Serum neurofilament light chain in functionally relevant coronary artery disease and adverse cardiovascular outcomes

Abstract

Background: Functionally relevant coronary artery disease (fCAD), causing symptoms of myocardial ischemia, can currently only be reliably detected with advanced cardiac imaging. Serum neurofilament light chain (sNfL) is a biomarker for neuro-axonal injury known to be elevated by cardiovascular (CV) risk factors and cerebrovascular small-vessel diseases. Due to their pathophysiological similarities with fCAD and the link to CV risk factors, we hypothesised that sNfL may have diagnostic and prognostic value for fCAD and adverse cardiovascular outcomes.

Methods: Of the large prospective Basel VIII study (NCT01838148), 4’016 consecutive patients undergoing cardiac work-up for suspected fCAD were included (median age 68 years, 32.5% women, 46.9% with history of CAD). The presence of fCAD was adjudicated using myocardial perfusion imaging single-photon emission tomography (MPI-SPECT) and coronary angiography. sNfL was measured using a high-sensitive single-molecule array assay. All-cause and cardiovascular death, myocardial infarction (MI), and stroke/transient ischaemic attack (TIA) during 5-year follow-up were the prognostic endpoints.

Results: The diagnostic accuracy of sNfL for fCAD as quantified by the area under the curve (AUC) was low (0.58, 95%CI 0.56–0.60). sNfL was strongly associated with age, renal dysfunction, and body mass index and was a strong and independent predictor of all-cause death, cardiovascular death, and stroke/TIA but not MI. Time-dependent AUC for cardiovascular-death at 1-year was 0.85, 95%CI 0.80–0.89, and 0.81, 95%CI 0.77–0.86 at 2-years.

Conclusion: While sNfL concentrations did not show a diagnostic role for fCAD, in contrast, sNfL was a strong and independent predictor of cardiovascular outcomes, including all-cause death, cardiovascular death and stroke/TIA.

Keywords:

• sNfL
• CAD
• cardiac marker
• risk-stratification
• clinical-utility

Acknowledgement

We thank the entire Basel VIII Team for their hard work on recruitment, data entry, data cleaning and follow-up. We thank all the cardiologists and nurses who were a great support for the study but also for the patients. We thank the researchers at the cardiovascular research institute of Basel as well as the University of Basel for their valuable contribution and support to the project.

Disclosure statement

J.K. received speaker fees, research support, travel support, and/or served on advisory boards by Swiss MS Society, Swiss National Research Foundation (320030_189140/1), University of Basel, Progressive MS Alliance, Bayer, Biogen, Bristol Myers Squibb, Celgene, Merck, Novartis, Octave Bioscience, Roche, Sanofi.

C.M. reports receiving research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the European Union, the University of Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, Brahms, Ortho Diagnostics, Quidel, Roche, Siemens, Singulex, Sphingotec, as well as speaker honoraria/consulting honoraria from Amgen, Astra Zeneca, Bayer Boehringer Ingelheim, BMS, Idorsia, Novartis, Roche, and Sanofi.

M.Z. is Advisory Board Member of Exploris AG, Zürich, Switzerland, outside of this work.

D.L. ist CEO of GeNeuro.

R.T. has received research support from the Swiss National Science Foundation (P300PB-167803/1) and speaker honoraria/consulting honoraria from Roche, Abbott, Brahms and Siemens, outside the submitted work.

T.Z. reports a research grant from the Freiwillige Akademische Gesellschaft Basel outside of this work.

C.P. reports grants from Roche Diagnostics and the University Hospital Basel dedicated to conduct of this study, as well as chaired an advisory board for Roche Diagnostics, during the conduct of the study.

J.W. reports a research grant from the Swiss Academy of Medical Sciences and the Bangerter Foundation (YTCR 23/17).

The remaining authors have nothing to disclose.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author [CM]. The data are not publicly available due to restrictions as they contain information that could compromise the privacy of patients.

Additional information

Funding

The BASEL VIII study was supported by research grants from the Swiss Heart Foundation, the KTI, the European Union, the University Hospital Basel, the University of Basel, Abbott, Roche, and Singulex.