Fibroblast growth factor 21 in cardio-metabolic disorders: a systematic review and meta-analysis

Background: Fibroblast growth factor 21 is a signalling protein involved in cell differentiation, morphogenesis, proliferation and metabolism. Recent studies have associated increased levels of FGF21 in the development of cardiovascular diseases, whereas others have reported no significant associations. Therefore, this systematic review and meta-analysis evaluated the value in predicting the risk of cardio-metabolic disorders and mortality. Methods: PubMed and EMBASE were searched until 5th September 2017 for studies that evaluated the roles of FGF21 levels in cardio-metabolic disorders. Results: A total of 183 and 301 entries were retrieved; 24 studies met the inclusion criteria. Four studies were identified by an additional search. Therefore, 28 studies were included in the final meta-analysis. High FGF21 levels significantly predicted the incidence of coronary artery disease (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.06–1.55; P < 0. 01; I² = 48%) and the risk of metabolic syndrome (HR: 1.70, 95% CI: 1.35–2.15; P < 0.0001 I² = 24%). In diabetes mellitus, FGF21 predicted disease incidence or progression (HR: 1.35, 95% CI: 1.06–1.72, P < 0.05, I² = 69%) and worsening renal failure (HR: 1.06, 95% CI: 1.03–1.09, P < 0.0001, I² = 47%). FGF21 also predicted all-cause mortality (HR: 3.00, 95% CI: 1.23–7.33; P < 0.05; I² = 51%), and cardiovascular mortality (HR: 2.33, 95% CI: 1.08–4.99, P < 0.05, I² = 75%). Conclusion: FGF21 significantly predicts the incidence of coronary artery disease, the risks of metabolic syndrome, diabetes mellitus and renal progression in diabetes. It also predicted all-cause and cardiovascular mortality.