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Kaess, B.M.* ; Preis, S.R.* ; Lieb, W.* ; Beiser, A.S.* ; Yang, Q.* ; Chen, T.C.* ; Hengstenberg, C.* ; Erdmann, J.* ; Schunkert, H.* ; Seshadri, S* ; Vasan, R.S.* ; CARDIoGRAM Consortium (Döring, A. ; Meisinger, C. ; Meitinger, T. ; Peters, A. ; Wichmann, H.-E.)

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

J. Am. Heart Assoc. 4:e001544 (2015)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cardiovascular Disease ; Growth Factors ; Mendelian Randomization ; Mortality ; Risk Factors; Coronary-artery-disease; Heart-disease; Mendelian Randomization; Framingham Heart; Loci; Metaanalyses; Association; Mortality; Obesity; Bdnf
e-ISSN 2047-9980
Quellenangaben Band: 4, Heft: 3, Seiten: , Artikelnummer: e001544 Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Begutachtungsstatus Peer reviewed