bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence, incidence, and outcomes across cardiovascular diseases in homeless individuals- a case-control study using national linked electronic health records
Authors: Banerjee A , Nanjo A , Evans H , Direk K , Hayward A , Story A 
Published: November 2020

Abstract

Background
Homelessness is increasing globally. The risk and burden of cardiovascular disease (CVD) are higher in homeless than in housed individuals but the population-based analyses, required for planning of effective interventions and policies, are lacking.

Purpose
Using national electronic health records (EHRs), we investigated prevalence, incidence and outcomes across a range of CVDs among homeless individuals.

Methods
Using linked UK primary care EHR and validated phenotypes, we identified homeless individuals aged ≥16 years between 1998 and 2019, and age- and sex-matched housed controls in a 1:5 ratio. For twelve CVDs (stable angina; unstable angina; myocardial infarction; sudden cardiac death or cardiac arrest; unheralded coronary death; heart failure; transient ischaemic attack; ischaemic stroke or stroke not further specified; subarachnoid haemorrhage; intracerebral haemorrhage; peripheral arterial disease; abdominal aortic aneurysm), we estimated prevalence, incidence and 1-year mortality risks, comparing homeless and housed groups.

Results
We identified 8492 homeless individuals and 32134 matched controls. Comorbidities and risk factors were more prevalent in the homeless group, e.g. smoking: 78.1% vs 48.3% and atrial fibrillation: 9.9% vs 8.6%, p&lt;0.001. CVD prevalence (11.6% and 6.5%), incidence (e.g. incidence rate ratio, 3.36, 1.99–5.66 and 2.18, 1.50–3.16 in men and women, respectively, aged &lt;35 years), and 1-year mortality risk were higher (adjusted hazard ratio 2.30, 1.70–3.12), and onset was earlier (difference: 4.6, 2.8–6.3 years, p&lt;0.001), in homeless, compared with housed people. Other than cerebrovascular and peripheral vascular diseases in women (where numbers of events were small), homeless individuals had higher incidence of CVD in all three arterial territories than housed people.

Conclusions
CVD in homeless individuals has high prevalence, incidence and 1-year mortality risk with early onset, and high burden of risk factors. Health and social care strategies in inclusion health should reflect this high burden of treatable risk factors and disease.
Incidence of CVD in homeless individuals

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research
Adapting neural network models to predict 10-year CVD development based on regional data calibration
Authors: Korsakov I , Gavrilov D , Serova L , Gusev A , Novitskiy R , Kuznetsova T 
Published: November 2020

Abstract

Background
The used tools for prediction the individual risk of developing cardiovascular diseases and their complications using machine learning methods have proven better prognostic value in comparison with commonly used scales (e.g., Framingham, SCORE). To create such methods, the long-term accumulation of large amount of qualitative data are required. Moreover, to improve the accuracy of models, it is necessary to take into account regional characteristics that affect health: ethnic, nutritional characteristics, climatic conditions, living standards and medical care. These regional characteristics could significantly affect the development and outcomes of CVDs. However, the amount of regional data is not enough to build a qualitative model. Therefore, it is proposed to create models based on publicly available data and validate them on regional medical data sufficient for validation and calibration.

Methods
Two models were trained using data from the Framingham study. Model 1 was trained on 2 588 patient data and predicts a 10-year CVD probability according to the following risk factors: age, gender, cholesterol, HDL, smoking, SBP, and BP medications. Model 2 was trained on 4,363 patient data and predicts a 10-year death probability from CVD according to the following criteria: age, gender, cholesterol, smoking, SBP, BMI, heart rate. To retrain the obtained models, we used dataset created from data from patients in the northwestern part of Russia. The dataset consists of 438 patients, including the signs used in the trained models. This dataset includes CVD and death from it during a 10-year follow-up

Evaluation
We used randomized data splitting: divided the dataset into a training and a test set with an 80/20 proportion. The models was implement with keras convolution neural network (CNN) using 3 hidden layers. For data validation was used a 10 K-fold method.

