bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of 18F FOL a PET tracer targeting folate receptor beta in a rat model of myocardial infarction
Authors: Iqbal I , Liljenback H L , Andriana P A , Stahle M S , Virta J V , Herre E A H , Miner M W M , Anand A A , Kyto V K , Li X G L , Low P S L , Srinivasarao M S , Knuuti J K , Roivainen A R , Saraste A S 
Published: October 2024

Abstract

Background
Expression of folate receptor-β (FR-β) on the activated macrophages is associated with inflammatory diseases. However, the role of FR-β in the immune response following myocardial infarction (MI) remains unknown.

Purpose
To investigate FR-β-targeted positron emission tomography (PET) tracer aluminium fluoride-18-labeled 1,4,7,-triazacylononane-1,4,7-triacetic acid conjugated folate ([18F]FOL) for imaging immune response in a rat model of MI.

Methods
Rats underwent PET scan from 20 to 40 minutes after injection of 50±6 MBq of [18F]FOL on 3 (n=6), 7 (n=21), 15 (n=9), and 90 (n=11) days after surgical ligation of the left coronary artery. As controls, rats were studied on 3 (n=6), 7 (n=14), 15 (n=5), and 90 (n=8) days after sham-operation. [18F]FDG PET was performed a day before [18F]FOL injection in order to localize myocardium and area of MI. After [18F]FOL PET, autoradiography, histology, and staining of CD68 were performed 3 (n=6), 7 (n=6), and 90 (n=11) days after MI in order to detect [18F]FOL uptake and activated macrophages in myocardial tissue sections. A subgroup of rats (n=15) underwent serial [18F]FOL PET 7 and 90 days after MI together with echocardiography in order to evaluate left ventricular function.

Results
The presence of MI was confirmed by histology in all rats after coronary ligation. PET images showed increased uptake of [18F]FOL in the area of MI. The uptake was significantly higher (p&lt;0.001) in the area of MI than in the myocardium of sham-operated rats on day 3 (SUV 2.04±0.25 vs. 0.74±0.12), and remained increased on day 7 (SUV 1.39±0.33 vs. 0.68±0.12), day 15 (SUV 1.24±0.20 vs. 0.59±0.07), and day 90 (SUV 1.39±0.25 vs. 0.69±0.11). On day 3, pre-treatment with folate glucosamine (n=3) reduced the [18F]FOL signal by 50% in the area of MI indicating specific binding to FR-β. Autoradiography confirmed focally increased uptake of [18F]FOL in the area of MI. A positive correlation was found between uptake of [18F]FOL in PET images and areal percentage of CD68-positivity in the area of MI (r2=0.447, p&lt;0.001). Uptake of [18F]FOL on day 7 after MI was associated with decline in left ventricular ejection fraction (R=-0.665, p&lt;0.01) and increase in left ventricular systolic volume (R=0.561, p=0.02) between 7 and 90 days after MI.

Conclusion
Cardiac [18F]FOL PET detects increased macrophage-associated FR-β expression after MI in a rat model. FR-β expression peaks early and remains elevated up to 3 months in the infarcted area. Increased FR-β expression early after MI is associated with worsening of left ventricular systolic function late after MI.
The triglyceride-glucose index is a predictor for cardiovascular events and all-cause mortality in young and middle-aged patients with metabolic syndrome
Authors: Chen W H , Hu Y , Zhao Y , Li Z Y , Chen Y T , Huang R C 
Published: October 2024

Abstract

Aims
The association between the triglyceride-glucose (TyG) index and cardiovascular risk in young and middle-aged individuals with Metabolic syndrome (MetS) remains unclear. This study aimed to investigate the relationship between baseline TyG index and cardiovascular events and all-cause mortality in these patients among American adults.

Methods
This study enrolled 4937 young and middle-aged patients with MetS from the National Health and Nutrition Examination Survey (1999–2018). Mortality outcomes were determined by linking to National Death Index records up to December 31, 2019. Multivariate Cox proportional hazards models were constructed to analyze explore the associations between baseline TyG index and cardiovascular events or all-cause mortality. Non-linear correlations were explored using restricted cubic splines, and a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.

