bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear masses and the equation of state of nuclear matter
Authors: Oyamatsu Kazuhiro
Published: June 2023

The incompressible liquid-drop (ILD) model reproduces masses of stable nuclei rather well. Here we show how the ILD volume, surface, symmetry, and Coulomb energies are related to the equation of state of nuclear matter using the Oyamatsu–Iida (OI) macroscopic nuclear model, which has reasonable many-body energy and isoscalar inhomogeneity gradient energy. We use 304 update interactions, covering wide ranges of the incompressibility K0 of symmetric matter and the density slope of symmetry energy L, which fit almost equally empirical mass and radius data of stable nuclei. Thus, the K0 and L dependences are nearly frozen in stable nuclei as in the ILD model, leading to clear correlations among interaction and saturation parameters. Furthermore, we assume that the surface energy of the OI model is twice as large as the gradient energy using the size equilibrium conditions of the ILD and OI models. Then, the four energies of the ILD and OI models agree well for stable nuclei with A ≳ 40. Meanwhile, the OI model with L ≲ 100 MeV predicts the latest mass data better than those of stable nuclei, and we suggest 20 ≲ L ≲ 90 MeV, although the lower boundary is not constrained well.
Chiral anomaly as a composite operator in the gradient flow exact renormalization group formalism
Authors: Miyakawa Yuki , Sonoda Hidenori , Suzuki Hiroshi
Published: June 2023

The gradient flow exact renormalization group (GFERG) is an idea that incorporates gauge-invariant gradient flows into the formalism of the exact renormalization group (ERG). GFERG introduces a Wilson action with a cutoff while keeping the vector gauge invariance manifestly. The details of the formalism are still to be worked out. In this paper, we apply GFERG to construct the Wilson action of massless Dirac fermions under the background chiral gauge fields. By formulating the chiral anomaly as a “composite operator”, we make the scale invariance of the anomaly manifest. We argue that the same result extends to QCD.
Small fractional parts of binary forms
Authors: Yeon Kiseok
Published: June 2023

We obtain bounds on fractional parts of binary forms of the shape $$\Psi(x,y)=\alpha_k x^k+\alpha_l x^ly^{k-l}+\alpha_{l-1}x^{l-1}y^{k-l+1}+\cdots+\alpha_0 y^k$$ with $\alpha_k,\alpha_l,\ldots,\alpha_0\in{\mathbb R}$ and $l\leq k-2.$ By exploiting recent progress on Vinogradov’s mean value theorem and earlier work on exponential sums over smooth numbers, we derive estimates superior to those obtained hitherto for the best exponent σ, depending on k and $l,$ such that $$ \min_{\substack{0\leq x,y\leq X\\(x,y)\neq (0,0)}}\|\Psi(x,y)\|\leq X^{-\sigma+\epsilon}. $$
Effect of the traffic-light system on nutrition labeling in processed food products in the Ecuadorian population
Authors: Sarasty Oscar , Carpio Carlos , Cabrera Tania
Published: June 2023

The 2012 Ecuadorian National Nutrition and Health Survey found that a high proportion of the country's population is overweight or obese. To address this health issue, in 2013, the Ecuadorian government implemented the use of a mandatory traffic-light (TL) nutritional labeling to be displayed on all processed food and beverages for sale in the country. We aimed to evaluate Ecuadorian consumers’ preferences for the nutritional attributes represented in the TL nutritional labels. In this cross-sectional study, 1,152 Ecuadorian consumers aged 18 and older in charge of food purchases completed an online survey. Results of a choice experiment with yogurt products revealed strong preferences and willingness to pay for yellow and green labels reaching price premiums of $1.15 for fat and $1.34 for sugar relative to red labels. The study provides evidence that consumers have high understanding of the TL nutritional labeling and prefer products with colors representing healthier alternatives.
Resolving Failed Banks: Uncertainty, Multiple Bidding and Auction Design
Authors: Allen Jason , Clark Robert , Hickman Brent , Richert Eric
Published: June 2023

The FDIC resolves insolvent banks with scoring auctions. Although the structure of the scoring rule is known to bidders, they are uncertain about how the FDIC trades off different bid components. Scoring-rule uncertainty motivates bidders to submit multiple bids for the same failed bank. To evaluate the effects of uncertainty and multiple bidding for FDIC costs, we develop a methodology for analysing multidimensional bidding when the auctioneer’s scoring weights are unknown to bidders. We estimate private valuations for failed-bank assets during the great financial crisis and compute counterfactuals in the absence of scoring uncertainty. Our findings imply a substantial reduction in FDIC resolution costs of between 29.8% ($8.2 billion) and 44.6% ($12.3 billion). These savings can reduce policy-driven banking-sector distortions, since FDIC resolution costs are covered either through special levies on banks or through loans from the US Treasury. Our analyses also shed new light on optimal bid portfolio choice in combinatorial auctions.
From improved sleep regularity to reduced sleep complaints and mental health conditions: a population-based interventional study using a smartphone-based virtual agent
Authors: Coelho Julien , Pecune Florian , Levavasseur Yannick , De Sevin Etienne , D’incau Emmanuel , Sagaspe Patricia , Sanchez-Ortuño Maria-Montserrat , Micoulaud-Franchi Jean-Arthur , Philip Pierre
Published: June 2023

Study Objectives

To explore the effect of sleep regularity on sleep complaints and mental health conditions (i.e. insomnia, fatigue, anxiety, and depressive symptoms) in a population-based interventional study using a smartphone-based virtual agent.

