Soluble Glycoprotein 130 Predicts Fatal Outcomes in Chronic Heart Failure Analysis From the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)

Background-Glycoprotein 130 (gp130) is the common signal-transducing receptor subunit of the interleukin-6 (IL-6) family, which may be involved in the progression of heart failure (HF). We hypothesized that soluble gp130 would provide prognostic information beyond that of IL-6 in a population with HF from the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Methods and Results-The associations of soluble gp130 and IL-6 with morbidity, mortality, and mode of death were assessed by immunoassays in a subset of 1452 patients enrolled in the CORONA trial, which included patients with HF, aged >= 60 years, in New York Heart Association classes II to IV, who had ischemic heart disease and a reduced left ventricular ejection fraction. In multivariable analyses, including C-reactive protein, IL-6, troponin T, and N-terminal pro-B-type natriuretic peptide, elevated soluble gp130 (fifth quintile versus all lower quintiles) was associated with all-cause mortality (hazard ratio, 1.47 [1.11-1.93]; P=0.006), cardiovascular mortality (hazard ratio, 1.38 [1.01-1.87]; P=0.042), and death from worsening HF (hazard ratio, 1.85 [1.09-3.14]; P=0.002), but not with the primary end point (composite of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke; hazard ratio, 1.12 [0.84-1.50]; P=0.44). Plasma IL-6 was not associated with outcomes in multivariable analyses. Conclusions-Marked elevations in soluble gp130 are associated with total and cardiovascular mortality, as well as deaths from worsening HF, in elderly patients with HF of ischemic cause.