{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:35:04Z","timestamp":1787654104642,"version":"build-2736575974"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>\n              Current European guidelines for the management of atrial fibrillation suggest using biomarkers to refine the risk stratification process. However, it is unclear whether \u22652 biomarkers incrementally improve risk prediction beyond 1 biomarker alone. We investigated whether the predictive performance of CHA\n              <jats:sub>2<\/jats:sub>\n              DS\n              <jats:sub>2<\/jats:sub>\n              -VASc and HAS-BLED scores could be enhanced by incrementally adding consecutive different biomarkers in real-world atrial fibrillation patients taking vitamin K antagonists therapy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              We included 940 atrial fibrillation patients stable on vitamin K antagonists (international normalized ratio, 2.0\u20133.0) for at least the previous 6 months. At inclusion, VWF (von Willebrand factor), high-sensitivity troponin T, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity IL (interleukin)-6, fibrin monomers, and BTP (\u03b2-trace protein) concentrations were quantified. During follow-up, all adverse events were recorded, and biomarkers were added to CHA\n              <jats:sub>2<\/jats:sub>\n              DS\n              <jats:sub>2<\/jats:sub>\n              -VASc and HAS-BLED scores depending on the C index.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              During 6.5 (4.3\u20137.9) years, there were 98 ischemic strokes (1.60% per year) and 172 major bleeds (1.60% per year). After the addition of biomarkers, the predictive performance of CHA\n              <jats:sub>2<\/jats:sub>\n              DS\n              <jats:sub>2<\/jats:sub>\n              -VASc was not significantly increased, although the model with 3 biomarkers (ie, NT-proBNP+BTP+VWF) showed a low gain in sensitivity (integrated discrimination improvement, 2.70%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). The predictive performance of HAS-BLED was enhanced in all biomarker-based models, with the best prediction shown by the model with 3 biomarkers (ie, VWF+NT-proBNP+high-sensitivity IL-6; C index, 0.600 [95% CI, 0.561\u20130.625] versus 0.639 [95% CI, 0.607\u20130.669];\n              <jats:italic>P<\/jats:italic>\n              =0.025). This model also confirmed an increased sensitivity (integrated discrimination improvement, 5.20%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and positive reclassification (net reclassification improvement, 19.20%;\n              <jats:italic>P<\/jats:italic>\n              =0.020).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              By adding consecutive biomarkers, the predictive ability of CHA\n              <jats:sub>2<\/jats:sub>\n              DS\n              <jats:sub>2<\/jats:sub>\n              -VASc for ischemic stroke was not increased, whereas the predictive ability of HAS-BLED for major bleeding was only slightly enhanced. The net benefit and clinical usefulness of the biomarker-based models were marginal in comparison to the original scores based on clinical factors.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.118.024305","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T09:00:30Z","timestamp":1557824430000},"page":"1372-1379","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Refining Stroke and Bleeding Prediction in Atrial Fibrillation by Adding Consecutive Biomarkers to Clinical Risk Scores"],"prefix":"10.1161","volume":"50","author":[{"given":"Jos\u00e9 Miguel","family":"Rivera-Caravaca","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, CIBERCV, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Murcia, Spain (J.M.R.-C., F.M., M.A.E.-P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, CIBERCV, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Murcia, Spain (J.M.R.-C., F.M., M.A.E.-P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Vilchez","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Hospital General Universitario Santa Luc\u00eda, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Cartagena, Spain (J.A.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefa","family":"G\u00e1lvez","sequence":"additional","affiliation":[{"name":"Department of Hematology and Clinical Oncology, Hospital General Universitario Morales Meseguer, Instituto Murciano de Investigaci\u00f3n Biosanitaria, University of Murcia, Spain (J.G., V.V., V.R.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Asunci\u00f3n","family":"Esteve-Pastor","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, CIBERCV, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Murcia, Spain (J.M.R.-C., F.M., M.A.E.-P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Vicente","sequence":"additional","affiliation":[{"name":"Department of Hematology and Clinical Oncology, Hospital General Universitario Morales Meseguer, Instituto Murciano de Investigaci\u00f3n Biosanitaria, University of Murcia, Spain (J.G., V.V., V.R.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y.H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, United Kingdom 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