bluuebunny/crossref_metadata_2025 huggingface dataset:
APSH-OP-2: INTRACELLULAR TRANSPORTATION OF AMYLOID BETA VIA INTERACTION BETWEEN ANGIOTENSIN II TYPE 1 RECEPTOR AND RECEPTOR OF ADVANCED GLYCATION END PRODUCTS
Authors: Huang Yibin , Yamamoto Koichi , Nakajima Tsuneo , Takeda Shuko , Rakugi Hiromi
Published: January 2023

Objective:

We recently reported that the binding of the receptor for advanced glycation end-products (RAGE) to AGE activates the G protein-coupled angiotensin II (AII) type 1 receptor (AT1) through membrane complex of the receptors (2021 Sci Rep). It has been reported that the binding of RAGE to amyloid beta is involved in the development of Alzheimer disease (AD) via processes involving intracellular transport of Amyloid beta. Here, we performed cell experiments and utilized animal models to investigate if the activation of AT1 is critically involved in Amyloid beta-RAGE-mediated cellular phenomenon, leading to the AD pathology.

Design and Methods:

We used CHO-cells stably transfected with either AT1 (CHO-AT1) or RAGE(CHO-RAGE), RAGE and AT1 (CHO-RAGE-AT1) and either mutation of AT1 G protein pathway(CHO-RAGE-AT1mb) or beta-arrestin pathway(CHO-RAGE-AT1 mg). Activation of Galphaq and Galphai were quantified by accumulation of IP1 and redcution of cAMP assay, respectively. Endocytosis of the Amyloid beta-RAGE complex through the AT1- beta-arrestin pathway was demonstrated by real-time imaging of the membrane dynamics of AT1 and RAGE by a spinning disk-type confocal super-resolution microscope, detection of the AT1- betaarrestin2 interaction by BRET, detection of beta-arrestin2-AP2 interaction by TR-FRET. Visualization of intracellular fluorescent Amyloid beta, and detection of intracellular aggregated Amyloid beta by PROTEOSTAT® reagent in several types of human endthelial cells and microlgilal cells. In vivo experiment, wild type and AT1 KO mice were used for analysis.

Results:

Using genetically modified CHO cells, we found that Amyloid beta activates Galphai, but not the Galphaq pathway of AT1, in the presence of RAGE. Furthermore, in the presence of both RAGE and AT1, we could detect and visualize Amyloid beta indcued beta-arrestin activation and endocytosis of receptors complex. We also found that inhibition of either AT1 or beta-arrestin pathway could attenuate intracellular Amyloid beta upatke and aggregation in several types of human endthelial cells and microlgilal cells. Finally, serum concentration of Amyloid beta 1–40 and Amyloid beta 1–42 was higher in AT1 knockout mice than wild type mice at 15–19 month, while the concentration of the Amyloid beta peptides in cerebrospinal fluid was equivalent between two types of mice.

Conclusions:

These findings indicate that Amyloid beta triggers selective G protein activation and the beta-arrestin-dependent internalization of AT1 whereby the Amyloid beta-RAGE complex undergo endocytosis. This machinery can be relevant in mice in which the deletion of AT1 led to increase in circulating Amyloid beta, implying the ablation of intracellular transporting system of Amyloid beta.
APSH-OP-5: MEASURES OF LONG-TERM SYSTOLIC BLOOD PRESSURE VARIABILITY AND THEIR ASSOCIATIONS WITH THE RISK OF INCIDENT TYPE 2 DIABETES MELLITUS
Authors: Song Zean , He Yupeng , Chiang Chifa , Alshoaibi Abubakr A A , Rahman KM Saif Ur , Mamun Md Razib , Aoyama Atsuko , Hirakawa Yoshihisa , Matsunaga Masaaki , Ota Atsuhiko , Tamakoshi Koji , Li Yuanying , Yatsuya Hiroshi
Published: January 2023

Objective:

The present study investigates the association between long-term systolic blood pressure (SBP) variability and the risk of type 2 diabetes mellitus (T2DM) by using different indicators of the variability including standard deviation (SD), coefficient of variation (CV), maximum and minimum difference (MMD), root mean square error (RMSE), variability independent of the mean (VIM), and average real variability (ARV).

Design and method:

A cohort of 3017 Japanese individuals (2446 male, 571 female) aged 36 to 65 was followed from 2007 through 2019. SD, CV, MMD, RMSE, VIM, and ARV of long term SBP changes were calculated per individual using SBP values obtained consecutively from 2003 to 2007. A multivariable Cox proportional model was applied to estimate hazard ratio (HR) and the corresponding 95% confidence interval (CI) for tertiles of the each variability measure, SD, CV, MMD, RMSE, VIM, and ARV, adjusted for age, sex, smoking status, regular exercise, family history of diabetes, sleep disorders, sodium intake, body mass index (BMI), BMI slope, fasting blood glucose (FBG), and 2007 SBP.

Results:

Of the variability measures examined, the highest RMSE tertile compared to the lowest was significantly associated with T2DM incidence (multivariable-adjusted HR: 1.79, 95% CI: 1.15–2.78). Also, the highest ARV tertile compared to the lowest was associated with T2DM incidence (multivariable-adjusted HR: 1.54, 95% CI: 1.00–2.35). The SD, CV, MMD and VIM were not significantly associated with T2DM incidence independent of the covariates.

