Atrial Fibrillation and Endothelial Dysfunction: A Potential Link?

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and coronary atherosclerosis is the leading cause of death in the United States and worldwide. Endothelial dysfunction is the earliest clinically detectable form of atherosclerosis. Control of shared AF and coronary atherosclerosis risk factors improves both AF-free survival and vascular endothelial function. Decades of AF research have yielded fundamental insight into AF pathophysiology, but current pharmacological and catheter-based invasive AF therapies have limited long-term efficacy and substantial side effects, possibly because of incomplete understanding of underlying complex AF pathophysiology. We hereby discuss potential mechanistic links between endothelial dysfunction and AF (risk-factor–associated systemic inflammation and oxidative stress, myocardial ischemia, common gene variants, vascular shear stress, and fibroblast growth factor-23), explore a potential new vascular dimension to AF pathophysiology, highlight a growing body of evidence supporting an association between systemic vascular endothelial dysfunction, AF, and stroke, and discuss potential common effective therapies.