| 1. |
- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 2. |
- Tabari, Hossein, et al.
(author)
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The contribution of anthropogenic influence to more anomalous extreme precipitation in Europe
- 2020
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 15:10
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Journal article (peer-reviewed)abstract
- Anthropogenic influences can modulate the low-frequency variability of extreme precipitation and increase the likelihood of flooding events. It is not, however, clear how much and in what manner the low-frequency variability has changed in recent decades as global warming has intensified. Here, we investigate the contribution of anthropogenic influences to the time evolution of extreme precipitation anomalies in different seasons using Coupled Model Intercomparison Project Phase 6 (CMIP6) and CMIP5 model simulations and observations over Europe. Our results show a latitudinal dependence of changes in extreme precipitation anomalies for all seasons due to anthropogenic impacts. While the contribution of anthropogenic influences to extreme precipitation anomalies at low latitudes (<50 degrees) is less than 8% in all seasons, it goes up to 26% and 41% at mid (50 degrees-60 degrees) and high (>60 degrees) latitudes. Without the offsetting effect of anthropogenic aerosols, anthropogenic emissions of greenhouse gases alone should have produced larger anomalies than observed. For all seasons, the more extreme the precipitation, the larger the anthropogenic influences.
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| 3. |
- Tavenier, Anne H., et al.
(author)
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Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial
- 2020
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In: Thrombosis and Haemostasis. - : GEORG THIEME VERLAG KG. - 0340-6245 .- 2567-689X. ; 120:1, s. 65-74
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Journal article (peer-reviewed)abstract
- Background Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. Methods 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. Results Compared with no GPI ( n = 930), routine GPI ( n = 525) or bailout GPI ( n = 175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p = 0.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32-6.64; p = 0.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88-3.61; p = 0.92). Conclusion Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.
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