Abstract 15062: Circulating Brain-Derived Neurotrophic Factor Concentrations and the Risk of Cardiovascular Disease in the Community
Context: Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide also involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD).
Objective: To investigate the association of circulating BDNF with CVD risk Design, Setting and Participants: First, we prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in the 3,687 participants (mean age 65 years, 2,068 women) from the Framingham Heart Study (FHS). Next, we evaluated the association of a common nonsynonymous SNP in the BDNF gene (rs6265) with circulating BDNF concentrations in FHS. Finally, we performed a Mendelian randomization experiment in the CARDIoGRAM consortium (>22,000 coronary artery disease [CAD] cases, >60,000 controls) to investigate whether the same SNP was associated with CAD risk in CARDioGRAM and if so, whether the direction and effect size differed from that predicted based on FHS data.
Results: On follow-up (median 8.9 years), 467 individuals (261 women) in the FHS sample experienced a CVD event, while 835 (430 women) died. In multivariable-adjusted Cox regression, serum BDNF was associated inversely with CVD risk (hazard ratio [HR] per SD increase 0.88, 95% CI 0.80-0.97, p=0.01) and with mortality risk (HR 0.87, 95% CI 0.80-0.93, 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 0.923-0.992), a magnitude consistent with the predicted effect size (HR per minor allele copy 0.99, 95% CI 0.98-1.0; 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.
- © 2013 by American Heart Association, Inc.