Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry

Background Growth differentiation factor 15 (GDF15) is a cytokine responding to oxidative stress and inflammation, and it regulates appetite and energy balance. The association between GDF15 and clinical factors and its prognostic value in elderly multimorbid patients with heart failure with preserv...

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Main Authors: Tetsuhisa Kitamura, Shungo Hikoso, Takahisa Yamada, Yoshio Yasumura, Akito Nakagawa, Toshihiro Takeda, Hirota Kida, Akihiro Sunaga, Tomoharu Dohi, Katsuki Okada, Daisaku Nakatani, Yasushi Matsumura, Yasushi Sakata, Shunsuke Tamaki, Takaharu Hayashi, Yoshiharu Higuchi, Masaharu Masuda, Mitsutoshi Asai, Toshiaki Mano, Hisakazu Fuji, Daisaku Masuda, Shizuya Yamashita, Masami Sairyo, Yusuke Nakagawa, Haruhiko Abe, Yasunori Ueda, Kunihiko Nagai, Masamichi Yano, Masami Nishino, Jun Tanouchi, Yoh Arita, Shinji Hasegawa, Takamaru Ishizu, Minoru Ichikawa, Yuzuru Takano, Eisai Rin, Tetsuya Watanabe, Shiro Hoshida, Masahiro Izumi, Hiroyoshi Yamamoto, Hiroyasu Kato, Kazuhiro Nakatani, Mayu Nishio, Keiji Hirooka, Takahiro Yoshimura, Akihiro Tani, Yasushi Okumoto, Yasunaka Makino, Katsuomi Iwakura, Yoshiyuki Kijima, Takashi Kitao, Masashi Fujita, Koichiro Harada, Masahiro Kumada, Osamu Nakagawa, Ryo Araki, Takayuki Yamada, Fusako Sera, Kei Nakamoto, Hidetaka Kioka, Tomohito Ohtani, Nobuyuki Ogasawara, Yukinori Shinoda, Koichi Tachibana, Yohei Sotomi, Taiki Sato, Yuji Yasuga, Toshinari Onishi, Kazunori Kashiwase, Ryu Shutta, Masahiro Seo, Yuki Matsuoka, Yasuhiro Akazawa, Daisuke Sakamoto
Format: Article
Language:English
Published: BMJ Publishing Group 2025-01-01
Series:Open Heart
Online Access:https://openheart.bmj.com/content/12/1/e003008.full
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author Tetsuhisa Kitamura
Shungo Hikoso
Takahisa Yamada
Yoshio Yasumura
Akito Nakagawa
Toshihiro Takeda
Hirota Kida
Akihiro Sunaga
Tomoharu Dohi
Katsuki Okada
Daisaku Nakatani
Yasushi Matsumura
Yasushi Sakata
Shunsuke Tamaki
Takaharu Hayashi
Yoshiharu Higuchi
Masaharu Masuda
Mitsutoshi Asai
Toshiaki Mano
Hisakazu Fuji
Daisaku Masuda
Shizuya Yamashita
Masami Sairyo
Yusuke Nakagawa
Haruhiko Abe
Yasunori Ueda
Kunihiko Nagai
Masamichi Yano
Masami Nishino
Jun Tanouchi
Yoh Arita
Shinji Hasegawa
Takamaru Ishizu
Minoru Ichikawa
Yuzuru Takano
Eisai Rin
Tetsuya Watanabe
Shiro Hoshida
Masahiro Izumi
Hiroyoshi Yamamoto
Hiroyasu Kato
Kazuhiro Nakatani
Mayu Nishio
Keiji Hirooka
Takahiro Yoshimura
Akihiro Tani
Yasushi Okumoto
Yasunaka Makino
Katsuomi Iwakura
Yoshiyuki Kijima
Takashi Kitao
Masashi Fujita
Koichiro Harada
Masahiro Kumada
Osamu Nakagawa
Ryo Araki
Takayuki Yamada
Fusako Sera
Kei Nakamoto
Hidetaka Kioka
Tomohito Ohtani
Nobuyuki Ogasawara
Yukinori Shinoda
Koichi Tachibana
Yohei Sotomi
Taiki Sato
Yuji Yasuga
Toshinari Onishi
Kazunori Kashiwase
Ryu Shutta
Masahiro Seo
Yuki Matsuoka
Yasuhiro Akazawa
Daisuke Sakamoto
author_facet Tetsuhisa Kitamura
Shungo Hikoso
Takahisa Yamada
Yoshio Yasumura
Akito Nakagawa
Toshihiro Takeda
Hirota Kida
Akihiro Sunaga
Tomoharu Dohi
Katsuki Okada
Daisaku Nakatani
Yasushi Matsumura
Yasushi Sakata
Shunsuke Tamaki
Takaharu Hayashi
Yoshiharu Higuchi
Masaharu Masuda
Mitsutoshi Asai
Toshiaki Mano
Hisakazu Fuji
Daisaku Masuda
Shizuya Yamashita
Masami Sairyo
Yusuke Nakagawa
Haruhiko Abe
Yasunori Ueda
Kunihiko Nagai
Masamichi Yano
Masami Nishino
Jun Tanouchi
Yoh Arita
Shinji Hasegawa
Takamaru Ishizu
Minoru Ichikawa
Yuzuru Takano
Eisai Rin
Tetsuya Watanabe
Shiro Hoshida
Masahiro Izumi
Hiroyoshi Yamamoto
Hiroyasu Kato
Kazuhiro Nakatani
Mayu Nishio
Keiji Hirooka
Takahiro Yoshimura
Akihiro Tani
Yasushi Okumoto
Yasunaka Makino
Katsuomi Iwakura
Yoshiyuki Kijima
Takashi Kitao
Masashi Fujita
Koichiro Harada
Masahiro Kumada
Osamu Nakagawa
Ryo Araki
Takayuki Yamada
Fusako Sera
Kei Nakamoto
Hidetaka Kioka
Tomohito Ohtani
Nobuyuki Ogasawara
