Fibroblast Growth Factors are Associated with Parenchymal Hemorrhagic Infarction Following ELVO

Abstract

ObjectiveThe goal of this study was to analyze possible associations between fibroblast growth factors (FGFs) and hemorrhagic conversion (HC) in patients with acute ischemic stroke that underwent mechanical thrombectomy (MT).BackgroundEmergent Large Vessel Occlusion (ELVO), often treated with MT, can lead to further complications such as HC. Little is known about predicting the risk and extent of HC. FGF‐21 and 23 are angiogenic proteins of the endocrine subfamily and are independent factors for overall risk of stroke and intracranial hemorrhage (PMID: 33967812). Comorbidities such as diabetes, obesity, hypertension, and hypercholesterolemia are also known to increase risk of HC and affect FGF levels.MethodsThe Center for Advanced Translational Stroke Science at the University of Kentucky utilizes the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (www.clinicaltrials.gov NCT03153683) for collection of systemic (i.e. proximal to thrombus) arterial blood during a MT procedure. Blood samples collected from 61 patients were sent to Olink Proteomics for proteomic analysis. The European Cooperative Acute Stroke Study (ECASS II) grading system was used to differentiate between the types of HT: Hemorrhagic Infarction (HI 1 and 2) and Parenchymal Hemorrhagic Infarction (PH 1 and 2). Logistic regressions were used to determine the association of FGF with the subtypes of hemorrhagic conversion. Data analyses were performed using IBM SPSS Statistics.ResultsFGF‐21 and FGF‐23 were significantly higher in patients with HI versus PH‐type HC (p=0.043 and p=0.004 respectively). Logistic regression yielded a significant model for only FGF‐21 (χ2= 5.196, p=0.023). Increasing levels of FGF‐21 were associated with a decreased likelihood of having PH‐type HC. Most patients receiving TPA had decreased levels of FGF‐21 (p=0.04). Various comorbidities were tested but were not found to be significant.DiscussionThe data provides an indication that lower levels of FGF‐21 increase the odds for a worse type of hemorrhagic transformation. Lower levels of FGF‐21 are reported in patients with hypercholesterolemia and hypertension. Our study found TPA correlated with lower levels of FGF‐21. Taken together, patients with comorbidities that decrease FGF‐21 levels, such as hypertension and hypercholesterolemia, and those who receive TPA should be monitored more carefully following thrombectomy. FGF‐21 should be evaluated further as a potential biomarker for hemorrhagic transformation to administer adjunctive therapies to MT.