Beyond the absence of sleep disorder: spotlighting the cardiovascular benefits of sleep health.

Cardiovascular diseases (CVDs) are the leading cause of death globally. Among the objectives of preventive cardiology is the design to understand and neutralise the clinical overlap between disordered sleep and CVDs. Seldom do studies measure 'sleep health' beyond the absence of disease. Explored herein are the cardiovascular (CV) outcomes of sleep health on the grounds that, more than a corollary of sleep disorder research, sleep health constitutes a critical determinant of cardiac health and disease not unlike diet and physical activity. That sleep interventions can reverse the CV consequences of poor sleep habits lends credence to the notion that sleep health benefits CV health, and that the importance of sleep health percolates far beyond sleep disorder research. Overall, sleep health, and its practicable correlate: sleep hygiene, are clinical imperatives in the foreseeable future of cardiology in the 24-hour society.

Deformation Parameters of the Heart in Endurance Athletes and in Patients with Dilated Cardiomyopathy-A Cardiac Magnetic Resonance Study.

A better understanding of the left ventricle (LV) and right ventricle (RV) functioning would help with the differentiation between athlete's heart and dilated cardiomyopathy (DCM). We aimed to analyse deformation parameters in endurance athletes relative to patients with DCM using cardiac magnetic resonance feature tracking (CMR-FT). The study included males of a similar age: 22 ultramarathon runners, 22 patients with DCM and 21 sedentary healthy controls (41 ± 9 years). The analysed parameters were peak LV global longitudinal, circumferential and radial strains (GLS, GCS and GRS, respectively); peak LV torsion; peak RV GLS. The peak LV GLS was similar in controls and athletes, but lower in DCM (p < 0.0001). Peak LV GCS and GRS decreased from controls to DCM (both p < 0.0001). The best value for differentiation between DCM and other groups was found for the LV ejection fraction (area under the curve (AUC) = 0.990, p = 0.0001, with 90.9% sensitivity and 100% specificity for ≤53%) and the peak LV GRS diastolic rate (AUC = 0.987, p = 0.0001, with 100% sensitivity and 88.4% specificity for >-1.27 s-1). The peak LV GRS diastolic rate was the only independent predictor of DCM (p = 0.003). Distinctive deformation patterns that were typical for each of the analysed groups existed and can help to differentiate between athlete's heart, a nonathletic heart and a dilated cardiomyopathy.

Altered Circulating MicroRNA Profiles After Endurance Training: A Cohort Study of Ultramarathon Runners.

BACKGROUND: Despite the positive effects of endurance training on the cardiovascular (CV) system, excessive exercise induces not only physiological adaptations but also adverse changes in CV system, including the heart. We aimed to evaluate the selected miRNAs expression based on bioinformatic analysis and their changes before and after an ultramarathon run. MATERIALS AND METHODS: Cardiac tissue-specific targets were identified with the Tissue 2.0 database. Gene-gene interaction data were retrieved from the STRING app for Cytoscape. Twenty-three endurance athletes were recruited to the study. Athletes ran to completion (100 km) or exhaustion (52-91 km, median 74 km). All participants completed pre- and post-run testing. miRNAs expressions were measured both before and after the race. RESULTS: Enrichment analysis of the signaling pathways associated with the genes targeted by miRNAs selected for qRT-PCR validation (miR-1-3p, miR-126, miR-223, miR-125a-5p, miR-106a-5p, and miR-15a/b). All selected miRNAs showed overlap in regulation in pathways associated with cancer, IL-2 signaling, TGF-ß signaling as well as BDNF signaling pathway. Analysis of metabolites revealed significant regulation of magnesium and guanosine triphosphate across analyzed miRNA targets. MiR-1-3p, miR-125a-5p, miR-126, and miR-223 expressions were measured in 23 experienced endurance athletes, before and after an ultramarathon wherein athletes ran to completion (100 km) or exhaustion (52-91 km, median 74 km). The expressions of miR-125a-5p, miR-126, and miR-223 were significantly increased after the race (p = 0.007, p = 0.001, p = 0.014, respectively). MiR-1-3p expression post-run showed a negative correlation with the post-run levels of high-sensitivity C-reactive protein (hs-CRP) (r = -0.632, p = 0.003). Higher miR-1-3p expression was found in runners, who finished the race under 10 h compared to runners who finished over 10 h (p = 0.001). Post-run miR-125a-5p expression showed a negative correlation with the peak lactate during the run (r = -0.576, p = 0.019). CONCLUSION: Extreme physical activity, as exemplified by an ultramarathon, is associated with changes in circulating miRNAs' expression related to inflammation, fibrosis, and cardiac muscle function. In particular, the negative correlations between miR-125a-5p and lactate concentrations, and miR-1-3p and hs-CRP, support their role in specific exercise-induced adaptation. Further studies are essential to validate the long-term effect of these observations.

