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

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. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.