Methods

A populational cohort based on the Kanopée application, which provided interactions with a virtual companion to collect data on sleep and make personalized recommendations to improve sleep over 17 days. A pre-intervention sleep diary and interview were used for cross-sectional analysis (n = 2142), and a post-intervention sleep diary and interview were used for longitudinal analysis (n = 732). The intra-individual mean (IIM) and standard deviation (ISD) of total sleep time (TST) were calculated to measure sleep quantity and sleep regularity.

Results

The mean age at baseline was 49 years, 65% were female, 72% reported insomnia, 58% fatigue, 36% anxiety, and 17% depressive symptoms. Before the intervention, irregular and short sleep was associated with a higher likelihood of insomnia (Relative risk [RR] = 1.26 [1.21–1.30] for irregular TST and RR = 1.19 [1.15–1.23] for short TST), fatigue, anxiety, and depressive symptoms. After the intervention, the IIM of the TST increased while the ISD of the TST and sleep complaints and mental health conditions decreased. More regular TST was associated with reduced insomnia and depressive symptoms (RR = 1.33 [1.10–1.52] and RR = 1.55 [1.13–1.98], respectively).

Conclusions

Our results reveal a longitudinal association between sleep regularity and sleep complaints and mental health conditions. Policymakers, health professionals, and the general population should be aware that, beyond its positive effect on sleep health, regular sleep could promote mental health.
Brokers and Boundary Managers: School Expulsions amid the Non-Punitive Turn
Authors: Gleit Rebecca D
Published: June 2023

Like many American institutions, K–12 schools are increasingly embracing a rhetoric of non-punitiveness and seeking to supply resources instead of imposing harsh punishment. Using ethnographic data from a diverse, suburban, well-resourced public high school, I explore how institutional actors manage this central role in the provision of goods and services. I find that school staff lack the capacity to successfully serve as brokers for all their constituents, forcing decisions about how to allocate their limited resources. Staff navigate these constraints by strategically managing the boundaries of the institution, redefining who gets to remain a member and who they will continue brokering for. I describe how and when these exclusions occur and show that students from less advantaged backgrounds are at higher risk of expulsion because they depend more on the school for resources than their privileged peers. Further, informal methods of exclusion become favored in this non-punitive pivot, meaning that official data likely undercount the number of students forcibly removed from their schools. As institutions take on more resource brokering amid the turn towards non-punitiveness, the decisions of boundary managers – those actors with the power to enroll and expel members – become increasingly consequential for the allocation of public resources.
17Visual Culture
Authors: Gordon-Orr Rose
Published: June 2023

The unauthorized movement of people across national borders, on land and sea, continues to be a matter of life and death for many migrants. In 2022, more than 2,000 people died attempting to cross the Mediterranean (Statista [2023]) and more than 800 died on the US–Mexico border (Villarreal [2022]). In both Europe and the US, migration remains a significant political issue and one that has a strong visual component: it is through visual representations of boats, bodies, and borders that most non-migrants apprehend the phenomenon. Visual surveillance from the air and at crossing points is a key part of state attempts to control migration. With the increasing availability of smartphones and social media platforms, migrants themselves are also visually documenting and sharing their experiences. This chapter focuses on six texts published within 2022 which explore aspects of visual culture in relation to migration. This has several facets: representation of migrants and associated colonial tropes; visual and ‘postvisual’ surveillance of migrant bodies; and digital self-representation and reclaiming the gaze through creative practices. In line with this, the chapter is divided into three sections: 1. Visual Policing; 2. Visual Narration; 3. Artistic Disruptions.
Contribution of Native Plasmids of Pantoea vagans C9-1 to Epiphytic Fitness and Fire Blight Management on Apple and Pear Flowers and Fruits
Authors: Klein-Gordon Jeannie M. , Johnson Kenneth B. , Loper Joyce E. , Stockwell Virginia O.
Published: June 2023

Pantoea vagans C9-1 (C9-1) is a biological control bacterium that is applied to apple and pear trees during bloom for suppression of fire blight, caused by Erwinia amylovora. Strain C9-1 has three megaplasmids: pPag1, pPag2, and pPag3. Prior bioinformatic studies predicted these megaplasmids have a role in environmental fitness and/or biocontrol efficacy. Plasmid pPag3 is part of the large Pantoea plasmid (LPP-1) group that is present in all Pantoea spp. and has been hypothesized to contribute to environmental colonization and persistence, while pPag2 is less common. We assessed fitness of C9-1 derivatives cured of pPag2 and/or pPag3 on pear and apple flowers and fruit in experimental orchards. We also assessed the ability of a C9-1 derivative lacking pPag3 to reduce populations of E. amylovora on flowers and disease incidence. Previously, we determined that tolerance to stresses imposed in vitro was compromised in derivatives of C9-1 lacking pPag2 and/or pPag3; however, in this study, the loss of pPag2 and/or pPag3 did not consistently reduce the fitness of C9-1 on flowers in orchards. Over the summer, pPag3 contributed to survival of C9-1 on developing apple and pear fruit in two of five trials, whereas loss of pPag2 did not significantly affect survival of C9-1. We also found that loss of pPag3 did not affect C9-1’s ability to reduce E. amylovora populations or fire blight incidence on apple flowers. Our findings partially support prior hypotheses that LPP-1 in Pantoea species contributes to persistence on plant surfaces but questions whether LPP-1 facilitates host colonization.
PREDITING THE RISK OF FRACTURE ASSOCIATED WITH ANTIHYPERTENSIVE TREATMENT: DEVELOPMENT OF THE STRATIFY-FRACTURE PREDICTION MODEL
Authors: Wang Ariel , Koshiaris Constantinos , Stevens Richard , Hobbs F.D. Richard , McManus Richard J. , Sheppard James P.
Published: June 2023

Objective:

The benefits of antihypertensive treatment are well known, but less is known about the potential risk of harm from antihypertensive medication. The STRAtifying Treatments. In the multi-morbid Frail elderlY (STRATIFY) study aimed to better understand the harms of antihypertensive treatment by quantifying an individual's baseline risk of different serious adverse events. This current study aimed to develop a prediction model for an individual's risk of hospitalisation or death from fracture.