Results
During the up to 9.3 years follow-up period, a total of 463 all-cause deaths and 143 cardiovascular events were recorded. The multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) escalate from the lowest to the highest TyG index quartile. Specifically, for cardiovascular events, the HRs range from 1.00 (reference) to 2.29 (1.22, 4.31) with a significant trend (P = 0.004). For all-cause mortality, the HRs vary from 1.00 (reference) to 1.59 (1.09, 2.32), also showing a significant trend (P = 0.003). The restricted cubic splines revealed a J-shaped association between the baseline TyG index with cardiovascular events and all-cause mortality in MetS patients.

Conclusions
The high TyG index was identified as an independent predictor of elevated rates of cardiovascular events among young and middle-aged patients with MetS. Additionally, a J-shaped curve pattern was observed in the association between these factors.
Anti-inflammatory effect of semaglutide: updated systematic review and meta-analysis
Authors: Lobo L , Masson W , Nogueira J P , Rodriguez Granillo M , Barbagelata L , Siniawski D , Molinero G , Levalle Cobo A , Salmieri E , Sarli V , Delgado J , Nemec M 
Published: October 2024

Abstract

Background
Glucagon-like peptide-1 (GLP-1RA) receptor agonists possess multiple favourable metabolic, anti-inflammatory effects and their use is associated with marked body weight reduction. More importantly, this drug class has been shown to reduce cardiovascular events in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk or with established cardiovascular disease. Accordingly, current guidelines recommend the use of GLP-1RA sas first-line antidiabetic therapies in patients at high cardiovascular risk.
Semaglutide is a potent GLP-1RA used in the treatment of T2DM with proven cardiovascular benefits. It is currently available in formulations for oral and subcutaneous administration.
The anti-inflammatory effect could be one of the mechanisms by which semaglutide reduces cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) and/or obesity. Determining the anti-inflammatory effect of semaglutide was the objective of this systematic review and meta-analysis.

Methods
This meta-analysis was performed according to the PRISMA guidelines. A literature search was performed to detect randomised clinical trials that have quantified the effect of semaglutide on C-reactive protein (CRP) levels compared to placebo or a control group (other glucose-lowering drugs). The primary outcome was CRP index (final CRP/basal CRP). A random-effects model was used.

Results
Overall, this meta-analysis shows that semaglutide therapy was associated with lower CRP index values compared to placebo (SMD -0.56; 95% CI -0.69 to -0.43, I2 92%) or when comparing semaglutide treatment versus a control group consisting of patients medicated with other glucose-lowering drugs (SMD -0.45; 95% CI -0.68 to -0.23, I 3 82%).
The stratified analysis was performed by analysing only the trials that used a placebo group as comparator, When the trials were analysed according to the different dosing schemes (subcutaneous vs. oral), the results were not statistically significantly different (oral semaglutide group: SMD -0.33; 95% CI -0.75 to 0.08, I2 95%); semaglutide subcutaneous dose group: SMD -0.69; 95% CI -0.78 to -0.60, I2 74%); interaction p = 0.098. Furthermore, when the trials were analysed according to the included populations (patients with or without T2DM), the results were similar (patients with T2DM: SMD -0.32; 95% CI -0.51 to -0.14, I2 86%); patients without T2DM: SMD -0.82; 95% CI -0.90 to -0.74, I2 58%); interaction p = &lt; 0.0001.

Conclusion
The present meta-analysis demonstrated that the use of semaglutide was associated with a reduction in inflammation irrespective of the population evaluated or the treatment regimen used. These findings would explain one of the mechanisms by which semaglutide reduces cardiovascular events.
Telomere length across spectrum of metabolic health
Authors: Banach M , Osadnik T , Goc A , Boniewska-Bernacka E , Panczyszyn A , Lejawa M , Strzelczyk J , Pawlas N , Krystek K , Gierlotka M , Golawski M , Osadnik K , Fronczek M , Gach A , Jozwiak J 
Published: October 2024

Abstract

Introduction
Telomere length is a marker of cellular aging and is correlated with various cardiovascular risk factors.

Aim
To assess the association between obesity, metabolic syndrome (MetS) and telomere length.

Methods
The LIPIDOGEN study was carried out in the primary care 2015. Patients recruited to LIPIDOGEN cohort (n=1788) were a random subset of patients from LIPIDOGRAM 2015 (n=13,724) study. Patients for LIPIDOGRAM2015/LIPIDOGEN study were recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatments and lifestyle and also had saliva secured for DNA analyses. Recruited patients were divided into four groups based on the presence of MetS: 1) HS – healthy slim 2) MHO – metabolically healthy obese 3) NOMS – Non-obese with MetS 4) MUO – metabolically unhealthy obese. MetS was diagnosed basing on Joint Interim Statement 2009 criteria. Relative telomere length (rTL) was measured using quantitative polymerase chain reaction.

