bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic cut-off values of caffeine and cardiovascular events in a cohort of unselected men and women from general population
Authors: Tikhonoff V , Ciaghi G , Lievore N , Casiglia E 
Published: October 2022

Abstract

Background
Several studies focused on the effect of caffeine on the cardiovascular (CV) system and on CV outcome, with fairly contrasting results. Dietary caffeine is usually taken into consideration as a continuous variable, but researcher would prefer to use cut-off values more useful in clinical setting.

Purpose
The present study is aimed at defining in epidemiological setting and in population-based context the cut-off values of caffeine, if any, having a CV prognostic values, to confirm them in men and women of general population, and to establish whether caffeine of food origin contained in multiple sources used in everyday life.

Methods
The study cohort was represented by 1,668 unselected men and women aged 59.6±17.1 years living in an area in North-East Italy and sharing homogeneous lifestyle, randomly taken from general population. Multivariate dichotomic Cox regression models having fatal and morbid CV event as dependent variables, adjusted for age, sex, basal heart rate, body mass index, LDLC, individualized FEV1, β-blocking therapy, ethanol intake, diabetes mellitus, arterial hypertension, smoking, smoking, blood pressure were preliminarily used to search for an association between caffeine as a continuous variable and incident CV event. Prognostic cut-off values, identified by means of receiver operating curves (ROC) and able to discriminate between subjects doomed to develop the CV event, were then used as independent predictors to divide people into those &lt;cut-off&gt;cut-off in further multivariate Cox models adjusted for the confounders listed above.

Results
Daily intake of caffeine over a specific cut-off determined via the ROC curve analysis are associated to lower incidence of CV events in a 20-year follow-up period. This cut-off corresponds, for each events, to an interval between two groups of quintiles of caffeine intake. The cerebrovascular events and those due to heart failure and arrhythmias were reduced also in multivariate models adjusted for confounders. On the contrary, intake of caffeine over the cut-off was only apparently associated to lower incidence of coronary disease, but this unadjusted crude association was wales and not confirmed after adjustment.

Conclusions
In men but not in women, higher voluntary daily consumption of caffeine from any source reduces significantly and to a considerable extent, in a long follow-up, the incidence of cerebrovascular events, heart failure and arrhythmias. To have preventive effects on events the consumption of caffeine must be higher than a cut-off that corresponds to 280, 230 and 280 mg/day respectively, cut-off values always falling between the third and fourth quintile of caffeine consumption. No prognostic cut-off can be identified in women and in any sex in the case of coronary events. Specific studies will be mandatory to understand the reason of this sex-specific difference.

Funding Acknowledgement
Type of funding sources: None.
Investigating myocardial energetic deficit across the spectrum of cardiac disease
Authors: Henry J A , Levelt E , Rayner J J , Hundertmark M J , Peterzan M A , Green P G , Watson W , Burrage M K , Arvidsson P , Lewis A J M , Chamley R , Neubauer S , Valkovic L , Rider O J 
Published: October 2022

Abstract

Introduction
The phosphocreatine-to-adenosine triphosphate ratio (PCr/ATP) is a sensitive marker of the energetic state of the heart and can be reliably measured non-invasively using 31Phosphorus magnetic resonance spectroscopy (31P-MRS). Derangements in cardiac energetics are a distinctive feature in the pathophysiology of several cardiac diseases, and thus potential therapeutic targets.

Purpose
We sought to compare cardiac PCr/ATP across a range of cardiac pathologies.

Methods
Using a 3D chemical shift 31P spectral acquisition we recorded PCr/ATP in 515 participants: athletes (n=17), healthy controls with normal weight (n=148), overweight (n=67) and with obesity (n=73), diabetes (n=23), heart failure with preserved ejection fraction (HFpEF) (n=33), heart failure with reduced ejection fraction (HFrEF) (n=63), amyloid (n=9), severe aortic stenosis (AS) (n=29), severe mitral regurgitation (MR) (n=18), and hypertrophic cardiomyopathy (HCM) (n=35).

