bluuebunny/crossref_metadata_2025 huggingface dataset:
JS-HR-12: BASIC RESEARCH: ELUCIDATION OF “MOSAIC” PATHOGENESIS OF HYPERTENSION
Authors: Shinohara Keisuke
Published: January 2023

Basic research plays critical roles in elucidating the “mosaic” pathogenesis of hypertension and developing its treatment.

In the field of brain and autonomic nervous system, Chen et al. demonstrated that mild cold exposure elicits autonomic dysregulation, such as increased sympathetic activity and decreased baroreflex sensitivity, and poor sleep quality, causing blood pressure (BP) elevation in normotensive rats. This finding may have critical implications for the cardiovascular event occurrence with low ambient temperature. Domingos-Souza et al. showed that the ability of baroreflex activation to modulate hemodynamics and induce lasting vascular adaptation is critically dependent on the electrical parameters and duration of carotid sinus stimulation in spontaneously hypertensive rats (SHRs), proposing a rationale for improving baroreflex activation therapy in humans.

In the kidney, Kasacka et al. showed that activity of Wnt/β-catenin pathway is increased in SHRs and 2K1C hypertensive rats, while it is inhibited in DOCA-salt rats. Intrarenal renin-angiotensin system (RAS) is involved in BP regulation. In renal damage with an impaired glomerular filtration barrier, liver-derived angiotensinogen filtered through damaged glomeruli regulates intrarenal RAS activity. Matsuyama et al. further showed that the glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure causes circadian rhythm of the intrarenal RAS. Otsuki et al. revealed that TWIST1, a transcription factor regulating mesodermal embryogenesis, transcriptionally upregulates complement 3, which has been demonstrated to activate intrarenal RAS, in the glomerular mesangial cells from SHRs.

The RAS in the vascular system also contributes to BP regulation. Soring nexins (SNXs) are cellular sorting proteins and can regulate the expression and function of G protein-coupled receptors (GPCRs). Liu C et al. demonstrated that SNX1 knockout mice exhibit hypertension through vasoconstriction mediated by increased expression of GPCR AT1R within the arteries. Liu X et al. found that sirtuin 6 (SIRT6) expression is downregulated in the aortae of aged rats and showed that SIRT6 knockdown enhances angiotensin II-induced vascular adventitial aging by activating NF-κB pathway in vitro studies.

The studies investigating extracellular vesicles (EVs) and gut microbiota have been increased. Ochiai-Homma et al. showed that pendrin in urinary EVs can be a useful biomarker for diagnosis and treatment of primary aldosteronism. Wu et al. demonstrated that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt hypertensive rats.

Several reports indicate the potential treatment for hypertension and the associated organ damages: rivaroxaban in cardiac hypertrophy; nebivolol, maximakinin, and Pinggan-Qianyang in hypertension; and melatonin and crocin in gestational hypertension.
RAG-AMERICAS-1: CLINICAL RESEARCH IN LATIN AMERICA: FROM SPONSORED TO INVESTIGATOR INITIATED RESEARCH
Authors: Piskorz Daniel Leonardo
Published: January 2023

Latin American clinical researchers had participated in many controlled clinical trials in the 80 s and 90 s sponsored initiated that confirmed the place of calcium channel blockers and RAS blockade in hypertension treatment. Later, non-inferiority or superiority trials like ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and VALUE, Valsartan Antihypertensive Long-term Use Evaluation were performed worldwide including Latin-American countries. In the last decade, the absence of new drugs in the pipeline and sponsors portfolios at one side, and the recommendation of fixed-dose combination as initial treatment tool at the other could be supposed as main causes of a dramatic reduction in sponsored hypertension research.

At the same time, a huge increase in investigator initiated research was observed. Scientific national and regional societies in many cases fueled this increase. In this scenario, the Cardiovascular Risk Factor Multiple Evaluation in Latin America, CARMELA study was the first large-scale population-based study that assessed cardiovascular risk factor prevalence in 7 Latin American cities and its relationship to hypertension mediated organ damage. CARMELA is an example of an epidemiological study investigator initiated supported by a sponsor in Latin America

The FOCUS study, Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention was another example of an investigator initiated research supported by a private company. FOCUS was funded by the 7th Framework Programme European Commission Consortium with the participation of the Centro Nacional de Investigaciones Cardiovasculares CNIC Madrid, Spain, World Heart Federation, Federación Argentina de Cardiología, and some European research organizations, supported by FERRER Internacional. FOCUS help to understand the reasons of treatment non-adherence in Latin American countries and also to recognize the potential benefits of fixed-dose combinations in secondary prevention.

More recently, the Interamerican Society of Cardiology SIAC developed the CorCOVID Latam study which aim was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19 during the pandemic. This study is a good example of the feasibility of non-sponsored research in Latam supported by a regional scientific society structure and members. Five publications related to gender differences in the impact of the pandemic in Latam, Influenza and Pneumococcal vaccination during the pandemic, and the psychological impact in more than 4 thousand patients were the fruit of this society research initiative.
RAG-SACA-4: A FIVE-YEAR SUMMARY OF THE MMM CAMPAIGN IN NEPAL
Authors: Neupane Dinesh
Published: January 2023

Objective:

To share the implementing experience of the May Measure (MMM) campaign in Nepal.