Results
We compared the initial model metrics and those obtained after local data retraining. The accuracy of model 1 before retraining is 78%, after – 81.3%, the area under the ROC curve (AUC) before retraining: 0.77 (at 95% CI: 0.72–0.82C), after – 0.803. The accuracy of model 2 before retraining is 79%, after – 85.6%, the area under the ROC-curve (AUC) before retraining: 0.78 (at 95% CI: 0.72–0.82), after – 0.828.

Conclusion
Using this method of retraining predictive models, we can take into account local characteristics of the population and significantly increase the accuracy of predicting events. Expand the population to use the model according to local characteristics.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): OOO K-SkAI
National cardiac registries: a systematic review
Authors: Dawson L , Biswas S , Stub D , Lefkovits J , Burchill L , Reid C , Eccleston D 
Published: November 2020

Abstract

Background
Over the last thirty years, there has been exponential growth in the number and scale of national cardiovascular disease registries. We aimed to provide a comprehensive outline of contemporary national cardiac registries across all subspecialties.

Methods
We performed a systematic literature review by searching OvidMedline in August 2019 to identify registries relating to six pre-specified domains (Table). For inclusion, registries had to be national in nature, actively collecting data, and publishing either peer-reviewed publications or online reports.

Results
A total of 24,076 records were identified from six domain-specific Medline searches; 24,057 abstracts were screened with 19,435 non-relevant records excluded; 4,624 full texts were screened with 4,473 non-relevant texts excluded; and 151 registries met inclusion criteria representing 51 countries. Of these, 15 related to cardiac surgery, 27 to arrhythmia (17 device, 5 ablation, 7 atrial fibrillation), 21 to congenital heart disease (14 general, 2 interventional, 4 surgical, and 1 disease specific), 43 to coronary disease or percutaneous coronary intervention (22 PCI, 21 CAD), 27 to heart failure (13 heart failure, 5 transplant, 2 mechanical support, 7 disease specific), and 18 related to structural intervention (3 any, 13 transcatheter aortic valve replacement, 2 mitral intervention). Nine national registries (USA, Sweden, Finland, Denmark, UK, Portugal, Norway, Taiwan, and Singapore) covered multiple domains. Quality scoring using the Monash University Clinical Quality Registry Grading System (a composite score of recruitment, and data completeness, definitions, reliability and validation), demonstrated marked heterogeneity in quality between registries.

Conclusions
Cardiac registries have seen rapid growth, however the use and quality among various subspecialties differs markedly across world regions. Given the multiple benefits, clinicians, funders and health bureaucrats should be encouraged to focus on the range, quality and uptake of national registries.
Figure 1

Funding Acknowledgement
Type of funding source: None
Mutations in CHMP4C cause dilated cardiomyopathy via dysregulation of autophagy
Authors: Zhou N.W , Tang L , Jiang Y.Y , Li X.J , Zhao W.P , Pan C.Z , Wang X.L , Shu X , Qiu Z.L , Ge J.B 
Published: November 2020

Abstract

Background
Gene mutations have been implicated in DCM. However, due to the difficulty of clinical genetic diagnosis, more causal genes potentially related to DCM remain to be discovered.

Methods
We screened for gene mutations in more than 400 cases from families with hereditary cardiovascular disease using whole-exome sequencing. Then we validated biological functions of CHMP4C mutations in zebrafish models. To further assess the mechanism of CHMP4C mutations, we evaluated the potential signaling pathway in the cells.

Results
We identification of CHMP4C variants that segregated with DCM variants in four families from a total of 411 families via whole-exome sequencing. We further validate the function of CHMP4C in heart function in zebrafish models and found that over-expression of CHMP4C variants in zebrafish resulted in cardiac malformation, pericardial edema and increased heart rate, consistent with CHMP4C mutation-associated findings in DCM patients. Furthermore, we found that mutations in CHMP4C impaired autophagy and activated apoptosis in HEK293T cells, suggesting that the molecular mechanism of CHMP4C is involved in heart development.

Conclusions
CHMP4C is a novel candidate gene for DCM and may play a critical role in cardiac development by regulating autophagy.

