Dataset Information

NT-proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme.

ABSTRACT:

Aims

Guidelines support the role of B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) for risk stratification of patients in programmes to prevent heart failure (HF). Although biologically formed in a 1:1 ratio, the ratio of NT-proBNP to BNP exhibits wide inter-individual variability. A report on an Asian population suggests that molar NT-proBNP/BNP ratio is associated with incident HF. This study aims to determine whether routine, simultaneous evaluation of both BNP and NT-proBNP is warranted in a European, Caucasian population.

Methods and results

We determined BNP and NT-proBNP levels for 782 Stage A/B HF patients in the STOP-HF programme. The clinical, echocardiographic, and biochemical associates of molar NT-proBNP/BNP ratio were analysed. The primary endpoint was the adjusted association of baseline molar NT-proBNP/BNP ratio with new-onset HF and/or progression of left ventricular dysfunction (LVD). We estimated the C-statistic, integrated discrimination improvement, and the category-free net reclassification improvement metric for the addition of molar NT-proBNP/BNP ratio to adjusted models. The median age was 66.6 years [interquartile range (IQR) 59.5-73.1], 371 (47.4%) were female, and median molar NT-proBNP/BNP ratio was 1.91 (IQR 1.37-2.93). Estimated glomerular filtration rate, systolic blood pressure, left ventricular mass index, and heart rate were associated with NT-proBNP/BNP ratio in a linear regression model (all P < 0.05). Over a median follow-up period of 5 years (IQR 3.4-6.8), 247 (31.5%) patients developed HF or progression of LVD. Log-transformed NT-proBNP/BNP ratio is inversely associated with HF and LVD risk when adjusted for age, gender, diabetes, hypertension, vascular disease, obesity, heart rate, number of years of follow-up, estimated glomerular filtration rate, and baseline NT-proBNP (odds ratio 0.71, 95% confidence interval 0.55-0.91; P = 0.008). However, molar NT-proBNP/BNP ratio did not increase the C-statistic (Δ -0.01) and net reclassification improvement (0.0035) for prediction of HF and LVD compared with NT-proBNP or BNP alone. Substitution of NT-proBNP for BNP in the multivariable model eliminated the association with HF and LVD risk.

Conclusions

This study characterized, for the first time in a Caucasian Stage A/B HF population, the relationship between NT-proBNP/BNP ratio and biological factors and demonstrated an inverse relationship with the future development of HF and LVD. However, this study does not support routine simultaneous BNP and NT-proBNP measurement in HF prevention programmes amongst European, Caucasian patients.

SUBMITTER: Sweeney C

PROVIDER: S-EPMC8712901 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02358-y.