Results
A spectrum of myocardial PCr/ATP exists ranging from normal in athletes (2.23±0.28) and those with normal weight (2.05±0.38) to severely impaired in severe MR (1.56±0.32) and cardiac amyloid (1.34±0.19, Figure 1). Despite normal systolic function (all LVEF &gt;57%) those living with obesity and diabetes have lower PCr/ATP than normal (all p&lt;0.001). In all groups with HF, regardless of aetiology, myocardial energetics were impaired (all p&lt;0.001). Across the whole cohort PCr/ATP was negatively correlated with body mass index (r −0.28, p&lt;0.001), age (r −0.34, p&lt;0.001) and LV mass (r −0.1, p&lt;0.001). PCr/ATP was not related to systolic or diastolic blood pressure in these cohorts.

Conclusions
We demonstrate a spectrum of energetic deficit in cardiac disease and this is affected by not only myocardial pathology but also by obesity and age. Derangements in myocardial energetics are present in myocardial pathologies independent of underlying aetiology.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): We acknowledge support from the British Heart Foundation Oxford Center of Research Excellence.
The AFLETES study: atrial fibrillation in veteran athLETEs and the risk of stroke
Authors: Pallikadavath S , Richards C , Bountziouka V , Sandilands A J , Graham-Brown M P M , Robinson T , Singh A , McCann G P 
Published: October 2022

Abstract

Background
Endurance athletes are at an increased risk of atrial fibrillation (AF) when compared to the general population. However, the risk of stroke in athletes who develop AF is not known.

Purpose
We aimed to assess the risk of stroke in endurance veteran athletes with AF when compared to those that remain in sinus rhythm.

Methods
A questionnaire was broadcasted through social media and sports clubs. Individuals that had competed in at least one competitive event and were ≥40 years old were included. Self-reported demographic, past medical history and training history data were collected and a CHA2DS2-VASc was calculated. Binary logistic regression was used to assess variables associated with AF and stroke.

Results
The survey received 1002 responses from 41 countries across Africa, Asia, Australasia, Europe, North and South America, and 942 were included in the final analysis. The average age was 52.4±8.5 years and 83.7% were male. The most common sports were cycling (n=677, 71.9%), running (n=558, 59.2%) and triathlon (n=245, 26%). There were 190 (20.2%) individuals who reported AF and 26 (2.8%) individuals who reported stroke, of which 14 (53.9%) had AF. Lifetime exercise dose (OR: 1.02, 95% CI: 1.00, 1.03, p=0.02) and swimming (OR: 1.56, 95% CI: 1.02, 2.39, p=0.04) were associated with AF in multivariable analysis. AF (OR: 4.18, 95% CI: 1.80, 9.72 p&lt;0.01) was positively associated with stroke, even in individuals with a CHA2DS2-VASc of 0 or 1 (OR: 4.20, 95% CI: 1.83, 9.66, p&lt;0.01) (Figure 1).

Conclusions
This survey provides early evidence that the risk of stroke in veteran endurance athletes who develop AF is not negligible, even in those deemed to be at low risk by CHA2DS2-VASc score. Longitudinal studies are needed to substantiate these findings to inform decisions around anticoagulation.

Funding Acknowledgement
Type of funding sources: None.
Relationships between plasma cytokine balance and cardiac magnetic resonance imaging in long-term post-COVID follow-up: a cross-sectional preliminary study
Authors: Simonini L , Sbrana S , Foffa I , Baroni M , Catapano G , Chiappino D , Grigoratos C , Marrone C , Losi P , Mannucci F , Salvadori S , Todiere G , Valenti E , Ait-Ali L , Aquaro G D 
Published: October 2022

Abstract

Background
COVID-19 infection can lead to a constellation of long-lasting post-infectious sequelae, including myocardial dysfunction, whose outcome is strongly affected by a fine-tuned balance between pro- and anti-inflammatory systemic immune responses. Plasma cytokines are key mediators of this immunological balance. In this preliminary study we evaluated the cross-sectional association between the circulating levels of the main pro- and anti-inflammatory cytokines and cardiac magnetic resonance (CMR) abnormalities.

Methods
71 subjects (59% female, mean age 52±14) with previous diagnosis of COVID-19 infection were enrolled at our institution for MULTICOVID protocol, comprehensive of CMR and biomarkers assessment performed &gt;3 months and &lt;1 year following the first negative swab test. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Plasma levels of cytokines TNF-α, IL-1β, IL-1α, IFN-α2, IL-6, IL-8, IL-13, IL-10, IL-17A, IL-18, IP-10, MIG and MCP-1 were quantified by Multiplex Immunoassays on the Luminex technology platform. Soluble cardiologic and biochemical biomarkers were measured by routine laboratory analysis.

