Potential new MI risk predictor identified

2 September 2010

MedWire News: German researchers claim they have identified a potential new predictor of the risk for myocardial infarction (MI).

They discovered a positive association between MI risk and circulating levels of cysteinyl-glycine (Cys-Gly), a thiol originating from the cleavage of glutathione that is mediated by γ-glutamyltransferase (GGT).

Dagmar Drogen, from the German Institute of Human Nutrition Potsdam-Rehbrücke, and co-workers say: “With Cys-Gly, we found a potential new predictor of MI risk whose impact needs to be further elucidated.”

Elevated blood GGT activity is an indicator of hepatobiliary dysfunction and alcohol misuse and has been recognized as a predictor of cardiovascular diseases, say the researchers.

GGT is present in blood and on the surface of most cell types, where it catalyzes the cleavage of extracellular glutathione to a γ-glutamyl moiety and Cys-Gly, with the latter triggering the iron-dependent oxidation of low-density lipoprotein (LDL).

To investigate these relationships further, the team compared baseline plasma GGT activity and Cys-Gly and oxidized (ox)LDL levels in 116 participants in the EPIC-Potsdam study who experienced incident MI during 6.0 years of follow-up with those of 837 individuals who did not.

There was a significant increase in MI risk per standard deviation increase in log-transformed levels of GGT, Cys-Gly, and oxLDL, with hazard ratios of 1.63, 1.36, and 1.37, respectively, after adjusting for established risk factors.

For the Cys-Gly association with MI, adjusting for plasma GGT activity only had a minor influence on the risk relation, which the researchers say suggests that Cys-Gly is not merely a reflection of GGT activity.

They add that although the impact of oxLDL was not strong, the Cys-Gly relation with MI lost statistical significance after including this as a covariate, suggesting a weak interrelation between Cys-Gly and LDL oxidation in plasma.

Unexpectedly, the researchers note that Cys-Gly and oxLDL only accounted for 2.3% of the relation between GGT and MI risk.

“Contrary to our hypothesis, plasma levels of Cys-Gly and oxLDL appear to have a negligible influence on the relationship between GGT and the endpoint,” they conclude in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

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Arterioscler Thromb Vasc Biol 2010; Advance online publication