Abstract 18401: The Immunoregulatory Cytokine FGL2 is Associated With Functional Impairment in Patients With Heart Failure

Abstract

Introduction: Chronic heart failure is a condition that is characterized by immune activation and release of pro-inflammatory cytokines, which are associated with worsening functional class. Fibrinogen-like protein 2 (FGL2) is a novel immunoregulatory protein that is involved in innate and adaptive immune responses. A connection between plasma FGL2 levels and heart failure has not been previously reported. Objective: To determine if there is an association between plasma FGL2 levels and functional impairment in heart failure. Methods: Seventy-four heart failure patients with NYHA FC I-IV, standard medical treatment, mean age 55 ± 11 years, mean ejection fraction of 29% ± 10%, and 23% females were included. Functional impairment was assessed by determination of peak VO2. Plasma levels of FGL2 and CRP were determined using ELISA in HF patients and healthy controls. We compared peak VO2 according to tertiles of FGL2 using ANOVA (tertile 1<39.7, tertile 2=39.7 to 63.2, and tertile 3>63.2 ng/ml). Correlations were assessed using Pearson’s correlation. We performed a multiple linear regression analysis to investigate the association between peak VO2 and FGL2 adjusting for variables of clinical significance and/or statistical significance. Results are provided as mean ± SD. Results: The plasma levels of FGL2 were significantly higher in HF patients compared with controls (58.6 ± 41.2 versus 32.4 ± 14.7 ng/ml, respectively, p<0.001). 28% of the patients had an ischemic cardiomyopathy, 34% had hypertension, and 18% had diabetes. In HF patients, the mean peak VO2 was 16.9 ± 5.0, 14.2 ± 4.9, and 12.7 ± 3.8 ml/kg/min in the 1 st , 2 nd and 3 rd tertile of FGL2, respectively (p= 0.012). FGL2 was negatively correlated with peak VO2 (r= -0.271, p=0.026) and positively correlated with CRP (r= 0.314, p=0.011). In the adjusted regression model, FGL2 was independently associated with peak VO2 (adjusted beta estimated=-0.031, test statistic=5.77, p=0.016). Conclusion: In heart failure patients, higher levels of plasma FGL2 were associated with a greater degree of functional impairment as measured by peak VO2. These results suggest that immune activation as measured by FGL2 is associated with the severity of heart failure.