Reliability of measurement of endothelial function across multiple institutions and establishment of reference values in Japanese.
OBJECTIVE
For the standardization of flow-mediated vasodilatation (FMD) assessment as a clinical tool, validation of its reliability across multiple institutions and the establishment of normal/reference values based on reliable data from multiple institutions are needed.


RESULTS
In Study 1, assessment of FMD (scan recording and analysis) using an ultrasonographic semi-automatic measuring system (sFMD) was conducted at 18 participating institutions (sFMD-INST) (n = 981). All of the brachial arterial scans were also analyzed at a core laboratory (sFMD-COLB). After 111 subjects with inadequate sFMD recordings were excluded (n = 880), the correlation between the sFMD-INST and sFMD-COLB improved from R = 0.725 to R = 0.838 (p < 0.001). In Study 2, based on good-quality sFMD data obtained from 6660 subjects without cardiovascular disease (CVD) and 729 subjects with CVD from 27 institutions, reference values of sFMD are proposed by the Framingham risk score (FRS)-based risk categories and according to gender and age. The receiver-operating characteristic curve analysis revealed a significant power of sFMD values in reference ranges to discriminate between subjects with and without CVD (e.g., area under curve = 0.64 in the FRS-low risk group).


CONCLUSIONS
When the analysis was limited to cases with clear sFMD recordings, the reliability of the sFMD assessment (scan and its analysis) conducted in individual institutions appeared to be acceptable. Reference sFMD values (lower cuff occlusion) for the Japanese population are proposed based on reliable data derived from multiple institutions, and the reference values may identify patients without advanced vascular damage.
Department of Cardiology, Tokyo Medical University, Tokyo, Japan. Electronic address: tomiyama@tokyo-med.ac.jp.
Hirofumi
H
Tomiyama
Department of Clinical Informatics, Jichi Medical University School of Medicine, Tochigi, Japan.
Takahide
T
Kohro
Department of Cardiovascular Physiology and Medicine, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan.
Yukihito
Y
Higashi
Division of Biomedical Engineering, National Defense Medical College Research Institute, Saitama, Japan.
Bonpei
B
Takase
Cardiovascular Medicine, University of Leicester, Leicester, UK.
Toru
T
Suzuki
Cardiovascular Division, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Tomoko
T
Ishizu
Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus School of Medicine, Okinawa, Japan.
Shinichiro
S
Ueda
Department of Clinical Epidemiology and Systems, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Tsutomu
T
Yamazaki
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
Tomoo
T
Furumoto
Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Tochigi, Japan.
Kazuomi
K
Kario
Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan.
Teruo
T
Inoue
Department of Medicine, Division of Cardiology, Showa University School of Medicine, Tokyo, Japan.
Shinji
S
Koba
Department of Neurology, Hematology, Metaboism, Endocrinology and Diabetology (DNHMED), Yamagata University School of Medicine, Yamagata, Japan.
Kentaro
K
Watanabe
Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Yasuhiko
Y
Takemoto
Department of Medical Education and Population-based Medicine, Postgraduate School of Medicine, Wakayama Medical University, Wakayama, Japan.
Takuzo
T
Hano
Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Masataka
M
Sata
Department of General Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
Yutaka
Y
Ishibashi
Department of Cardiovascular and Renal Medicine, Saga University, Saga, Japan.
Koichi
K
Node
Department of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Koji
K
Maemura
The Third Department of Internal Medicine, University of the Ryukyus, Okinawa, Japan.
Yusuke
Y
Ohya
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Taiji
T
Furukawa
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Hiroshi
H
Ito
Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
Hisao
H
Ikeda
Department of Cardiology, Tokyo Medical University, Tokyo, Japan.
Akira
A
Yamashina
D000328:Adult; D000367:Age Factors; D000368:Aged; D044466:Asian People; D050197:Atherosclerosis / Q000175:diagnosis / Q000208:ethnology / Q000503:physiopathology*; D001331:Automation; D001916:Brachial Artery / Q000503:physiopathology*; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012016:Reference Values; D015203:Reproducibility of Results; D014664:Vasodilation
Endothelial function; Reference value; Reliability; Standardization