Results
After a median of 9 (IQR 6–11) months following negative swab, CMR was normal in 48 subjects, while in 23 (32%) it revealed tissue characterization abnormalities (myocardial late enhancement and/or edema). By multivariate regression analysis (adjusted for age, sex, vaccination, severity degrees of the initial COVID disease, presence of comorbidities, smoke, time interval between COVID diagnosis and CMR assessment) the cytokine ratio TNF-α/(IL-10+IL-13) was independently associated (OR=2.89, 95% CI 1.19–7.04, p=0.02) with CMR abnormalities. Interestingly, the cumulative pro-/anti-inflammatory cytokine ratio (IL-1β+TNF-α+IFN-α2+IL-6+IL-17A+IL-8)/(IL-10+IL-13) showed a positive (OR=1.70, 95% CI: 1.04–2.75) and significant (p=0.03) association with CMR imaging aspects. Also, the ratio IFN-α2/(IL-10+IL-13), although without achieving a complete statistical significance (p=0.09), was associated positively with CMR findings.

Conclusions
The preliminary results of this cross-sectional study suggest that the systemic inflammatory environment, long-lasting unbalanced towards a prevalent cytokine-driven pro-inflammatory condition following COVID infection, could affect the development of CMR-detectable myocardial edema and fibrosis in long-term post-COVID subjects.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Tuscany Region
Effect of CPAP therapy on blood pressure in patients with OSA: a worldwide individual patient data meta-analysis
Authors: Pengo M , Schwarz E I , Barbe F , Drager L , Fava C , Ip M S M , Martinez Garcia M A , McEvoy D , Peker Y , Phillips C L , Soranna D , Steier J , Stradling J , Zambon A , Parati G 
Published: October 2022

Abstract

Background
Obstructive sleep apnoea (OSA) is a well-known cardiovascular risk factor and is frequently associated with hypertension. The treatment of OSA with continuous positive airway pressure (CPAP) can resolve apnoeas, hypoxia, and sympathetic hyperactivation. Meta-analyses of randomised controlled trials (RCTs) show that CPAP treatment modestly reduces blood pressure (BP) with a pronounced heterogeneity among different OSA patient subgroups.

Purpose
To study the effects of CPAP treatment on BP changes, and to identify predictors of BP response to CPAP through analysis of individual patient data from published RCTs.

Methods
Study groups who had published RCTs on the effect of CPAP therapy on BP in OSA were invited to share the individual patient data (i.e. BP values, history of hypertension and antihypertensive drugs use). The outcomes of interest were the group-difference (BP at follow-up – BP at baseline) in office and out-of-office BP. Data analysis was performed with a one-step approach using a linear regression model, with treatment as covariate, including a random effect. An additional analysis was performed by stratifying patients in three subgroups: normotension, controlled hypertension and uncontrolled hypertension, based on BP at baseline, history of hypertension or treatment with antihypertensive drugs. Lastly, we evaluated the determinants of CPAP associated BP changes.

Results
Individual patient data from 34 parallel-group RCTs (n=7,456, 72% males, body mass index, BMI 31.9±14.8 kg/m2, age 58.6±10.9 years, apnoea-hypopnoea index, AHI 35.5±20.6 /hour) were analysed. The overall CPAP effect was larger for 24-BP compared to office BP measurements (Table 1), the highest reductions being observed for nocturnal BP. The stratified analysis showed a consistent BP lowering effect in the group of patients with uncontrolled hypertension whereas there was no significant BP change in those with controlled hypertension or in normotensives (figure 1). Higher BP levels at baseline and history of hypertension were independent predictors of BP reduction by CPAP for office and 24-BP measurements. Younger age and more severe nocturnal oxygen desaturations predicted a larger treatment effect on office BP only.

Conclusions
BP response to CPAP in OSA patients varies in different patient groups as a function of baseline BP, the greatest reduction being observed in younger patients with uncontrolled BP. Thus, our individual patient data meta-analysis indicates that younger patients with uncontrolled hypertension and more severe nocturnal oxygen desaturations measured by minimum SpO2 are likely to benefit the most from CPAP treatment in terms of BP reduction.

