bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANALYSIS OF THE CONTRIBUTION OF GENES HP, ACE, HPSE1, MTHFR AND HFE TO THE DEVELOPMENT OF HEART FAILURE
Authors: Silva Pedro , Aguiar Laura , Gaspar Marcos , Falcão Luís , Bicho Manuel , Inácio Ângela 
Published: June 2023

Objective:
Heart Failure (HF) is a clinical syndrome characterised by typical symptoms, associated with a cardiac incapacity of pumping blood. Although there have been improvements in treating HF, this disease still has a high mortality rate. Genes HP, ACE, HPSE1, MTHFR, and HFE are involved in various events and regulatory mechanisms associated with the disease such as the functionality of Haptoglobin, the activity of ACE and Heparanase enzymes and the metabolisms of Folic Acid and Iron.
The purpose of this study is to investigate the contribution of the variants Hp1/2 (HP), I/D (ACE), rs4693608 (HPSE1), C677T (MTHFR), H63D and C282Y (HFE) to the development of HF individually or in epistasis.

Design and method:
Genotype data previously obtained in 143 HF patients and 246 healthy individuals was used to carry out analysis. The analysis of the data was performed with SPSS software. The association between genotypes and alleles was tested by Chi-Square or Fisher tests. Odds Ratios were calculated as well as the corresponding confidence intervals.

Results:
We have observed a higher risk for developing HF in the presence of: 1) the T allele [OR (IC, 95) = 2,932] and CT genotype [OR (IC, 95) = 3,618] of the C677T polymorphism; 2) epistasis between II and YY genotypes of the I/D and C282Y polymorphisms [OR (IC, 95) = 5,191]; 3) epistasis between II and DD genotypes of the I/D and H63D polymorphisms [OR (IC, 95) = 6,626]; 4) epistasis between the 2 and C alleles of HP gene and C677T polymorphism [OR (IC, 95) = 4,351]; 5) epistasis between the C and A alleles of the C677T and rs4693608 polymorphisms [OR (IC, 95) = 6,804]. A protective effect was observed for the CC genotype of the C677T polymorphism [OR (IC, 95) = 0,341]; between the D allele of the I/D variation and the Y [OR (IC, 95) = 0,233] and D [OR (IC, 95) = 0,279] alleles of the C282Y and H63D polymorphisms, respectively.

Conclusions:
We have concluded that HP, ACE, HPSE1, MTHFR, and HFE genes contribute to the susceptibility of developing HF individually or in epistasis.
CLINICAL AND ECHOCARDIOGRAPHIC DIVERSITY ASSOCIATED WITH PHYSICAL FITNESS: THE PROJECT BASELINE HEALTH STUDY
Authors: Cauwenberghs Nicholas , Daubert Melissa A. , Salerno Michael , Haddad Francois , Kuznetsova Tatiana , Douglas Pamela S. 
Published: June 2023

Objective:
Risk factors and subclinical changes in cardiac structure or function may indicate the development of heart failure (HF). However, different HF risk factors and echocardiographic phenotypes may be associated with different risk for HF progression. In community-dwelling individuals, we determined the heterogeneity in risk factor and echocardiographic profiles and assessed its association with physical performance metrics.

Design and method:
2036 participants (50.4 ± 17.0 years, 56.2% women, 37.8% hypertensive) without symptomatic HF underwent echocardiography and physical performance testing including 6-minute walk (6MWT) and treadmill exercise test. Echocardiographic profiles of left and right heart remodeling and dysfunction were defined using sex-specific internal reference values. The cohort was subdivided based on presence (+) or absence (-) of HF risk factors and echocardiographic abnormalities (Echo-/RF-, Echo-/RF+, Echo+/RF-, Echo+/RF+). Participants in Echo+/RF+ were stratified according to the most severe echocardiographic abnormality present (reduced ejection fraction (EF), left ventricular (LV) hypertrophy/diastolic dysfunction or other echo abnormalities). Associations between Echo/RF subgroups and physical performance metrics were assessed.

