Oxidative Stress and Atrial Fibrillation

Abstract

Atrial fibrillation (AF), one of the most prevalent cardiac arrhythmias, afflicts >3 million people in the United States.1 Because the risk of developing AF increases with age, the prevalence of AF is projected to be 7.6 million in 2050,1 when 1 in 5 Americans will be over the age of 65.2 AF not only causes debilitating symptoms and functional impairments owing to worsened hemodynamics and embolic stroke, it also increases the risk of mortality up to 1.5- to 1.9-fold.3 Despite the significant morbidity and mortality burden incurred with AF, there are limited therapeutic options that may improve the outcomes of AF patients, and these options are associated with significant AF recurrence rates.4 Article see p 1748 One possible explanation for the limitations of current therapies is that they do not address effectively or completely the underlying causes of AF. Evidence has been mounting that AF is associated with systemic and cardiac oxidation.4,5 Risk factors for AF are similar to those of atherosclerosis, a disease known to be perpetuated by oxidative stress. These risk factors, such as hypertension, aging, diabetes mellitus, and coronary artery bypass surgery, have each been associated with increases in the systemic markers of oxidation.4 In addition, there is also evidence of increased cardiac oxidation of myofibrillar protein5 and membrane lipids6 with AF or with risk factors linked to AF. Although it is not clear whether cardiac oxidation leads to systemic markers of oxidation or whether systemic oxidation leads to cardiac oxidation, the association of oxidative stress and AF is robust and suggests that AF is possibly a manifestation of a systemic disease. Despite the link between oxidative stress and AF, systemic antioxidant therapy for arrhythmias has not met with much success in clinical trials.7, …