Conclusion:

This study revealed that long-term SBP variability is possibly an independent risk factor for the future occurrence of T2DM, and such property can only be measured by either RMSE or ARV.
APSH-OP-6: ASSOCIATION BETWEEN THE GUT MICROBIOME AND THEIR METABOLITES WITH HUMAN BLOOD PRESSURE VARIABILITY
Authors: Dinakis Evany , Nakai Michael , Gill Paul , Ribeiro Rosilene , Yiallourou Stephanie , Sata Yusuke , Muir Jane , Carrington Melinda , Head Geoffrey A , Kaye David M , Marques Francine Z
Published: January 2023

Objective:

Blood pressure (BP) variability is an independent risk factor for cardiovascular events. Recent evidence supports a role for the gut microbiota in BP regulation. However, whether the gut microbiome is associated with BP variability is yet to be determined. Here, we aimed to investigate the interplay between the gut microbiome and their metabolites in relation to three separate parameters of BP variability.

Design and method:

Ambulatory BP monitoring was performed in 69 participants from two independent sites in Australia (55.1% women; mean ± SD 59.8 ± 7.26-years old, BMI 25.2 ± 2.83 kg/m2). This data was used to determine night-time dipping, morning BP surge (MBPS) and BP variability as standard deviation (SD). The gut microbiome was determined by 16S rRNA sequencing, mRNA expression levels of short-chain fatty acid (SCFA) receptors (FFAR2, FFAR3 and HCAR2) by real-time PCR (qPCR) and metabolite levels by gas chromatography.

Results:

We identified specific taxa associated with systolic BP variability, night-time dipping and MBPS. Notably, Alistipesfinegoldii and Lactobacillus spp. were only present in participants within the normal ranges of BP variability, MBPS and night-time dipping, while Prevotella spp. and Clostridium spp. were found to be present in extreme dippers and the highest quartiles of BP SD and MBPS. There was a negative association between MBPS and microbial alpha diversity (r = -0.244, P = 0.046). MBPS was also negatively associated with plasma levels of microbial metabolites (SCFAs) (r = -0.305, P = 0.020), particularly acetate (r = -0.311, P = 0.017). We identified a negative correlation between SD data and SCFA receptor FFAR2 mRNA, indicating that participants with higher BP SD had overall lower expression levels of FFAR2 (SD day: r = -0.31, P = 0.039; SD night: r = -0.36, P = 0.016; SD total: r = -0.32, P = 0.035). We also found that participants with a greater percentage in night-time dipping had higher levels of FFAR2 (r = 0.38, P = 0.0087).

Conclusions:

Gut microbiome diversity, levels of microbial metabolites, and the bacteria Alistipesfinegoldii and Lactobacillus were associated with lower BP variability, whereas a blunted level of SCFA receptor FFAR2 mRNA and Clostridium and Prevotella bacteria were associated with higher BP variability. Our findings suggest the gut microbiome and metabolites may be involved in the regulation of BP variability.
AW-AD-1: SEASONAL VARIATION IN DAY-BY-DAY BLOOD PRESSURE VARIABILITY AND ITS EFFECT ON CARDIOVASCULAR OUTCOMES
Authors: Narita Keisuke , Hoshide Satoshi , Kario Kazuomi
Published: January 2023

Although day-by-day home blood pressure (BP) variability has been associated with cardiovascular disease (CVD) risk, it remains unclear whether this association differs from season to season. The present study aimed to assess seasonal variation in day-by-day home BP variability (BPV) and its association with CVD risk. We analyzed the data from a nationwide, prospective observational study, the J-HOP (Japan Morning Surge-Home Blood Pressure) study, in which 14 consecutive days of home BP monitoring were conducted. The values of standard deviation (SDSBP), coefficient of variation (CVSBP), and average real variability (ARVSBP) of home systolic BP (SBP) were used as indices of day-by-day home BPV. Among 4231 participants (mean age, 64.9 ± 10.9 years, 46.7% male, 91.5% hypertensives), all three day-by-day home BPV indices were lower in summer than winter after adjusting for confounding factors. In winter, SDSBP, CVSBP, and ARVSBP were significantly associated with increased risk of CVD events (coronary artery disease, stroke, heart failure, and aortic dissection) (adjusted HR [95%CI] per 1-SD of SDSBP, 1.27 [1.03, 1.56]; CVSBP, 1.25 [1.03, 1.53]; ARVSBP, 1.44 [1.18, 1.77]). These relationships were also observed in the analysis of quartiles of BPV parameters (adjusted HR [95%CI] compared to the 1st quartile, 4th quartile of SDSBP 2.25 [1.05, 4.81]; CVSBP 2.91 [1.40, 6.03]; ARVSBP 2.71 [1.25, 5.89]). In other seasons, however, there were no significant associations between day-by-day home BPV and CVD event risk. Our findings indicate that day-by-day home BPV measured in winter is more strongly associated with future CVD incidence than that measured in other seasons.
AW-AD-6: PREVALENCE OF VALIDATED BLOOD PRESSURE MEASURING DEVICES BEING SOLD BY AMAZON: 12-MONTH PROSPECTIVE ANALYSIS ACROSS 10 COUNTRIES
Authors: Picone Dean S , Bui Tan , Chapman Niamh , Schultz Martin G , Delles Christian , Olsen Michael Hecht , Schutte Aletta E , Stergiou George , Padwal Raj , Whelton Paul K , Sharman James E
Published: January 2023

Objective:

The online purchase of automated blood pressure (BP) devices is a multibillion-dollar industry, but most BP devices available for online purchase have not passed adequate clinical validation testing. This study aimed to determine the extent to which BP devices available in best-selling lists of the e-commerce business Amazon were properly validated for accuracy, as well as their cost and ratings.