Results:
Prevalence was: 35.3% for Echo-/RF-, 39.3% for Echo-/RF+, 4.7% for Echo+/RF- and 20.6% for Echo+/RF+. Between the individuals with echocardiographic abnormalities (Echo+), we observed a large diversity in echocardiographic profiles. Yet, participants with echocardiographic abnormalities but no HF risk factors (Echo+/RF-, 18.6% of Echo+) predominantly had echo abnormalities other than LV diastolic dysfunction, hypertrophy and reduced EF, while their physical performance was similar to people with normal echocardiography without HF risk factors (Echo-/RF-). In contrast, Echo+ participants with risk factors (Echo+/RF+) were characterized by LV diastolic dysfunction, hypertrophy or reduced EF, which all related to lower 6MWT distance and lower exercise capacity (Figure panel A). The presence of both HF risk factors and LV dysfunction/hypertrophy was associated with worst physical performance.

Conclusions:
Subclinical echocardiographic abnormalities suggest HF pathogenesis, but the type of echo abnormality and presence of HF risk factors should be considered to distinguish adverse changes from adaptive (benign) remodeling and further stratify HF risk. Concomitant presence of risk factors and LV dysfunction/hypertrophy may identify individuals with poor exercise capacity and thus at high risk for progression towards overt HF (Figure panel B).
CARDIOVASCULAR HAEMODYNAMICS IN TWO GROUPS OF HYPERTENSION: RESISTANT HYPERTENSION AND MALIGNANT HYPERTENSION
Authors: Alsharari Reem , Thomas G. Neil , Lip Gregory , Shantsila Alena 
Published: June 2023

Objective:
Patients with malignant and resistant hypertension have poor prognosis and high rate of complications. Understanding the pathophysiological mechanisms underlying the severe forms of hypertension and their relationship to cardiac haemodynamics and vascular function is crucial to the management of blood pressure (BP).

Design and method:
In a cross-sectional comparison, of age and sex matched groups, we assessed left ventricle (LV) strain function using speckle tracking echocardiography (STE), (Figure 1), endothelial function using flow mediated dilation (FMD) and arterial stiffness using pulse wave velocity (PWV) in patients with confirmed RH (n = 23), treated malignant hypertension (MHT) (n = 54) and normotensive control (NC) (n = 23).

Results:
Characteristics pf study population are provided in table 1. Both hypertension groups showed markedly reduced global longitudinal strain (GLS) vs. NC (MHT -15.6% {-17 – -15}, RH -17.7% {-20 – -16} vs. NC -25% {-28 – -22]}, all p < 0.001) with GLS being lower in MHT vs. RH (p < 0.05). Both hypertensive groups also showed preserved but lower global circumferential strain (GCS) vs. NC (MHT -30.7% ± 4.7, RH -30.0% ± 4.3 vs. NC -34.3% ± 4.5, p = 0.004 and p = 0.03, respectively). FMD was markedly attenuated in both hypertensive groups (RH: 5.5 % ±2.6 and MHT: 5.9 % ± 2.6 vs. NC: 9.9 % ± 2.5%, p < 0.001). Carotid-femoral pulse wave velocity (cfPWV) was increased in both hypertensives compared to NC (p < 0.05). Subendocardial viability ratio (SEVR) and total peripheral resistance (TPR) were decreased in MHT compared to NC (p = 0.01 and p = 0.002, respectively). After adjustment for potential confounders (presence of hypertension, duration of hypertension, age, BMI, and eGFR), presence of MHT (p < 0.001), presence of RH (p < 0.001) and age (p = 0.01) showed significant negative association with GLS, whereas eGFR showed significant positive association with GLS (p = 0.03), (Table 2).

