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 1␤ and 6, and tumor necrosis factor ␣. 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

Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress.

Background-Little is known about long-term outcomes of patients who survive inhospital cardiac arrest.