bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug–drug interactions in nursing home residents: analysis from the COME-ON trial
Authors: Lion Simon , Evrard Perrine , Foulon Veerle , Spinewine Anne
Published: January 2023

Background

as a result of the high prevalence of polypharmacy in nursing homes (NHs), nursing home residents (NHRs) are exposed to numerous drug–drug interactions (DDIs) that can lead to adverse drug effects, and increased morbidity and mortality.

Objectives

to evaluate (i) the prevalence of DDIs among NHRs and its evolution over time, and (ii) factors associated with a favourable evolution.

Design

posthoc analysis of the COME-ON study, a cluster-randomised controlled trial aiming at reducing potentially inappropriate prescriptions in NHs, through the implementation of a complex intervention.

Setting and subjects

901 NHRs from 54 Belgian NHs.

Methods

DDIs were identified using a validated list of 66 potentially clinically relevant DDIs in older adults. We defined a favourable evolution at 15 months as the resolution of at least one DDI present at baseline, without the introduction of any new DDI. Factors associated with a favourable evolution were analysed using multivariable logistic regression.

Results

at baseline, 475 NHRs (52.7%) were exposed to at least 1 DDI and 225 NHRs (25.0%) to more than one DDI. Most common DDI was ‘Concomitant use of at least three central nervous system active drugs’. At 15 months, we observed a 6.3% absolute decrease in DDI prevalence in intervention group, and a 1.0% absolute increase in control group. The intervention, older age and private NH ownership were significantly associated with a favourable DDI evolution.

Conclusion

a high prevalence of DDI in Belgian NHs was observed, but the COME-ON intervention was associated with a favourable evolution over time.
Challenges of defining renal response in ANCA-associated vasculitis: call to action?
Authors: Odler Balazs , Bruchfeld Annette , Scott Jennifer , Geetha Duvuru , Little Mark A , Jayne David R W , Kronbichler Andreas
Published: January 2023

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome.
A case report of a myocardial ischaemic attack: a novel hyperenhancement pattern on cardiac magnetic resonance in focal ischaemic injury
Authors: Nies Hedwig M J M , Vromen Tom , Mihl Casper , Bekkers Sebastiaan C A M , Rasoul Saman , Holtackers Robert J , Smulders Martijn W
Published: January 2023

Background

Delayed enhancement cardiac magnetic resonance (DE-CMR) is the reference standard for the non-invasive assessment of myocardial fibrosis. DE-CMR is able to distinguish ischaemic from non-ischaemic aetiologies based on differences in hyperenhancement distribution patterns. Hyperenhancement caused by ischaemic injury typically involves the endocardium, while hyperenhancement confined to the mid- and epicardial layers of the myocardium suggests a non-ischaemic aetiology.

Case summary

This is a case of a 20-year-old male with an unremarkable medical history with an acute ST-elevation myocardial infarction. DE-CMR revealed two distinct patterns of hyperenhancement: (i) a ‘normal’ wavefront-ischaemic pattern, and (ii) multiple atypical mid-wall and epicardial areas of focal hyperenhancement. Invasive coronary angiography (ICA) and coronary computed tomographic angiography (CCTA) showed multiple intracoronary thrombi and distal emboli in the left anterior descending, ramus circumflexus, and in smaller branches of the LCA. All hyperenhancement patterns observed on DE-CMR perfectly matched the distribution territories of the affected coronary arteries.

Discussion

This case with an acute myocardial infarction showed intracoronary thrombi and emboli on ICA and CCTA. Interestingly, DE-CMR showed two different patterns of hyperenhancement in the same territories of the coronary thrombi. This observation may challenge the concept that these non-endocardial areas of hyperenhancement on DE-CMR are always of non-ischaemic aetiology. It is hypothesized that occlusion of smaller distal branches of the coronary arteries may result in mid-wall or epicardial fibrosis as opposed to subendocardial fibrosis commonly found in patients with a large epicardial coronary occlusion. Clinicians should be aware of these atypical patterns to be able to initiate adequate medical therapy.
Early adulthood exercise capacity, but not muscle strength, associates with subclinical atherosclerosis 40 years later in Swedish men
Authors: Fortuin-de Smidt Melony , Bergman Frida , Grönlund Christer , Hult Andreas , Norberg Margareta , Wennberg Maria , Wennberg Patrik
Published: January 2023

Aims

Poor exercise capacity and muscle strength in early adulthood are risk factors for cardiovascular disease (CVD). However, it is unclear how these factors relate to subclinical atherosclerosis due to a lack of longitudinal studies. This study investigated whether early adulthood exercise capacity and muscle strength associated with later adulthood subclinical atherosclerosis.

