bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-57-6: OBSTRUCTIVE SLEEP APNEA INDUCED GUT DYSBIOSIS STIMULATES A PROINFLAMMATORY RESPONSE THAT PROMOTES NEUROINFLAMMATION AND HYPERTENSION
Authors: Ayyaswamy Sriram , Zhang Bojun , Shi Huanan , Bryan Robert , Durgan David 
Published: January 2023

Objective:
Obstructive sleep apnea (OSA) is an independent risk factor for hypertension (HT). We have demonstrated that OSA induces gut dysbiosis, and a dysbiotic microbiota is causal in the development of HT. The mechanisms linking gut dysbiosis to blood pressure (BP) regulation are unclear. Recent studies demonstrate gut dysbiosis induces a pro-inflammatory host response resulting in peripheral- and neuro-inflammation, key factors in the development of HT. We hypothesized that OSA induced gut dysbiosis elicits a pro-inflammatory response that promotes neuroinflammation and HT.

Methods:
OSA was induced in 8-week-old male rats by repeatedly inflating a surgically implanted tracheal balloon. Sham rats underwent balloon implantation without inflations. After two weeks of apneas, lymphocytes were isolated from aorta, brain, cecum, ileum, mesenteric lymph node, and spleen for assessment by flow cytometry. In studies examining IL-17, a monoclonal antibody to neutralize IL-17 was injected every 48 hours during the 2 weeks of OSA. To track lymphocytes originating from the gut, cells in the Peyers patches of the small intestine were labelled by injection of carboxyfluorescein succinimidyl ester (CFSE) dye.

Results:
Two weeks of OSA significantly decreased anti-inflammatory regulatory T (Treg) cells and increased TH17 (IL-17+) in the brain, cecum, and ileum (n = 7, p < 0.05). A significant increase in the Th17/Treg ratio was observed in brain, cecum and ileum of OSA, versus sham, rats (n = 7, p < 0.05). To examine the role of TH17 cells, we injected an IL-17 neutralizing antibody or control IgG antibody during the 2 weeks of OSA. Compared to OSA rats receiving IgG control, neutralization of IL-17 significantly reduced BP of OSA rats (n = 6, p < 0.05). Additionally, neutralization of IL-17 resulted in a significant increase of Tregs and decreased Th1 cells in brain, cecum and ileum of OSA rats (n = 6, p < 0.01). To examine the distribution of lymphocytes originating from the gut, cells in the Peyers patches of sham and OSA rats were labelled with CFSE. We observed significant increases in CFSE+ Th1, Th2, and Th17 cells in the brain, MLN and spleen of OSA as compared to sham rats (n = 6, p < 0.05).

Conclusion:
Overall, we found that OSA induced gut dysbiosis is associated with a pro-inflammatory response in the gut and brain that involves IL-17 signaling. Our findings suggest that gut dysbiosis may serve as the trigger for widespread inflammation, and treatment strategies to prevent or reverse gut dysbiosis may prove useful in reducing neuroinflammation and HT.
S-58-1: PATIENT PERSPECTIVES OF A CUFFLESS BLOOD PRESSURE DEVICE COMPARED TO CLASSIC OUT-OF-CLINIC METHODS
Authors: Gnanenthiran Sonali Rukshana , Liu Hueiming , Tan Isabella , Chan Justine , Schlaich Markus P , Schutte Aletta E 
Published: January 2023

Objective:
Wearable cuffless blood pressure (BP) monitoring technology has emerged as a novel approach to continuously measure BP for weeks and months, rather than single snapshot clinic measures that are subject to substantial variability. Given poor patient engagement with home and 24-hour BP monitoring, we explored patient attitudes toward the use of a wrist-worn cuffless device, namely the Aktiia device (Switzerland) compared to classic methods.

Design and method:
Two researchers conducted in-depth, semi-structured audio-recorded interviews with consecutive participants (n = 15, age 59 ± 10 years, female 33%, hypertension 100%, coronary artery disease 6.7%) recruited in Perth, Australia. They compared experiences wearing the Aktiia device for at least 7 days versus a classic 24-hour ambulatory BP monitor (Microlife WatchBP O3, Switzerland) worn on 2 separate days within 14 days. Interview topics included device acceptability, factors affecting use and hypertension awareness. Transcribed interview data were analysed thematically and interpreted.

