Peripheral and local inflammatory markers associated with epicardial fat volume in patients underwent open heart surgery

Abstract Introduction Epicardial fat (EF) is a source of inflammation, and it is associated with cardiovascular diseases. However, the correlation between EF volume (EFV) and local and peripheral biomarkers as well as adipogenesis behavior were not studied yet. Our objective was to a) Find the peripheral and local markers related to EFV independent of age and BMI. b) Study the relationship between the adipogenesis capacity and the EFV in each patient. Materials and Methods We included 33 patients underwent open heart surgery with preoperative cardiac CT imaging. Blood samples of 24 patients were obtained, neutrophils were isolated using polymorphprep and 16 activity markers were analyzed. Twelve biomarkers in plasma associated with metabolism and inflammation were analyzed. The epicardial adipose tissue biopsies were obtained during the surgery. The fat pads were homogenized and RNA was isolated and retrotranscripted to cDNA. Then 17 markers associated with adipogenesis and inflammation were analyzed by real time PCR. Stromal cells from EF of 21 patients were isolated after collagenase activity and cultured for 14 days and then induced to adipogenesis for the next 14 days. Multimarkers on plasma, peripheral neutrophils, EF and primary cultures were analyzed by multiplex assay and real time PCR, respectively. EFV was measured from CT, percentage of EFV in total heart volume was calculated. The association between FV and biomarkers were evaluated with independent sample t-test, linear regression analysis and correlation analysis. Results The main clinical characteristics of studied patients were (69 ± 9 years old, 30 ± 4 kg/m², 76% HT, 67% DLP, 33% CAD, 27% HF, 30% AF, 30% T2DM). EFV (148±55 cm³) was more correlated with age (r=0.4, p=0.023), but not with BMI. Percentage of EFV in total heart volume (12.9±4.9%) was positively correlated with lymphocytes and monocytes markers, CD3G and CXCR2 levels (r=0.5, p=0.008; r=0.49, p=0.028 respectively), and inversely with FABP4 (r=0.46, p=0.043) in EF. Circulating inflammatory markers, plasma C5a and MPO on neutrophils were associated with a greater amount of EFV (r=0.7, p=0.001 for C5a and r=0.75, p=0.001 for MPO) and percentage of EFV in total heart volume (r=0.63, p=0.003 for C5a and r=0.84, p<0.000 for MPO). Neutrophils markers, NGAL (r=0.49, p=0.048), LF (r=0.52, p=0.034), DEFA3 (r=0.57, p=0.023) were also correlated with percentage of EFV to total heart volume. Lineal regression determined that among local markers CD3G was the best EF predictor (r=0.4, p=0.008); regarding peripheral markers, the C5a expression levels on neutrophils was the best EF predictor (r=0.61, p=0.002). There were no association between adipogenesis ability and EFV among studied patients. Conclusion EFV from patients undergoing open heart surgery were associated with local and peripheral inflammatory markers. It might contribute to cardiovascular disease progression. Long term follow-up is needed to clarify this process.