PMID- 25762803 OWN - NLM STAT- MEDLINE DCOM- 20160301 LR - 20220316 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 4 IP - 3 DP - 2015 Mar 11 TI - Circulating brain-derived neurotrophic factor concentrations and the risk of cardiovascular disease in the community. PG - e001544 LID - 10.1161/JAHA.114.001544 [doi] LID - e001544 AB - 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. CI - (c) 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. FAU - Kaess, Bernhard M AU - Kaess BM AD - 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 Munchen, Technische Universitat Munchen, Germany (B.M.K., C.H., H.S.) DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munchen, Germany (B.M.K., C.H., H.S.). FAU - Preis, Sarah R AU - Preis SR AD - 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.) Department of Biostatistics, Boston University School of Public Health, Boston, MA (S.R.P., A.S.B., Q.Y.). FAU - Lieb, Wolfgang AU - Lieb W AD - Institute of Epidemiology, Christian-Albrechts-University, Kiel, Germany (W.L.). FAU - Beiser, Alexa S AU - Beiser AS AD - 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.) Department of Biostatistics, Boston University School of Public Health, Boston, MA (S.R.P., A.S.B., Q.Y.) Department of Neurology, Boston University School of Medicine, Boston, MA (A.S.B., S.S.). FAU - Yang, Qiong AU - Yang Q AD - 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.) Department of Biostatistics, Boston University School of Public Health, Boston, MA (S.R.P., A.S.B., Q.Y.). FAU - Chen, Tai C AU - Chen TC AD - Sections of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA (T.C.C.). FAU - Hengstenberg, Christian AU - Hengstenberg C AD - Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Germany (B.M.K., C.H., H.S.) DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munchen, Germany (B.M.K., C.H., H.S.). FAU - Erdmann, Jeanette AU - Erdmann J AD - Institut fur Integrative und Experimentelle Genomik, Universitat zu Lubeck, Germany (J.E.) DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lubeck/Kiel, Lubeck, Germany (J.E.). FAU - Schunkert, Heribert AU - Schunkert H AD - Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Germany (B.M.K., C.H., H.S.) DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munchen, Germany (B.M.K., C.H., H.S.). FAU - Seshadri, Sudha AU - Seshadri S AD - 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.) Department of Neurology, Boston University School of Medicine, Boston, MA (A.S.B., S.S.). FAU - Vasan, Ramachandran S AU - Vasan RS AD - 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.) Sections of Preventive Medicine and Epidemiology and Cardiology, Boston University School of Medicine, Boston, MA (R.S.V.). CN - CARDIoGRAM FAU - Assimes, Themistocles L AU - Assimes TL FAU - Deloukas, Panos AU - Deloukas P FAU - Holm, Hilma AU - Holm H FAU - Kathiresan, Sekar AU - Kathiresan S FAU - Konig, Inke R AU - Konig IR FAU - McPherson, Ruth AU - McPherson R FAU - Reilly, Muredach P AU - Reilly MP FAU - Roberts, Robert AU - Roberts R FAU - Samani, Nilesh J AU - Samani NJ FAU - Stewart, Alexandre F R AU - Stewart AF LA - eng GR - N01-HC-25195/HC/NHLBI NIH HHS/United States GR - R01 NS017950/NS/NINDS NIH HHS/United States GR - R01 AG008122/AG/NIA NIH HHS/United States GR - AG031287/AG/NIA NIH HHS/United States GR - P30 AG010129/AG/NIA NIH HHS/United States GR - R01 AG031287/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150311 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) SB - IM EIN - J Am Heart Assoc. 