bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIFFERENTIAL EFFECTS OF RENAL DENERVATION ON SKIN AND MUSCLE SYMPATHETIC NERVE TRAFFIC IN RESISTANT AND UNCONTROLLED HYPERTENSION
Authors: Vanoli Jennifer , Dell’Oro Raffaella , Trevano Fosca Quarti , Cuspidi Cesare , Grassi Guido 
Published: June 2023

Objective:
Renal denervation (RDN) exerts profound sympathoinhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behaviour.

Design and method:
In 14 patients with resistant hypertension (RHT, age 58.3 ± 2.2 yrs, mean ± SEM) we recorded via the microneurographic technique muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) before, 1 month and 3 months following RDN. Measurements included clinic blood pressure (BP) and heart rate (HR), 24-hour BP and HR, together with routine laboratory and echocardiographic variables. Ten age-matched RHT patients who did not undergo RDN served as controls.

Results:
MSNA, but not SSNA, was markedky higher in RHT. RDN caused a significant reduction in MSNA 1 month following RDN, the reduction becoming greater for magnitude after 3 months (from 68.1 ± 2.5 to 64.8 ± 2.4 and 63.1 ± 2.6 bursts/100heartbeats, P < 0.05). This effect was not accompanied by any significant change in SSNA (from 13.1 ± 0.5 to 13.4 ± 0.6 and 13.3 ± 0.4 bursts/minute, P = NS). No quantitative and, in some cases, no qualitative relationship was found between the BP and the MSNA reduction induced by RDN. No significant change in the various sympathetic markers was detected in the control group who did not undergo RDN and followed for a 3 month observation.

Conclusions:
These data provide the first evidence that RDN exerts heterogeneous effects on sympathetic cardiovascular drive, inducing a marked reduction in MSNA but not in SSNA, which appears to be within the normal range in this condition. These effects may depend on the different reflex modulation regulating neuroadrenergic drive in these cardiovascular districts.
CARDIORESPIRATORY FITNESS AND STROKE INCIDENCE IN HYPERTENSIVE PATIENTS
Authors: Kokkinos Peter , Pittaras Andreas , Doumas Michalis , Samuel Immanuel Babu , Howard Dominique , Faselis Angelique , Gorsuch Balinda , Myers Jonathan 
Published: June 2023

Objective:
Stroke incidence is significantly higher in hypertensive patients compared to normotensive subjects. Cardiorespiratory fitness (CRF) is associated with a more favorable cardiovascular health. The CRF-stroke incidence association in hypertensive patients has not been fully explored. Thus, the objective of the current study was to evaluate the association between CRF assessed objectively by a standardized exercise test, and stroke incidence in hypertensive patients.

Design and method:
From 1999 to 2020, we identified 460,172 hypertensive patients (mean age: 63.1 ± 8.7 years) with a normal response to an exercise treadmill test (ETT) and no prior history of stroke. We established five CRF categories based on age-stratified quintiles of peak metabolic equivalents (MET) achieved: Least-Fit (4.5 ± 1.2 METs; n = 106,620); Low-Fit (6.9 ± 1.1; n = 120,327); Moderate-Fit (8.3 ± 1.2 METs; n = 89,748); Fit (10.3 ± 0.9 METs; n = 107,323); and High-Fit (13.1 ± 1.6 METs; n = 36,154). A multivariable Cox proportional hazards model was constructed to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of stroke across CRF categories. The model was adjusted for age, resting blood pressure, gender, race, coronary artery disease, smoking status, chronic kidney disease, atrial fibrillation, other cardiac risk factors, and medications. The Least-fit category was used as the reference group.

Results:
During follow-up (median = 10.6 years; 4,955,021 person-years), 11,868 individuals had a stroke (2.4 events per 1,000 person-years). The risk for stroke was 8% lower for each 1-MET increase in exercise capacity (HR = 0.92, CI: 0.91 - 0.93; p < 0.001). The risk across fitness categories, declined progressively with increased CRF and was by 15% for the Least-Fit individuals (HR = 0.85; CI: 0.81 - 0.89), approximately 30% to 40% for Moderate-fit and Fit individuals, and 45% lower (HR = 0.55; CI: 0.50 - 0.60; p < 0.001) for High-Fit individuals.

