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Heart and Vessels

, Volume 33, Issue 9, pp 997–1007 | Cite as

Comparable prognostic impact of BNP levels among HFpEF, Borderline HFpEF and HFrEF: a report from the CHART-2 Study

  • Shintaro Kasahara
  • Yasuhiko Sakata
  • Kotaro Nochioka
  • Takeshi Yamauchi
  • Takeo Onose
  • Kanako Tsuji
  • Ruri Abe
  • Takuya Oikawa
  • Masayuki Sato
  • Hajime Aoyanagi
  • Masanobu Miura
  • Takashi Shiroto
  • Jun Takahashi
  • Satoshi Miyata
  • Hiroaki Shimokawa
  • On behalf of the CHART-2 Investigators
Original Article

Abstract

We aimed to compare the usefulness of plasma levels of B-type natriuretic peptide (BNP) for long-term risk stratification among patients with heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF), borderline HFpEF, and HF with reduced LVEF (HFrEF) in the same HF cohort. In the CHART-2 Study (N = 10,219), we categorized 4301 consecutive Stage C/D HF patients (mean age 68.7 years, female 32.4%) into 3 groups: HFpEF (LVEF ≥ 50%, N = 2893), borderline HFpEF (LVEF 40–50%, N = 666), and HFrEF (LVEF ≤ 40%, N = 742). During the median 6.3-year follow-up, all-cause deaths occurred in 887 HFpEF, 330 borderline HFpEF, and 330 HFrEF patients. Although median BNP levels increased from HFpEF, borderline HFpEF to HFrEF (85.3, 126 and 208 pg/ml, respectively, P < 0.001), the relationship between log2 BNP levels and the mortality risk was comparable among the 3 groups. As compared with patients with BNP < 30 pg/ml, those with 30–99, 100–299 and ≥ 300 pg/ml had comparably increasing mortality risk among the 3 groups (hazard ratio 2.5, 4.7 and 7.8 in HFpEF, 2.1, 4.2 and 7.0 in borderline HFpEF, and 3.0, 4.7 and 9.5 in HFrEF, respectively, all P < 0.001). BNP levels have comparable prognostic impact among HFpEF, borderline HFpEF, and HFrEF patients.

Keywords

B-type natriuretic peptide Prognosis Heart failure Left ventricular ejection fraction 

Notes

Acknowledgements

We thank all the members of the Tohoku Heart Failure Association and the staff of the Departments of Cardiovascular Medicine and Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, for their contributions.