Yukinori Shinoda
Koichi Tachibana
Yohei Sotomi
Taiki Sato
Yuji Yasuga
Toshinari Onishi
Kazunori Kashiwase
Ryu Shutta
Masahiro Seo
Yuki Matsuoka
Yasuhiro Akazawa
Daisuke Sakamoto
collection DOAJ
description Background Growth differentiation factor 15 (GDF15) is a cytokine responding to oxidative stress and inflammation, and it regulates appetite and energy balance. The association between GDF15 and clinical factors and its prognostic value in elderly multimorbid patients with heart failure with preserved ejection fraction (HFpEF) have not been well unknown.Methods This exploratory analysis is part of the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF (UMIN000021831). A predefined subcohort of 212 patients underwent multi-biomarker testing. Of these, we analysed 181 patients with available GDF15 data. The primary endpoint was a composite of all-cause death and hospitalisation for HF.Results In this analysis population, the median age was 81 (75–85) years, with 48% male patients. GDF15 significantly correlated with cardiac burden, anaemia, renal dysfunction and inflammation. Notably, poor nutritional status was significantly associated with GDF15. GDF15 was linked to poor prognosis in this elderly multimorbid cohort with HFpEF (adjusted HR for log-transformed GDF15: 13.67, 95% CI: 2.78 to 67.22, p=0.001). Furthermore, GDF15 added significant incremental value to the MAGGIC risk score (net reclassification improvement=0.4955 (95% CI: 0.1367 to 0.8543), p=0.007; integrated discrimination improvement=0.0278 (95% CI: 0.0013 to 0.0543), p=0.040).Conclusions GDF15 was associated with anaemia, inflammation, renal dysfunction, cardiac burden and malnutrition. It demonstrated prognostic value in elderly multimorbid HFpEF patients, suggesting its potential role as a complementary marker for the prognostic risk assessment of HFpEF patients.Trial registration number UMIN-CTR ID: UMIN000021831.
format Article
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institution Kabale University
issn 2053-3624
language English
publishDate 2025-01-01
publisher BMJ Publishing Group
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series Open Heart
spelling doaj-art-e57ec1a03eda43febb09301667eb14142025-01-21T08:45:10ZengBMJ Publishing GroupOpen Heart2053-36242025-01-0112110.1136/openhrt-2024-003008Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry Tetsuhisa Kitamura0Shungo Hikoso1Takahisa Yamada2Yoshio Yasumura3Akito Nakagawa4Toshihiro TakedaHirota Kida5Akihiro Sunaga6Tomoharu DohiKatsuki Okada7Daisaku Nakatani8Yasushi MatsumuraYasushi Sakata9Shunsuke Tamaki10Takaharu Hayashi11Yoshiharu HiguchiMasaharu MasudaMitsutoshi AsaiToshiaki ManoHisakazu FujiDaisaku MasudaShizuya YamashitaMasami SairyoYusuke Nakagawa12Haruhiko AbeYasunori UedaKunihiko NagaiMasamichi Yano13Masami NishinoJun TanouchiYoh AritaShinji HasegawaTakamaru IshizuMinoru IchikawaYuzuru TakanoEisai RinTetsuya WatanabeShiro HoshidaMasahiro IzumiHiroyoshi YamamotoHiroyasu KatoKazuhiro NakataniMayu NishioKeiji HirookaTakahiro YoshimuraAkihiro TaniYasushi OkumotoYasunaka MakinoKatsuomi IwakuraYoshiyuki KijimaTakashi KitaoMasashi FujitaKoichiro HaradaMasahiro KumadaOsamu NakagawaRyo ArakiTakayuki YamadaFusako SeraKei NakamotoHidetaka KiokaTomohito OhtaniNobuyuki OgasawaraYukinori ShinodaKoichi TachibanaYohei Sotomi14Taiki Sato15Yuji YasugaToshinari OnishiKazunori KashiwaseRyu ShuttaMasahiro Seo16Yuki Matsuoka17Yasuhiro AkazawaDaisuke Sakamoto18Environmental Medicine, Osaka University, Suita, JapanDepartment of Cardiology, Nara Medical University, Kashihara, JapanOsaka General Medical Center, Osaka, JapanAmagasaki Chuo Hospital, Amagasaki, JapanShoushoukai healthcare corporation, Nakagawa Clinic, Suita, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanDepartment of Cardiology, Rinku General Medical Center, Izumisano, JapanCardiology, Osaka Police Hospital, Osaka, JapanKawanishi