Design and Methods:

Nepal has been a part of the MMM initiative since its inception. NeDS Nepal, a not-fort profit NGO was responsible for the overall coordination of the campaign. We trained and mobilized community health workers and health science students as volunteers. Although MMM was not executed globally due to the COVID-19 pandemic in 2020, it was conducted in Nepal by following safety measures.

Results:

The volunteers set up screening sites in supermarkets, temples, colleges, grocery stores, primary health care clinics, banks, government offices, and meeting halls. Some of the volunteers also did house-to-house visits. Between 2017–2021, we screened over 130,000 participants. We identified > 30,000 high blood pressure participants, provided lifestyle counseling, and referred them to the health facility for further diagnosis and treatment. Out of them, ∼18000 were newly identified hypertension.

Conclusions:

Opportunistic screening like MMM is feasible and needed in the context of Nepal. This could potentially be embedded in the national screening program. It is also important to have a strategy for linking the patients with the health system for further diagnosis and treatment.
RAG-SACA-5: HEALTH SYSTEM STRENGTHENING ACTIVITIES FOR BETTER HYPERTENSION CARE
Authors: Jose Arun Pulikkottil
Published: January 2023

Raised systolic BP was responsible for 10·4 million deaths and 218 million disability adjusted life years across the globe in 2017. A disease that largely affected high-income countries in the past, has now been shown to affect low-income and middle-income countries disproportionately.

Weak health infrastructure, poor access, high illiteracy rates, poverty, high costs of drugs, bad dietary habits and skewed national health priorities have been found to contribute to the poor performance of these countries in the hypertension care cascade. While there are several effective targeted as well as population-level interventions available to choose from, most countries have failed to integrate them effectively into their hypertension control strategies. Health system-strengthening activities such as capacity building, task shifting and appropriate use of digital health technologies can help bridge some of these gaps.

Certificate Course in Management of Hypertension (CCMH) is a joint certification program designed and implemented by the Public Health Foundation of India (PHFI) in collaboration with the British & Irish Hypertension Society (BIHS), the International Society of Hypertension (ISH) and the Centre for Chronic Disease Control (CCDC). CCMH is an ten month course with once- a- month contact sessions, being conducted on a designated weekend at regional training centres across India. It is fundamental objective is to enhance the knowledge, skills and core competencies of practicing PCPs in the management of Hypertension and to build their network with other PCPs and existing specialists. A total of over 2000 primary care physicians have been trained in the initiative so far. The course is being adapted in collaboration with the American Heart Association for online education of prescribers as well as non-prescribers. In addition, PHFI has also instituted an innovative assisted telemedicine healthcare delivery model - Digisahayam - which acts as an inter-operable system setting up multiple innovations in digital health technology on a single platform. It works on the model of task sharing and task shifting while embedding electronic health records (EHR), point-of-care diagnostics (13 common lab tests including ECG), in-built clinical decision support system and numerous state-of-the-art digital health technologies. Approximately 16,000 teleconsultations have been conducted in three clinics in India over the span of 18 months.
PS-B02-1: UPREGULATION OF KEY GENES ELN AND TGFB3 WERE ASSOCIATED WITH THE SEVERITY OF CARDIAC HYPERTROPHY
Authors: Zhang Rui , Xu Xuan , Chen Xi , Hao Chunshu , Ji Zhenjun , Zuo Pengfei , Yang Mingming , Ma Genshan , Li Yongjun
Published: January 2023

Background:

Hypertension induced cardiac hypertrophy is one of the most common pre-diseases of heart failure. This study aimed to identify the key pathogenic genes in the process of disease.

Methods:

GSE18224 was re-analyzed and obtained the differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and key module was further screened out from PPI network. GSE36074 dataset and our constructed transverse aortic constriction (TAC) mouse model were both used for validating expression of genes in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated.

Results:

Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological process including collagen fibril organization, cellular response to transforming growth factor beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway, etc. There were 387 miRNAs targeted to 257 DEGs, while 177 TFs targeted to 71 DEGs. The PPI network contains 222 nodes and 770 edges, and 18 genes were screened out in the module. After validation, eight genes, which were also significantly upregulated in GSE36074, were selected out from the 18 DEGs. Two of the eight DEGs including Eln and Tgfb3 were also significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were both positively correlated with level of the disease biomarkers.

Conclusion:

Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which will provide potential therapeutic targets for the disease.
PS-B02-7: THE LONG NON-CODING RNA CAREN IMPROVES CARDIAC DYSFUNCTION IN AGED MICE
Authors: Sato Michio , Miyata Keishi , Kadomatsu Tsuyoshi , Node Koichi , Oike Yuichi
Published: January 2023

Background:

Heart failure (HF) is the predominant cause of hospitalization and amongst the leading causes of death in developed countries. Especially, the prevalence of HFpEF is increasing and its prognosis is not improving. Our understanding of HFpEF pathophysiology is incomplete and optimal treatment remains uncertain. Under such circumstance, recently, it has been reported that some lncRNAs expressed in heart play important roles in cardiac development and disease.