The CHART-2 Study investigators: Executive committee: Hiroaki Shimokawa (Chair), Mitsumasa Fukuchi, Toshikazu Goto, Eiji Nozaki, Tetsuya Hiramoto, Satoru Horiguchi, Kanichi Inoue, Atsushi Kato, Hiroshi Kato, Masatoshi Ohe, Tsuyoshi Shinozaki, and Masafumi Sugi. Steering committee: Tetsuya Hiramoto, Kanichi Inoue, Atsushi Kato, Masahiko Ogata, Shoichi Sato, and Masafumi Sugi. Collaborating hospitals and active investigators by prefecture: Aomori prefecture: Shigeto Oyama, and Jun Demachi (Towada City Hospital). Iwate prefecture: Eiji Nozaki, Akihiro Nakamura, Tohru Takahashi, Hideaki Endo, Masateru Kondo, Kazuki Noda, Masanori Kanazawa, and Kenjiro Sato (Iwate Prefectural Central Hospital). Makoto Nakagawa, Tetsuji Nozaki, and Takuya Yagi (Iwate Prefectural Isawa Hospital). Akita prefecture: Toshiaki Takahashi, Satoru Horiguchi, Etsuko Fushimi, Kohei Fukahori, Satoru Takeda, and Sota Nakajima (Hiraka General Hospital). Yamagata prefecture: Masatoshi Ohe, Takurou Tashima, Katsuhiko Sakurai, and Tadashi Kobayashi (Kojirakawa Shiseido Hospital). Toshikazu Goto, Motoyuki Matsui, Yoshiaki Tamada, Tomoyasu Yahagi, Akio Fukui, Katsuaki Takahashi, Shigehiko Kato, and Hyuma Daidouji (Yamagata Prefectural Central Hospital). Miyagi prefecture: Akihiko Sugimura and Junko Ohashi (Sendai Red Cross Hospital). Hiroyuki Kanno and Junji Kaneko (Katta General Hospital). Shu Suzuki and Osamu Kitamukai (KKR Tohoku Kosai Hospital). Dai Katayose (Miyagi Rifu Ekisaikai Hospital). Kaoru Iwabuchi, Sachio Onodera, Seiji Komatsu, Masanobu Chida, Masaharu Takeuchi, Hirokazu Yahagi, and Nozomu Takahashi (Osaki Citizen Hospital). Keiji Otsuka, Yoshito Koseki, and Masaki Morita (Saito Hospital). Tsuyoshi Shinozaki, Takeshi Ishizuka, Noriko Onoue, Nobuhiro Yamaguchi, and Hiroshi Fujita (Sendai Medical Center). Atsushi Kato, Shigeto Namiuchi, Tadashi Sugie, Toru Takii, and Ryoichi Ushigome (Sendai Open Hospital). Yasuharu Matsumoto (Shizugawa Public Hospital). Kanichi Inoue, Jiro Koyama, Tomoko Tomioka, Hiroki Shioiri, and Yoshitaka Ito (South Miyagi Medical Center). Mitsuaki Tanaka, Chikako Takahashi, and Akiko Kawana (Tohoku Rosai Hospital). Tetsuya Hiramoto (Kurihara Central Hospital). Yasuhiko Sakata, Kenta Ito, Masaharu Nakayama, Koji Fukuda, Jun Takahashi, Satoshi Miyata, Koichiro Sugimura, Kimio Sato, Yasuharu Matsumoto, Makoto Nakano, Takashi Shiroto, Kotaro Nochioka, Masanobu Miura, Hiroaki Yamamoto, Tatsuo Aoki, Kiyotaka Hao, Shunsuke Tatebe, Saori Yamamoto, Yoku Kikuchi, Hideaki Suzuki, Shigeo Godo, Kensuke Nishimiya, Nobuhiro Yaoita, and Tomohiko Shindou (Tohoku University Hospital). Fukushima prefecture: Masafumi Sugi, Yoshito Yamamoto, Sunao Toda, Yusuke Takagi, Kentaro Aizawa, Taro Nihei, and Masato Segawa (Iwaki Kyouritsu Hospital). Koji Fukuda (Watanabe Hospital). Head office and coordinating center: Yasuhiko Sakata, Jun Takahashi, Satoshi Miyata, Takashi Shiroto, Kotaro Nochioka, Masanobu Miura, Takeshi Yamauchi, Kanako Tsuji, Takeo Onose, Ruri Abe, Takuya Oikawa, Shintaro Kasahara, Masayuki Sato, Hajime Aoyanagi, Chiharu Saga, Yoko Yamada, Junko Kimura, Hiromi Ogino, Izumi Oikawa, Sanae Watanabe, Yasuko Ikeno, Tomoyuki Suzuki, and Hiroko Hamada.

Compliance with ethical standards

Funding

This study was supported in part by the Grants-in Aid from the Japanese Ministry of Health, Labour, and Welfare and the Japanese Ministry of Education, Culture, Sports, Science, and Technology and the Agency for Medical Research and Development (nos. 15ek0210043h0001, 16ek0210056h0001, 6ek0210043h0002), Tokyo, Japan.

