Association of plasma cardiotrophin-1 with stage C heart failure in hypertensive patients: potential diagnostic implications

Abstract

Cardiotrophin-1 is a cytokine that induces hypertrophy and dysfunction in cardiomyocytes and has been shown to be increased in hypertensive patients. The objective of this study was to evaluate the association of cardiotrophin-1 with heart failure (HF) in hypertensive patients and its usefulness as a biomarker of stage C heart failure. Hypertensive patients without cardiac abnormalities (stage A, n = 64), with left ventricular hypertrophy (LVH) (stage B, n = 58), and with left ventricular hypertrophy and clinical manifestations of chronic heart failure (stage C, n = 39) were studied. Plasma cardiotrophin-1 was measured by an enzyme-linked inmunosorbent assay. Plasma cardiotrophin-1 progressively increased (P < 0.001), along with progression of heart failure stages, in hypertensive patients. Plasma cardiotrophin-1 was directly (r = 0.416, P < 0.001) and inversely (r = 0.263, P < 0.01) correlated with left ventricular (LV) mass index and ejection fraction, respectively, in all hypertensive patients. These associations were independent of a number of potential confounding factors. Receiver operating characteristic curves showed that a cut-off of 48.72 fmol/ml for cardiotrophin-1 provided higher sensitivity for diagnosing stage C heart failure than a cut-off of 375.54 pg/ml for amino-terminal probrain natriuretic peptide (NT-proBNP) (80% vs. 72%). Sixty-four percent of stage C hypertensive patients with NT-proBNP values below 375.54 pg/ml value exhibited cardiotrophin-1 values above 49.16 fmol/ml. These findings indicate that plasma cardiotrophin-1 is associated with progression of heart failure in hypertensive patients. Cardiotrophin-1 measurement may provide additional information to that afforded by NT-proBNP to diagnose stage C heart failure in these patients.