Methods and Results:

Using a gene trapping approach in mouse embryonic stem cells, we identified Caren (for cardiomyocyte-enriched noncoding transcript), a cytoplasmic lncRNA abundantly expressed in cardiomyocytes. Caren overexpression in cardiomyocytes activated mitochondrial biogenesis by upregulating of Tfam protein and attenuated TAC-induced activation of Ataxia Telangiectasia Mutated (ATM), a key regulator of DNA Damage Response (DDR). Moreover, TAC operated mice treated with AAV6-Caren relieved reduction of fractional shortening (%FS) and improved dilatation of left ventricular. Next, proteomics analysis revealed that Histidine triad nucleotide-binding protein1 (Hint1) which activates the ATM-DDR pathway was reduced in Caren transgenic mice. Moreover, 24-month-old WT mice treated with AAV6-Caren diminished systolic and dilatation capacity were improved. And electron microscopy analysis revealed that mitochondrial cristae were restored and the numbers of mitochondria were increased in the heart of 24-month-old WT mice treated with AAV6-Caren compared with the mice treated with AAV6-GFP as control.

Conclusion:

A cytoplasmic lncRNA Caren improves not only systolic function but also diastolic function in failing / aged heart by suppressing the ATM-DDR pathway and activating mitochondrial bioenergetics.
PS-B02-9: HEART RELATED CIRCULAR RNA (HRCR) INFLUENCES POLYGENIC CARDIAC HYPERTROPHY BY ALTERING CARDIAC MICRORNAS
Authors: Prestes Priscilla Ribeiro , Maier Michelle Carla , Byars Sean , Harrap Stephen B , Charchar Fadi J
Published: January 2023

Left ventricular hypertrophy (LVH) is the main risk factor for cardiovascular disease after age. Circular RNAs (circRNA), a novel and underexplored RNA type, are created by the back-splicing of pre-mRNA and have been proposed to regulate gene expression post-transcriptionally via targeting micro RNAs (miRNA). Heart related circRNA (Hrcr) has been proposed as an important regulator of LVH and has been shown to be downregulated in mice with cardiac hypertrophy induced by chronic infusion of isoproterenol.

Our aim was to investigate the expression of Hrcr in the hypertrophic heart during development and at maturity. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of LVH and heart failure, and its genetic control strain, the normal heart rat (NHR). We first measured the expression of Hrcr by quantitative real-time PCR in left ventricles of HHR and NHR at five ages (2 days old, 4-, 13-, 33- and 50-weeks old). Secondly, we silenced HRCR in human primary cardiomyocytes and performed small RNA sequencing to reveal its miRNA downstream targets. Lastly, we performed in silico investigations to predict miRNA-mRNA targets and explore enriched gene ontology terms in our dataset.We found that Hrcr is upregulated in the HHR at 13-, 33- and 50-weeks old (FC = 2.77-3.57; P < 0.05). The silencing of HRCR revealed novel downstream targets, including four miRNAs (miR-1-3p, miR-330, miR-27a-5p and miR-299-5p) and two noncoding RNAs (ribosomal RNA RNA5-8SP2 and piwi-interacting RNA piR-17153). The miRNA-mRNA interactions predicted a total of 359 mRNAs highly likely to be targeted by the differentially expressed miRNAs. Lastly, 206 gene ontology terms were enriched in our dataset, including terms related to heart development and cardiovascular disease.
PS-C01-10: BLOOD PRESSURE AND OUTCOMES OF TREATED MODERATE HYPERTENSION IN ELDERLY PATIENTS
Authors: Kim Ju Hyeon , Lim Subin , Chung Se Hwa , Yum Yunjin , Joo Hyung Joon , Kim Yong Hyun , Kim Eung Ju
Published: January 2023

Objective:

There is limited evidence of the growing population of elderly patients with hypertension, particularly the relationship between blood pressure (BP) and adverse outcomes. We sought to estimate outcomes according to attained BP in elderly patients treated for moderate hypertension.

Design and method:

This multicenter, retrospective study used the Korea University Medical Center database built on electronic health records from 2017 to 2020. Patients initiated with at least two antihypertensive drugs as combined therapy were followed up for 3 years. The patients were grouped by on treatment systolic BP (SBP) in 10 mmHg increments from less than 120 to 140 mmHg or more. The primary outcome was a composite of all cause mortality, myocardial infarction, and stroke. The relationships between attained BP and outcomes were assessed using adjusted Cox regression analyses and restricted cubic splines.

Results:

From Jan 2017 to Dec 2017, a total of 4760 patients aged over 75 years (mean age 79.9) were enrolled and grouped into SBP lower 120 mmHg (n = 1188), SBP 120 to 129 mmHg (n = 1221), SBP 130 to 139 mmHg (n = 1194), and SBP over 140 mmHg (n = 1157). After a median follow up of 4.5 years, the incidence of the primary outcome was lowest in individuals with SBP of 120 to 129 mmHg (9.2%, p = 0.087). The age adjusted hazard ratio for the primary outcome showed a J shaped relationship with on treatment SBP and diastolic BP.

Conclusions:

A J curve relationship between on treatment SBP and the composite outcome was found consistently. In real world practice, on treatment SBP less than 130 mmHg was associated with improved outcomes in the elderly with moderate hypertension.
PS-C01-14: IS SHORT STATURE A PROTECTIVE FACTOR IN AN OVERWEIGHT/OBESE AND HYPERTENSIVE OLD AGE POPULATION?
Authors: Paterno Carlos Alberto
Published: January 2023

Objective:

Age is the most powerful cardiovascular risk factor. Life expectancy is reduced due to hypertension and obesity. There is little information about height and longevity. Geographically in the human population, the short stature was observed as the island effect. The aim of this study is to know whether the short stature is a protective cardiovascular factor in the overweight/obese and hypertensive old age population.