Funding Acknowledgement
Type of funding sources: None.
Low blood levels of the lncRNA MRPL20-AS1 are associated with severe obstructive sleep apnea
Authors: Zietzer A , Nachtsheim L , Duesing P , Von Krosigk M , Hosen M R , Breitrueck N , Goody P R , Klussmann J P , Nickenig G , Jansen F , Jansen S 
Published: October 2022

Abstract

Introduction
Obstructive sleep apnea syndrome (OSAS) is the most common sleep disorder and it is associated with arterial hypertension, heart failure, coronary artery disease as well as atrial fibrillation. The underlying pathomechanisms for this association are only incompletely understood. In recent years long non-coding RNAs (lncRNA) have been shown to be involved in various cardiovascular pathologies. The aim of this study is to identify lncRNAs which are associated with OSAS in order to provide potential therapeutic targets.

Methods and results
In order to tackle this issue, we included 23 Patients with a suspected OSAS in a pilot study and sampled blood on the evening before and on the morning after polysomnographic analysis. Citrate was used to inhibit clotting of the blood and cellular components were removed by centrifugation, before the plasma was stored at −80°C. One patient had no sign of OSAS as indicated by an Apnea/Hypopnea-Index (AHI) &lt;5 per hour and was therefore excluded. The remaining 22 patients had a mean age of 44.45 years and a mean AHI of 28.38 per hour. Three of the patients were female and nineteen were male. In four of those patients with high AHI levels, we performed a RNA sequencing analysis from the citrate plasma and found MRPL20-AS1 to be the most significantly regulated lncRNA after the night of polysomnographic analysis (A). Low coding potential of MRPL20-AS1 was confirmed in silico via the Coding-Potential Assessment Tool (http://lilab.research.bcm.edu/) resulting in a coding probability of 0.06148. Then MRPL20-AS1 levels were measured via qPCR in the remaining patients. From 19 patients, we obtained evaluable results. We found that MRPL20-AS1 blood levels had the tendency to be lower after the night of polysomnographic assessment (B). Interestingly MRPL20-AS1 levels were inversely correlated with the AHI of the OSAS patients (C). This indicates that severe OSAS was associated with low levels of MRPL20-AS1 in our cohort (D). In order to further investigate these results in vitro, we subjected human coronary artery endothelial cells (HCAECs) to hypoxia (1% and 5% O2) for 24 h. We found that hypoxia leads to a significant downregulation of MRPL20-AS1 in HCAECs (E).

Conclusion
MRPL20-AS1 blood levels are lower in patients with severe OSAS after nocturnal hypoxia. In endothelial cells MRPL20-AS1 is downregulated after hypoxia. MRPL20-AS1 can therefore be useful to identify patients suffering from severe OSAS. Further investigations are needed to elucidate the biological function of MRPL20-AS1 in the context of OSAS and to investigate MRPL20-AS1 as a potential therapeutic target to counteract cardiovascular effects of OSAS

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Unviversity of BonnUniversity of Cologne
Access to cardiac rehabilitation programs in patients with acute coronary syndrome: can referral be a step towards improvement? Insights from a multicentre national registry
Authors: Cabral M , Antunes A , Santos B , Loureiro M F , Morais J 
Published: October 2022