Design and method:

Participants aged > = 40 years, registered to a UK primary care practice within the Clinical Pr: actice Research Datalink (CPRD) GOLD database, with at least one blood pressure measurement between 130-179 mm Hg were included in this cohort study. The outcome investigated was fracture that led to hospital admission or death within 10 years after the index date. The (prespecified) predictor variables based on the literature and expert opinions were patient characteristics, history of falls and fractures (from the age of 40), diagnosis of osteoporosis and rheumatoid arthritis, other comorbidities, and prescribed medications (including antihypertensive medications). Multiple imputation was used to account for missing data. The primary analysis used a Fine-Gray competing risks approach to adjust death from other causes. Results were reported as subdistribution hazard ratios (SHR).

Results:

A total of 1,772,601 participants were included, with a mean age of 59 years and median follow-up of 6.1 years. The 10-year incidence of fracture was 1.4%. All antihypertensive medications were significantly associated with the risk of fracture, as were a number of patient characteristics and co-morbidities (detailed in Table 1). Potential predictors with no significant association were chronic renal disease, mobility and transfer problems, hypogonadism, vitamin D deficiency and aromatase inhibitors. SHRs and 95% confidence intervals for the predictors are shown in Table 1.

Conclusions:

In this study, we identified a number of predictors of fracture using UK electronic health record and quantified an individual's baseline risk of fracture. The external validation of this model will use a different database (CPRD AURUM). Our findings could inform clinicians as to when it is appropriate to prescribe and deprescribe antihypertensive treatment.
CARDIOVASCULAR RISK, METABOLIC PROFILE AND INFLAMMATORY FINGERPRINT OF OBESE SUBJECTS UNDERGOING BARIATRIC SURGERY
Authors: Burrello Jacopo , Gonzalez Mary Julieth , Airale Lorenzo , Burrello Alessio , Kostler Thomas , Zingg Urs , Barile Lucio , Osto Elena
Published: June 2023

Objective:

Bariatric surgery has emerged as effective treatment for obesity not only for the substantial and durable weight loss, but also by improving several obesity-related comorbidities, including hypertension. Extracellular vesicles (EVs; membrane nanoparticles released by cells) and their cargo reflect endothelial dysfunction and inflammation, and may be used as indicators of post-surgical outcomes in these patients. The aim of the present study was to exploit an EV signature to assess cardiovascular (CV) risk, metabolic profile, and inflammatory fingerprint before and after bariatric surgery.

Design and method:

The study cohort was composed by 62 patients (age 39 years; 21% males); for each subject, clinical and biochemical parameters, disease status (including diabetes, dyslipidemia, and hypertension), medications, and EV profiling were evaluated at baseline (T0) and 1-/3-years (T1 and T2, respectively), after surgery (sleeve gastrectomy or Roux-en-Y gastric bypass). EVs were isolated from serum by beads-based immuno-capture and analyzed for the expression of 37 membrane-associated antigens.

Results:

After bariatric surgery, patients gradually lost weight from a median of 110 Kg at T0 down to 80 Kg at T2 (cumulative weight loss 31 Kg; 29.9% BMI reduction). Accordingly, the overall CV risk and metabolic-inflammatory profile of patients improved: systolic blood pressure, HbA1c, total cholesterol, triglycerides, LDL, uric acid, white blood cells, and C-reactive protein decreased, while HDL and renal function (expressed as eGFR) increased at follow-up (p < 0.05 for all comparisons); prevalence of hypertension, dyslipidemia, and diabetes decreased together with the number of assumed drugs (anti-hypertensives, statins, hypoglycemic, and anti-platelets agents). Consistently, levels of expression of EV specific markers (CD9-CD63-CD81) and 11 out of the 37 evaluated antigens (mainly from endothelium, platelets, and inflammatory cells) decreased at T1/T2, reflecting changes of main CV risk indicators. Interestingly, lower baseline levels of CD4, CD31, CD40, CD42a, and CD62P were associated to a complete post-surgical outcome, defined as no residual disease without medications, with a BMI at T2 lower than 30 Kg/sqm.

Conclusions:

EV-derived biomarkers reflect the improvement of CV profile in patients who underwent bariatric surgery and may become a new tool to predict post-surgical outcome.
RESULTS OF SIMULTANEOUS LEFT AND RIGHT UPPER ARM 24-HOUR AMBULATORY BLOOD PRESSURE MEASUREMENT: A WAKE UP-CALL FOR BETTER HYPERTENSION MANAGEMENT
Authors: Bothe Tomas L , Patzak Andreas , Pilz Niklas
Published: June 2023

Objective:

Cuff-based 24-hour ambulatory blood pressure (BP) measurement is considered as the gold standard for hypertension diagnosis and treatment monitoring, its clinical value being ubiquitously accepted. This study wants to quantify the measurement discrepancies in simultaneous and synchronized 24-hour ambulatory BP measurements on both arms. Identifying and understanding measurement uncertainties could improve future hypertension management and further stimulate research on alternative, cuff-less systems with adequate measurement precision.