Results
DNA quality was sufficient for further analyses in 1606 patients. After removing of outliers, 1342 patients (Females - 59.3%, mean age- 50.2 years) were included for further analyses (HS-488, MHO-180, NOMS-165, MUO-509). Increase in BMI, waist circumference, frequency of diabetes mellitus, hypertension, dyslipidemia and history of myocardial infarction moving from HS to MUO was observed. (Table 1.). MUO group exhibited the highest triglycerides and lowest HDL-C levels. RTL length, an indicator of cellular aging, was inversely correlated with metabolic health, being shortest in the NOMS and MUO groups, which may indicate a link between metabolic health and accelerated biological aging.

Conclusions
Telomere length is shorter in patients with obesity as compared to lean patients even without the presence of MetS. Telomere length in patients with MetS, regardless of concomitant obesity, is shorter than in patients without MetS.
Figure 1. Telomere length across metabolic health categories.
Table 1. Clinical characteristics of the study participants.Figure. 1.Table. 1.
Spermidine attenuates left ventricular dysfunction in estrogen deprived aging rats through mitigating lipid peroxidation and mitochondrial dysfunction
Authors: Kaorop W , Maneechote C , Pratchayasakul W , Kumfu S , Arunsak B , Chattipakorn S C , Chattipakorn N 
Published: October 2024

Abstract

Background
Aging women with postmenopause are particularly susceptible to cardiovascular diseases (CVDs), which are associated with the elevation of oxidative stress and mitochondrial dysfunction. Although hormone replacement therapy (HRT) has been reported to provide cardiometabolic protection, long-term HRT could be linked to CVD consequences. A novel organic therapy with spermidine has shown promise as cardioprotection in several CVDs. However, the effects of spermidine on left ventricular (LV) function, mitochondrial function and oxidative stress in estrogen-deprived aging rats have not been investigated.

Purpose
To evaluate the effects of spermidine on LV function, mitochondrial function and oxidative stress in estrogen-deprived and D-galactose-induced aging rats

Methods
Twenty female Wistar rats were randomly assigned to the sham and the ovariectomy (OVX) along with D-galactose (150 mg/kg/day, s.c.) administration throughout the experiment for 12 weeks. OVX with D-galactose-treated rats were divided into three interventional groups: vehicle (ODV), spermidine (20 mg/kg/day, p.o., ODS), and estradiol (50 ug/kg/day, s.c., ODE) (n=5/group) for 8 weeks. The sham group received a vehicle (SVV, n=5). At the end, all rats underwent echocardiography, followed by euthanasia. The hearts were removed for measuring mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes (ΔΨm), and malondialdehyde (MDA) levels.

Results
Rats with OVX-induced estrogen deprivation with D-galactose-induced aging had LV impairments indicated by decreased LV ejection fraction, reduced ratio of peak velocity blood flow from left ventricular relaxation in early diastole (E) to peak velocity flow by atrial contraction (A), and increased sympathovagal imbalance (elevated low/high frequency (LF/HF) ratio) (Fig. 1A-C). These estrogen-deprived aging rats also had an increase in cardiac tissue MDA levels, mitochondrial ROS production, and MMP depolarization (Fig. 1D-F). Both spermidine and estrogen similarly demonstrated a significant reduction in all of those detrimental effects, leading to improved LV function (Fig. 1A-F).

Conclusion
Spermidine exerted cardioprotection comparable to estrogen supplement through mitigating oxidative stress and mitochondrial impairments in cardiac tissue, resulting in improved LV dysfunction and cardiac autonomic balance due to estrogen deprived aging conditions in rats. These findings suggest that spermidine administration could be a promising strategy for cardioprotection in postmenopausal women with aging.
Effects of SGLT-2i and GLP-1RA in vascular function parameters: the impact of the weight loss
Authors: Stampouloglou P , Bletsa E , Oikonomou E , Katsarou O , Tsigkou V , Ikonomidis I , Korakas E , Lambadiari V , Tentolouris N , Tousoulis D , Siasos G 
Published: October 2024

Abstract

Background
Arterial stiffness and endothelial function markers flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients.

