Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD-J (Flow-Mediated Dilation Japan) Study A

Tatsuya Maruhashi; Junko Soga; Noritaka Fujimura; Naomi Idei; Shinsuke Mikami; Yumiko Iwamoto; Akimichi Iwamoto; Masato Kajikawa; Takeshi Matsumoto; Nozomu Oda; Shinji Kishimoto; Shogo Matsui; Haruki Hashimoto; Yoshiki Aibara; Farina Mohamad Yusoff; Takayuki Hidaka; Yasuki Kihara; Kazuaki Chayama; Kensuke Noma; Ayumu Nakashima; Chikara Goto; Hirofumi Tomiyama; Bonpei Takase; Takahide Kohro; Toru Suzuki; Tomoko Ishizu; Shinichiro Ueda; Tsutomu Yamazaki; Tomoo Furumoto; Kazuomi Kario; Teruo Inoue; Shinji Koba; Kentaro Watanabe; Yasuhiko Takemoto; Takuzo Hano; Masataka Sata; Yutaka Ishibashi; Koichi Node; Koji Maemura; Yusuke Ohya; Taiji Furukawa; Hiroshi Ito; Hisao Ikeda; Akira Yamashina; Yukihito Higashi

doi:10.1161/JAHA.118.008588

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD-J (Flow-Mediated Dilation Japan) Study A

J Am Heart Assoc. 2018 Jul 12;7(14):e008588. doi: 10.1161/JAHA.118.008588.

Authors

Tatsuya Maruhashi¹, Junko Soga¹, Noritaka Fujimura¹, Naomi Idei¹, Shinsuke Mikami¹, Yumiko Iwamoto¹, Akimichi Iwamoto¹, Masato Kajikawa¹, Takeshi Matsumoto¹, Nozomu Oda¹, Shinji Kishimoto¹, Shogo Matsui¹, Haruki Hashimoto¹, Yoshiki Aibara², Farina Mohamad Yusoff², Takayuki Hidaka¹, Yasuki Kihara¹, Kazuaki Chayama³, Kensuke Noma^{2

4}, Ayumu Nakashima⁴, Chikara Goto⁵, Hirofumi Tomiyama⁶, Bonpei Takase⁷, Takahide Kohro⁶, Toru Suzuki⁸, Tomoko Ishizu⁹, Shinichiro Ueda¹⁰, Tsutomu Yamazaki¹¹, Tomoo Furumoto¹², Kazuomi Kario¹³, Teruo Inoue¹⁴, Shinji Koba¹⁵, Kentaro Watanabe¹⁶, Yasuhiko Takemoto¹⁷, Takuzo Hano¹⁸, Masataka Sata¹⁹, Yutaka Ishibashi²⁰, Koichi Node²¹, Koji Maemura²², Yusuke Ohya²³, Taiji Furukawa²⁴, Hiroshi Ito²⁵, Hisao Ikeda²⁶, Akira Yamashina⁶, Yukihito Higashi^{27

4}

Affiliations

¹ Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
³ Department of Gastroenterology and Metabolism, Biomedical Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁴ Division of Regeneration and Medicine, Hiroshima University Hospital, Hiroshima, Japan.
⁵ Hiroshima International University, Hiroshima, Japan.
⁶ Department of Cardiology, Tokyo Medical University, Tokyo, Japan.
⁷ Division of Biomedical Engineering, National Defense Medical College Research Institute, Tokorozawa, Japan.
⁸ Cardiovascular Medicine, University of Leicester, United Kingdom.
⁹ Cardiovascular Division, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
¹⁰ Department of Clinical Pharmacology and Therapeutics, University of the Ryukyu School of Medicine, Okinawa, Japan.
¹¹ Clinical Research Support Center, Faculty of Medicine, The University of Tokyo, Japan.
¹² Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
¹³ Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Tochigi, Japan.
¹⁴ Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan.
¹⁵ Department of Medicine, Division of Cardiology, Showa University School of Medicine, Tokyo, Japan.
¹⁶ Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology (DNHMED), Yamagata University School of Medicine, Yamagata, Japan.
¹⁷ Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
¹⁸ Department of Medical Education and Population-Based Medicine, Postgraduate School of Medicine, Wakayama Medical University, Wakayama, Japan.
¹⁹ Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
²⁰ Department of General Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
²¹ Department of Cardiovascular and Renal Medicine, Saga University, Saga, Japan.
²² Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
²³ The Third Department of Internal Medicine, University of the Ryukyus, Okinawa, Japan.
²⁴ Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
²⁵ Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
²⁶ Faculty of Fukuoka Medical Technology, Teikyo University, Omuta, Japan.
²⁷ Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan yhigashi@hiroshima-u.ac.jp.

Abstract

Background: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known.

Methods and results: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed.

Conclusions: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification.

Clinical trial registration: URL: www.umin.ac.jp. Unique identifier: UMIN000012950.

Keywords: arterial stiffness; coronary artery disease; endothelial function; flow‐induced dilation; pulse wave velocity.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Brachial Artery / diagnostic imaging
Cardiovascular Diseases
Coronary Artery Disease / epidemiology
Coronary Artery Disease / physiopathology*
Death, Sudden, Cardiac / epidemiology*
Endothelium, Vascular / physiopathology
Female
Heart Failure / epidemiology*
Humans
Japan / epidemiology
Male
Middle Aged
Prognosis
Proportional Hazards Models
Prospective Studies
Pulse Wave Analysis
Risk Assessment
Stroke / epidemiology*
Vascular Stiffness / physiology*
Vasodilation