Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury framingham study

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2768-2775
Number of pages8
JournalStroke
Volume44
Issue number10
DOIs
StatePublished - Oct 2013

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Cerebrovascular Trauma
Brain-Derived Neurotrophic Factor
Vascular Endothelial Growth Factor A
Stroke
Transient Ischemic Attack
Serum
Brain
Confidence Intervals
Neuropsychological Tests
Executive Function
Neurogenesis
Nerve Growth Factors

Keywords

  • Brain mri
  • Brain-derived neurotrophic factor
  • Risk
  • Stroke
  • Subclinical
  • Vascular endothelial growth factor a

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury framingham study. / 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.

In: Stroke, Vol. 44, No. 10, 10.2013, p. 2768-2775.

Research output: Contribution to journalArticle

Pikula, A, Beiser, AS, Chen, TC, Preis, SR, Vorgias, D, DeCarli, C, Au, R, Kelly-Hayes, M, Kase, CS, Wolf, PA, Vasan, RS & Seshadri, S 2013, 'Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury framingham study', Stroke, vol. 44, no. 10, pp. 2768-2775. https://doi.org/10.1161/STROKEAHA.113.001447
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. / Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury framingham study. In: Stroke. 2013 ; Vol. 44, No. 10. pp. 2768-2775.
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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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T1 - Serum brain-derived neurotrophic factor and vascular endothelial growth factor levels are associated with risk of stroke and vascular brain injury framingham study

AU - Pikula, Aleksandra

AU - Beiser, Alexa S.

AU - Chen, Tai C.

AU - Preis, Sarah R.

AU - Vorgias, Demetrios

AU - DeCarli, Charles

AU - Au, Rhoda

AU - Kelly-Hayes, Margaret

AU - Kase, Carlos S.

AU - Wolf, Philip A.

AU - Vasan, Ramachandran S.

AU - Seshadri, Sudha

PY - 2013/10

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N2 - 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.

AB - 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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KW - Brain-derived neurotrophic factor

KW - Risk

KW - Stroke

KW - Subclinical

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