bluuebunny/crossref_metadata_2025 huggingface dataset:
Opium
Authors: Kitson Peter J.
Published: May 2024

This chapter reappraises the close association between opium use and the writers and artists of the Romantic period. Samuel Taylor Coleridge and Thomas De Quincey famously consumed the drug in its various forms and wrote about it as did other nineteenth-century figures. Coleridge’s ‘Kubla Khan’, ‘Christabel’, and ‘The Pains of Sleep’ (1816), and De Quincey’s ‘Confessions of an English Opium-Eater’ (1821) established the association between opium use, Romantic creativity, and the vexed question of addiction. This chapter describes the wider cultural impact of the growing use of opium, usually in the form of laudanum, both as a medicine and as a recreational and artistic stimulant, as well as setting its domestic British use in the global context of the triangular opium and tea trades between Britain, India, and China, leading up to the First Opium War of 1839–1842.
Religious Controversy
Authors: Duggett Tom
Published: May 2024

This chapter discusses the intersection of history, politics, and religion in three landmarks of Romantic prose, all published at full length in the year of Catholic Emancipation, 1829: William Cobbett’s History of the Protestant ‘Reformation’; Robert Southey’s Sir Thomas More: or, Colloquies on Society; and Samuel Taylor Coleridge’s On the Constitution of the Church and State. In keeping with the larger Catholic Emancipation debate itself, all three texts move between issues of ‘doctrine’ and ‘institution’, and the articulation of incommensurable Catholic and Protestant historiographies. While at a low level of resolution these texts seem to support a ‘secularization’ narrative of religion fading out, with the radical Cobbett and the increasingly conservative Lake Poets converging upon a kind of nostalgic medievalism, I discover more significant divisions over theology, ideas of progress, and the value of institutions, as well as over the nature and value of history itself.
Sexualities
Authors: Najarian James
Published: May 2024

During the late eighteenth and early nineteenth centuries, gender characteristics and roles were in flux. Literary Romanticism’s valorization of the ‘feelings’ created spaces for authors and individuals to re-imagine sexual stances, including same-sex sexuality, as well as androgynous states like ‘effeminacy’ or ‘mannishness’. The emphasis on the ‘feelings’, rather than on custom and legal codes, enabled authors as diverse as the legal scholar Jeremy Bentham, the poets Lord Byron, P. B. Shelley, and John Keats, the minor celebrities Lady Eleanor Butler and Sarah Ponsonby, and the diarist Anne Lister to imagine and confront these stances in sometimes astonishing ways: Shelley frankly wrote on male same-sex sexuality and Bentham encouraged legalizing it. In her diary, Lister determines to live her life as what we would now call a lesbian partnership, though she did not have the word. It is clear from a reading of the diary that she was influenced by her reading in Romanticism, particularly Jean-Jacques Rousseau.
War
Authors: Gurton-Wachter Lily
Published: May 2024

This chapter argues that nonfiction prose texts about war from the Romantic period—pamphlets, memoirs, newspapers, philosophical texts, and travelogues—sought to describe, negotiate, and prescribe a collective wartime responsibility, shame, and guilt by repeatedly translating war from an abstract term that obscured its own violence to a graphic description of, and confrontation with, war’s brutal and irrational violence. From military memoirs to travel writing about war’s aftermath, from satires mocking and critiquing war propaganda to sincere and serious political–philosophical enquiries, Romantic nonfiction prose tried to sensitize readers to war’s effects, emphasize war’s strangeness, and grapple with an increasing self-consciousness and anxiety about a growing and contagious sense of complicity and guilt, as writers asked who was responsible for the extensive violence happening in the name of the nation.
Social Learning and Culture in Mammals
Authors: Arbon Josh J. , Thornton Alex
Published: May 2024

Social learning is known to be widespread in the animal kingdom but research on mammals often focuses on primates and cetaceans. The greater experimental tractability of many other mammalian species, combined with their enormous diversity in morphology, foraging niches, and social systems, can offer unique insights. To date, work has focused primarily on social information use but there is growing evidence that this can lead to social learning and the emergence of culture. Here the authors outline the current state of research on social learning in mammals, focusing on anti-predator responses, foraging, space use, and vocal communication, highlighting key gaps in our collective knowledge and suggesting directions for future research. The authors consider the implications of the wide variety of sensory systems employed by mammals and highlight the diversity of social learning processes employed, including unique evidence for active teaching. The authors then discuss avenues from social learning to culture, highlighting how social learning can shape cultural diversity and evaluate opportunities for gene–culture coevolution.
Fertility Transitions
Authors: Lu Yi-Ta , Colleran Heidi
Published: May 2024

Demographic transitions in contemporary human societies have profound impacts on our social and economic lives. Across the population sciences, there are abundant empirical observations, but few causal explanations, of fertility transition. The seeming contradiction between observed fertility patterns and fitness-maximization assumptions pose a significant challenge for evolutionary theorists. This chapter explores evolutionary theories that can potentially help address this deep theoretical challenge. The authors argue that cultural evolutionary approaches can tackle aspects of fertility transitions that other approaches neglect. To bridge divides between evolutionary and non-evolutionary perspectives, the authors highlight intersections between cultural evolutionary theory and other social, economic, and political sciences.
Efficacy and safety of biologic drugs in Still's disease: a systematic review and network meta-analysis of randomized controlled trials
Authors: Kilic Berkay , Ozturk Admir , Karup Sejla , Hacioglu Ervanur , Ugurlu Serdal
Published: May 2024

Objectives

Still’s disease is a rare autoinflammatory disorder characterized by systemic inflammation, fever, rash and arthritis. The term ‘Still’s disease’ covers the paediatric subtype systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), which affects adults. Biologic drugs, including the anti-IL-1 agents anakinra, canakinumab and rilonacept and the IL-6 antagonist tocilizumab, are used in the management of Still’s disease.