Conflict of interest

The Department of Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine is supported in part by unrestricted research grants from Daiichi Sankyo (Tokyo, Japan), Bayer Yakuhin (Osaka, Japan), Kyowa Hakko Kirin (Tokyo, Japan), Novartis Pharma (Tokyo, Japan), Dainippon Sumitomo Pharma (Osaka, Japan), Astellas Pharma (Tokyo, Japan), AstraZeneca (Osaka, Japan), Chugai Pharmaceutical (Tokyo, Japan), GlaxoSmithKline (Tokyo, Japan), Kowa Pharmaceutical (Tokyo, Japan), Mitsubishi Tanabe Pharma (Osaka, Japan), Mochida Pharmaceutical (Tokyo, Japan), MSD (Tokyo, Japan), Nippon Boehringer Ingelheim (Tokyo, Japan), Otsuka Pharmaceutical (Tokyo, Japan), Shionogi (Osaka, Japan) and Takeda Pharmaceutical (Osaka, Japan). H.S. has received lecture fees from Bayer Yakuhin (Osaka, Japan), Daiichi Sankyo (Tokyo, Japan) and Novartis Pharma (Tokyo, Japan).

References

  1. 1.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 62:e147–e239CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Curtis LH, Whellan DJ, Hammill BG, Hernandez AF, Anstrom KJ, Shea AM, Schulman KA (2008) Incidence and prevalence of heart failure in elderly persons, 1994–2003. Arch Intern Med 168:418–424CrossRefPubMedGoogle Scholar
  3. 3.
    Writing Group Members, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jiménez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB, American Heart Association Statistics Committee; Stroke Statistics Subcommittee (2015) Heart disease and stroke statistics—2016 update a report from the American Heart Association. Circulation 133:e38–e360Google Scholar
  4. 4.
    United Nations, Department of Economic and Social Affairs, Population (2017) Division, profiles of aging 2015. https://esa.un.org/unpd/popdev/Profilesofageing2015/index.html. 29 Oct 2017
  5. 5.
    Gomez-Soto FM, Andrey JL, Garcia-Egido AA, Escobar MA, Romero SP, Garcia-Arjona R, Gutierrez J, Gomez F (2011) Incidence and mortality of heart failure: a community-based study. Int J Cardiol 151:40–45CrossRefPubMedGoogle Scholar
  6. 6.
    Shimokawa H, Miura M, Nochioka K, Sakata Y (2015) Heart failure as a general pandemic in Asia. Eur J Heart Fail 17:884–892CrossRefPubMedGoogle Scholar
  7. 7.
    Sakata Y, Shimokawa H (2013) Epidemiology of heart failure in Asia. Circ J 77:2209–2217CrossRefPubMedGoogle Scholar
  8. 8.
    Guo Y, Lip GY, Banerjee A (2013) Heart failure in East Asia. Curr Cardiol Rev 9:112–122CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Pillai HS, Ganapathi S (2013) Heart failure in South Asia. Curr Cardiol Rev 9:102–111CrossRefPubMedGoogle Scholar
  10. 10.
    Gerber Y, Weston SA, Redfield MM, Chamberlain AM, Manemann SM, Jiang R, Killian JM, Roger VL (2015) A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Intern Med 175:996–1004CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Komajda M, Lam CS (2014) Heart failure with preserved ejection fraction: a clinical dilemma. Eur Heart J 35:1022–1032CrossRefPubMedGoogle Scholar
  12. 12.
    Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O’Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM, Investigators TOPCAT (2014) Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370:1383–1392CrossRefPubMedGoogle Scholar
  13. 13.
    Francis GS, Felker GM, Tang WH (2016) A test in context: critical evaluation of natriuretic peptide testing in heart failure. J Am Coll Cardiol 67:330–337CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Oremus M, Don-Wauchope A, McKelvie R, Santaguida PL, Hill S, Balion C, Booth R, Brown JA, Ali U, Bustamam A, Sohel N, Raina P (2014) BNP and NT-proBNP as prognostic markers in persons with chronic stable heart failure. Heart Fail Rev 19:471–505CrossRefPubMedGoogle Scholar