Design and method:

The 100 best-selling automated (upper arm and wrist) cuff BP devices sold by Amazon in 10 countries located in Europe, Asia-Pacific, North and South America were recorded at seven time points during a 12-month period of observation.

Results:

81% of the 100 best-selling BP devices had not undergone adequate clinical validation (interquartile range [IQR] 74 to 90, averaged across all countries and time points) and this percentage was highly consistent within each country across the measurement period. The highest percentages of properly validated upper-arm BP devices being sold were 35% in Germany and 31% in Canada, whereas the lowest percentages were 3% in India and 5% in Australia. Non-validated upper-arm cuff BP devices were cheaper than clinically validated devices (median, IQR: $32.0 USD (26.0 to 43.9) versus $67.2 USD, (42.7 to 89.7)). Non-validated upper-arm cuff BP devices received fewer total numbers of consumer ratings than clinically validated devices (median, IQR: 210, 44 to 770 versus 651, 95 to 2962) despite near identical consumer ratings out of five stars (median, IQR: 4.5, 4.2 to 4.6 versus 4.5, 4.3 to 4.7). Similar patterns were observed for wrist-cuff BP devices. None of the wrist-cuff devices being sold in the US were clinically validated.

Conclusions:

Four out of five automated BP devices within the 100 best-selling lists of Amazon had not passed adequate clinical validation testing for BP measurement accuracy and precision. People should not buy a BP device online unless they can be certain it has passed adequate clinical validation testing.
AW-NI-1: ANGIOTENSIN II EXAGGERATES SARS-COV-2 SPECIFIC T-CELL RESPONSE IN CONVALESCENT INDIVIDUALS FOLLOWING COVID-19
Authors: Almutlaq Moudhi , Mansour Fatmah A , Alamri Hassan S , Alroqi Fayhan , Barhoumi Tlili
Published: January 2023

Background:

Coronavirus disease 2019 (COVID-19) is an emerging respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies have suggested numerous hypotheses that may explain multi-organ dysfunction during a COVID-19 infection. One possible hypothesis posits that the renin-angiotensin system dysregulation before SARS-CoV-2 infection could exacerbate disease symptoms and severity, especially in COVID-19 patients with underlying comorbidities.

Objective:

This study sought to investigate the effect of exogenous angiotensin II (Ang II) on peripheral blood mononuclear cells (PBMCs) stimulated with SARS-CoV-2 peptide pool.

Methods:

PBMCs from recovered COVID-19 patients (n = 18) were used in this study. SARS-CoV-2 specific t-cell responses were measured using activation induced cell marker assay and intracellular cytokine staining (ICS) assay, while enzyme-linked immunosorbent assay (ELISA) and ICS assays determined functional capability and polarization. Additionally, the relative level of protein phosphorylation in PBMCs was measured using a phosphokinase array.

Results:

Our results showed that in vitro Ang II treatment significantly increased the magnitude of SARS-CoV-2 specific t-cell response in stimulated PBMCs with SARS-CoV-2 peptide pool. Moreover, the phosphorylation level of numerous proteins implicated in cardiovascular diseases, inflammation, and viral infection showed significant increase in the presence of Ang II. Mitogenic stimulation of PBMCs after Ang II and SARS-CoV-2 peptide pool stimulation showed functional polarization of CD4+ and CD8+ t-cells toward Th1/Th17 and Th17 phenotypes, respectively. Meanwhile, ELISA showed an increased production of IL-1b and IL-6 in Ang II-stimulated PBMCs without affecting the reduction of IL-10 level resulting from SARS-CoV-2 peptide pool stimulation.

Conclusion:

To our knowledge, the present study is the first to demonstrate that Ang II exaggerates SARS-CoV-2 specific t-cells response. Therefore, during COVID-19 infection Ang II may aggravate the inflammatory response and change the immune response toward a more inflammatory profile against SARS-CoV-2 infection, leading to serious complications and worse outcomes during COVID-19 infection.
AW-NI-4: MAY MEASUREMENT MONTH 2021: AN ANALYSIS OF BLOOD PRESSURE SCREENING RESULTS FROM NEPAL
Authors: Inagaki Yoko , Koilala Sweta , Poudel Kiran , Tiwari Kiran , Sapkota Abhishek , Soti Pabitra Babu , Neupane Dinesh
Published: January 2023

Objective:

This study presents the result of May measurement Month 2021 in Nepal, a global initiative of the International Society of Hypertension (ISH) aiming to screen high blood pressure and raise awareness at the population level.

Design and Methods:

An opportunistic cross-sectional survey of> = 18 years of age was conducted in 15 out of 77 districts from September-December 2021. The trained enumerators administered the structured questionnaire of the ISH adopted into Nepali and took three blood pressure (BP) readings while in a sitting position at 1-minute intervals, using electronic BP machines. Participants were identified with hypertension using the following criteria: 1) mean of the 2nd and 3rd BP readings> = 140/90 mmHg or 2) being on at least one antihypertensive medicine taken for raised BP. Ethical approval was obtained from the Nepal Health Research Council.

