The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure
European Heart Journal
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
... culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During followup, 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, low 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.