Conclusions:
This is the first cardio-vascular assessment of two extreme phenotypes of hypertension. Patients with MHT and RH had persistent impaired cardiac remodelling independent of preserved EF, impaired endothelial function and elevated arterial stiffness. Early cardiac remodelling marker, GLS was more impaired in MHT patients.
THE RISKS AND BENEFITS OF RENAL ARTERY STENTING IN FIBROMUSCULAR DYSPLASIA. LESSONS FROM ARCADIA-POL STUDY
Authors: Kadziela Jacek , Jozwik-Plebanek Katarzyna , Pappaccogli Marco , Niepen Patricia Van Der , Prejbisz Aleksander , Dobrowolski Piotr , Michalowska Ilona , Talarowska Paulina , Warchol-Celinska Ewa , Strzyczynski Lukasz , Krekora Jan , Andziak Piotr , Maciag Rafal , Sterlinski Ignacy , Witkowski Adam , Januszewicz Andrzej , Adlam David , Januszewicz Magdalena , Persu Alexandre 
Published: June 2023

Objective:
Percutaneous transluminal angioplasty (PTA) is the recommended revascularization strategy in patients with renal artery stenosis (RAS) caused by fibromuscular dysplasia (FMD), limiting stenting to complications management. However this recommendation is based on cases reports and small series.
The main aim of the study was to retrospectively analyze immediate and long-term results of renal stenting and PTA in FMD patients. The second aim was to evaluate the results of stenting as support of renal artery aneurysm (RAA) closure.

Design and method:
The study group consisted of 58 patients percutaneously treated due to significant RAS (70 arteries) and 9 patients (10 RAAs) with a history of stent implantation before aneurysm embolization, derived from 343 ARCADIA-POL registry patients. PTA was performed as initial treatment in 61 arteries (PTA-group), whereas primary stenting was done in 9 arteries (STENT-group). Stent-related complications(SRC) were defined as: in-stent restenosis (>50%) or occlusion (ISR/O); stent fracture; stent underexpansion (SU) or migration.

Results:
In PTA-group, the first restenosis rate was 50.8%. Subsequently, 22 arteries underwent a second procedure: re-PTA(12 arteries) or stent implantation(10 arteries) . The incidence of recurrent restenosis after re-PTA was 41.7%. In the 10 arteries initially treated with PTA that underwent stenting for restenosis, complications occurred in 7 of them (70%), including 2 SUs and 5 ISR/Os .
In STENT-group, SU occurred in one case (11.1%) and in-stent restenosis in 33.3% (3 of 9 stents).
In combined analysis, SRC occurred following 11/19 stenting procedures (57.9%) including 3 periprocedural (SUs) and 8 late complications (ISR/Os). Finally, despite several subsequent revascularization attempts, 4 of 19 (21%) stented arteries were totally occluded and one remained significantly stenosed at follow-up imaging (Figure).
In contrast to FMD-RAS procedures, there was only one intraprocedural complication (partial stent migration) and no late SRC in RAA patients.

Conclusions:
Renal artery stenting in FMD provides modest benefit in terms of restenosis prevention but poses high risk of immediate and late complications, including stent occlusion. Our study supports recommendations limiting stenting to the management of complications. In contrast, renal artery stenting in FMD RAA closure is associated with favorable long-term outcomes.
A PROSPECTIVE MULTICENTER RANDOMIZED SHAM-CONTROLLED CLINICAL TRIAL TO EVALUATE THE SAFETY AND EFFECTIVENESS OF NETRODTM RADIOFREQUENCY RENAL DENERVATION SYSTEM FOR HYPERTENSION
Authors: Gao Fei , Li Yue Ping , Zhou Yu Jie 
Published: June 2023

Objective:
To evaluate the safety and effectiveness of a novel basket-like six-electrode radiofrequency renal denervation (RDN) system (NetrodTM RDN System) in treating patients with uncontrolled hypertension.

