bluuebunny/crossref_metadata_2025_split huggingface dataset:
1272Physical activity and mortality with and without cardiovascular disease
Authors: Jeong S , Kang S H , Yoon C H , Youn T J , Chae I H , Kim S H 
Published: October 2019

Abstract

Background/Introduction
Physical activity has been shown to reduce mortality in a dose-response fashion. Current guidelines recommend 500 to 1,000 MET-min per week of regular physical activity. However, evidence is limited regarding the specific dose-response relationship in patients with cardiovascular disease.

Purpose
Our aim was to compare the impact of physical activity on mortality in primary versus secondary cardiovascular prevention.

Methods
We analyzed 441,798 individuals with complete information on physical activity levels between 2009 and 2015 were extracted from a population-based cohort (National Health Insurance Service-National Health Screening cohort). Physical activity measured by self-report questionnaires. A rating of 2.9, 4.0, and 7.0 METs were assigned for light-intensity, moderate-intensity, and vigorous-intensity activities, respectively. Physical activity-related energy expenditure (MET-min/week) was calculated by summing the product of frequency, intensity, and duration. The level of physical activity was classified into 0, 0 to 499, 500 to 999, 1,000 to 1,499, and ≥1,500 MET-min/week. Study participants were stratified by the presence of cardiovascular disease, defined as prior myocardial infarction, ischemic heart disease, prior stroke, and/or chronic heart failure. The main study outcome was all-cause mortality. The median follow-up duration was 5.9 years.

Results
Individuals with cardiovascular disease had lower physical activity levels and a higher risk of mortality than those without cardiovascular disease. There was an inverse relationship between the physical activity level and the mortality risk in both groups. The benefit in the secondary prevention group was shown to be greater than that in the primary prevention group: every 500 MET-min/week increase in physical activity resulted in a 14% and 7% risk reduction in mortality in the secondary and primary prevention groups, respectively (interaction P<0.001). In addition, while individuals without cardiovascular disease benefited the most between 0 and 500 MET-min/week of physical activity, the benefit in those with cardiovascular disease continued above 500 to 1,000 MET-min/week. The adjusted mortality risk of individuals with cardiovascular disease who performed a high level of physical activity (≥1,000 MET-min/week) was shown to be comparable to or lower than that of their counterparts without cardiovascular disease.
Adjusted risk of mortality

Conclusion
Individuals with cardiovascular disease may benefit from physical activity to a greater extent than do healthy subjects without cardiovascular disease. Clinicians should encourage patients with cardiovascular disease to maintain a physically active lifestyle as much as possible.
1444Metabolically healthy obesity (MHO) in the Malmo Diet Cancer Study - epidemiology and prospective risks
Authors: Korduner J , Bachus E , Jujic A , Magnusson M , Nilsson P M 
Published: October 2019

Abstract

Background/Aims
Metabolically healthy obesity (MHO) is a controversial topic, since the underlying mechanisms and contributing factors behind this phenotype remain unclear. Here we aimed to investigate the characteristics of MHO, as well as prospective mortality risk.

Method
A cross-sectional analysis was carried out in a subsample of 3,812 obese subjects (BMI ≥30 kg/m2) selected from the Malmo Diet Cancer Study (MDCS) cohort (n=28,403). Subjects with MHO (n=1182; mean age 58±7 years) were defined by having no records of hospitalization in the national Swedish Hospital Discharge Register prior to the baseline examination, other than hospitalization due to normal deliveries or external injuries. MHO subjects were further compared to subjects with metabolically unhealthy obesity, MUO (n=2,630; mean age 60±7 years), and all non-obese individuals (n=24,591; mean age 58±8 years) in the cohort study. Moreover, prospective risk analyses for incident morbidity and mortality were carried out by Cox regression.

Results
Compared to MOU individuals (one-way ANOVA), MHO individuals were younger (58±7 years vs. 60±7 years, p=0.001) and more likely to be male (41.2% vs 37.1%, p=0.016). MHO individuals reported a significantly lower proportion of sedentary life style than MUO (17.4% vs. 21.9%, p=0.009), and were more likely to hold a university degree (13.4% vs. 9.4%, p=0.003). Furthermore, MHO individuals had significantly lower HbA1c (p=0.012), fasting plasma glucose (p=0.001) and triglyceride levels (p=0.011) as compared to their MOU counterparts. Cox-regression analysis adjusted for age, sex, smoking and blood pressure (follow-up time 20±6 years) showed both a significantly lower all-cause mortality risk for MHO individuals as compared to MUO (HR 0.74, 95% CI: 0.66–0.82; p=0.001), as well as lower total incident cardiovascular (CV) morbidity risk (HR 0.69, 95% CI: 0.60–0.80; p=0.001). Interestingly, when comparing MHO individuals to all non-obese individuals in the MDCS, there were no significant differences in neither mortality risk (p=0.9), nor incident CV morbidity risk (p=0.7).
All-cause mortality risk

