Higher serum neurofilament light chain levels were associated with an increased risk of major vascular events and mortality among patients with atrial fibrillation, according to a long-term cohort study published in JAMA Cardiology and presented at the American College of Cardiology 75th Annual Scientific Session.
In the Swiss Atrial Fibrillation Cohort, a prospective, multicenter observational study of 2,311 patients with atrial fibrillation (AF), each doubling of serum neurofilament light chain (NfL) levels was associated with a 35% higher risk of major vascular events, defined as cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Over a median follow-up of 8 years, 665 patients experienced a major vascular event, with incidence rising from 14% in the lowest quartile of NfL levels to 55% in the highest quartile.
Higher NfL levels were also associated with increased risk of several individual outcomes. Each doubling was linked to a 31% higher risk of nonfatal stroke, a 36% higher risk of cardiovascular death, a 25% higher risk of heart failure–related hospitalization, and a 41% higher risk of all-cause mortality. There was no statistically significant association with myocardial infarction.
Absolute event rates increased across quartiles. Heart failure–related hospitalization rose from approximately 1.5 to 9 events per 100 patient-years, and all-cause mortality increased from about 1.7 to 11 events per 100 patient-years.
In subgroup analyses, the association between NfL levels and major vascular events was stronger among patients not receiving anticoagulation at baseline compared with those receiving treatment. A stronger association was also observed among patients without prior stroke or transient ischemic attack. The association did not differ by AF type.
The study enrolled patients between 2014 and 2017 at 14 centers in Switzerland and included both inpatients and outpatients with documented AF. Serum NfL concentrations were measured at baseline using an ultrasensitive single-molecule array assay, and outcomes were assessed through April 2025. Multivariable models adjusted for demographic and clinical factors, including comorbidities and cardiovascular risk factors.
In sensitivity analyses, additional adjustment for N-terminal pro–B-type natriuretic peptide, C-reactive protein, and troponin T did not materially change the findings. Adding NfL levels to the ABC-AF risk score modestly improved prediction of major vascular events.
The study was observational, precluding causal inference, and was conducted exclusively in Switzerland, which may limit generalizability.
“Serum NfL may serve as a useful noncardiac biomarker to identify patients with AF at higher risk of adverse cardiovascular outcomes,” wrote Geethan Baskaran, BHSc, of the Population Health Research Institute in Hamilton, Ontario, Canada, and colleagues.
Krisai reported personal fees from Biosense Webster, Bristol Myers Squibb, and Pfizer. Kühne reported grants from the Swiss National Science Foundation, Swiss Heart Foundation, and multiple industry sources, as well as royalties from Springer Nature. Bonati, Beer, and Osswald reported grants during the conduct of the study. Moschovitis reported consulting fees, honoraria, and personal fees from multiple companies. Conen reported personal fees from Abbott. No other disclosures were reported.
Source: JAMA Cardiology
