N-Terminal Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide-to-Troponin - Ratios for Differentiating Type 1 From Type 2 Myocardial Infarction: A HIGH-US Substudy

Abstract

Background: Differentiating type 1 myocardial infarction (T1-MI) from type 2 MI (T2-MI) remains a diagnostic challenge, even with the availability of high-sensitivity cardiac troponin assays. This study explored whether N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), BNP, and their respective ratios to troponin could enhance the ability to distinguish between these MI subtypes.

Methods: As a High-Sensitivity Cardiac Troponin I Assays in the United States substudy, we examined data from 280 patients diagnosed with non-ST elevation MI (172 with T1-MI and 108 with T2-MI). We assessed NT-proBNP, BNP, high-sensitivity cardiac troponin I, and their ratios as potential discriminative biomarkers. Diagnostic accuracy was evaluated using receiver operating characteristic curves.

Results: NT-proBNP levels were markedly elevated in T2-MI patients compared with those with T1-MI (mean: 10,327 ± 12,923 vs. 4675 ± 11,740 ng/L; P = 0.006). Conversely, high-sensitivity cardiac troponin I concentrations were higher in T1-MI (1.4 ± 5.1 vs. 0.5 ± 1.1 ng/L; P = 0.030). Notably, the NT-proBNP-to-troponin ratio was more than 3 times greater in T2-MI cases (94,880 ± 152,648 vs. 24,209 ± 78,727; P = 0.007). NT-proBNP alone demonstrated fair discriminatory capacity [area under the receiver operating characteristic curve (AUC) 0.717, 95% confidence interval (CI): 0.578-0.856], closely matching the NT-proBNP-to-troponin ratio (AUC: 0.720, 95% CI: 0.566-0.873). In contrast, BNP and the BNP-to-troponin ratio offered lower diagnostic values. Mean BNP levels were 505.4 ± 576.6 ng/L for those with T2-MI and 437.1 ± 738.8 ng/L for patients with T1-MI. BNP-to-troponin ratio showed a poor discrimination for the 2 MI types (AUC: 0.660; 95% CI: 0.532-0.789).

Conclusions: Both NT-proBNP and its ratio to troponin show potential in differentiating T1-MI from T2-MI, reflecting distinct underlying pathophysiological processes. Given its comparable performance to the ratio, NT-proBNP alone may serve as a practical and cost-effective standalone marker. These findings support the hypothesis that incorporating NT-proBNP testing into routine clinical workflows may better inform the management of patients with suspected MI.

Keywords: N-terminal pro-B-type natriuretic peptide; biomarkers; diagnosis; differentiation; myocardial infarction; ratio; troponin.