Football spectatorship and selected acute cardiovascular events: lack of a population-scale association in Poland.

BACKGROUND: The status of football spectatorship-induced emotional stress as a risk factor for acute cardiovascular events remains a matter of dispute.              Aims: This study aimed to investigate the relationship between football spectatorship and the incidenceof selected acute cardiovascular events in the Polish male population. METHODS: Events that occurred in male patients aged 35 years and older in Poland during 3 tournaments(2012 and 2016 European Championships and 2018 World Cup) were retrospectively analyzed based onhospital admission codes (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD­10]) obtained from the Polish National Health Fund (Narodowy Fundusz Zdrowia). The followingprimary diagnoses were of interest: acute myocardial infarction (AMI; I21), sudden cardiac arrest (I46),sudden arrhythmias (I47-I49). The corresponding dates in the years before and after the tournamentsconstituted the reference periods. RESULTS: A total of 255 383 patients were included in this study. There were no significant differences in the incidence of events between the combined exposure and reference periods: relative risk [RR] = 1.05 (95% CI, 0.97-1.14; P = 0.2) for AMI, RR = 1.08 (95% CI, 0.87-1.35;P = 0.47) for sudden cardiac arrest, and RR = 1.02 (95% CI, 0.98-1.06; P = 0.32) for sudden arrhythmias. Individual tournament analyses revealeda higher incidence of AMI (RR = 1.2; 95% CI, 1.12-1.3; P <0.001) during the World Cup. However, day ­by ­­day analysis for the World Cup did not show a higher incidence of AMI on match versus match­free days. CONCLUSIONS: Emotional stress evoked by football spectatorship is insufficiently potent to precipitatea population­scale increase in the incidence of selected acute cardiovascular events.

Improved cryotolerance and developmental potential of in vitro and in vivo matured mouse oocytes by supplementing with a glutathione donor prior to vitrification.

