatinine and urea values were raised (Table) with elevated level of D-dimers (1690 mcg/L (< 250 mcg/L)). Head CT showed no signs of hemorrhage or ischemia. Ceftriaxone, ampicillin, and acyclovir were initiated for suspected neuro-infection, she also underwent transfusion with 4 units of platelets due to thrombocytopenia. Patients GCS fell from 11 to 9 over 13 hours, therefore she was transferred to the intensive care unit (ICU). Cerebrospinal fluid analysis showed cytosis 15 cells/mcL (predominance of lymphocytes) and protein level of 1,073 g/L; PCR panel for the most common bacterial and viral meningitis agents came back negative.

On day 2, lactate dehydrogenase level was raised at 3086 U/L (125–243 U/L), haptoglobin was < 0.08 g/L (0.3–2.0 g/L) and Coombs test was negative. Due to worsening renal function (Table) hemodialysis was initiated. The differential diagnosis included thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome (HUS), secondary thrombotic microangiopathy (TMA), immune thrombocytopenic purpura (ITP) and disseminated intravascular coagulation (DIC). ADAMTS-13, CH50, SC5b-9 levels were tested (0.53 TV/ml (0.40–1.50 TV/ml), 60 U Eq/ml (55–75 U Eq/ml), 4689 ng/ml (200–325 ng/ml), respectively). The patient started on plasmapheresis. On day 3, fundoscopy showed cotton wool spots (ischemia) with hemorrhages and soft exudates next to the optic nerve disc; intravenous methylprednisolone pulse therapy was administered (1 g daily for three days followed by oral methylprednisolone 32 mg daily). Renal biopsy on day 5 revealed active TMA damaging the glomeruli and acute tubular necrosis. After 15 days in the ICU, she remained hypertensive and anuric despite given treatment. Moreover, pulmonary edema occurred on day 15.

Malignant hypertension (MH) is characterized by severe hypertension and multi-organ ischemic complications. It can cause TMA and the overall presentation may imitate primary TMA. The approach of renal TMA in MH remains challenging. Herein, we reported a case of MHT with biopsy-proven TMA in the kidney.
JS-NG-7: ASSOCIATION BETWEEN PLASMA ALDOSTERONE CONCENTRATION AND AMBULATORY BLOOD PRESSURE PROFILE IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Morita Ryutaro , Azushima Kengo , Sunohara Sumire , Kanaoka Tomohiko , Wakui Hiromichi , Toya Yoshiyuki , Tamura Kouichi
Published: January 2023

Background:

Primary aldosteronism (PA) is a major cause of curable hypertension with its morbidity rate 5–10% in hypertensive patients reported, and thus is highly prevalent in patients with hypertension, a cause of resistant hypertension, and closely associated with target organ damage compared with essential hypertension. Although an altered circadian blood pressure (BP) rhythm estimated by ambulatory blood pressure monitoring (ABPM) has been highlighted as a major contributor of CVD in essential hypertension, there would be very few reports investigating clinical significance of ABPM in PA patients. Therefore, we aimed to examine a possible association between plasma aldosterone concentration (PAC) and ABPM profile in PA patients.

Methods:

Consecutive 27 PA patients, who had been diagnosed by the functional tests and underwent adrenal venous sampling (AVS) from April 2015 to March 2020, were included in this study. All clinical indexes including 24-hour ABPM were measured during the hospitalization, and all participants received dietary salt restriction with 6 g/day of salt. The 24-hour ABPM was performed from the first day of hospitalization to the next day, and AVS was performed on the third day in the morning. Regarding PAC measurement, we collected blood samples during AVS. After resting for 30 minutes in a supine position, blood samples were collected from inferior vena cava by catheterization. During AVS, we also performed ACTH stimulation, and blood samples were collected essentially 1 hour after the stimulation.

Results:

We firstly analyzed a correlation between PAC and ABPM profile and found that PAC measured after ACTH stimulation (post-PAC) was negatively correlated with nocturnal dipping rate in both systolic and diastolic BPs (SBP and DBP) (R = -0.430, P = 0.025, and R = -0.431, P = 0.025, respectively), while PAC measured before ACTH stimulation (pre-PAC) was not. Thus, according to the median of post-PAC, we divided participants into lower PAC and higher PAC groups and compared clinical characteristics between the two groups. Compared to the lower PAC group, nocturnal SBP and DBP dipping rates and serum potassium levels were significantly decreased in the higher PAC group (SBP dipping 10.3 ± 6.4 vs 3.5 ± 7.7 %, P = 0.02; DBP dipping 13.6 ± 7.7 vs 5.5 ± 6.3 %, P = 0.01; serum potassium 4.1 ± 0.3 vs 3.7 ± 0.4 mEq/L, P = 0.03).

