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Association of peak expiratory flow rate with clinical outcomes in pulmonary arterial hypertension

Hypertension Research (2026)Cite this article

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease characterized by a progressive increase in pulmonary arterial pressure, leading to right heart failure. In clinical practice, reduced exercise tolerance is commonly observed in patients with PAH. Several studies have identified skeletal muscle abnormalities and muscle weakness as factors contributing to impaired exercise capacity in these patients. Recently, peak expiratory flow rate (PEFR) has been shown to correlate with skeletal muscle mass. Given that PEFR can be easily and noninvasively measured using respiratory function tests, we investigated the relationship between PEFR and prognosis in patients with PAH. We enrolled consecutive untreated patients diagnosed with PAH at Kagoshima University Hospital between July 2005 and July 2024. A total of 85 patients were included and divided into the preserved PEFR group and the reduced PEFR group. There were no significant differences in hemodynamic parameters between the two groups; however, the 6-minute walk distance was significantly shorter (p = 0.0062) in the reduced PEFR group. Kaplan–Meier analysis revealed that the cumulative event-free rate was significantly lower in the reduced PEFR group (Log-rank p = 0.0048). Reduced PEFR was independently associated with poorer outcomes after adjusting for age, plus each of right atrial pressure, cardiac index, and pulmonary vascular resistance. In conclusion, PEFR, a method for measuring skeletal muscle, was associated with poor prognosis in patients with PAH when assessed at the time of diagnosis. PEFR can be easily and repeatedly measured, making it potentially useful for prognostic prediction and exercise rehabilitation in these patients.

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References

  1. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618–731.

    Article  PubMed  Google Scholar 

  2. Bauer R, Dehnert C, Schoene P, Filusch A, Bärtsch P, Borst MM, et al. Skeletal muscle dysfunction in patients with idiopathic pulmonary arterial hypertension. Respir Med. 2007;101:2366–9.

    Article  PubMed  Google Scholar 

  3. Mainguy V, Maltais F, Saey D, Gagnon P, Martel S, Simon M, et al. Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension. Thorax. 2010;65:113–7.

    Article  PubMed  Google Scholar 

  4. Batt J, Ahmed SS, Correa J, Bain A, Granton J. Skeletal muscle dysfunction in idiopathic pulmonary arterial hypertension. Am J Respir Cell Mol Biol. 2014;50:74–86.

    Article  PubMed  Google Scholar 

  5. Pavasini R, Serenelli M, Celis-Morales CA, Gray SR, Izawa KP, Watanabe S, et al. Grip strength predicts cardiac adverse events in patients with cardiac disorders: an individual patient pooled meta-analysis. Heart. 2019;105:834–41.

    Article  PubMed  Google Scholar 

  6. Kamiya K, Hamazaki N, Matsue Y, Mezzani A, Corra U, Matsuzawa R, et al. Gait speed has comparable prognostic capability to six-minute walk distance in older patients with cardiovascular disease. Eur J Prev Cardiol. 2018;25:212–9.

    Article  PubMed  Google Scholar 

  7. Yamashita M, Kamiya K, Matsunaga A, Kitamura T, Hamazaki N, Nozaki K, et al. Low skeletal muscle density combined with muscle dysfunction predicts adverse events after adult cardiovascular surgery. Nutr Metab Cardiovasc Dis. 2021;31:1782–90.

    Article  PubMed  Google Scholar 

  8. Meyer FJ, Borst MM, Zugck C, Kirschke A, Schellberg D, Kübler W, et al. Respiratory muscle dysfunction in congestive heart failure: clinical correlation and prognostic significance. Circulation. 2001;103:2153–8.

    Article  PubMed  Google Scholar 

  9. Kera T, Kawai H, Hirano H, Kojima M, Fujiwara Y, Ihara K, et al. Relationships among peak expiratory flow rate, body composition, physical function, and sarcopenia in community-dwelling older adults. Aging Clin Exp Res. 2018;30:331–40.

    Article  PubMed  Google Scholar 

  10. Park CH, Yi Y, Do JG, Lee YT, Yoon KJ. Relationship between skeletal muscle mass and lung function in Korean adults without clinically apparent lung disease. Medicine. 2018;97:e12281 https://doi.org/10.1097/MD.0000000000012281.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Deniz O, Coteli S, Karatoprak NB, Pence MC, Varan HD, Kizilarslanoglu MC, et al. Diaphragmatic muscle thickness in older people with and without sarcopenia. Aging Clin Exp Res. 2021;33:573–80.

    Article  PubMed  Google Scholar 

  12. Do Y, Lim Y, Kim J, Lee H. Establishing an optimal diagnostic criterion for respiratory sarcopenia using peak expiratory flow rate. Aging Clin Exp Res. 2024;36:116.

    Article  PubMed  PubMed Central  Google Scholar 

  13. The Japanese Circulation Society (JCS), The Japanese Pulmonary Circulation and Pulmonary Hypertension Society (JPCPHS). JCS/JPCPHS 2025 guideline on the management of pulmonary thromboembolism, deep venous thrombosis, and pulmonary hypertension. Tokyo: Japanese Circulation Society; 2025. (in Japanese)

  14. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 2020;21:300–7.

    Article  PubMed  Google Scholar 

  15. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39:412–23.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Delmonico MJ, Harris TB, Lee JS, Visser M, Nevitt M, Kritchevsky SB, et al. Alternative definitions of sarcopenia, lower extremity performance, and functional impairment with aging in older men and women. J Am Geriatr Soc. 2007;55:769–74.