Results:

A total of 5,172 participants were included. The median age was 37.0 (IQR 25–51) years and 49.9 % were female. Self-reported tobacco use, alcohol drinking, diabetes, and history of myocardial infarction (MI) or stroke were reported in 21.7%, 21.9%, 4.1%, and 0.5% of participants, respectively. The mean of 2nd and 3rd BP readings or history of anti-hypertensive medication use were available for 5,167 participants. The mean was 123.9 mmHg ± 10.3 for systolic blood pressure, and 81.2 mmHg ± 9.3 for diastolic blood pressure. 1,066 (20.6%) met the criteria for hypertension, of which 399 (39.5%) were aware and 298 (29.5%) were treated with at least one anti-hypertensive medicine. Of those who were treated, 167 (56.0%) had their BP under control. With the BP threshold of the AHA/ACC guideline (i.e., SBP> = 130 mmHg or DBP> = 80 mmHg), 3,015 (58.9%) were identified with hypertension. Multivariate logistic regression using age, sex, smoking, alcohol use, diabetes, and history of MI or stroke as covariates showed a significant association between hypertension and age (<40: OR = 1.13, 95 CI:1.11–1.15, > = 40: OR = 1.05 95% CI:1.04–1.06), male (OR = 1.57, 95% CI:1.33–1.89), alcohol use (OR = 1.59, 95% CI:1.30–1.93), and diabetes (OR = 2.63, 95% CI:1.93–3.58).

Conclusions:

MMM 2021 in Nepal found more than half of the adults in communities were undiagnosed and untreated. Community-based campaigns such as MMM are meaningful for countries to collect hypertension cascade data in hard-to-reach areas and identify those at high-risk.
ISH-PP-1: ISH POSITION PAPERS, PUBLICATIONS AND OTHER INITIATIVES OF THE SOCIETY
Authors: Tomaszewski Maciej
Published: January 2023

This session will discuss the new initiatives of the Research and Education Committee under ISH Presidency 2020–2022. We will provide the highlights from ISH position papers and the updates on Society's seminal reviews and collaborations.
ISH-PP-6: ADDRESSING GLOBAL DISPARITIES IN BLOOD PRESSURE CONTROL: PERSPECTIVES OF THE INTERNATIONAL SOCIETY OF HYPERTENSION
Authors: Schutte Aletta E
Published: January 2023

Raised blood pressure is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high and low resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in blood pressure control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanisation, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial and environmental determinants, and strengthening health systems implement a well-designed customised quality of care improvement framework.
ISH-PP-7: SCALING-UP HYPERTENSION CARE IN RESOURCE-CHALLENGED SETTINGS GLOBALLY
Authors: Jafar Tazeen H
Published: January 2023

High blood pressure (BP) is the leading modifiable risk factor for death. More than 1.4 billion people suffer from hypertension worldwide. BP control remains less than 30% in high-income countries and < 10% in low- and middle-income countries (LMIC) rural areas, leading to significant disparities in hypertension-related cardiovascular mortality. Immediate action is needed to address suboptimal hypertension care globally and related inequalities.

Evidence shows that strategies that leverage the existing infrastructure to deliver hypertension care are more likely feasible and rapidly scalable at marginal cost. The Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka (COBRA-BPS) trial demonstrated that a community health worker-led multicomponent intervention tailored to rural settings improved BP control. It was also cost-effective and affordable (less than US$2 per capita annually). Likewise, community health worker-led models of hypertension care were beneficial in urban slums in Argentina, China, Colombia, India, Indonesia, Malaysia, Nepal, Pakistan, and Kenya.

The partnership between WHO and Resolve to Save Lives is an excellent initiative to focus national attention on hypertension treatment in many low- and middle-income countries. Strong advocacy and multi-sectoral collaborations are also needed to implement policy strategies for hypertension prevention, including access to healthy foods and the built environment to promote physical activity.

A (proposed) Global Hypertension Care Task Force jointly led by WHO and ISH could catalyse improvement in BP control rates. Every country should establish a dedicated national coordinating center for stewardship and implementing the hypertension control agenda through multifaceted, cost-effective strategies, including population-level policy initiatives and health systems strategies targeting high-risk individuals. Such efforts could save the lives of more than 100 million people aged 30–70 years, who would otherwise die prematurely by 2030, and help achieve Sustainable Development Goal 3.4
JS-CME-3: EXERCISE IN THE PREVENTION AND TREATMENT OF HYPERTENSION AND ASSOCIATED CARDIOVASCULAR RISK
Authors: Hanssen Henner
Published: January 2023

Arterial hypertension and associated cardiovascular (CV) disease remain a health care challenge. The global prevalence of hypertension is estimated to be in the range of 30–45 %. In Europe, about 25 % of heart attacks have been linked with hypertension. Lifestyle interventions are an essential and established part of hypertension management and provide a most effective means to achieve recommended blood pressure targets. For example, patients with hypertension engaged in regular physical activity have been shown to have a reduced risk for CV mortality (20–60%), as opposed to sedentary patients with a twofold increased CV mortality risk. Independent of the severity of hypertension, lifestyle advice is a first line treatment modality for lowering blood pressure in all of the recent guidelines on management of hypertension. In 2021, the EAPC and ESC Council of Hypertension Consensus Document found consistent evidence from a meta-review that exercise prescription can be refined by recommending type of exercise treatment according to initial blood pressure levels as a more personalized lifestyle intervention. Moreover, the focus on recommendations for the treatment of hypertension may need to shift towards focusing on reduction of overall CV risk. Whereas anti-hypertensive drug treatment primarily lowers blood pressure, exercise treatment, for example, has the potential to beneficially affect most of the associated CV risk factors and thus very effectively reduce overall CV risk as well as prolong health span. Cumulative overall CV risk can be quantified by non-invasive assessment of micro- and macrovascular function. The susceptibility of vascular biomarkers in response to exercise treatment is vital to investigate the effects of exercise interventions on overall CV risk in patients with hypertension.
JS-ISH-ESH-4: SEASONAL VARIATION IN BLOOD PRESSURE AND THE RISK OF CARDIOVASCULAR DISEASES
Authors: Ohkubo Takayoshi
Published: January 2023

