B-type natriuretic peptide molecular forms for risk stratification and prediction of outcome after acute myocardial infarction

doi:10.1016/j.ahj.2018.02.016

American Heart Journal

Volume 200, June 2018, Pages 37-43

https://doi.org/10.1016/j.ahj.2018.02.016 Get rights and content

Abstract

Background

B-type natriuretic peptide (BNP) is known to be a risk marker following acute myocardial infarction (MI). More recently, truncated molecular forms of the BNP molecule have been identified, with the association of these forms and outcome in acute MI not known. The present study investigated their use as risk stratifying biomarkers of this condition.

Methods

BNP molecular forms (BNP 5–32, BNP 4–32 and BNP 3–32) were measured in plasma from 1078 acute MI patients using immunocapture followed by MALDI-ToF-mass spectrometry. Associations of molecular forms with short-term and long-term adverse outcomes were assessed.

Results

BNP molecular forms were independent predictors of mortality/reinfarction, mortality/rehospitalization due to heart failure, and a composite of all events at 6 months, 1 year and 2 years and showed prognostic ability comparable with conventional BNP measurements (P < .001–0.026 vs. N-terminal [NT]-proBNP P < .001–0.020, respectively). Reclassification analyses showed BNP molecular forms successfully reclassified patient risk when used in addition to the GRACE clinical risk score (P ≤ .005). BNP 5–32 showed utility as a secondary risk stratification biomarker when used in combination with the GRACE score and NT-proBNP by successful down-classification of high-risk patients.

Conclusions

BNP molecular forms were associated with poor prognosis at 6 months, 1 year and at 2 years in patients with acute MI. BNP 5–32 showed successful utility as a secondary marker in combination with NT-proBNP after GRACE scoring. This study suggests a potential role for BNP molecular forms in prognosis and risk stratification after acute MI.

Section snippets

Study population

One thousand and seventy-eight patients were admitted with acute MI to University Hospitals of Leicester, UK, between August 2004 and April 2007. Each patient consented (informed and written) to have blood samples taken and outcomes surveyed. This study was approved by the local ethics committee and adhered to the Declaration of Helsinki.

Diagnosis of acute MI was made on the basis that all patients had a cardiac troponin I (cTnI) concentration above the 99th percentile, with at least one of the

Patient characteristics

Plasma samples from 1078 patients admitted to hospital with acute MI were analyzed for the presence of BNP molecular forms. Mass spectral peaks for BNP molecular forms were detected in a total of 617 (57.2%) samples. A breakdown of the measured end points and clinical demographics for the patient cohort is shown in Table I.

Analyses with associated clinical measurements and outcomes

Spearman's rank-order correlation analyses showed clinical variables that were associated with one or more of the BNP molecular forms to be blood urea, eGFR, age, cTnI at

Discussion

This study reports that molecular forms of BNP are associated with poor outcome in patients hospitalized with acute MI, and the utility of these molecular forms in clinical risk prediction. The results showed that molecular BNP forms 5–32, 4–32 and 3–32 were all independently able to predict death/MI, death/HF and MACE at 6 months, 1 year and at 2 years after adjustment for traditional clinical and physiological factors. These prognostic qualities were comparable to conventional measurements of

Disclosures

The authors have no disclosures.

Acknowledgements

The authors are grateful to Sekisui Medical Co. for provision of antibodies and RapidPIA™ BNP kits.

