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Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease

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Abstract

Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by 15O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48 pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592–0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961 pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75–25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.

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Funding

This study was supported in part by a KAKENHI grant-in-aid for Scientific Research (#16K10264) from the Japan Society for the Promotion of Science (to M.N.) and funding from the Takeda Science Foundation (to M.N.).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, 060-8638, Japan

    Masanao Naya, Tadao Aikawa, Masahiko Obara & Kazuhiro Koyanagawa

  2. Department of Radiology, Saitama Medical Center, Jichi Medical University, Saitama, Japan

    Osamu Manabe

  3. Department of Biomedical Science and Engineering, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan

    Chietsugu Katoh

  4. Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Nagara Tamaki

Authors
  1. Masanao Naya
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  2. Tadao Aikawa
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  3. Osamu Manabe
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  4. Masahiko Obara
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  5. Kazuhiro Koyanagawa
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  6. Chietsugu Katoh
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  7. Nagara Tamaki
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Correspondence to Masanao Naya.

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Naya, M., Aikawa, T., Manabe, O. et al. Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease. Heart Vessels 36, 917–923 (2021). https://doi.org/10.1007/s00380-020-01767-x

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  • DOI: https://doi.org/10.1007/s00380-020-01767-x

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