The relationship of circulating fibroblast growth factor 21 levels with incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis

Background and aims: Elevated circulating levels of fibroblast growth factor 21 (FGF21) are associated with multiple cardiovascular disease (CVD) risk factors and incident events. Previous small cross-sectional studies, mainly in Chinese populations, have suggested FGF21 may play a role in the development of atrial fibrillation (AF). We therefore investigated the relationship of FGF21 levels with incident AF in participants free of clinically apparent CVD at baseline in a large, multi-ethnic cohort. Methods: A total of 5729 participants of four major ethnic groups (Caucasian, African American, Hispanic American, and Chinese American) from the Multi-Ethnic Study of Atherosclerosis (MESA), who were free of AF and had plasma FGF21 levels measured by ELISA at the baseline exam, were included in the analysis. Participants were followed up for incident AF over a median period of 12.9 years. Cox proportional hazards regression analysis was used. Results: Among the 5729 participants, 778 participants developed incident AF. Participants with incident AF had significantly higher baseline FGF21 levels than those without incident AF (median = 166.0 and 142.8 pg/mL, p < 0.001). After adjusting for possible confounders, including demographic, socioeconomic and lifestyle factors, traditional CVD risk factors and circulating inflammatory markers, higher baseline FGF21 levels did not predict incident AF over the follow up period. There was no effect modification by sex or ethnicity. Conclusions: Baseline FGF21 levels were not associated with the development of AF in an ethnically diverse population followed long-term. Our findings do not support an important role of FGF21 in AF development.