Serum brain natriuretic peptide in children with Kawasaki disease

Abstract

BACKGROUND:

Kawasaki disease (KD) is a common cause of acquired heart disease in children. Recent studies have focused on the biochemical markers of the myocardium, their high sensitivity and specificity and significance in the diagnosis of KD. This study aimed to determine the serum level of brain natriuretic peptide (BNP) and its relation with the heart function of children with KD and to explore its clinical value in diagnosis of KD.

METHODS:

Forty-three KD children, aged from 5 months to 8 years (mean 2.3±0.6 years), were admitted to Qingdao Children’s Hospital from February 2007 to April 2009. Among them 27 were male, and 16 female. The 43 patients served as a KD group. Patients with myocarditis, cardiomyopathy, congenital heart disease and other primary heart diseases were excluded. Thirty healthy children, aged from 3 months to 15 years (mean 2.5±0.8 years) or 17 males and 13 females served as a control group. There were no significant differences in age and gender between the two groups (P>0.05). In the KD group, ELISA was used to measure the levels of serum BNP in acute and convalescent stages; and in the control group, the levels of serum BNP were measured once randomly. Left ventricular ejection fraction (LVEF), left ventricular shorten fraction (LVSF), cardiac index (CI) and left ventricular inflow velocity through the mitral annulus (including E-velocity and A-velocity) were measured by two-dimensional echocardiography in the acute and convalescent stages in the KD group. All data were expressed as mean±SD. The methods of analysis included Student’s t test and the linear regression analysis test. P<0.05 was considered statistically significant.

RESULTS:

The level of serum BNP in the acute stage (517.26±213.40) ng/ml was significantly higher than that in the convalescent stage (91.56±47.97) ng/ml in the control group (37.55±7.56) ng/ml (P<0.01). The levels of LVEF, LVSF and CI in the acute stage were significantly lower than those in the convalescent stage (P<0.05), but the E/A level was not significantly different between the acute and convalescent stages (P>0.05). Linear regression analysis showed that the BNP level was negatively correlated with the levels of LVEF, LVSF and CI(r=-0.63, -0.52, -0.53, P<0.05), but not significantly correlated with the E/A level (r=-0.18, P>0.05).

CONCLUSION:

The levels of serum BNP are significantly increased in KD patients, and are negatively correlated with the levels of LVEF, LVSF, and CI. The detection of serum BNP level is of clinical significance in the diagnosis of KD.

INTRODUCTION

Kawasaki disease (KD) is characterized by the activation of the immune system and the extensive damage of the vascular endothelial system, as well as the pathological changes of non-specific systemic vasculitis.[1] It is a common cause of acquired heart disease in children.[2-4] KD is thought to affect small and medium-sized arteries, particularly the coronary artery.[5,6] Some patients develop aneurysm, and few develop progressive stenosis, occlusion or myocardial infarction.[7-9] At present, research has focused on the biochemical markers of the myocardium, their high sensitivity and specificity and their significance in the diagnosis of KD. In this study, we investigated the level of serum brain natriuretic peptide (BNP), its correlation with heart function in KD children, and its clinical value in the diagnosis of KD.

METHODS

Patients

Forty-three KD patients, 27 males and 16 females, who had been treated at the Department of Pediatric Cardioangiology in Qingdao Children’s Hospital from February 2007 to April 2009, served as a KD group. Their age ranged from 5 months to 8 years, with a median age of 2.3±0.6 years. They had complete clinical data,and met the diagnostic criteria of KD.[10-12] Patients with primary heart diseases such as myocarditis, cardiomyopathy, congenital heart disease were excluded.

Thirty healthy children served as a control group, including 17 males and 13 females. Their age ranged from 3 months to 15 years, with a median age of 2.5±0.8 years. Their age or gender was not significantly different between the two groups (P>0.05)

Methods

One ml of blood was collected from veins of each patient, kept in an anticoagulant tube with 1μl of aprotinin added in advance, was mixed and centrifuged at a speed of 3000 r/min. Serum was separated, frozen at -20 °C, and put together to detect BNP. BNP was detected within 48 hours. Specimens were taken from the KD group at 24 hours after final diagnosis (acute stage) and 2-3 weeks after treatment (convalescent stage), respectively. In the control group, the specimens were collected only once randomly.

Enzyme-linked immunosorbent assay (ELISA) was used to determine BNP, using the kit produced by Abbott Company, USA. Left ventricular ejection fraction (LVEF),ventricular shorten fraction(LVSF), cardiac index (CI) and left ventricular inflow velocity through the mitral annulus, including E-velocity and A-velocity, were measured by type-IE33 Doppler echocardiograph produced by Philip Company in the acute and convalescent stages in the KD group, respectively.

