Cited by 200Acute Ischemic Stroke ManagementNeurological Disease Mechanisms and TreatmentsDementia and Cognitive Impairment Research

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Serum Brain–Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Levels Are Associated With Risk of Stroke and Vascular Brain Injury: Framingham Study

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Pikula, Aleksandra, Beiser, Alexa S., Chen, Tai C., Preis, Sarah R., Vorgias, Demetrios, DeCarli, Charles, Au, Rhoda, Kelly-Hayes, Margaret, Kase, Carlos S., Wolf, Philip A., Vasan, Ramachandran S., Seshadri, Sudha·2013·Stroke

DOI 10.1161/strokeaha.113.001447PMC PMC3873715

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Abstract

Background and Purpose—: 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.

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“The BDNF genotype may also play a role in the development of cerebral ischemia [5,9].”

Authors: Pikula, A., Beiser, A. S., Chen, T. C., Preis, S. R., Vorgias, D., DeCarli, C., Au, R., Kelly-Hayes, M., Kase, C. S., Wolf, P. A., Vasan, R. S., & Seshadri, S.
Affiliations: Boston University (US)
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.).
ORCID: Pikula, Aleksandra
Beiser, Alexa S.
Chen, Tai C.
Preis, Sarah R.
DeCarli, Charles
Au, Rhoda
Kase, Carlos S.
Wolf, Philip A.
Vasan, Ramachandran S.
Seshadri, Sudha
Venue: Stroke
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2013-10
Volume: 44
Issue: 10
Pages: 2768-2775
ISSN: 0039-2499 (ISSN-L)
1524-4628
DOI: 10.1161/strokeaha.113.001447
PMC: PMC3873715
OpenAlex: W2111149177
Cited by: 200
References: 47
Citations by year: 2026: 5 · 2025: 7 · 2024: 15 · 2023: 51 · 2022: 16 · 2021: 10 · 2020: 18 · 2019: 15 · 2018: 12 · 2017: 15 · 2016: 13 · 2015: 17 · 2014: 6
FWCI: 8.66
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Stroke (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: American Heart Association
National Institutes of Health (UL1TR000157, n01hc25195-41-0-1, n01hv28178-12-0-0)
National Institute on Aging (R01AG031287, AG031287, AG08122, AG033193, R01AG016495, R01AG033193, R01AG008122)
National Heart, Lung, and Blood Institute (N01‐HC25195, K24HL004334, N01-HC-025195, N01-HV-028178, R01HL093029, U01HL096917)
National Institute of Neurological Disorders and Stroke (R01NS017950)
National Center for Research Resources
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: brain-derived neurotrophic factor, vascular endothelial growth factor, stroke risk, transient ischemic attack, white matter hyperintensities, vascular brain injury, visuospatial memory, executive function, serum biomarkers, Framingham Heart Study, angiogenesis, neurogenesis, ischemic brain injury, cognitive function, vascular risk factors, sex differences, neuroinflammation
MeSH terms: Age Factors, Aged, Brain Ischemia, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Radiography, Risk Factors, Sex Factors, Incidence, Brain-Derived Neurotrophic Factor, Stroke, Vascular Endothelial Growth Factor A

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Serum Brain–Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Levels Are Associated With Risk of Stroke and Vascular Brain Injury: Framingham Study

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