D to hospital due to heart failure decompensation, and followed them for 16 months [6]. In a mulivariate analysis, higher concentrations of Fas were associated with higher risk for combined end-point of death and heart failure, but not for death alone. Although TRAIL concentration were not able to predict the occurrence of the combined end-point in the multivariate model, TRAIL was a very FCCP chemical information strong inverse predictor of death. In our study, Fas was a predictorof the composite end-point in univariate analysis, but lost its significance in the multivariate mode. 
TRAIL was an independent predictor of both 22948146 death and the composite end-point. Compared to our study, the study by Niessner et al. was done with a different patient population, which included Met-Enkephalin chemical information patients with chronic heart failure irrespective of etiology (45 were ischemic). Although the number of patients in our study was lower, our patient population was much more homogenous (100 ischemic etiology). This can explain the small differences in results between our study and Niessner’s study. Michowitz et al. showed that serum levels of soluble TRAIL, but not Fas, were reduced significantly in patients with ACS compared to patients with stable atherosclerotic disease and healthy subjects [25]. Thus, TRAIL might be more specific for patients with ischemic etiology of left ventricular dysfunction relative to other etiologies. Secchierro et al. found significantly lower concentrations of serumTRAIL in patients after MI (measured within 24 hours after MI, 1662274 which was similar to the time-point of measurement in our study) compared to healthy subjects [26]. Moreover, low concentrations of TRAIL were associated with higher incidences of death or heart failure at the 1year follow-up. The number of patients enrolled in the study by Secchiero et al. was small (only 60 patients with MI), which means that especially data regarding prediction must be viewed cautiously. The predictive power of our results, based on a substantially larger population, is significant in that it confirms that low concentrations of TRAIL, in patients following an ACS, isPrognosis in ACS Patients by Apoptotic MoleculesFigure 2. Receiver-operating characteristic curve for the concentration of soluble TRAIL in relation to the primary end-point (death and heart failure). The closed black dot on the curve shows the concentration of TRAIL (44.6 ng/mL) with the optimal combination of sensitivity and specificity. doi:10.1371/journal.pone.0053860.ga strong marker of death and heart failure. As it can be seen in Kaplan ?Meier curve, the distribution of incidence 
of end-point was similar during the entire follow- up. Another recent paper by Secchiero et al. demonstrated that a high ratio between serum osteoprotegerin and TRAIL, in patients with acute MI, was associated with higher risk of developing heart failure [27]. The exact mechanism of the negative impact of higher TRAIL concentration on the prognosis of patients following MI is not known. However, there is agreement, based on recent trials, regarding the positive impact of low concentrations of TRAIL on patients prognoses.Precise measurement of cardiac apoptosis can only be done with cardiac tissue samples. Although scientifically interesting, it cannot be done routinely in clinical practice. Therefore, the search for (serum) biomarkers of apoptosis that are indicative of actual tissue level apoptosis as well as being indicative of clinical prognoses, is of great importance. Sever.D to hospital due to heart failure decompensation, and followed them for 16 months [6]. In a mulivariate analysis, higher concentrations of Fas were associated with higher risk for combined end-point of death and heart failure, but not for death alone. Although TRAIL concentration were not able to predict the occurrence of the combined end-point in the multivariate model, TRAIL was a very strong inverse predictor of death. In our study, Fas was a predictorof the composite end-point in univariate analysis, but lost its significance in the multivariate mode. TRAIL was an independent predictor of both 22948146 death and the composite end-point. Compared to our study, the study by Niessner et al. was done with a different patient population, which included patients with chronic heart failure irrespective of etiology (45 were ischemic). Although the number of patients in our study was lower, our patient population was much more homogenous (100 ischemic etiology). This can explain the small differences in results between our study and Niessner’s study. Michowitz et al. showed that serum levels of soluble TRAIL, but not Fas, were reduced significantly in patients with ACS compared to patients with stable atherosclerotic disease and healthy subjects [25]. Thus, TRAIL might be more specific for patients with ischemic etiology of left ventricular dysfunction relative to other etiologies. Secchierro et al. found significantly lower concentrations of serumTRAIL in patients after MI (measured within 24 hours after MI, 1662274 which was similar to the time-point of measurement in our study) compared to healthy subjects [26]. Moreover, low concentrations of TRAIL were associated with higher incidences of death or heart failure at the 1year follow-up. The number of patients enrolled in the study by Secchiero et al. was small (only 60 patients with MI), which means that especially data regarding prediction must be viewed cautiously. The predictive power of our results, based on a substantially larger population, is significant in that it confirms that low concentrations of TRAIL, in patients following an ACS, isPrognosis in ACS Patients by Apoptotic MoleculesFigure 2. Receiver-operating characteristic curve for the concentration of soluble TRAIL in relation to the primary end-point (death and heart failure). The closed black dot on the curve shows the concentration of TRAIL (44.6 ng/mL) with the optimal combination of sensitivity and specificity. doi:10.1371/journal.pone.0053860.ga strong marker of death and heart failure. As it can be seen in Kaplan ?Meier curve, the distribution of incidence of end-point was similar during the entire follow- up. Another recent paper by Secchiero et al. demonstrated that a high ratio between serum osteoprotegerin and TRAIL, in patients with acute MI, was associated with higher risk of developing heart failure [27]. The exact mechanism of the negative impact of higher TRAIL concentration on the prognosis of patients following MI is not known. However, there is agreement, based on recent trials, regarding the positive impact of low concentrations of TRAIL on patients prognoses.Precise measurement of cardiac apoptosis can only be done with cardiac tissue samples. Although scientifically interesting, it cannot be done routinely in clinical practice. Therefore, the search for (serum) biomarkers of apoptosis that are indicative of actual tissue level apoptosis as well as being indicative of clinical prognoses, is of great importance. Sever.
