Plasma cytokine parameters and mortality in patients with chronic heart failure.

Background: Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor 1 and 2 (sTNF-R1/sTNF-R2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CHF patients.
Methods and Results: In 152 CHF patients (age 61+/-1 years, New York Heart Association [NYHA] class 2.6+/-0.1, peak VO(2) 17.3+/-0.6 mL. kg(-1). min(-1), mean+/-SEM) plasma concentrations of immune variables were prospectively assessed. During a mean follow-up of 34 months (>12 months in all patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 months. In univariate analyses, increased total and trimeric TNF-alpha, sTNF-R1, and sTNF-R2 (all P</=0.0001), sCD14 (P=0.0007), and IL-6 (P=0.005) predicted 24-month mortality. With multivariate analysis and receiver operating characteristics, sTNF-R1 emerged among all cytokine parameters as the strongest and most accurate prognosticator in this CHF population, regardless of follow-up duration and independently of NYHA class, peak VO(2), VE/VCO(2) slope, left ventricular ejection fraction, and wasting (P<0.001). The receiver operating characteristic area under the curve for sTNF-R1 was greater than for sTNF-R2 at 6, 12, and 18 months (all P<0.05).
Conclusions: sTNF-R1 was the strongest and most accurate prognosticator, independent of established markers of CHF severity. Assessment of sTNF-R1 may be useful in identifying patients who are at high risk of death and in monitoring patients undergoing anti-TNF-alpha treatment.