The relationship of circulating fibroblast growth factor 21 levels with pericardial fat: The Multi-Ethnic Study of Atherosclerosis

Arsenios Magdas,Kwok Leung Ong,Jingzhong Ding,Kerry-Anne Rye,Philip J Barter,Robyn L Mcclelland,Matthew A Allison

doi:10.1038/s41598-019-52933-9

Abstract

Previous small studies have reported an association between circulating fibroblast growth factor 21 (FGF21) levels and pericardial fat volume in post-menopausal women and high cardiovascular disease (CVD) risk patients. In this study, we investigated the relationship of FGF21 levels with pericardial fat volume in participants free of clinical CVD at baseline. We analysed data from 5765 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) with both pericardial fat volume and plasma FGF21 levels measured at baseline. 4746 participants had pericardial fat volume measured in at least one follow-up exam. After adjusting for confounding factors, ln-transformed FGF21 levels were positively associated with pericardial fat volume at baseline (β = 0.055, p < 0.001). When assessing change in pericardial fat volume over a mean duration of 3.0 years using a linear mixed-effects model, higher baseline FGF21 levels were associated with higher pericardial fat volume at baseline (2.381 cm3 larger in pericardial fat volume per one SD increase in ln-transformed FGF21 levels), but less pericardial fat accumulation over time (0.191 cm3/year lower per one SD increase in ln-transformed FGF21 levels). Cross-sectionally, higher plasma FGF21 levels were significantly associated with higher pericardial fat volume, independent of traditional CVD risk factors and inflammatory markers. However, higher FGF21 levels tended to be associated with less pericardial fat accumulation over time. Nevertheless, such change in pericardial fat volume is very modest and could be due to measurement error. Further studies are needed to elucidate the longitudinal relationship of baseline FGF21 levels with pericardial fat accumulation.

Highlights

Pericardial fat is located between the external surface of the parietal pericardium and the internal surface of the mediastinum[1]
In humans, circulating fibroblast growth factor 21 (FGF21) levels are often elevated in different pathophysiological conditions such as metabolic syndrome, obesity, dyslipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease and coronary artery disease[5]
In multivariable linear regression analysis, higher plasma FGF21 levels were significantly associated with larger pericardial fat volume at baseline after adjusting for demographic, socioeconomic and lifestyle factors, the association was modest (Model 1, Table 2)

Summary

Introduction

Pericardial fat is located between the external surface of the parietal pericardium and the internal surface of the mediastinum[1]. A more recent study of the MESA cohort reported a significant association between pericardial fat and poorer CVD prognosis including higher annualised risk of all cause death, heart failure, all-cause CVD, coronary heart disease and stroke[4]. Small clinical studies have suggested a positive association of circulating FGF21 levels with epicardial or pericardial fat volume in post-menopausal women and people at high CVD risk[9,10]. It is not known whether such an association is relevant to men and healthy people, and whether there are any sex or racial/ethnic differences in the association of plasma FGF21 levels with pericardial fat volume. In the present study, the relationship of FGF21 levels and pericardial fat was investigated using a large-scale well-established cohort of participants, free of clinically apparent CVD

Methods

Results

Conclusion