bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of sodium-glucose contrasporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on vascular function and liver steatosis in diabetes
Authors: Ikonomidis I , Michalopoulou E , Pavlidis G , Prentza V , Katogiannis K , Kostelli G , Vythoulkas D , Kountouri A , Korakas E , Pliouta L , Thymis J , Lambadiari V 
Published: November 2023

Abstract

Background/Introduction
Patients with type-2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) present increase risk of cardiovascular disease. Sodium-glucose contrasporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to significantly reduce the risk of cardiovascular complications.

Purpose
The aim of the study was to investigate the effect of treatment with SGLT-2i or GLP-1RA on vascular function and liver steatosis and fibrosis in patients with T2DM and NAFLD.

Methods
Thirty patients with T2DM and NAFLD (mean age: 57±11 years) were randomized to receive SGLT-2i (dapagliflozin; n=15) or GLP-1RA (dulaglutide; n=15). At baseline and at 6 months post-treatment, we measured: (1) Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5-25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. (2) Pulse wave velocity (PWV) and augmentation index (AI) using Complior (ALAM Medical), (3) NAFLD fibrosis score (NFS), and (4) Controlled attenuation parameter (CAP) score to assess steatosis grade and liver stiffness (E) to evaluate fibrosis score using liver elastography (FibroScan, Echosens).

Results
At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of vascular function (p&gt;0.05). Compared with baseline, all patients had reduced PBR, PWV, AI, NFS, CAP and E (p&lt;0.05) after 6-month treatment. In the whole study population, the percentage reduction of markers of steatosis (NFS) correlated with the corresponding decrease in PBR (r=0.34, p=0.040) and PWV (r=0.31, p=0.043) post-treatment. Both treatments with SGLT-2i and GLP-1RA reduced markers of liver steatosis and fibrosis (Table).

Conclusion
Both treatments with SGLT-2i and GLP-1RA improve vascular function and reduce liver steatosis in patients with T2DM and NAFLD after 6-month treatment.Table
ZNF259 rs964184 genetic variant is associated with metabolic syndrome in a Portuguese population
Authors: Sa D , Mendonca M I , Santos M , Temtem M , Sousa F , Freitas S , Borges S , Henriques E , Rodrigues M , Guerra G , Drumond A , Sousa A C , Palma Dos Reis R 
Published: November 2023

Abstract

Background
Zinc finger protein (ZPR1) encoded by the ZNF259 gene has been associated with defects in transcription and cell cycle progression. Additionally, the promoter site of ZPR1 binds to peroxisome proliferator-activated receptor gamma (PPARG), which plays a crucial role in insulin sensitivity and obesity. It's not consensual in its association with Metabolic Syndrom (MetS).

Aim
To estimate the influence of the ZNF259 rs964184 variant in MetS appearance.

Methods
A case-control study was performed with 3134 subjects (mean age 52.8 ± 8.1 years, 76.4% male) recruited from the Research Unit database, a regional quality clinical registry of hospital admissions. 1756 were patients with MetS and 1378 controls without MetS. MetS was diagnosed according to the International Diabetes Federation (IDF) criteria. The ZNF259 rs964184 C&gt;G was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). The bivariate analysis evaluated the genotypic and allelic distribution in the two groups, with and without MetS. Multivariate Logistic Regression assessed the variables independently associated with MetS.

Results
There were significant differences in genotype and allele distributions for the ZNF259 C&gt;G variant between patients with MetS and without MetS. Wild-type genotype CC was increased in the non-MetS group, whereas the risk GG was higher in patients with MetS (P=0.008). Similarly, C allele frequencies were significantly higher in the non-MetS group, while the G allele was highly present MetS population (P=0.002). After multivariate logistic regression, GC genotype (OR=1.23; 95%CI:1.05–1.45; p=0.011) and GG genotype (OR=1.59; 95%CI:1.01–2.50; p=0.047) remained as independent risk factors for Metabolic Syndrome.

