ABC | Volume 111, Nº1, July 2018

Original Article Adropin and Irisin in Patients with Cardiac Cachexia Ali Kemal Kalkan, 1 Huseyin Altug Cakmak, 2 Mehmet Erturk, 1 Kübra Erol Kalkan, 3 Fatih Uzun, 1 Omer Tasbulak, 1 Vesile Ornek Diker, 4 Suleyman Aydin, 5 Ahmet Celik 6 Mehmet Akif Ersoy Thoracic and Cardiovascular Disease Education and Training Hospital, Department of Cardiology, 1 Istanbul, Turkey Mustafakemalpasa State Hospital, Department of Cardiology, 2 Bursa, Turkey Şişli Hamidiye Etfal Education And Research Hospital, Department of Internal Medicine, 3 Istanbul, Turkey Mehmet Akif Ersoy Thoracic and Cardiovascular Disease Education and Training Hospital, Department of Biochemistry, 4 Istanbul, Turkey Firat University, School of Medicine, Department of Clinical Biochemistry, 5 Elazig, Turkey Mersin University, School of Medicine, Department of Cardiology, 6 Mersin, Turkey Mailing Address: Mehmet Erturk • Yesil Vadi Cad, Metrokent Sitesi C6 D69 Basak Mah. Postal Code 34000, Basaksehir – Istanbul E-mail: drerturk@gmail.com Manuscript received July 09, 2017, revised manuscript December 14, 2017, accepted January 24, 2018 DOI: 10.5935/abc.20180109 Abstract Background: Cardiac cachexia is an important predictive factor of the reduction in survival of patients with heart failure with reduced ejection fraction. Objectives: To evaluate adropin and irisin levels in cachectic and non-cachectic subjects and the relationships between the levels of these proteins and clinical and laboratory parameters in patients with HFrEF. Methods: The clinical records of patients who were admitted to the cardiology outpatient clinic for heart failure with reduced ejection fraction were screened. Cachectic patients were identified and assigned to the study group (n = 44, mean age, 65.4 ± 11.2 y; 61.4% men). Heart failure with reduced ejection fraction patients without weight loss were enrolled as the control group (n = 42, mean age, 61.0 ± 16.5 y; 64.3% men). The serum adropin and irisin levels of all patients were measured. A p-value < 0.05 was considered significant. Results: Serum adropin and irisin levels were significantly higher in the cachexia group than in the controls (Adropin (ng/L); 286.1 (231.3-404.0) vs 213.7 (203.1-251.3); p < 0.001, Irisin (μg/mL); 2.6 (2.2-4.4) vs 2.1 (1.8-2.4); p = 0.001). Serum adropin and irisin levels were positively correlated with brain natriuretic peptide (BNP) levels and New York Heart Association (NYHA) class and negatively correlated with body mass index (BMI) and serum albumin levels (all p values: < 0.001). In a multivariate analysis, adropin was the only independent predictor of cachexia in the heart failure with reduced ejection fraction patients (OR: 1.021; 95% CI: 1.004−1.038; p = 0.017). Conclusions: 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. (Arq Bras Cardiol. 2018; 111(1):39-47) Keywords: Cachexia / complications; Heart Failure / physiopathology, Hypertrophy, Left Ventricular; Ventricular Function, Left; Adropin; Peptides; Hormones. Introduction Heart failure with reduced ejection fraction, which is a multifactorial and common disease, is considered a major public health problem worldwide. 1 Cardiac cachexia, which is characterized by loss of muscle, with or without loss of fat mass, is a serious and life-threatening complication of heart failure with reduced ejection fraction. Moreover, studies have demonstrated that it was an important independent prognostic factor for cardiovascular mortality after adjustment for age, left ventricular ejection fraction and functional capacity to perform physical activities. 2-4 Adropin is a novel membrane-bound protein, which contains 76 amino acids and is encoded by the energy homeostasis-associated gene. 5 It is expressed predominantly in the liver, brain, coronary arteries, vascular endothelium and heart (all layers). 6 A recent study reported that elevated plasma levels of adropin in heart failure with reduced ejection fraction patients were positively correlated with disease severity, as classified by the New York Heart Association (NYHA). 7 Irisin is a thermogenic protein, which is expressed in adipose tissue, cardiac muscle, heart and other peripheral tissues. The main functions of irisin are energy expenditure by converting white adipose tissue to brown adipose tissue and regulation of carbohydrate metabolism, resulting in improved glucose homeostasis and insulin sensitivity and weight loss. 6-11 Cardiac cachexia in heart failure with reduced ejection fraction is associated with impaired energy homeostasis due to anabolic and catabolic imbalance, and serum adropin and irisin levels play important roles in energy balance and metabolism. Based on the aforementioned, we hypothesized that both serum adropin and irisin levels would differ in cachectic heart failure with reduced ejection fraction patients and non-cachectic individuals. The aims of the present study were: 1) to investigate serum adropin and irisin levels in cardiac cachectic and non- 39