Abstract 14056: Prognostic Impact of Rho-kinase Activity in Circulating Leukocytes of Patients with Vasospastic Angina

Abstract

Background: Rho-kinase plays a central role in the pathogenesis of coronary artery spasm. We have recently demonstrated that Rho-kinase activity in circulating leukocytes is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). However, its prognostic impact in VSA patients remains to be examined. Methods: We prospectively enrolled 174 consecutive VSA patients (M/F 116/58, 62±12 [SD] yrs) and 53 non-VSA patients (M/F 32/21, 62±15 yrs) and followed them for 14±9 months. At the enrollment, Rho-kinase activity in circulating leukocytes (the ratio of phosphorylated/total form of myosin binding subunit, a Rho-kinase substrate) was measured. The primary endpoint was major adverse cardiac events (MACE). Results: Baseline Rho-kinase activity was significantly higher in VSA than in non-VSA patients (1.20±0.33 vs. 1.07±0.21, P<0.01) and all VSA patients were treated with calcium channel blockers. During the follow-up period, MACE occurred in 9 VSA patients (5.2%) but none in non-VSA patients. Baseline Rho-kinase activity was significantly higher in VSA patients with MACE than in those without it (1.33±0.13 vs. 1.20±0.33, P<0.001). Importantly, when we divided VSA patients into 2 groups by a median value of baseline Rho-kinase activity, Kaplan-Meier survival analysis showed a significantly worse prognosis in VSA patients with high Rho-kinase activity (p-MBS/t-MBS ≥1.20) ( Figure ). Univariate linear regression models showed that there was no association between established prognostic factors of VSA (e.g. history of out-of-hospital cardiac arrest, current smoking, angina at rest, significant organic stenosis and β-blocker use) and baseline increased levels of Rho-kinase activity. Conclusions: These results indicate that increased Rho-kinase activity in circulating leukocytes may be a useful and independent biomarker for long-term prognosis of VSA patients.