Results:
There was high participant preference, acceptability and engagement with the cuffless wearable device compared to 24-hour monitoring. Classic 24-hour monitoring was associated with low acceptability, sleep disturbance and functional limitation. Despite 14/15 participants owning a home BP device, they reported infrequent use and low acceptability of classic home BP monitoring. Key determinants of cuffless technology use identified by participants were affordability, availability, comfort and usability. Participant perception on the importance of the accuracy of cuffless BP devices was variable, with responses ranging from being uncertain about the importance of accuracy to stating that a 10% margin of error was acceptable given high usability and comfort. Knowledge of the harmful effects of hypertension was poor in the population. There was universal agreement that cuffless technology could improve long-term monitoring and management of BP. Participants also agreed that cuffless technology may better engage patients and promote improved identification of high BP in society, especially if marketed with additional functions such as timekeeping and steps.

Conclusions:
Cuffless BP wearable devices is a rapidly emerging alternative to conventional out-of-office cuff-based BP monitoring, with great promise due to the ability for numerous unobtrusive readings. Here we report high participant preference, acceptability and engagement. However, cuffless BP device accuracy is yet to be determined with appropriate methods as cuffless device validation protocols are still under development. Given the high proportion of people with undiagnosed hypertension in the community, there is need to balance high participant acceptability and need for increased BP awareness in the community with accuracy.
ISH-PL-3: MY ROAD TO ACADEMIC CARDIOLOGY
Authors: Oparil Suzanne 
Published: January 2023

My road to academic cardiology started on our dairy farm in upstate New York, where I learned the pleasures and responsibilities of work at very young age. We were given a little lamb by a neighbor and I was given major responsibility as a young child for caring for him. The work ethic extended to schooling. I studied hard and completed undergraduate studies at Cornell and medical school at Columbia, then began medical residency at Columbia's teaching hospital. There my career was interrupted when the residency class ahead of me filled up with Vietnam veterans. That bad luck turned out to be the best of fortunes when I was introduced to Edgar Haber, then Chief of the Cardiac Unit at the Massachusetts General Hospital. Ed was an innovative scientist, a great mentor and a great leader in cardiovascular medicine. He spurred my interest for the first time in biomedical research and laboratory medicine. Under his guidance, I completed studies that showed for the first time that conversion of the inactive decapeptide angiotensin I to the pressor octapeptide angiotensin II occurred in the pulmonary circulation, not the systemic circulation or in plasma. Another simple study demonstrated the critical role of renin release in maintaining blood pressure when a person assumed the upright posture. The study showed that the renin angiotensin system functions abnormally in people with upright posture-induced vasovagal syncope.
I also developed a burning interest in heart disease in women, specifically, on whether postmenopausal women should use hormone replacement therapy to prevent cardiovascular disease. At that time, women were recommended not to use estrogen replacement therapy for cardiovascular disease prevention because previous studies, carried out in older post-menopausal women, showed no benefit from estrogen. I hypothesized that the integrity of estrogen receptors and the vasoprotective effects of estrogen disappear with aging and tested the hypothesis that favorable responses to estrogen treatment are lost in injured arteries of aging animals (rats). I found that aged ovariectomized rats lost the vasoprotective and anti-inflammatory responses to exogenous estrogen that were seen in younger animals. These results may explain the lack of estrogen responsive in vasoprotection in the vasculature of elderly post-menopausal women treated with hormones.
More recently, findings from my studies in isolated cells and animal models have led to the design and conduct of a variety of clinical studies of hypertension and its treatment in human subjects, including, most recently, pregnant women.
JS-WHO: ACHIEVING SDG 3.4: WHO GLOBAL UPDATES ON HYPERTENSION
Authors: Khan Taskeen 
Published: January 2023

WHO and ISH have a recent MOU under which both organizations will work to reduce cardiovascular disease mortality and morbidity by focussing on treatment of hypertension through implementation of the HEARTS technical package.
This session serves to highlight the work WHO is doing at the global level on hypertension and highlight the recently launched WHO guideline on pharmacological treatment of hypertension in adults.
The second part of the sessions focuses on real examples of HEARTS (public health approach to managing hypertension at PHC) implementation highlighting progress of countries, as well as challenges and solutions.
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.