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.