Conclusions
This study presents novel data and findings that may have important implications for assessing MetS risk in our population. For the first time in a Portuguese population, we demonstrated that ZNF259 genetic changes are significantly associated with more than 60% increased probability of having Metabolic Syndrome.
Long-term spermidine therapy potentially protects the heart against estrogen deprivation in female rats via suppressing cardiac mitochondrial dysfunction, inflammation, oxidative stress, and apoptosis
Authors: Kaorop W , Maneechote C , Pratchayasakul W , Kumfu S , Arunsak B , Chattipakorn S C , Chattipakorn N 
Published: November 2023

Abstract

Background
Postmenopausal women have been associated with a higher risk of cardiovascular diseases (CVDs). Several pathophysiological mechanisms, including cardiac mitochondrial dysfunction, oxidative stress, inflammation, and cardiomyocyte apoptosis, played a key role in the development of postmenopausal CVDs. Long-term estrogen supplementation is widely used to treat postmenopausal symptoms, but it has been linked to an increased risk of breast cancer and cardiac complications. Spermidine is a natural organic compound which has been shown to exert cardioprotection under several pathological conditions. However, the benefits of spermidine against impaired cardiac function due to estrogen-deprivation are unknown.

Purpose
To investigate the effects of therapeutic intervention with spermidine on cardiac mitochondrial function, oxidative stress, inflammation, and programmed cardiomyocyte death in rats with estrogen deprivation.

Methods
Fifteen female Wistar rats underwent ovariectomy (OVX) to induce estrogen deprivation. After 12 weeks, all OVX-operated rats were randomly divided into three interventional groups as follows: 1) vehicle or OV (n = 5), 2) spermidine or OS (20 mg/kg/day, p.o., n = 5), and 3) estradiol or OE (50 µg/kg/day, s.c., n = 5) for an additional 8 weeks. At the end of the experiment, echocardiography for the heart’s function was performed. Then, all the rats were sacrificed, and their hearts were dissected for mitochondrial and molecular analysis, including the protein expressions of inflammation, oxidative stress, and apoptosis.

Results
Treatment with either spermidine or estrogen provided a similar cardioprotective efficacy against OVX-induced estrogen deprivation in reducing mitochondrial membrane potential depolarization and cardiac inflammation, as shown by increased red to green fluorescence and lowered p-NFkB to NFkB ratios, respectively (Fig. 1A, B). Spermidine and estrogen also exerted anti-oxidative stress via increasing glutathione peroxidase (GPX4) and anti-apoptosis via decreasing the cleaved caspase-3 to procaspase-3 ratio following OVX-induced estrogen deficiency (Fig. 1C, D). All of the beneficial effects of spermidine and estrogen led to an improved left ventricular ejection fraction (89% for OS and OE vs. 76% for OV).

Conclusion
Long-term treatment with spermidine rescued cardiac mitochondrial dysfunction, inflammation, oxidative stress, and apoptosis, resulting in the restoration of left ventricular function with the same efficacy as estrogen treatment. These findings suggest that spermidine could be a novel therapeutic strategy to alleviate the adverse cardiac complications associated with postmenopausal women.
Effect of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on markers of neurohumoral activation and left atrial strain
Authors: Ikonomidis I , Katogiannis K , Pavlidis G , Thymis J , Pliouta L , Kousathana F , Kountouri A , Prentza V , Michalopoulou E , Tsilivarakis D , Kostelli G , Katsanaki E , Maratou E , Lambadiari V 
Published: November 2023

Abstract

Background
We investigated the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on neurohumoral biomarkers, left ventricular and left atrial function in type 2 diabetes mellitus.

Patients and methods
A total of 200 patients (60.3±10.3 years old, 138 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n= 50 served as controls), liraglutide (n=50), empagliflozin (n=50) or their combination (GLP-1RA+SGLT-2i) (n= 50) as add-on. We measured at baseline and 6 months posttreatment: (a) Left atrial reservoir strain (LASr) (b) serum biomarkers of cardiac function as Growth/Differentiation Factor-15 (GDF-15), NTproBNP, Placental Growth Factor (PLGF).

