Neurofilament light chain (NFL) - a neuron-specific plasma biomarker for evaluating risk of ischemic cerebral events in atrial fibrillation
Bibliographic record
Abstract
Abstract Background A history of ischemic stroke is one of the strongest risk factors for future stroke in patients with atrial fibrillation (AF). Circulating biomarkers specific for the brain may be used to detect overt and covert cerebral ischemia. Neurofilament light chain (NFL) is a neuron-specific cytoskeleton protein that is released into blood at increased levels when the brain is injured and may be a complement to already established risk factors of AF. Purpose We hypothesized that NFL measured in plasma (pNFL) is an independent and incremental risk indicator of ischemic stroke in patients with AF. Methods pNFL was measured in venous blood samples from 1,056 patients with AF randomised to aspirin in the ACTIVE A trial. Samples were collected at randomisation and the median follow-up duration was 3.6 years. pNFL was analysed with a single molecule array. Associations between pNFL and subsequent clinical outcomes were evaluated by Cox-regression models adjusted for fifteen clinical characteristics and NT-proBNP levels. Results The median concentration of pNFL was 17.3 (interquartile range 10.9-28.3) ng/L. The variables most strongly associated with higher pNFL levels were advanced age, renal dysfunction, lower body mass index, prior stroke/transient ischemic attack and female sex. In multivariable analyses, pNFL was a stronger risk indicator for ischemic stroke than any clinical factor, including previous stroke (Figure 2), and of similar prognostic importance as NT-proBNP. pNFL was independently associated with ischemic stroke (per doubling of pNFL, hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.01-1.50, p=0.038), all-cause death (HR 1.30, 95% CI 1.12-1.51, p<0.001) and heart failure (HR 1.30, 95% CI 1.09-1.54, p=0.003) when adjusting for both clinical characteristics and other biomarkers including NT-proBNP. pNFL improved the discriminatory value (c-index) for ischemic stroke from 0.676 to 0.686 (p=0.038) when added to a fully adjusted model including NT-proBNP. Conclusions In patients with AF, pNFL was associated with an increased risk of ischemic stroke, independent of clinical characteristics and NT-proBNP. pNFL was a stronger risk factor for ischemic stroke than previous stroke and of similar prognostic importance as NT-proBNP. pNFL may be a novel plasma biomarker improving the evaluation of the risk of ischemic cerebral events in patients with AF.Stroke risk by pNFL quartile groupVariable importance for ischemic stroke
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".