Serum Lipids, Inflammation, and the Risk of Atrial Fibrillation: Pathophysiological Links and Clinical Evidence

Abstract

Dyslipidemia is a metabolic disorder characterized by quantitative and/or qualitative abnormalities in serum lipid levels. Elevated serum cholesterol levels can modify the turnover and recruitment of ionic channels in myocytes and cellular homeostasis, including those of inflammatory cells. Experimental and clinical data indicate that inflammation is implicated in the pathophysiology of atrial remodeling, which is the substrate of atrial fibrillation (AF). Data about the association between increased lipid serum levels and AF are few and contrasting. Lipoprotein (a), adiposity, and inflammation seem to be the main drivers of AF; in contrast, low-density lipoproteins, high-density lipoproteins and triglycerides are not directly involved in AF onset. The present review aimed to describe the pathophysiological link between dyslipidemia and AF, the efficacy of lipid-lowering therapies in atherosclerotic cardiovascular disease (ASCVD) patients with and without AF, and the impact of lipid-lowering therapies on AF incidence.

Keywords: alirocumab; atrial fibrillation; bempedoic acid; dyslipidemia; evolocumab; icosapent ethyl; inclisiran; statins.

Figure 1

Mechanistic pathways linking dyslipidemia, epicardial fat, and atrial fibrillation. Dyslipidemia leads to intracellular lipid accumulation and inflammation through elevated TNF-α and IL-6 levels, promoting atrial electrical remodeling. Epicardial fat contributes to oxidative stress, increased ROS, and fibrosis via activin A, matrix metalloproteinases, and aromatase-mediated estrogen production. Fibrosis and oxidative stress result in atrial structural remodeling, neuromodulation, and eventual atrial fibrillation. AF: atrial fibrillation; IL-6: interleukin-6; ROS: reactive oxygen species; TNF-a: tumor necrosis factor-alpha.