Design and method:
This is a prospective, multicenter, randomized sham-controlled trial. Patients with uncontrolled hypertension (office BP > = 150/90 and <180/110mmHg, and average SBP > = 135mmHg by 24-hour ambulatory BP monitoring (ABPM), after taking > = 2 antihypertensive drugs with stable dose for > = 4 weeks) were screened after informed consent. All eligible patients first entered a lead-in period for > = 4 weeks of standardized medication (Nifedipine + hydrochlorothiazide), and those continued to meet definition of uncontrolled hypertension were randomized 2:1 to RDN group (using NetrodTM RDN System) and sham control group (renal artery angiography only). All continued with the 2-drug regimen and were evaluated at 7 days or discharge (whichever comes first), 1, 2, 3 and 6 months post procedure. Both patients and site investigators who evaluate the patients were blinded to treatment assignment. The primary endpoint is office SBP change from baseline at 6 months post procedure. Secondary endpoints include changes from baseline of office DBP. 24-hour ABPM at 6 months post procedure and safety events.

Results:
A total of 205 patients from 25 centers were enrolled and 139 randomized to RDN group and 66 to sham control group, with no statistical difference of baseline clinical characteristics between the 2 groups including baseline BP. Compared to baseline, at 6 months post procedure RDN group has a significantly greater office SBP reduction than sham group (25.53 ± 12.62mmHg vs 8.39 ± 11.89mmHg, p < 0.001). Office DBP change was -13.49 ± 8.09mmHg (RDN) vs -3.93 ± 9.04mmHg (sham), p < 0.001. For 24-hour ABPM, the average SBP and DBP reduction were also significantly greater in the RDN vs sham group (11.91 ± 12.23 vs 3.87 ± 12.45mmHg, p < 0.001; 6.03 ± 7.50 vs 1.68 ± 7.30mmHg, p < 0.001, respectively). Device or procedure related serious adverse events were rare throughout the trial.

Conclusions:
The novel NetrodTM RDN System is safe and effective in treating uncontrolled hypertension with significant reduction in both office and 24-hour ambulatory BP.
RESPONSE OF BLOOD PRESSURE TO RENAL DENERVATION IS NOT ASSOCIATED WITH GENETIC VARIANTS
Authors: Delles Christian , Schmieder Roland E. , Daly Ronan , Hamilton Graham , Schmid Axel , Herzyk Pawel , Mahfoud Felix 
Published: June 2023

Objective:
Renal denervation (RDN) is an evidence-based therapeutic option in patients with hypertension. However, the blood pressure (BP) responses to RDN in individual patients is currently impossible to predict. We conducted an unbiased genomic screen to identify genetic variants that are associated with response to RDN.

Design and method:
We included 268 patients (34.7% female, mean age 62 ± 10 years, BMI 30.5 ± 5.1 kg/m2) with uncontrolled treatment resistant hypertension (baseline BP 166 ± 21 / 90 ± 15 mmHg) who underwent endovascular RDN using the Symplicity™ catheter (Medtronic Inc, USA). Response to 24 hour ambulatory BP was assessed after 6 months and divided into two groups, above and below the median response of 6.0 mmHg, taking pre-intervention 24-hour ambulatory BP and regression to the mean into account. Whole exome sequencing assessing 249,669 variants was conducted using Illumina NovaSeq technology read on a Nova Seq S4 Flow Cell device. Read quality was overall excellent with the eight poorest performing samples still covering 30 reads per base for 80% of the exome. Reads were analysed by a standardised variant calling pipeline, using principal component analysis followed by individual logistic regressions to model association of variants with phenotype where appropriate.

Results:
There has been no linkage found between individual gene variants and the response variable. These neutral findings were further confirmed after adjustment for sex and in a sensitivity analysis looking at tertiles of BP response. We also explored specific variants in AGT, ADD1, ADRB1, ADRB2 and SCNN1A that have been proposed as potential candidate genes for response of BP to RDN and again found no association (all p>0.13). Gene ontology analysis of variants across the two responder groups highlighted differences in biological processes such as cell adhesion and molecular function such as protein tyrosine kinase activity.

