ABC | Volume 111, Nº1, July 2018

Original Article Kalkan et al Adropin and Irisin Arq Bras Cardiol. 2018; 111(1):39-47 Table 4 – Logistic regression analyses to identify the independent risk factors associated with cardiac cachexia Univariate Multivariate p OR (95% CI) p OR (95% CI) Albumin 0.044 0.331 0.113-0.972 0.387 0.571 0.161-2.029 BNP 0.013 1.000 1.000-1.001 0.770 1.000 1.000-1.000 Age 0.151 1.023 0.992-1.056 Gender 0.779 1.133 0.472-2.720 Irisin 0.025 1.865 1.081-3.218 0.776 0.880 0.378-2.047 Adropin 0.002 1.016 1.006-1.026 0.017 1.021 1.004-1.038 Creatinine 0.760 1.098 0.604-1.994 Glucose 0.720 0.999 0.992-1.005 LVEF 0.880 0.996 0.939-1.056 Total cholesterol 0.239 0.994 0.984-1.004 Triglyceride 0.302 0.996 0.987-1.004 LDL 0.363 0.995 0.983-1.006 HDL 0.022 0.941 0.893-0.991 0.102 0.950 0.893-1.010 NYHA III - IV 0.016 3.000 1.226-7.339 0.463 0.550 0.111-2.717 BNP: Brain Natriuretic Peptide; LVEF: Left Ventricular Ejection Fraction; LDL: Low-Density Lipoprotein; HDL: High-Density Lipoprotein; NYHA: NewYork HeartAssociation. and serum albumin levels were inversely related with irisin. In patients with heart failure with reduced ejection fraction, muscle, fat and bone loss were reported to be associated with worse outcomes. 30 Moreover, a recent study reported a gradual decrease in irisin levels in patients with acute MI, suggesting that irisin may be a new diagnostic marker in this setting. 31 In a recently published study, Shen et al.32 have reported that serum irisin level was significantly higher in deceased acute heart failure (AHF) patients compared to that in survived AHF and predicted 1-year all-cause mortality in AHF patients. In that study irisin and NT-pro-BNP were determined by ROC curve analysis. NT-pro-BNP (AUC: 0.670) had only moderate prognostic values for AHF mortality risk compared to serum irisin level (AUC: 0.753). 32 The findings of that study are similar to ours. This increase may be the result of adipose tissue metabolism and insulin resistance. Studies are needed to determine whether irisin levels are the result of a reduced peripheral muscle mass in cachectic heart failure with reduced ejection fraction patients. In addition, in our study, adropin was found to be more predictive than irisin and BNP. In our study, only adropin was found to be an independent predictor of cachexia in patients with heart failure. Although irisin predicted cardiac cachexia in univariate analysis, it did not predict in multivariate analysis. Irisin was found to be a predictive biomarker for 1-year all-cause mortality in the study by Shen et al. 32 This difference may be due to the fact that the adropin molecule was not used in multivariate analysis at this work. Further studies are highly needed to examine this relationship. Similar to adropin, irisinwas significantly positively correlated with BNP levels and NYHA class. Natriuretic peptides, such as BNPs, in addition to diuretic peptides and vasodilators, trigger lipolysis in the human body and play a role in fat metabolism. 7 Hence, we hypothesized that lipolysis by BNPs might be associated with adropin and irisin synthesis in cachectic heart failure with reduced ejection fraction patients. A further study will be necessary to elucidate the precise mechanism of adropin and irisin release in patients with cardiac cachexia. Study Limitations The present study had some limitations. Firstly, the study population was relatively small. However, the results pointed to an important relationship between adropin and irisin levels and cardiac cachexia in patients with heart failure with reduced ejection fraction. Secondly, a lack of follow-up data on future major adverse cardiovascular events, including mortality or hospitalization for heart failure with reduced ejection fraction, meant that the prognostic value of the levels of both proteins could not be evaluated. Conclusions The present study showed that serum adropin and irisin levels were significantly increased in the cachectic heart failure with reduced ejection fraction group and that these were significantly associated with previously validated markers of heart failure with reduced ejection fraction severity, such as the BNP level and NYHA class. The results suggest that adropin and irisin may be novel markers of cardiac cachexia in heart failure with reduced ejection fraction patients. Adropin and irisin are related with the severity of heart failure. 45