title: Rho-associated kinase activity is a predictor of cardiovascular outcomes.
abstract: Cardiovascular diseases are associated with chronic activation of Rho-associated kinase. Rho-associated kinase activity is significantly correlated with endothelial function and Framingham risk score. However, there is no information on the prognostic value of Rho-associated kinase activity. We evaluated Rho-associated kinase activity in peripheral leukocytes by Western blot analysis in 633 subjects who underwent health-screening examination at Hiroshima University Hospital. We assessed the associations between Rho-associated kinase activity and first major cardiovascular events (death from cardiovascular causes, myocardial infarction, and stroke), death from cardiovascular causes, acute myocardial infarction, stroke, revascularization (percutaneous coronary intervention, coronary artery bypass grafting), and hospitalization for heart failure. During a median period of 42.0 months (interquartile range, 24.4-56.6 months) of follow-up, 29 subjects died (10 from cardiovascular causes), 2 myocardial infarction, 20 revascularization, 15 stroke, and 17 hospitalization for heart failure. After adjustment for age, sex, cardiovascular risk factors, and other relevant variables, Rho-associated kinase activity remained a strong independent indicator of first major cardiovascular events (hazard ratio, 2.19; 95% confidence interval, 1.35-3.70; P=0.002), death from cardiovascular disease (hazard ratio, 2.57; 95% confidence interval, 1.18-6.60; P=0.002), stroke (hazard ratio, 2.14; 95% confidence interval, 1.24-3.86; P=0.006), and revascularization (hazard ratio, 2.68; 95% confidence interval, 1.60-4.66; P<0.001). Leukocyte Rho-associated kinase activity may be a new biomarker of cardiovascular events. These findings suggest that inhibition of Rho-associated kinase activity may be a therapeutic target for prevention of cardiovascular events.
authors.affiliation: Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. yhigashi@hiroshima-u.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruhashi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Mikami
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Akimichi
authors.initials: A
authors.lastname: Iwamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hidaka
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications* / Q000175:diagnosis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D054460:rho-Associated Kinases / Q000097:blood*
chemical_list: D015415:Biomarkers; D054460:rho-Associated Kinases
keywords: Rho-associated kinase; atherosclerosis; biological markers; cardiovascular events; cardiovascular risk factors