Methods:

We conducted simultaneous 24-hour ambulatory BP measurements on both arms in 52 healthy young adults. Broadly used and validated cuff-devices (BoSo TM-2430) were synchronized to start BP measurement within one second of each other. Further, we recorded cuff-pressures of both cuff-based devices and the hydrostatic pressure differences between both cuffs throughout the recording. We then scored pressure curves for disturbances (e.g., pressure spikes during deflation) and were able to correct measurements for hydrostatic differences between the arms. This enabled us to not only quantify the extent of measurement inaccuracy but to describe its origins and possible countermeasures.

Design and method:

Measured BP levels from left and right arm showed limits of agreement in the Bland Altman Plot of > 33 mmHg for systolic and > 30 mmHg for diastolic values over 24 h. Daytime values deviated more than nocturnal values (systolic: > 35 mmHg vs. > 27 mmHg systolic, and diastolic: > 32 mmHg vs. > 24 mmHg, respectively). Linear regression retrieved R2 = 0.39 (p < 0.001) for systolic and R2 = 0.20 (p < 0.001) for diastolic values. Exclusion of artefactual cuff pressure curves improved limits of agreement to > 23 mmHg for systolic and > 19mmHg for diastolic measurements. Subsequently, it improved correlation coefficients to R2 = 0.54 (p < 0.001) for systolic and R2 = 0.35 (p < 0.001) for diastolic values. Correction of hydrostatic differences between the arms had a negligible effect on limits of agreement and strength of correlation.

Results:

Comparison of synchronized 24-hour BP measurements obtained on both arms showed large measurement uncertainties with possible implications on clinical grading of hypertension and dipping pattern. Exclusion of artefactual cuff pressure curves, not detected by the conventional software of BP devices, mitigates the effect but cannot eliminate worrying discrepancies. These results strongly support the need to further investigate the clinical implications of BP measurement uncertainty. They should further stimulate research on alternative means of BP measurement which might overcome some of the problems related to cuff-based BP monitoring.
COMPARISON OF ATTENDED WITH UNATTENDED BLOOD PRESSURE MEASUREMENTS PERFORMED BY TWO DIFFERENT DEVICES
Authors: Filipovsky Jan , Seidlerova Jitka Mlikova , Gelzinsky Julius , Mares Stepan , Mayer Otto
Published: June 2023

Objective:

Unattended blood pressure (uBP) is lower than blood pressure (BP) measured by physician or nurse (attended blood pressure, aBP). We aimed to compare the uBP values obtained in two population-based cohorts, where uBP was measured in different way.

Design and method:

In the MONICA Study, 1% random samples from general population were repeatedly examined. We selected two cohorts for the present analysis: cohort 1 (examined in 2016, n = 179), where uBP was measured by BPTru (six measurements, first skipped, with no pause before the measurements), and cohort 2 (year 2018, n = 166) where uBP was measured by Omron 907 (three measurements after a preset 5-minute pause). aBP was measured after uBP in triplicate by physician using auscultatory method.

Results:

The two cohorts did not differ in age (67 vs 69 years), sex distribution, prevalence of cardiovascular disease, prevalence of hypertension (74 vs 73%), atrial fibrillation, diabetes, antihypertensive or hypolipidemic treatment and smoking. Systolic aBP was 137.6 ± 16.6 vs 135.4 ± 17.8 mmHg (NS) and diastolic aBP was 81.4 ± 9.4 vs 77.2 ± 9.5 mmHg (<0.0001) in the two cohorts, respectively. Differences between aBP and uBP were significant in all cases (p < 0.001), ranging from 3.7 mmHg (diastolic aBP – BP by Omron) to 8.8 mmHg (systolic aBP – BPTru). When the BPTru and Omron uBP measurements were compared, no difference was found. This was true when the means of all measurements were compared (five by BPTru and three by Omron) and also when only two measurements were analyzed (2nd and 3rd one, available for both devices). Multiple regression of systolic aBP – uBP difference showed that the only significant determinant was aBP value (positive association, p < 0.0001).

Conclusions:

There was no difference between the uBP values measured by BPTru and Omron 907. The 2nd and 3rd measurements seem to be sufficient to be taken into account.
ABILITY OF A CUFFLESS 24 HOUR AMBULATORY BLOOD PRESSURE MEASUREMENT DEVICE TO TRACK BLOOD PRESSURE CHANGES COMPARED TO A CUFF-BASED DEVICE
Authors: Burkard Thilo , Derendinger Felicia , Krisai Philipp , Socrates Thenral , Schumacher Christina , Mayr Michael , Vischer Annina
Published: June 2023

Objective:

There is an increasing number of cuffless blood pressure (BP) measurement devices on the market. Beneath the absence of generally accepted validation protocols for these devices, the ability of these devices to track changes in BP levels over 24h in relation to an initial calibration BP is unknown. Aim of this study was to analyse this ability in a cuffless 24h BP device using pulse transit time.

Design and method:

We prospectively enrolled 166 participants for simultaneously performed cuffless (TestBP, Somnotouch NIBP) and cuff-based (RefBP, Spacelabs 90217A or IEM Mobil-o-graph) 24h BD measurements. Main exclusion criteria were atrial fibrillation or an inter-arm difference of >10 mmHg. TestBP calibration was based on initial RefBP measurement (CalibBP). As surrogate parameters for tracking individual changes in BP levels after the CalibBP, we used the difference between CalibBP and mean 24h, awake and asleep BP measured by RefBP and TestBP. Additionally, we analysed the relationship between the difference of CalibBP and RefBP vs the difference between RefBP and TestBP.