Blood pressure exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. The seasonal blood pressure variation can be confirmed by repeated office measurements. However, long term home blood pressure measurement under stable condition is the best tool to access seasonal blood pressure variation because it is highly reproducible and reliable. In this lecture, I would like to talk about evidences on the prognostic significance of seasonal blood pressure variation and some recommendations for clinical practice.
JS-NG-2: LONG-TERM EFFICACY AND SAFETY OF ALISKIREN IN FOUR CASES WITH MALIGNANT HYPERTENSION
Authors: Fujii Wataru , Yasukawa Minoru , Homma Fumika Ochiai , Morimoto Chikayuki , Asakawa Shinichiro , Nagura Michito , Arai Shigeyuki , Yamazaki Osamu , Tamura Yoshifuru , Fujigaki Yoshihide , Shibata Shigeru
Published: January 2023

Objective:

Malignant hypertension (MH) is a form of hypertensive emergency defined by a severe increase in blood pressure (BP) with multiple organ injuries. One possible pathophysiology of MH is an acute activation of the renin-angiotensin system (RAS) driven by the intense stimulation of renin secretion in the juxtaglomerulosa cells. Considering this mechanism, aliskiren, a direct renin inhibitor (DRI), can be a treatment option for MH. However, there is little information on the efficacy and safety of DRI in controlling MH. We herein report four cases with MH that have been successfully controlled by DRI for a long term.

Case description:

All of the four cases (three male and one female; 34 to 57 years of age) developed advanced retinopathy (III or IV grade on Keith-Wagener classification) and severe hypertension (> 200/120 mmHg) at presentation, meeting the criteria for MH according to the 2020 ISH global hypertension practice guideline. Mean systolic/diastolic BP was 215 ± 5/148 ± 8 mmHg. All developed acute kidney injury, with the mean serum creatinine (sCr) of 4.47 ± 1.13 mg/dl on admission. The ranges of plasma renin activity (PRA) and plasma aldosterone concentration (PAC, as measured by RIA) were 11–33 ng/mL/hr and 371–1370 pg/mL, respectively. Followed by initial treatment with an intra-venous calcium channel blocker, these patients were prescribed aliskiren, starting at 150 mg/day once daily, after confirmation of the elevated PRA levels. In general, aliskiren was well tolerated and BP was successfully controlled in all of the four cases (at discharge, mean systolic/diastolic BP was 123/74 mmHg and mean sCr was 3.84 mg/dL). Patients continued to receive aliskiren (at a dose of 150 or 300 mg/day) after the discharge and mean systolic/diastolic BP and sCr were 131 ± 4/84 ± 3 mmHg and 2.02 ± 0.16 mg/dl at two years of follow-up, respectively. The ranges of PRA and PAC of four cases have fallen to 0.2–0.8 ng/mL/hr and 105–203 pg/mL, respectively.

Conclusions:

In our cases, severe hypertension and target organ damage were fairly controlled with aliskiren on acute and chronic phases of MH. In all of the four cases, PRA declined with anti-hypertensive treatment and was useful in guiding the doses of medications. Although DRI is not a first-line anti-hypertensive drug class, it may be useful in a certain form of MH with high PRA, which merits further study.
JS-NG-10: A RARE CAUSE OF TREATMENT-RESISTANT HYPERTENSION
Authors: Hausberg Martin , Seitz Karl Heinz , Teber Dogu , Reimer Peter , Rueciger Thomas
Published: January 2023

Objective:

To present an educational case report.

Design and method:

In a 22-year old female arterial hypertension was diagnosed and she was treated to blood pressure target values with a combination of candesartan and lercanidipine. At the age of 27 years she planned a pregnancy, therefore antihypertensive treatment was switched to alpha-methyl-dopa and metoprolol. Blood pressure control was no longer achieved, the patient was symptomatic, mostly headaches.

A diagnostic work-up for secondary causes of hypertension was performed.

Results:

There were no signs of kidney disease, renal artery stenosis was ruled out by color-coded duplex-ultrasound, plasma metanephrines were normal, sleep apnea syndrome and hypercortisolism were clinically very unlikely and not formally ruled out.

No signs of hypertensive end-organ damage (left ventricular hypertrophy, microalbuminuria, carotid artery alterations) were detected.

The only pathologic finding confirmed was a marked secondary hyperaldosteronism. Plasma renin concentration was 230 pg/ml, plasma aldosterone concentration 508 pg/ml, along with low normal serum potassium (3.5 to 4 mmol/l).

Addition of nifedipine and low-dose HCT did not achieve blood pressure control, daytime ABPM mean was 144/102 mmHg, nighttime ABPM mean 127/86 mmHg.

Because of suspected missed renal artery stenosis (fibromuscular dysplasia) an MR-angiography of the renal arteries was performed revealing normal renal arteries and normal adrenal glands but a left kidney tumor - not observed in the previous ultrasound examination but confirmed with contrast-enhanced ultrasound.

Surgical removal of the tumor was performed. The histology was suggestive for a juxtaglomerular cell tumor (reninoma). After surgery, plasma aldosterone normalized to 57 pg/ml and plasma renin concentrations were low (3.4 pg/ml). Within 3 months after surgery, all antihypertensive medication could be discontinued and home blood pressure measurements averaged 119/78 mmHg. Soon thereafter the patient became pregnant and delivered a healthy girl. There were no pregnancy related complications and the patient remained normotensive.

