The dysregulation of plasma miR-497/FGF23 axis, and its association with clinical characteristics and major adverse cardiovascular event in female premature acute coronary syndrome patients

Abstract

Aim: MicroRNA-497 (miR-497) directly targets fibroblast growth factor 23 (FGF23) to participate in the pathology of acute coronary syndrome (ACS) by regulating atherosclerosis, inflammatory response, lipid metabolism, etc. This study intended to investigate the dysregulation of the miR-497/FGF23 axis, and its association with the major adverse cardiovascular event (MACE) in female premature ACS.

Methods: MiR-497 and FGF23 from plasma samples were detected by RT-qPCR and ELISA in 979 newly diagnosed female premature ACS patients and 100 healthy controls (HCs). MACE was recorded during follow-up (median: 27.0, range: 1.0-54.0 months) in female premature ACS patients.

Results: MiR-497/FGF23 axis was reduced in female premature ACS patients versus HCs [median (interquartile range): 0.7 (0.1-1.2) versus 1.9 (1.1-3.4)] (P < 0.001). Meanwhile, miR-497 negatively correlated with FGF23 in femal e premature ACS patients (P < 0.001), but not in HCs (P = 0.157). In female premature ACS patients, the miR-497/FGF23 axis was negatively associated with serum creatinine (P < 0.001), serum uric acid (P = 0.003), high-sensitivity C-reactive protein (P < 0.001), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.003). The 1-year, 2-year, 3-year, and 4-year accumulating MACE rate was 2.9%, 8.6%, 16.7%, and 26.0%, respectively. Interestingly, a high level of miR-497/FGF23 axis predicted decreased accumulating MACE risk (P < 0.001). After adjustment by multivariate Cox's regression analysis, the high miR-497/FGF23 axis (hazard ratio (HR) = 0.005, P = 0.001) independently correlated with reduced accumulating MACE risk.

Conclusion: The plasma miR-497/FGF23 axis represents favorable kidney function, decreased inflammation, and reduced lipid level; meanwhile, this axis possesses prognostic value in predicting decreased accumulating MACE risk in female premature ACS patients.

Keywords: Acute coronary syndrome; Clinical characteristics; Female premature patients; Major adverse cardiovascular event; miR-497/FGF23 axis.