Purpose
To investigate the effects of novel antidiabetic agents on arterial stiffness and endothelial function as well as the metabolic parameters of HbA1c and Weight in T2DM patients.
Patients and Methods: We enrolled 99 consecutive patients under stable antidiabetic therapy who did not reach therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Glycosylated hemoglobin (Hba1c) and weight expressed through Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) and flow-mediated dilatation (FMD), as biomarkers of arterial stiffness and endothelial function accordingly, were measured at baseline and 3 months after treatment intensification.

Results
There were no differences between the study groups in traditional risk factors of age and sex or baseline HbA1c, BMI, PWV, and FMD levels (ps=NS for all). In both groups PWV values displayed a statistically significant improvement from 11.2±2.5 to 9.3±2.2 m/sec (p&lt;0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group, as presented in Figure 1 through the differences in the values of PWV. FMD values were also significantly improve in both groups from baseline to follow-up; from 6.04±1.22 to 6.50±1.26% (p&lt;0,001) for the GLP-1RA group and from 6.38±1.21 to 6.81±1.29% (p&lt;0.001) for the SGLT-2i group. Moreover, both groups achieved better weight management goals in terms of BMI values between baseline and follow-up; from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group (p&lt;0.001) and from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p&lt;0.001), in addition to achieving better glycemic control in terms of HbA1c values, as seen in their paired differences: for GLP-1RA: 1.3±0.7% and for SGLT-2i: 0.8±0.5%. Interestingly, in the SGLT-2i group the magnitude of the PWV improvement was correlated with the weight loss (r=0.368, p=0.007).

Conclusion
These data provide evidence that the newer antidiabetic drugs, both GLP1-RA and SGLT-2i, have actions that benefit both vascular function, endothelium as well as metabolic parameters. Interestingly, in the patients receiving SGLT-2i the magnitude of the PWV improvement was correlated with the weight loss.delta PWV for SGLT-2i & GLP-1RA groupsCorrelation of deltaWeight & deltaPWV
Echocardiographic associates of impaired sleep quality in patients with anxiety and depression
Authors: Ozturk H M , Ciftci O , Inanc I H , Cilingiroglu M , Ozturk S 
Published: October 2024

Abstract

Objective
Sleep health, mental health and cardiovascular health are multidimensional constructs that are strongly associated with each other. Anxiety and depression are the most common psychiatric diseases in the community and frequently comorbid in routine clinical practice. This study sought to investigate whether there is an association between sleep quality and echocardiographic parameters in patients with anxiety and/or depression.

Methods
The clinical and instrumental find­ings of consecutive patients diagnosed with either of anxiety disorders and/or depressive disorders and underwent cardiac examination in our tertiary center on the same day were retrospectively reviewed. The diagnosis was made by a psychiatrist according to the criteria listed in the fifth edition of The Diagnostic and Statistical Manual of Mental Disorders. Afterwards, Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were applied to patients to assess symptom severity and sleep quality, respectively. Subsequent to psychiatric examination, the patients underwent echocardiographic examination that includes two-dimensional conventional echocardiography, tissue doppler imaging (TDI) echocardiography, atrial conduction times, and left atrium (LA) volumes and functions.

Results
The final study population consisted of 167 patients and divided into two groups according to their PSQI score: PSQI&lt;5 (normal sleep quality) (n=32) and PSQI≥5 (impaired sleep quality) (n=135). Aortic diameter, left ventricular (LV) end-systolic diameter, LV end-diastolic and -systolic volume, LV stroke volume and LV stroke volume index, LV outflow tract velocity–time integral (LVOT-VTI), and LA conduit volume calculations were significantly lower in patients with impaired sleep quality compared to patients with normal sleep quality. The other echocardiographic parameters including LV systolic functions, doppler and TDI echocardiography indices, atrial conduction times, atrial mechanical functions including LA function index (LAFI) were similar among groups. Correlation analysis yielded a negative, weak but statistically significant correlation between LAFI and PSQI score (r=-0.17, p=.030) (Figure 1A). Left intra-AEMD positively and significantly correlated with PSQI score at a weak level (r=0.16, p=.043) (Figure 1B). Aortic diameter, LV stroke volume index, LVOT-VTI and conduit volume were determined as echocardiographic parameters significantly associated with impaired sleep quality in univariate analysis. Among these parameters, only conduit volume remained as significant and independent associate of impaired sleep quality in multivariate logistic regression analysis (Odds ratio:0.91, 95% Confidence interval:0.85-0.98, p=.018) (Table 1).