STUDY QUESTION: Can supplementation of media with a glutathione (GSH) donor, glutathione ethyl ester (GEE), prior to vitrification protect the mouse oocyte from oxidative damage and critical changes in redox homeostasis, and thereby improve cryotolerance? SUMMARY ANSWER: GEE supplementation supported redox regulation, rapid recovery of spindle and chromosome alignment after vitrification/warming and improved preimplantation development of mouse metaphase II (MII) oocytes. WHAT IS KNOWN ALREADY: Cryopreservation may affect mitochondrial functionality, induce oxidative stress, and thereby affect spindle integrity, chromosome segregation and the quality of mammalian oocytes. GEE is a membrane permeable GSH donor that promoted fertilization and early embryonic development of macaque and bovine oocytes after IVM. STUDY DESIGN, SIZE, DURATION: Two experimental groups consisted of (i) denuded mouse germinal vesicle (GV) oocytes that were matured in vitro in the presence or absence of 1 mM GEE (IVM group 1) and (ii) in vivo ovulated (IVO) MII oocytes that were isolated from the ampullae and exposed to 1 mM GEE for 1 h prior to vitrification (IVO group 2). Recovery of oocytes from both groups was followed after CryoTop vitrification/warming for up to 2 h and parthenogenetic activation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reactive oxygen species (ROS), spindle morphology and chromosome alignment were analyzed by confocal laser scanning microscopy (CLSM) and polarization microscopy in control and GEE-supplemented MII oocytes. The relative overall intra-oocyte GSH content was assessed by analysis of monochlorobimane (MBC)-GSH adduct fluorescence in IVM MII oocytes. The GSH-dependent intra-mitochondrial redox potential (EmGSH) of IVM MII oocytes was determined after microinjection with specific mRNA at the GV stage to express a redox-sensitive probe within mitochondria (mito-Grx1-roGFP2). The absolute negative redox capacity (in millivolts) was determined by analysis of fluorescence of the oxidized versus the reduced form of sensor by CLSM and quantification according to Nernst equation. Proteome analysis was performed by quantitative 2D saturation gel electrophoresis (2D DIGE). Since microinjection and expression of redox sensor mRNA required removal of cumulus cells, and IVM of denuded mouse oocytes in group 1 induces zona hardening, the development to blastocysts was not assessed after IVF but instead after parthenogenetic activation of vitrified/warmed MII oocytes from both experimental groups. MAIN RESULTS AND ROLE OF CHANCE: IVM of denuded mouse oocytes in the presence of 1 mM GEE significantly increased intra-oocyte GSH content. ROS was not increased by CryoTop vitrification but was significantly lower in the IVM GEE group compared to IVM without GEE before vitrification and after recovery from vitrification/warming (P < 0.001). Vitrification alone significantly increased the GSH-dependent intra-mitochondrial redox capacity after warming (EmGSH, P < 0.001) in IVM oocytes, presumably by diffusion/uptake of cytoplasmic GSH into mitochondria. The presence of 1 mM GEE during IVM increased the redox capacity before vitrification and there was no further increase after vitrification/warming. None of the reproducibly detected 1492 spots of 2D DIGE separated proteins were significantly altered by vitrification or GEE supplementation. However, IVM of denuded oocytes significantly affected spindle integrity and chromosome alignment right after warming from vitrification (0 h) in group 1 and spindle integrity in group 2 (P < 0.05). GEE improved recovery in IVM group as numbers of oocytes with unaligned chromosomes and aberrant spindles was not significantly increased compared to unvitrified controls. The supplementation with GEE for 1 h before vitrification also supported more rapid recovery of spindle birefringence. GEE improved significantly development to the 2-cell stage for MII oocytes that were activated directly after vitrification/warming in both experimental groups, and also the blastocyst rate in the IVO GEE-supplemented group compared to the controls (P < 0.05). LARGE SCALE DATA: None LIMITATIONS, REASONS FOR CAUTION: The studies were carried out in a mouse model, in IVM denuded rather than cumulus-enclosed oocytes, and in activated rather than IVF MII oocytes. Whether the increased GSH-dependent intra-mitochondrial redox capacity also improves male pronuclear formation needs to be studied further experimentally. The influence of GEE supplementation requires also further examination and optimization in human oocytes before it can be considered for clinical ART. WIDER IMPLICATIONS OF THE FINDINGS: Although GEE supplementation did not alter the proteome at MII, the GSH donor may support cellular homeostasis and redox regulation and, thus, increase developmental competence. While human MII oocyte vitrification is an established procedure, GEE might be particularly beneficial for oocytes that suffer from oxidative stress and reduced redox capacity (e.g. aged oocytes) or possess low GSH due to a reduced supply of GSH from cumulus. It might also be of relevance for immature human oocytes that develop without cumulus to MII in vitro (e.g. in ICSI cycles) for ART. STUDY FUNDING AND COMPETING INTERESTS: The study has been supported by the German Research Foundation (DFG FOR 1041; EI 199/3-2). There are no conflict of interests.