Atrial fibrillation in patients with obstructive sleep apnea and metabolic syndrome: the role of cytokines in the development of left atrial myocardial fibrosis

Abstract

Objective. To determine the blood concentrations of biomarkers of fibrosis and inflammation in patients with metabolic syndrome (MS), atrial fibrillation (AF) and obstructive sleep apnea (OSA) and to establish their role in the formation of left atrial myocardial fibrosis. Design and methods. A cross-sectional case-control study included 286 patients aged 35 to 65 years: 78 patients with MS(+)/AF(+)/OSA(+), 79 patients with MS(+) / AF(+)/OSA(-), 73 patients with MS(+)/AF(-)/OSA(+) and 56 patients with MS(+)/AF(-)/OSA(-). Patients with AF and MS (n = 71) were assessed for the severity of left atrial myocardial fibrosis with electroanatomical mapping. Results. It was found that the concentration of profibrogenic biomarkers circulating in the blood of patients with MS(+)/AF(+)/OSA(+) is higher than in patients with MS(+)/AF(-)/OSA(+): galectin-3 (13,4 (8,5-17,6) and 8,4 (5,1-11,6) pg/ml, p < 0,0001), growth differentiation factor-15 (GDF-15) (1648,3 (775,32568,1) and 856,0 (622,5-1956,4) pg/ml, p < 0,0001), N-terminal peptide of type III procollagen (PIIINP) (95,6 (78,6-120,4) and 50,6 (38,9-68,3) ng/ml, p < 0,0001), N-terminal peptide of type I procollagen (PINP) (3459,4 (2167,1-4112,1) and 2355,3 (1925,0-3382,1) pg/ml, p < 0,0001). In the examined cohort of patients with OSA, positive correlations were found between galectin-3 and cardiotrophin-1 (r = 0,410, p = 0,00002), galectin-3 and GDF-15 (r = 0,430, p = 0,0003), galectin-3 and PIIINP (r = 0,451, p = 0,0001). Correlation analysis showed a strong positive relationship between the apnea/hypopnea index (AHI) and blood concentrations of GDF-15 (r = 0,661, p < 0,00001), galectin-3 (r = 0,519, p < 0,00001), interleukin 6 (r = 0,310, p = 0,0001) and C-reactive protein (CRP) (r = 0,361, p = 0,002). Negative correlations of the average level of SpO2 with CRP (r = -0,354, p = 0,001), galectin-3 (r = -0,451, p < 0,00001), GDF-15 (r = -0,637, p < 0,00001) were found. In patients with AF and OSA, fibrosis was more severe than in patients with AF without OSA (28,6 (23,6-36,6) and 13,5 (9,9-23,6) %, p = 0,0002). AHI positively correlated with the severity of fibrosis (r = 0,708, p < 0,00001). The patients with AF and OSA showed the strongest positive relationship between the severity of fibrosis and PINP (r = 0,572, p < 0,0001; в = 0,511, p < 0,0001) and galectin-3 (r = 0,449, p = 0,0009; в = 0,807, p < 0,0001). Conclusions. An increase in the concentration of fibrosis biomarkers in the blood is associated with an increase in the severity of left atrial myocardial fibrosis and probably has a pathogenetic role in increasing the risk of AF in patients with MS and OSA.