Lidani Karita Claudia Freitas, Trainor Patrick James, Bhatia Harpreet S, Nasir Khurram, Blaha Michael J, Tsai Michael Y, Gottesman Rebecca F, Post Wendy S, Thanassoulis George, Tsimikas Sotirios, Heckbert Susan R, DeFilippis Andrew Paul
Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, USA; School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Atherosclerosis. 2024 Mar;390:117451. doi: 10.1016/j.atherosclerosis.2024.117451. Epub 2024 Jan 10.
Although several biomarkers have been studied in thromboembolic stroke, measuring the balance between thrombus formation and thrombolysis and data on its role in predicting stroke and atrial fibrillation (AF)-related stroke is limited. We sought to assess atherothrombotic biomarkers grouped into composite factors that reflect thrombotic and thrombolytic potential, and the balance between these factors as it relates to incident stroke or transient ischemic attack (TIA) and stroke/TIA in AF.
A Thrombotic Factor, derived from fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a); and a Thrombolytic Factor, derived from plasminogen and oxidized phospholipids on plasminogen, were evaluated at baseline in 5,764 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We evaluated the association between these two factors representative of thrombotic and thrombolytic potential and incident stroke/TIA (n = 402), and AF-related stroke/TIA (n = 82) over a median of 13.9 and 3.7 years, respectively. Cox proportional hazard models adjusted for medication use, cardiovascular risk factors and CHADS-VASc score were utilized. Harrell's C-index was estimated to evaluate model performance.
In models including both factors, Thrombotic Factor was positively while Thrombolytic Factor was inversely associated with incident stroke/TIA and AF-related stroke/TIA. Incorporating these factors along with the CHADS-VASc in adjusted models resulted in a small improvement in risk prediction of incident stroke/TIA and AF-related stroke/TIA compared to models without the factors (C-index from 0.697 to 0.704, and from 0.657 to 0.675, respectively).
Composite biomarker factors, representative of the balance between thrombotic and thrombolytic propensity, provided an improvement in predicting stroke/TIA beyond CHADS-VASc score.
尽管已经对血栓栓塞性卒中的多种生物标志物进行了研究，但衡量血栓形成与溶栓之间的平衡以及其在预测卒中和心房颤动（AF）相关卒中方面作用的数据有限。我们试图评估分组为反映血栓形成和溶栓潜力的复合因子的动脉粥样硬化血栓形成生物标志物，以及这些因子之间的平衡与新发卒中或短暂性脑缺血发作（TIA）以及AF中的卒中/TIA的关系。
在5764名动脉粥样硬化多族裔研究（MESA）参与者的基线时，评估了源自纤维蛋白原、纤溶酶 - 抗纤溶酶复合物、因子VIII、D - 二聚体和脂蛋白（a）的血栓形成因子，以及源自纤溶酶原和纤溶酶原上氧化磷脂的溶栓因子。我们分别在中位数为13.9年和3.7年的时间里，评估了这两个代表血栓形成和溶栓潜力的因子与新发卒中/TIA（n = 402）以及AF相关卒中/TIA（n = 82）之间的关联。使用了针对药物使用、心血管危险因素和CHADS - VASc评分进行调整的Cox比例风险模型。估计Harrell's C指数以评估模型性能。
在包含这两个因子的模型中，血栓形成因子与新发卒中/TIA以及AF相关卒中/TIA呈正相关，而溶栓因子呈负相关。在调整模型中纳入这些因子以及CHADS - VASc，与不包含这些因子的模型相比，新发卒中/TIA和AF相关卒中/TIA的风险预测有小幅改善（C指数分别从0.697提高到0.704，从0.657提高到0.675）。
代表血栓形成和溶栓倾向之间平衡的复合生物标志物因子，在预测卒中/TIA方面比CHADS - VASc评分有改进。