Methods and results

This study included Swedish men (n = 797) who were eligible for military conscription (at ∼18-years of age) and who participated in the baseline assessment of the visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention trial between 2013 and 2016 (at 60 years of age). At conscription, isometric muscle strength (dynamometer) and maximum exercise capacity (maximal load cycle ergometer test) were measured. During later adulthood (at 60 years old), the presence of carotid plaques and intima media thickness were measured by using high-resolution ultrasound. At follow-up, plaques were present in 62% (n = 493) of men. Exercise capacity in early adulthood associated with 19% lower odds of plaques [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.68–0.96], independent of muscle strength. This association was not mediated by any single CVD risk factor. However, the total indirect effect of later, but not early, adulthood CVD risk factors was significant, while the direct effect was non-significant (OR 0.85, 95% CI 0.71–1.02). Associations between muscle strength and subclinical atherosclerosis were non-significant.

Conclusion

Higher exercise capacity during early adulthood, but not muscle strength, may protect against carotid plaque development during adulthood mediated by the combination rather than a single later adulthood CVD risk factors.
Characterization of the chemical fungicides-responsive and bacterial pathogen-preventing Bacillus licheniformis in rice spikelet
Authors: Zhan Chengfang , Wu Mengchen , Fang Hongda , Liu Xiaoyu , Pan Jiuyue , Fan Xiaoyan , Wang Mengcen , Matsumoto Haruna
Published: January 2023

Seed-borne bacterial pathogens cause severe yield loss and biotoxin contamination in rice, leading to increasing concern on the global food supply and environmental safety. Plant native microbes play an important role in defending against diseases, but their actions are often influenced by the chemical fungicides applied in the field. Here, Bacillus licheniformis mmj was isolated from rice spikelet, which uniquely showed not only fungicide-responsiveness but also broad-spectrum antimicrobial activity against major rice bacterial pathogens including Xanthomonas oryzae pv. oryzae, Burkholderia plantarii and Burkholderia glumae. To understand the hallmark underlying the environmental adaptation and antimicrobial activity of B. licheniformis mmj, the genome sequence was determined by SMRT and subjected to bioinformatics analysis. Genome sequence analysis enabled the identification of a set of antimicrobial-resistance and antibacterial activity genes together with an array of harsh environment-adaptive genes. Moreover, B. licheniformis mmj metabolites were analyzed with gas chromatography coupled to triple quadrupole mass spectrometry, and the volatile components that were linked with the antimicrobial activity were preliminarily profiled. Collectively, the present findings reveal the genomic and metabolic landscapes underlying fungicide-responsive B. licheniformis, which offers a new opportunity to design harsh environment-adaptive biopesticides to cope with prevalent bacterial phytopathogens.
Mediated Audience Costs: Jordan–Israeli Diplomacy before the 1967 Arab–Israeli War
Authors: Cebul Matthew D
Published: January 2023

Audience cost theory remains prominent in scholarship on international crises. However, the theory suffers from several weaknesses, including a lack of historical evidence and concerns about the visibility of audience costs to foreign adversaries. This article engages with both concerns. I theorize that third-party diplomacy can help leaders signal their audience costs by corroborating their vulnerability to domestic punishment. I illustrate this mediated audience cost mechanism with an archival case study of Jordan–Israeli relations surrounding the 1966 Samu incident. I find that US crisis diplomacy helped Jordanian King Hussein to signal his vulnerability to a military coup d’état, and thus his resolve to retaliate against Israeli aggression, which in turn led Israel to refrain from further counterterror raids into the West Bank. The analysis integrates audience cost theory with crisis diplomacy in practice, and suggests several implications for future audience cost scholarship.
Effect of 0.05% chlorhexidine gluconate in water on the hydrophilic inflatable penile prosthesis: biocompatibility, adherence, and dip time
Authors: Griggs Ryan , Karpman Edward , Jones LeRoy , Twomey Carolyn , Henry Gerard
Published: January 2023

Background

Rates of infection after inflatable penile prosthesis range from 1% to 3%; however, a new surgical irrigation solution is Food and Drug Administration cleared as antimicrobial wound lavage and appears to be safe for patients and noncaustic during hydrophilic inflatable penile prosthesis (hIPP) dipping and irrigation.

Aim

To evaluate if 0.05% chlorhexidine (CHG) lavage is caustic to the hIPP coating and if dip adherence is dependent on time.

Methods

Preconnected hIPP devices were tested at a Coloplast research and development laboratory. The devices were soaked in the 0.05% CHG lavage solution or normal saline for 1, 15, 30, and 60 minutes. Subsequently, all parts were dried for 15 minutes in a 35 °C oven. A Congo red dye test was performed following a Coloplast-validated and Food and Drug Administration–cleared test method to ensure product reliability. Implants were then visually inspected for deleterious effects as well as dip coverage. In addition, we evaluated 0.05% CHG lavage solution vs previously published hIPP dipping solutions.

Outcomes

0.05% CHG lavage does not appear to damage the hIPP coating, and adherence of this solution is not dependent on dip time.

Results

All components of the preconnected hydrophilic IPPs were tested for coating adherence and defects. All tested IPPs achieved a “satisfactory” coating, meaning a uniform coat without flaking or clumping. Furthermore, there were no noticeable caustic effects or differences in coating adherence between the normal saline–soaked control and 0.05% CHG–coated arms with increasing dip time. A review of the literature for 0.05% CHG lavage solutions vs previously published hIPP dipping solutions revealed that it may have some advantages over previously reported antibiotic solutions.

