title: Combination of Flow-Mediated Vasodilation and Nitroglycerine-Induced Vasodilation Is More Effective for Prediction of Cardiovascular Events.
abstract: Measurement of nitroglycerine-induced vasodilation has been performed to differentiate endothelium-dependent vasodilation from endothelium-independent vasodilation as a control test for flow-mediated vasodilation (FMD). Recently, nitroglycerine-induced vasodilation per se has been reported to be a useful marker of the grade of atherosclerosis. The present study aimed to evaluate the prognostic value of FMD combined with nitroglycerine-induced vasodilation for future cardiovascular events. We measured FMD and nitroglycerine-induced vasodilation in 402 subjects, including patients with cardiovascular diseases. During a median follow-up period of 32.3 months, 38 first major cardiovascular events (death from cardiovascular causes, acute myocardial infarction, stroke, and coronary revascularization) occurred. Receiver-operator characteristic curve analysis revealed that FMD alone and nitroglycerine-induced vasodilation alone can predict cardiovascular events with areas under the curve of 0.671 (cutoff 3.3%) and 0.692 (cutoff 11.6%), respectively. FMD combined with nitroglycerine-induced vasodilation predicts cardiovascular events with an area under the curve of 0.701. After adjustment for age, sex, and cardiovascular risk factors, above cutoff FMD (≥3.3%) and below cutoff nitroglycerine-induced vasodilation (<11.6%; hazard ratio, 5.55; 95% confidence interval, 1.61-25.46;P=0.006) and below cutoff FMD (<3.3%) and below cutoff nitroglycerine-induced vasodilation (<11.6%; hazard ratio, 7.20; 95% confidence interval, 2.37-31.36;P<0.001) remained strong independent indicator of cardiovascular events. These findings suggest that the combination of FMD and nitroglycerine-induced vasodilation measurements can more accurately predict cardiovascular events compared with FMD alone.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: UMIN000001167.
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Masato
authors.initials: M
authors.lastname: Kajikawa
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruhashi
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Eisuke
authors.initials: E
authors.lastname: Hida
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Akimichi
authors.initials: A
authors.lastname: Iwamoto
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Nozomu
authors.initials: N
authors.lastname: Oda
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Shinji
authors.initials: S
authors.lastname: Kishimoto
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Shogo
authors.initials: S
authors.lastname: Matsui
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hidaka
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Aibara
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.).
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.affiliation: From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (M.K., Y.A., A.N., Y.H.), Global Career Design Center (M.K.), Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences (T. Maruhashi., Y.I., T. Matsumoto., A.I., N.O., S.K., S.M., T.H., Y.K.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Center for Integrated Medical Research (E.H.) and Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research (K.N., Y.H.), Hiroshima University Hospital, Hiroshima, Japan; and Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan (C.G.). yhigashi@hiroshima-u.ac.jp.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000175:diagnosis* / Q000188:drug therapy; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D005996:Nitroglycerin
keywords: atherosclerosis; biomarkers; cardiovascular diseases; endothelium; myocardial infarction