Methods

We conducted a systematic review and network meta-analysis of randomized controlled trials, and the study protocol was registered in PROSPERO (CRD42023450442). MEDLINE, EMBASE and CENTRAL were screened from inception until 17 September 2023. We included patients with Still’s disease who received placebo or biologic drugs: anakinra, canakinumab, rilonacept or tocilizumab. The primary efficacy and safety outcomes were achievement of ACR50 response and occurrence of serious adverse events, respectively. The interventions were ranked using rankograms and SUCRA values.

Results

Nine trials with 430 patients were included. All biologic drugs were associated with greater odds of ACR50 response compared with placebo. There was no statistically significant association between biologic drugs and serious adverse events. The multivariate meta-analysis found no difference between biologic drugs. As per SUCRA rankings, anakinra was the most effective and safe option with respect to ACR50 response and occurrence of serious adverse events.

Conclusion

This is the first systematic review and meta-analysis to assess the efficacy and safety of biologic drugs in paediatric and adult patients with Still’s disease. Biologic drugs were effective in achieving ACR response and demonstrated a low adverse event profile in the management of Still’s disease.
From Microbes to Microbiomes: Applications for Plant Health and Sustainable Agriculture
Authors: Beattie Gwyn A. , Bayliss Kirsty L. , Jacobson Daniel A. , Broglie Richard , Burkett-Cadena Marleny , Sessitsch Angela , Kankanala Prasanna , Stein Joshua , Eversole Kellye , Lichens-Park Ann
Published: May 2024

Plant−microbe interaction research has had a transformative trajectory, from individual microbial isolate studies to comprehensive analyses of plant microbiomes within the broader phytobiome framework. Acknowledging the indispensable role of plant microbiomes in shaping plant health, agriculture, and ecosystem resilience, we underscore the urgent need for sustainable crop production strategies in the face of contemporary challenges. We discuss how the synergies between advancements in ‘omics technologies and artificial intelligence can help advance the profound potential of plant microbiomes. Furthermore, we propose a multifaceted approach encompassing translational considerations, transdisciplinary research initiatives, public-private partnerships, regulatory policy development, and pragmatic expectations for the practical application of plant microbiome knowledge across diverse agricultural landscapes. We advocate for strategic collaboration and intentional transdisciplinary efforts to unlock the benefits offered by plant microbiomes and address pressing global issues in food security. By emphasizing a nuanced understanding of plant microbiome complexities and fostering realistic expectations, we encourage the scientific community to navigate the transformative journey from discoveries in the laboratory to field applications. As companies specializing in agricultural microbes and microbiomes undergo shifts, we highlight the necessity of understanding how to approach sustainable agriculture with site-specific management solutions. While cautioning against overpromising, we underscore the excitement of exploring the many impacts of microbiome−plant interactions. We emphasize the importance of collaborative endeavors with societal partners to accelerate our collective capacity to harness the diverse and yet-to-be-discovered beneficial activities of plant microbiomes.
TIME-SERIES CLUSTERING OF RAW RECORDINGS OF 24-HOUR AMBULATORY BLOOD PRESSURE FOR RISK STRATIFICATION IN GENERAL POPULATION
Authors: Ntalianis Evangelos , Sabovcik Frantisek , Cauwenberghs Nicholas , Kuznetsova Tatiana
Published: May 2024

Objective:

24-hour ambulatory blood pressure measurements (ABPM) is the best out-of-office BP measurement used to refine cardiovascular (CV) risk stratification. Currently, only summary ABPM indexes are used in the clinical practice while the temporal characteristics of the raw BP recordings have not been explored. Therefore, in this study we employed an unsupervised machine learning (ML) algorithm suitable for multivariate time-series analysis to identify distinct BP and heart rate (HR) profiles associated with the incidence of adverse CV events.

Design and method:

In 1391 community-dwelling individuals (mean age, 46.9 years; 50.97% women), we acquired 24-hour ABPM and clinical data and collected CV events (n=399) on average 22 years later. We employed multivariate dynamic time warping and k-medoids algorithm on the raw recordings of systolic and diastolic BP and HR. To assess the clinical significance of the derived clusters, we compared the clinical characteristics and the incidence of adverse events. We validated the trained model using 24-hour ABPM obtained from external population cohort (n=1137).

Results:

The silhouette score and Dunn index showed that the optimal number of clusters was 4. Across all clusters we observed significant difference in age and sex distribution. Cluster 4 had the worst CV risk factors profiling, with higher office BP and anti-hypertensive medication intake compared to the other clusters. We observed differences in the incidence of adverse events between clusters (Figure), with cluster 1 representing the lowest risk group and cluster 4 the highest. After adjusting for traditional CV risk factors, including office systolic BP, cluster 1 had the lowest risk (HR:0.92; 95%CI:0.84-0.99; P=0.036) and cluster 4 the highest (HR:1.13; 95%CI:1.03-1.24; P=0.006) as compared to the average population risk. The analysis of the external validation cohort revealed similar ABPM patterns and clinical characteristics.

