{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:58:16Z","timestamp":1780959496942,"version":"3.54.1"},"reference-count":31,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Tuscany region and Italian Ministry of Health","doi-asserted-by":"publisher","award":["GR-2013-02355523"],"award-info":[{"award-number":["GR-2013-02355523"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.<\/jats:p>","DOI":"10.3390\/jcm12216866","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T13:20:07Z","timestamp":1698672007000},"page":"6866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of Extracellular Matrix and Inflammation in the Stratification of Bleeding and Thrombotic Risk of Atrial Fibrillation on Oral Anticoagulant Therapy: Insights from Strat-Af Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Francesco","family":"Alfano","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Center for Atherothrombotic Diseases, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cesari","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Center for Atherothrombotic Diseases, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Gori","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Center for Atherothrombotic Diseases, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-4734","authenticated-orcid":false,"given":"Martina","family":"Berteotti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Center for Atherothrombotic Diseases, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-0053","authenticated-orcid":false,"given":"Emilia","family":"Salvadori","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Neuroscience Section, University of Florence, 50134 Florence, Italy"},{"name":"Stroke Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8708-9444","authenticated-orcid":false,"given":"Betti","family":"Giusti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Center for Atherothrombotic Diseases, Careggi University Hospital, 50134 Florence, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Formelli","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Neuroscience Section, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4565-5601","authenticated-orcid":false,"given":"Francesca","family":"Pescini","sequence":"additional","affiliation":[{"name":"Stroke Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Fainardi","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Careggi University Hospital, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Chiti","sequence":"additional","affiliation":[{"name":"Health Physics Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1791-3573","authenticated-orcid":false,"given":"Chiara","family":"Marzi","sequence":"additional","affiliation":[{"name":"Institute of Applied Physics \u201cNello Carrara\u201d (IFAC), National Research Council of Italy (CNR), 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8778-7819","authenticated-orcid":false,"given":"Stefano","family":"Diciotti","sequence":"additional","affiliation":[{"name":"Department of Electrical, Electronic, and Information Engineering \u201cGuglielmo Marconi\u201d, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Marcucci","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, 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