Cytokines and cytokine receptors in advanced heart failure - An analysis of the cytokine database from the vesnarinone trial (VEST)

Background-Previous reports have shown that elevated circulating levels of cytokines and/or cytokine receptors predict adverse outcomes in patients wi th heart failure. However, these studies were limited by small numbers of p atients and/or they were pet-formed in a single center. In addition, these studies did not have sufficient size to address the influence of age, race, sex, and cause of heart failure on the circulating levels of these inflamm atory mediators in patients with heart failure. Methods and Results-We analyzed circulating levels of cytokines (tumor necr osis factor [TNF] and interleukin-6) and their cognate receptors in 1200 co nsecutive patients who were enrolled in a multicenter clinical trial of pat ients with advanced heart failure. This analysis constitutes the largest an alysis of cytokines and cytokine receptors; to date. Analysis of the patien ts receiving placebo showed that increasing circulating levels of TNF. inte rleukin-6, and the soluble TNF receptors were associated with increased mor tality. In men there was a linear increase in circulating levels of TNF wit h advancing age. Women less than or equal to 50 years of age had relatively low levels of TNF, but TNF levels were disproportionately higher in women >50 years of age. No differences existed in cytokines and/or cytokine recep tors in whites versus nonwhites, and circulating levels of cytokines and cy tokine receptors were significantly greater in patients with ischemic heart disease. Conclusions-Cytokines and cytokine receptors are independent predictors of mortality in patients with advanced heart failure. Moreover, circulating le vels of cytokines are modified by age, sex, and cause of heart failure.