Results:

Mean (±SD) age was 51.2 (15.1) years and 53% were male. Mean (±SD) difference between CalibBP and mean 24h BP by RefBP / TestBP were 7.4 (13.2) versus 1.8 (8.3) mmHg for systolic (p < 0.0001) and 6.6 (6.8) versus 1.6 (5.8) mmHg for diastolic (p < 0.0001). Corresponding ranges for CalibBP-RefBP were -35 – 55 mmHg vs. -14 – 34 for CalibBP-Test BP. Figure 1 shows a near linear relationship between the difference between CalibBP and RefBP and the difference between RefBP and TestBP for systolic and diastolic BP values. Red line indicates the theoretical situation that TestBP follows CalibBP without tracking changes in BP levels, green line an ideal agreement of RefBP and TestBP.

Conclusions:

This is the first study to show the lower ability of the cuffless BP device to track changes of BP levels after an initial calibration measurement compared to a standard cuff-based device over 24h. Additionally, the difference between the RefBP and the TestBP was nearly linearly associated with the difference between a CalibBP and the changes of the BP level.
DETERMINANTS OF WITHIN-VISIT OFFICE BLOOD PRESSURE VARIABILITY AND INSTABILITY: EUROPEAN DATA FROM 1.053 INDIVIDUALS
Authors: Theodosiadi Aikaterini , Kollias Anastasios , Ntineri Angeliki , Kyriakoulis Konstantinos , Niiranen Teemu , Lindroos Annika , Jula Antii , Schwartz Claire , Andreadis Emmanuel , McManus Richard , Stergiou George S.
Published: June 2023

Objective:

Blood pressure (BP) variability is the physiological sequelae of the complex interaction of multiple neural, humoral, reflex, and behavioral factors. This analysis aimed to evaluate the determinants of BP variability and instability within a single office visit, which is routinely used for hypertension evaluation in clinical practice.

Design and method:

A retrospective analysis of cross-sectional data was performed, comprising adults with triplicate office BP measurements in a single office visit and 24h ambulatory BP monitoring collected within the context of prospective clinical studies in Finland, Greece, and United Kingdom. Indices of BP variability and instability included: (i) standard deviation (SD) (ii) coefficient of variation (CV) (iii) average real variability (ARV) (iv) maximum office BP (Max) (v) maximum-minimum difference (MMD) of office BP (vi) ratio of the difference between 1st-3rd measurement to the mean office BP (Relative change). White-coat effect was defined as the difference between office and daytime ambulatory BP.

Results:

Data from 1.053 individuals were analyzed (mean age 57.7 ± 11.3 years, males 50%, treated hypertensives 50.3%, average office BP 133.5 ± 18.7/83.5 ± 10.9 mmHg, daytime ambulatory BP 132.5 ± 14.1/80.7 ± 9.9 mmHg). All the indices of BP variability and instability were positively associated with average office BP, age, BMI, and white-coat effect, but with an inverse association between age and maximum diastolic BP (all p < 0.05). In multivariable linear regression analysis systolic BP variability was mainly determined by average office systolic BP, and treatment for hypertension, while diastolic BP variability was determined by office diastolic BP and female sex (Table).

Conclusions:

These results suggest that the variability and instability of BP within a single office visit is mainly influenced by the BP level, female sex and the administration of antihypertensive treatment.
VEGF INHIBITION-INDUCED PARP OVERACTIVATION LEADS TO ENDOTHELIAL DYSFUNCTION AND INFLAMMATION: ROLE OF SIRTUIN 1 SIGNALLING
Authors: Neves Karla , Alves-Lopes Rheure , Montezano Augusto C. , Touyz Rhian
Published: June 2023

Objective:

Hypertension is a common unwanted effect of VEGF inhibitors (VEGFi), which are used as anti-angiogenic drugs in cancer treatment. Clinical observations indicate that the magnitude of blood pressure elevation is lower in patients with cancer who are treated with combination VEGFi and olaparib (PARP inhibitor [PARPi]), versus monotherapy. However putative vascular mechanisms are unknown. PARP plays major role in the activation of TRPM2, a redox-sensitive Ca2+ channel, which is associated with hypertension-induced vascular dysfunction. PARP also regulates sirtuin deacetylases activity, especially sirtuin 1 (SIRT1), which is involved in vascular homeostasis and diseases. Here our aim is to investigate whether VEGFi, via PARP activation, leads to vascular dysfunction through disruption of SIRT1 signalling.

Design and method:

Human aortic endothelial cells (HAEC) and mouse mesenteric arteries were studied. Cells were exposed to axitinib (VEGFi; 1uM) alone or in combination with olaparib (PARPi; 1uM) in the presence or absence of a SIRT1 activator (SRT1720; 2uM). Wire myograph was used to assess vascular function.

Results:

Axitinib increased PARP activity in a ROS-dependent manner in HAEC (au: [Veh]0.31 vs. [Axi]0.55; [Tiron+Axi] 0.38] whereas SIRT1 activity was reduced by VEGF inhibition (au: [Veh]33760 vs. [Axi]23367), which was prevented by olaparib. This was followed by an increase in expression of acetyl-p53. Activation of SIRT1 decreased levels of MCP-1 and IL-6 and VCAM-1 and ICAM-1 mRNA levels in HAEC exposed to axitinib, which, similarly to olaparib, was accompanied by a reduction in monocytes adhesion to HAEC. U46619- and ET-1-induced vasoconstriction were increased by axitinib, an effect not observed with axitinib plus Olaparib. Pre-incubation with SRT1720 exacerbated the anti-contractile effects of olaparib. Axitinib impaired ACh-induced vasodilation (% relaxation: 70.5 [Ct] vs. 34.8 [Axi]), which was blocked by olaparib and SRT1720. Phosphorylation of the inhibitory site of eNOS was also increased in HAEC (au: [Veh] 0.18 vs. [Axi] 0.37) and restored by SRT1720.

