Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events: Multi-Ethnic Study of Atherosclerosis

Background and aims: Fibroblast growth factor 21 (FGF21) has been suggested as a novel biomarker for cardiovascular disease (CVD), especially in people with high CVD risk. However, it is not known whether FGF21 is a CVD biomarker in an initially healthy cohort. We therefore investigated the relationship of plasma FGF21 levels with measures of subclinical atherosclerosis and cardiovascular events in Multi-Ethnic Study of Atherosclerosis participants without known CVD at baseline. Methods: A total of 5788 participants had plasma FGF21 levels measured at the baseline exam (2000-2002). Carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcification (CAC) were measured at baseline. Participants were followed up for incident CVD events over a median period of 14 years. Results: In cross-sectional analyses adjusting for socio-demographic variables, participants with higher FGF21 levels had higher carotid IMT, lower ABI, and higher prevalence of CAC (p < 0.001). However, these associations were not significant after simultaneously adjusting for demographic, socioeconomic and lifestyle factors, traditional CVD risk factors, and biomarkers of inflammation and hemostasis. Among 5768 patients with follow-up data, 820 developed incident CVD endpoints. Higher baseline FGF21 levels were not associated with the risk for incident CVD endpoints after adjusting for multiple confounding factors (odds ratio 1.03; 95% confidence interval, 0.94-1.12, per SD increase in In-transformed FGF21 levels). Conclusions: Although FGF21 has been suggested as a CVD biomarker for people with high CVD risk, our findings do not support a role of FGF21 as a CVD biomarker in those without a history of CVD.