ABC | Volume 114, Nº4, April 2020

Original Article Souza et al. NT-proBNP in acute coronary syndromes Arq Bras Cardiol. 2020; 114(4):666-672 Methods Sample selection Patients consecutively admitted to the coronary care unit (CCU) of a tertiary-care hospital, between September 2007 and October 2013, due to suspected ACS (unstable angina and myocardial infarction) were prospectively included in the study. Inclusion criteria was chest discomfort in addition to at least one of the three objective criteria: 1) positive biological marker of myocardial necrosis, defined as troponin T ≥ 0.01 ug/L or troponin I > 0.034 g/L, corresponding to values above the 99 th percentile; 13 2) ischemic electrocardiographic alteration, consisting of T wave inversion (≥ 0.1 mV) or ST segment changes (≥ 0.05 mV); and 3) previously documented coronary artery disease, defined as a history of myocardial infarction with Q wave or previous angiography demonstrating coronary obstruction ≥ 70%. Patients without NT-proBNP dosage or who did not agree to participate in the study were excluded. The protocol was in compliance with the Declaration of Helsinki, was approved by the Research Ethics Committee of the Institution, and all participants provided written informed consent. NT-proBNP Measurement NT-proBNP measurement was performed on a blood sample collected at patient’s arrival at the hospital, aiming for a minimum delay between the onset of symptoms and the collection of material. Plasma was frozen at –70 °C for simultaneous dosing of the samples. The immunoassay method (Biomérieux) was used, considering the following definitions of high NT-proBNP: 1) Values above 450 pg/ml in patients under 50 years of age; 2) Values above 900 pg/ml in patients over 50 years of age. 2 GRACE score The GRACE score calculation was based on clinical data at admission, electrocardiogram performed within 6 hours of admission, troponin T or troponin I dosages in the first 12 hours, and the first plasmatic creatinine. Elevation of myocardial necrosis markers (as a component of the scores) was defined as troponin above the 99 th percentile. The GRACE score includes eight variables: five semi-quantitative, meaning different weight for each age stratum (systolic blood pressure, heart rate, plasma creatinine and Killip class), and three dichotomic ones (ST segment depression, elevation of myocardial necrosis marker, and cardiac arrest at admission). The final score can range from 0 to 372. 3 Clinical end-point The clinical end-point was cardiovascular death during hospitalization, defined by one of the following mechanisms: cardiac failure, arrhythmia or due to complications from treatments related to ACS. Statistical Analyses Numerical variables were expressed as mean and standard deviation as they presented normal distribution or small deviation from normality, while median and interquartile range were preferred in case of significant deviation from normality. Categorical variables were expressed in proportions. Preliminary results were accompanied by a 95% confidence interval as a measure of uncertainty. Initially, predictive values of NT-proBNP and Killip class were evaluated by the area under the ROC curve (C-statistic), considering cardiovascular death as an outcome. These two curves were statistically compared by the Hanley-McNeil paired test. 14 In addition, Kappa Test was used to assess concordance between high NT-proBNP and Killip > I in the definition of heart failure. Logistic regression was used to assess the incremental value of NT-proBNP to the GRACE Score. The technique of modifying the GRACE Score was used, by replacing Killip for NT-proBNP, and then comparing this GRACE-BNP model to the traditional GRACE. The modification of GRACE was performed in two ways, one numerical and another categorical. In the first case, the regression coefficient of NT‑proBNP represented the change in log odds promoted by each unit of NT-proBNP. In this case, the logistic regression equation determined the weight of NT-proBNP (numerical GRACE-BNP). In the second case, a high NT-proBNP added 20 points to the Killip free GRACE, which is the equivalent of Killip II value in the score (categorical GRACE-BNP). The C-statistics of both models were compared with the traditional GRACE Score by the Hanley-McNeil test. Finally, net reclassification index analysis by Pencina 15 was used to evaluate the reclassification value of logistic and categorical GRACE-BNP in relation to the definition of high risk. For this reclassification, the best cutoff points for these new scores were used in the ROC curve. Regarding sample size definition, two criteria were used. Firstly, aiming to reach a power of 80% to detect a difference of 0.05 between two ROC curves (referring to scores) and predicting a correlation of 0.80 between the scores, it would be necessary to enroll 192 patients. Secondly, in order to insert two variables in a logistic regression model, 10 to 20 events would be necessary. 16 All of the tests above were considered statistically significant if p-value < 0.05. The SPSS Version 21 was the software used for the analysis. Results Sample characteristics The sample consisted of 352 patients, mean age 63 ± 14 years, 60% male, 26% presenting with ST-segment elevationmyocardial infarction. The GRACE score had amedian of 104 (IIQ 82 - 131), which corresponds to intermediate risk. The median of NT-proBNP was 340 pg/ml (IIQ 86-1212), elevated in 29%of patients. Themedian time between symptom onset and NT-pro-BNP dosage was 15.5 hours (IIQ 8.2 - 32.5). The incidence of cardiovascular death in the hospital phase was 4.8%. Sample characteristics are described in Table 1. 667