Conclusions:

Employing an unsupervised ML model on the raw ABPM recordings we identified clinically meaningful clusters associated with an increasing cumulative incidence of CV events. This ML analysis paves the way towards utilization of temporal BP and HR information and subsequently optimization of CV risk stratification.
DIAGNOSTIC PERFORMANCE OF SINGLE-LEAD ELECTROCARDIOGRAMS FOR ARTERIAL HYPERTENSION DIAGNOSIS: A MACHINE LEARNING APPROACH
Authors: Marketou Maria , Angelaki Eleni , Barmparis Georgos , Maragkoudakis Spyros , Fragkiadakis Kostantinos , Plevritaki Anthi , Kampanieris Emmanouil , Kalomoirakis Petros , Kassotakis Spyros , Kochiadakis George , Tsironis Giorgos
Published: May 2024

Objective:

Awareness and early identification of hypertension is among the most crucial components in reducing the burden of cardiovascular disease (CVD). Artificial intelligence-based analysis of electrocardiograms (ECGs) can improve diagnosis and patients’ management. ECG technology is now ubiquitous in smartwatches and other wearables and can record a single-lead ECG which is equivalent to lead I on a standard 12-lead ECG. Our aim was to develop machine learning (ML) algorithms to diagnose hypertension from single-lead ECGs.

Design and method:

We enrolled 1254 subjects (539 male, aged 60.22±12.46 years), with and without essential hypertension, and no indications of CVD. A 12-lead ECG of 10 seconds duration in resting position was performed on each subject using a digital electrocardiograph. A Random Forest (RF) was then trained on features derived only from lead I tracings.

Results:

The RF model was able to distinguish hypertensive from normotensive subjects on a hold-out test set, with 81% accuracy, AUC/ROC 0.82, sensitivity 88%, and specificity 70% (both using a threshold of 0.5) using only features from lead I. Age, body mass index, the area under the T wave divided by the QRS complex area, the area under QRS segment adjusted for BMI, the QT corrected interval, and the PQ interval, were the most important anthropometric and ECG-derived features in terms of the success of our model (Figure 1).

Conclusions:

This study demonstrates the promising potential of detecting an undiagnosed hypertension opportunistically, using a single-lead ECG. Our findings offer the opportunity to evolve innovative technologies to improve hypertension awareness at the community level.
ASSOCIATION OF CLINIC AND AMBULATORY BLOOD PRESSURE WITH MORTALITY IN PATIENTS WITH AND WITHOUT DIABETES
Authors: Lauder Lucas , Böhm Michael , De La Sierra Alejandro , Mahfoud Felix , Schwantke Igor , Haring Bernhard , Vinyoles Ernest , Gorostidi Manuel , Segura Julián , Williams Bryan , Staplin Natalie , Ruilope Luis M.
Published: May 2024

Objective:

To explore whether different levels of ambulatory and office blood pressure (BP) and different hypertension phenotypes associate with differences of risk in diabetes and no-diabetes.

Design and method:

This analysis assessed outcome data from patients with complete data included in the Spanish Ambulatory BP (ABP) Monitoring Registry. The associations between office BP, mean, daytime and nighttime ABP and the risk in patients with diabetes and no-diabetes were explored. The effects of diabetes on mortality in different hypertension phenotypes compared with normotension were studied. Analyses were done with Cox regression analyses and adjusted for demographic and clinical confounders.

Results:

A total of 59,124 patients were recruited from 223 primary care centres in Spain. The majority had an office SBP >140 mmHg (36,700 patients), 23,128 (40.6%) patients were untreated. Diabetes was diagnosed in 10,935 patients (19.2%). Cardiovascular (CV) disease was present in 2,521 patients (23.1%) with and 4,616 (10.0%) without diabetes. Twenty-four-hour mean, daytime and nighttime ABP were associated with increased risk in diabetes and no-diabetes, whereas there was no clear association for office BP. While the relative association of BP with CV death risk was similar in diabetes compared to no-diabetes (mean interaction p=0.80, daytime interaction p=0.97 and nighttime interaction p=0.32), increased event rates occurred in diabetes for all ABP monitoring parameters for CV death and all-cause death. White-coat hypertension was not associated with risk for CV death (HR 0.86; 95% CI 0.72-1.03) and slightly reduced risk for all-cause death in no-diabetes (HR 0.89; 95% CI 0.81-0.98) but without significant interaction between diabetes and no-diabetes. Sustained hypertension and masked hypertension in diabetes and no-diabetes were associated with even higher risk. There were no significant interactions in hypertensive phenotypes between diabetes and no-diabetes (interaction p=0.26) and CV death risk, while, some interaction was present for all-cause death (interaction p=0.043) and non-CV death (interaction p=0.053).

Conclusions:

Diabetes increased the risk for all-cause death, CV, and non-CV death at every level of office and ABP. Masked and sustained hypertension confer the highest risk, while white-coat hypertension appears grossly neutral without interaction of relative risk between diabetes and no-diabetes.
SYNERGIA-MOROCCO: EFFECTIVENESS OF HYPERTENSION MANAGEMENT WITH AN AMLODIPINE AND PERINDOPRIL ARGININE-BASED STRATEGY IN MOROCCO: STUDY DESIGN AND PRELIMINARY DATA
Authors: Siham El Khayat Selma , Mba Camille Maadjhou , Mbanya Armand , Mbanya Jean -CLAUDE , Benouna El Ghali Mohamed
Published: May 2024

Objective:

In Morocco, 1 in 3 adults currently live with hypertension; over 70%1 are not aware or not effectively treated. Among treated hypertensive patients, many receive monotherapy and remain uncontrolled. WHO recommends the addition of an angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker or a diuretic in patients who are uncontrolled on a calcium-channel blocker and a monthly follow-up after initiation until patients reach targets. However, there is limited evidence from real-world observational studies in Morocco on the effectiveness of this approach on blood pressure control.

