bluuebunny/crossref_metadata_2025_split huggingface dataset:
Not chronic exercise but acute exercise is related with increased cell survival, enhanced cell proliferation and decreased cell apoptosis
Authors: Postula M , Wicik Z , Eyileten C , Soplinska A , Czajka P , Nowak A , Jarosz-Popek J , Malek L 
Published: November 2020

Abstract

Background
Endurance training can be described as long-time activity characterized by high dynamic and low to high power and was proven beneficial in CVD prevention. Nevertheless, studies reported that excessive endurance training can act as double-edged sword inducing the inflammatory response and cell apoptosis. This negative effect can be the reason of exercise duration.

Purpose
In order to investigate the effect of the training duration we compared and analysed acute vs chronic exercise by using in silico technique and we performed two different bioinformatics analysis: tissue-specific and cardiovascular process specific.

Materials
Bioinformatics analysis miRNA targets predictions, data filtering and visualization as interaction networks were performed. We used multiMiR 1.4 R package, hemopoiesis, angiogenesis, cardiac muscle functions, muscle hypertrophy process was performed a screening of the GO terms for the presence of the key words using the biomaRt package in R, Gene-gene interaction data were retrieved from String App, Cytoscape. Enrichment analysis of Reactome and KEGG pathways using String App. p&lt;0.05.

Results
Enrichment analysis of Reactome and Kegg pathways revealed strong regulation of senescence-related pathways, RUNX1 expression and activity, Ca2+ signaling involving AGO genes. For the first time our in silico analysis showed that AGO, HMGA2 genes may be associated with adaptive changes in response to exercise. Importantly, we found, that PI3K/AKT signalling (pathway incusing cell survival, growth, and proliferation) was present only in acute but not in chronic exercise.

Conclusions
In our analysis long-term training miRNA-gene target interaction was different than the short-term training. As PI3K/AKT signaling was present only in acute exercise, we suggest that not long-term but short-term training can be related with increased cell survival, enhanced cell proliferation, and decreased cell apoptosis.
Genes associated cardiac muscle function

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): “Preludium” from the National Science Center, Poland
Sleep disordered breathing: prevalence and association with cardiovascular disease in the French general population
Authors: Balagny P , Wiernik E , Matta J , Frija-Masson J , Vidal-Petiot E , Steg P.G , Ribet C , Goldberg M , D'Ortho M.P , Zins M 
Published: November 2020

Abstract

Background
Sleep Disordered Breathing (SDB) is highly prevalent and associated with cardiovascular disease (CVD) but many studies have a limited sample size or uncertain generalizability.

Purpose
The aim of this study was to obtain contemporary data on SDB prevalence and to assess its impact on CVD occurrence in a large French population-based sample.

Methods
Data came from participants of the French population-based CONSTANCES cohort, included between 2012 and 2016, with clinical interview, examination and standard biology at inclusion and who were screened for SDB in 2017 using the Berlin Questionnaire (BQ). Follow-up was performed through yearly CONSTANCES questionnaires. CVD occurrence was defined by self-declared myocardial infarction or stroke between 2013 and 2017. Exposure variables were SDB diagnosis on the basis on BQ and its related sleeping symptoms (snoring, apnea and sleepiness). Odds Ratios (OR) were computed with their 95% Confidence Interval (95% CI) and adjusted for age, sex, smoking, dyslipidemia, diabetes, hypertension and body mass index (except for SDB since BQ considers these variables).

Results
Among 54 228 participants, SDB prevalence was 16.1%. Over four years of follow-up, CVD occurred in 2.23% of SDB participants vs 0.72% in non SDB (OR=1.72, 95% CI [1.41–2.09]). CVD occurrence did not increase significantly with snoring (OR=0.95, 95% CI [0.78; 1.17]), but with apnea (OR=1.34, 95% CI [1.05; 1.71]) and with sleepiness (OR=1.42, 95% CI [1.18–1.72] when fatigue occurred after-sleep and OR=1.62, 95% CI [1.33–1.97] during waking time). These associations remained non-significant for snoring regardless of its frequency or noise, were significant for sleepiness as soon as it happened at least once a week and tended to increase with its frequency whenever fatigue occurred (p for trend&lt;0.001). Subgroups analysis in hypertensive and non-hypertensive participants found similar results concerning snoring and sleepiness.

