Plasma neurofilament light chain and risk of death and stroke in community-dwelling elderly individuals.
- 1Department of Medical Sciences, Cardiology, Uppsala University, 751 85 Uppsala, Sweden.
- 2Uppsala Clinical Research Center, Uppsala University, Dag Hammarskjölds väg 38, 751 85 Uppsala, Sweden.
- 3Department of Medical Sciences, Neurology, Uppsala University, 751 85 Uppsala, Sweden.
Abstract
Aims
Circulating neuroinjury biomarkers such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have emerged as indicators of brain health. While NFL predicts stroke in patients with atrial fibrillation, its prognostic value in unselected elderly populations is uncertain. We investigated the associations of NFL and GFAP with cardiovascular events and death in community-dwelling older adults.Methods and results
Baseline plasma NFL and GFAP concentrations were determined using high-sensitivity Simoa® assays in 806 participants aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Cox regression models with sequential adjustment for demographics, comorbidities, renal function, and NT-proBNP assessed associations with ischaemic stroke, myocardial infarction, cardiovascular death, all-cause death, and major adverse cardiovascular events (MACE; stroke, myocardial infarction, and all-cause death). During a median follow-up of 10 years, 55 ischaemic strokes, 48 myocardial infarctions, 52 cardiovascular deaths, and 188 all-cause deaths occurred. Neurofilament light chain was not independently associated with ischaemic stroke or myocardial infarction and showed no independent association with cardiovascular death after adjustment including NT-proBNP. In contrast, higher NFL was independently associated with all-cause death (adjusted hazard ratio per doubling 1.91; 95% CI 1.49-2.46) and MACE (1.53; 95% CI 1.21-1.93), and improved discrimination for all-cause death beyond established risk factors. Glial fibrillary acidic protein was not associated with any outcome.Conclusion
In community-dwelling elderly individuals, higher NFL was associated with increased risk of death but not with specific cardiovascular events. These findings suggest that NFL reflects overall physiological vulnerability rather than discrete vascular risk.
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BibTeX
@article{aulin2026plasma,
title = {{Plasma neurofilament light chain and risk of death and stroke in community-dwelling elderly individuals.}},
author = {Julia Aulin and Karl Sjölin and Erika Frank and Johan Lindbäck and Lars Lind and Joachim Burman},
journal = {European heart journal open},
year = {2026},
month = sep,
doi = {10.1093/ehjopen/oeag143},
url = {https://europepmc.org/article/MED/42923677},
note = {CC BY},
}
RIS
TY - JOUR
TI - Plasma neurofilament light chain and risk of death and stroke in community-dwelling elderly individuals.
AU - Julia Aulin
AU - Karl Sjölin
AU - Erika Frank
AU - Johan Lindbäck
AU - Lars Lind
AU - Joachim Burman
PY - 2026
DA - 2026/09/16
JO - European heart journal open
DO - 10.1093/ehjopen/oeag143
UR - https://europepmc.org/article/MED/42923677
AB - Aims Circulating neuroinjury biomarkers such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have emerged as indicators of brain health. While NFL predicts stroke in patients with atrial fibrillation, its prognostic value in unselected elderly populations is uncertain. We investigated the associations of NFL and GFAP with cardiovascular events and death in community-dwelling older adults.Methods and results Baseline plasma NFL and GFAP concentrations were determined using high-sensitivity Simoa® assays in 806 participants aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Cox regression models with sequential adjustment for demographics, comorbidities, renal function, and NT-proBNP assessed associations with ischaemic stroke, myocardial infarction, cardiovascular death, all-cause death, and major adverse cardiovascular events (MACE; stroke, myocardial infarction, and all-cause death). During a median follow-up of 10 years, 55 ischaemic strokes, 48 myocardial infarctions, 52 cardiovascular deaths, and 188 all-cause deaths occurred. Neurofilament light chain was not independently associated with ischaemic stroke or myocardial infarction and showed no independent association with cardiovascular death after adjustment including NT-proBNP. In contrast, higher NFL was independently associated with all-cause death (adjusted hazard ratio per doubling 1.91; 95% CI 1.49-2.46) and MACE (1.53; 95% CI 1.21-1.93), and improved discrimination for all-cause death beyond established risk factors. Glial fibrillary acidic protein was not associated with any outcome.Conclusion In community-dwelling elderly individuals, higher NFL was associated with increased risk of death but not with specific cardiovascular events. These findings suggest that NFL reflects overall physiological vulnerability rather than discrete vascular risk.
SN - 2752-4191
ER -