The role of obesity, different fat compartments and sleep apnea severity in circulating leptin levels: the Icelandic Sleep Apnea Cohort study.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.To assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between obstructive sleep apnea (OSA) severity and leptin levels differs depending on obesity level.Cross-sectional study of 452 untreated OSA patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±s.d.), body mass index (BMI) 32.7±5.3 kg m(-2) and apnea-hypopnea index 40.2±16.1 events per h. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed, as well as fasting serum morning leptin levels were measured.Leptin levels were more highly correlated with BMI, total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI or =35 kg m(-2)). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (P=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199).Obesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.NIH/HL72067/HL94307, Eimskip Fund of the University of Iceland, Landspitali University Hospital Research Fun

New‐Onset Atrial Fibrillation is Associated With Cardiovascular Events Leading to Death in a First Time Myocardial Infarction Population of 89 703 Patients With Long‐Term Follow‐Up:A Nationwide Study

BACKGROUND: New‐onset atrial fibrillation (AF) is reported to increase the risk of death in myocardial infarction (MI) patients. However, previous studies have reported conflicting results and no data exist to explain the underlying cause of higher death rates in these patients. METHODS AND RESULTS: All patients with first acute MI between 1997 and 2009 in Denmark, without prior AF, were identified from Danish nationwide administrative registers. The impact of new‐onset AF on all‐cause mortality, cardiovascular death, fatal/nonfatal stroke, fatal/nonfatal re‐infarction and noncardiovascular death, were analyzed by multiple time‐dependent Cox models and additionally in propensity score matched analysis. In 89 703 patients with an average follow‐up of 5.0±3.5 years event rates were higher in patients developing AF (n=10 708) versus those staying in sinus‐rhythm (n=78 992): all‐cause mortality 173.9 versus 69.4 per 1000 person‐years, cardiovascular death 137.2 versus 50.0 per 1000 person‐years, fatal/nonfatal stroke 19.6/19.9 versus 6.2/5.6 per 1000 person‐years, fatal/nonfatal re‐infarction 29.0/60.7 versus 14.2/37.9 per 1000 person‐years. In time‐dependent multiple Cox analyses, new‐onset AF remained predictive of increased all‐cause mortality (HR: 1.9 [95% CI: 1.8 to 2.0]), cardiovascular death (HR: 2.1 [2.0 to 2.2]), fatal/nonfatal stroke (HR: 2.3 [2.1 to 2.6]/HR: 2.5 [2.2 to 2.7]), fatal/nonfatal re‐infarction (HR: 1.7 [1.6 to 1.8]/HR: 1.8 [1.7 to 1.9]), and non‐ cardiovascular death (HR: 1.4 [1.3 to 1.5]) all P<0.001). Propensity‐score matched analyses yielded nearly identical results (all P<0.001). CONCLUSIONS: New‐onset AF after first‐time MI is associated with increased mortality, which is largely explained by more cardiovascular deaths. Focus on the prognostic impact of post‐infarct AF is warranted

Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation:nationwide cohort study

Study question What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation? Methods This Danish cohort study (1996-2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models. Study answer and limitations 4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with non-resumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment. What this study adds Among patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding. Funding, competing interests, data sharing This study was supported by a grant from Boehringer-Ingelheim. Competing interests are available in the full paper on bmj.com. The authors have no additional data to share

Stream hydraulics and temperature determine the metabolism of geothermal Icelandic streams