Conclusions
These results confirm that SDB is highly prevalent in the general French population and is associated with a higher occurrence of CVD particularly in sleepy and apneic subjects. Screen for SDB and its symptoms should be relevant to identify high cardiovascular risk people who would benefit from preventive measures.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Plan d'Investissement d'Avenir-3 (PIA3-RHU, Ministry of Health)
The Finnish Diabetes Risk Score (FINDRISC) and incident diabetes and low-grade inflammation
Authors: Pesaro A , Bittencourt M.S , Franken M , Carvalho J.A.M , Silva D.J.B , Santos R.D 
Published: November 2020

Abstract

Background
The Finnish Diabetes Risk Score (FINDRISC) (FR) was developed in Europe to predict type 2 diabetes mellitus (T2DM) risk without need of laboratory tests. Since T2DM is associated with low-grade inflammation, we evaluated the ability of FR to predict either T2DM or elevation in high sensitivity C- reactive protein (CRP), a biomarker of higher cardiovascular risk.

Methods
We included 41,880 subjects (age 41.9±9.7 years; 31% female) who underwent health evaluation between 2008 and 2016 in a single centre in Brazil. The cross-sectional association of FR with T2DM and hs-CRP ≥2.0 mg/L was tested in multivariate models. During a follow-up of 5±3 years, the predictive value of FR for incident T2DM and elevated CRP was tested, respectively, in 10,559 non-diabetic individuals and a subset of 2,816 subjects with baseline low CRP, using logistic regression. Models were adjusted for confounders such as sex, use of medications for dyslipidemia, smoking, and baseline plasma levels of glucose, creatinine and lipids. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative and predictive values of FR for T2DM and CRP ≥2.0 mg/L.

Results
In the cross-sectional analysis, 1,146 (2.7%) individuals had T2DM. In a subgroup of 26,667 individuals in which CRP was measured, 9,229 (34.6%) had CRP ≥2.0 mg / L. During follow-up, there were 364 cases (3.5%) of incidental T2DM, and in the subgroup in which CRP was reassessed (n=2,816 individuals), there were 520 individuals (18.5%) with CRP ≥2.0 mg/L. FR was associated with either T2DM or elevated CRP in cross sectional analysis (respectively, OR 1.24, 95% CI: 1.23–1.26, P&lt;0.001; and OR 1.10, 95% CI: 1.09–1.11, P&lt;0.001; per FR unit), and in longitudinal analysis (respectively OR 1.17, 95% CI: 1.14–1.20, P&lt;0.001; and OR 1.04, 95% CI: 1.02–1.07, P&lt;0.001; per FR unit). In comparison with individuals with low FR, those with moderate, high and very high values showed significant and proportional increases of 3 to 22 fold in the chance of current DMT2 (P&lt;0.001) and 2 to 4 fold in the chance of high CRP (P&lt;0.001). During follow-up, these increases were 2 to 8 fold in the chance of incidental T2DM (P&lt;0.001) and 1.3 to 2 fold in the chance of high CRP (P&lt;0.005). AUC from cross-sectional analysis for DMT2 and CRP ≥2.0 mg/L were respectively 0.82 (95% CI 0.80–0.83) and 0.63 (95% CI 0.63–0.64), and in longitudinal analysis 0.79 (95% CI 0.77–0.82) and 0.54 (95% CI 0.52–0.58), respectively.

Conclusion
FR was associated with the presence and onset of DMT2 and low-grade inflammation, but it predicted better T2DM risk than low-grade inflammation. Therefore, this inexpensive score can be useful for screening and prediction of T2DM. In addition, elevated serum inflammation in individuals with higher FR, may help explain the increased cardiovascular risk in this subset of patients.