Conclusions:
Response to RDN is not robustly associated with the genetic make-up of patients with uncontrolled treatment resistant hypertension. Our data do not support the use of a genetic score to predict BP response. We found, however, different regulation of biological processes and cellular/molecular function that could provide insights into the mechanisms of RDN.
CHANGES ON RIGHT VENTRICULAR DIMENSIONS, FUNCTION, AND PULMONARY CIRCULATION LOADING ACCORDING TO THE DEGREE OF INTERDIALYTIC WEIGHT GAIN IN MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Anastasiou Vasileios , Alexandrou Maria Eleni , Kamperidis Vasileios , Daios Stylianos , Tsilonis Konstantinos , Theodorakopoulou Marieta , Moysidis Dimitrios , Iatridi Fotini , Giannakoulas George , Ziakas Antonios , Sarafidis Pantelis 
Published: June 2023

Objective:
The right ventricle (RV) is a thin-walled cardiac chamber, whose sizing and pressure characteristics are susceptible to altered loading conditions. This study aimed to investigate changes in RV's function, right heart's dimensions, and pulmonary pressures in relation to the degree of fluid accumulation between hemodialysis sessions, evaluated according to the recommended threshold of interdialytic-weight-gain corrected for dry weight (IDWG%).

Design and method:
Forty-one patients receiving standard thrice-weekly hemodialysis were divided into a higher (> 4.5%) and a lower ( < 4.5%) IDWG% group for the present analysis, according to the recommended higher threshold of IDWG%. All participants underwent a 2-dimensional echocardiographic assessment at the start and the end of the 3-day and the 2-day interdialytic interval in a crossover design.

Results:
RV systolic pressure (RVSP) increments were more pronounced in the higher compared to the lower IDWG% group (16.43 ± 5.37 vs 14.11 ± 13.38 mmHg respectively, p = 0.015) over the 3-day interval, while changes in RV filling pressures, assessed by RV E/Em did not differ significantly between the two groups (p = 0.84). Significant right heart chambers’ enlargement was observed in both groups and during both intervals, but a more prominent dilatation of inferior vena cava was noted in patients with higher IDWG% (0.44 ± 0.25 vs 0.2 ± 0.31cm, p = 0.014) over the 2-day interval.

Conclusions:
During the 3-day interdialytic interval, pulmonary circulation is particularly overloaded in patients with fluid accumulation higher that the recommended thresholds, as evidenced by higher RVSP elevations. This finding may add another plausible mechanism for increased cardiovascular morbidity and mortality during the long interval.
CARDIOVASCULAR AND ALL-CAUSE MORTALITY ARE NOT CLOSER ASSOCIATED WITH CENTRAL THAN PERIPHERAL BLOOD PRESSURE IN AN ELDERLY CHINESE POPULATION: THE NORTHERN SHANGHAI STUDY
Authors: Yu Shikai , Zhao Song , Tang Jiamin , Zhao Yifan , Xu Yawei , Zhang Yi 
Published: June 2023

Objective:
Controversy exists in the comparison between central and peripheral blood pressure (BP) in prediction of cardiovascular and all-cause mortality. To examine whether central BP predicts cardiovascular and all-cause mortality better than brachial BP in a large cohort of elderly Chinese.

Design and method:
A total of 3050 participants enrolled in the Northern Shanghai Study, a prospective cohort study focusing on the cardiovascular risk of community-dwelling elderly Chinese living in the north of Shanghai, China between 2014 and 2019, were included. Central BP was estimated tonometrically from the redial pulse waveform. Vital status of all participants was confirmed by reviewing the regional morality record system in October 2020. Cox proportional hazards models were conducted to evaluated the predictive value of central and peripheral systolic BP (SBP) and pulse pressure (PP).

