Abstract 9894: Rho-associated Kinase Activity and Cardiovascular Disease Prediction
Background: 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, but there is no information on the prognostic value on Rho-associated kinase activity.
Methods: 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.
Results: During a median period of 42.0 months (interquartile range, 24.4 to 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 percent confidence interval, 1.35 to 3.70; P=0.002), death from cardiovascular disease (hazard ratio, 2.57; 95 percent confidence interval, 1.18 to 6.60; P=0.002), stroke (hazard ratio, 2.14; 95 percent confidence interval, 1.24 to 3.86; P=0.006) and revascularization (hazard ratio, 2.68; 95 percent confidence interval, 1.60 to 4.66; P<0.001).
Conclusions: Leukocyte Rho-associated kinase activity may be a new biomarker of cardiovascular events. These findings suggest that inhibition of leukocyte Rho-associated kinase activity may be a therapeutic target for prevention of cardiovascular events.
- © 2013 by American Heart Association, Inc.