Rho-associated kinase activity is an independent predictor of cardiovascular events in acute coronary syndrome.
Rho-associated kinases play an important role in a variety of cellular functions. Although Rho-associated kinase activity has been shown to be an independent predictor for future cardiovascular events in a general population, there is no information on Rho-associated kinase activity in patients with acute coronary syndrome. We evaluated leukocyte Rho-associated kinase activity by Western blot analysis in 73 patients with acute coronary syndrome and 73 age- and gender-matched control subjects. Rho-associated kinase activity within 2 hours of acute coronary syndrome onset was higher in patients with acute coronary syndrome than in the control subjects (0.95±0.55 versus 0.69±0.31; P<0.001). Rho-associated kinase activity promptly increased from 0.95±0.55 to 1.11±0.81 after 3 hours and reached a peak of 1.21±0.76 after 1 day (P=0.03 and P=0.03, respectively) and then gradually decreased to 0.83±0.52 after 7 days, 0.78±0.42 after 14 days, and 0.72±0.30 after 6 months (P=0.22, P=0.29, and P=0.12, respectively). During a median follow-up period of 50.8 months, 31 first major cardiovascular events (death from cardiovascular causes, myocardial infarction, ischemic stroke, and coronary revascularization) occurred. After adjustment for age, sex, cardiovascular risk factors, and concomitant treatment with statins, increased Rho-associated kinase activity was associated with increasing risk of first major cardiovascular events (hazard ratio, 4.56; 95% confidence interval, 1.98-11.34; P<0.001). These findings suggest that Rho-associated kinase activity is dramatically changed after acute coronary syndrome and that Rho-associated kinase activity could be a useful biomarker to predict cardiovascular events in Japanese patients with acute coronary syndrome.
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Masato
M
Kajikawa
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Kensuke
K
Noma
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Ayumu
A
Nakashima
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Tatsuya
T
Maruhashi
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Yumiko
Y
Iwamoto
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Takeshi
T
Matsumoto
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Akimichi
A
Iwamoto
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Nozomu
N
Oda
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Takayuki
T
Hidaka
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Yasuki
Y
Kihara
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Yoshiki
Y
Aibara
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Kazuaki
K
Chayama
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Shota
S
Sasaki
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Masaya
M
Kato
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Keigo
K
Dote
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Chikara
C
Goto
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
James K
JK
Liao
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), 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; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.). yhigashi@hiroshima-u.ac.jp.
Yukihito
Y
Higashi
D054058:Acute Coronary Syndrome / Q000150:complications / Q000201:enzymology*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000453:epidemiology* / Q000209:etiology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000453:epidemiology* / Q000209:etiology; D013997:Time Factors; D054460:rho-Associated Kinases / Q000097:blood*
D015415:Biomarkers; D054460:rho-Associated Kinases
acute coronary syndrome; biological markers; cardiovascular diseases; myocardial infarction; stroke