Clinical Implications

This study serves as a foundation to introduce 0.05% CHG lavage to the urologic literature as a potentially new “magic bullet” irrigation.

Strengths and Limitations

Major strengths of the study are that it is the first study of its kind to address the question of what dip duration should be used and whether it is scientifically reproducible. A limitation is the in vitro model, thus needing validation in a clinical setting.

Conclusion

0.05% CHG does not appear to negatively affect the hIPP coating or differ in adherence with increasing dip time; however, long-term device performance has not been verified.
Helicobacter pylori Treatment Regimen Selection and Eradication Rates Across Department of Defense Patients for Fiscal Years 2016-2018
Authors: Junga Zachary C , Mertz Andrew , Pak Kevin , Singla Manish
Published: January 2023

Introduction

The objective of this study was to measure the number of treatment successes and failures of various Helicobacter pylori treatment regimens among DoD beneficiaries.

Materials and Methods

This was a retrospective cross-sectional study of all adult DoD beneficiaries with H. pylori diagnosis, treatment, and eradication testing from October 2015 to September 2018. All stool antigen testing, urea breath test, and immunoglobulin G serologies were identified. Patients were excluded if they did not have a positive test, did not have treatment, or did not have eradication testing.

Results

In total, 20,548 H. pylori diagnostic tests were performed over the study period. A total of 1,592 non–active duty and 374 active duty patients were diagnosed with H. pylori, were treated, and had eradication testing. The best performing regimens were tetracycline-based bismuth quadruple therapy and tinidazole-based clarithromycin triple therapy with eradication rates of 85% and 82%, respectively. Clarithromycin triple therapy was the most prescribed (63.9% of all regimens included in analysis). Of the 1,592 non–active duty and 374 active duty patients, 75.5% (1,202) and 70.6% (264) cleared the infection with treatment, respectively (P = 0.0449). Although trends were identified in differences in geographic eradication rates, none of these achieved the threshold of significance.

Conclusions

This is the largest and most geographically widespread H. pylori treatment efficacy study in the USA over 20 years. None of the treatment regimens (when used in over five patients) achieved an eradication rate greater than 90%, but tetracycline-based bismuth quadruple therapy performed best among all regimens and populations. Eradication rates were lower in the active duty populations, with no treatment regimen achieving an eradication rate greater than 80%.
Bioprocess inspired formation of calcite mesocrystals by cation-mediated particle attachment mechanism
Authors: Wang Qihang , Yuan Bicheng , Huang Wenyang , Ping Hang , Xie Jingjing , Wang Kun , Wang Weimin , Zou Zhaoyong , Fu Zhengyi
Published: January 2023

Calcite mesocrystals were proposed, and have been widely reported, to form in the presence of polymer additives via oriented assembly of nanoparticles. However, the formation mechanism and the role of polymer additives remain elusive. Here, inspired by the biomineralization process of sea urchin spine comprising magnesium calcite mesocrystals, we show that calcite mesocrystals could also be obtained via attachment of amorphous calcium carbonate (ACC) nanoparticles in the presence of inorganic zinc ions. Moreover, we demonstrate that zinc ions can induce the formation of temporarily stabilized amorphous nanoparticles of less than 20 nm at a significantly lower calcium carbonate concentration as compared to pure solution, which is energetically beneficial for the attachment and occlusion during calcite growth. The cation-mediated particle attachment crystallization significantly improves our understanding of mesocrystal formation mechanisms in biomineralization and offers new opportunities to bioprocess inspired inorganic ions regulated materials fabrication.
The centers of discrete groups as stabilizers of dark matter
Authors: Jurčiukonis Darius , Lavoura Luís
Published: January 2023

The most usual option to stabilize dark matter (DM) is a $\mathbb {Z}_2$ symmetry. In general, though, DM may be stabilized by any $\mathbb {Z}_N$ with N ≥ 2. We consider the way that $\mathbb {Z}_N$ is a subgroup of the internal-symmetry group G of a model; we entertain the possibility that $\mathbb {Z}_N$ is the center of G, yet G is not of the form $\mathbb {Z}_N \times G^\prime$, where G′ is a group smaller (i.e., of lower order) than G. We examine all the discrete groups of order smaller than 2001 and we find that many of them cannot be written as the direct product of a cyclic group and some other group, yet they have a non-trivial center that might be used in model building to stabilize DM.
S-09-2: POLYPILLS FOR HYPERTENSION CONTROL IN ASIANS
Authors: Sukonthasarn Apichard
Published: January 2023

The number of cardiovascular disease (CVD) cases and deaths have continued to rise in Asian population. These unfavorable trends are expected to continue, particularly in low-income and middle-income countries.Raised blood pressure and LDL-cholesterol are among the leading modifiable risk factors for this problem.

From the year 1990–2019, the prevalence of hypertension in many low-income and middle-income countries in Asia remained unchanged or increased. Most of the increase was in those without a previous diagnosis. However, the hypertension treatment and control were not improved in many countries since 1990.

