Serum NfL (Neurofilament Light Chain) Levels and Incident Stroke in Adults With Diabetes Mellitus

Abstract

Background and Purpose— Effective stroke prevention depends on accurate stroke risk prediction. We determined the discriminative ability of NfL (neurofilament light chain) levels for distinguishing between adults with diabetes mellitus who develop incident stroke and those who remain stroke free during a 7-year follow-up period. Methods— We performed a case-control study of participants selected from the previously completed ACCORD trial (Action to Control Cardiovascular Risk in Diabetes). Cases were all ACCORD subjects who were stroke free at enrollment and developed incident stroke during follow-up (n=113). Control subjects (n=250) were randomly selected ACCORD subjects who had no stroke events either before or after randomization. NfL was measured in baseline samples using Single Molecule Array technology (Quanterix). Results— Baseline NfL levels were higher in stroke subjects, compared to controls, after adjusting for age, race, blood pressure, weight, and the Framingham Stroke Risk Score. Relative to the subjects in the lowest quintile of NfL levels, the hazard ratios of incident stroke for subjects in the second to fifth quintiles were 3.91 (1.45–10.53), 4.05 (1.52–10.79), 5.63 (2.16–14.66), and 9.75 (3.84–27.71), respectively, after adjusting for race and Framingham Stroke Risk Score. Incorporating NfL levels into a predictive score that already included race and Framingham Stroke Risk Score increased the score’s C statistic from 0.71 (95% CI, 0.66–0.77) to 0.78 (95% CI, 0.73–0.83), P <0.001. Older age, nonwhite race, higher systolic blood pressure, glomerular filtration rate <60, and higher hemoglobin A1C were independent predictors of serum NfL in this cohort but diastolic blood pressure, durations of hypertension or diabetes mellitus, and lipid levels were not. In total, cardiovascular disease risk factors explained 19.2% of the variability in baseline NfL levels. Conclusions— Serum NfL levels predict incident stroke and add considerably to the discriminatory power of the Framingham Stroke Risk Score in a cohort of middle-aged and older adults with diabetes mellitus.

Renal function is associated with blood neurofilament light chain level in older adults

“…Two reports assessed relationships between blood NfL level and renal function. Consistent with the present data, Korley et al have reported poor renal function as associated with a higher serum NfL level in a single cohort of patients with type 2 diabetes (mean age = 62.8 years) 16 . Concurrently, Hermansson et al reported that plasma NfL level is not correlated with serum creatinine levels among patients with HIV infection (median age = 41 years) 17 .…”

“…A recent study has reported an association between plasma NfL level and body mass index (BMI) or blood volume 15 . However, the evidence is inconsistent on whether there is an association between blood NfL level and renal function 16,17 . Blood NfL and renal function both change with age, but to our knowledge, no study had investigated the association between plasma NfL level and renal function adjusted for age.…”

Serum neurofilament measurement improves clinical risk scores for outcome prediction after cardiac arrest: results of a prospective study

“…In the case of OHCA, NfL could be a synergistic prognostic indicator for poor outcome due to first an increase in its level in the initial period of cardiac-arrest induced anoxic brain injury, and later due to an increase caused by neurologically stunned myocardium which again causes brain injury [ 36 ]. In addition, lifestyle and cardiovascular health have been shown to influence NFL baseline levels and could thus help to identify a high-risk group of patients regarding cardiovascular outcome [ 37 ]. Further, in many of these conditions NfL levels are now established on the group level as predictors for later functional neurological and neuropsychological outcome.…”

Blood neurofilament light: a critical review of its application to neurologic disease

“…In addition, blood NfL may be helpful in those who have not had a stroke, but who are at risk for stroke, such as subjects with diabetes. 55 Blood NfL levels are increased by subclinical ischemic events 21 and the risk of these subclinical events is associated with cardiovascular risk factors. 116 Of note, the use of NfL in stroke should take into account the time between event and blood NfL measurement and the long half-life of the biomarker.…”