Conclusions:
Increased CRF was inversely related to stroke incidence in hypertensive patients. The association was independent and graded. These finding support the concept that health care professional should encourage patients to engage in habitual physical activity of moderate intensity and progressively aim to meet the physical activity guidelines proposed by authorities.
HIGH SODIUM INTAKE - EFFECTS ON AFFERENT RENAL NERVE ACTIVITY
Authors: Rodionova Kristina , Ditting Tilmann , Linz Peter , Hilgers Karl F. , Ott Christian , Schmieder Roland E. , Schiffer Mario , Amann Kerstin , Veelken Roland 
Published: June 2023

Objective:
Previous work of ours suggests that the sensitivity of renal afferent neurons is decreased under pathological conditions. Here we tested the hypothesis that pathologically decreased sensitivity of renal afferent neurons due to high salt diet is normalized after renal denervation.

Design and method:
Six male Sprague Dawley (SD) rats were put on high salt diet (HS; 8% NaCl) for 10 days. In another group of 18 rats on high salt diet (HS) left kidneys were denervated (DNX) 7 days prior to examination. 17 rats on standard diet with and without DNX were used as controls. Dorsal root ganglion neurons with renal afferents were investigated in primary neuronal cell culture using current clamp mode to assess action potential generation during current injection. Neurons were characterized as tonic highly active (less than 5 action potentials, AP) and phasic less active neurons (more than 5 AP upon stimulation).

Results:
In renal neurons from rats on HS the relation of tonic to phasic neurons shifted towards less active phasic units (62% tonic neurons in control vs. 42% on HS, p < 0.05, z-test). Denervation (DNX) of the left kidney in rats on high salt diet (HS-DNX) led to a recovery of afferent renal DRG neurons remaining vital after denervation. They regained their electrophysiological property of mainly tonic firing (42% tonic neurons in HS vs. 71% HS-DNX, p < 0.05, z-test).

Conclusions:
In rats on high salt diet the proportion of highly active tonic neurons with renal afferents decreased at the expense of less active phasic neurons. This HS effect could be abolished by DNX. Hence the input of afferent renal pathways to the central nervous system was normalized form the first neuron onward to the brain.
PATIENT'S PERSPECTIVES ON TREATMENT ADHERENCE IN HYPERTENSION: RESULTS OF AN ESH SURVEY IN POLAND
Authors: Prejbisz Aleksander , Dobrowolski Piotr , Burnier Michel , Azizi Michel , Cornelissen Veronique , Cunha Vitoria , Gupta Pankaj , Persu Alexandre , Vaclavik Jan , Versmissen Jorie , Kreutz Reinhold , Januszewicz Andrzej 
Published: June 2023

Objective:
The ESH Working group on Lifestyle, Cardiovascular Therapy and Adherence has developed a web-based questionnaire in different languages to investigate patients’ perspectives on hypertension and treatment adherence. The objective of this survey was to decipher patients’ perception of motivations for and barriers to treatment adherence in hypertension.

Design and method:
In Poland, a dedicated recruitment strategy has been developed to invite adult patients to complete the survey via targeted information on patient group websites and social media only. In other countries a direct communication from healthcare professional to patient was preferred. Data were collected from May to September 2022. Descriptive statistics were used for analyses.

Results:
We included 1359 participants (962 men (71%); 67% were hypertensive for >5 years, 88% were treated with antihypertensive medications for at least 3 months). The total median number of tablets taken every day was 4 of which 2 were antihypertensive medications. Antihypertensive medications were prescribed most frequently once (56%) or twice (36%) daily. On a 10-point Likert scale, participants reported a modest impact of hypertension on their quality of life (4), social and family life (2). The median level of stress was 5 out of 10 points. Ninety two of patients performed self-blood pressure measurements at home, most frequently every day (34%) and a few times a week (28%). Self-reported adherence to treatment was perfect in 43% of patients, very high in 30% and intermediate-low in 26% of patients. Main reasons for low adherence to medication included forgetfulness (41%), improvement in well-being (15%), side effects (14%) and running out of medications (11%). The most useful approaches to support adherence reported by participants were cheaper and single-pill combinations as well as leaflets providing better information on treatment. Information provided by physicians on hypertension and its treatment was considered sufficient only for 54% of patients.

Conclusions:
In a web-based ESH survey in Poland, over 1,300 participants reported a modest impact of hypertension on their quality of life and a moderate level of anxiety, usually non-intentional non-adherence to prescribed antihypertensive medications, and the necessity to improve the information provided to them.
URBAN-RURAL DISPARITIES IN THE PREVALENCE AND MANAGEMENT OF ATRIAL FIBRILLATION IN ELDERLY CHINESE
Authors: Zhang Wei , Chen Yi , Hu Lei-Xiao , Xia Jia-Hui , Ye Xiao-Fei , Wang Wen-Yuewang , Wang Xin-Yu , Li Yan , Wang Ji-Guang 
Published: June 2023

Objective:
Atrial fibrillation is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese.