A meta-analysis concluded that combination anti-hypertensive therapies results in a greater reduction in blood pressure compared with increasing the dose of a single drug, regardless of the class of drugs used in combination. In term of safety, two-drug combinations have been shown to be safe and well tolerated with only a small increase in the risk of hypotension.

The 2019 Thai hypertension Guidelines recommend using statin in high risk hypertensive patients. Adding a statin together with a combination of antihypertensive drug can further reduce the risk of future CVD.

Such Polypill may offer many advantages and potential to solve many challenges and barriers in management of hypertension and CVD control in many, if not all, Asian Countries.
S-10-4: THE ASSOCIATION BETWEEN BLOOD PRESSURE PER THE 2019 JSH AND 2017 ACC/AHA GUIDELINES AND HEART FAILURE RISK: THE SUITA STUDY
Authors: Arafa Ahmed , Kokubo Yoshihiro , Teramoto Masayuki , Kashima Rena , Shimamoto Keiko , Nakao Yoko , Matsuo Miki , Yoshihara Fumiki , Izumi Chisato
Published: January 2023

Objective:

Hypertension is a significant risk factor for heart failure (HF). Since hypertension definition varies across guidelines, identifying blood pressure (BP) categories that should be targeted to prevent HF is required. We, therefore, investigated the association between hypertension per the 2019 Japanese Society of Hypertension (JSH) and 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines and HF risk.

Design and method:

A total of 2,809 urban Japanese people registered in the Suita Study were followed up for incident HF, which was defined as participants with B-type natriuretic peptide levels of equal or higher than100 pg/mL or starting HF medications. Cox regression was used to assess HF risk for different BP categories in both guidelines compared to a reference category defined as systolic BP (SBP) less than120 mmHg and diastolic BP (DBP) less than 80 mmHg.

Results:

Within 8 years of median follow-up, 339 HF cases were detected. Per the 2019 JSH guidelines, elevated BP (SBP 130 to139 and/or DBP 80 to 89 mmHg), hypertension I (SBP 140 to159 and/or DBP 90 to 99 mmHg), hypertension II (160 to179 and/or DBP 100 to109 mmHg), hypertension III (SBP equal to or higher than180 and/or DBP equal to or higher than110 mmHg), and isolated systolic hypertension (SBP equal to or higher than 140 mmHg and DBP < 90 mmHg) were associated with increased HF risk with HRs (95% CIs): 1.82 (1.34 to 2.49), 1.57 (1.13 to 2.16), 2.10 (1.34 to 3.29), 2.57 (1.15 to 5.77), and 1.51 (1.04 to 2.19), respectively. Per the 2017 ACC/AHA guidelines, hypertension I (SBP 130 to 39 or DBP 80 to 89 mmHg), hypertension II (SBP equal to or higher than140 and/or DBP equal to or higher than 90 mmHg), and isolated systolic hypertension (SBP equal to or higher than 130 and DBP less than 80 mmHg) were associated with increased HF risk with HRs (95% CIs): 1.81 (1.33 to 2.47), 1.68 (1.24 to 2.27), and 1.64 (1.13 to 2.39), respectively. The associations were modestly attenuated among participants with no history of cardiovascular diseases (coronary heart disease or stroke). Hypertension medication dissolved the association between increased BP and HF risk.

Conclusions:

Increased BP, even without fulfilling the hypertension definition per the 2019 JSH guidelines, can elevate the risk of HF.
S-11-2: AORTIC PULSE WAVE VELOCITY AND CARDIOVASCULAR RISK
Authors: Weber Thomas
Published: January 2023

Aortic pulse wave velocity (PWV), which can be non-invasively approached by measuring carotid-femoral (cf) PWV, but also to a certain degree by measuring brachial-ankle (ba) PWV, is currently thought to be the gold standard assessment of aortic / large artery stiffness, an important physical property of the arterial system. The assessment of cfPWV/baPWV can be recommended at several stages in the cardiovascular continuum:

+ Primordial and primary prevention: cfPWV/baPWV increase the risk of incident hypertension and diabetes mellitus (thus, cardiovascular (CV) risk) in apparently healthy adolescents and young and middle aged adults.

+ Patients with arterial hypertension: Increased PWV is associated with masked hypertension and is the most prevalent measure of hypertension-mediated organ damage (which is, in turn, an important marker of increased CV risk in patients with hypertension)

+ Patients with diabetes mellitus: PWV is associated with CV and renal complications in patients with type 1 and type 2 diabetes (and, thus, with very high CV risk in these patients).

+ Young and middle-aged patients up to their 60ies with intermediate CV risk: Increased cfPWV/baPWV can reclassify CV risk in many of these patients, which was confirmed in a metaanalysis including individual participant data of 17.635 patients of 16 observational studies. Associations stratified by sex, diabetes and hypertension were similar, but decreased with age. Adding cfPWV to the traditional CV risk estimation method resulted in net reclassification indices of 25%, 10%, 13% and 11% for 10-year CV mortality, CHD events, CVD events, and stroke events, respectively. In a large meta-analysis including individual participant data of 14.673 Japanese participants (mean age 59–66 years) from 8 cohort studies without a history of CV disease, similar findings were reported for baPWV. Addition of baPWV to a model incorporating the Framingham risk score (FRS) significantly improved the category-free net reclassification (0.247).