City Medical Center, Kawanishi, JapanOsaka Rosai Hospital, Sakai, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanOsaka General Medical Center, Osaka, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanOsaka University Graduate School of Medicine Department of Cardiovascular Medicine, Suita, JapanBackground Growth differentiation factor 15 (GDF15) is a cytokine responding to oxidative stress and inflammation, and it regulates appetite and energy balance. The association between GDF15 and clinical factors and its prognostic value in elderly multimorbid patients with heart failure with preserved ejection fraction (HFpEF) have not been well unknown.Methods This exploratory analysis is part of the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF (UMIN000021831). A predefined subcohort of 212 patients underwent multi-biomarker testing. Of these, we analysed 181 patients with available GDF15 data. The primary endpoint was a composite of all-cause death and hospitalisation for HF.Results In this analysis population, the median age was 81 (75–85) years, with 48% male patients. GDF15 significantly correlated with cardiac burden, anaemia, renal dysfunction and inflammation. Notably, poor nutritional status was significantly associated with GDF15. GDF15 was linked to poor prognosis in this elderly multimorbid cohort with HFpEF (adjusted HR for log-transformed GDF15: 13.67, 95% CI: 2.78 to 67.22, p=0.001). Furthermore, GDF15 added significant incremental value to the MAGGIC risk score (net reclassification improvement=0.4955 (95% CI: 0.1367 to 0.8543), p=0.007; integrated discrimination improvement=0.0278 (95% CI: 0.0013 to 0.0543), p=0.040).Conclusions GDF15 was associated with anaemia, inflammation, renal dysfunction, cardiac burden and malnutrition. It demonstrated prognostic value in elderly multimorbid HFpEF patients, suggesting its potential role as a complementary marker for the prognostic risk assessment of HFpEF patients.Trial registration number UMIN-CTR ID: UMIN000021831.https://openheart.bmj.com/content/12/1/e003008.full
spellingShingle Tetsuhisa Kitamura
Shungo Hikoso
Takahisa Yamada
Yoshio Yasumura
Akito Nakagawa
Toshihiro Takeda
Hirota Kida
Akihiro Sunaga
Tomoharu Dohi
Katsuki Okada
Daisaku Nakatani
Yasushi Matsumura
Yasushi Sakata
Shunsuke Tamaki
Takaharu Hayashi
Yoshiharu Higuchi
Masaharu Masuda
Mitsutoshi Asai
Toshiaki Mano
Hisakazu Fuji
Daisaku Masuda
Shizuya Yamashita
Masami Sairyo
Yusuke Nakagawa
Haruhiko Abe
Yasunori Ueda
Kunihiko Nagai
Masamichi Yano
Masami Nishino
Jun Tanouchi
Yoh Arita
Shinji Hasegawa
Takamaru Ishizu
Minoru Ichikawa
Yuzuru Takano
Eisai Rin
Tetsuya Watanabe
Shiro Hoshida
Masahiro Izumi
Hiroyoshi Yamamoto
Hiroyasu Kato
Kazuhiro Nakatani
Mayu Nishio
Keiji Hirooka
Takahiro Yoshimura
Akihiro Tani
Yasushi Okumoto
Yasunaka Makino
Katsuomi Iwakura
Yoshiyuki Kijima
Takashi Kitao
Masashi Fujita
Koichiro Harada
Masahiro Kumada
Osamu Nakagawa
Ryo Araki
Takayuki Yamada
Fusako Sera
Kei Nakamoto
Hidetaka Kioka
Tomohito Ohtani
Nobuyuki Ogasawara
Yukinori Shinoda
Koichi Tachibana
Yohei Sotomi
Taiki Sato
Yuji Yasuga
Toshinari Onishi
Kazunori Kashiwase
Ryu Shutta
Masahiro Seo
Yuki Matsuoka
Yasuhiro Akazawa
Daisuke Sakamoto
Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry
Open Heart
title Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry
title_full Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry
title_fullStr Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry
title_full_unstemmed Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry
title_short Role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF registry
title_sort role and prognostic value of growth differentiation factor 15 in patient of heart failure with preserved ejection fraction insights from the pursuit hfpef registry
url https://openheart.bmj.com/content/12/1/e003008.full
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