Funding Acknowledgement
Type of funding source: None
Epicardial adipose tissue: the genetics behind an emerging cardiovascular marker
Authors: Sousa J.A , Serrao M.G , Temtem M , Pereira A , Santos M , Mendonca F.V , Monteiro J.P , Ferreira A , Freitas P , Henriques E , Ornelas I , Freitas A.I , Freitas A.D , Reis P , Mendonca M.I 
Published: November 2020

Abstract

Background
Increasing evidence points epicardial adipose tissue (EAT) as an emerging cardiovascular risk marker. Whether genetic polymorphisms are associated with a higher EAT burden is still unknow. Genetic risk score (GRS) is an emerging method that attempts to establish correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes.

Aim
Evaluate the role of genetic burden and its association to EAT.

Methods
996 patients (mean age 59±8, 78% male) were prospectively enrolled in a single center. EAT was measured on cardiac CT using a modified simplified method. Patients were divided into 2 groups (above vs. below the median EAT volume).
We studied different polymorphisms across the following gene-regulated pathways: oxidation, renin-angiotensin system, cellular, diabetes/obesity and dyslipidemia pathways. Genotyping was performed by TaqMan allelic discrimination assay. A multiplicative genetic risk score (mGRS) was constructed and represents the genetic burden of the different polymorphisms studied. To evaluate the relation between genetics and EAT volume, we compared both groups by: global mGRS, gene cluster/axis mGRS and individual SNPs.

Results
Patients with above-median EAT volume were older, had higher body mass index (BMI) and higher prevalence of hypertension, diabetes and dyslipidemia (p&lt;0.05). Patients with higher EAT volumes presented a higher global mean GRS (p&lt;0.001), with the latter remaining an independent predictor for higher EAT volumes (OR 1.3, 95% CI 1.2–1.5), alongside age and BMI.
In the analysis by gene clusters, patients with more epicardial fat consistently presented a higher polymorphism burden (translated by a higher mGRS level) across numerous pathways: oxidation, renin-angiotensin system, cellular, diabetes/obesity and dyslipidemia. After adjusting for confounders and other univariate predictors of higher fat volume, the following have emerged as independently related to higher EAT volumes: mGRS comprising the genes of different clusters, age and BMI.
Amongst the 33 genes analyzed, only MTHFR677 polymorphisms (a gene with a critical role in regulating plasma homocysteine levels) emerged as significantly related to higher EAT volumes in our population (OR 1.4, 95% CI: 1.100–1.684, p=0.005).

Conclusion
Patients with a higher polymorphism burden in genes involved in the oxidation, renin-angiotensin, cellular, diabetes/obesity and dyslipidemia pathways present higher levels of epicardial fat. This potential association seems to be independent from the expected association between epicardial fat and cardiovascular risk factors. To our knowledge, this is the first time such genetic profiling has been done, casting further insight into this complex matter.

Funding Acknowledgement
Type of funding source: None
Aetiology-dependent impairment of mitochondrial function in the failing human heart
Authors: Borger J , Scheiber D , Horn P , Pesta D , Boeken U , Akhyari P , Lichtenberg A , Kelm M , Roden M , Szendroedi J , Westenfeld R 
Published: November 2020

Abstract

Background
Alterations of mitochondrial function have been identified to play a role in Heart Failure (HF) pathophysiology. Oxidative phosphorylation (OXPHOS) capacity of the myocardium was shown to be reduced in the failing heart. Ineffective mitochondrial function promotes formation of reactive oxygen species (ROS) that may affect remodelling in ischemia. Thus far, human mitochondrial function comparing dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) resembling the main aetiologies of heart failure with reduced ejection fraction (HFrEF) has not been investigated.

Purpose
We hypothesised that
1. ROS production is elevated in left ventricular myocardial tissue specimens of ICM patients compared to DCM.
2. Mitochondrial OXPHOS capacity is higher in left ventricular myocardial tissue specimens of DCM compared to ICM patients.