Design and method:
Consecutive participants aged above 65 years attending outpatient clinics were enrolled for atrial fibrillation screening using handheld single-lead electrocardiogram (ECG, BP7900, Omron Healthcare, Kyoto, Japan and Kardia Mobile®, Mountain View, California, USA) from April 2017 to December 2022 (NCT04111419). Each ECG rhythm strip was reviewed form the research team. Atrial fibrillation or uninterpretable single-lead ECGs were referred for 12-lead ECG. Blood pressure was measured 3 times consecutively with a 30-60 seconds interval using an automated oscillometric blood pressure monitor (HEM-9200T; Omron Healthcare, Kyoto, Japan).

Results:
The mean age of the 29,166 participants was 72.2±5.8 years, and 54.6% were women. The overall prevalence of atrial fibrillation was 4.6% (n = 1347). Atrial fibrillation was more prevalent in 7073 rural than 22093 urban participants (5.6% vs. 4.3%, P<0.0001). Multivariate logistic regression analysis identified that overweight/obesity (odds ratio [OR], 1.35; 95% confidence interval [CI] 1.17 to 1.54) in urban areas, whereas current smoking (OR, 1.62; 95% CI 1.20 to 2.17) and alcohol consumption (OR, 1.42; 95% CI 1.04 to 1.93) in rural areas were specific risk factors for prevalent atrial fibrillation. In patients with known atrial fibrillation in urban (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received atrial fibrillation treatment (P<0.0001), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.047). Similar proportions of atrial fibrillation patients in urban and rural areas had concomitant hypertension (78.1%). However, in patients with known atrial fibrillation and treated hypertension, systolic/diastolic blood pressure was significantly (P< = 0.01) higher in rural (n = 475, 140.0/83.9 mmHg) than urban areas (n = 222, 135.7/79.0 mmHg).

Conclusions:
In China, there are urban-rural disparities in atrial fibrillation in the elderly, with a higher prevalence and worse management in rural than urban areas.
THE INFLUENCE OF HYPERTENSION ON HEART FAILURE'S PHENOTYPES IN PATIENTS WITH HEART FAILURE AND ATRIAL FIBRILLATION, IN COMPARISON TO PATIENTS WITH HEART FAILURE AND SINUS RHYTHM
Authors: (Pogacean) Manuela-Claudia Lacatusu , German-Sallo Marta , Tatar Maria Cristina 
Published: June 2023

Objective:
Atrial fibrillation is being characterised as both an etiological factor and a consequence for developing heart failure, while it does the same for the latter.
Our aim was to identify whether and in which way, the presence of hypertension influences the development of the three phenotypes of heart failure in patients with heart failure and atrial fibrillation, as well as in patients with heart failure alone.

Design and method:
We analysed 194 patients: 97 with heart failure and atrial fibrillation (group A) and 97 patients with heart failure in sinus rhythm (group B), randomly selected from 2019 to 2021. The phenotypes of heart failure were selected according to 2021 European Society of Cardiology Guidelines: patients with heart failure with reduced ejection fraction (1), with mildly reduced ejection fraction (2) and with preserved ejection fraction (3).

Results:
In patients belonging to A1 group (n = 44) the result was that hypertension has not played a significant role in developing this phenotype (p = 0.1347), in comparison to patients in B1 group (n = 30), where the association between hypertension and heart failure with reduced ejection fraction was statistically significant (p = 0.0263). What is more, patients in A2 group (n = 14), as well as those in B2 group (n = 24), were not associated with the presence of hypertension (p = 0.4686, respectively p = 0.5638). As well as the latter, hypertension did not influence the development of heart failure with preserved ejection fraction in both groups.

Conclusions:
Taking into consideration that hypertension illustrates a common aetiology for both pathologies mentioned above, we discovered that hypertension's presence influenced more the heart failure in sinus rhythm group, concluding that atrial fibrillation associated with heart failure did not pose an additive risk factor for hypertension developing. In addition, regarding the phenotypes, it was heart failure with a reduced ejection fraction that was influenced by hypertension. Further researches will improve the comprehensive relationship between hypertension, atrial fibrillation and heart failure, leading towards better management strategies.
ASSOCIATION OF G894T NOS3 GENE POLYMORPHISM WITH ATRIAL FIBRILLATION IN PATIENTS WITH ARTERIAL HYPERTENSION IN UZBEK POPULATION
Authors: Radjabova Guliruh , Abdullayeva Guzal , Pulatova Muazzam , Sherbadalova Nigora , Zakirova Dilorom , Ibragimova Iroda , Shukurova Dilyafruz , Mashkhurova Zarina , Abdullayev Alisher 
Published: June 2023

Objective:
To estimate influence of G894T polymorphism of NOS3 gene on risk of developing AF with AH in Uzbekistan.

