What is the role of profibrogenic and proinflammatory factors in developing atrial fibrillation associated with metabolic syndrome components?

Aim. To determine the concentration of blood fibrotic and inflammatory biomarkers in patients with atrial fibrillation (AF) associated with metabolic syndrome (MS) components.Material and methods. The study included 646 patients aged 35-65 years: patients with AF and MS (n=142), those with AF and without MS (n=113), those with MS and without AF (n=175) and the control group consisted of healthy subjects without cardiovascular and metabolic diseases (n=107). All participants underwent anthropometric and laboratory investigations. Profibrogenic (aldosterone, galectin-3, TGF-beta1, CTGF) and proinflammatory (CT-1, IL-6) factors were determined in serum and plasma by ELISA. Statistical analysis was performed using IBM SPSS Statistics software (version 22.0).Results. The highest concentrations of fibrotic and inflammatory biomarkers were found in patients with AF in combination with MS. In MS patients without AF, the concentration of aldosterone, galectin-3, TGF-beta1, CTGF, CT-1, and IL-6 was also higher than in healthy subjects. The levels of aldosterone, CT-1 and IL-6 in patients with AF were higher in the presence of three or more MS components, while the highest values of these parameters were found in patients with five MS components. The lowest concentrations of galectin-3, CTGF, and CT-1 in patients with AF were found in patients without MS components, and in the presence of even 1 MS component, they were significantly higher. Correlation analysis made it possible to establish a stronger relationship between aldosterone and TGF-betal with systolic blood pressure (p=0,493, p<O,O001 and p=0,530, p<O,O001), and CT-1, CTGF and IL-6 in a greater degree correlated with waist circumference (p=0,563, p<0,0001; p=0,626, p<0,0001; p=0,480, p<O,O001). The concentrations of galectin-3 and CTGF were more positively correlated with an increase in the number of MS components. In patients with AF and hypertension (HTN), but without abdominal obesity (AO), higher values of aldosterone (108,1±70,3 pg/ml and 89,3±32,2 pg/ml, p=0,003) and TGF-beta1 (3680,1±1863,3 pg/ml and 1968,1±1611,5 pg/ml, p=0,015) in serum than in AF patients without HTN and without AO. In the group of patients with AF and AO, but without HTN, higher concentrations of IL-6 (2,9±0,7 pg/ml and 1,9±0,6 pg/ml, p=0,001) and CTGF (162,9±92,2 pg/ml and 116,3±63,4 pg/ml, p=0,0001).Conclusion. It can be assumed that hypertension through the aldosterone system and TGF-beta1, as well as abdominal obesity through the cytokine system CT-1 and IL-6 activate various mechanisms and pathways for myocardial remodeling. Integral molecules galectin-3 and CTGF mediate their interactions, in particular in patients with a combination of several MS components and contribute to a higher AF risk

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

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