This study aims to evaluate the effectiveness of an amlodipine and perindopril arginine-based strategy for 90 days in hypertensive patients previously uncontrolled on monotherapy of amlodipine.

Design and method:

This is a multicenter prospective observational study. Eighty (80) primary care physicians across Morocco will recruit about 1 600 uncontrolled hypertensive adult patients who start perindopril-arginine on top of previous amlodipine monotherapy. During the study, physicians will be free to adapt treatment per their judgement, including dose adaptations, the addition of a third drug or the use of a single pill combination (SPC) as a substitute for the free combination of amlodipine/perindopril at the same dose when patients become controlled.

The primary outcome will be the change in sitting office blood pressure between baseline and day 90. Secondary outcomes will include; the change in the blood pressure between baseline and the initiation of the SPC and between the initiation of the SPC and the end of the study, and the difference in the proportion of participants with side effects between the free combination and SPC.

Results:

The first patient was enrolled in the study on October 30, 2023. On January 10, 2024, 1 400 patients were recruited, and 760 had the 30-day follow-up visit.

Conclusions:

In Morocco, hypertension is a significant public health issue but current treatment optimisation strategies lack evidence from real-world data. The recruitments started as planned, and this will be the first real-world study from Morocco on the short-term effectiveness of treating hypertension with an amlodipine and perindopril arginine-based combination strategy on blood pressure control.
WHY HAPPENS A PROGRESSIVE DECREASE OF BLOOD PRESSURE AFTER RENAL DENERVATION
Authors: Bosch Agnes , Schmid Axel , Kannenkeril Dennis , Harazny Joanna , Ott Christian , Striepe Kristina , Guenes-altan Merve , Roth Hannah , Schiffer Mario , Uder Michael , Schmieder Roland
Published: May 2024

Objective:

Long-term follow-up data from the SYMPLICITY 3 trial (Bhatt et al, Lancet, 2022) and the Global Symplicty Register data (Mahfoud et al, JACC, 2020) show a further decrease in BP over time up to 3 years post procedure. Yet these observations lack a mechanistic explanation. A decrease in vascular resistance could possibly explain the observed phenomenon. Scanning Laser Doppler Flowmetry (SLDF) allows the non-invasive assessment of vascular resistance and capillary density by using the retinal vasculature as a mirror of the systemic circulation.

Design and method:

Retinal parameters were assessed using SLDF together with office and 24-hour ambulatory BP before and 6 as well as 12 months after renal denervation in 63 patients with treatment resistant hypertension (TRH) (NCT01687725). SLDF allows the assessment of retinal capillary flow (RCF), pulsed retinal capillary flow (systolic retinal capillary flow – diastolic retinal capillary flow) (pRCF), retinal vascular resistance, capillary area (CapA) and intercapillary distance (ICD).

Results:

Mean age of the study cohort was 60±11 years, mean BMI 30.6±4.9 kg/m2. Patients took 5.8 antihypertensive medications on average.

There was a significant reduction of systolic and diastolic 24-hour ambulatory as well office BP 6 as well as 12 months after RDN (table 1). There was no significant reduction in the number of antihypertensive medications taken between baseline and 12 months after RDN (5.8vs.5.7 antihypertensive pills, p=0.159).

Retinal vascular resistance was reduced 6 months after RDN (table 1), pRCF was reduced 6 as well as 12 months after RDN and capillary density improved 12 months after RDN.

Conclusions:

In high-risk patients with TRH endovascular RDN improved vascular resistance and reversed capillary rarefaction in the retinal circulation, a prognostic marker of further end-organ damage. The reduction of pRCF indicates a decrease of shear stress on the vascular wall by the pulsed blood flow. Increment of capillary density was observed not already 6 months, but only 12 months after RDN. We conclude that, improvement of capillary rarefaction happens slowly after RDN and requires long-term effective BP control and, that reduction in vascular resistance might explain the prolonged BP reduction after RDN.
HOME BLOOD PRESSURE DURING NIGHT-TIME SLEEP AS A BETTER TREATMENT TARGET FOR PATIENTS WITH HYPERTENSOIN: A PROOF-OF-CONCEPT RANDOMIZED CONTROLLED TRIAL
Authors: Lee Eric Kam-pui , Yip Benjamin Hk , Yan Bryan , Wong Samuel , Chung Wai -Ho , Chow Kam -Fai , Han Jing -Hao , Leung Shuk -Yun , Choi Shirley , Yu Esther , Mihailidou Anastasia , Mcmanus Richard
Published: May 2024

Objective:

Nocturnal blood pressure (BP) has been shown be a stronger predictor of cardiovascular disease and death compared to daytime, office, and 24-hour BP, the feasibility of implementing repeated measurement of nocturnal BP and treating it to target with medications has not been examined. This pilot randomized controlled trial (RCT) aimed to determine the feasibility of measuring home nocturnal BP and treating nocturnal systolic BP (SBP).