Conclusion
Compared to MUO individuals, MHO individuals presented with a higher level of education- and physical activity together with a more favorable lipid- and glucose profile. MHO individuals were at significantly lower prospective risk of total- and cardiovascular mortality during 20-years follow-up, as compared to MOU individuals. Notably, no significant differences could be seen in mortality and CV morbidity risks when comparing MHO subjects to all non-obese individuals in the total cohort.

Acknowledgement/Funding
The Research Council of Sweden and Skane University Hospital Funds and Foundations (Sweden)
2177Cardiac resynchronization therapy in patients greater than 75 years of age - results from the European Society of Cardiology Survey II with 11 088 patients
Authors: Normand C , Dickstein K , Linde C 
Published: October 2019

Abstract

Background
Cardiac Resynchronization Therapy (CRT) reduces morbidity and mortality in selected patients with heart failure (HF) and electrical dyssynchrony. The median age for patients included in the CRT landmark trials ranged from 62–68 years, therefore limited trial evidence exists on CRT in patients ≥75 years of age.

Purpose
To assess similarities and differences in patient demographics and implantation practice in different age groups implanted with a CRT device.

Methods
Between 2015 and 2017, two European Society of Cardiology (ESC) associations, European Heath Rhythm Society and the Heart Failure Association, conducted the CRT Survey II, a survey of CRT implantations in 11,088 patients in 42 ESC member states.

Results
In our survey 32% of patients included were ≥75 years of age. These patients were more frequently in NYHA Class III or IV, had more comorbidity (including hypertension, atrial fibrillation, anaemia and renal dysfunction) and had significantly higher NT-pro BNP levels than younger patients. Slightly fewer patients ≥75 years of age had LBBB but all groups had the same median QRS duration. Despite substantially more patients ≥75 years of age having HF of ischaemic aetiology compared with those <65 year of age, far fewer patients in oldest age group category were implanted with a CRT-defibrillator (CRT-D) compared with those in the youngest group.
CRT Survey II Patients by Age Categories Demographics Age <65 years Age 65–74 years Age ≥75 years N 3478 (32%) 4025 (36%) 3536 (32%) NYHA class III & IV 52% 59% 66%* Ischaemic HF aetiology 33% 49% 50%* Atrial fibrillation 17% 27% 33* NT proBNP (pg/ml, median, IQR) 1651 (670, 3811) 2319 (1070, 5169) 3510 (1647, 7631)* CRT-D 81% 76% 52%* Peri-procedural complications 5% 6% 6% Adverse Events during hospitalization 4% 5% 5% CRT-D, Cardiac resynchronization therapy – defibrillator; HF, heart failure; IQR, interquartile range. *Differences between groups is significant with p<0.001.

Conclusions
Patients ≥75 years of age had greater comorbidity and experienced more symptoms from their heart failure. However, they did not suffer more complications or adverse events during the index hospitalization, suggesting that CRT may safely be offered to elderly patients.

Acknowledgement/Funding
The work was supported by EHRA, the HFA, Biotronik, Boston Scientific, Medtronic, Sorin, St. Jude, Abbott, Bayer, Bristol-Myers Squibb and Servier
2181The prothrombotic transcriptome of reticulated platelets
Authors: Bongiovanni D , Santamaria G , Klug M , Santovito D , Felicetta A , Hristov M , Aslani M , Weber C , Peano C , Condorelli G , Laugwitz K L , Bernlochner I 
Published: October 2019

Abstract

Introduction
Reticulated platelets (RPs) are young, hyper-reactive platelets that are larger and contain significantly more RNA compared to older mature platelets. High levels of RPs in peripheral blood are predictors of an insufficient response to dual antiplatelet therapy in cardiovascular patients and of adverse cardiovascular events also in non-cardiac patients. However, the mechanisms underlying these correlations remains widely unknown and the biology of RPs has not been investigated yet.

Purpose
We aimed to compare for the first time the transcriptomic profiles of RPs and mature platelets (MPs).

