Air pollution and liver enzymes.

To the Editor: Growing evidence indicates that elevated levels of the liver enzymes γ-glutamyltransferase (GGt), aspartate transaminase (ASt), and alanine transaminase (ALt) are independently associated with increased risk of cardiovascular disease (CVD).1–4 GGt may also increase due to environmental pollution.1 Ambient particulate matter has been shown to induce oxidative stress and being linked to CVD5 and might potentially affect liver enzymes’ levels. therefore, we assessed the association between chronic ambient air pollution and serum liver enzymes, as a possible component in the mechanisms linking air pollution to CVD. We analyzed data collected in two KOrA (Cooperative Health research in the region of Augsburg) surveys, conducted in Augsburg and two adjacent counties in southern Germany between 2004 and 2008. Blood was drawn from 5,892 adults aged 31 to 85 years, and the serum liver enzymes GGt, ASt, and ALt were analyzed. Air pollution exposure was estimated within the eSCAPe study (european Study of Cohorts for Air Pollution effects, http://www.escapeproject.eu/) between 2008 and 2009 by a combination of measurements and modeling. We estimated the annual average concentrations of particles below 2.5 μm (PM2.5), below 10 μm (PM10), coarse particles (PMcoarse), absorbance of PM2.5, nitrogen oxides (NOx), and nitrogen dioxide (NO2) at the residential address of each participant. We assessed the associations by multivariable linear models with log-transformed outcome variables. All models were adjusted for socioeconomic, lifestyle, and clinical covariates. For a detailed description of the outcome and exposure variables as well the covariates see the eAppendix (http://links.lww.com/eDe/A717). Percent changes of liver enzymes means associated with an increase in air pollutants from 5% of the distribution to 95% are shown in the table. For GGt, elevated levels of pollutants were associated with increased mean serum level, most strongly for PM2.5. An increase of the annual average concentration of PM2.5 at residences of 2.77 μg/m3 (5%–95% range) increased mean serum concentration of GGt among the study participants by 5.1% (95% confidence interval = 0.1% to 10.4%). the association was stronger for participants with CVD (12.0% [4.4% to 20.2%]), whereas those without CVD showed no association. For ASt and ALt, we observed no consistent patterns. One biological insight into the association of serum GGt and CVD induction is a possible role of GGt in oxidative stress.1 GGt is present in atherosclerotic plaques and may catalyze oxidation of low-density lipoproteins, contributing to plaque evolution and rupture.1 Also, GGt acts as a protein catalyst in the catabolism of glutathione, the major thiol antioxidant in the body.1 the role of GGt in oxidative stress and in the progression of atherosclerosis has been supported by the association with carotid intima-media thickness.2,4,6 Moreover, GGt is more strongly associated with cardiovascular outcomes than ALt,1,7 which is considered to be a marker of liver injury but not of oxidative stress.1 thus, our findings concerning GGt may strengthen the hypothesis that particulate air pollution affects the cardiovascular system through mechanisms related to systemic oxidative stress. As correlations between PM2.5 and other pollutants were weak, this suggests that the pathway of PM2.5 might differ from the pathways of other pollutants. For example, PM2.5 can penetrate deeper into the pulmonary tree compared with PM10 or PMcoarse because of its smaller aerodynamic diameter. Additionally, our finding regarding strong effect modification by CVD might indicate that people with CVD are more susceptible to air pollution. However, as our reported association has not been assessed previously, it has to be replicated in other studies.