Results
In all patients, increasing GDF-15 levels at baseline were positively related with NTproBNP (r=0.230, p=0.017), PWV (r=0.357, p&lt;0.001), GLS (r=0.425, p=0.005) and negatively related with LASr (r=-0,388, p=0.005).
Increasing NTproBNP concentration at baseline was positively related with GLS (r=0.454, p=0.002) and negatively related with LASr (r=-0,424, p=0.002).
Treatment with SGLT-2i improved GDF-15 and NTproBNP (2032±187 vs 1803±178 pg/mL, p=0.016, 215±67 vs 124±52 pg/mL, p=0.005, respectively), while treatment with GLP-1RA had a neutral effect on these biomarkers (p&gt;0.05). However, the combined treatment of SGLT-2i with GLP-1RA also improved the examined biomarkers (p&lt;0.05).
Compared to baseline, no significant change in GDF-15 and NTproBNP levels was observed in patients treated with insulin (1815±234 vs 1730±192 pg/mL, p=0.235, 245±43 vs 232±32 pg/mL, p=0.583, respectively).
After intervention, all patients treated with GLP1RA, SGLT2i and their combination improved left atrial reservoir strain (GLP1RA: 30.7±9.3 vs 33.9±9.7%, p=0,011, SGLT2i 30±8.3 vs 32.3±7.3%, p=0.04/ GLP1&SGLT2i :29.1±8,7 vs 31.3±8.2, p=0.007) in comparison with insulin (33±8.3% vs 32.8±7,4, p=0.829).

Conclusions
Treatment with GLP-1RA, SGLT-2i and their combination for 6 months showed a greater improvement of markers of neurohumoral activation and left atrial function compared to insulin, suggesting a role in heart failure prevention.
Men with non-obstructive coronary disease have higher risk of exercise-induced myocardial ischemia detected by cardiopulmonary exercise test
Authors: Li S , Zhao L T , Yuan Y F , Zhang P 
Published: November 2023

Abstract

Background
Non-obstructive coronary artery disease (NOCAD) had similar morbidity and mortality as patients with obstructive coronary artery disease but less understood. Limited studies analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD.

Methods
A total of 289 NOCAD patients (mean age 60, 56% women) who had ischemic symptoms and ⫹ 50% coronaries stenoses confirmed by coronary angiography performed the symptom-limited CPET. We used the predicted % peak VO2, O2 pulse trajectory, and exercise ECG test to assess inducible myocardial ischemia.

Results
Compared with women, men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%) and downward pattern of O2 pulse trajectory (2% vs. 0%) (P &lt; 0.0001). Instead, women with NOCAD had higher prevalence of shallow pattern of O2 pulse trajectory (21% vs. 6%, P &lt; 0.0001). Men with NOCAD had higher proportions of increased risk of exercise-induced myocardial ischemia (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, P &lt; 0.0001). After adjustment, men with NOCAD demonstrated significantly lower predicted % peak VO2 (β -27.4, 95% CI -30.74 – -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 – 9.19) and myocardial ischemia risk detected by CPET (OR 3.14, 95% CI 1.78 – 5.54) (P &lt; 0.0001).

Conclusion
Men with NOCAD had higher risk of exercise-induced myocardial ischemia detected by CPET that should be given rigorous management and follow-up to prevent cardiovascular events.
Exercise performance and the risk of incident atrial fibrillation
Authors: Lu C T , Sung S H 
Published: November 2023

Abstract

Background
Atrial fibrillation (AF) is a global health problem that correlates with the increased risks of cardiovascular diseases, quality of life, mortality and global health expenditures. While many of cardiovascular risk factors have been related to the development of AF, a satisfied lifestyle behavior, including regular exercise and a good cardiorespiratory fitness, could be the upstream intervention to modify the risk factors and reduce the AF incidence.

Purpose
We examined the relationship of the exercise performance with risk of incident atrial fibrillation and its subsequent comorbidities.

Methods
From 2003 to 2012, we retrospectively included 19,680 consecutive patients without previous diagnosis of AF, who were referred to exercise treadmill testing for clinical reasons. The baseline characteristics and the exercise parameters during exercise testing were accessed in all enrolled subjects. Multivariable Cox proportional hazard models identified the independent association between exercise performance and risk of new-onset atrial fibrillation, risk of ischemic stroke and major adverse cardiovascular events (MACE). Cubic spline regression model assessed the risk of new-onset AF across fitness level.