Design and method:

This RCT utilized blocked and stratified (sex/age) randomization to assign hypertensive patients in a 1:1 ratio to the control or intervention group. Participants were patients with daytime hypertension (SBP >=135mmHg) and nighttime hypertension (SBP >=120mmHg) based on a 24-hour ambulatory BP measurement (ABPM). In the intervention group, patients were instructed to measure their nocturnal BP for three days using the WatchBP home N device, measuring 3 BP readings per night during sleep (maximum possible nocturnal BP readings = 9) a week before the doctor’s visit. In the control group, patients were asked to measure their BP in the morning and evening for seven consecutive days using the same device before the consultation. Medications were adjusted every four weeks until respective BP targets (SBP <135mmHg for the control group and <120mmHg for the intervention group) were reached or until the study endpoint (6 months).

Results:

Within one year, we successfully recruited 78 patients, with a dropout rate of 5.1% (n=4). Both groups had similar baseline characteristics, including age, sex, and BP levels on ABPM. The feasibility of targeting home nocturnal BP measurements was confirmed, with patients in the intervention group providing >=6 nocturnal BP readings in 77.5% of the 160 follow-ups and had similar medication adherence to patients in the control group. At the 6-month, both groups showed similar 24-hour, daytime, and nighttime BP levels, office BP levels, lifestyle adherence, number of visits to primary care clinics, and hospitalizations.

Conclusions:

This proof-of-concept RCT demonstrates the feasibility of targeting home nocturnal BP as the primary treatment goal for patients with hypertension. A full RCT will examine whether nocturnal BP should be a primary treatment target for hypertension.
THE INTERPLAY BETWEEN SYMPATHETIC NERVOUS SYSTEM OVERACTIVITY, BLOOD PRESSURE LEVELS AND NON-ALCOHOLIC FATTY LIVER DISEASE IN HYPERTENSIVE PATIENTS
Authors: Kakouri Niki , Andrikou Ioannis , Konstantinidhs Dimitrios , Siafi Eirini , Manta Eleni , Koullias Manolis , Papageorgiou Haralampos , Grigoriou Kalliopi , Leontsinis Ioannis , Iliakis Panagiotis , Mantzouranis Emmanouil , Tsioufis Panagiotis , Tousoulis Dimitrios , Thomopoulos Costas , Dimitriadhs Kyriakos , Tsioufis Costas
Published: May 2024

Objective:

Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease and a marker of increased cardiovascular risk. The purpose of this study was to investigate the interrelations between sympathetic nervous system (SNS) tone, as assessed by microneurography, blood pressure levels and NAFLD in hypertensive subjects.

Design and method:

131 newly diagnosed untreated hypertensive patients (mean age 55±10 years, 63 males, office systolic/diastolic blood pressure 141±21/89±9 mmHg) without a history of cardiovascular disease were included in the study. NAFLD was diagnosed by liver ultrasound, and then patients were categorized into two groups according to the presence or absence of fatty liver. SNS over-activity levels were assessed by direct recording of muscle sympathetic nerve activity (MSNA), based on an established technique (microneurography).

Results:

Hypertensive subjects with NAFLD (n=79) compared to controls (n=52) were younger (53±10 vs. 57±9 years, respectively, p=0.01) and had higher body mass index (33±9 vs. 26±3 kg/m2, p<0.001). They also had statistically significant higher levels of office blood pressure (systolic/diastolic blood pressure 142±14.8 vs 140±14.6 mmHg, 90±10 vs 87±8 mmHg, respectively). Subjects with fatty liver had also higher levels of triglycerides (122±50 vs 104±43 mg/dl, p<0.04), while there was no statistically significant difference between the two groups in hemoglobin A1c, total cholesterol and glomerular filtration rate. Hypertensive subjects with NAFLD showed greater activation of the sympathetic nervous system, with increased levels of MSNA compared to the control group (45 ± 9.5 vs. 39 ± 7 bursts per minute, respectively, p<0.04). Also, according to the multiple logistic regression analysis, MSNA proved to be an independent determinant for the presence of NAFLD (OR 1.13, 95% CI 1.01-1.26, p=0.03).

Conclusions:

Higher stimulation of sympathetic nervous system, as reflected by MSNA, is significantly associated with the presence of NAFLD in hypertensive subjects, which is also related to higher office systolic blood pressure. These findings may partly explain the increased cardiovascular risk of hypertensive patients with NAFLD.
A NOVEL ELECTRO-HYDRAULIC ACOUSTIC THERAPY REDUCES BLOOD PRESSURE IN HYPERTENSIVE PATIENTS WITH CHRONIC KIDNEY DISEASE: 12-MONTH FOLLOW-UP
Authors: Wolak Talya , Lerman Amir , Glikson Michael , Sukholutsky Ivetta , Silberman Shuli , Lerman Lilach
Published: May 2024

Objective:

Arterial hypertension (HTN) coexisting with chronic kidney disease (CKD) presents a significant global healthcare challenge, with limited effective clinical interventions. Electro-Hydraulic Acoustic Therapy (eHAT), a lower-energy modality vs. lithotripsy, emerges as a promising technique for relieving ischemia and promoting tissue regeneration. We hypothesized that eHAT would reduce blood pressure (BP) and preserve renal function in patients with hypertension and CKD.

Design and method:

Twenty medically treated patients with HTN and Stage IIIa/b CKD enrolled in this prospective, single-arm study were treated over 3-weeks with six eHAT sessions (2400 shockwaves/kidney; 0.09 mJ/mm2 at 2.66Hz; NephrospecTM, Curespec, Yehud, Israel). Follow-up (FU) visits at 1, 3, 6, and 12 months involved measurements of attended and unattended office BP, ambulatory BP and estimated glomerular filtration rate (eGFR).

Results:

The treatment was well tolerated. All BP measurements strongly tended to decline over 12 months and showed a similar pattern.(Table 1, Figs. 1-3), whereas eGFR was well preserved (Table 1, Fig. 4).