Conclusions:

In this cross-sectional study, higher PAC was significantly associated with a non-dipper circadian BP profile characterized by lower nocturnal BP dipping rates in PA patients. Prospective longitudinal study is warranted to seek for a causal relationship between hyperaldosteronism and ABPM profile.
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.
PS-B02-14: DISCOVERY OF A NEW DRUG FOR PRIMARY ALDOSTERONISM TARGETING THE CYP11B2 AND KCNJ5 MUTANTS
Authors: Otsubo Yuri , Shimada Hiroki , Nakamura Yasuhiro , Yokoyama Atsushi , Sugawara Akira
Published: January 2023

Primary aldosteronism (PA) is a common cause of secondary hypertension. PA induces damage to cardiovascular and renal blood vessels. Therefore, PA is regarded as a problem because it increases the risk of stroke, cardiomyopathy, kidney disease, etc. Aldosterone-producing adenomas (APA) are one of the major causes of PA, and gene mutations are often identified in tumor cells. KCNJ5 mutation is well known as a gene mutation that causes the loss of ion selectivity in APA. KCNJ5 is an inwardly rectifying potassium channel. KCNJ5 induces sodium ion influx due to mutations in APA. The sodium ion influx induces depolarization, and which overexpresses CYP11B2. CYP11B2 is the rate-determining enzyme for aldosterone synthesis, overexpression of CYP11B2 induces aldosterone overproduction.

Examples of therapeutic drugs for PA and APA include calcium channel blockers, aldosterone antagonist and β;-blockers. However, therapeutic drugs for PA and APA targeting cell membrane depolarization have not been developed yet. We aim to find compounds that suppress CYP11B2 expression by membrane depolarization to develop novel therapeutic drugs for PA and APA. By developing a therapeutic drug that targets depolarization, we hope to establish an effective therapeutic method for APA caused by gene mutations such as KCNJ5 mutation. We performed high-throughput screening (HTS) using Tohoku University Compound Library (6080 compounds). First, we generated H295R-CYP11B2 N-Luc cells in which the luciferase gene is inserted downstream of the CYP11B2 locus. The cells H295R-CYP11B2 N-Luc were stimulated with KCl to cause depolarization, after which candidate compounds were added and HTS was performed by Luc assay. As a result, 101 compounds were selected. Furthermore, 25 of 101 compounds were selected by examining the cytotoxicity and dose response.

Also, 11 of the 25 compounds suppressed CYP11B2 mRNA expression in KCl stimulated H295R cells. Secondary, we generated KCNJ5 mutant cells that expressed the KCNJ5 mutant (L168R) in a Doxycycline-inducible manner. 3 of 11 compounds that suppressed the expression of CYP11B2 mRNA were selected by examination using KCNJ5 mutant cells. After that, 2 of 3 compounds decreased the aldosterone production.

These compounds have a different structure from existing therapeutic drugs such as calcium channel blockers. Since these can be novel therapeutic drugs for PA and APA caused by depolarization such as KCNJ5, we are examing the detailed mechanism of action of the compounds. In addition, we would like to further experiment the effects of the compounds in vivo using hypertensive model mice, Task1 /Task3 double KO mice.
PS-C01-3: ACCURACY OF THE AKTIIA BRACELET IN THE ELDERLY IN DIFFERENT BODY POSITIONS
Authors: Theiler Kenji , Sola Josep , Alexandre Jeremy , Vermare Pascale , Durgnat Virginie , Wuerzner Gregoire
Published: January 2023

Objective:

Accurate blood pressure (BP) measurement is essential for the correct diagnosis and management of hypertension (HTN) especially in the elderly population, which has the highest prevalence of HTN. Recently cuffless devices have been developed with the hope of facilitating blood pressure measurement. However, validation studies of cuffless are scarce and a universally accepted validation protocol has yet to be published. The objective of the second arm of this study (NCT04027777) was to test the accuracy of the Aktiia bracelet in an elderly population cohort in different body positions.

Design and method:

We recruited 40 patients aged from 65 to 85 years with different blood pressure categories and without diabetes. BP measures from Aktiia Bracelet were compared to reference double auscultatory measurement in various body positions: sitting, standing and lying (including after aerobic physical activity in supine position) on four separate visits distributed over one month.

Results:

The average participant's age was 73 ± 6 years with 52.5% female participants. A total of 469 comparison measurements were made, with an overall acceptance rate of 79% (percentage of optical recordings with sufficient quality to be analyzed by the cuffless device). Five participants were excluded either due to failed initialization or to ensure a distribution of blood pressure categories compliant to the requirements of ISO 81060-2. After initialization procedures on day 1, we observed means and standard deviations of differences for systolic BP of 1.23 ± 7.88 mmHg in sitting position, -1.81 ± 11.11 mmHg in the standing and -1.8 ± 9.96 mmHg in the lying position (including after aerobic exercise). Differences for diastolic BP were 0.2 ± 5.55 mmHg, -5.35 ± 7.75 mmHg and -0.94 ± 7.47 mmHg respectively. The acceptance rate for each position was 86%, 69% and 75% respectively. When considering all possible body positions representative of a realistic use of the device, and along the entire monitoring period of one month, systolic and diastolic BP differences were -0.26 ± 9.96 mmHg and -0.75 ± 7.0 mmHg respectively. Figure 1 illustrates the Bland-Altman plots for SBP and DBP for the sitting position.

Conclusions:

This study demonstrates that the Aktiia bracelet can accurately estimate the BP in an elderly population in the sitting position (according to the requirements of ISO 81060-2) and in other body positions representative of a realistic use of the device. The use of more comfortable, non-invasive and non-occlusive BP monitoring may contribute to better diagnosis and treatment of hypertension in the elderly through patient empowerment.