Abstract 444: Effectiveness Of The Ratio Of L-cysteine To L-glutathione In Serum For Prediction Of Cardiovascular Events

Abstract

Background: Aminothiols play an important role in the antioxidant defense system and the profile may be a predictor of prognosis and cardiovascular events. Methods: Two hundred sixty-two patients (202 men, 60 women, age 65 ± 13 years) undergoing coronary catheterization were followed up to 10 years. The patients were divided equally into two groups according to the median ratio of total L-cysteine to total L-glutathione (tCys/tGSH) in serum at enrollment. Results: During 5.5 ± 3.2 years, 31 patients (12%) died, of whom 20 (8%) had cardiovascular death and 32 (12%) had MACE. In addition, 29 (11%) were hospitalized for heart failure. Log-rank test showed that the high group (tCys/tGSH>=80.70) had a higher mortality from all causes (Fig.A, p=0.025) than the low group (tCys/tGSH<80.70). Univariate COX regression analysis showed that tCys/tGSH was a predictive marker of death, cardiovascular death, MACE, and heart failure (p<0.001, all), but these aminothiol alone did not predict any of these endpoints. After adjustment for age, sex, body mass index, coronary risk factors, renal function, and log-transformed brain natriuretic peptide, tCys/tGSH had predictive value for death (p=0.007), cardiovascular death (p=0.019), and heart failure (p=0.004). The adjusted hazard ratio for heart failure in the high tCys/tGSH group versus the low tCys/tGSH group was 3.071 (95% confidence interval: 1.186-7.952), p=0.021. tCys/tGSH ratio can be substituted by the GSH index obtained from the approximation curve (Fig.B, GSH index=142.7255*tGSH -0.777682 ). GSH index was also a prognostic biomarker, but we found tCys information was necessary to predict heart failure and was lost in GSH index. In addition, γ-glutamyl transpeptidase (GGT), which is responsible for extracellular catabolism of GSH to Cys, was a prognostic factor. Conclusions: Our results suggest that tCys and tGSH can be a useful marker of cardiovascular events by ratioing and may be an indicator of GGT activity.