2016 Jul;5(7). pii: e002098. doi: 10.1161/JAHA.116.002098. PMID: 27431646 MH - Aged MH - Biomarkers/blood MH - Brain-Derived Neurotrophic Factor/*blood/genetics MH - Cardiovascular Diseases/*blood/diagnosis/*epidemiology/genetics/mortality MH - Case-Control Studies MH - Female MH - Gene Frequency MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Humans MH - Incidence MH - Linear Models MH - Male MH - Massachusetts/epidemiology MH - Middle Aged MH - Multivariate Analysis MH - Phenotype MH - Polymorphism, Single Nucleotide MH - Predictive Value of Tests MH - Prognosis MH - Proportional Hazards Models MH - Prospective Studies MH - Protective Factors MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Up-Regulation PMC - PMC4392437 OTO - NOTNLM OT - Mendelian randomization OT - cardiovascular disease OT - growth factors OT - mortality OT - risk factors FIR - Kathiresan, Sekar IR - Kathiresan S FIR - Reilly, Muredach P IR - Reilly MP FIR - Samani, Nilesh J IR - Samani NJ FIR - Schunkert, Heribert IR - Schunkert H FIR - Erdmann, Jeanette IR - Erdmann J FIR - Assimes, Themistocles L IR - Assimes TL FIR - Boerwinkle, Eric IR - Boerwinkle E FIR - Erdmann, Jeanette IR - Erdmann J FIR - Hall, Alistair IR - Hall A FIR - Hengstenberg, Christian IR - Hengstenberg C FIR - Kathiresan, Sekar IR - Kathiresan S FIR - Konig, Inke R IR - Konig IR FIR - Laaksonen, Reijo IR - Laaksonen R FIR - McPherson, Ruth IR - McPherson R FIR - Reilly, Muredach P IR - Reilly MP FIR - Samani, Nilesh J IR - Samani NJ FIR - Schunkert, Heribert IR - Schunkert H FIR - Thompson, John R IR - Thompson JR FIR - Thorsteinsdottir, Unnur IR - Thorsteinsdottir U FIR - Ziegler, Andreas IR - Ziegler A FIR - Konig, Inke R IR - Konig IR FIR - Thompson, John R IR - Thompson JR FIR - Absher, Devin IR - Absher D FIR - Chen, Li IR - Chen L FIR - Cupples, L Adrienne IR - Cupples LA FIR - Halperin, Eran IR - Halperin E FIR - Li, Mingyao IR - Li M FIR - Musunuru, Kiran IR - Musunuru K FIR - Preuss, Michael IR - Preuss M FIR - Schillert, Arne IR - Schillert A FIR - 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Rupprecht, Hans J IR - Rupprecht HJ FIR - Perret, Claire IR - Perret C FIR - Proust, Carole IR - Proust C FIR - Munzel, Thomas IR - Munzel T FIR - Barbalic, Maja IR - Barbalic M FIR - Bis, Joshua IR - Bis J FIR - Boerwinkle, Eric IR - Boerwinkle E FIR - Chen, Ida Yii-Der IR - Chen IY FIR - Cupples, L Adrienne IR - Cupples LA FIR - Dehghan, Abbas IR - Dehghan A FIR - Demissie-Banjaw, Serkalem IR - Demissie-Banjaw S FIR - Folsom, Aaron IR - Folsom A FIR - Glazer, Nicole IR - Glazer N FIR - Gudnason, Vilmundur IR - Gudnason V FIR - Harris, Tamara IR - Harris T FIR - Heckbert, Susan IR - Heckbert S FIR - Levy, Daniel IR - Levy D FIR - Lumley, Thomas IR - Lumley T FIR - Marciante, Kristin IR - Marciante K FIR - Morrison, Alanna IR - Morrison A FIR - O'Donnell, Christopher J IR - O'Donnell CJ FIR - Psaty, Bruce M IR - Psaty BM FIR - Rice, Kenneth IR - Rice K FIR - Rotter, Jerome I IR - Rotter JI FIR - Siscovick, David S IR - Siscovick DS FIR - Smith, Nicholas IR - Smith N FIR - Smith, Albert IR - 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Stark, Klaus IR - Stark K FIR - Schreiber, Stefan IR - Schreiber S FIR - Wichmann, H-Erich IR - Wichmann HE FIR - Ziegler, Andreas IR - Ziegler A FIR - Schunkert, Heribert IR - Schunkert H FIR - Aherrahrou, Zouhair IR - Aherrahrou Z FIR - Bruse, Petra IR - Bruse P FIR - Doering, Angela IR - Doering A FIR - Erdmann, Jeanette IR - Erdmann J FIR - Hengstenberg, Christian IR - Hengstenberg C FIR - Illig, Thomas IR - Illig T FIR - Klopp, Norman IR - Klopp N FIR - Konig, Inke R IR - Konig IR FIR - Diemert, Patrick IR - Diemert P FIR - Loley, Christina IR - Loley C FIR - Medack, Anja IR - Medack A FIR - Meisinger, Christina IR - Meisinger C FIR - Meitinger, Thomas IR - Meitinger T FIR - Nahrstedt, Janja IR - Nahrstedt J FIR - Peters, Annette IR - Peters A FIR - Preuss, Michael IR - Preuss M FIR - Stark, Klaus IR - Stark K FIR - Wagner, Arnika K IR - Wagner AK FIR - Wichmann, H-Erich IR - Wichmann HE FIR - Willenborg, Christina IR - Willenborg C FIR - Ziegler, Andreas IR - Ziegler A FIR - Schunkert, Heribert IR - 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Salomaa V FIR - Schwartz, Stephen M IR - Schwartz SM FIR - Melander, Olle IR - Melander O FIR - Altshuler, David IR - Altshuler D FIR - Kathiresan, Sekar IR - Kathiresan S FIR - Stewart, Alexandre F R IR - Stewart AF FIR - Chen, Li IR - Chen L FIR - Dandona, Sonny IR - Dandona S FIR - Wells, George A IR - Wells GA FIR - Jarinova, Olga IR - Jarinova O FIR - McPherson, Ruth IR - McPherson R FIR - Roberts, Robert IR - Roberts R FIR - Reilly, Muredach P IR - Reilly MP FIR - Li, Mingyao IR - Li M FIR - Qu, Liming IR - Qu L FIR - Wilensky, Robert IR - Wilensky R FIR - Matthai, William IR - Matthai W FIR - Hakonarson, Hakon H IR - Hakonarson HH FIR - Devaney, Joe IR - Devaney J FIR - Burnett, Mary Susan IR - Burnett MS FIR - Pichard, Augusto D IR - Pichard AD FIR - Kent, Kenneth M IR - Kent KM FIR - Satler, Lowell IR - Satler L FIR - Lindsay, Joseph M IR - Lindsay JM FIR - Waksman, Ron IR - Waksman R FIR - Knouff, Christopher W IR - Knouff CW FIR - Waterworth, Dawn M IR - Waterworth DM FIR - Walker, Max C IR - Walker MC FIR - Mooser, Vincent IR - Mooser V FIR - Epstein, Stephen E IR - Epstein SE FIR - Rader, Daniel J IR - Rader DJ FIR - Samani, Nilesh J IR - Samani NJ FIR - Thompson, John R IR - Thompson JR FIR - Braund, Peter S IR - Braund PS FIR - Nelson, Christopher P IR - Nelson CP FIR - Wright, Benjamin J IR - Wright BJ FIR - Balmforth, Anthony J IR - Balmforth AJ FIR - Ball, Stephen G IR - Ball SG FIR - Hall, Alistair S IR - Hall AS EDAT- 2015/03/13 06:00 MHDA- 2016/03/02 06:00 PMCR- 2015/03/01 CRDT- 2015/03/13 06:00 PHST- 2015/03/13 06:00 [entrez] PHST- 2015/03/13 06:00 [pubmed] PHST- 2016/03/02 06:00 [medline] PHST- 2015/03/01 00:00 [pmc-release] AID - jah3893 [pii] AID - 10.1161/JAHA.114.001544 [doi] PST - epublish SO - J Am Heart Assoc. 2015 Mar 11;4(3):e001544. doi: 10.1161/JAHA.114.001544.