B-type natriuretic peptide in cardiovascular disease

doi:10.1016/S0140-6736(03)13976-1

The Lancet

Volume 362, Issue 9380, 26 July 2003, Pages 316-322

https://doi.org/10.1016/S0140-6736(03)13976-1 Get rights and content

Summary

Natriuretic peptide hormones, a family of vasoactive peptides with many favourable physiological properties, have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The rapid incorporation into clinical practice of bioassays to measure natriuretic peptide concentrations, and drugs that augment the biological actions of this system, show the potential for translational research to improve patient care. Here, we focus on the physiology of the natriuretic peptide system, measurement of circulating concentrations of B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (N-terminal BNP) to diagnose heart failure and left ventricular dysfunction, measurement of BNP and N-terminal BNP to assess prognosis in patients with cardiac abnormalities, and use of recombinant human BNP (nesiritide) and vasopeptidase inhibitors to treat heart failure.

Published online April 23,2003 http://image.thelancet.com/extras/02art2325web.pdf

Section snippets

Historical perspective

A series of experiments done in the mid 1950s established the heart as an endocrine organ. First, Kisch and colleagues¹ detected secretory granules in guineapig atria. Henry and Pearce² subsequently described increased urinary flow after balloon stretch of the canine left atrium. In an experiment done 25 years later, de Bold³ injected homogenised atrial tissue into rats and noted increased sodium excretion and urinary volume. In 1984, the structure of atrial natriuretic peptide (ANP) was

Natriuretic peptides as cardiac biomarkers

For a biomarker to be valuable in clinical practice, it should be able to be measured rapidly and accurately at a reasonable cost; add diagnostic or prognostic information to available methods; and help to guide patient management. BNP and N-terminal BNP fulfil most of these criteria in patients with suspected heart failure. BNP predicts disease state and prognosis better than ANP or N-terminal ANP.42, 43, 44, 45 Although adequately powered head-to-head comparisons have not been done,

Heart failure

Heart failure can be difficult to diagnose accurately, because the signs and symptoms of this disorder are neither sensitive nor specific.⁴⁷ These limitations are especially relevant when symptoms are mild or when patients are elderly or have comorbid disorders that mimic heart failure, such as pulmonary disease or obesity. In early pilot studies, raised concentrations of BNP distinguished heart failure from other causes of dyspnoea more accurately than did left-ventricular ejection fraction,

Limitations of diagnostic use of BNP

There are several important limitations to note when considering the diagnostic role of BNP. First, patients sometimes present with concomitant disorders, such as pneumonia and decompensated heart failure. Thus, a very high concentration of BNP, although specific for decompensated heart failure, does not exclude presence of other important diseases. Second, patients with chronic heart failure might have persistently high concentrations of BNP despite adequate treatment; here, accurate diagnosis

BNP for prognostic assessment

In patients with chronic heart failure, higher concentrations of BNP are associated with increased cardiovascular and all-cause mortality, independent of age, NYHA class, previous myocardial infarction, and left-ventricular ejection fraction.71, 72, 73 In multivariate analyses,71, 72, 73 BNP was more closely associated with mortality than was NYHA class or left-ventricular ejection fraction, and in one study of outpatients with chronic heart failure,⁷⁴ plasma concentrations of natriuretic

Effect of treatment on BNP concentrations

In patients with decompensated heart failure who are treated aggressively with diuretics and vasodilators, BNP concentrations fall rapidly together with intracardiac filling pressures.59, 90 ACE inhibitors,52, 91, 92 angiotensin-II receptor antagonists (valsartan),⁹³ and an aldosterone antagonist (spironolactone)⁹⁴ also lead to modest reductions in BNP concentrations. The effects of β blockers on BNP concentrations are more complex. On the one hand, because adrenergic stimulation inhibits

BNP concentrations and decision-making in chronic heart failure

Beyond its diagnostic and prognostic value, BNP can also help physicians to make clinical decisions about patients with heart failure, although much work remains in this emerging field. The premise of this approach is that decisions to start or titrate pharmacological treatments, or to use a more invasive strategy such as cardiac transplantation,⁹⁹ might be based not only on symptoms and physical examination findings, but also on the concentrations of BNP.71, 76 Two provocative pilot studies92,

Therapeutic potential

The physiological properties of ANP and BNP, including natriuresis, arterial and venous dilation, inhibition of the sympathetic nervous system, and antagonism of the renin-angiotensin-aldosterone axis, fulfil many criteria for an ideal agent to treat heart failure. As a result, interest has focused on development of drugs that modulate the natriuretic peptide hormone system. Two approaches have reached late-stage clinical development: administration of exogenous natriuretic peptides and

Nesiritide

Recombinant human BNP (nesiritide) is now available for treatment of decompensated heart failure. In early phase 1 and 2 studies, BNP infusion decreased pulmonary capillary wedge pressure and improved cardiac index and urinary flow rate in a dose-dependent manner;101, 102, 103, 104 the reduction in cardiac filling pressures was independent of the diuretic effect of the agent.¹⁰⁵ In addition, favourable neurohormonal effects were recorded, including a reduction in norepinephrine and aldosterone

