11 Copeptin improves early risk stratification by Grace Score in non ST-elevation myocardial infarction; NT-proBNP does not

Abstract

<h3>Background</h3> Risk stratification is vital to the optimal management of patients with non ST-elevation myocardial infarction (NSTEMI) however, current tools are not fully discriminatory. Copeptin, the stable 39 amino acid C-terminal portion of pro-vasopressin, is a recognised prognostic marker in ST elevation myocardial infarction (STEMI) that is also useful to exclude MI as levels rise early after onset. Copeptin has not been evaluated in a NSTEMI population to date. <h3>Aims</h3> We hypothesised that copeptin is an independent predictor of mortality following NSTEMI and, in accordance with AHA criteria for the evaluation of novel biomarkers, assess whether copeptin adds prognostic information to GRACE risk score (GRACE-RS). We use NT-proBNP for comparison. <h3>Methods and Results</h3> In this prospective observational study plasma copeptin and NT-proBNP was measured in 754 NSTEMI patients (519 men, median age 70±13 years) within 36 h of symptoms. The primary endpoint of all-cause mortality at 6 months was reached by 56 (7.4%) patients. Median copeptin levels were 7.9 range 0.3 to 523.0 pmol/l and were significantly higher in those that reached the primary endpoint than the event free survivors; median (IQR), 32.0 (12.0–88.7) vs 7.2 (4.0–16.7) respectively p&lt;0.001. Both copeptin and NT-proBNP were predictive of the primary endpoint on univariate Cox regression analysis (HR 5.98 p&lt;0.0005 and HR 6.07 p&lt;0.0005 respectively). On adjustment for baseline clinical and biochemical variables copeptin remained predictive (HR 3.03 p=0.009) but NT-proBNP did not (p=0.70). Kaplan-Meier analysis revealed that supra-median levels of copeptin were associated with increased mortality (log rank 28.4 p&lt;0.001). ROC curve c-statistics for GRACE-RS of 0.799 increased to 0.835 when combined with copeptin (0.785), when combined with NT-proBNP (0.730) increased to 0.802. Re-classification analysis shows that copeptin improves accuracy of risk stratification when combined with the GRACE-RS as determined by net reclassification improvement (NRI 13.3% p=0.008) whereas, NT-proBNP does not (NRI −4.9% p=0.21). The relative utilities for logistic regression models using GRACE-RS alone, GRACE-RS + copeptin and GRACE-RS + NTproBNP as covariates are shown in Abstract 11 figure 1. The relevant region was the region to the right of the sample risk for 6 months mortality, 0.074. The relative utility for GRACE-RS + copeptin was consistently more than the relative utility for GRACE-RS + NTproBNP across a range of risks; for example at a risk threshold of 15% the additional utility of adding copeptin to the GRACE-RS was 0.097 compared to 0.009 for NTproBNP. <h3>Conclusions</h3> High plasma copeptin levels indicate a worse outcome in NSTEMI patients. We have demonstrated that copeptin fulfils AHA criteria by improving risk stratification over established markers GRACE score and NT-proBNP. Copeptin is also useful for rapid rule-out of MI and the current findings further support clinical uptake.