Design & Methods:

For this cross-sectional epidemiological study was registered female-male 1145–729 overweight/obese hypertensive patients with an average age of 54.9–59.2 years. The range of age was from 18 to 94 years. Anthropological data, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and central hemodynamics parameters (CHP) were compared between the upper and the under quintile of stature, in each decade, and assessed the difference of them. The CHP was measured with a SphygmoCor System PVX, a validated device employing the high-fidelity technique of applanation tonometry according to established protocols. Patients, when entered at the registration were hypertensive with or without treatment or awareness that had hypertension.

Results:

The relation females-males were 1.57, similar to the Italian population 1.51 according to the National Institute of Statistics (census 2021) assessed between the 80 s years to the 90 s years. The body mass index of females-males was 30.4–29.7, respectively. When were assessed the first with the fifth quintile of the stature of each decade, the body mass index, SBP, DBP, HR, central aortic pressure, end-systolic pressure, mean arterial pressure, and pulse pressure does not find a clear statistically significant difference. Obviously, in the upper quintile, the stature and the weight were highest with statistically significant differences. In both sexes with increasing age were observed gradually a population with shorter statures. In this sample the population from the 30 s years to the oldest, the stature decreased in the female group from 162.5 cm to 147.7 cm (difference of 14.8 cm), and in the male group from 176.8 cm to 162.5 cm (difference of 14.3 cm), into both sexes near 2.9 cm by decade.

Conclusion:

High stature, over time, might cause a pernicious overload of work to the cardiovascular system in subjects with several risk factors at old age. The short stature in subjects of both sexes could be a protective factor in a population of older overweight/obese hypertensive, a fact more evident in the female group than the male group.
PS-C03-11: FACTORS ASSOCIATED WITH BLOOD PRESSURE CHANGES IN RESPONSE TO DIGITAL THERAPEUTICS SYSTEM: A RETROSPECTIVE ANALYSIS OF THE HERB-DH1 TRIAL
Authors: Aga Mitsuharu , Hisaki Fumi , Tanigawa Tomoyuki
Published: January 2023

Digital therapeutics are evidence-based therapeutic interventions driven by software. Recently, the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial was conducted to investigate the efficacy of the digital therapeutics in patients with hypertension. It has demonstrated that the difference between digital therapeutics group and control group in mean change in 24 h ambulatory SBP from baseline to 12 weeks was -2.4 (95% confidence interval [CI]: -4.5 to -0.3). However, The mechanism that led to the decrease in blood pressure has not been elucidated.

We retrospectively analyzed the digital therapeutics group (HERB system + standard lifestyle modification) of the HERB-DH1 trial. Spearman's correlation test between the blood pressure change from baseline to 12 weeks and clinical variables in patients with hypertension was performed. Of the 199 patients, 148 patients with available data for initial and final blood pressures were included. In the univariate analysis, age (r = -0.1761; 95% CI: -0.3324 to -0.01033; P = 0.0323), baseline blood pressure (r = -0.3697; 95% CI: -0.5048 to -0.2170; P < 0.0001), body weight change (r = 0.1704; 95% CI: 0.004451 to 0.3271; P = 0.0385), baseline BMI (r = -0.1738; 95% CI: -0.3303 to -0.008007; P = 0.0346) and BMI change (r = 0.1653; 95% CI: -0.0007627 to 0.3225; P = 0.0447) were related to blood pressure change. In conclusion, it is indicated that intervention in the digital therapeutics group of HERB-DH1 trial leads to lifestyle modification and body weight change, which impact on effective blood pressure control.
PS-C04-6: ASSOCIATION BETWEEN SERUM URATE LEVEL AND CAROTID ATHEROSCLEROSIS: AN INSIGHT FROM A POST-HOC ANALYSIS OF THE RANDOMIZED CLINICAL TRIAL (PRIZE)
Authors: Tanaka Atsushi , Node Koichi
Published: January 2023

Objectives:

Elevated serum urate (SU) levels are associated with arterial atherosclerosis and subsequent cardiovascular events. However, an optimal therapeutic target SU level for delaying atherosclerotic progression in patients with hyperuricemia remains uncertain. The aim of this analysis was to assess an association between changes in SU level and carotid intima-media thickness (IMT) to examine whether an optimal SU concentration exists to delay atherosclerotic progression.

Design and method:

This was a post-hoc analysis of the PRIZE (program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled) study of Japanese adults with asymptomatic hyperuricemia (UMIN000041322). Among the full analysis set population treated with febuxostat (n = 239), subjects who had both data on SU level and mean common carotid artery (CCA)-IMT at baseline and 24 months were included in the present analysis. The primary endpoint of this analysis was an association between changes in SU levels and mean CCA-IMT after 24 months of febuxostat treatment.

Results:

A total of 204 eligible subjects were included in this analysis. The mean age was 69.1 +/- 9.6 years, and one fifth were female. Most had a history of treated hypertension and/or dyslipidemia. The mean baseline SU level was 7.7 ± 1.0 mg/dL, and febuxostat treatment significantly reduced SU concentrations at 24 months (estimated mean change -3.1 mg/dL, 95% confidence interval -3.2 to -2.9). A multivariable linear regression analysis revealed that a reduction in SU level was associated with changes in mean CCA-IMT values at 24 months (Figure A). In contrast, the achieved SU concentrations were not associated with changes in mean CCA-IMT at 24 months (Figure B).