Funding Acknowledgement
Type of funding source: None
Association between the FINDRISC score and the risk of metabolic syndrome and hepatic steatosis
Authors: Godoi Bernardes Da Silva D , Dias Santos R , Sommer Bittencourt M , Carvalho J.A.M , Franken M , Pereira Pesaro A.E 
Published: November 2020

Abstract

Introduction
The Finnish Diabetes Risk Score (FINDRISC) was developed in Europe to predict type 2 diabetes mellitus (T2DM) risk without need of laboratory tests. Small cross-sectional studies analyzed the association between RF with metabolic syndrome (MS) or hepatic steatosis (HS). Our objective was to test the association of FINDRISC with MS or HS, in a transversal and longitudinal way.

Methods
In 41,668 individuals (age 41.9±9.7 years; 30.8% women) who underwent health evaluation between 2008 and 2016 in a single centre in Brazil, we tested the transversal association between FINDRISC and MS or HS, in multivariate models. The same analyzes were performed longitudinally in non-diabetic subgroups, followed for 5±3 years, to test the predictive value of FINDRISC and the incidental risk of MS (n=10,075 individuals) or HS (n=7,097 individuals), using logistic regression. Models were adjusted for confounders such as sex, use of medications for dyslipidemia, smoking, and baseline plasma levels of glucose, creatinine and lipids. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative and predictive values of FINDRISC for MS and HS.

Results
In the cross-sectional analysis, 2,252 (5%) individuals had MS and 14,176 (34%) HS. In the longitudinal analysis, there were 302 cases of incidental MS (2%) and 1,096 cases of HS (15%). FINDRISC was independently associated with MS and HS in the cross-sectional analysis (respectively, OR 1.27, 95% CI: 1.25–1.28, P&lt;0.001; and OR 1.21, 95% CI: 1.20–1.22, P&lt;0.001, per FINDRISC unit) and in longitudinal analysis (respectively, OR of 1.18, 95% CI: 1.15–1.21, P&lt;0.001; and OR of 1.10, 95% CI: 1.08–1.11, P&lt;0.001, per FINDRISC unit). In comparison with individuals with low FINDRISC, those with moderate, high and very high values showed significant and proportional increases of the 12 to 77 fold in the chance of current SM (P&lt;0.001) and 3 to 10 fold in the chance of HS (P&lt;0.001). During follow-up, these increases were 3 to 10 fold in the chance of incidental MS (P&lt;0.001) and 1 to 3 fold in the chance of HS (P&lt;0.001). The AUC from cross-sectional analysis for MS and HS were respectively 0.82 (95% CI 0.81–0.83) and 0.76 (95% CI 0.75–0.76), and in longitudinal analysis 0.73 (95% CI 0.70–0.76) and 0.63 (95% CI 0.61–0.65), respectively.

Conclusion
FINDRISC was associated with the presence and onset of MS and HS, but it predicted better metabolic syndrome risk than hepatic steatosis. Therefore, this simple, practical and low-cost score can be useful for population screening and identification of subgroups of individuals at higher risk future metabolic diseases.

Funding Acknowledgement
Type of funding source: None
Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure – a Mendelian randomization study in the FINRISK cohort
Authors: Boerschel C , Geelhoed B , Niiranen T , Havulinna A.S , Fouodo C.J.K , Scheinhardt M.O , Blankenberg S , Jousilahti P , Kuulasmaa K , Zeller T , Salomaa V , Schnabel R.B 
Published: November 2020

Abstract

Background
Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and in previous studies several single nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified.

Purpose
We investigated whether a causal relationship exists between natriuretic peptides and AF as well as HF using a Mendelian randomization approach.

Methods
N-terminal pro B-type natriuretic peptide (NT-proBNP) (N=6669), B-type natriuretic peptide (BNP) (N=6674) and mid-regional pro atrial natriuretic peptide (MR-proANP) (N=6813) were measured in the FINRISK 1997 cohort. Thirty common SNPs related to NT-proBNP, BNP and MR-proANP were selected from prior studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF separately. Polygenic risk scores (PRS) based on multiple SNPs were used as the genetic instrumental variable in Mendelian randomizations.