A juxtaglomerular cell tumor represents a rare curable cause of hypertension. The first report dates for 1967, until 2019 only about 100 cases were reported in the literature. It may be suspected that the diagnosis juxtaglomerular cell tumors is missed in many cases since these tumors are not easy to detect in standard diagnostic workup of hypertension and many antihypertensive drugs interfere with plasma renin concentrations.
JS-ISH-KSH-2: DIAGNOSTIC APPROACH TO PSEUDO-RESISTANT HYPERTENSION
Authors: Tomaszewski Maciej
Published: January 2023

The lecture will discuss the most common types of pseudo-resistant hypertension. It will highlight the recent advances in this area of clinical research and the proposed strategy to exclusion of pseudo-resistant hypertension.
JS-ISH-KSH-4: EPIDEMIOLOGY OF RESISTANT HYPERTENSION IN KOREA: ABPM REGISTRY DATA
Authors: Shin Jinh
Published: January 2023

Resistant hypertension (RH) may be one of the major challenges in improving the control rate in hypertension (HTN) management. Accurate diagnosis is usually difficult only by measuring office blood pressure(OBP).

For 1230 subjects taking one or more antihypertensive medication (AHM) enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) registry, the prevalence of RH was calculated when RH was defined as uncontrolled BP by three AHM classes including diuretic or controlled BP by 4 or more classes. Prevalence of RH was 11.9 % (146/1230). By using nighttime BP criteria, there was significant difference in the prevalence of RH for OBP versus nighttime BP. Masked uncontrolled HTN was 16.9 % and white-coat uncontrolled HTN was 14.1 %. For nighttime BP control status, odd ratios for smoking (odds ratio(OR), 0.624), drinking (OR, 1.512), coronary artery disease (OR, 0.604), calcium antagonist (OR, 1.705), and loop diuretics (OR, 0.454) were all significant. The prevalence of RH by nighttime BP was significantly higher than using daytime BP criteria.
JS-ECCR/HBPRCA-2: HOMOCYSTEINE AND LIPOPROTEIN (A) AS A DETERMINANT OF ARTERIAL STIFFNESS AND A PREDICTOR OF HYPERTENSION MEDIATED TARGET ORGAN DAMAGE (HMOD)
Authors: Carnagarin Revathy , MwiPatayi Patrice , Schlaich Markus
Published: January 2023

Background:

Despite advances in modern medicine, cardiovascular disease (CVD) remains a leading cause of global mortality. Among the many CVD determinants, hypertension is a leading modifiable risk factor and blood pressure control and prevention of hypertension mediated target organ damage (HMOD) has become the hallmark of cardiovascular risk management. Homocysteine and lipoprotein (a) are independent CVD risk factors, proposed to contribute to vascular compromise by facilitating thrombogenesis and atherosclerosis.

Aims:

We sought to determine in a real-world clinical setting whether these risk factors interact to facilitate vascular organ damage in hypertension.

Methods:

We performed a cross-sectional analysis of prospectively collected data in 131 hypertensive patients referred to our tertiary hypertension clinic at Royal Perth Hospital. The Lipoprotein (a), homocysteine and other biochemical parameters studied were assayed in the central hospital laboratory. We analysed the effect of the interaction between Lipoprotein (a) and homocysteine (Lpa-Hcy) on markers of HMOD including arterial stiffness, as assessed by pulse wave velocity (PWV).

Results:

The average age of participants was 56 ± 0.9 years, and there was a greater proportion of males than females (62% vs. 38%). The regression analysis demonstrated that Lp(a)-Hcy interaction was significantly associated with PWV [beta = 0.33; 95% CI 0.12, 0.55; p < 0.005], 24 h urinary protein excretion [beta = -10.9; 95% CI -14.5, -7.4; p < 0 .001], and estimated glomerular filtration rate [beta = 103.9; 95% CI 93.9, 113.8; p < 0.001], which persisted after adjusting for potential confounders such as age, sex, 24 h BP, inflammation, smoking, diabetes mellitus and other metabolic risk factors. Interaction analysis showed that increasing homocysteine and lipoprotein (a) concentration was associated with increasing arterial stiffness. Hcy levels does not affect the PWV if Lp(a) levels are normal and the knowledge of both Lp(a) and Hcy are necessary to determine arterial damage. Furthermore, Lp(a)-Hcy product exhibited a positive predictive relationship with every unit increase in Lp(a)-Hcy product associated with a 0.3 m/s increase in PWV which may represent a useful marker for cardiovascular risk stratification and may suggest the need for rigorous treatment to minimise HMOD progression. These clinical findings provide novel insights into the potential interaction between Lp(a) and Hcy in the pathogenesis of hypertension mediated vascular damage
JS-WHL-ISH-LANCET-4: VALIDITY OF AUTOMATED BPMD IN CLINICAL PRACTICE AND PUBLIC HEALTH. A GLOBAL NEED FOR HYPERTENSION MANAGEMENT
Authors: Ordunez Pedro , Lombardi Cintia
Published: January 2023