Methods
RPs and MPs from peripheral blood of healthy donors were identified and isolated using FACS/Sorting based on their RNA-content. Immediately after sorting, RNA was extracted and quality, concentration and integrity was assessed with the Tapestation 4200 platform (Agilent). Total- and small-RNA libraries were prepared, multiplexed and sequenced on a NextSeq 500 Illumina platform

Results
Total-RNA-sequencing revealed 1744 differentially expressed genes (670 downregulated 1074 upregulated) in RPs compared to MPs (Figure 1A, B). In particular, transcripts for the collagen receptor GP6, thromboxane receptor A2 (TBXA2R), thrombin receptor PAR4 (F2RL3) and ATP receptor P2RX1 were significantly enriched in RPs, whereas several RNA regulators as the ribonuclease PARN, the RISC-component TNRC6A and the splicing factor LUC7L3 were downregulated in RPs. Gene ontology analysis revealed an enrichment of relevant biological categories in RPs including platelet activation and blood coagulation (Figure 1C). Gene Set Enrichment Analysis showed an enrichment of several activation pathways like thrombin, thromboxane and GPIIb/IIIa signaling in RPs. Small-RNA-sequencing reported 9 miRNAs significantly downregulated in RPs with targets involved in platelet reactivity.
Figure 1

Conclusions
This study represents the first comparative transcriptome analysis of RPs and MPs and reports for the first time a differential enrichment of transcripts involved in platelet activation. The clear upregulation of prothrombotic signaling in RPs could explain, at least in part, their hyper-activity and their correlation with cardiovascular events in different pathological settings (trancripts enriched in RPs: Figure 1D).

Acknowledgement/Funding
German Society of Cardiology (DGK Nr.102018) ESC First conctact initiative grant 2018
2200Predictors of patient decision time in ST elevation myocardial infarction data from an observational cross sectional survey study
Authors: Ericsson M , Thylen I , Hellstrom Angerud K , Swahn E , Stromberg A , Sederholm Lawesson S 
Published: October 2019

Abstract

Background
Short time from symptom onset until reperfusion is imperative in ST-elevation myocardial infarction (STEMI). System delay has been successfully shortened but patients delay has had less favorable development. The aim of this study was to find out clinical, contextual, behavioral and cognitive factors associated with decision time in STEMI.

Method
SymTime was a multicenter observational cross-sectional self-reported survey study performed at five Swedish hospitals representing geographic diversity. Early and late action was defined as decision to seek care <20 min and >90 min, respectively.

Results
532 patients were included. Among those 19.5% called Emergency Medical Services (EMS) as first medical contact (FMC) within 20 min, whereas 10.7% acted within 20 min, but did not call EMS as FMC. Twenty-eight % called EMS as FMC, but delayed >20 min and 41.7% neither acted promptly, nor called EMS as FMC.
Predictors associated with decision time OR 95% CI Factors associated with decision time <20 min   Previous AF 0.43 0.19–0.94   Believing the symptoms originated from the heart 3.10 1.93–4.96   Symptoms waxing and waning 0.58 0.36–0.94   Getting STEMI off hours 0.66 0.45–0.97   Bystanders calling or recommending EMS (Emergency Medical Services) contact 1.67 1.07–2.59   Bystanders calling or recommending SHD (Swedish healthcare Direct) contact 0.56 0.37–0.85 Factors associated with decision time >90 min   Female gender 1.67 1.06–2.62   Diaphoresis 0.67 0.46–0.998   Nausea 0.60 0.36–0.998   Stomach pain 0.46 0.23–0.91   Believing the symptoms originated from the heart 0.46 0.32–0.68   Getting STEMI off hours 1.68 1.16–2.14   Low educational level 0.58 0.40–0.86   Bystanders calling or recommending EMS contact 0.45 0.30–0.67 Variable significant at the p 0.05 presented.

Conclusion
Surprisingly, no specific symptom or severity of symptom were associated with early action, neither age, nor gender. Instead correct interpretation of symptoms and bystanders assisting were factors associated with early action. Frightening symptoms such as diaphoresis was negatively associated, whereas female gender and getting MI off hours were positively associated with late action.
2229Apoptotic and non-apoptotic circulating microparticles in patients with acute coronary syndromes
Authors: Zacharia E , Papageorgiou N , Antonopoulos A S , Pallantza Z , Oikonomou E , Miliou A , Mistakidi C V , Kriebardis A , Orologas N , Valasiadi E , Papaioannou S , Tousoulis D 
Published: October 2019

Abstract

Background
Circulating microparticles (MP) are surrogate biomarkers of atherosclerosis but their role in patients with acute coronary syndromes (ACS) remain unknown.

