Российский кардиологический журнал (Aug 2021)

Molecular mechanisms of left atrial fibrosis development in patients with atrial fibrillation and metabolic syndrome: what biomarkers should be used in clinical practice?

  • V. A. Ionin,
  • E L Zaslavskaya,
  • E I Barashkova,
  • V A Pavlova,
  • G I Borisov,
  • K A Averchenko,
  • A N Morozov,
  • E I Baranova,
  • E V Schlyachto

DOI
https://doi.org/10.15829/1560-4071-2021-4579
Journal volume & issue
Vol. 26, no. 7

Abstract

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Aim. To determine the blood concentration of fibrosis biomarkers in patients with atrial fibrillation (AF) in combination with metabolic syndrome (MS) and to analyze the relationship with myocardial fibrosis.Material and methods. This cross-sectional case-control study included 547 patients aged 35 to 65 years: experimental group — patients with MS (n=373), of which 202 patients had AF; comparison group — AF patients without MS (n=110); healthy subjects without cardiovascular diseases and metabolic disorders (n=64). Patients with AF and MS who underwent electroanatomic mapping before pulmonary vein isolation (n=79) were assessed for left atrial (LA) fibrosis severity.Results. It was found that the blood concentration of circulating profibrogenic biomarkers in patients with AF and MS is higher than in patients with AF without MS: aldosterone (135,1 (80,7-224,1) and 90,1 (68,3-120,3) pg/ml, p<0,0001), galectin-3 (10,6 (4,8-15,4) and 5,8 (4,8-8,3) pg/ml, p=0,0001), GDF15 (938,3 (678,3-1352,1) and 671,0 (515,7-879,5) pg/ml, p=0,001), TGF-beta-1 (4421,1 (2513,5-7634,5) and 2630,5 (2020,7-3785,4) pg/ml, p=0,001), CTGF (167,8 (78,9-194,3) and 124,3 (74,4-181,9) pg/ml, p<0,0001), PIIINP (88,5 (58,6120,4) and 58,9 (40,7-86,1) ng/ml, p<0,0001), PINP (3421,4 (1808,1-4321,7) and 2996,1 (2283,8-3894,3) pg/ml, p<0,0001). Patients with paroxysmal AF have higher concentrations of TGF-beta1, CTGF and PINP than patients with persistent and permanent AF. In patients with persistent AF and MS, the concentrations of galectin-3, aldosterone, and PIIINP were higher than in patients with paroxysmal AF, while in patients with permanent AF, they were significantly lower. The plasma concentration of galectin-3 positively correlated with levels of PINP (p=0,465, p<0,0001), PIIINP (p=0,409, p<0,0001), GDF-15 (p=0,369, p<O,O001), CTGF (p=0,405, p<0,0001). According to multivariate regression, of all studied biomarkers, GDF-15 had a greater effect on PIIINP concentration (в=0,234, p=0,038), and galectin-3 — on PINP (в=0,248, p<0,021). Positive correlations of the severity of left atrial fibrosis with the concentration of galectin-3 (p=0,563, p<0,0001), PINP (p=0,620, p<0,0001), TGF-beta-1 (p=0,390, p<0,0001) and CTGF (p=0,551, p<0,0001). According to linear multivariate regression, the most significant effect on LA fibrosis severity among the studied biomarkers is exerted by galectin-3 (в=0,432, p<0,0001), PINP (в=0,343, p=0,001) and PIIINP (в=0,286, p=0,008).Conclusion. An increase in the blood concentration of profibrogenic biomarkers galectin-3, TGF-beta-1, CTGF, PIIINP, and PINP is associated with an increase in LA fibrosis severity and probably has a pathogenetic role in increasing the AF risk in patients with MS.

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