| 1. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 3. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 4. |
- Ingegnoli, Francesca, et al.
(författare)
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A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study
- 2015
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 102, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.
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| 5. |
- Barnes, Ashley T., et al.
(författare)
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Mother of dragons: A massive, quiescent core in the dragon cloud (IRDC G028.37+00.07)
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
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Tidskriftsartikel (refereegranskat)abstract
- Context. Core accretion models of massive star formation require the existence of massive, starless cores within molecular clouds. Yet, only a small number of candidates for such truly massive, monolithic cores are currently known. Aims. Here we analyse a massive core in the well-studied infrared-dark cloud (IRDC) called the dragon clouda'(also known as G028.37+00.07 or Cloud Ca). This core (C2c1) sits at the end of a chain of a roughly equally spaced actively star-forming cores near the center of the IRDC. Methods. We present new high-angular-resolution 1 mm ALMA dust continuum and molecular line observations of the massive core. Results. The high-angular-resolution observations show that this region fragments into two cores, C2c1a and C2c1b, which retain significant background-subtracted masses of 23 M· and 2 M· (31 M· and 6 M· without background subtraction), respectively. The cores do not appear to fragment further on the scales of our highest-angular-resolution images (0.2 , 0.005 pc ∼ 1000 AU). We find that these cores are very dense (nH2 > 106 cm-3) and have only trans-sonic non-thermal motions ( 3s ∼ 1). Together the mass, density, and internal motions imply a virial parameter of
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| 6. |
- Becher, Peter M., et al.
(författare)
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Use of sodium-glucose co-transporter 2 inhibitors in patients with heart failure and type 2 diabetes mellitus : data from the Swedish Heart Failure Registry
- 2021
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:6, s. 1012-1022
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Tidskriftsartikel (refereegranskat)abstract
- Aims Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use. Methods and results Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52-0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all-cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke. Conclusion In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity.
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| 7. |
- Cosentino, Giuliana, 1990, et al.
(författare)
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Deuterium fractionation across the infrared-dark cloud G034.77-00.55 interacting with the supernova remnant W44
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
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Tidskriftsartikel (refereegranskat)abstract
- Supernova remnants (SNRs) may regulate star formation in galaxies. For example, SNR-driven shocks may form new molecular gas or compress pre-existing clouds and trigger the formation of new stars. Aims. To test this scenario, we measured the deuteration of N2H+, DNfrac 2H+- a well-studied tracer of pre-stellar cores - across the infrared-dark cloud (IRDC) G034.77-00.55, which is known to be experiencing a shock interaction with the SNR W44. Methods. We use N2H+ and N2D+ J = 1-0 single pointing observations obtained with the 30m antenna at the Instituto de Radioastronomia Millimetrica to infer DN2H+ frac towards five positions across the cloud, namely a massive core, different regions across the shock front, a dense clump, and ambient gas. Results. We find DN2H+ frac in the range 0.03-0.1, which is several orders of magnitude larger than the cosmic D/H ratio (∼10-5). The DN2H+ frac across the shock front is enhanced by more than a factor of 2 (DNfrac 2H+∼ 0.05-0.07) with respect to the ambient gas (=0.03) and similar to that measured generally in pre-stellar cores. Indeed, in the massive core and dense clump regions of this IRDC we measure DN2H+ frac ∼ 0.1.
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| 8. |
- Cosentino, Giuliana, et al.
(författare)
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Interstellar Plunging Waves: ALMA Resolves the Physical Structure of Nonstationary MHD Shocks
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 881:2
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Tidskriftsartikel (refereegranskat)abstract
- Magnetohydrodynamic (MHD) shocks are violent events that inject large amounts of energy in the interstellar medium dramatically modifying its physical properties and chemical composition. Indirect evidence for the presence of such shocks has been reported from the especial chemistry detected toward a variety of astrophysical shocked environments. However, the internal physical structure of these shocks remains unresolved since their expected spatial scales are too small to be measured with current instrumentation. Here we report the first detection of a fully spatially resolved, MHD shock toward the infrared dark cloud (IRDC) G034.77-00.55. The shock, probed by silicon monoxide (SiO) and observed with the Atacama Large Millimeter/submillimeter Array (ALMA), is associated with the collision between the dense molecular gas of the cloud and a molecular gas flow pushed toward the IRDC by the nearby supernova remnant (SNR) W44. The interaction is occurring on subparsec spatial scales thanks to the enhanced magnetic field of the SNR, making the dissipation region of the MHD shock large enough to be resolved with ALMA. Our observations suggest that molecular flow-flow collisions can be triggered by stellar feedback, inducing shocked molecular gas densities compatible with those required for massive star formation.
