TY - JOUR
T1 - Serum NfL (Neurofilament Light Chain) Levels and Incident Stroke in Adults with Diabetes Mellitus
AU - Korley, Frederick K.
AU - Goldstick, Jason
AU - Mastali, Mitra
AU - Van Eyk, Jennifer E.
AU - Barsan, William
AU - Meurer, William J.
AU - Sussman, Jeremy
AU - Falk, Hayley
AU - Levine, Deborah
N1 - Funding Information:
Drs Korley, Goldstick, Mastali, Levine, and Van Eyk are supported by 5R21HL140274 from the National Heart, Lung, and Blood Institute. Dr Van Eyk is supported by the Erika J. Glazer chair in Women’s Heart Health and the Advanced Clinical Biosystems Institute at Cedars-Sinai Medical Center. Dr Sussman is supported by the Veterans Affairs Career Development Award 13–021 and the Veterans Affairs Investigator-Initiated Research Award 15–432. Dr Levine reports research grants R01 NS102715 (National Institute of Neurological Disorders and Stroke) and R01 AG051827 (National Institute on Aging) and consulting for National Institutes of Health grants (modest) and University of California San Francisco on the platelet-oriented inhibition in POINT trial (New TIA and Minor Ischemic Stroke; modest).
Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - adult
KW - diabetes mellitus
KW - primary prevention
KW - risk factors
KW - stroke
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U2 - 10.1161/STROKEAHA.119.024941
DO - 10.1161/STROKEAHA.119.024941
M3 - Article
C2 - 31138085
AN - SCOPUS:85068810889
SN - 0039-2499
VL - 50
SP - 1669
EP - 1675
JO - Stroke
JF - Stroke
IS - 7
ER -