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- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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- Meershoek, Armelle J.A., et al.
(författare)
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Clinical Response to Procedural Stroke Following Carotid Endarterectomy : A Delphi Consensus Study
- 2021
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884. ; 62:3, s. 350-357
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Tidskriftsartikel (refereegranskat)abstract
- Objective: No dedicated studies have been performed on the optimal management of patients with an acute stroke related to carotid intervention nor is there a solid recommendation given in the European Society for Vascular Surgery guideline. By implementation of an international expert Delphi panel, this study aimed to obtain expert consensus on the optimal management of in hospital stroke occurring during or following CEA and to provide a practical treatment decision tree. Methods: A four round Delphi consensus study was performed including 31 experts. The aim of the first round was to investigate whether the conceptual model indicating the traditional division between intra- and post-procedural stroke in six phases was appropriate, and to identify relevant clinical responses during these six phases. In rounds 2, 3, and 4, the aim was to obtain consensus on the optimal response to stroke in each predefined setting. Consensus was reached in rounds 1, 3, and 4 when ≥ 70% of experts agreed on the preferred clinical response and in round 2 based on a Likert scale when a median of 7 – 9 (most adequate response) was given, IQR ≤ 2. Results: The experts agreed (> 80%) on the use of the conceptual model. Stroke laterality and type of anaesthesia were included in the treatment algorithm. Consensus was reached in 17 of 21 scenarios (> 80%). Perform diagnostics first for a contralateral stroke in any phase, and for an ipsilateral stroke during cross clamping, or apparent stroke after leaving the operation room. For an ipsilateral stroke during the wake up phase, no formal consensus was achieved, but 65% of the experts would perform diagnostics first. A CT brain combined with a CTA or duplex ultrasound of the carotid arteries should be performed. For an ipsilateral intra-operative stroke after flow restoration, the carotid artery should be re-explored immediately (75%). Conclusion: In patients having a stroke following carotid endarterectomy, expedited diagnostics should be performed initially in most phases. In patients who experience an ipsilateral intra-operative stroke following carotid clamp release, immediate re-exploration of the index carotid artery is recommended.
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- van Laarhoven, Constance J H C M, et al.
(författare)
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Carotid tortuosity is associated with extracranial carotid artery aneurysms.
- 2022
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Ingår i: Quantitative imaging in medicine and surgery. - : AME Publishing Company. - 2223-4292 .- 2223-4306. ; 12:11, s. 5018-5029
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tortuous arteries may be associated with carotid dissection. The intima disruption caused by a carotid dissection is a possible cause of extracranial carotid artery aneurysms (ECAAs). The aim was to investigate if carotid tortuosity is also associated with ECAA in patients without presence or history of a carotid artery dissection.METHODS: A retrospective case-control study was performed including 35 unilateral ECAA patients (cases) and 105 age- and sex-matched controls. Tortuosity was expressed as tortuosity-index (TI), curvature, and torsion measured on computed tomography angiography (CTA) data in 3Mensio Vascular and MATLAB by two independent investigators. Primary comparison was tortuosity in ipsi- versus contralateral carotid artery within the cohort of ECAA patients. Secondary comparison was tortuosity with ipsilateral carotid arteries in control patients. All observations were assessed on inter- and intra-operator reproducibility.RESULTS: Carotid tortuosity was comparable within the cohort of ECAA patients (Spearman correlation 0.76, P<0.001), yet distinctively higher in comparison with unilateral controls. After adjustment for patient characteristics, presence of ECAA was associated with TI (β 0.146, 95% CI: 0.100-0.192). All tortuosity observations showed excellent inter- and intra-operator reproducibility.CONCLUSIONS: Carotid tortuosity seems to be a risk factor for development of ECAA. Surveillance of individuals with increased carotid tortuosity therefore potentially ensures prompt diagnosis and treatment of ECAA. However, future research should investigate if persons with an increased tortuosity do indeed develop ECAA.
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