P403Byproducts of oxidative stress in cardiac remodeling in patients with chronic heart failure


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Abstract

Purpose: Serum uric acid levels (a surrogate marker of xantine oxidase activity) and gamma-glutamyl transferase (GGT) activity emerged as predictors of mortality in patients with ischemic chronic heart failure (CHF), but precise mechanisms of this effect remain unclear. We addressed the role of these enzymatic sources of free radicals as well as markers of oxidative lipid or protein damage and antioxidant enzyme activities in the development of left ventricle remodeling in CHF. We also sought to determine prognostic significance of oxidative stress markers in CHF patients in relation to new cardiac events or survival.Methods: We enrolled 120 consecutive patients with varying CHF according to New York Heart Association classification (NYHA) and 69 controls. Serum uric acid levels and GGT activity as well as plasma malondialdehyde (MDA), protein thiol (P-SH) and reactive carbonyl groups (RCD), together with glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined spectrophotometrically and/or by ELISA methods and correlated with echocardiographic indices of remodeling.Results: Levels of uric acid and GGT activity gradually increased with degree of CHF progression. Patients with severe CHF (NYHA III/IV) exhibited elevated MDA and RCD levels and decreased P-SH groups when compared to asymptomatic patients (NYHA I/II) or controls. Oxidative stress in severe patients was associated with significant fall in plasma GSH-Px activity. Regarding remodeling, the main effect observed in all patients, was significant correlation of serum GGT and uric acid levels with changes in endsystolic left ventricle diameter (r=0.356 and r=0.364, respectively, p=0.001) and volume (r=0.334 and r=0.326, respectively, p=0.001). Correlation also existed between RCD or MDA levels and remodeling indices, but only in severe disease. Cox analysis revealed that MDA was independent predictor of survival (OR=3.18, p=0.002), while P-SH groups were independent predictor of adverse cardiac events (OR =3.13, p=0.003).Conclusion: Elevated free radical production mediated by xantine oxidase and GGT plays significant role in the development of CHF remodeling. Down-regulated antioxidant enzymes in severe disease enhance oxidative stress, which becomes important in further deterioration of left ventricular structure. Plasma MDA and P-SH groups should be considered for monitoring of CHF patients due to their prognostic significance in cardiac events and survival.

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