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European Heart Journal 1997 18(10):1620-1625;
Copyright © 1997 by the European Society of Cardiology.
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© 1997 The European Society of Cardiology

Haemodynamic, neuroendocrine and metabolic correlates of circulating cytokine concentrations in congestive heart failure

J. Lommi*, K. Pulkki{dagger}, P. Koskinen*, H. Näveri*, H. Leinonen*, M. Härkönen{ddagger} and M. Kupari*,

*Division of Cardiology (Department of Medicine) Helsinki University Central Hospital Helsinki, Finland
{dagger}Department of Clinical Chemistry, Helsinki University Central Hospital Turku, Finland
{ddagger}Department of Clinical Chemistry, Helsinki University Central Hospital Helsinki, Finland

Received 28 April 1997; accepted 2 May 1997.

Correspondence: Dr M. Kupari, Division of Cardiology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290, Helsinki, Finland

Abstract

OBJECTIVES: Increased activity of pro-inflammatory cytokines in the circulation has been observed in many, though not all, patients with congestive heart failure. To identify the predictors of cytokine activation in congestive heart failure, we assessed the relationship of peripheral and hepatic venous cytokines to central haemodynamics, neuroendocrine status and intermediary metabolism in patients with moderate or severe congestive heart failure.

PATIENTS AND METHODS: Concentrations of tumour necrosis factor-{alpha}, soluble tumour necrosis factor-receptor II and interleukin 6 were measured from peripheral and hepatic venous plasma in 58 adult cardiac patients, of whom 44 had congestive heart failure, undergoing heart catheterization, echocardiography and assessment of selected neuroendocrine and metabolic characteristics.

RESULTS: Peripheral venous soluble tumour necrosis factor-receptor II was directly related to NYHA class (rs=0·46 P>0·001) and inversely to 6-min walking distance (rs–0·46, P>0·001). Peripheral venous tumour necrosis factor-{alpha} was related to 6-min walking distance (rs=–0·37, P>0·01), but like soluble tumour necrosis factor-receptor II, was unrelated to other haemodynamic and neuroendocrine measurements. Peripheral venous interleukin 6 correlated with NYHA class (rs=0·66, P>0·001) and 6-min walking distance (rs –0·52, P>0·001). In addition, interleukin 6 was related to right atrial pressure (rs0·55, P>0·001 pulmonary artery wedge pressure (rs=–0·50, P>0·001 and left ventricular ejection fraction (rs=–0·39, P>0·01); in multivariate analysis, only right atrial pressure was an independent predictor of interleukin 6 concentration (P>0·001). Comparisons between patients with and without congestive heart failure showed significantly higher hepatic venous tumour necrosis factor-{alpha}, soluble tumour necrosis factor-receptor II and interleukin 6 in the heart failure group; the differences in peripheral venous cytokines were less consistent.

CONCLUSIONS: In cardiac patients, increased plasma tumour necrosis factor-{alpha} and soluble tumour necrosis factor-receptor II are associated with symptoms of heart failure and poor exercise capacity, while the most important predictor of increased interleukin 6 is elevated systemic venous pressure. Different but still unknown mechanisms may be responsible for the increased release of cytokines in congestive heart failure.

Key Words: Heart failure • cytokines • tumour necrosis factor • interleukin 6


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