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Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome

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Abstract

The importance of the central nervous system in cardiovascular events has been recognized. Recently, brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is involved in depression mechanisms and also in stress and anxiety. Because BDNF is reported about cardioprotective role, we elucidated whether BDNF is associated with cardiovascular events in patients with chronic heart failure (CHF). We examined serum BDNF levels in 134 patients with CHF and 23 control subjects. The patients were followed to register cardiac events for a median of 426 days. BDNF was significantly lower in CHF patients than in control subjects (25.8 ± 8.4 vs 14.7 ± 8.4, P < 0.0001). Serum BDNF was also lower in patients with cardiac events than in event-free patients (16.1 ± 8.0 vs 12.5 ± 8.5, P < 0.0001). The cutoff value of BDNF was determined by performing receiver operating characteristic curve analysis. Kaplan–Meier analysis demonstrated that patients with low levels of BDNF experienced higher rates of cardiac events than those with high levels of BDNF. Multivariate Cox hazard analysis demonstrated that low BDNF levels (≤12.4 ng/mL) were an independent prognostic factor for cardiac events (hazard ratio 2.932, 95 % confidence interval 1.622–5.301; P = 0.0004). Adding levels of BDNF to the model with BNP levels, age, and eGFR for the prediction of cardiac events yielded significant net reclassification improvement of 0.429 (P < 0.001) and an integrated discrimination improvement of 0.101 (P < 0.001). Low serum BDNF levels were found in patients with CHF, and these levels were found to be independently associated with an increased risk of cardiac events.

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Acknowledgement

This work was supported in part by a grant-in-aid for Scientific Research (Nos. 24659380 to I. K., and 23790830 to T. S.) from the Ministry of Education, Science, Sports, and Culture, Japan, a grant-in-aid from the 21st Global Century Center of Excellence (COE) program of the Japan Society for the Promotion of Science to I. K. T. S. was supported by the Japan Heart Foundation Research Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan

    Shinpei Kadowaki, Tetsuro Shishido, Yuki Honda, Taro Narumi, Yoichiro Otaki, Daisuke Kinoshita, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Takuya Miyamoto, Tetsu Watanabe & Isao Kubota

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  1. Shinpei Kadowaki
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  2. Tetsuro Shishido
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  3. Yuki Honda
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  4. Taro Narumi
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  5. Yoichiro Otaki
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  6. Daisuke Kinoshita
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  7. Satoshi Nishiyama
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  9. Takanori Arimoto
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  11. Tetsu Watanabe
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  12. Isao Kubota
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Correspondence to Tetsuro Shishido.

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Kadowaki, S., Shishido, T., Honda, Y. et al. Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome. Heart Vessels 31, 535–544 (2016). https://doi.org/10.1007/s00380-015-0628-6

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