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| 9. |
- Entekhabi, N., et al.
(författare)
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Astrochemical modelling of infrared dark clouds
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 662
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Tidskriftsartikel (refereegranskat)abstract
- Context. Infrared dark clouds (IRDCs) are cold, dense regions of the interstellar medium (ISM) that are likely to represent the initial conditions for massive star and star cluster formation. It is thus important to study the physical and chemical conditions of IRDCs to provide constraints and inputs for theoretical models of these processes. Aims. We aim to determine the astrochemical conditions, especially the cosmic ray ionisation rate (CRIR) and chemical age, in different regions of the massive IRDC G28.37+00.07 by comparing observed abundances of multiple molecules and molecular ions with the predictions of astrochemical models. Methods. We have computed a series of single-zone, time-dependent, astrochemical models with a gas-grain network that systematically explores the parameter space of the density, temperature, CRIR, and visual extinction. We have also investigated the effects of choices of CO ice binding energy and temperatures achieved in the transient heating of grains when struck by cosmic rays. We selected ten positions across the IRDC that are known to have a variety of star formation activity. We utilised mid-infrared extinction maps and sub-millimetre (sub-mm) emission maps to measure the mass surface densities of these regions needed for abundance and volume density estimates. The sub-mm emission maps were also used to measure temperatures. We then used Instituto de Radioas-tromía Milimétrica (IRAM) 30 m observations of various tracers, especially C18O(1-0), H13CO+(1-0), HC18O+(1-0), and N2H+(1-0), to estimate column densities and thus abundances. Finally, we investigated the range of astrochemical conditions that are consistent with the observed abundances. Results. The typical physical conditions of the IRDC regions are nH ∼ 3 ×-104 to 105 cm-3 and T ∼ 10 to 15 K. Strong emission of H13CO+(1-0) and N2H+(1-0) is detected towards all the positions and these species are used to define relatively narrow velocity ranges of the IRDC regions, which are used for estimates of CO abundances, via C18O(1-0). We would like to note that CO depletion factors are estimated to be in the range fD ∼ 3 to 10. Using estimates of the abundances of CO, HCO+, and N2H+, we find consistency with astrochemical models that have relatively low CRIRs of ζ ∼ 10-18 to ∼10-17 s-1, with no evidence for systematic variation with the level of star formation activity. Astrochemical ages, which are defined with a reference to an initial condition of all H in H2, all C in CO, and all other species in atomic form, are found to be <1 Myr. We also explore the effects of using other detected species, that is HCN, HNC, HNCO, CH3OH, and H2CO, to constrain the models. These generally lead to implied conditions with higher levels of CRIRs and older chemical ages. Considering the observed fD versus nH relation of the ten positions, which we find to have relatively little scatter, we discuss potential ways in which the astrochemical models can match such a relation as a quasi-equilibrium limit valid at ages of at least a few free-fall times, that is 3;0.3 Myr, including the effect of CO envelope contamination, small variations in temperature history near 15 K, CO-ice binding energy uncertainties, and CR-induced desorption. We find general consistency with the data of ∼0.5 Myr-old models that have ζ ∼ 2-5-10-18 s-1 and CO abundances set by a balance of freeze-out with CR-induced desorption. Conclusions. We have constrained the astrochemical conditions in ten regions in a massive IRDC, finding evidence for relatively low values of CRIR compared to diffuse ISM levels. We have not seen clear evidence for variation in the CRIR with the level of star formation activity. We favour models that involve relatively low CRIRs (≲ 10-17 s-1) and relatively old chemical ages (≳ 3;0.3 Myr, i.e. 3;3tff). We discuss potential sources of systematic uncertainties in these results and the overall implications for IRDC evolutionary history and astrochemical models.
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| 10. |
- Law, Chi Yan, 1990, et al.
(författare)
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Polarized Light from Massive Protoclusters (POLIMAP). I. Dissecting the Role of Magnetic Fields in the Massive Infrared Dark Cloud G28.37+0.07
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 967:2
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic fields may play a crucial role in setting the initial conditions of massive star and star cluster formation. To investigate this, we report SOFIA-HAWC+ 214 μm observations of polarized thermal dust emission and high-resolution GBT-Argus C18O(1-0) observations toward the massive Infrared Dark Cloud (IRDC) G28.37+0.07. Considering the local dispersion of B-field orientations, we produce a map of the B-field strength of the IRDC, which exhibits values between ∼0.03 and 1 mG based on a refined Davis-Chandrasekhar-Fermi method proposed by Skalidis & Tassis. Comparing to a map of inferred density, the IRDC exhibits a B-n relation with a power-law index of 0.51 ± 0.02, which is consistent with a scenario of magnetically regulated anisotropic collapse. Consideration of the mass-to-flux ratio map indicates that magnetic fields are dynamically important in most regions of the IRDC. A virial analysis of a sample of massive, dense cores in the IRDC, including evaluation of magnetic and kinetic internal and surface terms, indicates consistency with virial equilibrium, sub-Alfvénic conditions, and a dominant role for B-fields in regulating collapse. A clear alignment of magnetic field morphology with the direction of the steepest column density gradient is also detected. However, there is no preferred orientation of protostellar outflow directions with the B-field. Overall, these results indicate that magnetic fields play a crucial role in regulating massive star and star cluster formation, and therefore they need to be accounted for in theoretical models of these processes.
