NT-proBNP and CA 125 levels are associated with increased pro-inflammatory cytokines in coronary sinus serum of patients with chronic heart failure

Purpose: Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF). We aimed to measure the levels of NT-proBNP, CA 125, pro-anti-inflammatory cytokines (IL-6, IL-1 beta, IL-8, TNF-alpha and IL-4), from peripheral venous (PV) and coronary sinus (CS) blood samples, in patients with CHF and to assess their correlation with echocardiographic indices. Methods: We enrolled 32 subjects (20M/12F) with CHF (III-IV NYHA functional class) who were to undergo cardiac resynchronization therapy (CRT) device implantation and 30 healthy controls (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT for each CHF patient. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. Results: All investigated biomarkers were significantly higher in CHF patients than in non-CHF controls (P < 0.001). There were positive correlations between biomarkers concentrations in PV and CS (r between 0.54 and 0.98, all P < 0.003). NT-proBNP, IL-6 and IL-1 beta levels were 17%, 86% and 36% higher in CS than in PV, these increases being very well correlated each other, while CA 125 levels were 86% higher in PV than in CS. Moreover, CS NT-proBNP, CS IL-6 and CS IL-1 beta serum concentrations were inversely related to the echo cardiographically determined left ventricular ejection fraction (LVEF) (r = -0.61, P < 0.001; r = -0.71, P < 0.001 and r = -0.48, P = 0.005, respectively). A positive relationship was found between CA 125 and IL-1 beta (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL-6 (r = 0.43, P = 0.015), TNF-alpha (r = 0.46, P = 0.008) in PV serum. CA 125 concentrations were closely related to NT-proBNP both in CS (r = 0.46, P = 0.008) and PV (r = 0.52, P = 0.002). Conclusions: CS sampling of NT-proBNP, CA 125 and pro-anti-inflammatory cytokines provides an additional insight into the possible mechanisms by which these biomarkers lead to left ventricular remodeling. Our results clearly suggest that serum NT-proBNP and CA 125 levels not only in PV, but also in CS of patients with CHF, may be dependent on inflammation as a consequence of cytokine network activation.