Relationship of fibroblast growth factor 21 with the prevalence and progression of vascular and valvular calcification: Multi-ethnic study of atherosclerosis

Abstract

Background: Elevated circulating levels of fibroblast growth factor 21 (FGF21) are associated with cardiovascular disease (CVD). Therefore, we investigated the relationship of plasma FGF21 with calcification at different vascular and valvular sites.

Methods: A total of 5786 participants, free of clinically apparent CVD at baseline and with valid data on plasma FGF21 and calcification (Agatston score, volume and density) at coronary arteries, thoracic arteries, mitral and aortic valves, and aortic valve ring, were included in the analysis. Vascular calcification was measured at 2-3 follow-up visits.

Results: At baseline, higher FGF21 levels were associated with prevalent descending thoracic aortic calcification (DTAC) (prevalence ratio = 1.06 [95% CI 1.01-1.11] per SD increase in log-transformed unit, P = 0.016). Among participants without prevalent calcification, higher FGF21 levels were associated with incident DTAC (relative risk [RR] = 1.13 [95% CI 1.04-1.22], P = 0.002). Among all participants, higher FGF21 levels were also associated with the progression of DTAC score and volume (RR = 1.07 [95% CI 1.03-1.12] and 1.08 [95% CI 1.03-1.12] respectively, both P < 0.01). No significant association of FGF21 was found for prevalence (prevalence ratio = 0.89-1.05), incidence (RR = 0.97-1.16) and progression of calcification (RR = 0.94-1.14) at the other sites.

Conclusion: Higher FGF21 levels were associated with the presence, incidence and progression of DTAC. However, the magnitude of this association was similar to those of the non-significant associations of FGF21 levels with calcifications at other sites. Further research is needed to assess the potential of FGF21 as a biomarker for vascular calcification.

Keywords: Aortic calcification; Fibroblast growth factor 21; Multi-ethnic study of atherosclerosis; Vascular calcification.