Oxidized LDL, Gamma-Glutamyltransferase and Adverse Outcomes in Older Adults

Abstract

Objectives: Gamma-glutamyltransferase (GGT) is a biomarker of liver disease and oxidative stress which was associated with all-cause and cardiovascular (CV) mortality in the general population and in patients with high risk conditions. This study aims at assessing whether oxLDL modifies the relationship between GGT, all-cause, and CV mortality in elderly individuals from the general population.

Design: Observational longitudinal study.

Setting: Population-based cohort of older individuals (>65 years) free of liver disease.

Participants: One thousand and thirty-eight individuals from the Invecchiare in Chianti (InCHIANTI) study.

Measurements: Serum GGT level, oxidized low-density lipoprotein (oxLDL), CV comorbidities, all-cause and CV mortality.

Results: The median age of the study population (n = 1,038) was 74 years (inter-quartile range: 69-79), 152 individuals (15%) had past CV events. During a median follow-up of 9 years, 401 individuals died, 168 of them (42%) for CV causes. In adjusted analyses, GGT predicted all-cause mortality (HR for 20 U/L increase in serum GGT: 1.11, 95% CI: 1.02-1.21, P = .02) and CV mortality (HR: 1.17, 95% CI: 1.03-1.33; P = .02). Furthermore, in an analysis for interaction circulating oxLDL amplified the effect of GGT on all-cause mortality (P = .003).

Conclusion: Circulating oxLDL amplifies the effect of GGT on mortality in the elderly. The mechanism for this association remains unknown and requires further research, including studying the potential role of GGT in oxidative stress. These results are consistent with the hypothesis of a causal role of GGT in the CV morbidity and mortality in older individuals and indicate that oxLDL plays a crucial role in the interpretation of the link between GGT and the risk of adverse clinical events in this population.

Keywords: GGT; CV events; elderly; mortality; oxidized LDL.