Finally, improvement in PWV over a few years is associated with improved prognosis.

Although no randomised study so far has proven a reduction of CV events, based on a PWV driven strategy (as compared to a strategy based on traditional CV risk factors), prevention of the normal age-related increase in PWV has been shown recently in the SPARTE study. Furthermore, it is reasonable to treat high and very-high risk patients, detected by measurement of PWV, according to the respective risk category in current prevention guidelines.
S-11-5: CLINICAL IMPLICATION OF FMD
Authors: Higashi Yukihito
Published: January 2023

A healthy endothelium maintains vascular tone and structure by regulating the balance between vasodilation and vasoconstriction, growth inhibition and growth promotion, antithrombosis and prothrombosis, anti-inflammation and proinflammation, and also antioxidation and pro-oxidation. The vascular endothelium is involved in the release of various vasodilators, including nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor as well as vasoconstrictors. NO plays an important role in the regulation of vascular tone, the inhibition of platelet aggregation, and the suppression of smooth muscle cell proliferation. Cardiovascular diseases are associated with endothelial dysfunction. In addition, endothelial dysfunction is an early feature of atherosclerosis and vascular diseases in humans. Therefore, it is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. Measurement of flow-mediated vasodilation (FMD) using an ultrasound is noninvasive and is an accurate indicator of NO production. Measurement of FMD is widely performed as an index of conduit artery endothelial function. Several investigators have shown that FMD is an independent predictor for cardiovascular outcomes. It is thought that FMD is useful for surrogate endpoint of cardiovascular outcomes and index of atherosclerotic treatment. However, the evaluation technique by the FMD measurement system still requires skills in measurement of the vessel diameter by an ultrasound system, and is difficult to handle. In addition, there is a problem in that the technique requires a large-scale apparatus and lacks in simplicity. In this session, we would like to explain in detail concerning the methods of assessing and clinical importance of endothelial function, especially FMD.
S-15-5: GAPS AND ADVANCES FOR THE PREVENTION OF HYPERTENSION IN AFRICA: INSIGHTS FROM THE EXAMIN YOUTH SA STUDY
Authors: Kruger Ruan
Published: January 2023

Paediatric hypertension is becoming a global health problem which is paralleled by overweight and obesity in children and adolescents, and tracks into adulthood. Therefore, promoting primary prevention of hypertension at early ages will reduce the increasing trends of hypertension in Africa. The prevalence of hypertension in South African children ranges between 7.5% and 22.3%, while care and treatment of hypertension remains a major challenge and health crisis. From the Exercise, Arterial Modulation and Nutrition in Youth South Africa (ExAMIN Youth SA) study using the latest 2017 American Academy of Pediatrics Clinical Practice Guidelines, we reported unique sex and ethnic differences of blood pressure (BP) in 5–9 year old children (n = 1062) and identified 14.1% children with elevated BP and almost 23% within the range of stage 1 or 2 hypertension. We also reported that 15.2% of the children were overweight and 4.4% obese according to the age and sex standardized body mass index (BMI) z-scores. Overweight and obesity were more prevalent in white children, while diastolic BP and total vascular resistance were higher in black children. The odds of having elevated BP were 60% higher with every standard deviation increase of BMI z-score. We analysed cortisol reactivity in relation to physical fitness to underpin the role of environmental stressors and physiological responses after inducing physical stress. We showed that white children had lower cardiorespiratory fitness (CRF) compared to children of African ancestry. However, African children had lower cortisol reactivity and unfavourable lower morning cortisol levels compared to white children. We demonstrated that lower CRF and higher BP are associated with lower cortisol responses in young children. In the same children and in comparison with a Swiss cohort, we investigated the role of high BP, obesity and ethnicity on retinal microvascular phenotype. We reported that obesity, hypertension and African ancestry are the main factors contributing to arteriolar narrowing. Since the microvasculature is also well represented by the kidneys, and the kidneys regulate BP, we also analysed a marker of proximal tubular function, alpha-1 microglobulin (A1 M), to identify early pathways of hypertension development in children. A1 M levels increased with higher BP, especially in children of African ancestry. With childhood lifestyle and behavioural risk factors being the most important for the prediction of cardiovascular events in adulthood, we argue that targeting health behaviour and optimising health education in early life are the most promising prospects to prevent early cardiovascular disease development in Africa.
S-18-1: THE USUAL HEMODYNAMIC MECHANISM CAUSING SALT-INDUCED HYPERTENSION: ABNORMALLY INCREASED CARDIAC OUTPUT OR VASCULAR RESISTANCE?
Authors: Kurtz Theodore
Published: January 2023

