Oxidative stress markers are associated with persistent atrial fibrillation

Abstract

Background: Atrial fibrillation (AF) has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. We compared serum markers of oxidation and associated inflammation in individuals with or without AF.

Methods: Serum markers of oxidative stress and inflammation were compared in a cross-sectional, case-control design study of 40 male individuals, with or without persistent or permanent AF, who were matched for age, sex, diabetes, and smoking status, known confounding variables for the measurement of oxidative stress. We used derivatives of reactive oxidative metabolites (DROMs) and ratios of oxidized to reduced glutathione (E(h) GSH) and cysteine (E(h) CySH) to quantify oxidative stress. We also measured inflammatory markers, including high-sensitivity C-reactive protein, interleukins 1beta and 6, and tumor necrosis factor alpha.

Results: Univariate, conditional logistical regression analysis showed that oxidative stress but not inflammatory markers were statistically associated with AF (P <0.05). The increase in the odds ratios for AF for E(h) GSH, E(h) CySH, and DROMs were 6.1 (95% CI, 1.3-28.3; P = 0.02), 13.6 (95% CI, 2.5-74.1; P = 0.01), and 15.9 (95% CI, 1.7-153.9; P = 0.02), respectively. There was a stronger correlation between E(h) GSH and E(h) CySH (r = 0.66) than between E(h) GSH and DROMs (r = 0.41). In multivariate analysis corrected for statins and other AF risk factors differing between the groups, the association of AF and oxidative stress remained significant.

Conclusions: These data suggest that oxidative stress markers may have predictive value in AF management.

Figures

Fig. 1

Oxidative stress markers between subjects with and without AF. (A), comparison of oxidized (GSSG) to reduced (GSH) glutathione and oxidized (cystine) to reduced cysteine thiol couples in subjects with AF (black columns) as compared with matched controls in normal sinus rhythm (NSR; open columns). (B), DROMs in the AF group (black columns) as compared with the controls in NSR (open columns). Data are presented as mean ± SE; * indicates a P <0.05.

Fig. 2

The univariate odd ratios for AF as a function of an interquartile increase in various markers. *, Eh GSH, Eh CySH, and DROMs significant at P ≤0.02.

Fig. 3

The odds ratio for AF for a given change in Eh GSH. The dashed lines indicate 95% CIs.