Conclusion
There is an independent association between LA conduit volume and impaired sleep quality in patients suffering from anxiety and/or depressive disorders.Figure 1Table 1
The optimal cut-off value for the one-minute sit-to-stand test to determine functional impairment in patients with pulmonary hypertension
Authors: Kronberger C , Willixhofer R , Ermolaev N , Rassoulpour N , Bedirxan Kaya M , Poledniczek M , Krall C , Litschauer B , Badr Eslam R 
Published: October 2024

Abstract

Introduction
Pulmonary hypertension (PH) often leads to reduced functional capacity, commonly assessed by the six-minute walk test (6MWT). The 1-min sit-to-stand test (1-min STST) is a shorter test with smaller space requirements. Despite its potential utility, to our knowledge no studies have determined the optimal cut-off value for the 1-min STST in patients with PH.

Aim
This study aimed to assess the optimal cut-off value for the 1-min STST by utilizing three established 6MWT thresholds (165m, 320m, and 440m) recommended in current European PH guidelines published by Humbert et al. (1).

Methods
A receiver operating characteristics (ROC) curve analysis was conducted to identify a threshold for the 1-min STST, aligning with the three 6MWT cut-offs. Clinical parameters and health-related quality of life (HRQoL) assessed through the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire were evaluated.

Results
A total number of 114 patients with PH (mean age 66±14 years, 57% female) were included in the analysis. Patients performed a mean number of 17±7 repetitions in the 1-min STST and achieved a mean 6MWT distance of 351±137m. The &lt;165m 6MWT threshold revealed the highest area under the curve (AUC=0.90; 95%-CI 0.84-0.97). The optimal cut-off for the 1-min STST was 14.5 repetitions, exhibiting 69% sensitivity and 100% specificity. Patients below this threshold demonstrated significantly worse clinical parameters and reported worse HRQoL (p&lt;0.001), as shown in Table 1.

Conclusion
A 1-min STST cut-off of 14.5 repetitions identified PH patients with functional impairment, suggesting its potential utility for risk stratification.
The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects on the right ventricular load in patients with hypertrophic cardiomyopathy
Authors: Popovic D , Tesic M , Seman S , Babic M , Mikic L , Okwose N C , Velicki L , Filipovic N , Ristic A , Jakovljevic D G 
Published: October 2024

Abstract

Aim
We sought the cardiopulmonary exercise testing (CPET) parameter that is the most reflective of right ventricular (RV) load and its coupling with pulmonary artery (PA) in patients diagnosed with hypertrophic cardiomyopathy (HCM) undergoing medical therapy.

Methods
CPET on recumbent bike was performed in adult patients with symptomatic non-obstructive HCM with NYHA class I–III, during phase II, randomised, open-label multicentre study, before and after diverse medical treatment for 16 weeks. Endpoints were the changes in: 1) peak oxygen consumption (peak VO2); 2) minute ventilation (VE)/carbon-dioxide (CO2) production slope during the whole CPET; 3) VE/VCO2 slope before anaerobic threshold (AT); 4) VE/VCO2 slope after AT; 5) VE/VCO2 nadir; 6) VE/VCO2 at AT; and 7) VE/VCO2 intercept. Standard ehocardiography at rest was performed concomitantly with CPET to assess tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), severity of mitral regurgitation (MR) and TAPSE/PASP ratio as a measure of RV-PA coupling.

Results
Of 115 screened patients, 61 (mean age 52 years [SD 14], 43% women) met the study inclusion criteria and underwent CPET. On regression analysis, among all CPET end-point variables, the best independent predictor of the change in PASP, TAPSE and MR severity after 16 weeks of medical treatment was VE/VCO2 below AT (B=-0.28, -0.01,-0.11; SE=0.10, 0.05, 0.01; CI=-0.48 to -0.08, -0.22 to -0.01; -0.02 to 0.01; p=0.007, 0.035, 0.004, respectively), whereas the best predictor of TAPSE/PASP ratio was intercept of the VE/VCO2 curve (B=0.014, CI=0.01to 0.03, p=0.005).

Conclusion
The changes in VE/VCO2 slope below anaerobic threshold, and intercept of the VE/VCO2 curve outperform peak VO2 in the monitoring of therapy effects on the right heart load and RV-PV coupling in patients with hypertrophic cardiomyopathy.