The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Oxygen-regulated protein-150 prevents calcium homeostasis deregulation and apoptosis induced by oxidized LDL in vascular cells.

International audienceOxidized LDLs (oxLDLs) induce apoptosis, which contributes to the pathogenesis of atherosclerosis. The 150 kDa oxygen-regulated protein (ORP150), an endoplasmic reticulum (ER)-resident chaperone, is upregulated by hypoxia and prevents ischemia-induced cell death. The aim of this work was to investigate whether and how ORP150 can prevent apoptosis induced by oxLDLs in vascular cells. OxLDLs induced ORP150 expression in the ER of human microvascular endothelial cell line (HMEC-1). ORP150 expression was blocked by antioxidants, by the permeant calcium chelator BAPTA-AM, and by inhibitors of the inositol-1,4,5 trisphosphate (IP3) receptors, 2-aminoethyl diphenylborinate (2-APB) and xestospongin C. ORP150 silencing by siRNA-enhanced oxLDL-induced apoptosis, while forced ORP150 expression increased the resistance of cells via an inhibition of the oxLDL-induced calcium rise, and of subsequent calpain activation, cytochrome c release, caspase 3 activation and apoptosis. A similar protective effect was achieved by BAPTA-AM, 2-APB and xestospongin C. Altogether, these data indicate that (i)ORP150 inhibits oxLDL-induced apoptosis by blocking calcium signaling and subsequent apoptosis, (ii)calcium released from ER stores through IP3 channels is involved in the oxLDL-induced calcium rise and apoptosis, and is inhibited by ORP150. Finally, ORP150 is expressed in advanced atherosclerotic lesions, where it may locally participate to reduce the apoptotic effect of oxLDLs and the subsequent risk of plaque rupture

Polarization Calibration of the Chromospheric Lyman-Alpha SpectroPolarimeter for a 0.1% Polarization Sensitivity in the VUV Range. Part II: In-Flight Calibration

line (121.6 nm). The instrument was successfully launched on 3 September 2015 and observations were conducted at the solar disc center and close to the limb during the five-minutes flight. In this article, the disc center observations are used to provide an in-flight calibration of the instrument spurious polarization. The derived in-flight spurious polarization is consistent with the spurious polarization levels determined during the pre-flight calibration and a statistical analysis of the polarization fluctuations from solar origin is conducted to ensure a 0.014% precision on the spurious polarization. The combination of the pre-flight and the in-flight polarization calibrations provides a complete picture of the instrument response matrix, and a proper error transfer method is used to confirm the achieved polarization accuracy. As a result, the unprecedented 0.1% polarization accuracy of the instrument in the vacuum ultraviolet is ensured by the polarization calibration. This is a post-peer-review, pre-copyedit version of an article published in Solar Physics. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11207-017-1062-

Discovery of Scattering Polarization in the Hydrogen Lyα Line of the Solar Disk Radiation

There is a thin transition region (TR) in the solar atmosphere where the temperature rises from 10,000 K in the chromosphere to millions of degrees in the corona. Little is known about the mechanisms that dominate this enigmatic region other than the magnetic field plays a key role. The magnetism of the TR can only be detected by polarimetric measurements of a few ultraviolet (UV) spectral lines, the Lyα line of neutral hydrogen at 121.6 nm (the strongest line of the solar UV spectrum) being of particular interest given its sensitivity to the Hanle effect (the magnetic-field-induced modification of the scattering line polarization). We report the discovery of linear polarization produced by scattering processes in the Lyα line, obtained with the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) rocket experiment. The Stokes profiles observed by CLASP in quiet regions of the solar disk show that the Q/I and U/I linear polarization signals are of the order of 0.1% in the line core and up to a few percent in the nearby wings, and that both have conspicuous spatial variations with scales of ~10 arcsec. These observations help constrain theoretical models of the chromosphere–corona TR and extrapolations of the magnetic field from photospheric magnetograms. In fact, the observed spatial variation from disk to limb of polarization at the line core and wings already challenge the predictions from three-dimensional magnetohydrodynamical models of the upper solar chromosphere. © 2017. The American Astronomical Society. All rights reserved

Correction to:Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry (Clinical Research in Cardiology, (2022), 111, 5, (560-573), 10.1007/s00392-022-01996-2)

In this article, the name of the GLORIA-AF investigator Anastasios Kollias was given incorrectly as Athanasios Kollias in the Acknowledgements. The original article has been corrected.</p

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice:GLORIA-AF Registry

BACKGROUND AND PURPOSE: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF).METHODS: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest.RESULTS: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79-2.03), major bleeding 0.59 (0.40-0.88), myocardial infarction 0.68 (0.40-1.16), and all-cause death 0.86 (0.67-1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76-1.78), myocardial infarction 0.84 (0.48-1.46), major bleeding 0.98 (0.63-1.52) and all-cause death 1.01 (0.79-1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52-1.19), myocardial infarction 0.96 (0.63-1.45), major bleeding 1.54 (1.14-2.08), and all-cause death 0.97 (0.80-1.19).CONCLUSIONS: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death.REGISTRATION: URL: https://www.CLINICALTRIALS: gov . Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013.</p