Conclusion:

A greater reduction in SU, but not its achieved concentrations, may be associated with delayed progression of carotid IMT in patients with asymptomatic hyperuricemia treated with febuxostat.
PS-C04-10: THE ASSOCIATION OF ORAL HYPOFUNCTION AND ARTERIAL STIFFNESS
Authors: Matsumoto Chisa , Tomiyama Hirofumi , Matsuura Mari , Shiina Kazuki , Nakano Hiroki , Yamashina Akira
Published: January 2023

Objective:

Frailty is associated with higher risk of cardiovascular disease (CVD) and mortality. Recently, oral hypofunction, a disease in which the oral function is complexly reduced not only by ageing but also by a variety of factors, is regarded as a major risk factor for frailty, as it develops malnutrition and sarcopenia. However, no studies have evaluated the association of oral hypofunction and arterial stiffness, a marker for CVD. The objective of this study is to evaluate the association of oral hypofunction and arterial stiffness.

Design and method:

Japanese subjects above 50 years old who underwent annual health checkup were enrolled in this cross-sectional study. Subjects with history of CVD and dementia were excluded. Arterial stiffness was evaluated by brachial-ancle pulse wave velocity (baPWV). Oral hypofunction was evaluated based on the guidance by the Japanese Association for Dental Science. Seven oral functional factors, oral hygiene, oral moisture, occlusal force, tongue-lip motor function, tongue pressure, masticatory function, and swallowing function were assessed. Oral hypofunction was diagnosed if more than 3 factors showed deterioration. The association of oral hypofunction and baPWV was evaluated by multivariate linear regression analysis adjusted for conventional CVD risk factors. We also performed secondary analysis to evaluate the association of each oral functional factors and arterial stiffness.

Results:

Among 138 subjects (mean age: 59 ± 6 years), 29 subjects (21%) had oral hypofunction. After adjustment for CVD risk factors, oral hypofunction was not significantly associated with baPWV (β; = 24 ± 52, p = 0.65). In secondary analysis, higher oral bacterial count, a marker of oral hygiene, was significantly associated with increased baPWV even after adjustment for conventional CVD risk factors (1SD increase of oral bacterial count; β; = 51 ± 23, P = 0.03). But, this association was not observed with other oral functional factors and arterial stiffness.

Conclusions:

Oral hypofunction was not associated with increase of arterial stiffness. However, higher oral bacterial count was associated with increased arterial stiffness. Further research on oral hypofunction and CVD is warranted.
PS-C04-11: EFFECT OF ANKLE BRACHIAL INDEX EXAMINATION ON CENTRAL AORTIC BLOOD PRESSURE IN PATIENTS WITH PERIPHERAL ARTERY DISEASE
Authors: Sonoda Shinjo , Miura Toshiya , Anai Reo , Kashiyama Kuninobu , Natsuaki Masahiro , Node Koichi
Published: January 2023

Background:

Ankle brachial index (ABI) measurements are useful for detecting peripheral artery disease (PAD) as a screening test. In general, ABI examinations are contraindicated in patients with aortic aneurysm and history of aortic aneurysm. However, little is known whether ABI examinations elevate central aortic blood pressure (CBP).

Method:

From June 2018 to August 2020, we prospectively analyzed 66 patients who were performed cardiac catheterization through femoral approach and divided into peripheral artery disease complicated (PAD, N = 27) and uncomplicated (non-PAD, N = 39) groups. After insertion of pigtail catheter into both ascending (Asc), abdominal (Abd) positions, resting CBPs at Asc and Abd were measured. Subsequently, we measured each CBP during ABI, respectively. We compared resting CBP (R-CBP) and CBP during ABI (ABI-CBP) between PAD and non-PAD groups.

Results:

In non-PAD group, ABI-CBP at Abd was significantly higher than BL-CBP (P < 0.05). On the other hand, there were no significant ABI-CBP elevation at Asc and Abd in PAD. There was no case with CBP elevation more than 20mmHg during ABI measurements in both groups. Furthermore, no clinical events were observed after ABI measurements in both groups.

Conclusion:

ABI was considered a safe testing in patients with suspected PAD.
PS-C05-3: ESTIMATION OF PULMONARY PULSATILE ARTERIAL LOAD IN PATIENTS UNDERGOING INVESTIGATION FOR PULMONARY HYPERTENSION
Authors: Adji Audrey , Kearney Katherine , Hungerford Sara , Kotlyar Eugene , Lau Edmund , Jabbour Andrew , Hayward Christopher
Published: January 2023

Objective:

Diagnosis of pulmonary hypertension (PH) is typically confirmed by elevation of the pulmonary artery (PA) pressure and/or pulmonary vascular resistance (PVR). However, PVR may overlook the pulsatile component of RV hydraulic work which involves the dynamic interplay between PA resistance and compliance. PA vascular impedance (PVZ) offers a more comprehensive assessment of RV and PA load. This study aims to apply a method of PA pulsatile load as PVZ determination in a cohort of patients referred for PH evaluation.

