Dataset Information

Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community.

ABSTRACT: BACKGROUND:Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD). METHODS AND RESULTS:We prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (FHS). Using a common nonsynonomous single nucleotide polymorphism (SNP) in the BDNF gene (rs6265), we then performed a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis) consortium (>22,000 coronary artery disease [CAD] cases, >60,000 controls) to investigate whether SNP rs6265 was associated with CAD in CARDIoGRAM and, if so, whether the effect estimate differed from that predicted based on FHS data. On follow-up (median 8.9 years), 467 individuals (261 women) in FHS experienced a CVD event, and 835 (430 women) died. In multivariable-adjusted Cox regression, serum BDNF was associated inversely with CVD risk (hazard ratio [HR] per 1-SD increase 0.88, 95% CI 0.80 to 0.97, P=0.01) and with mortality (HR 0.87, 95% CI 0.80 to 0.93, P=0.0002). SNP rs6265 was associated with BDNF concentrations (0.772 ng/mL increase per minor allele copy) in FHS. In CARDIoGRAM, SNP rs6265 was associated with CAD (odds ratio 0.957, 95% CI 0.923 to 0.992), a magnitude consistent with the predicted effect (HR per minor allele copy 0.99, 95% CI 0.98 to 1.0; P=0.06 for difference between predicted and observed effect). CONCLUSION:Higher serum BDNF is associated with a decreased risk of CVD and mortality. Mendelian randomization suggests a causal protective role of BDNF in the pathogenesis of CVD.

SUBMITTER: Kaess BM

PROVIDER: S-EPMC4392437 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community.

Kaess Bernhard M BM Preis Sarah R SR Lieb Wolfgang W Beiser Alexa S AS Yang Qiong Q Chen Tai C TC Hengstenberg Christian C Erdmann Jeanette J Schunkert Heribert H Seshadri Sudha S Vasan Ramachandran S RS Assimes Themistocles L TL Deloukas Panos P Holm Hilma H Kathiresan Sekar S König Inke R IR McPherson Ruth R Reilly Muredach P MP Roberts Robert R Samani Nilesh J NJ Stewart Alexandre F R AF

Journal of the American Heart Association 20150311 3

<h4>Background</h4>Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD).<h4>Methods and results</h4>We prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (FHS). Using a common nonsynonomous single ...[more]

PMID: 25762803

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Project description:Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and regeneration. We investigated the diagnostic and prognostic values of serum BDNF in traumatic brain injury (TBI). We examined serum BDNF in two independent cohorts of TBI cases presenting to the emergency departments (EDs) of the Johns Hopkins Hospital (JHH; n?=?76) and San Francisco General Hospital (SFGH, n?=?80), and a control group of JHH ED patients without TBI (n?=?150). Findings were subsequently validated in the prospective, multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study (n?=?159). We investigated the association between BDNF, glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) and recovery from TBI at 6 months in the TRACK-TBI Pilot cohort. Incomplete recovery was defined as having either post-concussive syndrome or a Glasgow Outcome Scale Extended score <8 at 6 months. Median day-of-injury BDNF concentrations (ng/mL) were lower among TBI cases (JHH TBI, 17.5 and SFGH TBI, 13.8) than in JHH controls (60.3; p?=?0.0001). Among TRACK-TBI Pilot subjects, median BDNF concentrations (ng/mL) were higher in mild (8.3) than in moderate (4.3) or severe TBI (4.0; p?=?0.004. In the TRACK-TBI cohort, the 75 (71.4%) subjects with very low BDNF values (i.e., <the 1st percentile for non-TBI controls, <14.2?ng/mL) had higher odds of incomplete recovery than those who did not have very low values (odds ratio, 4.0; 95% confidence interval [CI]: 1.5-11.0). The area under the receiver operator curve for discriminating complete and incomplete recovery was 0.65 (95% CI: 0.52-0.78) for BDNF, 0.61 (95% CI: 0.49-0.73) for GFAP, and 0.55 (95% CI: 0.43-0.66) for UCH-L1. The addition of GFAP/UCH-L1 to BDNF did not improve outcome prediction significantly. Day-of-injury serum BDNF is associated with TBI diagnosis and also provides 6-month prognostic information regarding recovery from TBI. Thus, day-of-injury BDNF values may aid in TBI risk stratification.

Dataset Information

Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community.

Publications

Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community.

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