Conclusions:

Conclusion. eHAT is a tolerable and safe procedure and, moreover, a 3-week regimen tends to reduce BP and preserve eGFR in patients with HTN and CKD.

Therefore, eHAT may constitute a novel, safe, and non-invasive alternative therapeutic approach in the management of HTN in the context of CKD.
NIGHTTIME BLOOD PRESSURE ASSESSED USING HOME MONITORING IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES/PREDIABETES: ASSOCIATION AND AGREEMENT WITH AMBULATORY MONITORING
Authors: Ntousopoulos Vasileios , Kollias Anastasios , Bountzona Ioanna , Destounis Antonios , Menti Ariadni , Theodosiadi Aikaterini , Kyriakoulis Konstantinos , Stergiou George
Published: May 2024

Objective:

To investigate the agreement between nighttime blood pressure (BP) measurements using home (HBPM) or ambulatory BP monitors (ABPM) in individuals with hypertension and type 2 diabetes mellitus (DM2) or prediabetes.

Design and method:

Adults with hypertension (treated or untreated) and DM2 or prediabetes underwent ABPM (measurements at 20 minutes intervals, Microlife WatchBP03) and HBPM (duplicate morning/evening measurements for 7 days, 3 nights with 3 measurements/night, Microlife WatchBP Home-N). Nighttime hypertension was defined as BP >= 120/70 mmHg (systolic/diastolic). Nighttime BP dipping was calculated as the ratio of nighttime BP decline to the daytime levels. Individuals with nighttime BP dip (systolic and/or diastolic) <10% were classified as non-dippers.

Results:

Data from 113 participants were analyzed (mean age [SD] 65±9.1 years, 67% men, body mass index 30.7±4.8 kg/m2, 84% with DM2, 22% cardiovascular disease, 94% treated hypertension). Average daytime HBPM was 129.2±13.2/73.3±7.8 mmHg and ABPM 126.7±12.1/72.5±7.4 mmHg (systolic/diastolic, p<0.01/p=NS), whilst nighttime HBPM was 115.3±13.1/63.6±7.6 mmHg and ABPM 113.9±13.4/63±7.1 mmHg (systolic/diastolic, p<0.05/p=NS). Strong correlation was observed between HBPM and ABPM levels: daytime r=0.71/0.74 and nighttime 0.86/0.78, systolic/diastolic, p<0.01)]. Good agreement was also found between ABPM and HBPM in diagnosing nighttime hypertension (81%/90%; kappa=0.55/0.70 systolic/diastolic). Among the participants, 32%/31% were classified as non-dippers (HBPM/ABPM, p=NS), with a 74% agreement (kappa=0.41) in detecting non-dippers.

Conclusions:

These preliminary findings indicate that in individuals with hypertension and DM2 or prediabetes, nighttime BP assessed by a novel home monitor is feasible and shows strong correlation and satisfactory agreement with reference ABPM in detecting nighttime hypertension and non-dipping.
MICROWAVE TISSUE DIGESTION AND FLAME ATOMIC ABSORPTION SPECTROSCOPY FOR MEASURING TISSUE SODIUM CONTENT IN HYPERTENSIVE AND CARDIOVASCULAR RISK PATIENTS
Authors: Van Duin Robert , Oppelaar Jetta J. , Heisel Annalena G.U. , Annor Ataa Akua Kromo , Wouda Rosa , Van Zuilen Kirsten , Naessens Daphne M.P. , De Vos Judith , Bakker Erik Ntp , Hagner Matthias , Conradt Frieder , Engberink Rik H. Olde , Vogt Liffert
Published: May 2024

Objective:

Skin sodium accumulation has been demonstrated in hypertensive patients and may contribute to the pathophysiology of hypertension. Various methods are available for measuring tissue sodium content. However, the accuracy and reproducibility of these methods remain unknown. Dry ashing is the most used digestion method, but is expensive, time consuming and has a risk of incomplete digestion. This study compared microwave digestion, dry ashing, and two electrolyte quantification methods for quantifying tissue sodium and potassium.

Design and method:

We compared microwave digestion (Ethos LEAN Compact Microwave Digestion System, Milestone SRL) and dry ashing (Nabertherm S27) as sample preparation methods, and flame atomic absorption spectroscopy (FAAS, Model 425 Flame Photometer, Sherwood Scientific) and inductively coupled plasma optical emission spectrometry (ICP-OES, Varian 720-ES, Varian Inc.) as electrolyte quantification methods. Skin and muscle samples were obtained from rats and mice, and human skin samples were used. Tissues biopsies were cut in three pieces and digested separately. The methods were compared using interclass correlation coefficient (ICC) and Bland-Altman analysis. The third piece of tissue was microwave-digested by another operator to test inter-operator reproducibility by calculating the ICC and absolute overall mean difference.

Results:

With microwave digestion and FAAS median (IQR) human skin concentration was 114.8 (99.2-157.0, n=12) mmol/L, confirming tissue sodium storage. When including all tissues, FAAS and ICP-OES showed high agreement for sodium (ICC 0.98, bias -0.00008 mmol/g, n=141 and potassium (ICC 0.98, bias -0.005 mmol/g, n=141). Microwave digestion and ashing showed agreement for sodium (ICC 0.93, bias -0.002 mmol/g, n=61) and potassium (ICC 0.93, bias -0.02 mmol/g, n=61). The inter-operator agreement was good for sodium (ICC 0.95, absolute mean difference (SD) 0.044 mmol/g (0.073), n=70) and potassium (ICC 0.96, absolute mean difference (SD) 0.031 mmol/g (0.032), n=70).