HEARTS in the Americas is the flagship program to improve population hypertension control and to reduce the CVD burden. Currently, the initiative is being implemented in 2095 primary health care facilities in 24 countries. Accurate BP measurement is key to effective management of hypertension and is one of the six strategic pillars of HEARTS. A pivotal action to facilitate the progress of the agenda was to examine the regulatory frameworks related to BPMDs in participating countries. Study found that most countries had an existing medical devices law, or the foundation for such a law, that stipulated a regulatory bodies responsibilities. However, only six countries had regulations that applied explicitly to BPMDs, and just two had regulations that mandated accuracy and precision validation criteria as a condition of premarket approval. Seven countries had government bodies responsible for enforcing medical device regulations, and seven had mechanisms to remove devices from the market that did not comply with regulations. Seven countries had a centralized system of acquiring BPMDs, but the acquisition was only regulated in six of these countries. In summary, BPMDs can be approved for sale in most countries without the manufacturer providing evidence of passing an internationally accepted clinical validation standard. The efforts to improve access to validated automated BPMDs are different for each country, in line with its priorities, health system maturity including regulatory, economic, and political conditions. Indeed, most of the facilities implementing HEARTS began to use accuracy-validated automated BPMDs. The general achievements showed in concrete actions are twofold: sectors of governments have been investing politically and administratively in modifications to regulations that do not require a substantive legislative process; and improved procurement toward exclusive access of validated automated BPMDs has been at least partially achieved. The improvement of procurement mechanisms has focused on defining technical specifications that include accuracy validation. The challenges that the countries face to reach the goal of exclusive use of validated BPMDs in PHC are enormous and multifactorial. This confirms the need for a robust regulatory framework and comprehensive strategic approach to exclusive use of clinically validated automated BPMDs at regional level. The successful implementation of the initiative depends on a coordinated effort across government and other stakeholders that will contribute to better diagnosis and management of hypertension in the Americas.
JS-AHA: AHA SESSION CLINICAL CASE; CLINICAL-PATHOLOGICAL CONFERENCE (CPC) IN COOPERATION WITH HYPERTENSION, AN AMERICAN HEART ASSOCIATION JOURNAL
Authors: Fanelli Elvira , Persu Alexandre
Published: January 2023

A 35-year-old woman, with a known history of right renal artery FMD, presented at the Hypertension Outpatient Clinic for evaluation of resistant hypertension. The patient was an active smoker and had a single kidney after left nephrectomy for kidney malformation during childhood.

The diagnosis of FMD had been made on the occasion of a previous pregnancy at 23 years, complicated by preeclampsia and an angioplasty had been performed. Work-up disclosed a recurrence of right renal artery stenosis, and a new renal angioplasty was performed. Blood pressure normalized after the procedure.

At 36 years, the patient had another pregnancy, also complicated by preeclampsia and preterm delivery. An Echo-Doppler performed during pregnancy and an Angio-CT after delivery, allowed ruling out recurrence of renal artery stenosis.

At 43 years, she was admitted to the emergency room for thoracic pain. The coronarography was in favour of a coronary spasm. There was no coronary stenosis or image suggestive of a Spontaneous Coronary Artery Dissection.

At 54 years, the patient was again admitted in emergency for malignant hypertension associated with severe acute renal failure. She also reported a history of lower limbs claudication since several months. An abdominal CT disclosed dissection complicated by occlusion of the right renal artery, dissection of both iliac arteries as well as a severe stenosis of the infra-renal aorta. An angioplasty with insertion of stents in the right renal artery and the aorta was performed. After the procedure, a partial normalization of renal function was observed, and blood pressure control was achieved on 3 medications.

During the recovery, the patient presented a skin rash associated with a general feeling of discomfort, with spontaneous resolution after a few days. One year later, following a control Angio-CT of the abdomen, an anaphylaxis episode occurred, requiring Adrenaline administration. Iodine contrast allergy was suspected, but milder hypersensitivity symptoms occurred in the following months, without exposition to a clear trigger. An allergology work-up was performed with final diagnosis of secondary Mast Cell Activation Syndrome. B-Blockers and ACE-inhibitors were contra-indicated and cautious premedication before further exposure to iodine contrast was recommended.
JS-HR-1: UPDATE OF VASCULAR FUNCTION
Authors: Maruhashi Tatsuya , Higashi Yukihito
Published: January 2023

Atherosclerosis has two aspects: vascular dysfunction and vascular structural alterations. Both vascular dysfunction and vascular structural alterations are associated with future cardiovascular events. Therefore, the assessments of vascular function and vascular structural alterations may be useful not only for the assessment of the severity of atherosclerosis but also for the stratification of cardiovascular risk. Flow-mediated vasodilation and reactive hyperemia index as indices of endothelial function, nitroglycerine-induced vasodilation as an index of vascular smooth muscle function, and pulse wave velocity as an index of arterial stiffness, have been used for the assessment of vascular function in clinical settings. In this session, we summarize the updated information on the usefulness of vascular function tests in the management of patients with cardiovascular risk factors.
JS-HR-3: HEART DISEASE-FOCUS ON LEFT ATRIUM STRUCTURE-
Authors: Nagai Michiaki
Published: January 2023

Investigating potential biological relationships between heart failure (HF) with preserved ejection fraction (HFpEF) and associated diseases has been the focus of much research to establish personalized therapies. Hypertension is the most common concomitant disease in HFpEF patients, but the functional links between HFpEF and hypertension are still not fully understood and effective therapeutic strategies are still lacking. The structure of the left atrium (LA) is important for the diagnosis of HFpEF. In the SPRINT sub-analysis, intensive blood pressure control was not associated with ECG-defined LA abnormalities. In the ARGO-SIIA project, LA volumes indexed by height2 were more sensitive to subclinical hypertensive organ damage than those indexed by body surface area (BSA) in females. In the ARIC study, minimal LA volume index, but not standard assessment by maximum LA volume index, was associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP. In this presentation, the latest findings regarding the structure of the LA are updated and summarized in relation to HFpEF.
JS-HR-6: CONSIDERING FRAILTY AND EXERCISE FOR MANAGEMENT OF HYPERTENSION AND HYPERTENSIVE ORGAN DAMAGE
Authors: Toba Ayumi
Published: January 2023