Vasopeptidase inhibitors

ANP and BNP clearance involves two mechanisms: binding to the clearance (NPR-C) receptor and degradation by neutral endopeptidase, an enzyme that is upregulated in heart failure.¹⁰⁹ In addition to natriuretic peptides, neutral endopeptidase degrades the vasodilators bradykinin and adrenomedullin, and the vasoconstrictors endothelin-1 and angiotensin II¹¹⁰. Therefore, selective neutral endopeptidase inhibitors can cause either vasodilation or vasoconstriction, depending on whether vasodilator or

The future

Measurement of BNP will probably become a routine component of care for patients with known or suspected heart failure. In patients presenting with dyspnoea, a low concentration of BNP can accurately rule out decompensated heart failure, whereas a very high concentration of this peptide clearly supports the diagnosis of heart failure but does not exclude presence of other processes contributing to dyspnoea. Small rises in BNP are not specific since many diseases have concentrations of BNP

Search strategy and selection criteria

We searched the National Library of Medicine's electronic database using the keywords natriuretic peptide, atrial natriuretic peptide, brain natriuretic peptide, B-type natriuretic peptide, ANP, BNP, CNP, nesiritide, omapatrilat, vasopeptidase inhibitors, and neutral endopeptidase. Articles about basic physiology and with applications to people with cardiac disease were reviewed. We also searched the references of selected articles.