Conclusions:

Microwave digestion with FAAS is a reliable and consistent method for sodium and potassium trace analysis in animal and human tissues compared to ashing and ICP-OES, respectively. This method showed more quantification of cations than the most frequently reported method, representing an easier, and less time-consuming way to quantify tissue sodium in hypertension and cardiovascular research.
HYPERTENSION, UNCONTROLLED HYPERTENSION AND RESISTANT HYPERTENSION: PREVALENCE, COMORBIDITIES AND PRESCRIBED MEDICATIONS IN 228,406 ADULTS RESIDENT IN URBAN AREAS. A POPULATION-BAS
Authors: Sartorio Andrea , Romano Simone , Rigon Giulio , Albrigi Martina , Tebaldi Giacomo , Cristin Luca , Burrei Giulia , Fava Cristiano , Minuz Pietro
Published: May 2024

Objective:

Although hypertension is the leading cause of cardiovascular disease and premature death worldwide, it remains difficult to control. The prevalence of uncontrolled and resistant hypertension (RH) may be underestimated and can reach up to 50% of all hypertensive patients. The aim of this observational study was to analyze the prevalence of hypertension, uncontrolled hypertension and RH, and their associations with risk factors or diseases in a large cohort of patients referred to primary care physician.

Design and method:

In a population of 228406 adults, we only collected data from people with a diagnosis of arterial hypertension for a total of 43,526 patients. For this purpose, we used the MySQL database, run by Azalea.NET, built on the medical records of 150 General Practitioners (GPs). Patient data included sex, age, blood pressure (BP) values, number of antihypertensive drugs and presence of major cardiovascular comorbidities. We classified patients with RH as those treated with 3 different antihypertensive agents, with recorded BP greater than or equal to 140/90 mmHg, or patients taking 4 or more medications.

Results:

The prevalence of hypertension was 19.06%, that of resistant hypertension was 2.46% of the whole population and 20.85% of the hypertensive group. Thirteen thousand hundred, forty-six patients (30.20% of the hypertensive group) had uncontrolled BP (greater than or equal to 140/90 mmHg), whereas 16,577 patients did not have BP measurements done in the last 2 years (38.09% of the hypertensive group). Patients with uncontrolled BP were mainly female, used less drugs and showed a lower prevalence of all major cardiovascular comorbidities, except for diabetes. Instead, patients with RH had a significantly higher prevalence of all considered comorbidities compared to those without RH.

Conclusions:

Our results evidence that a broad number of patients with hypertension, especially those without comorbidities or with a low number of antihypertensive drugs, do not achieve adequate BP control. To improve the clinical management of these patients it is very important to increase the collaboration between GPs and clinical specialists of hypertension.
ANTIHYPERTENSIVE DRUG THERAPY AND RISK OF DEMENTIA: REAL-WORLD EVIDENCE FROM A LARGE OLD POPULATION
Authors: Rea Federico , Corrao Giovanni , Mancia Giuseppe
Published: May 2024

Objective:

Evidence exists that lowering high blood pressure reduces the risk of dementia. However, the generalizability of this evidence to very old and frail patients remains uncertain. The aim of this study was to evaluate the protective effect of adherence to antihypertensive treatment on the risk of dementia in a large and heterogeneous general population.

Design and method:

A nested case–control study was carried out by including the cohort of 215,547 patients from Lombardy (Italy), aged >=65 years, who started antihypertensive drug therapy during 2009-2012. Cases were the 13,812 patients who developed dementia or Alzheimer’s disease during follow-up (up to 2019). Up to five controls were selected for each case. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drug prescriptions. Conditional logistic regression was used to model the risk of outcome associated with adherence to antihypertensive drugs. Sensitivity analyses were performed to account for possible sources of systematic uncertainty.

Results:

The incidence of dementia showed a progressive increase with age, while the incidence of Alzheimer’s disease showed the highest incidence among patients aged 80-84 years. Progressive increase in adherence to treatment was associated with a progressive decrease in the risk of dementia. Compared to patients with very low adherence, those with high adherence exhibited a 24% risk reduction. This was also the case in each stratum of sex, age, and clinical status, including very old subjects (>=85 years) and those characterized by a very high risk of early mortality (36% at 1 year). Similar results were obtained when outcomes were decomposed, i.e. Alzheimer’s disease and other dementias were separately analysed.

Conclusions:

In elderly hypertensive patients from a general population, increased adherence to antihypertensive drugs was associated with a reduction in the risk of dementia regardless of the patients’ clinical status and age.
COMPARING BLOOD PRESSURE CONTROL TARGETS GLOBALLY: AN ANALYSIS OF THE MAY MEASUREMENT MONTH 2022 CAMPAIGN IN 60 COUNTRIES
Authors: Beaney Thomas , Kerr Gabriele , Schlaich Markus , Schutte Aletta , Stergiou George , Poulter Neil
Published: May 2024

Objective:

Many contemporary hypertension guidelines recommend controlling blood pressure (BP) to less than 130/80 mmHg in most people, but it is unclear how control rates compare globally to the hitherto ubiquitous control target of 140/90 mmHg. In this analysis, we compare global and regional BP control rates based on targets of 140/90 mmHg versus 130/80 mmHg from the latest May Measurement Month 2022 (MMM22) campaign, an opportunistic screening campaign which aims to raise awareness of BP.