    Article  PubMed  Google Scholar 

  17. Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006;61:1059–64.

    Article  PubMed  Google Scholar 

  18. Tsukioka K, Makino S, Miyamoto T, Tanabe N, Akazawa K. Peak expiratory flow in normal healthy Japanese adults: comparisons with values reported in other races. Allergol Int. 2002;51:101–11.

    Article  Google Scholar 

  19. Sawaya Y, Ishizaka M, Kubo A, Sadakiyo K, Yakabi A, Sato T, et al. Correlation between skeletal muscle mass index and parameters of respiratory function and muscle strength in young healthy adults according to gender. J Phys Ther Sci. 2018;30:1424–7.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Borda MG, Salazar-Londoño S, Lafuente-Sanchis P, Patricio Baldera J, Venegas LC, Tarazona-Santabalbina FJ, et al. Neutrophil-to-lymphocyte ratio and lymphocyte count as an alternative to body mass index for screening malnutrition in older adults living in the community. Eur J Nutr. 2024;63:1889–9.

    Article  PubMed  Google Scholar 

  21. Yamashita M, Kamiya K, Hamazaki N, Nozaki K, Uchida S, Maekawa E, et al. Predictive value of cholinesterase in patients with heart failure: a new blood biochemical marker of undernutrition. Nutr Metab Cardiovasc Dis. 2023;33:1914–22.

    Article  PubMed  Google Scholar 

  22. Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2000;161:487–92.

    Article  PubMed  Google Scholar 

  23. Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation. 2010;122:164–72.

    Article  PubMed  Google Scholar 

  24. Nakashima M, Akagi S, Ejiri K, Nakamura K, Ito H. Impact of malnutrition on prognosis in patients with pulmonary arterial hypertension. Pulm Circ. 2023;13:e12286. https://doi.org/10.1002/pul2.12286.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Luo D, Xie N, Yang Z, Zhang C. Association of nutritional status and mortality risk in patients with primary pulmonary hypertension. Pulm Circ. 2022;12:e12018. https://doi.org/10.1002/pul2.12018.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kubota K, Miyanaga S, Iwatani N, Higo K, Tokushige A, Ikeda Y, et al. Geriatric nutritional risk index is associated with prognosis in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Circ Rep. 2020;2:372–7.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Breda AP, Pereira de Albuquerque AL, Jardim C, Morinaga LK, Suesada MM, Fernandes CJ, et al. Skeletal muscle abnormalities in pulmonary arterial hypertension. PLoS ONE. 2014;9:e114101 https://doi.org/10.1371/journal.pone.0114101.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nakayama M, Konishi M, Sugano T, Okamura M, Gohbara M, Iwata K, et al. Association between sarcopenia and exercise capacity in patients with pulmonary hypertension without left heart disease. Int J Cardiol. 2023;387:131115.

    Article  PubMed  Google Scholar 

  29. Hoeper MM, Pausch C, Grünig E, Klose H, Staehler G, Huscher D, et al. Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry. J Heart Lung Transplant. 2020;39:1435–44.

    Article  PubMed  Google Scholar 

  30. Prokopidis K, Morwani-Mangnani J, McDowell G, Lip GYH, Venturelli M, Sankaranarayanan R, et al. Sarcopenia is linked to higher levels of B type natriuretic peptide and its N-terminal fragment in heart failure: a systematic review and meta-analysis. Eur Geriatr Med. 2024;15:893–901.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kenchaiah S, Pocock SJ, Wang D, Finn PV, Zornoff LA, Skali H, et al. Body mass index and prognosis in patients with chronic heart failure: insights from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. Circulation. 2007;116:627–36.

    Article  PubMed  Google Scholar 

  32. Grünig E, MacKenzie A, Peacock AJ, Eichstaedt CA, Benjamin N, Nechwatal R, et al. Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial. Eur Heart J. 2021;42:2284–95.

    Article  PubMed  Google Scholar 

  33. Sánchez-Milá Z, Abuín-Porras V, Romero-Morales C, Almazán-Polo J, Velázquez Saornil J. Effectiveness of a respiratory rehabilitation program including an inspiration training device versus traditional respiratory rehabilitation: a randomized controlled trial. PeerJ. 2023;11:e16360.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Rashid FA, Anwar W, Kandakurti PK, Al Qawasmeh KHA, Latif MF, Tirmazy SH, et al. Physical rehabilitation program for cardiorespiratory health and quality of life among breast. cancer survivors in UAE: a randomized control trial. BMC Cancer. 2025;16:25–705.

    Google Scholar 

  35. Sanchez H, Bigard X, Veksler V, Mettauer B, Lampert E, Lonsdorfer J, et al. Immunosuppressive treatment affects cardiac and skeletal muscle mitochondria by the toxic effect of vehicle. J Mol Cell Cardiol. 2000;32:323–31.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

    Kokoro Mitsuyoshi, Kayoko Kubota, Sunao Miyanaga, Mitsumasa Akao & Mitsuru Ohishi

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  1. Kokoro Mitsuyoshi
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  2. Kayoko Kubota
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  3. Sunao Miyanaga
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Correspondence to Kayoko Kubota.

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Mitsuyoshi, K., Kubota, K., Miyanaga, S. et al. Association of peak expiratory flow rate with clinical outcomes in pulmonary arterial hypertension. Hypertens Res (2026). https://doi.org/10.1038/s41440-025-02511-6

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