Abstract 3475: Decreased Soluble Tweak Levels Predict an Adverse Prognosis in Patients With Chronic Stable Heart Failure
TNF- like weak inducer of apoptosis (sTWEAK) is a multifunctional cytokine that has recently been implicated in cardiovascular disease. The aim of this study was to define the plasma levels of sTWEAK in patients with stable chronic heart failure and evaluate the possibility of a prognostic impact of sTWEAK. Plasma samples of 364 patients with systolic heart failure were compared to 36 control patients with respect to their sTWEAK levels. The median levels of heart failure patients were significantly lower than those of the control group (217 pg/ml, interquartile range 136 to 311 pg/ml vs. 325 pg/ml, interquartile range 250 to 394 pg/ml). Moreover, TWEAK levels were lower in patients with ischemic cardiomyopathy vs. dilated cardiomyopathy and correlated significantly with functional NYHA class. Patients with plasma levels below a ROC-derived cutoff value of 227 pg/ml revealed a significantly higher mortality rate after 4 years. Upon multivariate analysis, sTWEAK levels below 227 pg/ml emerged as an independent predictor of subsequent death. As high NT-proBNP levels and a low ejection fraction are known predictors of death in heart failure patients, we sought to evaluate the role of sTWEAK specifically in these high risk subgroups. Again, cox proportional hazard analyses revealed that TWEAK levels below 227 pg/ml predicted mortality patients after 48 months. Thus, in contrast to other cytokines shown to be increased in heart failure patients, plasma levels of sTWEAK are significantly reduced in chronic stable heart failure. In addition, lower plasma levels of sTWEAK predict an adverse prognosis independent of established risk markers such as NT-proBNP.