Two competing theories have been proposed for the hemodynamic mechanism that usually mediates salt sensitivity and the initiation of salt-induced hypertension. The historical natriuretic dysfunction theory holds that impaired renal excretion of sodium initiates hypertension by causing abnormally large increases in cardiac output secondary to abnormally large increases in salt and water retention. In contrast, the contemporary vasodysfunction theory holds that abnormal vascular resistance responses to salt, not abnormal increases in cardiac output, mediate salt sensitivity and the initiation of salt-induced hypertension. Primary aldosteronism is one of the most common causes of salt sensitivity and salt-dependent hypertension. This presentation will discuss new studies showing that hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in systemic vascular resistance, not cardiac output. The findings are consistent with the results of other studies showing that an abnormal vascular resistance response to salt (vasodysfunction) is also usually responsible for the initiation of salt-induced hypertension in humans and animals without hyperaldosteronism. The vasodysfunction framework for the pathogenesis of salt sensitivity and salt-induced hypertension has implications for: 1) understanding how various genetic and non-genetic factors influence BP responses to high salt diets, and 2) development of new methods for preventing and treating salt-dependent hypertension.
S-18-2: HYPERTENSION AS A DRIVER OF CEREBRAL SMALL VESSEL DISEASE AND DEMENTIA
Authors: Pritchard Harry Anthony , Taylor Jade , Evans Lowri , Greenstein Adam
Published: January 2023

Hypertension is the principal cause of vascular dementia. Unfortunately however, lowering blood pressure after the onset of cognitive decline does not slow disease progression and currently, vascular dementia is a disease with no available treatment. A principal feature of hypertension-related vascular dementia is a reduction in cerebral blood flow. Precisely how elevated blood pressure reduces cerebral blood flow is unknown and to investigate this further we used a polygenic model of hypertension, the BPH/2 mouse. Aged 8 months, BPH/2 mice exhibited cognitive impairment mimicking the human presentation of vascular dementia and in addition, cerebral blood flow was reduced. Small cerebral resistance arteries which run across the surface of the brain (pial arteries) showed enhanced pressure-induced constriction due to lack of activity of large conductance Ca2+ activated K+ channels (BK channels), key vasodilatory ion channels of cerebral vascular smooth muscle cells. BK channels are activated by transient intracellular signals from the sarcoplasmic reticulum called Ca2+ sparks, leading to hyperpolarisation and vasodilation. Combining patch clamp electrophyiology, high speed confocal imaging and proximity ligation assays we demonstrated that while the biophysical properties of BK channels and Ca2+ sparks remained intact, physical separation of the plasma membrane from the sarcoplasmic reticulum uncoupled the vasodilatory mechanism. This novel pathogenic mechanism is responsible for the increased constriction and can be now targeted as a possible avenue to restore healthy cerebral blood flow in vascular dementia.
S-19-4: ANGIOTENSINOGEN SIRNA FOR HYPERTENSIVE PATIENTS
Authors: Danser A.H. Jan
Published: January 2023

Multiple types of renin-angiotensin system (RAS) blockers exist, allowing interference with the system at the level of renin, angiotensin-converting enzyme or the angiotensin II receptor. Yet, in particular for the treatment of hypertension, the number of patients with uncontrolled hypertension continues to rise, either due to patient non-compliance, or because of the significant renin rises that may, at least partially, overcome the effect of RAS blockade (RAS escape). New approaches to target the RAS are either direct antisense oligonucleotides (ASO) that inhibit angiotensinogen RNA translation, or small interfering ribonucleic acids (siRNA) that function via the RNA interference pathway. Since all angiotensins stem from angiotensinogen, lowering angiotensinogen has the potential to circumvent the RAS escape phenomenon. Moreover, ASO and siRNA require injections only every few weeks to months, which might reduce non-compliance. Of course, angiotensinogen suppression also poses a threat in situations where the RAS is acutely needed, for instance in women becoming pregnant during treatment, or in cases of emergency, when severe hypotension occurs. This presentation discusses all preclinical data on angiotensinogen suppression, as well as the limited clinical data that are currently available. It concludes that it is an exciting new tool to target the RAS with high specificity and a low side effect profile. Its long-term action might revolutionize pharmacotherapy, as it could overcome compliance problems. Preclinical and clinical programs are now carefully investigating its efficacy and safety profile, allowing an optimal introduction as a novel drug to treat cardiovascular and renal diseases in due time.
S-20-2: IS HYPERTENSION A CAUSE OF ATRIAL CARDIOMYOPATHY IN PATIENTS WITH ATRIAL FIBRILLATION? -EVIDENCE FROM ATRIAL BIOPSY-
Authors: Takahashi Yuya , Yamaguchi Takanori , Otsubo Toyokazu , Nakashima Kana , Shinzato Kodai , Osako Ryosuke , Shichida Shigeki , Node Koichi
Published: January 2023

Objective:

Hypertension is considered to be associated with the development of ventricular cardiomyopathy, however, little is known about its impact on atrial cardiomyopathy. The purpose of this study is to investigate the relationship between hypertension and atrial cardiomyopathy in patients with atrial fibrillation (AF).

