Plasma cytokine parameters and mortality in patients with chronic heart failure

Background-Inflammatory immune activation is an important feature in chroni c heart failure (CHF). Little is known labout the prognostic importance of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor 1 and 2 (sTNF -R1/sTNFR2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CH F patients. Methods and Results-In 152 CHF patients (age 61+/-1 years, New York Heart A ssociation [NYHA] class 2.6+/-0.1, peak (V) over dotO(2), 17.3+/-0.6 mL.kg( -1).min(-1), mean+/-SEM) plasma concentrations of immune variables were pro spectively assessed. During a mean follow-up of 34 months (>12 months in al l patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 mon ths. In univariate analyses, increased total and trimeric TNF alpha, sTNF-R 1, and sTNF-R2 (all P less than or equal to0.0001), sCD14 (P=0.0007), and I L-6 (P=0.005) predicted 24-month mortality. With multivariate analysis and receiver operating characteristics, sTNF-R1 emerged among all cytokine para meters as the strongest and most accurate prognosticator in this CHF popula tion, regardless of follow-up duration and independently of NYHA class, pea k (V) over dotO(2), (V) over dot(E)/(V) over dotCO(2) slope, left ventricul ar ejection fraction, and wasting (P<0.001). The receiver operating charact eristic 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, ind ependent 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 moni toring patients undergoing anti-TNF-alpha treatment.