VPB0504 - Elevated 8-isoprostane concentration is associated with thromboembolic events in patients with atrial fibrillation

Background: There is evidence that atrial fibrillation (AF) is associated with increased oxidative stress, however, its role in prediction of thromboembolic events is unknown.

Aims: To evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels may predict clinical outcomes in AF patients.

Methods: In this prospective study 243 AF patients (median age 69 years) were assessed. Serum levels of 8-isoprostane, a marker of oxidative stress, along with plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF) were measured at baseline. Stroke or documented transient ischemic attacks (TIA), major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, including 70.4% on direct oral anticoagulants. The study was approved by the Ethical Committee and conducted in accordance with the Declaration of Helsinki. Patients provided written informed consent.

Results: Increased 8-isoprostane levels were observed in women, in patients with arterial hypertension, and those with paroxysmal or persistent AF. Patients with 8-isoprostane levels ≥559 pg/mL (top quartile) compared with those with 8-isoprostane < 250 pg/mL (bottom quartile) had 20% higher fibrinogen, 8% lower VWF concentrations, along with 10% lower Ks with no difference in CHA2DS2-VASc score, CLT or ETP. Patients, who experienced thromboembolic events (n=20, 1.9% per year) had 49% higher 8-isoprostane concentrations compared to those free of such events (P < 0.01). Levels of 8-isoprostane >459 pg/mL based on the optimal cut-off value were associated with the thromboembolic events during follow-up (hazard ratio 2.87, 95% confidence interval 1.17-7.03, P=0.02). There were no associations between 8-isoprostane levels and major bleeding (2.0%/year) or all-cause mortality (1.9%/year).

Conclusion(s): Increased 8-isoprostane levels in AF patients are predictive of thromboembolic events despite anticoagulant therapy. We showed that enhanced oxidative stress in AF is associated with prothrombotic features which might explain its association with ischemic cerebrovascular events on anticoagulation.