Meteorin-like plasma levels as a novel biomarker for heart failure

Abstract

Abstract Introduction Meteorin-like (metrnl), a new adipokine with insulin-sensitizing and anti-inflammatory action, has recently drawn much attention due to its protective effects in the cardiovascular system. Metrnl promotes heart repair after insults like ischemia/reperfusion, cardiotoxicity, or diabetic cardiomyopathy in mice, and its circulating levels in patients have been associated with the presence and severity of coronary artery disease and heart failure, although in the latter with contradictory results. Purpose Our aim was to study the correlation between plasma metrnl levels and biochemical and echocardiographic parameters in patients hospitalized with de novo heart failure (HF) to determine whether this adipokine could be a useful biomarker/therapeutic target for HF. Methods Blood samples of 400 patients hospitalized with de novo HF were collected in a multicenter clinical study. Plasma levels of metrnl were measured by enzyme-linked immunosorbent assay. Results In de novo HF patients, metrnl plasma levels were positively correlated with age (r = 0.322, P < 0.0001), NT-proBNP (r = 0.293, P < 0.0001), troponin (r = 0.192, P < 0.001), creatinine (r = 0.353, P < 0.0001) and urea (r = 0.322, P < 0.0001), while negatively correlated with albumin (r = -0.308, P < 0.0001) and alanine aminotransferase (r = -0.183, P < 0.0001). Metrnl plasma levels were also positively correlated with echocardiographic data of cardiac morphology as intraventricular septum thickness (r = 0.197, P < 0.0001) and left ventricular posterior wall thickness (r = 0.150, P < 0.004). On the other hand, Cox regression analysis suggested that higher plasma metrnl was associated with increased cardiovascular mortality (HR, 1.004, P < 0.004)) and rate of readmission for HF (HR, 1.002, P < 0.008). Regarding the different types of HF, we found that metrnl plasma levels were lower in HF with reduced ejection fraction (HFrEF) in comparison those with preserved ejection fraction (HFpEF) [408.06 (354.05 - 537.71) pg/mL vs. 486.06 (391.94 – 607.80), median (interquartile range), respectively; P < 0.0001]. Conclusion Metrnl plasma levels were associated with markers of cardiac (troponin), renal (creatinine and urea) and hepatic (alanine aminotransferase and albumin) damage. The HF marker NT-proBNP and the echocardiographic parameters intraventricular septum thickness and left ventricular posterior wall thickness are also linked to metrnl plasma levels. Moreover, metrnl levels were found to be independent predictors of cardiovascular mortality and readmission for heart failure. And finally, metrnl plasma levels in patients hospitalized with de novo HF were increased in patients with HFpEF vs. HFrEF. Our results reinforce the relevance of the adipokine metrnl in the pathophysiology and diagnosis of HF, and supports its possible use in the future as biomarker/therapeutic target for HF.