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.

Journal

Journal ID (nlm-ta): J Am Heart Assoc

Journal ID (iso-abbrev): J Am Heart Assoc

Journal ID (hwp): ahaoa

Journal ID (publisher-id): jah3

Title: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Publisher: Blackwell Publishing Ltd

ISSN (Electronic): 2047-9980

Publication date Collection: March 2015

Publication date (Electronic): 11 March 2015

Volume: 4

Issue: 3

Affiliations

National Heart, Blood, and Lung Institute's Framingham Heart Study, Framingham, MA (B.M.K., S.R.P., A.S.B., Q.Y., S.S., R.S.V.)

Deutsches Herzzentrum München, Technische Universität München, Germany (B.M.K., C.H., H.S.)

DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany (B.M.K., C.H., H.S.)

Department of Biostatistics, Boston University School of Public Health, Boston, MA (S.R.P., A.S.B., Q.Y.)

Institute of Epidemiology, Christian‐Albrechts‐University, Kiel, Germany (W.L.)

Department of Neurology, Boston University School of Medicine, Boston, MA (A.S.B., S.S.)

Sections of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA (T.C.C.)

Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Germany (J.E.)

DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany (J.E.)

Sections of Preventive Medicine and Epidemiology and Cardiology, Boston University School of Medicine, Boston, MA (R.S.V.)

Author notes

Correspondence to: Ramachandran S. Vasan, MD, Framingham Heart Study, 73 Mt Wayte Ave, Suite 2, Framingham, MA 01702‐5803. E‐mail: vasan@ 123456bu.edu Bernhard M. Kaess, MD, Deutsches Herzzentrum München, Lazarettstr. 36, 80363 Munich, Germany. E‐mail: bernhard_kaess@ 123456gmx.de

An accompanying Appendix S1, which list the members of the CARDIoGRAM Consortium is available at http://jaha.ahajournals.org/content/4/3/e001544/suppl/DC1

Article

Publisher ID: jah3893

DOI: 10.1161/JAHA.114.001544

PMC ID: 4392437

PubMed ID: 25762803

Copyright statement: © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

License:

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Categories

Subject: Original Research

Subject: Epidemiology