Conclusions:

Our data indicate that VEGF inhibition-induced PARP overactivation leads to endothelial dysfunction and inflammatory responses via disruption of SIRT1 signalling. We define a putative vasoprotective effect of olaparib that may ameliorate vascular injury induced by VEGFi in cancer treatment.
HYPERTENSION IN CANCER PATIENTS TREATED WITH ANTI-ANGIOGENIC BASED THERAPY: A POPULATION-BASED COHORT STUDY
Authors: Franchi Matteo , Torrigiani Ginevra , Corrao Giovanni , Mancia Giuseppe
Published: June 2023

Objective:

Data from randomized clinical trials showed that new-onset hypertension is a common side effect of anti-angiogenic drugs. We compared the cumulative incidence of new-onset hypertension in cancer patients treated with either anti-angiogenic based therapy (AAG) or other chemotherapy only, and in patients who did not received antineoplastic agents (untreated).

Design and method:

Retrospective population-based cohort study based on the healthcare utilization databases of Lombardy Region (Italy). We identified the cohort of patients aged 40 years or older with a new diagnosis of cancer between 2009 and 2017. We excluded patients with antihypertensive treatment in the five years before cancer diagnosis. We 1:1:1 matched each patient who started a therapy with AAG (index case) with one patient treated with other chemotherapy only and with one untreated patient by date of cancer diagnosis, tumoral site and date of start of antineoplastic therapy. We followed-up each of the three matched patients from the date of start of AAG of the index case until the first date between onset of antihypertensive treatment with at least 3 prescriptions (the outcome of interest), death, migration or 2 years after the start of follow-up. We estimated the incidence cumulative function by considering death as competing event and we fitted a Fine and Grey regression model, adjusted for age, sex and Cancer Multimorbidity Score, in order to estimate the association between treatment and new-onset hypertension.

Results:

The final cohort included 3,333 1:1:1 matched patients (median age 62 years; 43.6% males). The cumulative incidence of new-onset hypertension was higher among patients treated with AAG, as compared to others. The cumulative incidence rapidly increased 1 year (26.3%) after starting therapy with AAG. The adjusted hazard ratios were 3.73 (95% CI 3.34 to 4.15) and 4.00 (3.56 to 4.48), when compared to patients treated with other chemotherapy and with those untreated, respectively. Moreover, patients treated with AAG also showed a significant increased risk of major cardiovascular events compared to others.

Conclusions:

Cancer patients treated with AAG showed a markedly higher risk of new-onset hypertension. The risk rapidly increased 1 year after the start of therapy.
FACTOR ASSOCIATED WITH HYPERURICEMIA DEVELOPMENT DURING A 25 YEARS FOLLOW-UP: THE PAMELA STUDY
Authors: Maloberti Alessandro , Quarti-Trevano Fosca , Dell’Oro Raffaella , Facchetti Rita , Mancia Giuseppe , Grassi Guido
Published: June 2023

Objective:

HyperUricemia (HU) has been associated with future fatal and non fatal CV events as well as with hypertension and metabolic syndrome development. However, only few data exist regarding the change in Uric Acid (UA) and the development of HU during a population follow-up. In particular, no study analyzed the variations during a very long follow-up. The present study was aimed at evaluating the factors associated with UA changes and HU development during a 25-years follow-up in the PAMELA study. Both the classic cut-off for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study were used to define HU.

Design and method:

We analyzed data collected in 561 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA who complete the 3rd wave study (mean follow-up time 25.2 ± 0.5 years). The classic cut-off of 6/7 mg/dL (females and males respectively) and URRAH one (5.1/5.6 mg/dL for females and males) were used for HU definitions.

Results:

Mean UA value during follow-up increase from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dL (p < 0.001) with a mean increase of 0.3 ± 1.1 mg/dL. UA changes significanlty correlated with baseline UA (r = -0.39, p < 0.001) and creatinine (r = -0 - 21, p < 0.001). With the classic cut-off (6/7 mg/dL) 9.1% of the subjects develop HU and this was associated at the multivariate model with age, sex (male), baseline diastolic Blood Pressure (BP) (OR 1.038, p = 0.02) and UA (OR 2.62, p < 0.001). With the new URRAH cut-off 19.1% of the subjects develop HU. At the multivariate model variables associated were gender (male) and baseline 24h systolic BP (OR 1.05, p < 0.001), tryglicerides (OR 1.01, p = 0.01) and UA (4.99, p < 0.001).

Conclusions:

The present study provide evidence that in the PAMELA study during the 25 year follow-up there is a progressive increase in UA. Baseline UA is the most important factor associated with HU development. However, also age, gender, triglycerides and BP could help to identify subjects that most probably will develop HU.
THE IMPACT OF THE 3-YEAR COVID-19 PANDEMIC IN THE HYPERTENSIVE POPULATION OF A EUROPEAN SOCIETY OF HYPERTENSION EXCELLENCE CENTER
Authors: Triantafyllidi Helen , Birmpa Dionyssia , Benas Dimitrios , Fambri Anastasia , Kavatha Dimitra , Iliodromitis Efstathios
Published: June 2023

Objective:

The 3-year COVID-19 pandemic resulted in increased morbidity and mortality in patients with cardiovascular (CV) disease. We aimed to investigate the impact of COVID-19 pandemic in the hypertensive population of a European Society of Hypertension (ESH) Excellence Center.

Design and method:

We retrospectively studied 426 hypertensive patients (61 + 14 years, 48% males) visited our Hospital (March 2020-November 2022) regarding clinical characteristics, CV risk factors and comorbidities All patients were interviewed regarding COVID-19 disease by a phone call during a 2-month period (October-November 2022).