Results
PRS were significantly associated with the three natriuretic peptides. PRS were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation, other than a weak one, is unlikely.

Conclusion
In our Mendelian randomization approach, based on common genetic variation at the NPPA-NPPB locus, associations of the common polymorphisms with natriuretic peptides and the protein biomarkers themselves with incident disease could be confirmed. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.
Comparison of hazard ratios

Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, German Ministry of Research and Education
Resting levels of cardiac markers in athletes
Authors: Kiss O , Frivaldszky L , Tokodi M , Babity M , Bognar C.S , Skopal J , Kovacs A , Vago H , Lakatos B , Zamodics M , Rakoczi R , Czimbalmos C.S , Dohy Z.S , Menyhart-Hetenyi A , Merkely B 
Published: November 2020

Abstract

Introduction
Examination of specific cardiac enzymes and peptide fragments is essential in cases of acute myocardial ischemia and heart failure. According to previous data, exhausting physical effort may cause temporary increase of cardiac necroenzyme levels, while no information is available on their resting values in athletes.

Methods
Resting serum levels of hsTroponinT, CKMB, LDH and NT-proBNP were measured as part of extended sports cardiology screening in healthy athletes and a healthy sedentary non-athlete control group. Depending on normality, groups were compared with two-tailed Student's t-test or Mann-Whitney U-test. Statistical analysis was processed in RStudio integrated development environment.

Results
Results of 237 healthy athletes from different sports (male: 144, age: 19.1±5.9 years, training: 16.0±6.7 hours/week) and 53 sedentary non-athletes (male: 23, age: 19.8±3.2 years, training: 2.6±2.3 hours/week) were analysed. In athletes, increased resting cardiac marker levels were measured as follows: CKMB: 6.3% (n=15), LDH: 3.4% (n=8), hsTroponinT: 4.2% (n=10), NT-proBNP: 0.8% (n=2) of the cases. No elevation of CKMB and hsTroponin T levels were measured in the control group, while only single cases of increased LDH and NT-proBNP were detected. We measured higher levels of CKMB (17.6±7.3 vs. 12.3±3.4 U/l, p&lt;0.001), LDH (322.4±60.8 vs. 286.0±51.1 U/l, p&lt;0.001) and hsTroponinT (6.2±4.7 vs. 4.3±1.4 ng/l, p&lt;0.05), while lower levels of NT-proBNP (23.9±27.2 vs. 49.8±38.7 pg/ml, p&lt;0.001) in athletes compared to the control group. In male athletes, higher levels of CKMB (18.5±6.6 vs. 16.0±8.2 U/l, p&lt;0.001), LDH (337.0±62.2 vs. 300.7±51.9 U/l, p&lt;0.001) and hsTroponinT (7.0±5.3 vs. 4.3±1.9 ng/l, p&lt;0.001), and lower levels of NT-proBNP (19.8±23.1 vs. 35.0±34.1 pg/ml, p&lt;0.001) were measured compared to female athletes. Levels of hsTroponinT decreased in athletes due to increasing age (r=−0.20, p&lt;0.05).

Discussion
According to our results, resting levels of cardiac markers show significant alterations due to sport adaptation of the heart. These changes depend on age and sex as well.

Conclusions
Our research attract attention to different assessment of cardiac markers in athletes in respect of recognition of cardiovascular pathologies.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): This project was supported by a grant from the National Research, Development and Innovation Office (NKFIH) of Hungary.
Combined effect of cigarette smoking and prediabetes on structural and functional changes of large arteries
Authors: Ioakeimidis N , Dima I , Terentes-Printzios D , Georgakopoulos C , Angelis A , Gourgouli I , Solomou E , Skoumas I , Tousoulis D , Vlachopoulos C 
Published: November 2020

Abstract

Purpose
Smoking is a major risk factor for cardiovascular disease and prediabetes is associated with excess risks for adverse cardiovascular outcomes and death. Aim of this study was to explore whether smoking and prediabetes exert a synergistic unfavourable effect on functional and structural parameters of large arteries.