Purpose
To explore the levels of apoptotic and non-apoptotic MP in patients with ACS.

Methods
We enrolled a total of 153 patients as follows: 49 patients with STEMI, 35 NSTEMI, 38 with unstable angina (UA), 15 with stable CAD (SCAD) and 16 non-CAD (controls). Flow cytometry analysis was used to quantify circulating apoptotic (annexin+) and non-apoptotic endothelial cell (EMP), red blood cell (RMP) and platelet (PMP) derived microparticles. Circulating C-reactive protein (hsCRP) levels and cardiac troponin I (cTnI) were also assessed. Brachial FMD was also determined as a marker of endothelial function.

Results
There was a stepwise increase in the total number of EMP, RMP and PMP in patients with ACS (STEMI/NSTEMI) compared to UA, SCAD and non-CAD patients. This was mainly explained by the increase in the number of apoptotic EMP, RMP and PMP (a-c), while there were no significant differences in the level of apoptotic EMP, RMP or PMP between patient subgroups (not shown). There was no association between circulating levels of apoptotic or non-apoptotic EMP, RBP or PMP with hsCRP (p=NS for all). Apoptotic EMP only were negatively associated with brachial FMD (rho=−0.185, p=0.04) and positively with cTnI levels (rho= 0.307, p<0.0001).

Conclusions
Circulating apoptotic (but not non-apoptotic) MP are increased in patients with ACS. A negative association is observed between the numbers of circulating apoptotic EMP only and systemic endothelial function. The biological role of circulating apoptotic microparticles' in the pathogenesis of ACS merits further investigation.
2232Circulating levels of ST2 are associated with myocardial injury, left ventricular function and future adverse clinical events in patients with ST-elevation myocardial infarction
Authors: Shetelig C , Ueland T , Limalanathan S , Hoffmann P , Aukrust P , Yndestad A , Seljeflot I , Eritsland J , Andersen G.Ø 
Published: October 2019

Abstract

Background
Soluble ST2, a member of the IL-1 receptor family, seems to be associated with adverse outcome in acute myocardial infarction and heart failure (HF), and is suggested to be involved in left ventricular (LV) remodelling.

Purpose
To elucidate a possible role of ST2 in LV injury, remodelling and prognosis in ST-elevation myocardial infarction (STEMI) patients. The main objectives of the study were to investigate whether circulating ST2 levels were associated with infarct size, LV function, adverse remodeling and clinical outcome in a cohort of patients with STEMI.

Methods
270 patients with clinically stable first-time STEMI treated with primary percutaneous coronary intervention (PCI) were included. Blood samples were drawn before and immediately after the PCI procedure, at day 1 (median 18.3 hours after PCI) and after 4 months. Cardiac magnetic resonance (CMR) was performed in the acute phase and after 4 months. Clinical events and all-cause mortality were registered during 12 months' and 70 months' follow-up, respectively. A composite endpoint was defined as death, MI, unscheduled revascularisation >3 months after the index infarction, rehospitalisation for HF or stroke. Associations between ST2 and CMR parameters and clinical events were evaluated with linear regression and logistic regression, respectively.

Results
There was a significant increase in ST2 levels from the PCI procedure to day 1 with a subsequent decline from day 1 to 4 months in the POSTEMI cohort. Patients with high ST2 levels (>median) at all sampling points during hospitalisation had significantly larger infarct size, lower myocardial salvage, lower LVEF, larger increase in EDV and higher frequency of MVO. After adjustment for relevant clinical variables, peak CRP and peak troponin T, ST2 measured at day 1 remained associated with infarct size (β 2.0 per SD of ST2, p<0.001) and LVEF (β −1.8 per SD of ST2, p=0.02) at 4 months. High levels of ST2 measured at day 1 (>75th percentile) were associated with increased risk of having an adverse clinical event during the first year and with long-term all-cause mortality (Figure). High levels of ST2 measured in a stable phase 4 months after STEMI were also associated with an increased risk of all-cause mortality (Figure).
Figure 1

Conclusions
High levels of ST2 in STEMI patients were associated with large infarct size, impaired recovery of LV function, and adverse clinical outcome in patients with STEMI. ST2 measured 4 months after STEMI remained associated with all-cause mortality.
2284Sex and age differences in short-term exposure to ambient fine particulate matter and out-of-hospital cardiac arrest: a nationwide case-crossover study in Japan
Authors: Zhao B , Johnston F H , Salimi F , Negishi K 
Published: October 2019

Abstract

Introduction
Accumulating evidence has shown the elevated risk for cardiovascular diseases (CVD) with exposure to air pollution, such as fine particles <2.5μm in aerodynamic diameter (PM2.5). A bi-directional relationship exists between air pollution and traditional CV risk factors like obesity, diabetes, and hypertension. However, little is known about the effect of age and sex on association between ambient air pollution and out-of-hospital cardiac arrest (OHCA).