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We performed a retrospective analysis of patients admitted with STEMI included in the Portuguese Registry of Acute Coronary Syndromes (ProACS) between 2010 and 2019. Patients were divided into three groups according to BNP level (<100 pg/ml, 100-399 pg/ml and ≥400 pg/ml) and compared. Independent predictors of a composite of all-cause mortality and rehospitalization for cardiovascular causes were assessed by multivariate logistic regression. For sample homogenization, propensity score matching and pairwise matching with a tolerance level of 0.005 were performed.
A total of 1650 patients were included, of whom 21.5% presented high BNP levels (≥400 pg/ml). These were older and had more comorbidities, lower admission systolic blood pressure and hemoglobin, higher heart rate, Killip class and creatinine, worse left ventricular systolic function and severe coronary anatomy. Higher BNP was associated with more in-hospital complications, in-hospital mortality and adverse outcomes at one year.
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Avaliar o valor diagnóstico e prognóstico dos níveis de BNP numa coorte portuguesa de doentes com enfarte do miocárdio com elevação de ST (STEMI).
Realizámos uma análise retrospectiva de pacientes admitidos com STEMI incluídos no Registo Português de Síndromes Coronarianas Agudas (ProACS) entre 2010 e 2019. Os pacientes foram divididos em três grupos de acordo com o nível BNP (<100 pg/ml, 100-399 pg/ml e ≥400 pg/ml) e comparados. Preditores independentes de um composto de mortalidade por todas as causas e re-hospitalização para causas cardiovasculares foram avaliados por regressão logística multivariada. Para a homogeneização da amostra, foi realizada uma correspondência de propensão e uma correspondência em pares com um nível de tolerância de 0,005.
Foram incluídos 1650 doentes; 21,5% apresentaram níveis elevados de BNP (≥400 pg/ml). Estes doentes eram mais velhos; apresentavam mais comorbilidades; menor pressão arterial sistólica e hemoglobina à admissão; frequência cardíaca, classe Killip e creatinina mais elevados; pior função sistólica ventricular esquerda e anatomia coronária mais grave. A elevação de BNP associou-se a maior taxa de complicações intra-hospitalares, mortalidade intra-hospitalar e outcomes adversos a ano.
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This response includes activation of various immune cells, elevation of circulating chemokines, cell adhesion molecules and inflammatory cytokines and activation of the complement system (Hasdai et al., 1996). Evidence suggests that markers for systemic inflammatory response are predictors for adverse clinical outcomes, such as death, recurrent myocardial infarction, and heart failure in patients with AMI (Israr et al., 2018). The development of cardiac repair begins after 20 min of severe ischemia; cardiomyocytes exhibit irreversible changes that ultimately result in cell death.
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: Conflicts of interest: The authors declare no conflicts of interest.

¹: LLN and TS contributed equally to this manuscript.

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Clinical InvestigationB-type natriuretic peptide molecular forms for risk stratification and prediction of outcome after acute myocardial infarction

Abstract

Background

Methods

Results

Conclusions

Section snippets

Study population

Patient characteristics

Analyses with associated clinical measurements and outcomes

Discussion

Disclosures

Acknowledgements

J Am Coll Cardiol

Int J Cardiol

Am J Cardiol

Association between Natriuretic Peptides and Mortality among Patients Admitted with Myocardial Infarction: A Report from the ACTION Registry®–GWTG

Clin Chem

Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction

Circulation

B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction

Circulation

N-terminal pro-B–type natriuretic peptide and long-term mortality in acute coronary syndromes

Circulation

Value of brain natriuretic peptide after acute myocardial infarction/Akut miyokard infarktusu sonrasi beyin natriuretik peptid'in degeri

Anadolu Kardiyol Derg

Plasma brain natriuretic peptide (BNP) as an indicator of left ventricular function, early outcome and mechanical complications after acute myocardial infarction

Clin Med Insights Cardiol

Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure

Circ Heart Fail

Profiling B-type natriuretic peptide cleavage peptidoforms in human plasma by capillary electrophoresis with electrospray ionization mass spectrometry

J Proteome Res

Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form

Clin Chem

Hydrolysis of human and pig brain natriuretic peptides, urodilatin, C-type natriuretic peptide and some C-receptor ligands by endopeptidase-24.11

Biochem J

Processing of pro-B-type natriuretic peptide: furin and corin as candidate convertases

Clin Chem

Clinical Investigation
B-type natriuretic peptide molecular forms for risk stratification and prediction of outcome after acute myocardial infarction