Methods
Myocardial tissue was obtained from the left ventricular apex from 63 patients (38 ICM, 25 DCM) with advanced HFrEF requiring implantation of a Left Ventricular Assist Device (LVAD). We performed high-resolution respirometry (HRR, OROBOROS Oxygraph-2k) in saponine-permeabilised myocardial fibres and measured ROS production fluoroscopically via the Amplex Red method. Statistical analysis was conducted using GraphPad Prism 7 and IBM SPSS v26.0.

Results
Groups were of comparable age (61.5±1.2 vs. 59.3±2.4 years, p=n.s.), sex (87% vs 85% male, p=n.s.), diabetic status (32% vs 38.4% type 2 diabetes mellitus, p=n.s.), and body mass index (28.1±0.8 vs. 26.3±1.1 kg/m2, p=n.s.). We detected reduced myocardial mitochondrial OXPHOS capacity in ICM under state 3 conditions by about 15% (68.7±34.0 vs. 80.9±30.5 pmol/(s*mg), p&lt;0.05), after addition of Glutamate by 25% (78.9±38.7 vs. 104.8±41.2 pmol/(s*mg), p&lt;0.01) as well as after Succinate (115.5±65.5 vs. 155±62.0 pmol/(s*mg), p&lt;0.01), uncoupling agent FCCP (114.1±56.8 vs. 150.5±47.3 pmol/(s*mg), p&lt;0.01), and by about 40% after addition of Complex I inhibitor Rotenone (55.5±25.9 vs. 96.9±28.0 pmol/(s*mg), p&lt;0.001). We detected no difference in ROS production between ICM and DCM (0.6±0.05 vs. 0.76±0.08 pmol/(s*ml), p=n.s.).

Conclusion
This is the first human study deciphering distinct alterations in mitochondrial function (OXPHOS capacity) in ventricular myocardium of HFrEF patients. Future studies may address how distinct metabolic patterns at the time of implantation may relate to long-term outcome of HFrEF in terms of remodelling and recovery.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): DFG (German Research Foundation)
RBP4 induces pyroptosis in cardiomyocytes via activating NLRP3/Caspase-1/GSDMD pathway in acute myocardial infarction
Authors: Gao W , Zhang K.Z 
Published: November 2020

Abstract

Aims
Myocardial infarction (MI) is the most common cause of cardiac morbidity and mortality worldwide. Pyroptosis is a novel form of inflammatory cell death that could be driven by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation following MI. Retinol binding protein 4 (RBP4) is an pro-inflammatory adipokine with adverse effects on cardiovascular system. We investigated the role and underlying mechanism of RBP4 in inducing pyroptosis in cardiomyocytes in acute MI.

Methods and results
We established a mice MI model which ligated with the left anterior descending coronary artery and a cardiomyocytes injury model treated by oxygen-glucose deprivation (OGD). Western blot showed that RBP4 expression was exclusively increased in the heart following MI, as RBP4 expression remains unchanged in adipose tissues and liver. Cardicac pyroptosis was induced in MI mice as evidenced by increased expression of pyroptosis-related proteins, including NLRP3, Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18. Moreover, increased cardiac RBP4 level was positively correlated with serum IL-1β and IL-18 levels in MI mice. Immunofluorescence identified that RBP4 was expressed in cardiomyocytes and was up-regulated along with increased pyroptosis-related proteins after treatment with OGD. Transfection of RBP4 adenovirus promoted pyroptosis while inhibition of RBP4 ameliorated OGD-induced pyroptosis in cardiomyocytes. Mechanically, transfection of NLRP3 siRNA or GSDMD siRNA along with RBP4 adenovirus could attenuate RBP4-induced pyroptosis in cardiomyocytes. Furthermore, in situ injection of adenovirus containing RBP4 siRNA could also attenuate pyroptosis and cardiac inflammation following MI in mice.

Conclusion
RBP4 is presented in cardiomyocytes and induces cardiac pyroptosis via activating NLRP3/Caspase-1/GSDMD pathway in acute MI

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): National Nature Science Foundation of China
Procalcific effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) in chronic kidney disease (CKD)
Authors: Ferri N , Lupo M.G.P , Rattazzi M.R 
Published: November 2020

Abstract

Aim
PCSK9 has been recently associated with a higher rate of calcification in hypercholesterolemic, diabetes and CKD patients. The aim of this study was thus to investigate the role of PCSK9 in VC process, under uremic condition, both on in vivo and in vitro experimental settings.

