Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: report from the studies of left ventricular dysfunction (SOLVD)

This study sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization. Background. Elevated levels of tumor necrosis factor-alph have been identified in 30% to 40% of patients with heart failure. However, it is unclear which subsets of patients with heart failure elaborate tumor necrosis factor-alpha. It is also unclear what the mechanism for the increased expression of proinflammatory cytokines is. Methods. Tumor necrosis factor-alph and interleukin-6 levels were analyzed by enzyme-linked immunoassay using randomly selected plasm samples from patients in functional classes I to III who were enrolled in neurohormonal substudies of the SOLVD trial; age-matched healthy subjects served as the control group. Results. Plasm levels of tumor necrosis factor-alph (p < 0.001) were elevated in patients in functional classes I to III ([mean ± SD] 1.95 ± 0.54, 2.63 ± 0.48, 6.4 ± 1.9 pg/ml, respectively) compared with age-matched control subjects (0.75 ± 0.05 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Plasm levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 ± 0.55, 6.2 ± 1.1, 5.22 ± 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 ± 0.5 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Cox proportional-hazards analysis showed that there was trend toward significance between plasm tumor necrosis factor-alph (p < 0.07) and survival, whereas there was no significant relation for plasm interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakly (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alph levels, there was no significant correlation between neurohormonal and proinflammatory cytokine levels.