Results
Among a total of 15,450 subjects (mean age, 54.9 ± 11 years; 59% male) with a median follow-up duration of 137 months, 515 (3.33%) new-onset AF cases were found. There was an 8% lower risk of AF incidence (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97), a 12% lower risk of ischemic stroke incidence (hazard ratio, 0.88; 95% confidence interval, 0.83-0.94), and a 14% lower risk of MACE (hazard ratio, 0.86; 95% confidence interval, 0.84-0.88) for every 1 peak achieved metabolic equivalents (METs) increase in the exercise treadmill testing after adjusting confounding factors. In the subgroup analysis, the peak achieved METs during exercise treadmill testing was significantly associated with the risk of new-onset AF across various subgroups, including age, gender, body mass index (BMI) and underlying diseases. There were significant interactions in age subgroup (P for interaction 0.0047) and subgroup stratified by the presence of chronotropic incompetence (P for interaction 0.0212).

Conclusions
Exercise capacity is inversely correlated with AF incidence across fitness level. A better exercise performance indicates a lower AF incidence, ischemic stroke incidence and MACE. Regular physical activity may help to reduce inflammation and improve the function of the heart, which may help to prevent the development of AF. Further research is needed to fully understand the underlying mechanisms.Kaplan–Meier curveSubgroup analysis
Agreement between two independent raters in identifying exercise oscillatory ventilation in patients with heart failure
Authors: Silva F M F , Milani M , Silveira A D , Cipriano Junior G , Cipriano G F B 
Published: November 2023

Abstract

Background
Heart failure (HF) leads to several functional and ventilatory limitations, including exercise oscillatory ventilation (EOV), whose presence is associated with an adverse prognosis, with a risk more than 4 times higher for a cardiovascular event. Methods to identify the presence of EOV were created and are being reformulated based on the amplitude and duration in the oscillation of the ventilatory cycles. Despite the documented association between EOV and prognosis in HF, the diversity of methods and subjective interpretation can compromise the diagnosis and adequate risk stratification.

Purpose
To analyze the agreement of the EOV identification between two independent raters and compare the clinical characteristics of the patients with and without EOV.

Methods
A cross-sectional study was carried out using an electronic questionnaire containing graphs of exercise ventilation over time from treadmill cardiopulmonary stress tests (CPET) performed in patients with HF, with preserved or reduced left ventricular ejection fraction (LVEF). The graphs were interpreted by two cardiologists with extensive experience in performing CPET. The research was approved by the institution's ethics and research committee. Agreement was evaluated by Cohen Kappa statistics and the proportion of agreements between raters. Differences among variables according to the presence of EOV (identified by at least one of the raters) were analyzed with Mann-Whitney test. A two-sided p-value &lt; 0.05 was considered significant for all analyses.

Results
The sample consisted of 31 patients (74% men, 56 years ± 10 years) with a LVEF of 44 ± 12%, 61% with reduced LVEF, 80% with NYHA functional classification I/II, and peak oxygen uptake (VO2peak) of 17.6 ± 4.3 mL/kg/min. The EOV identification by the raters revealed a moderate agreement, with Kappa of 0.56. The proportion of agreement was 84% (26 of 31 cases) and the specific agreement (presence of EOV) was 50% (5 of 10 cases) (Figure 1). Regarding the clinical characteristics of patients with and without EOV (Figure 2), the only variable with statistical difference was VO2peak, with lower values in the patients with EOV (14.9 versus 17.9 mL/kg/min; p = 0.019).

Conclusion
The agreement between two experienced raters was only moderate, which demonstrate that the identification of EOV remains challenging. The only clinical characteristics associated with presence of EOV in our sample was VO2peak, suggesting a poor prognosis in patients with HF and EOV.
Laughter therapy cardiac rehabilitation in patients with stable coronary artery disease: a randomized clinical trial
Authors: Saffi M , Franzoni L , Nery R , Donelli Da Silveira A , Andrade C , Carvalho G , Stein R 
Published: November 2023

Abstract

Background
Different non-pharmacological strategies have been studied in patients with stable coronary artery disease (CAD). However, the potential benefits of laughter therapy cardiac rehabilitation (LTRehab) for patients with stable CAD have not been fully investigated, especially through randomized clinical trials (RCT).

Purpose
This study aimed to evaluate the impact of LTRehab on functional capacity, endothelial function, and inflammatory biomarkers in CAD patients.