Methods
Sprauge Dawley rats were fed a standard diet (SD, n=11) or uremic diet (UD, n=11) for 6 weeks. Calcium crystals in aortas were visualized by von Kossa staining and quantified by a colorimetric assay and plasma total cholesterol determined. Control and PCSK9-overexpressing smooth muscle cells (SMCsPCSK9) were cultured with 2.5% FCS ± Pi for 7 days. Hydroxyapatite deposition by SMCs was measured by a colorimetric assay. The number and the content of pro-calcific extracellular vesicles (EVs) budding from the cells were determined.

Results
The hyperphosphatemia secondary to CKD lead to rat aortic calcification (+7.3-fold) and a significant increase in TC and PCSK9 levels (+1.4 and +2.7-fold, respectively). Higher expression of PCSK9 was also observed in kidney (+4.8-fold) and liver (+1.5-fold). SMCsPCSK9 showed higher extracellular calcium deposition (+1.4-fold) in response to Pi and increase EVs production (+7-fold). The incubation of control cells with recombinant PCSK9 did not induce extracellular calcium deposition.

Conclusions
Our study suggest a positive effect of intracellular PCSK9 on vascular calcification in CKD condition. Pro-calcific budding of EVs seems one of the possible mediators of this process.
PCSK9 and calcification

Funding Acknowledgement
Type of funding source: None
Evaluation of noninvasive electrophysiological imaging accuracy for focal atrial arrhythmias
Authors: Budanova M , Chmelevsky M , Zubarev S , Treshkur T , Lebedev D 
Published: November 2020

Abstract

Background
High accuracy of noninvasive electrocardiographic imaging (ECGI) has recently been shown for topical diagnostics of ventricular arrhythmias. However, the precision of diagnostics of atrial focal arrhythmias requires clarification. To estimate the accuracy of ECGI for premature atrial contraction (PAC) we performed atrial pacing in patients with CRT system and compared early activation zone (EAZ) with pacemaker's tip location.

Purpose
To determine the accuracy of ECGI for focal atrial arrhythmias using atrial pacing.

Methods
Twenty-six patients (m/f – 18/9), age (min–max) 52 (26–78) with CRT system and pacemaker's tip location in the right atrium (RA) appendage underwent ECGI (“Amycard 01C”) in combination with CT or MR imaging. Thirty-four atrial pacing (mono- and bipolar) was performed in all patients using standard amplitude 1.5–3.8 mV. Epi-/endocardial polygonal heart models were created and isopotential maps were calculated. The distance between EAZ and the pacemaker's tip were measured for ECG recordings without using the isoline filter on endocardial surface (Fig. 1) as well as for epicardial surface. The time between epicardial and endocardial EAZ breakthrough was calculated also.

Results
On endocardial surface the EAZ was located in RA appendage, the base of superior cava vena or superior lateral RA wall. The distance (mm) (Me (min; max)) between EAZ and the pacemacer's tip was 28 (6; 68). For epicardial surface in most cases the EAZ was also located in RA appendage, the base of superior cava vena or superior lateral RA wall. In two cases the EAZ was located in inferior septal RA wall, in one case - in superior septal RA wall and in five cases the EAZ was undetectable. The distance between EAZ and the pacemacer's tip was 22 (6; 48). The time (ms) (Mean; Me (min; max)) between EAZ of the endocardial and epicardial surfaces was 16; 7 (0; 68).

Conclusion
ECGI allows to assess the location of focal atrial arrhythmias on endocardial surface and sometimes on epicardial surface also within the three segments. The results of this study revealed that accuracy of ECGI for atrial arrhythmias is worse than for ventricular arrhythmias. However, it is better on epicardial surface of atrium when EAZ can be determined.

Funding Acknowledgement
Type of funding source: None