{"entity": "researcher", "timestamp": "2026-08-17T01:16:42.204Z", "family": "Pol", "given": "Tymon", "initials": "T", "orcid": "0000-0001-6239-199X", "affiliations": ["Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden tymon.pol@medsci.uu.se.", "Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/f0bf1df0dd904b579b081a3680627005.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/f0bf1df0dd904b579b081a3680627005"}}, "publications": [{"entity": "publication", "iuid": "a02c0a3eaf1e456fb1859569031908a7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a02c0a3eaf1e456fb1859569031908a7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a02c0a3eaf1e456fb1859569031908a7"}}, "title": "Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation.", "authors": [{"family": "Pol", "given": "Tymon", "initials": "T", "orcid": "0000-0001-6239-199X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0bf1df0dd904b579b081a3680627005.json"}}, {"family": "Hijazi", "given": "Ziad", "initials": "Z", "orcid": "0000-0002-7420-743X", "researcher": {"href": "https://publications.scilifelab.se/researcher/03d1c858fbab4b7d9c9574adf5ad51af.json"}}, {"family": "Lindb\u00e4ck", "given": "Johan", "initials": "J"}, {"family": "Oldgren", "given": "Jonas", "initials": "J", "orcid": "0000-0002-9969-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/14e1774fd1674edeaaa64a3f86d051d7.json"}}, {"family": "Alexander", "given": "John H", "initials": "JH", "orcid": "0000-0002-1444-2462", "researcher": {"href": "https://publications.scilifelab.se/researcher/468ce17f14a04afd9cfe979103f1f849.json"}}, {"family": "Connolly", "given": "Stuart J", "initials": "SJ"}, {"family": "Eikelboom", "given": "John W", "initials": "JW"}, {"family": "Ezekowitz", "given": "Michael D", "initials": "MD", "orcid": "0000-0003-3623-2252", "researcher": {"href": "https://publications.scilifelab.se/researcher/43f3a6f18de74bb6a632b1b16d1b778c.json"}}, {"family": "Granger", "given": "Christopher B", "initials": "CB"}, {"family": "Lopes", "given": "Renato D", "initials": "RD", "orcid": "0000-0003-2999-4961", "researcher": {"href": "https://publications.scilifelab.se/researcher/a98c4a6d5300452b9a3a770cff4d97e9.json"}}, {"family": "Yusuf", "given": "Salim", "initials": "S"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}], "type": "clinical study", "published": "2022-07-20", "journal": {"title": "Cardiovasc. Res.", "issn": "1755-3245", "volume": "118", "issue": "9", "pages": "2112-2123", "issn-l": "0008-6363"}, "abstract": "Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.\n\nA case-cohort design with 1.8- to 1.9-year follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analysed with conventional immunoassays and the OLINK proximity extension assay panels: CVDII, CVDIII, and Inflammation. Association between biomarkers and CV death was evaluated using Random Survival Forest, Boruta, and adjusted Cox-regression analyses. The biomarkers most strongly and consistently associated with CV death were as follows (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide [NT-proBNP; 1.63 (1.37-1.93)], cardiac troponin T [cTnT-hs; 1.60 (1.35-1.88)], interleukin-6 [IL-6; 1.29 (1.13-1.47)], growth differentiation factor-15 [GDF-15; 1.30 (1.10-1.53)], fibroblast growth factor 23 [FGF-23; 1.21 (1.10-1.33)], urokinase receptor [uPAR; 1.38 (1.16-1.64)], trefoil factor 3 [TFF3; 1.27 (1.10-1.46)], tumour necrosis factor receptor 1 [TNFR1; 1.21 (1.01-1.45)], TNF-related apoptosis-inducing ligand receptor 2 [TRAILR2; 1.18 (1.04-1.34)], and cathepsin L1 [CTSL1; 1.22 (1.07-1.39)].\n\nIn this comprehensive screening of 268 biomarkers in anticoagulated patients with AF, the underlying mechanisms most strongly associated with CV death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR), and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV death in AF.\n\nNCT00412984 and NCT00262600.", "doi": "10.1093/cvr/cvab262", "pmid": "34358298", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9302885"}, {"db": "pii", "key": "6343453"}, {"db": "ClinicalTrials.gov", "key": "NCT00412984"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}], "notes": [], "created": "2021-12-10T09:12:08.560Z", "modified": "2022-12-02T08:57:56.429Z"}, {"entity": "publication", "iuid": "52d2c20d8ad9462fb85791c90e67b9aa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/52d2c20d8ad9462fb85791c90e67b9aa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/52d2c20d8ad9462fb85791c90e67b9aa"}}, "title": "Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas.", "authors": [{"family": "Pol", "given": "Tymon", "initials": "T", "orcid": "0000-0001-6239-199X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0bf1df0dd904b579b081a3680627005.json"}}, {"family": "Hijazi", "given": "Ziad", "initials": "Z"}, {"family": "Lindb\u00e4ck", "given": "Johan", "initials": "J", "orcid": "0000-0002-6473-8798", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cea1044231d40b5a3bf186485d97cd4.json"}}, {"family": "Alexander", "given": "John H", "initials": "JH"}, {"family": "Bahit", "given": "M Cecilia", "initials": "MC"}, {"family": "De Caterina", "given": "Raffaele", "initials": "R", "orcid": "0000-0003-1637-574X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3fdb2475ea649c8b2f4fef1fe8417e5.json"}}, {"family": "Eikelboom", "given": "J W", "initials": "JW"}, {"family": "Ezekowitz", "given": "Michael D", "initials": "MD"}, {"family": "Gersh", "given": "Bernard J", "initials": "BJ"}, {"family": "Granger", "given": "Christopher B", "initials": "CB"}, {"family": "Hylek", "given": "Elaine M", "initials": "EM"}, {"family": "Lopes", "given": "Renato", "initials": "R"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2021-03-00", "journal": {"title": "Open Heart", "issn": "2053-3624", "volume": "8", "issue": "1", "issn-l": null}, "abstract": "Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions.\n\nData were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region.\n\nGDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AF-death score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions.\n\nIn patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions.\n\nClinicalTrials.gov Registry NCT00412984 and NCT00262600.", "doi": "10.1136/openhrt-2020-001471", "pmid": "33741689", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "openhrt-2020-001471"}, {"db": "pmc", "key": "PMC7986788"}, {"db": "ClinicalTrials.gov", "key": "NCT00412984"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}], "notes": [], "created": "2021-12-10T09:26:47.498Z", "modified": "2021-12-10T09:26:47.604Z"}]}