Soluble Glycoprotein 130 Predicts Fatal Outcomes in Chronic Heart Failure

Abstract

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 Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00206310.