Design and method:

We examined 234 patients (67 ± 12 years old, 72 female genders, 145 non-paroxysmal AF type) who underwent right atrial septum biopsy from the limbus of fossa ovalis under the guidance of intracardiac echocardiography during catheter ablation for AF. High-density bipolar voltage mapping was also performed using a grid mapping catheter during high right atrial pacing. Atrial cardiomyopathy was evaluated based on quantitative histological analyses including the extent of fibrosis (%Fibrosis), extent of intercellular space (%Intercellular-space), severity of myofibrillar loss (%Myofibrillar-loss), extent of adipocyte (%Adipocyte), myocyte size, and nuclear density were quantified using a digital image platform based on the Masson Trichrome and Hematoxylin and Eosin staining (Figure A). Mean voltage at the biopsy site and the whole left atrium (LA) was evaluated (Figure B). Univariate analyses were performed on these histological factors between patients with hypertension and those without. Covariate correction for age and gender was also performed.

Results:

A total of 132 patients had hypertension. Univariate analysis showed no significant difference in %Fibrosis, %Intercellular-space, %Myofibrillar-loss, %Adipocyte, Myocyte size, mean voltage at the biopsy site and of the whole LA, LA volume/body surface area, and LA diameter between patients with and without hypertension. Nuclear density was significantly lower in patients with hypertension than those without hypertension (368 ± 128 vs. 409 ± 151/mm2, p = 0.006) (Figure C). After adjusting for age and gender, there was no significant difference in the nuclear density (p = 0.129).

Conclusions:

Arterial hypertension is not associated with the severity of atrial cardiomyopathy in patients with AF.
S-21-1: IMPLEMENTING HEARTS HYPERTENSION CONTROL PROJECT IN CHINA
Authors: Zhang Xin-Hua , Guan Tingrui , Wang Hao , Zhao Haiying , Huang Hongxia , Liu Lisheng , Frieden Tom
Published: January 2023

Hypertension is the leading cause of death and disability worldwide, due to its high prevalence and severe complications (stroke, heart attack, etc). Control of hypertension could prevent most unnecessary outcomes. However, detecting hundreds of millions of hypertensive patients globally and controlling BP to target for the rest of their lives could be a huge burden to all health care systems. The HEARTS technical package developed by WHO provides tools for governments and professional organizations to support primary care services (PCS) to apply evidence-based strategies to control and prevent cardiovascular diseases. The HEARTS China hypertension control project was initiated in 2017. It is owned by governments, technically supported by a hypertension specialist committee and managed by the secretariat. The standard protocol with screening for all adult visitors, and stepwise treatment with calcium channel blockers + ARB + thiazide-like diuretic was selected by the advisory committee. The supply of selected medications was supported by governments. The HEARTS monitoring system, with ID card-driven automatic BP measurement and data transfer to the doctors web page (no data entry), records screening, registration and prescriptions during daily practice. The information helps physicians with decision making in diagnosis and treatment and provides regular quality and progress reports to PSCs and health authorities.

Up to December 2021, a cumulative total of 894 PSCs participated in the project. They screened more than 620,000 adults, registered over 268,000 and treated 190,000 hypertensive patients. A total of 86,523 patients achieved the goal of BP control at their last visit. The awareness, treatment and control rates improved continuously in the project-involved areas. Consequently, the episodes of hospitalization for cardiovascular disease among all-cause hospitalizations reduced by 13%. It reduced more in the service areas that screened and treated more hypertensive patients, than in those that screened and treated fewer patients (-15% vs -6%).

However, the data recorded in the monitoring system indicated serious clinical inertia in the implementation of the HEARTS protocol: screening does not yet involve all visitors; nearly 30% of diagnosed patients were untreated, 70% of treated patients were not regularly followed-up; only 19% of patients with BP> = 160/100 initiated treatment with combined medications; 64% of revisited patients with uncontrolled BP failed to intensify treatment. More training courses and incentive mechanisms may help PSCs to improve the quality of care.

Implementing HEARTS has improved quality and coverage for hypertension control. Overcoming clinical inertia should be able to accelerate this progress.
S-21-2: MAY MEASUREMENT MONTH IN NEPAL: FIVE-YEAR COMPARISON OF BLOOD PRESSURE SCREENING RESULTS IN 2017 - 2021
Authors: Inagaki Yoko , Koilala Sweta , Bhattarai Harikrishna , Mishra Shiva Raj , Adhikari Tara Ballav , Khanal Pratik , Acharya Pawan , Mclachlan Craig , Poulter Neli R , Koilala Baghawan , Oslen Michael Hecht , Neupane Dinesh
Published: January 2023

Objective:

Nepal has been participating in the May Measurement Month (MMM) aiming to raise hypertension awareness and improve health seeking behavior to control high blood pressure in communities and present data for policymakers. This study compares the results from 2017 to 2021.

Design and Methods:

Opportunistic cross-sectional surveys to measure the proportion of hypertension, its awareness, treatment, control, and risk factors among> = 18 years of age annually from 2017 to 2021 in Nepal. Although MMM was not executed globally due to the COVID-19 pandemic in 2020, it was conducted in Nepal by following safety measures. We administered the structured questionnaire and took three BP readings while sitting at 1-minutes intervals. Measures of association were calculated using the logistic regression model adjusting for age and sex. The same definition of hypertension (a mean of 2nd and 3rd BP reading> = 140/90 mmHg, or participants were treated with medicines for known hypertension) was applied for all years.

