Abstract
Introduction: Atrial fibrillation (AF) is associated with oxidative stress. Hydrogen sulfide and nitric oxide (NOx) are gasotransmitters involved in cardiovascular redox homeostasis. Free sulfide is increased in the plasma of human patients with atrial fibrillation. Although nitric oxide synthase expression and polymorphism has been studied in atrial fibrillation, NOx levels have not been measured in AF patients Hypothesis: AF is associated with altered NOx levels, and sulfide: nitrite ratio. Methods: Free NOx, total NOx, and nitrotyrosine levels were measured in patients without AF (n = 65), paroxysmal AF (PAF, n = 26) and persistent AF (n = 25) and compared between groups. Previously published sulfide levels from these patients were used to calculate free sulfide: total NOx ratio. Clinical characteristics of these patients were compared. Student’s t-test and nominal logistic regression were used for statistical analysis. Results: The patients without AF were younger but comparable to AF patients with regard to race, sex, diabetes, sleep apnea, and smoking history. Patients with AF were more likely to have hypertension (82% versus 54% non-AF patients, p = 0.002) and heart failure (47% versus 25% of non-AF, p = 0.02). On the other hand, non-AF patients were more likely to have coronary artery disease and/or peripheral arterial disease (43% versus 17% in patients with AF, p = 0.005). Compared to non-AF patients, AF patients had significantly lower total NOx (212 vs 268nM, p=0.005), free NOx (192 vs 237nM, p=0.039), and total sulfide: total NOx ratio (0.028 vs 0.020, p<0.01). Compared to PAF patients, persistent AF patients had further significant reduction in total NOx (177 vs 243nM, p=0.04). At 3-month follow up, free NOx levels increased from baseline in patients who underwent successful conversion to normal sinus rhythm (n=11, p=0.048). Levels of oxidative stress marker, nitrotyrosine, trended higher in patients with AF compared to non-AF patients (1.10 vs 1.01 p=0.08). Multivariable logistic regression showed that total NOx was associated with AF independent of age, sex, race, HTN, DM and heart failure (OR per 10nM decrease in NOx= 1.04, CI=1.001-1.094, p=0.0471*) Conclusion: Reduced NOx levels and increased free sulfide to NOx ratio are associated with AF.
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