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| 11. |
- Rydén, Lars, et al.
(författare)
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ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
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Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
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| 12. |
- Sanchez-Ceinos, Julia, et al.
(författare)
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Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium
- 2024
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Ingår i: CARDIOVASCULAR DIABETOLOGY. - 1475-2840. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium.Methods We studied human aortic endothelial cells exposed to high glucose (HAEC) or isolated from individuals with diabetes (D-HAEC). RT-qPCR, immunoblotting, chromatin immunoprecipitation (ChIP-qPCR), and confocal microscopy were performed to investigate the role of H3K27me3. We determined superoxide anion (O2 -) production by ESR spectroscopy, NF-kappa B binding activity, and monocyte adhesion. Silencing/overexpression and pharmacological inhibition of chromatin modifying enzymes were used to modulate H3K27me3 levels. Furthermore, isometric tension studies and immunohistochemistry were performed in aorta from wild-type and db/db mice.Results Incubation of HAEC to high glucose showed that upregulation of EZH2 coupled to reduced demethylase UTX and JMJD3 was responsible for the increased H3K27me3. ChIP-qPCR revealed that repressive H3K27me3 binding to superoxide dismutase and transcription factor JunD promoters is involved in glucose-induced O2 - generation. Indeed, loss of JunD transcriptional inhibition favours NOX4 expression. Furthermore, H3K27me3-driven oxidative stress increased NF-kappa B p65 activity and downstream inflammatory genes. Interestingly, EZH2 inhibitor GSK126 rescued these endothelial derangements by reducing H3K27me3. We also found that H3K27me3 epigenetic signature alters transcriptional programs in D-HAEC and aortas from db/db mice.Conclusions EZH2-mediated H3K27me3 represents a key epigenetic driver of hyperglycemia-induced endothelial dysfunction. Targeting EZH2 may attenuate oxidative stress and inflammation and, hence, prevent vascular disease in diabetes.
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| 13. |
- Savarese, Gianluigi, et al.
(författare)
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Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum : A blueprint for clinical trial design
- 2020
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 313, s. 76-82
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundComorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.Methods and resultsOf 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.ConclusionHFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.
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| 14. |
- Savarese, Gianluigi, et al.
(författare)
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Comparative associations between angiotensin converting enzyme inhibitors, angiotensin receptor blockers and their combination, and outcomes in patients with heart failure and reduced ejection fraction
- 2015
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 36, s. 22-23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are recommended in heart failure with reduced ejection fraction (HFREF), but there is limited data on ARB vs. ACE-I and their combination in unselected populations. The purpose of this study was to compare the associations between the use of ACE-I, ARB and their combination, and outcomes in HFREF. Methods and results: We prospectively studied 22,947 patients with HFREF (ejection fraction b 40%) enrolled in the Swedish Heart Failure Registry who received ACE-I but not ARB (n = 15,801, 69%), ARB but not ACE-I (n = 4335, 19%), their combination (n = 571, 2%) or neither (n = 2240, 10%). As compared with ACE-I alone, the hazard ratios (HRs) for ARB alone for all-cause mortality was 0.97 (95% CI = 0.91-1.03; p = 0.27), for HF hospitalization 1.08 (CI = 1.02-1.15; p less than 0.01) and for the composite outcome 1.03 (CI = 0.99-1.08; p = 0.15). ACE-I and ARB combination had for death HR = 0.98 (95% CI = 0.84-1.14; p = 0.76), for HF hospitalization HR = 1.49 (CI = 1.33-1.68; p less than 0.01) and for the composite outcome HR = 1.35 (CI = 1.21-1.50; p less than 0.01). Use of neither ACE-I nor ARB was associated with HR for death 1.41 (CI = 1.33-1.50; p less than 0.01), for HF hospitalization 1.16 (CI = 1.08-1.25; p less than 0.01) and for the composite outcome 1.28 (CI = 1.21-1.35; p less than 0.01). Conclusion: This large generalizable analysis confirms the current recommendation of using ACE-I as first choice in HFREF. ARB can be considered an alternative in patients who cannot use ACE-I but should not routinely replace ACE-I. The combination of ACE-I and ARB was not associated with additional benefit over either one alone, and may potentially be harmful. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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| 15. |
- Savarese, Gianluigi, et al.
