Plasma neurofilament light as a risk marker cardiovascular disease in healthy elderly

Abstract Background Plasma levels of the neuron-specific biomarker neurofilament light (NFL) have been linked to an increased risk of stroke and other cardiovascular events in patients with atrial fibrillation. However, the significance of NFL as a risk marker for adverse events in healthy elderly individuals remains unknown. Purpose To investigate whether plasma NFL is an independent risk marker for adverse events in healthy elderly individuals. Methods NFL was measured in venous blood samples collected at baseline from 806 community-dwelling 75-year-olds in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. NFL was analysed in plasma with an electrochemiluminescence assay. Associations between NFL and subsequent adverse events including ischaemic stroke, myocardial infarction, cardiovascular (CV) death and all-cause death were assessed by Cox-regression models assuming linear association adjusted for clinical risk factors and other biomarkers. Results The median NFL concentration was 21.3 (interquartile range 16.7-27.6) pg/mL. Higher NFL levels were most strongly associated with renal dysfunction and lower body mass index. Over a median follow-up of 10 years, there were in total 55 ischaemic strokes, 48 myocardial infarctions, 52 CV deaths and 188 all-cause deaths. NFL was independently associated with all-cause death (a doubling of NFL in the centre of the distribution, hazard ratio HR 1.91, 95% CI 1.49-2.46, p0.001) when adjusting for both clinical variables and NT-proBNP, however, not with CV death in presence of NT-proBNP. NFL was not associated with ischaemic stroke or myocardial infarction. Adding NFL to the fully adjusted model improved discrimination for all-cause death (c-index increased from 0.693 to 0.707, p0.001). Conclusions In healthy elderly individuals, higher NFL levels were independently associated with all-cause death, but not with ischaemic stroke or CV death.