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Association of cardiovascular disease risk and changes in renin levels by mineralocorticoid receptor antagonists in patients with primary aldosteronism

Hypertension Research volume 45, pages 1476–1485 (2022)Cite this article

A Comment to this article was published on 14 July 2022

Abstract

A recent report stated that patients with primary aldosteronism who remain renin suppressed during mineralocorticoid receptor antagonist treatment might have a higher risk of developing cardiovascular disease than those with unsuppressed renin activity. We retrospectively investigated the incidence of composite cardiovascular disease and risk factors for cardiovascular disease in 1115 Japanese patients with primary aldosteronism treated with mineralocorticoid receptor antagonists. The median follow-up period was 3.0 years, and the incidence of cardiovascular events was very low (2.1%) throughout 5 years of follow-up. Changes in plasma renin activity from before to after mineralocorticoid receptor antagonist treatment were divided into three groups based on tertile, low, intermediate, and high plasma renin activity change groups, with incidences of cardiovascular disease events of 2.1%, 0.5%, and 3.7%, respectively. Multivariate Cox regression analysis revealed age (adjusted hazard ratio, 1.07; 95% confidence interval, [1.02–1.12]) and body mass index (adjusted hazard ratio, 1.13 [1.04–1.23]) as independent risk factors for cardiovascular disease. The high plasma renin activity change group had significantly higher cardiovascular disease risk with mineralocorticoid receptor antagonist treatment than the intermediate plasma renin activity change group (adjusted hazard ratio, 5.71 [1.28–25.5]). These data suggest that a high change in renin level after mineralocorticoid receptor antagonist treatment may not necessarily predict a better prognosis of cardiovascular disease in patients with primary aldosteronism.

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Acknowledgements

This study was conducted as part of the JPAS and JRAS by a Research Grant from the Japan Agency for Medical Research and Development (AMED) [grant number JP17ek0109122 and JP20ek0109352] and the National Center for Global Health and Medicine, Japan [grant number 27–1402, 30–1008]. This study was partly supported by the Research Committee on Disorders of Adrenal Hormones, a Grant-in-Aid from the Ministry of Health, Labor, and Welfare of Japan (Nanjiseisikkanseisakukenkyujigyo [grant number 20FC1020]).

JPAS/JRAS Study Group

Hisashi Fukuda25, Yasushi Tanaka26, Yoshiyu Takeda27, Hironobu Umakoshi28, Yui Shibayama29, Takanobu Yoshimoto30, Junji Kawashima31, Katsutoshi Takahashi32, Megumi Fujita33, Minemori Watanabe34, Yuichi Matsuda35, Hirotaka Shibata36, Kohei Kamemura37, Yuichi Fujii38, Hiromi Rakugi39, Atsushi Ogo40, Shintaro Okamura41, Shozo Miyauchi42, Toshihiko Yanase43, Takashi Kawamura44, Tomikazu Fukuoka45, Tatsuya Kai46, Yuichiro Yoshikawa47, Shigeatsu Hashimoto48, Masanobu Yamada49, Ryuichi Sakamoto50, Chiba Yoshiro51

Author information

Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Nephrology, School of Medicine Keio University, Tokyo, Japan

    Motoko Nomura, Isao Kurihara & Hiroshi Itoh

  2. Department of Medical Education, National Defense Medical College, Tokorozawa, Japan

    Isao Kurihara

  3. Department of Endocrinology and Metabolism, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan

    Takamasa Ichijo

  4. Division of Metabolism and Endocrinology, Department of Internal Medicine, St Marianna University School Yokohama City Seibu Hospital, Yokohama, Japan

    Takuyuki Katabami

  5. Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Mika Tsuiki

  6. Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

    Norio Wada

  7. Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

    Takashi Yoneda

  8. Division of Metabolism and Endocrinology, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan

    Masakatsu Sone

  9. Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Kenji Oki

  10. Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Tetsuya Yamada

  11. Division of Nephrology, Hypertension, and Endocrinology, Nihon University School of Medicine, Tokyo, Japan

    Hiroki Kobayashi

  12. Department of Medical Science and Cardiovascular Medicine, Yokohama City University Graduate School of Medicine, Kanagawa, Japan

