Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury: Framingham Study.
OBJECTIVE
Brain-derived neurotrophic factor (BDNF), a major neurotrophin and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. In animal experiments, they impact infarct size and functional motor recovery after an ischemic brain lesion. We sought to examine the association of serum BDNF and VEGF with the risk of clinical stroke or subclinical vascular brain injury in a community-based sample.


METHODS
In 3440 Framingham Study participants (mean age, 65±11 years; 56% women) who were free of stroke/transient ischemic attack (TIA), we related baseline BDNF and logVEGF to risk of incident stroke/TIA. In a subsample with brain MRI and with neuropsychological tests available (n=1863 and 2104, respectively; mean age, 61±9 years, 55% women, in each), we related baseline BDNF and logVEGF to log-white matter hyperintensity volume on brain MRI, and to visuospatial memory and executive function tests.


RESULTS
During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA. In multivariable analyses adjusted for age, sex, and traditional stroke risk factors, lower BDNF and higher logVEGF levels were associated with an increased risk of incident stroke/TIA (hazard ratio comparing BDNF Q1 versus Q2-Q4, 1.47; 95% confidence interval, 1.09-2.00; P=0.012 and hazard ratio/SD increase in logVEGF, 1.21; 95% confidence interval, 1.04-1.40; P=0.012). Persons with higher BDNF levels had less log-white matter hyperintensity volume (β±SE=-0.05±0.02; P=0.025), and better visual memory (β±SE=0.18±0.07; P=0.005).


CONCLUSIONS
Lower serum BDNF and higher VEGF concentrations were associated with increased risk of incident stroke/TIA. Higher levels of BDNF were also associated with less white matter hyperintensity and better visual memory. Our findings suggest that circulating BDNF and VEGF levels modify risk of clinical and subclinical vascular brain injury.
From the Boston University Schools of Medicine and Public Health, Boston, MA (A.P., A.S.B., T.C.C., S.R.P., D.V., R.A., M.K.-H., C.S.K., P.A.W., R.S.V., S.S.); Framingham Heart Study, Framingham, MA (A.P., A.S.B., S.R.P., C.D., R.A., M.K.-H., C.S.K., P.A.W., R.S.V., S.S.); and University of California at Davis, Sacramento (C.D.).
Aleksandra
A
Pikula
Alexa S
AS
Beiser
Tai C
TC
Chen
Sarah R
SR
Preis
Demetrios
D
Vorgias
Charles
C
DeCarli
Rhoda
R
Au
Margaret
M
Kelly-Hayes
Carlos S
CS
Kase
Philip A
PA
Wolf
Ramachandran S
RS
Vasan
Sudha
S
Seshadri
D000367:Age Factors; D000368:Aged; D002545:Brain Ischemia / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D019208:Brain-Derived Neurotrophic Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C579455:BDNF protein, human
brain MRI; brain-derived neurotrophic factor; risk; stroke; subclinical; vascular endothelial growth factor A