The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure

Aim Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF. Methods and results We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P = 0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, tow blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR = 1.85 per %, P = 0.008), elevated pro-BNP levels (HR = 9.35 per log[pro-BNP], P = 0.001), and low blood pressure (HR = 0.96 per mmHg, P = 0.041) remained as independent predictors of death. Conclusion In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.