Serum Neurofilament Light Chain and Cardiovascular Outcomes in Patients With Atrial Fibrillation

Importance Serum neurofilament light chain (sNfL) is a blood-based biomarker initially investigated for neuronal injury and is elevated in patients with atrial fibrillation (AF). Whether sNfL is associated with other adverse outcomes in this population is less well studied. Objective To determine the association between sNfL and cardiovascular outcomes in patients with AF. Design, Setting, and Participants The Swiss Atrial Fibrillation Cohort (SWISS-AF) is a prospective, multicenter, observational cohort study. The present analysis included patients enrolled from April 2014 through August 2017, with follow-up until April 23, 2025. Data analysis was conducted in June 2025. SWISS-AF enrolled inpatients and outpatients across 14 secondary or tertiary care centers in Switzerland. This analysis included 2311 of 2415 (95.7%) patients with documented AF in SWISS-AF after the exclusion of 76 patients without sNfL measurements and 28 patients with missing follow-up data. Exposures Concentrations of sNfL were measured from baseline serum samples using an ultrasensitive single-molecule array assay. Main Outcomes and Measures The primary outcome was major vascular events (MVEs), defined as a composite of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction. Other outcomes included the individual components of MVEs, heart failure–related hospitalization, and all-cause mortality. Results Of 2311 included patients, mean (SD) age was 73.2 (8.5) years, and 1683 (73%) were male. Over a median (IQR) follow-up of 8.0 (5.2-9.0) years, there were 665 first MVE events, corresponding to an incidence per 100 patient-years of 4.4 (95% CI, 4.1-4.8). Every doubling of sNfL concentration was associated with an adjusted hazard ratio (aHR) for MVEs of 1.35 (95% CI, 1.22-1.50; P < .001). Increasing sNfL levels were associated with nonfatal stroke (aHR, 1.31; 95% CI, 1.09-1.57; P = .004), cardiovascular death (aHR, 1.36; 95% CI, 1.20-1.54; P < .001), heart failure–related hospitalization (aHR, 1.25; 95% CI, 1.11-1.41; P < .001), and all-cause mortality (aHR, 1.41; 95% CI, 1.27-1.56; P < .001) but not myocardial infarction (aHR, 1.04; 95% CI, 0.81 to 1.34; P = .76). Conclusions and Relevance After multivariable adjustment, sNfL levels were associated with a broad range of adverse cardiovascular events and mortality in patients with AF. Serum NfL may serve as a biomarker of cardiovascular risk in patients with AF.