Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation

Area of Science:

• Biomarkers and Diagnostics
• Neurology
• Cardiology

Background:

• Brain injury biomarkers are underutilized in stroke risk assessment for atrial fibrillation (AF) patients.
• Neurofilament light chain (NFL) is a novel blood biomarker indicating cerebral insults.
• This study investigates NFL's association with stroke and death risk in AF patients not on oral anticoagulation.

Purpose of the Study:

• To determine the association between plasma NFL concentrations and the risk of stroke and death in AF patients.
• To evaluate NFL's utility as a risk assessment tool in AF patients, including those without prior stroke.

Main Methods:

• Observational study of 3077 AF patients from the ACTIVE A and AVERROES trials.
• Plasma NFL levels measured using Single Molecule Array (Simoa).
• Cox regression models used to analyze associations with stroke, systemic embolism, and death outcomes.

Main Results:

• Higher NFL levels were independently associated with increased risk of stroke or systemic embolism (HR 1.27 per doubling), cardiovascular death, and all-cause death.
• NFL improved stroke risk prediction, with a C-index of 0.642, comparable to existing clinical scores.
• Combining NFL with clinical factors and other biomarkers (NT-proBNP, troponin T) further enhanced stroke risk discrimination (C-index 0.727).

Conclusions:

• Plasma NFL levels reflect cerebral ischemia and significantly improve stroke and death risk assessment in AF patients.
• NFL is a valuable biomarker for risk stratification, particularly in AF patients without a history of stroke.
• Future stroke risk assessments in AF patients should consider incorporating NFL alongside clinical data and other biomarkers.