Abstract

The burden of cardiovascular disease remains on top of society's health problems, and acute coronary syndromes are undoubtedly a major cause. Cardiac rehabilitation programs (CRP) have been demonstrated to be a cost-effective strategy in reducing morbimortality and improving quality of life after an acute event. Despite this evidence and clinical recommendations, CRP are still globally underused. The lack of referral patients to CRP has been appointed as an important impediment to patients' participation.
This study aimed to clarify the main features of referred patients to CRP vs non-referred patients after an acute coronary syndrome (ACS).
The authors performed a retrospective analysis of adult patients with information about CRP destination, included in the Portuguese Registry on Acute Coronary Syndromes (ProACS) between October 2010 and December 2021. Comparison tests for parametric and non-parametric variables were performed. Logistic regression was applied for multivariate analysis. A p-value less than 0.05 was considered statistically significant.
A total of 28809 patients admitted for ACS were analysed, 22896 (79.5%) not referred for CRP (group 1) and 5913 (20.5%) were referred or even had a planned CRP. Table 1 shows the most important baseline characteristics and differences between groups. Table 2 demonstrate the group differences regarding admission diagnosis, complementary study results and in-hospital complications. Multivariate analysis established the following variables as independent factors for non-referral for CRP: age greater than 75 years (OR 0.80, 95% CI [0.72, 0.89]), history of valvular disease (OR 0.76, 95% CI [0.59, 0.97]), history of kidney disease (OR 0.65, 95% CI [0.54, 0.79]), admission diagnosis of unstable angina (UA) (OR 0.37, 95% CI [0.27, 0.50]), multivessel disease (OR 0.73, 95% CI [0.67, 0.80]), left ventricular ejection fraction less than 50% (OR 0.76, 95% CI [0.68, 0.84]), mechanical complication of myocardial infarction (OR 0.26, 95% CI [0.10, 0.67]) and acute heart failure during hospitalization (OR 0.67, 95% CI [0.58, 0.77]).
In conclusion, contrary to international results, women and patients with non-ST-segment elevation myocardial infarction were not negative predictors for referral to CRP. However, we observed that in our country, older patients, those with UA as an admission diagnosis, comorbidities and/or reduced systolic function are less referred to CRP by physicians. Paradoxically, these patients often have greater disease management complexity and poor outcomes. Besides that, the beneficial effects of cardiac rehabilitation in these groups have been demonstrated. Thus, it is extremely important to understand the limitations of referral in our country and implement strategies to overcome them.

Funding Acknowledgement
Type of funding sources: None.
Association between the changes in walking speed during 6 months after discharge and subsequent prognosis in older patients with heart failure: report from a multicenter prospective cohort study
Authors: Hanada S , Adachi T , Iwatsu K , Kamisaka K , Kamiya K , Yamada S 
Published: October 2022

Abstract

Background
Walking speed (WS) is one of the key components of physical frailty associated with a prognosis in patients with heart failure (HF). However, the prognostic impact of changes in WS after discharge in patients with HF remains to be examined.

Purpose
The purpose of this study was to examined the association between the change in WS during 6 months after discharge and subsequent prognosis in older patients with HF.

Methods
This study was performed as a sub-analysis of the multicenter cohort study in Japan (FLAGSHIP). We analyzed patients hospitalized for HF aged ≥65 years whose WS was measured at discharge and after 6 months of discharge. Based on the patterns of WS at the two points, patients were divided into four groups (A: WS ≥0.98 m/s both at discharge and 6-month; B: ≥0.98 m/s at discharge, &lt;0.98 m/s at 6-month; C: &lt;0.98 m/s at discharge, ≥0.98 m/s at 6-month; D: &lt;0.98 m/s both at discharge and 6-month). WS &lt;0.98 m/s has been identified as a cut-off value predicting the prognosis of HF in the main analysis of the FLAGSHIP. Kruskal - Wallis test was used to compare among groups. Furthermore, Cox proportional hazards model was performed to evaluate the association between the WS subgroups and HF rehospitalization after 6-month of discharge. Additionally, adjustments were made for age and sex in model 1, and for age, sex, cognitive function (Mini-mental state examination, MMSE ≤23), past HF hospitalization, rehospitalization within 6 months after discharge, and variables with a p value &lt;0.05 both at discharge and 6 months in univariate analysis in model 2.

Results
A total of 890 patients were included in this study (Group A: n=386, B: n=51, C: n=143, D: n=310). There was a significant difference in HF rehospitalization after 6-month of discharge among the four groups (Log-rank test, p=0.01, Figure 1). In the crude model, hazard ratio (HR) of group B compared with A was 2.26 [95% confidence interval: 1.19–4.27, p=0.013], HR of C was 1.00 [0.56–1.77, p=0.988], and HR of D was 1.66 [1.11–2.47, p=0.013]. In model 1, HR of B was 2.12 [1.11–4.07, p=0.023], HR of C was 0.99 [0.56–1.75, p=0.964], and HR of D was 1.56 [1.01–2.42, p=0.047]. In model 2, HR of B was 0.95 [0.45–1.97, p=0.897], HR of C was 0.67 [0.35–1.26, p=0.212], and HR of D was [0.25–0.80, p=0.007].

Conclusion
Although slow WS is associated with poor prognosis, the prognosis might be improved if WS increases by 6 months after discharge.

Funding
This study is supported by a Grant-in-Aid for Scientific Research (A) from the Japanese Society for the Promotion of Science [16H01862].

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): The Japanese Society for the Promotion of Science