Design and method:

In MMM22, adults aged 18 years or over were screened via convenience sampling in 60 countries using a single standardised protocol. Three seated BP measurements were taken, and a questionnaire was administered collecting information including demographics, co-morbidities and antihypertensive medication use. Hypertension was defined as systolic BP 140 mmHg or more, and/or diastolic BP 90 mmHg or more, based on the average of the second and third BP readings, or the taking of antihypertensive medication. Multiple imputation using chained equations was used to estimate BP readings, where missing for any participant.

Results:

A total of 765,718 participants were screened during MMM22, of whom 282,488 (36.9%) were hypertensive. Of those with hypertension 51.4% were on antihypertensive medication, of whom 52.7% were taking only a single drug. Of those on antihypertensive medication, 54.2% had BP <140/90 mmHg and 28.2% had BP <130/80 mmHg. Of all hypertensives, 27.8% had BP <140/90 mmHg and 14.5% had BP <130/80 mmHg. There were large differences between regions, ranging from 13.5% of those on medication being controlled to <130/80 mmHg in South-East Asia and Australasia, to 37.4% in Europe.

Conclusions:

MMM22 identified significant numbers of people worldwide with inadequately treated hypertension. Of those treated for hypertension, only half were controlled to <140/90 mmHg and less than one third to the stricter target of <130/80 mmHg. Most of those on antihypertensive medication were prescribed only a single drug class, highlighting the scope for achieving better control using antihypertensive drug combinations as recommended by current guidelines.
COMPUTATIONAL FLUID DYNAMIC SIMULATIONS TO ASSESS HEMODYNAMICAL SIGNIFICANCE OF FIBROMUSCULAR DYSPLASIA–RELATED RENAL ARTERY STENOSIS: A FEASIBILITY STUDY
Authors: Soliveri Luca , Stoenoiu Maria Simona , Bozzetto Michela , Meris Francesco , Robberechts Tom , Remuzzi Andrea , Caroli Anna , Persu Alexandre
Published: May 2024

Objective:

Fibromuscular dysplasia (FMD), is a potentially curable cause of renovascular hypertension occurring predominantly in women. Percutaneous angioplasty is the recommended treatment in young patients with hemodynamically significant stenosis. Unfortunately, there is currently no established non-invasive method to estimate pressure gradients and thus the hemodynamical impact of FMD-related stenosis. The aim of our study was to assess the feasibility of an image-based computational fluid dynamic (CFD) method for non-invasively assessing fractional flow reserve (FFR) and trans-stenotic pressure gradients in patients with FMD-related renal artery stenosis.

Design and method:

For each subject included in the study a 3D model was reconstructed from CT images and CFD simulations were performed using SimVascular software, as shown in Figure 1a. A steady state aorta inflow, derived from peak-systolic velocity measurements and scaled according to the vessel cross-section, was imposed. The aorta-outlet resistance was calibrated to match the pressure measurements obtained from each patient. The resistances at the end of renal arteries were calculated based on peak-systolic velocities measured by ultrasound. FFR (distal pressure/proximal pressure) and pressure gradients were assessed across each renal artery.

Results:

The analysis included 10 women, 6 with FMD-related stenosis (30-63 years, 2 focal and 4 multifocal) and 4 controls: 2 with atherosclerotic renal artery stenosis (58 and 64 years) and 2 healthy subjects (50 and 51 years). Representative examples of pressure CFD findings are shown in Figure 1b. The results of FFR and pressure gradients for each of the 10 subjects (20 arteries) are shown in Table 1. A wide range of FFRs (0.57 to >0.95) and pressure gradients (up to 73 mmHg) was observed, with values consistent with visually estimated severity of lesions.

Conclusions:

The proposed CT-to-CFD pipeline represents a promising non-invasive approach to assess the hemodynamical significance of FMD-related artery stenosis and may thus inform on the need for revascularization. Future studies involving catheter-based pressure gradient measurements are needed to validate the proposed pipeline. Besides pressure gradients, FFR measurements may represent an interesting parameter to evaluate the need for revascularization, as was shown in coronary arteries.
HYPERTENSION MANAGEMENT OF CKD PATIENTS REFERRED TO HYPERTENSION EXCELLENCE CENTRES IN 27 COUNTRIES; ON BEHALF OF THE ESH HYPERTENSION AND KIDNEY WORKING GROUP
Authors: Halimi Jean -MICHEL , Sarafidis Pantelis , Persu Alexandre , Kurtz Reinhold , Vogt Liffert
Published: May 2024

Objective:

Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear and may vary across countries. Our aim was to identify unmet needs and heterogeneity of management in this population of patients in Europe and the Midlle-East through our network of European Society of Hypertension (ESH) Excellence Centers.

Design and method:

A survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate pre-existing CKD management quality and data for their management are reported here.

Results:

Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 (75.0%).

ESH-ECs reported that 28% (median, interquartile range: 15-50%) had pre-existing CKD, of whom 10% (5-30%) were previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine Albumin-Creatinine Ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively.

The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates for SGLT2 inhibitors (27.5% (20-40%) vs 15% (10-25), p=0.003), GLP1-RA (10% (10-20%) vs 5% (5-10%), p=0.003) and mineralocorticoid receptor antagonists (20% (10-30%) vs 15% (10-20%), p=0.05) use were greater as compared to ESH-ECs without nephrologist participation.

The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across centres in Europe countries and in the Middle-East.

Conclusions:

Our results indicate deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across centres. This information can be used to build specific programs to improve care in hypertensives with CKD.