Plasma level of cardiotrophin‐1 as a prognostic predictor in patients with chronic heart failure

Abstract

Background: Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in patients with chronic heart failure (CHF). Aims: To evaluate the prognostic role of CT-1 in patients with CHF. Methods and results: We measured the plasma levels of CT-1, brain natriuretic peptide (BNP), and IL-6 in 125 patients with CHF. Patients were monitored for a mean follow-up period of 2.9 years. Plasma levels of CT-1 increased with severity of CHF. There was a significant negative correlation between plasma CT-1 and left ventricular ejection fraction. There was a significant correlation between plasma CT-1 and log IL-6. During the follow-up period, 37 patients died. High plasma levels of CT-1, BNP, and IL-6 were independent predictors of mortality on stepwise multivariate analysis. The hazard ratio for mortality in patients with plasma BNP N 170 pg/mL and CT-1 N 658 fmol/mL was 2.48 (95% confidence interval, 1.217-5.060) compared to those with plasma BNP N 170 pg/mL and CT-1 b 658 fmol/mL (p = 0.0124). Conclusion: These findings indicate that plasma CT-1 measurement provides additional prognostic information and that combined levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone.

Cardiotrophin-1 Review

“…The hazard ratio for mortality in patients with plasma BNP > 170 pg/mL and CT-1>658 fmol/mL was 2.48 compared to those with plasma BNP>170 pg/mL and CT-1<658 fmol/mL. These fi ndings indicate that plasma CT-1 measurement provides additional prognostic information and that combined levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone 114 .…”

Cardiotrophin-1: A new predictor of atrial fibrillation relapses after successful cardioversion

“…Two experimental studies revealed the importance of CT-1 in the pathogenesis of atrial myocardial fibrosis and developing arrhythmias over the release of high concentrations of calcium during diastole [16,17]. There are evidence that CT-1 plasma levels can be elevated in patients with hypertension [20], coronary artery disease [21,22], and heart failure [23]. A recent experimental study indicated that CT-1 accelerates the development of atherosclerotic lesions by stimulating the inflammasome, foam cell formation associated with CD36 and acyl-CoA: cholesterol acyltransferase-1 upregulation in macrophages, and migration, proliferation, and collagen-1 production in vascular smooth muscle cells [24].…”

“…CT-1 was also proposed as a prognostic biomarker for death and heart failure in patients with acute myocardial infarction [29] as well as increased levels of CT-1 were reported to be associated with fibrosis, remodeling and depression of myocardial contractility in patients with heart failure [23]. We think that inflammation leads structural and electrical remodeling that consequently induces AF relapse and investigation of this vicious circle may provide pivotal information for the prevention of AF.…”

STAT3 and cardiac remodeling

“…Furthermore, serum levels of upstream activators of STAT3, in particular the interleukin IL-6 cytokines, such as leukemia inhibitory factor (LIF), and cardiotrophin (CT)-1 are elevated in patients with cardiac insufficiency and serve as a strong independent predictor for the morbidity and mortality in patients with chronic heart failure after myocardial infarction [132][133][134]. Additionally, serum levels of the soluble form of the gp130 receptor (sgp130), the common receptor subunit of all IL-6 cytokines, appear to correlate with the severity of left ventricular dysfunction in addition to already established prognostic markers such as B-type natriuretic peptides [135,136].…”