Associations of GSTM1*0 and GSTA1*A genotypes with the risk of cardiovascular death among hemodialyses patients.

BACKGROUND: The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. METHODS: Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. RESULTS: GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype. CONCLUSIONS: Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention.

Markers of oxidative damage and antioxidant enzyme activities as predictors of morbidity and mortality in patients with chronic heart failure.

BACKGROUND: Although the majority of previous findings unequivocally confirmed the existence of systemic oxidative stress in chronic heart failure (CHF) patients, data on prognostic potential of biomarkers of oxidative lipid and protein damage are limited. We aimed to address the relation of oxidative stress markers to severity and prognosis in CHF secondary to ischemic cardiomyopathy. METHODS AND RESULTS: Plasma malondialdehyde (MDA), protein thiol groups (P-SH), reactive carbonyl derivatives (RCD), together with glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined in 120 CHF patients and 69 healthy controls. Increased lipid peroxidation (MDA) and oxidation of plasma proteins (RCD; P-SH) s well as downregulated GSH-Px activity were found in CHF patients compared with controls. Significant correlation was obtained only for RCD content and remodeling indices (LVEDV: r = 0.469, P = .008; LVESV: r = 0.452; P = .011). Cox regression analysis demonstrated only MDA (HR = 3.33; CI: 1.55-7.12; P = .002) as independent predictor of death, whereas SOD was associated with unstable angina pectoris (HR = 2.09; CI: 1.16-3.78; P = .011). CONCLUSIONS: In the course of CHF progression, carbonyl stress is implicated in the LV remodeling. Malondialdehyde level might be a useful parameter for monitoring and planning management of CHF patients.

Are all criteria of metabolic syndrome equally harmful?

OBJECTIVE: The metabolic syndrome (MS) is associated with subclinical damage of different organs.The aim of this study was to determine which risk factors of MS were independently associated with left ventricular structure and function (diastolic and global). METHODS: The study included 204 subjects with MS and 88 control subjects with no risk factors. The metabolic syndrome was defined by the presence of three or more of ATP-NCEP III criteria. All subjects underwent laboratory blood tests, and complete two-dimensional echocardiography which also included tissue Doppler. The echocardiography was used to assess left ventricular (LV) structure (LVmass/Ht2.7), systolic (LVEF, Ssepptal, Slateral) and diastolic function, by pulse-wave Doppler (E/A ratio) and tissue Doppler imaging (E/e'average), and global function (Tei index). Appropriate time intervals for the estimation of the Tei index were obtained by tissue Doppler. RESULTS: The LV mass index, E/e'average and Tei index were significantly higher in the MS group, whereas there was no difference in LV systolic function. Multiple regression analysis showed that LVmass/Ht2 was independently associated with systolic blood pressure (beta = 0.41, P < 0.001) and waist circumference (beta = 0.22, P = 0.016).The same analysis revealed that E/e'verage was independently associated with systolic blood pressure (3 = 0.35, P < 0.001), waist circumference (beta = 0.24,P = 0.004) and triglycerides level (3 = 0.21,P = 0.012); while theTei index was independently associated with systolic blood pressure (beta = 0.42, P < 0.001) and fasting glucose (beta = 0.31, P < 0.001). CONCLUSION: MS impairs left ventricular structure and diastolic and global function. Systolic blood pressure was the only MS criterion which was, at the same time, independently associated with LVmass/Ht27, E/e'averag3, and the Tei index.

Markers of oxidative damage in chronic heart failure: role in disease progression.

BACKGROUND: We aimed to study the relationship between markers of oxidative lipid or protein damage and ventricular remodeling and the validity of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) as an indicator of disease severity in patients with ischemic chronic heart failure (CHF). PATIENTS AND METHODS: We enrolled four groups of 12 patients with varying CHF according to the New York Heart Association (NYHA) classification and 25 controls. Urinary 8-epi-PGF(2alpha) and plasma malondialdehyde and protein thiol (P-SH) groups were correlated with echocardiographic indices of remodeling. The reliability of isoprostanes was analyzed by a receiver operating characteristics (ROC) curve. RESULTS: NYHA class III and IV patients exhibited elevated 8-epi-PGF(2alpha) levels, increased malondialdehyde concentrations and decreased P-SH groups when compared to controls and NYHA I and II patients. 8-Epi-PGF(2alpha) and P-SH groups correlated significantly with indices of remodeling. The ROC curve drawn for 8-epi-PGF(2alpha) allowed us to differentiate NYHA class III and IV patients from NYHA class I and II patients with a sensitivity of 95.8% and specificity of 95.8% (cut off 0.84 ng/mg creatinine; area under curve 0.99; P < 0.001). CONCLUSIONS: Markers of oxidative damage are unlikely to play a significant role in early stages of CHF. However, they might become important in the course of CHF when their concentrations reach critical levels. Urinary 8-epi-PGF(2alpha) is a reliable indicator of symptomatic CHF.