Circulating Tissue Factor Levels and Risk of Stroke

Abstract

Background and Purpose-Tissue factor (TF) expression is increased in inflammatory atherosclerotic plaques and has been related to their thrombogenicity. Blood-borne TF has been also demonstrated to contribute to thrombogenesis. However, few studies have evaluated the association of circulating levels of TF with stroke. We investigated the association of baseline circulating levels of TF with stroke events occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Methods-Using a nested case-cohort design, a center-stratified random sample of 839 subjects (66% women; age range, 35-71 years) was selected as subcohort and compared with 292 strokes in a mean follow-up of 9 years. Blood samples were collected at baseline in citrate, plasma was stored in liquid nitrogen and TF was measured by ELISA (IMUBIND, TF ELISA, Instrumentation Laboratory, Milan, Italy). The odd ratios and 95% confidence intervals, adjusted by relevant confounders (covariates of TF) and stratified by center, were estimated by a Cox regression model using Prentice method. Results-Individuals in the highest compared with the lowest quartile of TF plasma levels had significantly increased risk of stroke (odds ratio IVvsI quartile , 2.01; 95% confidence interval, 1.25-3.23). The association was independent from several potential confounders (odds ratio IVvsI quartile , 1.91; 95% confidence interval, 1.15-3.19). No differences were observed between men and women. The increase in risk was restricted to ischemic strokes (odds ratio IVvsI quartile , 2.13; 95% confidence interval, 1.10-4.12; fully adjusted model), whereas high levels of TF were not associated with the risk of hemorrhagic stroke (odds ratio IVvsI quartile , 1.12; 95% confidence interval, 0.49-2.55; fully adjusted model). Conclusions-Our data provide evidence that elevated levels of circulating TF are potential risk factors for ischemic strokes.

COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception—A Systematic Review

“…Increased expression of TF has previously also been shown to be associated with thrombus formation in patients with ischemic stroke (109,110). The EPICOR study in 2015 revealed that patients with elevated TF doubled the risk of stroke (109). Experimental studies also demonstrated that the inhibition of TNF-α-induced TF significantly reduces atheromatous plaque formation (30).…”

Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2

“…19 This type of feed-forward prothrombotic signaling cascade helps to coat infected cells with fibrin, potentially shielding them from immune cell targeting. Importantly, individuals with higher levels of circulating tissue factor harbor a 2-fold increased risk of stroke 20 that may place them in a baseline prothrombotic state and therefore more susceptible to virally-mediated activation of coagulation. Whether similar direct molecular interactions between viral proteins and proteins in the coagulation cascade occurs in Sars-CoV-2 infection is largely unknown but given the high rate of prothrombotic complications including stroke seen in severe COVID-19 infections, this molecular hijacking deserves further study.…”

Can tissue factor, a multifactorial molecule of the hemostasis, be used as a biomarker for thrombosis, inflammation and cancer?

“…Atherosclerotic cardiovascular and cerebrovascular diseases are still major causes of morbidity and mortality worldwide. [13][14][15][16][17] Tissue factor, which is present as Factor III in the clotting pathway and also known as "CD 142" and "thromboplastin", is a transmembrane protein which enables thrombin formation and is multifunctional. Parallel to today's technology, there are many studies aiming to better know the structure of tissue factor, while reporting that this protein is not only effective in the clotting system, but also in inflammation and cancer formation.…”