Design and Methods:

Fifty-eight participants (71% females, mean 53 ± 18 years) were recruited, and underwent right heart catheterisation (RHC) to measure systolic (sPAP), diastolic (dPAP), mean (mPAP), and PA wedge pressures (PAWP), cardiac output (CO) and PVR; classified as precapillary PH (PrecPH), isolated postcapillary PH (IpcPH), combined PH (CpcPH) and control group. PA flows were recorded using 3T cardiac magnetic resonance (CMR); RV volume (V) were obtained by contouring endocardial and epicardial borders on the short axis at end diastolic (ED) and end systolic (ES) phases, and ejection fraction (RVEF) was calculated as (RVEDV - RVESV)/RVEDVx100. Volumetric flow was measured using phase-contrast velocity quantification using 3T cardiac magnetic resonance (CMR). PVZ was expressed as the relationship of pulsatile pressure to pulsatile flow in the frequency domain.

Results:

76% of patients had evidence of PH on RHC (8 PrecPH, 17 IpcPH, 9 CpcPH). CpcPH and PrecPH patients tended to show poorer RV contractility compared with control and IpcPH groups, albeit not statistically significant. PVZ was highest in patients with PrecPH and CpcPH, while lowest in those with IpcPH. A correlation analysis was performed to seek association between mPAP, PVR and PVZ and other variables thought to be related to PH. In PrecPH, increased mPAP was found to be associated with raised PVR (p < 0.001; R = 0.94) and PVZ (p < 0.001; R = 0.78). However, there was no association between elevated mPAP and PVZ in IpcPH and CpcPH, despite a significant correlation with PVR (IpcPH P = 0.03, R = 0.55; CpcPH P = 0.01, R = 0.77).

Conclusion:

We describe a straightforward method to measure and compare pulsatile vascular load of the systemic and pulmonary circulations simultaneously, allowing further quantification of systemic/pulmonary vascular interactions. Further research is required to evaluate small-vessel contributions to the arterial circulation, especially in the pulmonary system.
PS-C05-5: CLINICAL IMPACT OF CREDO-KYOTO RISK SCORE ON IN-HOSPITAL BLEEDING IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Natsuaki Masahiro , Minematsu Yuki , Yoshioka Goro , Shinzato Kodai , Node Koichi
Published: January 2023

Background:

CREDO-Kyoto bleeding risk score was developed to predict the post-discharge bleeding events in patients with percutaneous coronary intervention. However, there were limited reports of the effectiveness of this score to predict the in-hospital bleeding events in patients with acute coronary syndrome (ACS).

Methods:

We evaluated 562 consecutive ACS patients in Saga university hospital between 2014 and 2019. Primary outcome was major bleeding during hospitalization. Major bleeding was defined as the GUSTO moderate/severe bleeding. Patients were classified into three groups according to the CREDO-Kyoto bleeding risk score (low, intermediate and high).

Results:

Major bleeding events occurred in 12.1% of all patients during hospitalization. Patients in the high risk group (n = 22) had significantly higher incidence of major bleeding than those in the intermediate (n = 113) and the low risk groups (n = 427) (22.7%, 18.6%, versus 9.8%, respectively, p = 0.02). Multivariate analysis showed that intermediate and high risk groups were independent predictors for the in-hospital major bleeding.

Conclusions:

CREDO-Kyoto risk score successfully identified high risk ACS patients for the major bleeding during hospitalization.
PS-C05-12: OMENTIN-1 PREDICTS MEMBRANE FLUIDITY OF RED BLOOD CELLS AND MICROCIRCULATORY FUNCTION IN HYPERTENSIVE SUBJECTS BY THE NITRIC OXIDE-DEPENDENT MECHANISM
Authors: Tsuda Kazushi
Published: January 2023

Objective:

It has been shown that abnormalities in physical properties of the cell membranes may strongly be linked to hypertension. Recent evidence indicates that omentin-1, an adipokine with anti-inflammatory properties, may actively participate in the pathophysiology of hypertension, atherosclerosis and other cardiovascular diseases. However, few studies have evaluated the association between omentin-1 and membrane function in hypertension. The present study was performed to investigate possible relationships among omentin-1, endothelial function and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in patients with essential hypertension and normotensive subjects.

Design and method:

We measured the membrane fluidity of RBCs with an electron spin resonance (ESR) and spin labeling method. In each ESR spectrum, we calculated the order parameter (S) for the spin-label agent (5-nitroxide stearate). The greater the value of the order parameter (S) was, the lower the membrane fluidity of RBC was.

Results:

(1) The order parameter (S) obtained from the ESR spectra of RBC membranes was significantly greater in hypertensive subjects (0.727 ± 0.001, n = 64) than in normotensive subjects (0.719 ± 0.001, n = 49, P < 0.0001), indicating that membrane fluidity of RBCs might be reduced in hypertensive subjects compared with normotensive subjects. (2) Plasma omentin-1 levels were lower in hypertensive subjects than in normotensive subjects (HT 0.486 ± 0.014 ng/mL, n = 64, NT 0.537 ± 0.019 ng/mL, n = 49, P < 0.05). Plamsa omentin-1 significantly correlated with plasma nitric oxide (NO)-metabolite levels (an index of endothelial function) (r = 0.392, n = 113, P < 0.0001). (3) Furthermore, the order parameter (S) of RBCs inversely correlated with both plasma omentin-1 (r = -0.347, n = 113, P < 0.001) and plasma NO-metabolites, suggesting that reduced membrane fluidity of RBCs might be associated with decreased levels of plasma omentin-1 and endothelial dysfunction. (4) Multivariate regression analysis showed that, after adjusting for confounding factors, plasma omentin-1 might be an independent predictor of membrane fluidity of RBCs.

