Alfano Francesco, Cesari Francesca, Gori Anna Maria, Berteotti Martina, Salvadori Emilia, Giusti Betti, Bertelli Alessia, Kura Ada, Barbato Carmen, Formelli Benedetta, Pescini Francesca, Fainardi Enrico, Chiti Stefano, Marzi Chiara, Diciotti Stefano, Marcucci Rossella, Poggesi Anna
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Center for Atherothrombotic Diseases, Careggi University Hospital, 50134 Florence, Italy.
J Clin Med. 2023 Oct 30;12(21):6866. doi: 10.3390/jcm12216866.
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.
在接受抗凝治疗的心房颤动（AF）患者中，推荐用于权衡获益与出血风险比值分层的模型的有效性有限。我们推测，循环标志物和基于神经影像学的标志物可能会改善对抗凝治疗的AF患者出血和血栓形成风险的预测。Strat-AF研究是一项观察性、前瞻性、单中心研究，纳入了170例AF患者；通过全面方案对招募的患者进行评估，包括临床评估、脑磁共振成像和循环生物标志物评估。主要结局是评估与炎症和细胞外基质（ECM）重塑的循环生物标志物水平相关的脑微血管病变。在对年龄、性别、CHA2DS2-VASc、HAS-BLED和抗凝剂类型进行校正的多因素逻辑回归分析中，基质金属蛋白酶（MMP）-2水平与脑微出血（CMB）的存在呈显著正相关。还发现MMP-2、金属蛋白酶组织抑制剂（TIMP）-1、-2、-4水平与白质高信号之间存在显著关联。关于小血管疾病（SVD）评分，MMP-2和TIMP-1、-2水平与存在两种及三种或更多SVD体征相关，而TIMP-4水平与无SVD器械体征的患者相比，与存在三种SVD体征相关。至于血管周围间隙扩大（EPVS）的存在，发现白细胞介素（IL）-8和TIMP 1-2-3水平较高与之存在显著关联。这些结果表明，AF患者存在ECM降解受损的证据，这是接受口服抗凝治疗的AF患者发生血栓并发症的独立危险因素。将这些标志物纳入预后方案可能会提高其预测中风风险和血栓并发症的临床能力。
