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Adjustment of the GRACE score by growth differentiation factor 15 enables a more accurate appreciation of risk in non-ST-elevation acute coronary syndrome.

ABSTRACT: The aim of the study was to evaluate whether knowledge of the circulating concentration of growth differentiation factor 15 (GDF-15) adds predictive information to the Global Registry of Acute Coronary Events (GRACE) score, a validated scoring system for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). We also evaluated whether GDF-15 adds predictive information to a model containing the GRACE score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), a prognostic biomarker already in clinical use.The GRACE score, GDF-15, and NT-proBNP levels were determined on admission in 1122 contemporary patients with NSTE-ACS. Six-month all-cause mortality or non-fatal myocardial infarction (MI) was the primary endpoint of the study. To obtain GDF-15- and NT-proBNP-adjusted 6-month estimated probabilities of death or non-fatal MI, statistical algorithms were developed in a derivation cohort (n = 754; n = 66 reached the primary endpoint) and applied to a validation cohort (n = 368; n = 33). Adjustment of the GRACE risk estimate by GDF-15 increased the area under the receiver-operating characteristic curve (AUC) from 0.79 to 0.85 (P < 0.001) in the validation cohort. Discrimination improvement was confirmed by an integrated discrimination improvement (IDI) of 0.055 (P = 0.005). A net 31% of the patients without events were reclassified into lower risk, and a net 27% of the patients with events were reclassified into higher risk, resulting in a total continuous net reclassification improvement [NRI(>0)] of 0.58 (P = 0.002). Addition of NT-proBNP to the GRACE score led to a similar improvement in discrimination and reclassification. Addition of GDF-15 to a model containing GRACE and NT-proBNP led to a further improvement in model performance [increase in AUC from 0.84 for GRACE plus NT-proBNP to 0.86 for GRACE plus NT-proBNP plus GDF-15, P = 0.010; IDI = 0.024, P = 0.063; NRI(>0) = 0.42, P = 0.022].We show that a single measurement of GDF-15 on admission markedly enhances the predictive value of the GRACE score and provides moderate incremental information to a model including the GRACE score and NT-proBNP. Our study is the first to provide simple algorithms that can be used by the practicing clinician to more precisely estimate risk in individual patients based on the GRACE score and a single biomarker measurement on admission. The rigorous statistical approach taken in the present study may serve as a blueprint for future studies exploring the added value of biomarkers beyond clinical risk scores.

SUBMITTER: Widera C

PROVIDER: S-EPMC3888120 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Adjustment of the GRACE score by growth differentiation factor 15 enables a more accurate appreciation of risk in non-ST-elevation acute coronary syndrome.

Widera Christian C Pencina Michael J MJ Meisner Allison A Kempf Tibor T Bethmann Kerstin K Marquardt Ivonne I Katus Hugo A HA Giannitsis Evangelos E Wollert Kai C KC

European heart journal 20111223 9

<h4>Aims</h4>The aim of the study was to evaluate whether knowledge of the circulating concentration of growth differentiation factor 15 (GDF-15) adds predictive information to the Global Registry of Acute Coronary Events (GRACE) score, a validated scoring system for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). We also evaluated whether GDF-15 adds predictive information to a model containing the GRACE score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), a ...[more]

PMID: 22199121

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Project description:Background: The Global Registry of Acute Coronary Events (GRACE) risk score (GRS) is an established powerful model in predicting prognosis of patients with acute coronary syndrome. However, it does not contain pathophysiological biomarkers. Myeloperoxidase (MPO) and trimethylamine N-oxide (TMAO) are novel biomarkers of different pathophysiological processes of acute myocardial infarction, and each of them predicts risk of adverse clinical outcomes. We aimed to investigate whether the addition of MPO and TMAO could improve a GRS-based prediction model in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A prospective cohort of 444 consecutive patients with STEMI who underwent primary percutaneous coronary intervention were enrolled in this study. Plasma levels of MPO and TMAO were measured using samples collected before the interventional procedure. GRS at admission was calculated. Death and nonfatal myocardial infarction were recorded as major adverse cardiac events (MACEs). Kaplan-Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of MPO and TMAO. Area under the receiver-operator characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to evaluate the increment of predictive value for the combination of MPO and TMAO with GRS in predicting adverse clinical outcomes. Results: During 6 months follow-up, 27 patients suffered MACEs. Both MPO (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.11-5.87; p < 0.05) and TMAO (HR: 4.50, 95% CI: 1.78-11.40, p < 0.01) predicted MACEs at 6 months. The AUC for MPO, TMAO, GRS, and their combination in predicting risk of MACEs at 6 months is 0.642, 0.692, 0.736, and 0.760, respectively. The addition of MPO and TMAO significantly improved the net reclassification of GRS for predicting MACEs at 6 months (NRI: 0.42, p = 0.032). Conclusion: Plasma MPO and TMAO each predict near-term risk of adverse outcomes in patients with STEMI. Furthermore, the combination of MPO and TMAO with GRS enables more accurate prediction of cardiovascular events compared with GRS alone.

Project description:BackgroundThe Global Registry of Acute Coronary Events (GRACE) score is a widely recognized tool for predicting adverse cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The triglyceride-glucose index (TyG index) is a new biomarker of insulin resistance and has a close association with the occurrence of adverse cardiovascular events. We investigated whether the addition of the TyG index to the GRACE score could improve prognosis prediction in patients with NSTE-ACS undergoing percutaneous coronary intervention (PCI).MethodsIn total, 515 patients with NSTE-ACS undergoing PCI were included in this retrospective study. Kaplan-Meier analysis was performed to describe the cumulative incidence of the primary endpoint based on the median TyG index. The relationship between the TyG index and GRACE score was analyzed using Spearman's rank correlation. Univariate and multivariate Cox proportional hazards analyses were used to identify independent risk factors. Based on the receiver operating characteristic curve, net reclassification improvement (NRI), integrated differentiation improvement (IDI), and decision curve analysis, the TyG index was evaluated for its predictive value when added to the GRACE score. ROC curve analyses, NRI, and IDI were used to compare the gain effect of the TyG index and the levels of HbA1C, FBG, TG, and LDL-C on the GRACE score for predicting adverse cardiovascular events.ResultsThe TyG index was an independent predictor of 2-year adverse cardiovascular events in patients with NSTE-ACS undergoing PCI. The addition of the TyG index to the GRACE score demonstrated an improved ability to predict 2-year adverse cardiovascular events compared with the GRACE score alone (AUCs: GRACE score 0.798 vs. GRACE score+TyG index 0.849, P = 0.043; NRI = 0.718, P < 0.001; IDI = 0.086, P < 0.001). The decision curve analysis suggested that the clinical net benefit of the new model (GRACE score+TyG index) was superior to that of the GRACE score alone, with a probability range of 0.04 to 0.32. When including the TyG index, HbA1C, FBG, TG, and LDL-C in the GRACE score system, we found that the TyG index had a greater incremental impact on risk prediction and stratification compared to the other parameters.ConclusionCombining the TyG index and GRACE score could improve the prediction of 2-year adverse cardiovascular events. This new risk model could identify patients with NSTE-ACS at higher risk of adverse events following PCI so that they can be monitored more carefully.

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Adjustment of the GRACE score by growth differentiation factor 15 enables a more accurate appreciation of risk in non-ST-elevation acute coronary syndrome.

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Adjustment of the GRACE score by growth differentiation factor 15 enables a more accurate appreciation of risk in non-ST-elevation acute coronary syndrome.

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