Conclusions:

The ESR study demonstrated that lower plasma omentin-1 levels might have a close correlation with reduced membrane fluidity of RBCs and impaired hemorheologic behavior in hypertensive subjects by the NO-dependent mechanism. It is strongly suggested that plasma omentin-1 could be a putative biomarker for the microcirculatory function in hypertension.
PS-C06-2: EXTRACELLULAR VESICLES AS DIAGNOSTIC BIOMARKER OF ARTERIAL HYPERTENSION A COMPARATIVE OBSERVATIONAL STUDY
Authors: Raghav Alok , Giri Richa , Agarwal Saurabh , Singh Manish
Published: January 2023

Objective:

Arterial hypertension is a major cardiovascular risk factor that contributes to cardiovascular diseases and associated target organ injuries. World Health Organization estimated that hypertension affected around 1.28 billion adults aged between 30 to 79 years worldwide making it a prime cause of premature death.

Design:

Observational study

Methods:

The present study compared the blood derived extracellular vesicles from the American Heart Association guidelines classified study subjects as normal elevated stage 1 stage 2 and hypertensive crisis. EVs were isolated and characterized for surface tetraspanin expression marker CD 41 using flow cytometer and nano tracking analysis Total protein from each sample was extracted and mass spectrometry was performed.

Results:

Study subjects with mean age of 57 years with arterial hypertension more prevalent in women 62 percent compared to men 38 percent. Positive expressions of tetraspanin CD41 were found in EVs isolated from all patients of each group. Nanotracking analysis of isolated EVs showed an average size of 167 nm with no comparable differences among study groups. Significant differences were found in the mass spectrometric analysis within the study groups in 28 proteins compared using ANOVA with the Kruskall Wallis test followed by Dunns test.

Conclusion:

The results of the study concluded that proteomic analysis of isolated proteins within the study groups can be explored as diagnostic biomarkers for screening of arterial hypertension and these specific proteins can be further explored for fabricating point of care devices for a community screening of arterial hypertension
PS-C06-9: THE PREDICTIVE VALUE OF RED CELL DISTRIBUTION WIDTH IN VENOUS THROMBOEMBOLISM AND RELATED MORTALITY
Authors: Addai Muhamad Fajri , Maulana Rido , Widyantoro Bambang
Published: January 2023

Background:

Red cell distribution width (RDW) is a measure of red blood cell size variation and heterogeneity. Recent meta-analyses demonstrated this measurement could be strong predictor in coronary artery disease, chronic heart failure, and atrial fibrillation. Nevertheless, there is no meta-analysis evaluating the role of RDW in prediction of the occurrence of venous thromboembolism (VTE), the third most common cardiovascular disease, and related mortality.

Objective:

To investigate the association of RDW and VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE) and related mortality.

Methods:

Major medical databases were systematically searched for observational studies which assessed the association of RDW and VTE published until May 2022. The databases were searched with predefined protocol without language restriction based on PRISMA guidelines. The analysis was performed in RevMan 5.3 to provide pooled measures for Risk Ratio (RR) and weighted mean difference (WMD).

Results:

Twenty-three studies were enrolled including 6,737 cases and 58,831 controls. Higher RDW was indicated as independent predictors for VTE compared to lower RDW (RR = 1.82, p < 0.00001), comprising DVT and PE (RR = 1.6, p < 0.00001, and RR = 2.05, p = 0.002, respectively). There was also an association between higher RDW and risk of mortality after PE episode with RR = 1.4 (p = 0.0004), involving short- (30-day) and long-term (> 1 year) mortality (RR = 1.79, p = 0.04, and RR = 1.15,p = 0.03, respectively). Compared to lower RDW, higher RDW also revealed a significant association with unprovoked VTE (RR = 2.18, p = 0.02). VTE-group had a higher mean of RDW compared to control with WMD = 1.13% (p < 0.00001), consisting of PE-group (WMD = 0.99%, p < 0.00001) and DVT-group (WMD = 1.07%, p < 0.00001). Among PE patients, The PE-related mortality group also had a higher mean of RDW in comparison to the survivor group with WMD = 1.97%, (p < 0.00001).

Conclusions:

Higher RDW value was associated with the occurrence of VTE, including DVT, PE, unprovoked VTE, and PE-related mortality. Therefore, the use of the potential role of RDW should be emphasized since it is low-cost and simple to obtain, even in a low-resource setting.
PS-C06-11: IRISIN ASSOCIATION WITH NON DIPPER HYPERTENSION DEVELOPMENT IN OBESE PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Shelest Borys , Kovalova Yuliia , Martovytskyi Dmytro , Brek Valeria
Published: January 2023

Objective:

Recent investigations showed that irisin, as a possible inflammatory marker, can be closely related to heart function, vessels tone regulation and possible development of arterial hypertension HTN.

The purpose of the work was to study the relationship between irisin and the development of non dipper hypertension in obese patients with coronary artery disease CAD.

Design and method:

97 obese hypertensive patients with CAD were enrolled into the study. CAD was presented as chronic coronary syndrome CCS according to 2019 ESC Guidelines, essential HTN as systolic blood pressure SBP ≧ 140 mmHg and or diastolic blood pressure DBP ≧ 90mmgHg. Obesity was assessed as body mass index BMI ≧ 30 kg per m2 according to WHO criteria. The mean age of participants was 53.61 ± 4.88 years. Patients were divided into 2 groups. The first one was with dipper HTN, n 46, and the second one with non dipper HTN, n 51. Dippers were established by Holter monitoring. Serum irisin levels were measured by ELISA.

