CO071 | ATRIAL FIBRILLATION, CEREBRAL SMALL VESSEL DISEASE, AND GENDER MEDICINE: FOCUS ON BIOMARKERS AND NEUROIMAGING

F. Alfano^1|2, M. Berteotti^1|2, F. Cesari^1|2, AM. Gori^1|2, E. Salvadori¹, B. Giusti^1|2, A. Bertelli^1|2, L. Bicchi^1|2, F. Fratini³, B. Formelli³, G. Salti³, E. Fainardi^1|4, A. Ginestroni^1|4, S. Chiti⁵, A. Poggesi^1|3, R. Marcucci^1|2 | ¹Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy; ²Center for Atherothrombotic Diseases, Careggi University Hospital, Firenze, Italy; ³NEUROFARBA Department, Neuroscience Section, University of Florence, Firenze, Italy; ⁴Neuroradiology Unit, Careggi University Hospital, Firenze, Italy; ⁵Health Physics Unit, Careggi University Hospital, Firenze, Italy

Background. Atrial fibrillation (AF) is the most common supraventricular arrythmia and one of the most commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role of inflammation, endothelial dysfunction, and extracellular matrix (ECM) remodeling in the pathogenesis of AF. Population studies have also suggested an association between AF and cerebral small vessel disease (CSVD) with growing evidence indicating that the burden of certain markers of CSVD is greater in women. However, the association between female sex and CSVD remains poorly understood.
Objectives. The main outcome of the study was thus to investigate the role of gender in the association between circulating biomarkers and the progression of CSVD in AF patients undergoing oral anticoagulant therapy.
Methods. The Strat-AF study is an observational, prospective, single-center, hospital-based study enrolling elderly patients with AF. Results refer to 170 patients (60 women and 110 men). Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging (MRI), and circulating biomarker assessment.
Results. At multivariate logistic regression analysis adjusted for age, CHA2DS2-VASc HAS-BLED and type of anticoagulant, independent predictors were: high levels of vWF for the presence of lacunar infarcts in women [OR 95% CI 3,24 (1,23-8,55), p=0.018]; high levels of TIMP-1 for having at least one sign of SVD at the SVD score in men [OR 95% CI 7,25 (2.18-24.15), p=0.001]; high levels of MMP-12, TIMP-1, TIMP-2 and TIMP-4 for the presence of CMB in women [OR 95% CI 7,76 (1,60-37,69), p=0,021; OR 95% CI 1,90 (1,02-3,52), p=0,042; OR 95% CI 2,46 (1,27 4,80), p=0,008 e OR 95% CI 2,36 (1,12-4,95), p=0,023, rispectively]; high levels of TIMP-1 for the presence of bgEPVS in men [OR 95% CI 2,20 (1,11-4,38), p=0,025] and high levels of MMP-12 and TIMP-2 for the presence of bgEPVS in women [OR 95% CI 2,57 (1,22-5,93), p=0,027 and OR 95% CI 2,15 (1,03-4,53), p=0,043, respectively]; elevated IL-6 and MMP-2, levels for the presence the presence of white matter hyperintensities in women [OR 10.65 (1.31–86.67), p = 0.027; OR 3.36 (1.23–9.15), p = 0.018, respectively]; elevated TIMP-1 levels for the presence the presence of white matter hyperintensities in men [OR 2.10 (1.08–4.08), p = 0.030].
Conclusions. These results from the Strat-AF study demonstrated that a complete biohumoral and instrumental assessment can jointly identify female patients with AF at higher risk of SVD. These findings pave the way for the implementation of clinical protocols incorporating brain MRI and circulating biomarkers as potential innovative tools for an increasingly refined—and sex-specific—stratification of cardiovascular risk in AF patients undergoing oral anticoagulant therapy.