  15. 15.
    Grewal J, McKelvie RS, Persson H, Tait P, Carlsson J, Swedberg K, Ostergren J, Lonn E (2008) Usefulness of N-terminal pro-brain natriuretic peptide and brain natriuretic peptide to predict cardiovascular outcomes in patients with heart failure and preserved left ventricular ejection fraction. Am J Cardiol 102:733–737CrossRefPubMedGoogle Scholar
  16. 16.
    Anand IS, Rector TS, Cleland JG, Kuskowski M, McKelvie RS, Persson H, McMurray JJ, Zile MR, Komajda M, Massie BM, Carson PE (2011) Prognostic value of baseline plasma amino-terminal pro-brain natriuretic peptide and its interactions with irbesartan treatment effects in patients with heart failure and preserved ejection fraction findings from the I-PRESERVE Trial. Circ Heart Fail 4:569–577CrossRefPubMedGoogle Scholar
  17. 17.
    Cleland JG, Taylor J, Freemantle N, Goode KM, Rigby AS, Tendera M (2012) Relationship between plasma concentrations of N-terminal pro brain natriuretic peptide and the characteristics and outcome of patients with a clinical diagnosis of diastolic heart failure: a report from the PEP-CHF Study. Eur J Heart Fail 14:487–494CrossRefPubMedGoogle Scholar
  18. 18.
    Anand IS, Fisher LD, Chiang YT, Latini R, Masson S, Maggioni AP, Glazer RD, Tognoni G, Cohn JN, Investigators Val-HeFT (2003) Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 107:1278–1283CrossRefPubMedGoogle Scholar
  19. 19.
    Hartmann F, Packer M, Coats AJ, Fowler MB, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Anker SD, Amann-Zalan I, Hoersch S, Katus HA (2004) Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Circulation 110:1780–1786CrossRefPubMedGoogle Scholar
  20. 20.
    Cleland JG, McMurray JJ, Kjekshus J, Cornel JH, Dunselman P, Fonseca C, Hjalmarson A, Korewicki J, Lindberg M, Ranjith N, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J, CORONA Study Group (2009) Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J Am Coll Cardiol 54:1850–1859CrossRefPubMedGoogle Scholar
  21. 21.
    Al-Najjar Y, Goode KM, Zhang J, Cleland JG, Clark AL (2009) Red cell distribution width: an inexpensive and powerful prognostic marker in heart failure. Eur J Heart Fail 11:1155–1162CrossRefPubMedGoogle Scholar
  22. 22.
    Zile MR, Claggett BL, Prescott MF, McMurray JJ, Packer M, Rouleau JL, Swedberg K, Desai AS, Gong J, Shi VC, Solomon SD (2016) Prognostic implications of changes in N-terminal pro-B-type natriuretic peptide in patients with heart failure. J Am Coll Cardiol 68:2425–2436CrossRefPubMedGoogle Scholar
  23. 23.
    Lam CS, Solomon SD (2014) The middle child in heart failure: heart failure with mid-range ejection fraction (40–50%). Eur J Heart Fail 16:1049–1055CrossRefPubMedGoogle Scholar
  24. 24.
    Tsuji K, Sakata Y, Nochioka K, Miura M, Yamauchi T, Onose T, Abe R, Oikawa T, Kasahara S, Sato M, Shiroto T, Takahashi J, Miyata S, Shimokawa H, On behalf of the CHART-2 investigators (2017) Characterization of heart failure patients with mid-range left ventricular ejection fraction—a report from the CHART-2 Study. Eur J Heart Fail 19:1258–1269CrossRefPubMedGoogle Scholar
  25. 25.
    Shiba N, Nochioka K, Miura M, Kohno H, Shimokawa H, CHART-2 Investigators (2011) Trend of westernization of etiology and clinical characteristics of heart failure patients in Japan—first report from the CHART-2 Study. Circ J 75:823–833CrossRefPubMedGoogle Scholar