Results:

It was found that irisin levels were significantly lower in non dipper hypertensive subjects compared with dippers 125.72 ± 15.09 vs 141.53 ± 21.84 ng per mL, p < 0.001. Irisin has a negative correlation with SPR r = 0.29, p < 0.01, and after adjusted for age, sex and BMI it remained a significant link between irisin and SBP, r = 0.21, p = 0.044. In multivariate logistic regression analysis of the irisin odds ratio OR 0.859, 95 per cent Confidence Interval 0.471 to 0.993, p < 0.001 was found to be independent predictors for non dipper hypertension in obese patients with CCS.

Conclusions:

This study shows that decreased irisin levels are significantly associated with the development of non dipper hypertension in obese patients with coronary artery disease.
PS-C06-12: HETEROGENEITY AND OVERLAP OF THE LONGITUDINAL ASSOCIATIONS AMONG INCREASED ARTERIAL STIFFNESS, HYPERTENSION AND DIABETES MELLITUS: A 16-YEAR PROSPECTIVE OBSERVATIONAL STUDY
Authors: Nakano Hiroki , Shiina Kazuki , Takahashi Takamichi , Fujii Masatsune , Iwasaki Yoichi , Matsumoto Chisa , Chikamori Taishiro , Yamashina Akira , Tomiyama Hirofumi
Published: January 2023

Background:

Hypertension and diabetes mellitus frequently coexist; however, differences in the bi-directional longitudinal relationships of arterial stiffness with hypertension and diabetes mellitus have not yet been clarified.

Methods:

In this 16-year prospective observational study, 3981 middle-aged Japanese subjects without hypertension/diabetes mellitus at the study baseline underwent annual measurements of the blood pressure, serum glycosylated hemoglobin A1c (HbA1c), and brachial-ankle pulse wave velocity (baPWV).

Results:

By the end of the study period, 664, 779, 154 and 406 subjects developed hypertension, prehypertension, diabetes mellitus and prediabetes, respectively. Increased baPWV at the baseline was associated with a significant odds ratio for new onset of prehypertension/hypertension without (beta = 5.0 x 10–3, P < 0.01) or with (beta = 4.0 x 10–3, P < 0.01) coexisting prediabetes/diabetes mellitus; no such association was found with new onset of prediabetes/diabetes mellitus alone. Furthermore, baPWV showed significant longitudinal associations with the development of all of the above conditions. Conversely, elevated mean blood pressure, even in the pre-hypertensive range, showed a significant longitudinal association with increase of the baPWV.

Conclusions:

In middle-aged Japanese subjects, a vicious cycle may be triggered between elevated blood pressure, even from the prehypertensive stage, and arterial stiffening and development of diabetes mellitus may be observed as a cross phenomenon of this vicious cycle with a collateral event. Arterial stiffness may be a key element in the development of hypertension, so that its contribution to cardiovascular risk may be greater in patients with hypertension than in those with diabetes mellitus.
PS-C07-5: ASSOCIATION OF OVERNIGHT URINARY INDICATORS AND BMI WITH NIGHT TIME AND DAYTIME BLOOD PRESSURE IN ELDERLY
Authors: Yamasue Kotaro , Tochikubo Osamu , Ishikawa Yoshihiro
Published: January 2023

Reportedly, the mean nighttime blood pressure (BP) is the sensitive predictor of cardiovascular diseases and the associated mortality. In this study, we investigated the effect of overnight urinary indicators (levels of sodium, potassium, and sodium to potassium ratio) on daytime and nighttime BP. A total of 108 volunteers (56 males, 52 females) aged between 51 and 76 years (mean age: 65.7 ± 4.9 years) who were not taking any antihypertensive medication participated in the study. Their 24-hour (24-h) BP was measured every 30 minutes with an ambulatory BP monitoring, four times (spring, summer, autumn, and winter) in a year. Overnight urine samples (after the last urination before sleeping and until the first urination on waking up the next day) were easily collected at home using a proportional urine-sampling device, Urine mate P. The ion electrode method was used to measure the sodium and potassium levels excreted in urine. The average values of daytime and nighttime BP were calculated.

Multiple regression and simple linear regression analyses were used to evaluate the association of daytime and nighttime BP with the above-mentioned overnight urinary indicators, age, sex, and BMI.

There were a total of 353 participants over the four seasons. The average values of daytime SBP and DBP were 130.4 ± 20.2 and 83.4 ± 12.7 mmHg, respectively; nighttime SBP and DBP were 113.7 ± 15.8 and 69.8 ± 9.4 mmHg, respectively. Multiple regression analysis of the six factors revealed that none of the variables were linearly combined. For nighttime SBP, the adjusted standard regression coefficients was 0.219 (p < 0.01) for the urinary Na/K ratio, 0.142 (p < 0.05) for age, and 0.119 (p < 0.05) for BMI. However, for daytime SBP it was 0.124 (p < .0.05) for age, -0.232(p < 0.01) for sex, and 0.175 (p < 0.01) for BMI.

Simple linear regular regression analysis showed that nighttime SBP was significantly related to the Na/K ratio, Na, age, and BMI; daytime SBP to sex, BMI, and age.

This demonstrates that overnight urinary Na/K ratio has greater effect on nighttime SBP than BMI and age; therefore, its optimal level should be achieved to control nighttime SBP in the elderly.