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High brain natriuretic peptide level is associated with severe stroke in patients taking oral anticoagulants: A sub-analysis of the PASTA registry study
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Brain natriuretic peptides (BNP) are an important diagnostic and prognostic marker in patients with heart failure. However, the relationship between BNP levels and stroke severity in patients with atrial fibrillation (AF) remains unelucidated. In this study, we aimed to investigate the association between stroke severity at admission and BNP levels.
In this prospective observational study, we used data from 513 patients with AF and acute ischemic stroke treated with oral anticoagulants (OAC) registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study. The patients were divided into two groups: high-BNP (≥200 pg/mL) and low-BNP level (<200 pg/mL) groups. We compared the clinical characteristics between the two groups and determined the effect of BNP levels on stroke severity on admission.
Among the 513 enrolled patients, 248 (females, n = 30; median age, 82 years) and 265 (females, n = 76; median age, 71 years) were assigned to the high- and low-BNP level groups, respectively. The high-BNP level group had a higher proportion of patients with severe stroke (National Institutes of Health Stroke Scale score, ≥10) on admission (49.2% vs. 32.8%, p = 0.002) and major vessel occlusion (57.5% vs. 39.2%, p < 0.0001) than that had by the low-BNP level group. Multivariate analysis showed that high BNP level was independently associated with severe stroke on admission (odds ratio 1.07, 95% confidence interval 1.00–1.15; p = 0.0478).
High BNP level compared with low BNP level was associated with severe stroke and major vessel occlusion, even before OAC treatment.
Left ventricular hypertrophy phenotype to predict incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis
2024, Nutrition, Metabolism and Cardiovascular Diseases
Left ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, the predictive value of the LVH phenotype for incident AF remains uncertain. This study aimed to investigate the predictive value of LVH phenotype for incident AF.
This study utilized the Multi-Ethnic Study of Atherosclerosis (MESA) data. LVH was defined by cardiac magnetic resonance measured LV mass index. Isolated LVH was determined as LVH without elevated cardiac biomarker and malignant LVH was determined as LVH with at least 1 elevated biomarker. Receiver-operating characteristic (ROC) analysis was performed to calculate areas under the curves (AUC) for predicting AF. A total of 4983 community-dwelling participants were included, with a mean age of 61.5 years. 279 (5.6 %) had isolated LVH, and 222 (4.5 %) had malignant LVH. During a median follow-up of 8.5 years, 272 incident AF was observed. Compared to participants without LVH and elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95 % CI, 1.03–3.20) and malignant LVH (HR, 4.13; 95 % CI, 2.77–6.16) had a higher risk of incident AF. Malignant LVH carried a 1.5-fold increased risk of AF compared to isolated LVH (HR: 2.48, 95 % CI: 1.30–4.73). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (AUC increase: 0.03, p < 0.001).
The risks of AF incidence varied across LVH phenotypes. Malignant LVH carried the highest risk among LVH phenotypes. LVH phenotype provides incremental predictive value over the variables included in the CHARGE-AF model.
The liver-heart axis in patients with severe obesity: The association between liver fibrosis and chronic myocardial injury may be explained by shared risk factors of cardiovascular disease
2024, Clinical Biochemistry
Severe obesity is associated with increased risk of non-alcoholic fatty liver disease and cardiovascular disease. We hypothesized that liver fibrosis as quantified by the Enhanced Liver Fibrosis (ELF) test would be predictive of myocardial injury and fibrosis, expressed by higher concentrations of cardiac troponin T and I measured by high-sensitivity assays (hs-cTnT and hs-cTnI, respectively).
We performed cross-sectional analyses of baseline data from 136 patients (mean age 45 years, 38 % male) with severe obesity participating in the non-randomized clinical trial Prevention of Coronary Heart Disease in Morbidly Obese Patients (ClinicalTrials.gov NCT00626964). Associations between ELF scores, hs-cTnT, and hs-cTnI concentrations were assessed using linear regression analysis.
ELF scores were associated with hs-cTnT in the unadjusted model (B 0.381, 95 % Confidence Interval [CI] 0.247, 0.514), but the association was attenuated upon adjustment for potential confounders (B −0.031, 95 % CI −0.155, 0.093). Similarly, for hs-cTnI, an observed association with ELF scores in the unadjusted model was attenuated upon adjustment for potential confounders ((B 0.432, 95 % CI 0.179, 0.685) and (B 0.069, 95 % CI −0.230, 0.367), respectively). Age, sex, hypertension, and estimated glomerular filtration rate were amongst the shared predictors of ELF score, hs-cTnT, and hs-cTnI that provided the univariable models with the highest R-squared and lowest Akaike Information Criterion values.
Contrary to our hypothesis, ELF score did not predict myocardial injury and fibrosis, but we rather demonstrated an association between liver fibrosis and myocardial injury and fibrosis may be explained by shared risk factors of cardiovascular disease.
Left Atrial Remodeling Related to Disproportionately Low B-Type Natriuretic Peptide in Acute Heart Failure Patients with Atrial Fibrillation
2023, American Journal of Cardiology
The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling. We hypothesized that LA remodeling affects BNP secretion in acute HF conditions. The study investigated the clinical impact of LA remodeling on admission BNP levels in acute HF patients with and without AF. Consecutive acute HF hospitalized patients (n = 899) were divided into groups with (n = 382) or without AF (n = 507) and subdivided into disproportionately low BNP (LB) (≤200 pg/ml), medium BNP (200 to 600 pg/ml) and high BNP (≥600 pg/ml) subgroups. The AF group had a higher proportion of patients with LB than the non-AF group (23.6% vs 16.6%, p = 0.009). BNP levels in both groups were positively correlated with LV end-diastolic volume and negatively correlated with LV ejection fraction in both groups. In contrast, BNP was positively correlated with LA volume index in the non-AF group, but negatively correlated in the AF group. The survival rates were significantly higher in the LB group than in the other groups in non-AF. Conversely, there were no significant differences across all groups in AF patients. In conclusion, in patients with acute HF and AF, disproportionately low BNP levels are associated with LA structural remodeling and poor prognosis.
Postmortem biochemistry in deaths from ischemic heart disease
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Ischemic heart disease (IHD) is one of the leading causes of morbidity and sudden cardiac death worldwide and is an important public health problem. The presence of ischemia in clinical applications can be detected by ECG, biochemical markers, and radiological methods. Myocardial infarction is also frequently encountered in forensic autopsies. Postmortem diagnosis is determined as a result of histopathological examinations and additional exclusionary examinations (toxicology, microbiology, etc.). However, routine histopathological examinations are insufficient, especially when death occurs in the early period of ischemia. It creates a problem for forensic pathologists and forensic medicine specialists in such cases of sudden cardiac death. Postmortem biochemistry is one of the important and promising disciplines in which forensic applications work in order to diagnose these cases correctly. The issue of whether biomarkers used in the diagnosis of myocardial infarction in clinical studies can be used reliably in postmortem cases has been discussed by forensic medicine researchers for some time. This manuscript aims to review and summarize biomarkers belonging to various categories that have been studied in IHD-related deaths, in biological fluids taken at autopsy, or in animal experiments. Our study shows that the postmortem use of biochemical markers in the diagnosis of IHD yields promising results. However, it should not be forgotten that postmortem biochemistry is different from clinical applications due to its dynamics and that the body causes unpredictable changes in markers in the postmortem process. Therefore, comprehensive studies are needed to evaluate the postmortem stability of these markers in different biological fluids, their significance among various causes of death, and whether they are affected by any variable (Cardiopulmonary resuscitation, Postmortem interval, medications, etc.) before they are routinely applied. It is suggested by the authors that the cut-off values of biomarkers whose significance has been proven by these studies should be determined and that they should be used in this way in routine applications.
Recent advances in electrochemical aptasensors for detecting cardiac biomarkers: A review
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ReviewB-type natriuretic peptide in cardiovascular disease

Summary

Section snippets

Historical perspective

Natriuretic peptides as cardiac biomarkers

Heart failure

Limitations of diagnostic use of BNP

BNP for prognostic assessment

Effect of treatment on BNP concentrations

BNP concentrations and decision-making in chronic heart failure

Therapeutic potential

Nesiritide

Vasopeptidase inhibitors

The future

Search strategy and selection criteria

Life Sci

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Biochem Biophys Res Commun

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Lancet

Electron microscopy of the atrium of the heart: I Guinea pig

Exp Med Surg

The possible role of cardiac stretch receptors in the induction of changes in urine flow

J Physiol

A new natriuretic peptide in porcine brain

Nature

Review
B-type natriuretic peptide in cardiovascular disease