Addition of B-type natriuretic peptide to the GRACE score to predict outcome in acute coronary syndrome: a retrospective (development) and prospective (validation) cohort-based study
ABSTRACT The present study was designed to build and validate a composite score based on the Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) concentrations to predict outcome in patients with acute coronary syndromes (ACS).
The GRACE risk score and BNP concentrations were obtained in a retrospective and a prospective cohort. A composite score including the GRACE score and BNP concentrations was first developed in a retrospective cohort of 248 patients with ACS and then validated in a prospective cohort of 575 patients. The primary outcome was 6-month death or myocardial infarction.
End points were reached in 34 patients in the retrospective cohort and in 68 patients in the prospective cohort. Both higher BNP concentration and GRACE score were independently associated with outcome in the retrospective cohort (p=0.003 and p<0.0001). The composite score could be obtained as follows: GRACE+BNP/60. The use of the composite score increased the accuracy of the GRACE score, with an increase in the C statistic from 0.810 (0.727 to 0.892) to 0.822 (0.745 to 0.902) in the retrospective cohort and from 0.724 (0.657 to 0.791) to 0.750 (0.686 to 0.813) in the prospective cohort. Finally, 7% of patients in the prospective study population were reclassified from low to high risk or from high to low risk using this composite score.
Plasma BNP levels refine the accuracy of the GRACE score. A comprehensive risk score, which includes BNP concentration and the GRACE risk score, might improve ACS risk stratification in clinical practice.
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ABSTRACT: THROMBOLYSIS IN MYOCARDIAL INFARCTION (TIMI), PLATELET GLYCOPROTEIN IIB/IIIA IN UNSTABLE ANGINA: Receptor Suppression Using Integrilin (PURSUIT) and Global Registry of Acute Coronary Events (GRACE) scores have been developed for risk stratification in myocardial infarction (MI). The latter is the most validated score, yet active research is ongoing for improving prognostication in MI. Derivation and validation of a new model for intrahospital, post-discharge and combined/total all-cause mortality prediction - ACHTUNG-Rule - and comparison with the GRACE algorithm. 1091 patients admitted for MI (age 68.4 ± 13.5, 63.2% males, 41.8% acute MI with ST-segment elevation (STEMI)) and followed for 19.7 ± 6.4 months were assigned to a derivation sample. 400 patients admitted at a later date at our institution (age 68.3 ± 13.4, 62.7% males, 38.8% STEMI) and followed for a period of 7.2 ± 4.0 months were assigned to a validation sample. Three versions of the ACHTUNG-Rule were developed for the prediction of intrahospital, post-discharge and combined (intrahospital plus post-discharge) all-cause mortality prediction. All models were evaluated for their predictive performance using the area under the receiver operating characteristic (ROC) curve, calibration through the Hosmer-Lemeshow test and predictive utility within each individual patient through the Brier score. Comparison through ROC curve analysis and measures of risk reclassification - net reclassification improvement index (NRI) or Integrated Discrimination Improvement (IDI) - was performed between the ACHTUNG versions for intrahospital, post-discharge and combined mortality prediction and the equivalent GRACE score versions for intrahospital (GRACE-IH), post-discharge (GRACE-6PD) and post-admission 6-month mortality (GRACE-6). Assessment of calibration and overall performance of the ACHTUNG-Rule demonstrated a good fit (p value for the Hosmer-Lemeshow goodness-of-fit test of 0.258, 0.101 and 0.550 for ACHTUNG-IH, ACHTUNG-T and ACHTUNG-R, respectively) and high discriminatory power in the validation cohort for all the primary endpoints (intrahospital mortality: AUC ACHTUNG-IH 0.886 ± 0.035 vs. AUC GRACE-IH 0.906 ± 0.026; post-discharge mortality: AUC ACHTUNG-R 0.827 ± 0.036 vs. AUC GRACE-6PD 0.811 ± 0.034; combined/total mortality: AUC ACHTUNG-T 0.831 ± 0.028 vs. AUC GRACE-6 0.815 ± 0.033). Furthermore, all versions of the ACHTUNG-Rule accurately reclassified a significant number of patients in different, more appropriate, risk categories (NRI ACHTUNG-IH 17.1%, p (2-sided) = 0.0021; NRI ACHTUNG-R 22.0%, p = 0.0002; NRI ACHTUNG-T 18.6%, p = 0.0012). The prognostic performance of the ACHTUNG-Rule was similar in both derivation and validation samples. All versions of the ACHTUNG-Rule have shown excellent discriminative power and good calibration for predicting intrahospital, post-discharge and combined in-hospital plus post-discharge mortality. The ACHTUNG version for intrahospital mortality prediction was not inferior to its equivalent GRACE model, and ACHTUNG versions for post-discharge and combined/total mortality demonstrated apparent superiority. External validation in wider, independent, preferably multicentre, registries is warranted before its potential clinical implementation.12/2012; 1(4):320-36. DOI:10.1177/2048872612466536
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ABSTRACT: Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes. The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone. During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03-0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1-54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05-0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004-0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02-1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56-145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters. Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.PLoS ONE 09/2013; 8(2):e53860. DOI:10.1371/journal.pone.0053860 · 3.53 Impact Factor