Ospedale "Maggiore della Carità", University of Piemonte Orientale, Novara, Italy.
Campus Bio-Medico University of Rome, Italy.
Am J Cardiol. 2020 Mar 1;125(5):751-758. doi: 10.1016/j.amjcard.2019.11.030. Epub 2019 Dec 9.
Recent findings in atrial fibrillation (AF) patients receiving oral anticoagulation showed that diabetes without insulin therapy has a thromboembolic risk comparable to nondiabetic patients, whereas only diabetic patients on insulin have a heightened thromboembolic risk. We explored possible pathophysiological correlates of such finding on 90 AF patients on oral anticoagulation, divided according to diabetes status (n = 30 without diabetes; n = 29 with diabetes on oral antidiabetic drugs; n = 31 with insulin-requiring diabetes). We assessed von Willebrand Factor (VWF) concentration (VWF:Ag) and activity (VWF R:Co) as measures of endothelial dysfunction; and thrombin-activatable fibrinolysis inhibitor (TAFI) and prothrombin fragment 1 + 2 (F1+2) levels as markers of fibrinolytic activity and thrombin generation. Values of VWF:Ag, VWF:RCo, and TAFI were similar in the 3 groups. Patients with diabetes requiring insulin had significantly higher levels of F1+2 (median 23.1 pg/ml [interquartile range 17.6; 33.5]) than those without diabetes (16.3 pg/ml [11.5; 22.5], p = 0.036) and diabetic patients on oral antidiabetic drugs (20.6 pg/ml [13.3; 29], p = 0.046). Thus, in AF patients receiving oral anticoagulation, those with diabetes, regardless of the diabetes type (with or without insulin therapy), and those without diabetes have comparable indices of the explored parameters of endothelial dysfunction and fibrinolytic activity. Despite anticoagulant therapy, thrombin generation is selectively higher in diabetic patients' on insulin than in those without diabetes or with diabetes on oral antidiabetic drugs, with no differences between these latter 2 conditions. Thrombin generation might thus be a predominant contributor to the excess of thromboembolic risk in AF patients on insulin-requiring diabetes.
最近在接受口服抗凝治疗的心房颤动 (AF) 患者中的发现表明,无需胰岛素治疗的糖尿病患者的血栓栓塞风险与非糖尿病患者相当,而仅接受胰岛素治疗的糖尿病患者的血栓栓塞风险更高。我们在 90 名接受口服抗凝治疗的 AF 患者中探索了这种发现的可能病理生理学相关性,这些患者根据糖尿病状况进行了分组(n=30 名无糖尿病患者;n=29 名接受口服降糖药物治疗的糖尿病患者;n=31 名需要胰岛素治疗的糖尿病患者)。我们评估了血管性血友病因子 (VWF) 浓度(VWF:Ag)和活性(VWF R:Co)作为内皮功能障碍的指标;以及凝血酶激活的纤溶抑制物 (TAFI) 和凝血酶片段 1+2 (F1+2) 水平作为纤溶活性和凝血酶生成的标志物。3 组患者的 VWF:Ag、VWF:RCo 和 TAFI 值相似。需要胰岛素治疗的糖尿病患者的 F1+2 水平明显高于无糖尿病患者(中位数 23.1 pg/ml [四分位距 17.6;33.5])和接受口服降糖药物治疗的糖尿病患者(20.6 pg/ml [13.3;29]),差异均有统计学意义(p=0.036 和 p=0.046)。因此,在接受口服抗凝治疗的 AF 患者中,无论糖尿病类型(有无胰岛素治疗)以及无糖尿病患者,其内皮功能障碍和纤溶活性的探索参数的指数相当。尽管进行了抗凝治疗,但接受胰岛素治疗的糖尿病患者的凝血酶生成选择性更高,高于无糖尿病或接受口服降糖药物治疗的糖尿病患者,后两种情况之间无差异。因此,凝血酶生成可能是 AF 患者中需要胰岛素治疗的糖尿病患者血栓栓塞风险增加的主要原因。