  26. 26.
    Ushigome R, Sakata Y, Nochioka K, Miyata S, Miura M, Tadaki S, Yamauchi T, Sato K, Onose T, Tsuji K, Abe R, Oikawa T, Kasahara S, Takahashi J, Shimokawa H, CHART-2 Investigators (2015) Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure in Japan—report from the CHART studies. Circ J 79:2396–2407CrossRefPubMedGoogle Scholar
  27. 27.
    Miyata S, Sakata Y, Miura M, Yamauchi T, Onose T, Tsuji K, Abe R, Oikawa T, Kasahara S, Sato M, Nochioka K, Shiroto T, Takahashi J, Shimokawa H, On behalf of the CHART-2 investigators (2017) Long-term prognostic impact of the Great East Japan earthquake in patients with cardiovascular disease—report from the CHART-2 Study. J Cardiol 70:286–296CrossRefPubMedGoogle Scholar
  28. 28.
    Takada T, Sakata Y, Miyata S, Takahashi J, Nochioka K, Miura M, Tadaki S, Shimokawa H (2014) Impact of elevated heart rate on clinical outcomes in patients with heart failure with reduced and preserved ejection fraction—a report from the CHART-2 Study. Eur J Heart Fail 16:309–316CrossRefPubMedGoogle Scholar
  29. 29.
    Schou M, Gustafsson F, Corell P, Kistorp CN, Kjaer A, Hildebrandt PR (2007) The relationship between N-terminal pro-brain natriuretic peptide and risk for hospitalization and mortality is curvilinear in patients with chronic heart failure. Am Heart J 154:123–129CrossRefPubMedGoogle Scholar
  30. 30.
    Lemon SC, Roy J, Clark MA, Friedmann PD, Rakowski W (2003) Classification and regression tree analysis in public health: methodological review and comparison with logistic regression. Ann Behav Med 26:172–181CrossRefPubMedGoogle Scholar
  31. 31.
    R Core Team (2016) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. https://www.R-project.org/
  32. 32.
    Iwanaga Y, Nishi I, Furuichi S, Noguchi T, Sase K, Kihara Y, Goto Y, Nonogi H (2006) B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: comparison between systolic and diastolic heart failure. J Am Coll Cardiol 47:742–748CrossRefPubMedGoogle Scholar
  33. 33.
    van Veldhuisen DJ, Linssen GC, Jaarsma T, van Gilst WH, Hoes AW, Tijssen JG, Paulus WJ, Voors AA, Hillege HL (2013) B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J Am Coll Cardiol 61:1498–1506CrossRefPubMedGoogle Scholar
  34. 34.
    Yasue H, Yoshimura M, Sumida H, Kikuta K, Kugiyama K, Jougasaki M, Ogawa H, Okumura K, Mukoyama M, Nakao K (1994) Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90:195–203CrossRefPubMedGoogle Scholar
  35. 35.
    Bermingham M, O’Callaghan E, Dawkins I, Miwa S, Samsudin S, McDonald K, Ledwidge M (2011) Are beta2-agonists responsible for increased mortality in heart failure? Eur J Heart Fail 13:885–891CrossRefPubMedGoogle Scholar
  36. 36.
    Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350:655–663CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Shintaro Kasahara
    • 1
  • Yasuhiko Sakata
    • 1
  • Kotaro Nochioka
    • 1
  • Takeshi Yamauchi
    • 1
  • Takeo Onose
    • 1
  • Kanako Tsuji
    • 1
  • Ruri Abe
    • 1
  • Takuya Oikawa
    • 1
  • Masayuki Sato
    • 1
  • Hajime Aoyanagi
    • 1
  • Masanobu Miura
    • 1
  • Takashi Shiroto
    • 1
  • Jun Takahashi
    • 1
  • Satoshi Miyata
    • 2
  • Hiroaki Shimokawa
    • 1
    • 2
  • On behalf of the CHART-2 Investigators
  1. 1.Department of Cardiovascular MedicineTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of Evidence-Based Cardiovascular MedicineTohoku University Graduate School of MedicineSendaiJapan

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