Results:

A small percentage of our population suffered from DM (17%) or had a history of CAD and/or previous stroke (11%). Regarding COVID-19 disease, 55% hypertensives were infected by SARS-CoV-2 virus (Group A, 58 + 14 years, 48% males), 43% patients were not infected (Group B, 65 + 14 years, 50% males) while 2% patients were lost. We found that Group A patients were younger (p < 0.001) while they didn’t differ as for BMI, systolic and diastolic BP, LDL, left ventricular EF, and the history of DM, CAD, stroke, CTD, CKD and cancer compared to Group B. A 89% of the population has received at least one dose of a COVID-19 vaccine. Regarding morbidity and mortality in Group A, 50% patients had minor/no symptoms, 43% patients had fever >38oC, 6% patients were hospitalized for pneumonia due to SARS-CoV-2 virus but only 2 patients (0.8%) died. We hypothesized that, 74% patients infected by the Omicron subtype (50% of them since May 2022), 13% patients by the Delta subtype and 13% patients by the Alpha subtype.

Conclusions:

Hypertensives showed an increased compliance regarding vaccination against COVID-19. Half of the population (the younger ones) affected by SARS-CoV-2 virus, mainly by the Omicron subtype, while just a small percentage was hospitalized or died. Interestingly, about 1/5 of the whole hypertensive population was infected during the last six months of COVID-19 pandemic when the strict protection measures were removed worldwide. We conclude that the majority of hypertensive patients protected themselves against COVID-19 while risk factors and comorbidities didn’t play a significant role regarding infection from SARS-CoV-2 virus.
POSITIVE ASSOCIATION BETWEEN BASELINE ARTERIAL STIFFNESS AND NEW-ONSET DIABETES: A POPULATION-BASED COHORT STUDY
Authors: Beros Angela , Sluyter John , Scragg Robert
Published: June 2023

Objective:

The temporal relationship between increased arterial stiffness and diabetes remains unclear. This study aimed to investigate whether arterial stiffness was associated with new-onset diabetes.

Design and method:

The study population comprised participants from the Vitamin D Assessment (ViDA) Study, a randomised controlled trial of vitamin D supplementation that recruited participants mostly from family practices in Auckland, New Zealand from 5 April 2011 to 6 November 2012. Arterial stiffness was measured at baseline by aortic pulse wave velocity (aPWV), augmentation index (AIx) and pulse pressure (PP). Vitamin D did not affect the risk of the main study outcomes including cardiovascular disease. The final study population was 4479 participants after excluding those with existing diabetes (as determined by dispensed prescriptions and self-report). New-onset diabetes was determined by linkage to dispensed prescription and national hospital discharge registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to aPWV, AIx and PP.

Results:

The mean (SD) age of participants at baseline was 66.2 (8.3), 2556 (57.1%) were male and 3880 (86.6%) were of European or other ethnicity, with the remainder being Polynesian (including indigenous Maori) or South Asian. During a mean (SD) follow-up of 6.86 ± 0.43 years, 364 (8.1%) participants developed diabetes. Following adjustment for age, sex, ethnicity, mean arterial pressure, body mass index and vitamin D supplementation (vitamin D vs placebo), aPWV and PP, but not AIx were associated with an increase in new onset-diabetes (per SD increase, aPWV hazard ratio, 1.36, 95% CI, 1.13 to 1.64; PP hazard ratio, 1.40 95% CI, 1.16 to 1.68; AIx hazard ratio, 1.02, 95% CI, 0.91 to 1.14).

Conclusions:

Arterial stiffness, as measured by aPWV and PP, independent of other risk factors, may be a useful predictor of new-onset diabetes.
VASCULAR FUNCTION AS POSSIBLE MARKER OF FUTURE SUSTAINED HYPERTENSION IN YOUNG TO-MIDDLE AGE STAGE I HYPERTENSIVES ACCORDING TO DIFFERENT HYPERTENSION SUBTYPES
Authors: Saladini Francesca , Rattazzi Marcello , Mos Lucio , Vriz Olga , Mazzer Andrea , Garbelotto Raffaella , Battista Francesca , Ermolao Andrea , Palatini Paolo
Published: June 2023

Objective:

The risk of adverse CV outcomes in young patients with isolated systolic hypertension (ISH) or isolated diastolic hypertension (IDH) is still debated and whether these hypertension subtypes should undergo pharmacological treatment is unclear. Aim of the present the study was to investigate the vascular characteristics and the risk of progression to sisto-diastolic hypertension (SDH) associated with these hypertension subtypes from the HARVEST study.

Design and method:

We examined 1231 young-to middle age subjects (mean age 33.1 ± 8.6 years, 72.3% males). ISH (11.9%) IDH (22.8%) NT (6.6%) and SDH (58.7%) were defined using the office 140/90 mmHg cutoffs. Vascular stiffness was assessed by radial-carotid pulse wave velocity (PWV) and vascular compliance by radial tonometry among 371 participants. Risk of future hypertension needing antihypertensive treatment was assessed with Cox analysis adjusting for several clinical confounders.

Results:

Metabolic parameters did not differ significantly among subgroups. Peripheral resistance was 1297.1 ± 326 among NT, 1371.3 ± 281 among ISH, 1502.5 ± 261 among IDH and 1531.6 ± 308 dynesxsecxcm-5 among SDH (p = 0.048 IDH vs NT and <0.001 SDH vs NT), while did not differ significantly between ISH and NT. Large artery compliance was 15.0 ± 4.2, 15.5 ± 4.9, 15.1 ± 4.9 and 14.0 ± 4.3 ml/minx10 respectively, again with similar values between NT and ISH and a significant difference between IDH and SDH p = 0.016. PWV and AIx did not differ significantly among groups, while central SBP was similar among NT, ISH, IDH (122.2 ± 12.0, 122.6 ± 12.4 mmHg respectively, p = n.s.) and higher among SDH (p < 0.001 SHD vs IDH). Progression to sustained HT was 59.2%, 66.4%, 77.9% and 87.5%, in NT, ISH, IDH and SDH respectively, p < 0.001. At cox analysis, considering SDH as reference, ISH presented a lower risk of progression to unfavourable outcome (H.R. 0.70, 95%CI 0.58 - 0.88; p = 0.0023).

