LIPCAR Is Increased in Chronic Symptomatic HF Patients. A Sub-Study of the GISSI-HF Trial

BACKGROUND: The long noncoding RNA LIPCAR (Long Intergenic noncoding RNA Predicting CARdiac remodeling) has emerged as a promising biomarker in cardiac disease and cardiac remodeling. To determine whether LIPCAR levels help for a molecular phenotyping of chronic heart failure (HF) patients, this study assessed the association of LIPCAR with severity of the disease and its progression, and with risk of death or hospitalization in HF patients. METHODS: LIPCAR was measured in plasma of 967 HF patients with symptomatic heart failure participating in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca - Heart Failure (GISSI-HF) biohumoral sub-study. RESULTS: Plasma levels of LIPCAR were significantly associated with functional impairment as assessed by the New York Heart Association (NYHA) class, kidney function as reflected by estimated glomerular filtration rate, and creatinine, hemoglobin and mitral insufficiency. In females, these associations were more marked as compared to males. LIPCAR plasma levels were significantly related to the two cardiac markers, N-terminal pro-B type natriuretic peptide and high-sensitivity cardiac troponin T, but not to inflammatory markers such as high sensitivity C-reactive protein and pentraxin-3, nor to patient reported outcomes such as depression and quality of life. HF patients with high LIPCAR levels univariately showed significantly higher incidence of cardiovascular hospitalizations but not of death; after adjusting for covariates, no significant effects of LIPCAR were found for cardiovascular hospitalizations. CONCLUSION: The circulating long noncoding RNA LIPCAR was increased in HF patients with higher NYHA class, impaired kidney function, and lower hemoglobin, which are indicators of patients' overall state.