Abstract 8198: Serum Heat Shock Protein 60 Level Predicts Cardiac Events in Chronic Heart Failure Patients with Preserved Left Ventricular Systolic Function

Abstract

Background: More than 40% of patients hospitalized with chronic heart failure (CHF) have preserved left ventricular ejection fraction (LVEF) and are at high risk for cardiac events. Heat shock protein 60 (Hsp60) are induced by a variety of stressors including infection, anoxia, oxidative stress, and inflammation and have a protective role against stress-induced cardiomyocyte injury. Recently, it has been reported that Hsp60 exists in the circulation and serum Hsp60 levels are positively associated with serum TNF-α level, interleukin-6 level, and an important proinflammatory cytokines. CHF is characterized by systemic abnormalities and the myocardium is continually exposed to various stressors, such as anoxia, ischemia, inflammation, and free radicals. We have been reported that serum Hsp60 level was related to severity of CHF and associated with a high risk for adverse cardiac events in CHF patients. The purpose of this study was to examine whether Hsp60 is useful to determine the prognosis of CHF patients with preserved LVEF. Methods and Results: Serum Hsp60 level was measured in 141 CHF patients with preserved LVEF and 62 control subjects by the competitive enzyme-linked immunosorbent assay. Patients were prospectively followed with endpoints of cardiac death or re-hospitalization for worsening CHF during a median follow-up period of 786 days. Serum Hsp60 level was increased with advancing NYHA functional class (P < 0.0001). There were 45 cardiac events during follow-up period (31%). Serum Hsp60 level was significantly higher in patients with cardiac events than those in event free patients. Kaplan-Meier analysis clearly demonstrated that the high Hsp60 group had a significantly higher incidence of cardiac events than the low Hsp60 group (P < 0.0001). Patients were divided into 3 groups based upon Hsp60 level, and the highest 3 rd tertile was associated with the highest risk of cardiac events (6.27-fold compared to the 1 st tertile). In the multivariate Cox analysis, Hsp60 level was an independent risk factor for cardiac events (hazard ratio 3.51, 95% confidence interval 1.46-5.01, P = 0.0031). Conclusion: Serum Hsp60 level is an independent and powerful prognostic factor and may be useful for risk stratification of CHF patients with preserved LVEF.