Related factors and changes of angiopoietin-like protein 2 with chronic heart failure patients participating in phase III cardiac rehabilitation

Abstract

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): the research grant D2 from Kansai Medical University Objectives Angiopoietin-like protein 2 (ANGPTL2) is a protein, whose structure is similar to that of angiopoietin, but binds to a different receptor. Overexpression of ANGPTL2 promotes chronic inflammation and relates to the development of aging-related diseases. ANGPTL2 has been reported to be mainly secreted by adipose tissue. Although ANGPTL2 has been implicated in the pathogenesis of heart failure, there are no studies about serum ANGPTL2 levels in patients with heart failure participating in cardiac rehabilitation program. The aim of this study was to investigate the characteristics, related factors and changes of ANGPTL2 in patients with chronic heart failure during phase III of cardiac rehabilitation program. Methods The subjects included 57 patients (70.1 ± 10.2 years old; 46 men) with chronic heart failure whose serum ANGPTL2 levels were measured during the maintenance phase of cardiac rehabilitation program. Furthermore, we classified 25 patients (70.6 ± 7.5 years old; 23 men) from the 6-month course into a reduced group and an unchanged group to characterize change in ANGPTL2. We excluded patients who were admitted or discharged within 3 months of the evaluation of serum ANGPTL2. We evaluated exercise tolerance using the cardiopulmonary exercise test, grip strength, body composition using a body composition analyzer, blood examinations, and echocardiography. Serum ANGPTL2 was measured by solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). Results The median value of ANGPTL2 was 4.05 ng/ml. ANGPTL2 was positively correlated with body weight, body mass index, body fat mass, body fat percentage, C-reactive protein (CRP) and total protein (TP) levels, and negatively correlated with skeletal muscle mass percentage and anaerobic threshold (AT). From the result of the logistic regression analysis, AT (OR=0.68, 95% CI:0.47-0.97and TP (OR=20.1, 95% CI:2.52-160.63) were extracted as independent factors related to the level of ANGPTL2. In addition, overall serum ANGPTL2 levels decreased significantly after 6 months. Changes in ANGPTL2 in the reduced group showed a positive correlation between baseline peak VO2, left ventricular ejection fraction and skeletal muscle rate, and a negative correlation with baseline ANGPTL2, CRP, body fat mass. In an unchanged group, HbA1c increased, but no significant change was observed in other factors. Conclusions Exercise tolerance in patients with chronic heart failure during maintenance phase might be related to the inflammation marker ANGPTL2. Serum ANGPTL2 levels with stable chronic heart failure patients decreased significantly 6 months after continued cardiac rehabilitation.