Purpose
This study aimed to identify sex and age differences in the associations between exposure to PM2.5 and OHCA in Japan.

Methods
A case-crossover design was used to determine the odds ratio (OR) of OHCA across Japan with daily PM2.5 exposure on the day of the arrest or 1–3 days before it (lag 0–3). OHCA cases were identified through the All-Japan Utstein registry of the Fire and Disaster Management Agency from January 1, 2014 to December 31, 2015. OHCAs were investigated by conditional logistic regression adjusted for daily temperature and relative humidity with stratification by sex and age.

Results
A total of 249,372 OHCAs were included during study period. Their mean age was 75 years and 57% were male. Each 10 μg/m3 increase in daily PM2.5 exposure over 4 days was associated with all cause OHCA risk for male (lag 0: OR 1.022, 95% confidence interval (CI) 1.013, 1.031; lag 1: OR 1.016, 95% CI 1.007, 1.025; lag 2: OR 1.016, 95% CI 1.007, 1.026; lag 3: OR 1.017, 95% CI 1.008, 1.027; lag 0–1: OR 1.025, 95% CI 1.015, 1.036). Increased risk in OHCA was also found with lag 1 to lag 3 PM2.5 exposure among women. Lag 0 to lag 3 PM2.5 exposures were significantly associated with OHCA among patients older than 65 years. Among 35 to 64 years, only lag 3 PM2.5 exposure was associated with an increased risk in OHCA. No significant association was observed between PM2.5 exposure and OHCA among patients less than 35 years.

Conclusions
Short-term exposure to PM2.5 is associated with an increased risk of OHCA in both sexes. Patients older than 65 years were more susceptible to PM2.5 exposure than younger age group.
2289Extracellular Vesicle-incorporated Long Noncoding RNA PUNISHER as a novel biomarker and effector of vascular function
Authors: Li Q , Liu Y Y , Hosen M R , Levermann P , Flender A , Latz E , Nickenig G , Werner N , Jansen F 
Published: October 2019

Abstract

Background
Circulating long noncoding RNAs (lncRNAs) have emerged as biomarkers and regulators in cardiovascular diseases. Whether small extracellular vesicles (sEV)-incorporated lncRNAs expression is regulated in coronary artery disease (CAD) is largely unknown. We aimed to explore the expression of plasma sEV-lncRNAs in patients with and without CAD as well as elucidate specific cellular function of sEV-incorporated lncRNA PUNISHER (also known as AGAP2-AS1) in vascular endothelial cells.

Methods and results
We quantified the expression level of 13 cardiac- or atherosclerosis-related lncRNAs by quantitative real-time PCR (qRT-PCR) in plasma sEV from 6 stable CAD, 6 ACS and 6 non-CAD (NCAD) patients. 4 lncRNAs showing stable expression (PUNISHER, GAS5, MALAT1, and H19) were further evaluated in the validation study including 65 stable CAD, 43 ACS and 42 NCAD patients. Among those, PUNISHER was significantly increased in patients with stable CAD and ACS compared to NCAD. Area under the curve (AUC) value was 0.7 for stable CAD and 0.8 for ACS respectively, suggesting plasma sEV-PUNISHER as a potential diagnostic biomarker for CAD. In vitro, atherosclerotic stimuli consisting of oxLDL or TNF-a treatment upregulated PUNISHER level in human coronary artery endothelial cell (HCAEC) and in corresponding sEV in a dose-dependent way. Mechanistically, RNA immunoprecipitation (RIP) assay identified hnRNPK as an interaction partner of PUNISHER regulating its packaging into sEV. In vitro, endothelial-derived sEV were internalized into recipient ECs and transported incorporated PUNISHER into recipient cells promoting an angiogenic response. Mechanical downstream analysis using PCR array showed that sEV-mediated PUNISHER transfer altered expression of vascular endothelial growth factor A (VEGFA) in recipient ECs.

Conclusion
This translational study highlights sEV-incorporated lncRNA PUNISHER as biomarker and effector in vascular disease.