Stream ecosystem metabolism plays a critical role in planetary biogeochemical cycling. Stream benthic habitat complexity and the available surface area for microbes relative to the free-flowing water volume are thought to be important determinants of ecosystem metabolism. Unfortunately, the engineered deepening and straightening of streams for drainage purposes could compromise stream natural services. Stream channel complexity may be quantitatively expressed with hydraulic parameters such as water transient storage, storage residence time, and water spiralling length. The temperature dependence of whole stream ecosystem respiration (ER), gross primary productivity (GPP) and net ecosystem production (NEP = GPP−ER) has recently been evaluated with a “natural experiment” in Icelandic geothermal streams along a 5−25 ◦C temperature gradient. There remained, however, a substantial amount of unexplained variability in the statistical models, which may be explained by hydraulic parameters found to be unrelated to temperature. We also specifically tested the additional and predicted synergistic effects of water transient storage and temperature on ER, using novel, more accurate, methods. Both ER and GPP were highly related to water transient storage (or water spiralling length) but not to the storage residence time. While there was an additional effect of water transient storage and temperature on ER (r2 = 0.57; P = 0.015), GPP was more related to water transient storage than temperature. The predicted synergistic effect could not be confirmed, most likely due to data limitation. Our interpretation, based on causal statistical modelling, is that the metabolic balance of streams (NEP) was primarily determined by the temperature dependence of respiration. Further field and experimental work is required to test the predicted synergistic effect on ER. Meanwhile, since higher metabolic activities allow for higher pollutant degradation or uptake, river restoration and management should promote habitat diversity and complexity (hyporheic zone, macrophyte patches, substrate heterogeneity), especially for microbial activity.Le métabolisme des écosystèmes aquatiques fluviaux joue un rôle critique dans les cycles biogéochimiques planétaires. La complexité des habitats benthiques et l’aire disponible pour les microbes par rapport au volume d’eau qui s’écoule sont considérées comme des facteurs importants pour le métabolisme de l’écosystème. Malheureusement, le creusement et l’alignement des cours d’eau pour le drainage des terres pourraient compromettre les services naturels fournis par les cours d’eau. Cette complexité peut être exprimée quantitativement avec des paramètres hydrauliques tels que le stokage transitoire de l’eau dans le lit de la rivière, la durée de résidence du stockage transitoire, et la longueur du flux en hélice (ou spirale) de l’eau (distance moyenne parcourue par une molécule d’eau dans la zone d’eau courante libre avant d’entrer dans la zone calme). L’effet de la température sur la respiration globale des ruisseaux (ER), productivité primaire brute (GPP) et production nette de l’écosystème (NEP) a récemment été évalué au travers d’une « expérience naturelle » dans des ruisseaux géothermiques islandais le long d’un gradient de température de 5−25 ◦C. Il resta, cependant, une quantité substantielle de variabilité non expliquée par les modèles statistiques, qui pourrait être expliquée par les paramètres hydrauliques non reliés à la température. Nous avons aussi tout particulièrement testé les effets additionnels et en synergie du stokage transitoire de l’eau et de la température sur la respiration, en utilisant de nouvelles méthodes. ER and GPP furent hautement corrélées au stockage transitoire de l’eau (ou flux en hélice de l’eau), mais pas à la durée de résidence du stockage. Le stokage transitoire de l’eau et de la température eurent un effect additionnel sur ER (r2 = 0,57 ; P = 0,015), en revanche GPP était plus liée au stockage transitoire de l’eau qu’à la température. L’effet en synergie ne put être confirmé, probablement dû aux limitations des données. Notre interpretation, basée sur un modèle statistique causal, est que l’équilibre métabolique des cours d’eau (NEP) était principalement contrainte par la réponse de la respiration à la température. D’autres travaux de terrain et expérimentaux sont nécessaires pour tester notre nouvelle hypothèse d’un effet en synergie sur ER. Dans l’attente, puisqu’une plus haute activité métabolique permet une rétention ou dégradation plus importante des polluants, la restoration et la gestion des cours d’eau devraient promouvoir la diversité et la complexité des habitats (hyporhéos, touffes de macrophytes, hété- rogénéité du substrat) particulièrement pour l’activité microbienne.This study was funded by the Scottish Government Rural and Environment Research and Analysis Directorate (RERAD), now Rural and Environment Science and Analytical Services (RESAS). J.R.M. acknowledges the support of the Richard Stockton College of New Jersey. We would like to thank Tryggvi Thordarson, director of the Research Station at Hveragerdi for lodging and his warm hospitality, Marc Stutter and two anonymous referees for their insightful comments on the manuscript.Peer ReviewedRitrýnt tímari