Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure
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Background—Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-α (TNF-α), 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 V̇o2 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-α, 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 V̇o2, V̇e/V̇co2 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-α treatment.
- Received May 12, 2000.
- Revision received July 26, 2000.
- Accepted August 1, 2000.
- Copyright © 2000 by American Heart Association