Frailty is defined as physiological decline and a state of vulnerability to stress and results in adverse health outcomes. It consists of multiple domains such as physical, social, and psychological factors. Cognitive decline is one of the factors concerning frailty, and blood pressure (BP) control reduced dementia or cognitive decline significantly in meta-analysis. However, in elderly population above 80 years, positive effect of antihypertensive therapy for preventing dementia was not proved. In the latest study in hypertension research, meta-analysis of prevalence of mild cognitive impairment (MCI) among hypertensive patients were conducted. Overall prevalence of MCI was 30% in a sample of 47179 patients. Another study which prospectively followed elderly hypertensive patients for 41 months, mortality rates were lowest in those with systolic blood pressure < 140mmhg with no frailty, and highest in those with systolic blood pressure < 140mmHg with frailty. Since frailty and cognitive decline is common in hypertensive patients, adequate blood pressure management in frailty patients are required. Further research accumulating scientific evidence with longitudinal data is needed for the guidance of blood pressure control in such patients. On the other hand, treatment of elderly hypertensive patients is complicated because their comorbidity, frailty, cognitive function, and social status should be taken into consideration. Individual assessment and constant follow up is imperative for the treatment of these patients.

In the era of technically advanced, people are spending less active which leads to cardiovascular risks including hypertension. However, guidelines emphasize the importance of non-pharmacological strategies such as life style modification and exercise to prevent diseases. In the latest study in hypertension research, a study compared different types of exercise which is beneficial for health. As for the result, combination exercise of aerobic and resistance training was most effective at improving cardiorespiratory fitness, muscle strength BMI, fat mass, glucose, cholesterol and triglyceride. Several studies showed isometric exercise training reduced systolic blood pressure. Other study showed vascular function improved with daily exercise habits such as stair climbing.
RAG-AMERICAS-2: TRENDS, OPPORTUNITIES AND FUNDS IN LATIN AMERICA
Authors: Colombari Debora Simoes Almeida
Published: January 2023

Hypertension is one of the most important risk factors for major cardiovascular diseases, the leading cause of death in Latin America, which comprise Central America, Caribbean and South America. It is estimated that up to 40% of the adult in Latin America population have hypertension. Studies done in different cities from Argentina, Chile, Uruguay and in Brazil have demonstrated the low rates of awareness, treatment and control of hypertension revealing the difficulty and inadequacy in managing this chronic disease on a population level. In addition, mortality risk associated with hypertension in Latin America significantly exceeds that in developed nations. One characteristic of hypertension in the Latin America is the strong association with metabolic syndrome (type 2 diabetes and lipid abnormalities) or the opposite, children, adolescents, and adults with nutritional stunting. Taking Brazil as an example, the cost in the Unified Health System for treating hypertension was around US$ 534 billion in 2018. However, the research and publication in cardiovascular diseases in Latin America are much lower than in high income countries, despite the high qualified researchers and Universities/Institutes of Research. In Brazil, for instance, the funds from National Council for Scientific and Technological Development (CNPq), the major federal agency that support research in Brazil has been decreasing over the years. Thus, in the face of the high prevalence of hypertension in Brazil and in the other countries of Latin American, not only public health initiatives and policy are needed, but also more funds for clinical and basic research in hypertension.
RAG-APAC-1: SOCIAL AGING IN THE ASIA-PACIFIC REGION
Authors: Kotruchin Praew
Published: January 2023

There will be twice as many individuals over the age of sixty worldwide, including in the Asia-Pacific region by the year 2050, according to a report by WHO. The rise in hypertension prevalence, therefore, will be fueled by the anticipated rise in the elderly population.

Even though cardiovascular (CV) risk factors continue throughout a lifespan, older people are more likely to develop cardiovascular diseases (CVDs). Hypertension accounts for a significant share of major morbidities and mortalities in the Asia-Pacific area. Therefore, the main objectives of integrated healthcare for older populations are to minimize CV risks as well as to provide optimal treatment of CVDs and life-threatening conditions. Another critical factor is the continuity of healthy metabolic profiles including blood pressure from childhood to old age.

There are many challenges in hypertension management with social aging in the Asia-Pacific region. First, the common type of hypertension in the elderly is isolated systolic hypertension. Its prevalence is expected to rise in many parts of Asia, however, clear guidance for the management is not yet provided. Second, a relatively high salt intake which is known as one of the most important risk factors for hypertension has been reported in the Asia-Pacific region. The genetic epidemiology network of salt sensitivity dietary feeding study reported that nearly 40 percent of Chinese adults were salt-sensitive. Moreover, salt sensitivity is more common in older individuals who are more susceptible to CVDs. Therefore, the action to lower salt intake is an immediate requirement. Finally, relatively poor compliance is more common in older individuals, whether it is because of their impaired functions or because of possible intolerance of medications, and drug-drug interactions. The recent trials of fixed-dose combinations and polypills showed that they may help improve compliance. However, reimbursement is still a problem in some areas.

The Asia-Pacific regional strategy including adapting the healthcare systems to solve these challenges is needed to reduce CVD-associated morbidity and mortality in our older populations.