Design and method:
Study included 206 patients with AH I–III degree (JSC/JSC, 2018) of both sexes. Mean age of patients was 58.82 ± 11.91 years, the mean duration of hypertension was 10.9 ± 7.2 years. To verify AF, ECG Holter monitoring was performed using a Cardiospy monitor. Genotyping of G894T polymorphism of the NOS3 gene was performed using real-time PCR using gene-specific primers of allele-specific probes, followed by fluorescence detection of corresponding alleles. Results of all studies were considered statistically significant at p<0.05

Results:
Relationship between G894T polymorphism of NOS3 gene and risk of developing AF, patients were divided into two groups: cases, n = 91 - with AF and controls, n = 115 - without AF. Among cases, following distribution of genotypes and alleles of G894T polymorphism of the NOS3 gene was revealed: GG genotype - determined in 52.7%, GT genotype - in 45.1%, TT genotype - 2.2%, p = 0.000. Allelic distribution showed predominance of carriage of the G allele: G allele - 75.3%, T allele - 24.7%, p = 0.000. Among controls, allelic distribution was with significant prevalence of the G allele: G allele in 75.7%, T allele in 24.3%, respectively, Xi = 119.035, p = 0. 000. Ratio of GG:GT:TT - genotypes was as follows: 60.0%: 31.3%: 8.7%, Xi = 68.426, p = 0.000.
An analysis revealed protective effect of G allele G894T gene polymorphism on risk of developing AF with AH. Based on general model of inheritance, protective effect of GG genotype on risk of developing AF in hypertensive patients was found: general model of inheritance demonstrated significant accumulation of GG genotype among controls 60.0% (Xi2 = 6.72 P = 0.03; OR = 0.74, 95% CI 0.43-1.30), while GT genotype was less common in 31.3% and the TT genotype is even rarer in - 8.7%. Whereas in cases GG and GT genotypes were found in same ratio: 52.7%: 45.1%, respectively.

Conclusions:
Results obtained indicate significantly greater accumulation of GG genotype G894T gene polymorphism among AH without AF. Carriage of GG genotype G894T gene polymorphism is associated with low risk of developing AF with AH.
PREDICTION OF CORONARY ARTERY DISEASE USING URINARY PROTEOMICS
Authors: Wei Dongmei , Melgare Jesus D. , Aelst Lucas van , Vanassche Thomas , Verhamme Peter , Janssens Stefan , Peter Karlheinz , Zhang Zhen-Yu 
Published: June 2023

Objective:
Coronary artery disease (CAD) is multifactorial, caused by complex pathophysiology, and contributes to a high burden of mortality worldwide. Urinary proteomic analyses may help to identify predictive biomarkers and provide insights into the pathogenesis of CAD.

Design and method:
Urinary proteome was analyzed in 965 participants using capillary electrophoresis coupled with mass spectrometry. A proteomic classifier was developed in a discovery cohort with 36 individuals with CAD and 36 matched controls using the support vector machine. The classifier was tested in a validation cohort with 115 individuals who progressed to CAD and 778 controls and compared with a previously developed CAD-associated classifier, ACSP75. The Framingham risk score was available in 737 participants. Bioinformatics analysis was performed based on the CAD-associated peptides.

Results:
The novel proteomic classifier was comprised of 160 urinary peptides, mainly related to collagen turnover, lipid metabolism, and inflammation. In the validation cohort, the classifier provided an AUC of 0.82 (95% CI: 0.78-0.87) for the CAD prediction in 8 years, superior to ACSP75 (AUC: 0.53, 95% CI: 0.47-0.60). On top of ACSP75, the addition of the novel classifier improved the AUC to 0.84 (95% CI: 0.80-0.89). In a multivariable Cox model, a 1-SD increment in the novel classifier was associated with CAD (HR: 1.54, 95% CI: 1.26-1.89, P<0.0001) higher risk of CAD. The new classifier further improved the risk reclassification of CAD on top of the Framingham risk score (net reclassification index: 0.61, 95% CI: 0.25-0.95, P = 0.001).