Statistical analysis

The data measured were described as mean±SD. Two-dependent-sample t-test was used to compare the levels of serum BNP in the acute stage of both groups, the KD group and the control group. Matched t-test was used to compare the levels of serum BNP and heart function in the acute and convalescent stages of the KD patients. Student’s t test was applied if there was heterogeneity of variance. Linear correlation analysis was performed to detect the relationship between the level of serum BNP and the heart function. Statistical analyses were made with the statistical software package of SPSS version 11.5. A P value <0.05 was considered statistically significant.

RESULTS

Compared to the stage of convalescence in the control group, the level of serum BNP in the acute stage in the KD group was significantly higher (P<0.01) but the levels of LVEF, LVSF, and CI decreased (P<0.05).There were no significant differences in E/A between the two groups (P>0.05) (Table 1).

Table 1.

Comparison of the BNP level and cardiac function parameters between the KD and control groups (mean±SD)

The level of serum BNP in the acute stage of the AD group was negatively correlated with the levels of LVEF, LVSF, and CI (P<0.05) but it was not significantly correlated with E/A (P>0.05) (Table 2).

Table 2.

The correlation analysis between BNP and cardiac function parameters in the KD group in the acute stage

DISCUSSION

The diagnosis of KD is mainly based on whether clinical manifestations of KD meet the diagnostic criteria and are differentiated from those of other diseases. Although the diagnostic criteria have been revised repeatedly by the MCLS Cooperative Research Group in Japan, the diagnosis of KD is always dependent on its clinical manifestations nonspecifically. Besides, the early manifestations of KD are similar to those of infections caused by streptococcus, staphylococci, adenovirus, rubella virus and other pathogens, ultimately resulting in the misdiagnosis and mistreatment of the disease. Therefore, it is necessary to find out valuable laboratory parameters for the diagnosis of KD.

Brain natriuretic peptide (BNP), a neuroendocrine hormone, secreted by the left ventricle myocyte. Its secretion is increased when the heart is overloaded or dilated. BNP can be used as a sensitive and specific target for the early diagnosis of heart failure in children because of its rapid composition and secretion,[13-17] and it has been widely used in assessing the diagnosis and therapeutic efficacy of heart function.[18-21] Recent studies[22] have found that compared to other viral infectious diseases, the plasmatic level of BNP changed evidently in KD patients, which is sufficient to be a biological marker. In the present study the plasmatic level of BNP in the KD patients in the acute stage was significantly higher than that in the control group in the convalescent stage. Hence we consider that it can be used as a reference target for the early diagnosis of KD.

In the acute stage of KD patients, the disorder of blood supply to cardiac muscle caused by coronaritis and microvascular damage may result in a wall motion abnormality, and heart function will be anomalous to some extent, consequently. Liu[23,24] reported that KD patients have intact heart dysfunction, and there are significant differences in LVEF between the acute stage and convalescent stage. In the present study, the levels of LVEF, LVSF, and CI were significantly decreased in the acute stage in the KD patients, and then gradually returned to normal in the convalescent stage, while E/A was not significantly changed. The increased level of BNP in the acute stage was negatively correlated with the levels of LVEF, LVSF, and CI.[25] Thus the combination of BNP detection in the acute stage and heart function may contribute to KD diagnosis in the early stage.

Currently, the mechanism of plasmatic level of BNP in KD children is still unclear, but it is considered to be associated with changed ventricular wall stress and stretched cadiocytes, which are caused by decreased function of the left ventricle; thus BNP is synthesized and secreted largely by the stimulated myocardial cells.[26] Kurotobi et al[27] found that there were some relationships between the increased NT-proBNP plasmatic level in acute stage of the disease and the diastolic dysfunction of the ventricule in KD patients, whereas in our study no clear correlation was observed between BNP and E/A. Possibly it is due to the small sample size, and a large number of cases are needed for further study in future. In the acute and subacute stages of KD, considerable cytokines and inflammatory mediators such as interleukins, TNF-α, interferons, superoxide radicals, which are released by abnormal actived T cells and monocytes, appear in peripheral blood and cause immunologic injury of cadiocytes and secretion of BNP.[28-31]

In short, the marked elevation of BNP in the acute stage of KD patients, which is negatively correlated with the systolic function of the left ventricle, is valuable to the early diagnosis of KD.