    Kouichi Tamura

  13. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yoshihiro Ogawa

  14. Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Nobuya Inagaki

  15. Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    Koichi Yamamoto

  16. Department of Endocrinology, Tokyo Women’s Medical University, Tokyo, Japan

    Michio Otsuki

  17. Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    Michio Otsuki

  18. Department of Diabetes, Endocrinology and Metabolism, Gifu University Graduate School of Medicine, Gifu, Japan

    Daisuke Yabe

  19. Division of Endocrinology and Metabolism, Tottori University Faculty of Medicine, Yonago, Japan

    Shoichiro Izawa

  20. Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Japan

    Yutaka Takahashi

  21. Department of Public Health, International University of Health and Welfare School of Medicine, Chiba, Japan

    Tomoko Suzuki

  22. Clinical Research Center, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Akihiro Yasoda & Mitsuhide Naruse

  23. Division of Endocrinology, National Center for Global Health and Medicine, Tokyo, Japan

    Akiyo Tanabe

  24. Endocrine Center, Ijinkai Takeda General Hospital, Kyoto, Japan

    Mitsuhide Naruse

  25. Division of Metabolism and Endocrinology, Department of Internal Medicine, St Marianna University School Yokohama City Seibu Hospital, Yokohama, Japan

    Hisashi Fukuda

  26. Division of Metabolism and Endocrinology, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan

    Yasushi Tanaka

  27. Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

    Yoshiyu Takeda

  28. Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Hironobu Umakoshi

  29. Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

    Yui Shibayama

  30. Department of Molecular Endocrinology and Metabolism, Tokyo Medical and Dental University, Tokyo, Japan

    Takanobu Yoshimoto

  31. Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Kumamoto, Japan

    Junji Kawashima

  32. Division of Metabolism, Showa General Hospital, Tokyo, Japan

    Katsutoshi Takahashi

  33. Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan

    Megumi Fujita

  34. Department of Endocrinology and Diabetes, Okazaki City Hospital, Okazaki, Japan

    Minemori Watanabe

  35. Department of Cardiology, Sanda City Hospital, Sanda, Japan

    Yuichi Matsuda

  36. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan

    Hirotaka Shibata

  37. Department of Cardiology, Akashi Medical Center, Akashi, Japan

    Kohei Kamemura

  38. Department of Cardiology, JR Hiroshima Hospital, Hiroshima, Japan

    Yuichi Fujii

  39. Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    Hiromi Rakugi

  40. Clinical Research Institute, National Hospital Organization Kyusyu Medical Center, Fukuoka, Japan

    Atsushi Ogo

  41. Department of Endocrinology, Tenriyorozu Hospital, Tenri, Nara, Japan

    Shintaro Okamura

  42. Department of Internal Medicine, Uwajima City Hospital, Uwajima, Japan

    Shozo Miyauchi

  43. Department of Endocrinology and Diabetes Mellitus, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

    Toshihiko Yanase

  44. Department of Preventive Services, Kyoto University School of Public Health, Kyoto, Japan

    Takashi Kawamura

  45. Department of Internal Medicine, Matsuyama Red Cross Hospital, Matsuyama, Japan

    Tomikazu Fukuoka

  46. Department of Cardiology, Saiseikai Tondabayashi Hospital, Tondabayashi, Japan

    Tatsuya Kai

  47. Department of Endocrinology and Diabetes Mellitus, Misato Kenwa Hospital, Misato, Japan

    Yuichiro Yoshikawa

  48. Division of Nephrology, Hypertension, Endocrinology, and Diabetology/ Metabolism, Fukushima Medical University Hospital, Fukushima, Japan

    Shigeatsu Hashimoto

  49. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan

    Masanobu Yamada

  50. Department of Diabetes and Endocrinology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan

    Ryuichi Sakamoto

  51. Endovascular Treatment Group, Mito Saiseikai General Hospital, Mito, Japan

    Chiba Yoshiro

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  1. Motoko Nomura
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Consortia

JPAS/JRAS Study Group

  • Hisashi Fukuda
  • , Yasushi Tanaka
  • , Yoshiyu Takeda
  • , Hironobu Umakoshi
  • , Yui Shibayama
  • , Takanobu Yoshimoto
  • , Junji Kawashima
  • , Katsutoshi Takahashi
  • , Megumi Fujita
  • , Minemori Watanabe
  • , Yuichi Matsuda
  • , Hirotaka Shibata
  • , Kohei Kamemura
  • , Yuichi Fujii
  • , Hiromi Rakugi
  • , Atsushi Ogo
  • , Shintaro Okamura
  • , Shozo Miyauchi
  • , Toshihiko Yanase
  • , Takashi Kawamura
  • , Tomikazu Fukuoka
  • , Tatsuya Kai
  • , Yuichiro Yoshikawa
  • , Shigeatsu Hashimoto
  • , Masanobu Yamada
  • , Ryuichi Sakamoto
  •  & Chiba Yoshiro

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Correspondence to Isao Kurihara.

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Nomura, M., Kurihara, I., Itoh, H. et al. Association of cardiovascular disease risk and changes in renin levels by mineralocorticoid receptor antagonists in patients with primary aldosteronism. Hypertens Res 45, 1476–1485 (2022). https://doi.org/10.1038/s41440-022-00960-x

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