(författare)
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Utilizing NT-proBNP for Eligibility and Enrichment in Trials in HFpEF, HFmrEF, and HFrEF
- 2018
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Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1779 .- 2213-1787. ; 6:3, s. 246-256
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESThe purpose of this study was to assess the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiovascular (CV) versus non-CV events and between NT-proBNP and potential treatment effects in heart failure (HF) with preserved, mid-range, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF, respectively) and clinically relevant subgroups.BACKGROUNDOptimizing patient eligibility criteria in HF trials requires biomarkers that enrich for CV but not for non-CV events and select patients most likely to respond to the tested intervention.METHODSIn the Swedish HF registry population stratified by EF category, we used Kaplan-Meier curves to estimate unadjusted CV and non-CV risks (mortality or hospitalization); Poisson regressions to calculate crude event rates of CV and non-CV events according to NT-proBNP levels; and Cox regressions to calculate the adjusted hazard ratios for HF therapies according to NT-proBNP <= or > median.RESULTSIn a cohort of 15,849 patients (23% HFpEF, 21% HFmrEF, 56% HFrEF), median NT-proBNP was 2,037, 2,192, and 3,141 pg/ml, respectively. With increasing NT-proBNP, CV event rates increased more steeply than non-CV rates (range 20 to 160 and 30 to 100 per 100 patient-years in HFpEF; 20 to 130 and 20 to 100 in HFmrEF; and 20 to 110 and 20 to 50 in HFrEF, respectively). The CV-to-non-CV ratio increased with increasing NT-proBNP in HFpEF and HFrEF, but only in the lower range in HFmrEF. The association between treatments (e.g., angiotensin-converting enzyme-inhibitor, angiotensin II receptor blockers, and beta-blockers) and outcomes was consistent in NT-proBNP <= and > median.CONCLUSIONSIn HF trial design in different EF categories, NT-proBNP may be a useful tool for eligibility and enrichment for CV events, but its role in predicting a potential treatment response remains unclear.
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| 16. |
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| 17. |
- Seferovic, Petar M., et al.
(författare)
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Sodium-glucose co-transporter 2 inhibitors in heart failure: beyond glycaemic control. A position paper of the Heart Failure Association of the European Society of Cardiology
- 2020
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:9, s. 1495-1503
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is common and associated with a poor prognosis, despite advances in treatment. Over the last decade cardiovascular outcome trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus have demonstrated beneficial effects for three SGLT2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) in reducing hospitalisations for HF. More recently, dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in patients with chronic HF with reduced left ventricular ejection fraction, with or without type 2 diabetes mellitus. A number of additional trials in HF patients with reduced and/or preserved left ventricular ejection fraction are ongoing and/or about to be reported. The present position paper summarises recent clinical trial evidence and discusses the role of SGLT2 inhibitors in the treatment of HF, pending the results of ongoing trials in different populations of patients with HF.
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| 18. |
- Thorvaldsen, Tonje, et al.
(författare)
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Eligibility for Dapagliflozin and Empagliflozin in a Real-world Heart Failure Population
- 2022
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Ingår i: Journal of Cardiac Failure. - : Churchill Livingstone. - 1071-9164 .- 1532-8414. ; 28:7, s. 1050-1062
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Tidskriftsartikel (refereegranskat)abstract
- Background: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Methods and Results: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic, and label scenarios was 35%, 61%, and 80% for DAPA-HF; 31%, 55%, and 81% for EMPEROR-Reduced; 30%, 61%, and 74% for DELIVER; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity. Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice. Lay summary: When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits. Conclusions: In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibi-tors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility. (J Cardiac Fail 2022;28:1050-1062)
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- Wallner, Markus, et al.
(författare)
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Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes: data from the Swedish Heart Failure and Swedish National Diabetes Registries
- 2024
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Ingår i: EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY. - 2055-6837 .- 2055-6845. ; 10:4, s. 296-306
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Tidskriftsartikel (refereegranskat)abstract
- Aims To assess the use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes mellitus (T2DM). Methods and results The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions and associations with outcomes were assessed by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-21, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age <75 years, worse glycaemic control, impaired renal function, obesity, and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with a lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischaemic attack, or myocardial infarction), and CV and all-cause death. In patients with body mass index >= 30 kg/m2, GLP-1 RA use was also associated with a lower risk of HHF/CV death and HHF alone. Conclusions In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF, and obesity and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM.
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