Conclusions:

Young-to-middle age hypertensives have different endothelial function according to different hypertensive subtypes and this may contribute to the future development of hypertension needing treatment. The assessment of vascular function may help to identify those patients who should be treated earlier.
RELATIONS OF PLASMA ALDOSTERONE CONCENTRATION TO CARDIAC STRUCTURE AND FUNCTION: ARE THERE ANY ETHNIC-RELATED DIFFERENCES?
Authors: Faconti Luca , Chowienczyk Philip , McNally Ryan , Farukh Bushra , Bacca Alessandra , Taddei Stefano , Buralli Simona
Published: June 2023

Objective:

Plasma aldosterone concentration (PAC) is related to left ventricular hypertrophy (LVH) and diastolic dysfunction in primary hyperaldosteronism but conflicting data exists in primary hypertension. Here we investigated whether this association might differ in hypertensive subjects of African-origin background (black) vs Caucasian (white).

Design and method:

Subjects with hypertension and self-defined ethnicity (SDE) as black or white whose clinical assessment was not suggestive of secondary forms of hypertension and with an aldosterone/renin ratio < 90 pmol/mU were recruited in London (UK) and Pisa (Italy). Transthoracic echocardiography was used to calculate left ventricular mass index (LVMI) and diastolic function using the ratio of early (E)) transmitral filling velocity to tissue Doppler early diastolic velocity (E/e’).

Results:

167 black (51% male) and 273 white (69% male) subjects of whom 55% and 73% on pharmacological treatment were recruited. Compared to white individuals, black subjects had higher blood pressure (BP) (mean ± SD) (153/93 ± 15/12 mmHg vs 139/88 ± 15/11 mmHg) and lower prevalence of dyslipidaemia (9 % vs 38 %, both P < 0.05) but the two groups were similar for age, prevalence of diabetes, smoking, duration of hypertension. Compared to white subjects, black individuals had lower renin and PAC level (42.4 ± 11.2mU/L vs 79.5 ± 12.7 mU/L and 312 ± 26.5 pmol/L vs 420 pmol/L respectively) while LVMI and E/E’ were greater (95.9 ± 25.2 g/m2 vs 88.7 ± 20.5 g/m2 and 9.1 ± 2.8 vs 7.8 ± 2.4 respectively) all P < 0.001. In the entire population we found a significant interaction between ethnicity and PAC in relation to LVMI and E/e’. After stratifying the population according to SDE, PAC positively correlated with LVMI (R2 0.249, P = 0.01) and E/e’ (R2 0.207, P = 0.009) in black but not in white subjects. Multivariate adjustment for sex, BP, diabetes, dyslipidaemia, heart rate, pharmacological treatment, body mass index did not alter the relationship.

Conclusions:

Aldosterone is related to cardiac remodelling and diastolic function in patients with primary hypertension of African origin. The reasons behind the ethnic difference needs to be elucidated.
IMPACT OF PREVIOUS DIAGNOSIS OF HYPERTENSION ON RENAL FUNCTION IN HEART FAILURE PATIENTS
Authors: Diaz Javier , Calderon Jose M. , Martínez Fernando , Sauri Inma , Fernandez Antonio , Trillo Jose L. , Lidon Laura , Redon Josep
Published: June 2023

Objective:

The aim of this study is to evaluate the impact of previous diagnosis of HTN in the reduction of the estimated glomerular filtration rate (eGFR) and the development of chronic kidney disease (CKD) in heart failure (HF) patients by using real world data.

Design and method:

The study population was selected from a database with electronic health records information from 2012 to 2016 of patients older than 24 years of age. Patients with an active diagnosis of HF at some point during this period were selected, and then stratified according to the presence of previous diagnosis of hypertension. eGFR and Kidney Disease Global Outcomes (KDIGO) risk scale during the observational period were analyzed. Two events were studied using survival and Cox proportional hazards regression models: i) reduction of 20% compared to basal eGFR value and ii) increased risk in the KDIGO scale. Other clinically relevant factors were selected as adjustment variables: age, sex, comorbidities (atrial fibrillation, diabetes, dyslipidaemia and coronary heart disease) and drugs used for HF treatment or anticoagulation.

Results:

The study population included 80631 HF patients, 37426 of them classified with the KDIGO scale. The proportion of patients with hypertension was 87% and the mean baseline eGFR was 64.2 ml/min/1.73m2. The average age was 75.63 years and 54.7% women. Significant increments in risk were found in patients diagnosed of hypertension for the two events, being 1.28 (CI95% 1.21–1.36) for the eGFR reduction and 1.36 (CI95% 1.25–1.48) for the KDIGO increased risk (Figures). This effect increased as the baseline CKD risk was higher, with 1.45 (CI95% 1.37–1.53) times the risk in the case of base high-risk group (eGFR at baseline <60ml/min/1.73m2; N = 5980) compared to the low risk one (N = 15460).

Conclusions:

Hypertension is a very prevalent comorbidity of patients with HF, and has a negative impact on kidney function, increasing the risk of reduction of eGFR and development of CKD. The prognosis is significantly worse as the baseline risk is higher.