Results:

The summary characteristics from 2017 to 2021 are presented in Table 1. Baseline characteristics were similar for all five studies except for low tobacco use in 2017. The proportion of hypertension ranges from 20.6% to 31.3% (24.4% in 2017, 27.8% in 2018, 27.5% in 2019, 31.3% in 2020, and 20.6% in 2021). Awareness, treatment, and control were also similar across five years, ranging from 39.5% to 49.9%, 29.5% to 39.1%, and 46.0% to 56.0% respectively. Smoking, alcohol use, body mass index> = 25, diabetes, and history of myocardial infarction (MI) or stroke were associated with hypertension after adjusting for age and sex across multiple studies.

Conclusions:

A five-year comparison of the MMM study in Nepal showed that hypertension awareness, treatment, and control have been suboptimal, suggesting an urgent need to implement a nationwide prevention and control program together with a national screening program.
S-22-1: GENETIC MECHANISMS OF HYPERTENSION IN DIFFERENT FORMS OF PRIMARY ALDOSTERONISM
Authors: Zennaro Maria-Christina , Fernandes-Rosa Fabio L , Boulkroun Sheerazed
Published: January 2023

Primary aldosteronism is the most common form of secondary arterial hypertension, affecting up to 10% of hypertensive patients. It is responsible for treatment resistance and increased risk of cardiovascular complications. Due to the difficulty of its diagnosis, PA is frequently missed, and as a result, treatment of the condition is either delayed by many years after the onset of hypertension, or is not initiated at all. Over the past 10 years, important discoveries have been made regarding the genetic basis of aldosterone producing adenoma and familial forms of primary aldosteronism. In most cases, genetic abnormalities are found in genes coding for ion channels (KCNJ5, CACNA1D, CACNA1H, CLCN2) as well as ion pumps (ATP1A1, ATP2B3). They occur as somatic mutations in aldosterone producing adenoma and as germline mutations in familial forms of the disease. Mutations in these genes affect intracellular ion homeostasis and/or cell membrane potential, leading to increased intracellular calcium concentrations and activation of calcium signalling, which is the main regulator of aldosterone biosynthesis. In addition, double mutations in CTNNB1 and GNAQ/GNA11 have been identified in aldosterone producing adenoma presenting in puberty, pregnancy and menopause. Genetic studies have opened interesting diagnostic and treatment opportunities. While surrogate biomarkers of the mutation status may facilitate diagnosis and subtype identification in primary aldosteronism, innovative therapies are currently studied targeting mutated proteins. Finally, recent evidence suggests a continuum between unilateral and bilateral forms of primary aldosteronism, with somatic mutations being found in aldosterone producing cell clusters and aldosterone producing adenoma in patients with bilateral forms. We have recently identified genetic risk loci for primary aldosteronism through genome wide association studies, which may explain shared susceptibility and reveal new mechanisms involved in adrenal gland function and the development of aldosterone producing adenoma and bilateral adrenal hyperplasia.
S-22-2: PHENOME-WIDE ANALYSIS OF A BLOOD PRESSURE POLYGENIC RISK SCORE
Authors: Vaura Felix , Niiranen Teemu
Published: January 2023

Objective:

Blood pressure (BP) is a polygenic trait with > 1400 known single nucleotide polymorphisms (SNPs), and BP polygenic risk scores (PRSs) strongly predict future hypertension. However, 90% of BP SNPs are also associated with other traits, such as anthropometric, biochemical, brain-related, hematological, and lifestyle traits. We conducted a phenome-wide survival analysis to explore the longitudinal associations between systolic BP (SBP) PRS and all major disease end points.

Design and method:

We used FinnGen study release 7 with 321,302 individuals (mean age at the end of follow-up 59.4 years, 56.2% women). Because Finnish permanent residents are linked to nationwide electronic health care registers, follow-up with virtually no loss to follow-up is possible for all major disease end points. First, we computed an SBP PRS based on 1,098,015 SNPs using PRS-CS and independent summary statistics from the UK Biobank. Then, using Cox models, we estimated the association between the SBP PRS and 2,350 incident disease end points across all ICD-10 categories and major medication classes. We considered a P value < 10–5 significant.

Results, and Conclusions:

In total, we observed 157 phenome-wide significant associations between SBP PRS and incident disease end points (Figure). As expected, circulatory disease phenotypes had the highest number of significant associations (73), followed by endocrine and metabolic diseases (32), obstetric diseases (10), and respiratory diseases (8). Overall, 14 out of 17 ICD-10 categories had at least one phenome-wide significant association, with only neoplasms, ear-related, and perinatal diseases lacking any associations. Our results demonstrate that due to the high pleiotropy in BP genetics, SBP PRS is associated with a wide range of outcomes besides cardiovascular disease. The mechanisms underlying these links warrants further investigation. More broadly, our study also underlines the potential for PRSs from high-powered genome-wide association studies of pleiotropic traits to be utilized in the prediction of other incident diseases.