{"doi":"10.1161/jaha.114.001544","title":"Circulating Brain‐Derived Neurotrophic Factor Concentrations and the Risk of Cardiovascular Disease in the Community","abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background</jats:title>\n            <jats:p xml:lang=\"en\">\n              Brain‐derived neurotrophic factor (\n              <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              ) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating\n              <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              levels are associated with risk of cardiovascular disease (\n              <jats:styled-content style=\"fixed-case\">CVD</jats:styled-content>\n              ).\n            </jats:p>\n          </jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results</jats:title>\n            <jats:p xml:lang=\"en\">\n              We prospectively investigated the association of circulating\n              <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (\n              <jats:styled-content style=\"fixed-case\">FHS</jats:styled-content>\n              ). Using a common nonsynonomous single nucleotide polymorphism (\n              <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>\n              ) in the\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              </jats:italic>\n              gene (rs6265), we then performed a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease Genome‐Wide Replication And Meta‐Analysis) consortium (&gt;22 000 coronary artery disease [\n              <jats:styled-content style=\"fixed-case\">CAD</jats:styled-content>\n              ] cases, &gt;60 000 controls) to investigate whether\n              <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>\n              rs6265 was associated with\n              <jats:styled-content style=\"fixed-case\">CAD</jats:styled-content>\n              in CARDIoGRAM and, if so, whether the effect estimate differed from that predicted based on\n              <jats:styled-content style=\"fixed-case\">FHS</jats:styled-content>\n              data. On follow‐up (median 8.9 years), 467 individuals (261 women) in\n              <jats:styled-content style=\"fixed-case\">FHS</jats:styled-content>\n              experienced a\n              <jats:styled-content style=\"fixed-case\">CVD</jats:styled-content>\n              event, and 835 (430 women) died. In multivariable‐adjusted Cox regression, serum\n              <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              was associated inversely with\n              <jats:styled-content style=\"fixed-case\">CVD</jats:styled-content>\n              risk (hazard ratio [\n              <jats:styled-content style=\"fixed-case\">HR</jats:styled-content>\n              ] per 1‐\n              <jats:styled-content style=\"fixed-case\">SD</jats:styled-content>\n              increase 0.88, 95%\n              <jats:styled-content style=\"fixed-case\">CI</jats:styled-content>\n              0.80 to 0.97,\n              <jats:italic>P</jats:italic>\n              =0.01) and with mortality (\n              <jats:styled-content style=\"fixed-case\">HR</jats:styled-content>\n              0.87, 95%\n              <jats:styled-content style=\"fixed-case\">CI</jats:styled-content>\n              0.80 to 0.93,\n              <jats:italic>P</jats:italic>\n              =0.0002).\n              <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>\n              rs6265 was associated with\n              <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              concentrations (0.772 ng/mL increase per minor allele copy) in\n              <jats:styled-content style=\"fixed-case\">FHS</jats:styled-content>\n              . In CARDIoGRAM,\n              <jats:styled-content style=\"fixed-case\">SNP</jats:styled-content>\n              rs6265 was associated with\n              <jats:styled-content style=\"fixed-case\">CAD</jats:styled-content>\n              (odds ratio 0.957, 95%\n              <jats:styled-content style=\"fixed-case\">CI</jats:styled-content>\n              0.923 to 0.992), a magnitude consistent with the predicted effect (\n              <jats:styled-content style=\"fixed-case\">HR</jats:styled-content>\n              per minor allele copy 0.99, 95%\n              <jats:styled-content style=\"fixed-case\">CI</jats:styled-content>\n              0.98 to 1.0;\n              <jats:italic>P</jats:italic>\n              =0.06 for difference between predicted and observed effect).\n            </jats:p>\n          </jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusion</jats:title>\n            <jats:p xml:lang=\"en\">\n              Higher serum\n              <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              is associated with a decreased risk of\n              <jats:styled-content style=\"fixed-case\">CVD</jats:styled-content>\n              and mortality. Mendelian randomization suggests a causal protective role of\n              <jats:styled-content style=\"fixed-case\">BDNF</jats:styled-content>\n              in the pathogenesis of\n              <jats:styled-content style=\"fixed-case\">CVD</jats:styled-content>\n              .\n            </jats:p>\n          </jats:sec>","journal":"Journal of the American Heart Association","year":2015,"id":14481,"datarank":5.814969770679925,"base_score":5.0238805208462765,"endowment":5.0238805208462765,"self_citation_contribution":0.7535820781269416,"citation_network_contribution":5.061387692552984,"self_endowment_contribution":0.7535820781269416,"citer_contribution":5.061387692552984,"corpus_percentile":null,"corpus_rank":null,"citation_count":151,"citer_count":137,"citers_with_citation_signal":121,"citers_with_endowment":121,"datacite_reuse_total":10,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":114206,"name":"Sarah R. 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