N-terminal prohormone of brain natriuretic peptide predicts recurrent cardiovascular events in patients with acute coronary syndrome both in the acute and post-discharge setting: a TRACER substudy

Abstract Background N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a circulating peptide released by the heart in response to increased wall tension and stretching, for example, occurring during myocardial and/or atrial dysfunction. NT-proBNP is a diagnostic and prognostic marker in patients with heart failure but might also have prognostic utility in the acute phase of patients with acute coronary syndrome (ACS) and at one month after ACS. Purpose To assess the prognostic value of NT-proBNP over time in patients with ACS both in the acute setting and when re-assessed after one month. Methods The TRACER study randomized 12,944 patients with non-ST-segment elevation ACS (NSTE-ACS) to treatment with vorapaxar vs. placebo. Plasma samples for biomarker analyses were obtained at randomization (median 21 hours after hospital admission) in 6,800 patients and at an outpatient visit after one month in 5,313 patients. NT-proBNP was analysed using the Elecsys electrochemiluminescence immunoassays method. The primary composite endpoint in this substudy was the one-year risk of cardiovascular (CV) mortality, myocardial infarction, or ischaemic stroke. Associations between continuous natural log-transformed NT-proBNP levels and outcomes were assessed using Cox regression models accounting for study treatment and established risk factors. Results The median concentration of NT-proBNP during hospitalization for ACS and after one month was 496 ng/L and 264 ng/L, respectively. Higher age, female sex, a history of heart failure, and lower body mass index were independently associated with higher levels of NT-proBNP among patients in the acute setting, with renal disease also being an important factor after one month. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 901 patients (incidence rate 10.1 per 100 person-years) included at baseline and in 381 patients (incidence rate 5.4 per 100 person-years) included at one month. Higher circulating levels of NT-proBNP were independently associated with a higher risk of the composite endpoint at baseline (adjusted hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 1.25 [1.03 – 1.51]) and at one month (1.56 [1.15 – 2.11]) (Figure 1 and 2). Incorporating NT-proBNP at baseline into a model with other established risk factors increased the concordance index of the multivariable model from 0.656 to 0.660 (p < 0.001), and after one month, from 0.711 to 0.733 (p < 0.001). These findings remained consistent across the various components of the composite endpoint. Conclusions In patients with ACS, the level of NT-proBNP is an indicator of increased risk of CV outcomes both in the acute setting and, even more pronounced, one month after the index ACS. Measuring NT-proBNP provided incremental prognostic information beyond established risk factors, both in the acute and post-discharge settings.Fig 1.NT-proBNP quartile groupsFig 2.NT-proBNP and CV outcome