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Peer-reviewedCC BY-NCBleeding, Thrombosis and Vascular Biology

CO024 | THE ROLE OF BLOOD CLOTTING AND ENDOTHELIAL ACTIVATION IN THE STRATIFICATION OF BLEEDING AND THROMBOTIC RISK OF ATRIAL FIBRILLATION ON ORAL ANTICOAGULANT THERAPY: INSIGHTS FROM THE STRAT-AF 2 STUDY

Abstract

Background. Atrial fibrillation (AF) is associated with a prothrombotic milieu characterized by activation of coagulation and endothelial dysfunction, as indicated by increased D-dimer and von Willebrand factor levels. However, the relation between blood clotting activation, endothelial activation, and neuroimaging-based markers remains to be completely understood. Objectives. The aim of the present study was to evaluate the association between blood clotting activation, endothelial dysfunction, and the neuroimaging markers evaluated by CT scan in the STRATAF-2 population. Methods. The STRAT-AF 2 is a prospective observational extension of the STRAT-AF study, including a de novo cohort of anticoagulated patients with atrial fibrillation aged ≥ 65 years who underwent baseline and 1-year follow-up brain computed tomography (CT) (n=100). Neuroimaging assessment included the Van Swieten scale on CT for white matter lesions, identification of lacunes (≤15 mm), and cortical atrophy grading using the Pasquier scale. Medial temporal lobe atrophy (MTA) was evaluated on coronal CT images. Overall small vessel disease burden was estimated by the SVD score (0–3). TC cohort patients were followed for at least 1 year. Results. At baseline, a moderate-to-severe leukoencephalopathy was associated with higher D-dimer levels compared with absent or mild white matter changes (p=0.024), and this association persisted at 12 months (p=0.046). Similarly, the presence of lacunar infarcts was associated with higher D-dimer levels both at baseline (p=0.022) and at follow-up (p=0.049). Neither D-dimer nor von Willebrand factor levels were associated with non-lacunar infarcts. Higher D-dimer levels were also associated with cortical atrophy (p=0.029) and severe MTA (p=0.016) at baseline, with consistent associations at 12 months (p=0.016 and p=0.004, respectively). Moreover, D-dimer levels were positively associated with increasing SVD burden, with higher levels observed in patients with three SVD features both at baseline (p=0.026) and follow-up (p=0.005). No significant association between neuroimaging markers by CT and von Willebrand factor levels was found. In multivariable logistic regression analysis adjusted for age, sex, CHA₂DS₂-VASc, HAS-BLED, and type of anticoagulant, D-dimer levels were significantly and positively associated with the presence of lacunar infarcts at baseline [OR (95% CI) = 3.3 (1.1–10.7), p = 0.046]. D-dimer levels were also significantly associated with cortical atrophy at 12-month follow-up [OR (95% CI) = 3.0 (1.1–8.9), p = 0.044]. Conclusions. These findings indicate that D-dimer, but not von Willebrand factor, is consistently associated with CT markers of cerebral small vessel disease in anticoagulated AF patients. Overall, coagulation activation may play a key role in the pathophysiology of lacunar damage and brain structural changes, supporting its potential use in risk stratification.

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BibTeX
@article{alfano2026co024,
  title = {{CO024 | THE ROLE OF BLOOD CLOTTING AND ENDOTHELIAL ACTIVATION IN THE STRATIFICATION OF BLEEDING AND THROMBOTIC RISK OF ATRIAL FIBRILLATION ON ORAL ANTICOAGULANT THERAPY: INSIGHTS FROM THE STRAT-AF 2 STUDY}},
  author = {Francesco Alfano},
  journal = {Bleeding, Thrombosis and Vascular Biology},
  year = {2026},
  month = oct,
  url = {https://www.btvb.org/btvb/article/view/726},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - CO024 | THE ROLE OF BLOOD CLOTTING AND ENDOTHELIAL ACTIVATION IN THE STRATIFICATION OF BLEEDING AND THROMBOTIC RISK OF ATRIAL FIBRILLATION ON ORAL ANTICOAGULANT THERAPY: INSIGHTS FROM THE STRAT-AF 2 STUDY
AU  - Francesco Alfano
PY  - 2026
DA  - 2026/10/26
JO  - Bleeding, Thrombosis and Vascular Biology
UR  - https://www.btvb.org/btvb/article/view/726
AB  - Background. Atrial fibrillation (AF) is associated with a prothrombotic milieu characterized by activation of coagulation and endothelial dysfunction, as indicated by increased D-dimer and von Willebrand factor levels. However, the relation between blood clotting activation, endothelial activation, and neuroimaging-based markers remains to be completely understood. Objectives. The aim of the present study was to evaluate the association between blood clotting activation, endothelial dysfunction, and the neuroimaging markers evaluated by CT scan in the STRATAF-2 population. Methods. The STRAT-AF 2 is a prospective observational extension of the STRAT-AF study, including a de novo cohort of anticoagulated patients with atrial fibrillation aged ≥ 65 years who underwent baseline and 1-year follow-up brain computed tomography (CT) (n=100). Neuroimaging assessment included the Van Swieten scale on CT for white matter lesions, identification of lacunes (≤15 mm), and cortical atrophy grading using the Pasquier scale. Medial temporal lobe atrophy (MTA) was evaluated on coronal CT images. Overall small vessel disease burden was estimated by the SVD score (0–3). TC cohort patients were followed for at least 1 year. Results. At baseline, a moderate-to-severe leukoencephalopathy was associated with higher D-dimer levels compared with absent or mild white matter changes (p=0.024), and this association persisted at 12 months (p=0.046). Similarly, the presence of lacunar infarcts was associated with higher D-dimer levels both at baseline (p=0.022) and at follow-up (p=0.049). Neither D-dimer nor von Willebrand factor levels were associated with non-lacunar infarcts. Higher D-dimer levels were also associated with cortical atrophy (p=0.029) and severe MTA (p=0.016) at baseline, with consistent associations at 12 months (p=0.016 and p=0.004, respectively). Moreover, D-dimer levels were positively associated with increasing SVD burden, with higher levels observed in patients with three SVD features both at baseline (p=0.026) and follow-up (p=0.005). No significant association between neuroimaging markers by CT and von Willebrand factor levels was found. In multivariable logistic regression analysis adjusted for age, sex, CHA₂DS₂-VASc, HAS-BLED, and type of anticoagulant, D-dimer levels were significantly and positively associated with the presence of lacunar infarcts at baseline [OR (95% CI) = 3.3 (1.1–10.7), p = 0.046]. D-dimer levels were also significantly associated with cortical atrophy at 12-month follow-up [OR (95% CI) = 3.0 (1.1–8.9), p = 0.044]. Conclusions. These findings indicate that D-dimer, but not von Willebrand factor, is consistently associated with CT markers of cerebral small vessel disease in anticoagulated AF patients. Overall, coagulation activation may play a key role in the pathophysiology of lacunar damage and brain structural changes, supporting its potential use in risk stratification.
SN  - 2785-5309
ER  -