Conclusions:
A novel urinary proteomic classifier related to collagen metabolism, lipids, and inflammation showed potential for the risk prediction of CAD. Urinary proteome provides an alternative approach to personalized prevention.
ASSOCIATIONS OF SERUM BIOMARKERS WITH BLOOD PRESSURE IN EX-PRETERM CHILDREN AND ADOLESCENTS
Authors: Chainoglou Athanasia , Sarafidis Kosmas , Taparkou Anna , Farmaki Evangelia , Chrysaidou Katerina , Gidaris Dimos , Kollios Konstantinos , Kotsis Vasilios , Stabouli Stella 
Published: June 2023

Objective:
Preterm birth is considered a risk factor for the development of hypertension throughout life course. The aims of the present study were to assess the levels of serum biomarkers in ex-preterm children and adolescents compared to healthy controls and to examine for associations with office, ambulatory BP parameters, and pulse wave velocity.

Design and method:
The study population included 52 preterm and 26 term born children and adolescents who underwent office, ambulatory BP monitoring, and assessment of pulse wave velocity. Serum biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-2, -9 (MMP-2, -9) were measured using double-antibody sandwich enzyme-linked Immunosorbent assay.

Results:
Thirty-five % of the study population presented office hypertension, 38.5% of the ex-preterm and 28% of the term children. Seventeen % of the ex-preterm group presented ABP hypertension. None of the controls had ABP hypertension. Half of the ex-preterm children had white-coat hypertension. Serum NGAL and MMP-2 and -9 levels did not differ between ex-preterm and term groups. NGAL and MMP-9 presented significant correlations with office systolic BP z score (r = 0.33, p<0.005, and r = 0.30, p<0.05, respectively) and day systolic BP z score (r = 0.29, p<0.01, and r = 0.23, p<0.05, respectively). The above associations were also observed in the ex-preterm, but not in the term group. There was no association between any biomarker and PWV. In univariate analysis NGAL presented significant correlations with office (B = 0.009, 95%CI 0.001-0.017, p<0.05) and day systolic BP z-score (B = 0.009, 95%CI 0.001-0.017, p< 0.05) in the ex-preterm group after adjustment for age, sex, birth weight and gestational age. The receiver operating characteristic (ROC) curve analysis showed that NGAL predicted hypertension in ex-preterm children with area under the curve (AUC) 0.713, 95% CI 0.57-0.85, p = 0.010.

Conclusions:
In ex-preterm children and adolescents NGAL and MMP-9 presented significant associations with systolic BP. The associations for NGAL persisted after adjustment for birth parameters, age and sex suggesting that NGAL should be further investigated as it could serve as early biomarker of hypertension evolution in ex-preterm children and adolescents.
BIOFLUID SPECIFICITY OF LONG NON-CODING RNA PROFILE IN HYPERTENSION: RELEVANCE OF EXOSOMAL FRACTION
Authors: Martinez-Arroyo Olga , Ortega Ana , Riffo-Campos Angela L. , Perez-Hernandez Javier , Flores-Chova Ana , Redon Josep , Cortés Raquel 
Published: June 2023

Objective:
Non-coding RNA (ncRNA)-mediated targeting of various genes regulates the molecular mechanisms of the pathogenesis of hypertension (HTN). However, very few circulating long ncRNAs (lncRNAs) have been reported to be altered in essential HTN. The aim of this study was to identify simultaneously the lncRNA profiles in circulating plasma and packaged them into exosomes associated with UAE in HTN using deep sequencing technology. We also assessed the effect of the biofluid origin on lncRNA signature and regulated pathways.

Design and method:
In a cohort of hypertensive patients with (n = 22) or without urinary albumin excretion (UAE) (n = 26), we analyzed by next generation sequencing the lncRNA profile associated to UAE. Then, long Non-Coding RNA target predictions and molecular pathways analyses were performed through GO terms and KEGG pathways.

Results:
Plasma exosomes showed higher diversity and fold change of lncRNAs than plasma, and low transcript overlapping was found between the two biofluids. The majority of unique differentially expressed lncRNA in the exosome fraction were downregulated (71%) in albuminuric patients and 61% in plasma samples. In addition, in plasma samples only 40% of statistically significant transcripts had a log2 fod change higher or equal to 2 or lower or equal to -2, compared with 100% top lncRNAs in exosomal fraction. Enrichment analysis identified different biological pathways regulated in plasma or exosome fraction, which were implicated in fatty acid metabolism, extracellular matrix, and mechanisms of sorting ncRNAs into exosomes, while plasma pathways were implicated in genome reorganization, interference with RNA polymerase, and as scaffolds for assembling transcriptional regulators.

Conclusions:
Our study found a biofluid specific lncRNA profile associated with albuminuria, with higher diversity in exosomal fraction, which identifies several potential targets that may be utilized to study mechanisms of albuminuria and cardiovascular damage.