Results:
During the median follow-up of 5.6 years, 203 deaths, 77 of which were cardiovascular, occurred. When central and peripheral SBP were analyzed separately, both central and peripheral SBP predicted all-causes mortality (Peripheral: HR 1.040, 95% CI 1.002 to 1.080; Central: HR 1.038, 95%CI 1.000 to 1.078; Per 5 mm Hg), but not cardiovascular mortality, after adjusting age, sex, BMI, current smoking, lipid, cerebrocardiovascular disease, diabetes, antihypertensive treatment, statin treatment, hypoglycemic treatment and estimated glomerular filtration rate. When central and peripheral SBP were included in the same stepwise regression of all-cause mortality, only peripheral SBP were stayed in the final model (HR 1.037, 95%CI 1.000 to 1.074, per 5 mm Hg), after adjustment for covariates. Neither central nor peripheral PP predicted mortality after adjusted covariates.

Conclusions:
Central BP was not superior than peripheral BP in predicting cardiovascular and all-cause mortality in the elderly Chinese.
EFFECTS OF 2-WEEK DIETARY NITRATE SUPPLEMENTATION AND ANTIBACTERIAL MOUTHWASH TREATMENT ON RESERVOIR-EXCESS PRESSURE PARAMETERS IN HEALTHY OLDER ADULTS
Authors: Aizawa Kunihiko , Thompson Christopher , Hughes Alun D. , Parker Kim H. , Shore Angela C. , Vanhatalo Anni , Jones Andrew M. 
Published: June 2023

Objective:
The nitrate-nitrite-nitric oxide pathway contributes to blood pressure (BP) regulation in humans. However, it is unknown if the pathway alters arterial haemodynamic parameters derived from reservoir-excess pressure analysis. We therefore determined whether an enhancement/disruption of nitrate-nitrite-nitric oxide pathway by dietary nitrate and antibacterial mouthwash, respectively, would alter reservoir-excess pressure parameters in older adults.

Design and method:
Healthy older adults (n = 30, 71.0 ± 2.6 yrs, 19F, 133 ± 11 mmHg for systolic BP and 70 ± 6 mmHg for diastolic BP) participated in this study. Participants were randomised to either a 2-week active nitrate treatment (BR: ∼12.4 mmol beetroot juice daily as a nitrate source) or 2-week placebo treatment (PL: nitrate-depleted beetroot juice) followed by 2-week washout. They then crossed-over to the alternate treatment which was followed by another 2-week washout. Thereafter, they completed a twice-daily antibacterial mouthwash treatment (MW) for two weeks with the aim of disrupting enterosalivary nitrate circulation. Prior to and following each 2-week treatment, reservoir-excess pressure parameters including reservoir pressure integral, excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant were obtained through radial artery tonometry along with brachial systolic and diastolic BP. Aortic pulse wave velocity (aPWV) was estimated as previously described (Hughes et al., Front Physiol 2020;11:550).

Results:
Circulating plasma nitrate [614 (95%CI: 545, 683) microM] and nitrite [0.51 (95%CI: 0.30, 0.72) microM] increased with BR, and decreased with MW [nitrate, -17.1 (95%CI: -28.1, -6.1) microM; nitrite, -0.03 (95%CI:-0.05, -0.01) microM]. Relative to PL, BR reduced brachial systolic BP [-2.0 (95%CI: -3.9, -0.1) mmHg], INTXSP [-0.4 (95%CI: -0.7, -0.1) mmHg·s], and aPWV [-0.2 (95%CI: -0.4, 0.0) m/s]. MW increased brachial systolic [2.0 (95%CI: 0.0, 3.9) mmHg], diastolic [1.2 (95%CI: 0.4, 2.0) mmHg] BP, and decreased SRC [-0.2 (95%CI: -0.3, 0.0) 1/s] relative to PL.

Conclusions:
Favourable (INTXSP with BR) and unfavourable (SRC with MW) alterations in reservoir-excess pressure parameters were observed with 2-week dietary nitrate and antibacterial mouthwash treatments, which was accompanied by a small change in brachial systolic BP. These observations may suggest a potential link between enhancing/disrupting nitrate-nitrite-nitric oxide pathway and cardiovascular health in older adults.