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Predictors of confirmatory test results for the diagnosis of primary hyperaldosteronism in hypertensive patients with an aldosterone-to-renin ratio greater than 20. The SHRIMP study

Abstract

It remains unknown which surrogate markers can predict diagnostic test results for primary hyperaldosteronism (PA). The Secondary Hypertension Registry Investigation in Mie Prefecture (SHRIMP) study has sequentially and prospectively recruited 128 patients with hypertension with an aldosterone-to-renin ratio (ARR) greater than 20, evaluated the differences among essential hypertension (EHT), idiopathic hyperaldosteronism (IHA), and aldosterone-producing adenoma (APA), and analyzed the predictors for the confirmatory tests. The patients underwent saline-loading, captopril-challenge, and upright furosemide-loading tests. Carotid, renovascular, and cardiac echography, brachial ankle pulse wave velocity (baPWV), endothelial function, nocturnal blood pressure decline, and the apnea hypopnea index were evaluated. Multivariate regression analyses showed that the plasma aldosterone concentration (PAC) at screening was a strong predictor of the saline and captopril test results. The plasma renin activity (PRA) at screening, urine β2-microglobulin, and left ventricular mass index (LVMI) were independent predictors for the captopril test. The estimated saline PAC and captopril 60 and 90 min ARRs predicted by the equations were highly correlated with the real values. The ROC curve analysis showed PAC at screening among each of predictors for the diagnostic tests and PAC after the saline-loading test had the highest diagnostic abilities of APA. Patients with IHA were older and had glucose intolerance and increased U-Alb/gCre and resistive indices. In patients with APA, the levels of U-Alb/gCre and urine β2-microglobulin were increased, and levels of insulin and the HOMA-IR were decreased. In conclusion, our proposed equations may be useful for estimating saline PAC and captopril ARR. Diagnostic predictors may differ for each confirmatory test.

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Acknowledgments

The authors thank Masumi Matsuda, Hidetomo Onuma, Hitomi Kurata, and Mayumi Furlong for their excellent technical assistance.

Funding

This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 24591113 to R.O.), the Japan Vascular Disease Research Foundation, the Mie Medical Foundation, and the Okasan-Kato Foundation (to R.O.).

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Correspondence to Ryuji Okamoto.

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Conflict of interest

The Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, received research grants from Bristol-Myers Squibb, MSD K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo Pharmaceutical Co., Ltd., Genzyme Japan, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Corporation, Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., and Boehringer Ingelheim Co., Ltd. Masaaki Ito received lecture fees from Daiichi Sankyo Co. Pharmaceutical Co., Ltd., Mitsubishi Tanabe Corporation, Bayer Yakuhin, Ltd. and Takeda Pharmaceutical Co., Ltd.

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Appendix

Appendix

The complete list of SHRIMP Study Investigators is as follows: Ryuji Okamoto, MD; Masaya Taniguchi, MD; Yuki Onishi, MD; Naoto Kumagai, MD; Junji Uraki, MD; Naoki Fujimoto, MD; Yasuhiro Hotta, MD; Ken Sasaki, MD; Noriko Furuta, MD; Eitato Fujii, MD; Yutaka Yano, MD; Norikazu Yamada, MD; Toru Ogura, PhD; Yoshiyuki Takei, MD; Hajime Sakuma, MD; Masaaki Ito, MD; Kaoru Dohi, MD; Kazuhito Eguchi, MD; Satoshi Fujita, MD; Shusuke Fukuoka, MD; Tomoyuki Fukuma, MD; Itaru Goto, MD; Rei Hashimoto, MD; Chisa Inoue, MD; Ryoichi Ishisu, MD; Junko Ishiura, MD; Masaki Ishiyama, MD; Yoshihiko Kagawa, MD; Kentaro Kakuta, MD; Akemi Kida, MD; Katsuhisa Konishi, MD; Manabu Kato, MD; Rikiya Kawarada, MD; Tairo Kurita, MD; Kanako Maki, MD; Akimasa Matsuda, MD; Hiroshi Matsuo, MD; Hana Mizutani, MD; Tatsuya Mori, MD; Keishi Moriwaki, MD; Yuki Muneyoshi, MD; Hiroshi Nakajima, MD; Shiro Nakamori, MD; Mashio Nakamura, MD; Tomoyuki Nakata, MD; Atsuhiro Nakatsuka, MD; Hitoshi Nakaya, MD; Kota Nishihama, MD; Shinya Okamoto, MD; Yuko Okano, MD; Yoshito Ogihara, MD; Taku Omori, MD; Masako Sakamoto, MD; Takeshi Sasaki, MD; Kei Sato, MD; Yuichi Sato, MD; Toshiki Sawai, MD Yoshiki Sugimura, MD; Yuichi Sugino, MD; Emiyo Sugiura, MD; Shinya Sugiura, MD; Toshinari Suzuki, MD; Yasuo Suzuki, MD; Takeo Takahashi, MD; Atsuro Takeshita, MD; Te-tsushiro Takeuchi, MD; Yasuyuki Tamai, MD; Muneyoshi Tanimura, MD; Yuji Ueda, MD; Mei Uemura, MD; Takashi Yamanaka, MD; Kiyotaka Watanabe, MD; and Taro Yasuma, MD.

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Okamoto, R., Taniguchi, M., Onishi, Y. et al. Predictors of confirmatory test results for the diagnosis of primary hyperaldosteronism in hypertensive patients with an aldosterone-to-renin ratio greater than 20. The SHRIMP study. Hypertens Res 42, 40–51 (2019). https://doi.org/10.1038/s41440-018-0126-1

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  • DOI: https://doi.org/10.1038/s41440-018-0126-1

Keywords

  • Primary aldosteronism
  • Hypertension
  • Aldosterone
  • Renin
  • Blood pressure

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