Methods
This is a randomized, parallel-design, examiner-blinded, controlled clinical trial conducted from August 2016 to December 2020. Peak oxygen uptake (VO2peak) and flow-mediated dilation (FMD) were measured using maximal cardiopulmonary exercise testing (CPET) and ultrasound, respectively. Inflammatory biomarkers, including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, vascular cell adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM), were measured. Thirteen patients were assigned to the LTRehab group, who watched two self-selected comedy sessions per week, and thirteen patients to the control group (CG), who watched two neutral documentaries (24 movies per group). Generalized Estimated Equations were used to identify the main factors of Group, Time, and the interaction between Group*Time. The Bonferroni correction was applied to identify differences. P &lt; 0.05 was considered statistically significant. This study was approved by the Institutional Review Board (protocol No. 13-0124). Furthermore, it was conducted in accordance with Resolution no.466/12 of the National Health Council.

Results
A total of 26 CAD patients (69% male; mean age of 63.58 ± 9.97 years) were included in the study. There was a significant interaction between Group*Time (P&lt;0.01) for VO2peak (LTRehab group: 19.09±0.85 to 21.06±1.00 vs. CG: 23.21±1.74 to 22.24±1.96 mL.kg-1.min-1). There was a mean difference of 1.98±0.45 between times for the LTRehab group with significant Bonferroni correction (P&lt;0.01), but not for the control group (-0.96±0.75, P=0.20). Nitroglycerin-mediated vasodilation (endothelium-independent function) and VCAM showed significant differences in the Time factor (P = 0.02 and P = 0.05, respectively). All CPET tests reached maximal criteria (R&gt;1.10).

Conclusion
This is the first RCT to evaluate the impact of LTRehab on CAD patients, showing an increase in VO2peak and improvements in endothelium-independent function and inflammatory biomarkers. LTRehab may constitute an effective form of cardiac rehabilitation in this patient population.
Treatment effect of respiratory therapy with intermittent hypoxic-hyperoxic training (IHHT) on functional capacity in patients with post COVID19 conditions: a controlled treatment trial
Authors: Shafieesabet A , Alimi B , Muhar J , Schueller P O , Doehner W 
Published: November 2023

Abstract

Introduction
COVID-19 can cause long-term lung and systemic damage that will lead to increasing numbers of patients disabled by reduced functional capacity. Intermittent hypoxia-hyperoxia training (IHHT) is a respiratory therapeutic concept which has been suggested to improve exercise performance via controlled hypoxic conditioning. The purpose of the present study is to investigate the therapeutic effect of IHHT on the recovery process during inpatient rehabilitation in post-COVID conditions.

Methods
A prospective, single-center, randomized controlled trial was conducted in 145 (37 men) patients with post COVID19 conditions aged 27-84 years, who were admitted to a hospitalized rehabilitation program (duration 27±5 days). Patients were 1:1 allocated to the standard rehabilitation program or IHHT on top of standard rehabilitation. The patients in IHHT group attended regular (alternate days) treatments of hypoxia-hyperoxia breathing sessions (10–12% O2 hypoxia breathing followed by 30-35% O2 hyperoxia breathing in 6-8 cycles for a total of 45 min). The primary endpoint of the trial was improvement in walking distance in a six-minute walk test (6MWT) between groups. Further endpoints of functional testing included stair climbing test (SCT), patient global assessment, fatigue assessment scale (FAS) and Quality of life (QoL) assessed by EQ5-D analog scale. Subjective perceived health was assessed by Median Corona Recovery Score (MCRS).

Results
The IHHT group demonstrated in comparison to controls a significant improved primary endpoint (6MWT difference, IHHT group vs controls: 91.7 vs. 32.5m, P&lt;0.001), improved stair climbing (SCT -1.9 vs. -0.5 sek, P&lt;0.001), improved QoL (EQ5-D analog scale change 31.3 vs. 2.9, P&lt;0.001), improved fatigue (FAS -8.9 vs. 3.6, P&lt;0.001) and improved perceived health (MCRS -10.3 vs. -2, P&lt;0.001, all IHHT group vs. controls). The IHHT group exhibited a significant increase in hemoglobin content and a significant decrease in CRP compared to baseline (P&lt;0.001), whereas these changes were not observed in the control group.

Conclusion
Respiratory treatment by IHHT in patients with post COVID conditions resulted in improved functional capacity in multiple of functional tests and in improved QoL and perceived health.