Methods
We measured carotid-femoral pulse wave velocity (cfPWV), augmentation index (AIx) and carotid intima media thickness (cIMT) in 407 individuals without known atherosclerotic disease (mean age: 52±8 years) categorized into four age-matched groups according to glucose metabolic and smoking status: Smokers with diabetes (n=68), Smokers with prediabetes (n=87), Non-smokers with prediabetes (n=98) and Non- smokers with normal fasting blood glucose (FBG) (n=154). Prediabetes was defined as impaired fasting glucose (100–125 mg/dL), impaired glucose tolerance (2-hour glucose level of 140–199 mg/dL during an oral glucose tolerance test), or glycosylated hemoglobin (HbA1c) level of 5.7% to 6.4%. High sensitivity C-reactive protein (hsCRP) was measured in all patients.

Results
Systolic pressure, pulse pressure were increased and hsCRP levels were higher in smokers with diabetes compared to the three other groups (overall P&lt;0.05, P&lt;0.01 and P&lt;0.05, respectively, ANOVA). The cumulative tobacco exposure (measured in pack-years) was similar between smokers with diabetes and smokers with prediabetes (45 pack-years). Figure 1 shows cfPWV, AIx and cIMT of the four groups. Interestingly, smokers with diabetes and smokers with prediabetes have similar mean cfPWV and cIMT and significantly higher values compared to non-smokers with prediabetes and non-smokers with normal FBG. The associations remained statistically significant even after adjusting for systolic pressure and hsCRP level. AIx was not different between the four study groups.

Conclusion
The combination of prediabetes and smoking is associated with higher cfPWV and cIMT values compared to prediabetes alone. The smokers with impaired glucose regulation have functional and structural alterations of large arteries similar to that of smokers with established diabetes. Considering the risk for developing prediabetes in relation to smoking status and the number of cigarettes smoked daily and the independent predictive value of assessing vascular changes in large arteries, the present findings may have important clinical and prognostic implications.
Figure 1. Smoking, prediabetes and vascular changes

Funding Acknowledgement
Type of funding source: None
Using coronary artery calcium to guide cardiovascular risk reduction: insights from the CAUGHT-CAD trial
Authors: Venkataraman P , Marwick T , Marwick T , Huynh Q , Huynh Q 
Published: November 2020

Abstract

Introduction
International guidelines now recognise the value of CT coronary artery calcium scoring (CAC) to guide statin prescribing decisions. However, evidence is conflicting on CAC's potential to reinforce clinical advice, promote adherence and facilitating positive health behavioural change.

Purpose
We sought to assess the impact of a CAC-guided statin treatment protocol on cardiovascular risk at 12 months.

Methods
The CAUGHT-CAD trial recruited 455 asymptomatic, statin-naïve individuals at intermediate risk CVD risk with a family history of premature coronary artery disease (CAD) and CAC scores between 1 and 400. Participants were randomised to visualisation of their CAC or remain blinded. Both groups were provided standard risk factor advice. We calculated the 10-year SCORE predicted risk based on participant's baseline and 12 month risk factor profile. Paired t test and regression analysis was used to assess change in predicted risk both within and between treatment group.

Results
CAC-visualisation and statin treatment resulted in a 0.45% absolute and 21% relative risk reduction in predicted SCORE risk at 1 year. The CAC exposure group demonstrated 2.78 mmHg reduction in systolic blood pressure compared to the blinded group (p&lt;0.01); accounting for 25% of the predicted absolute risk reduction despite both groups reporting the same level of dietary and physical activity goals achieved. 9 blinded participants who were commenced on statins off-protocol showed attenuated reductions in lipids compared to the CAC exposed group (total cholesterol: m-0.5 vs. −1.5 mmol/L, p&lt;0.01; LDL −0.6 mmol/L vs. −1.4 mmol/L, p&lt;0.01) suggesting poorer adherence.

Conclusion
CAC visualisation can augment primary CVD prevention by improving systolic blood pressure and absolute reduction in lipids with statin treatment.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): NHMRC project grant