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Clinical significance of plasma levels of N-terminal brain natriuretic peptide and copeptin in patients with acute cerebral haemorrhage

Niu Ruina* and Teng Fangjun

Neural Severe Division, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China

*Corresponding Author:
Niu Ruina
Neural Severe Division
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, PR China

Accepted on December 30, 2016

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Abstract

Objective: To investigate the clinical significance of plasma levels of N-terminal Brain Natriuretic Peptide (NT-proBNP) and copeptin in patients with acute cerebral haemorrhage.

Methods: 126 patients with acute cerebral haemorrhage from June 2015 to August 2016 in our hospital were chosen as the observation group. In the same period, 60 health participants were included into the control group. The plasma levels of NT-proBNP and copeptin of the two groups were tested and compared. According to the different amount of bleeding, the observation group were divided into massive cerebral haemorrhage group (29 cases), medium cerebral haemorrhage group (57 cases) and a small cerebral haemorrhage group (40 cases). According to the prognosis of the patients, the observation group were divided into death group (24 cases) and survival group (102 cases). The plasma levels of NTproBNP and copeptin in patients with different bleeding volume and prognosis were analysed.

Results: Plasma levels of NT-proBNP and copeptin of the observation group were significantly higher than that of the control group, with significant difference (t=34.21 P<0.05, t=34.85 P<0.05 respectively). Plasma levels of NT-proBNP and copeptin of the massive cerebral haemorrhage group (29 cases), the medium cerebral haemorrhage group and the small cerebral haemorrhage group were synchronously decreased, and there were significant differences among three groups (small group vs. mild group, q=6.36, P<0.05, small group vs. massive group, q=41.67, P<0.05, mild group vs. massive group, q=38.83, P<0.05). Compared with the death group, plasma levels of NT-proBNP and copeptin of the survival group were significantly reduced, the difference was statistically significant (t=26.86, P<0.05, t=6.98, P<0.05 respectively). There were a significant positive correlation between the plasma levels of NTproBNP, copeptin and the amount of cerebral haemorrhage (r=0.54, P<0.05, r=0.48, P<0.05 respectively), GCS score (r=0.43, P<0.05, r=0.37, P<0.05 respectively).

Conclusion: Early combined detection of plasma levels of NT-proBNP and copeptin in patients with acute cerebral haemorrhage can reflect the severity of cerebral haemorrhage; assess the prognosis of patients, which have a certain clinical referential value.

Keywords

Acute cerebral haemorrhage, N-terminal brain natriuretic peptide, Copeptin, Clinical significance.

Introduction

Acute Intracerebral Haemorrhage (AICH) is a common and frequently occurring disease in the neurology. It is also an acute and serious disease with high morbidity and mortality, becoming one of familiar diseases that threaten human health seriously [1]. In recent years, blood biochemical indicators of cardiovascular diseases in the clinical study gradually have increased, which also played an important clinical role in the risk stratification of patients with acute cerebral haemorrhage, and have an important meaning in the occurrence, development and prognosis of disease. Copeptin is the precursor of Arginine Vasopressin (Vasopressin, AVP), which is significantly increased in a variety of patients. Some studies have shown that the increased levels of copeptin had a correlation with poor prognosis of cerebrovascular disease and increased mortality, indicating it can help to optimize the prognosis stratification assessment of cerebrovascular disease [2,3]. Brain Natriuretic Peptide (BNP) is a kind of peptide neurohormone with sodium excretion and diuretic effect, which can effectively alleviate cerebral oedema. N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) is an N-terminal fragment of BNP-derived hormone, which has a long half-life, high sensitivity and easy detection, and is widely used in clinic [4,5]. In this study, the levels of plasma NT-proBNP and copeptin in patients with acute intracerebral haemorrhage were measured, and the relationship between plasma NT-proBNP, copeptin, the severity of the disease and prognosis were explored, which could provide scientific basis for clinical treatment of acute cerebral haemorrhage.

Materials and Methods

General information

A total of 126 patients with acute intracerebral haemorrhage in our hospital from June 2015 to August 2016, including 75 males and 51 females aged from 26 to 79 years (mean age of 63.80 ± 8.46 years), were enrolled as the observation group. All patients were in line with the relevant diagnostic criteria by the Fourth National Cerebrovascular Disease Conference [6]. They are in the first incidence with onset time within 24 h, excluding patients with the history of stroke and mental illness, heart, liver and kidney hematopoietic system. In addition, 60 healthy subjects were selected as the control group at the same time, including 40 males and 20 females aged 25-75 years (mean age of 63.52 ± 8.60 years). All participants gave their informed consent in the study, the trial was approved by the Ethics Committee in our hospital, and there was no significant difference between the general data of the two groups (P>0.05).

Method

According to the maximum diameter and thickness of the hematoma displayed by the CT scan of the patient, the hematoma size was calculated by the Tuo's formula (π/6 × length × width × number of CT layers) [4], and Glasgow Coma Scale (GCS) is used to evaluate neurological status. On the basis of the hematoma size, the observation group were divided into massive cerebral haemorrhage group (bleeding volume: >30 ml, 29 cases), moderate cerebral haemorrhage (bleeding volume: 10~30 ml, 57 cases) and small intracerebral haemorrhage (bleeding volume<10 ml, 40 cases). All patients were followed up for 6 months, and then were divided into survival group (102 cases) and death group (24 cases), the patients. Patients with acute cerebral haemorrhage within 24 h after admission and physical examinees in the morning of the day of examination were extracted for 5 ml fasting venous blood with Ethylenediaminetetraacetic Acid (EDTA) in the tube. NT-proBNP was detected with automatic electrochemiluminescence immunoassay analyser (Cobase4112010, Roche, Switzerland), using the instrument supporting the detection reagent. The Enzyme-Linked Immunosorbent Assay (ELISA) was used to determine copeptin. The kit was supplied by R & D (USA). All test procedures are carried out in accordance with the operating instructions.

Statistical analysis

The statistical analysis was conducted with SPSS 19.0 software, quantitative data was presented as mean ± standard deviation (x̄ ± s). Comparison between the two groups was conducted with t test, while multiple groups with analysis of variance, comparison between any two groups using by SNK-q test. The correlation was analysed with Pearson correlation analysis, P<0.05 means the difference with statistical significance.

Results

Plasma levels of NT-proBNP and copeptin in the observation group and control group

As shown in Table 1, plasma NT-proBNP and copeptin levels in the observation group were significantly higher than that in the control group, with statistical significance (P<0.05).

Groups Number of cases NT-proBNP (pg/ml) Copeptin (ng/ml)
Control group 60 87.65 ± 24.72 0.91 ± 0.15
Observation group 126 728.40 ± 143.86 3.52 ± 0.57
t-value   34.21 34.85
P-value   <0.001 <0.001

Table 1. Comparison of plasma levels of NT-proBNP and copeptin in the two groups (͞x ± s).

The plasma NT-proBNP, copeptin and GCS in the patients with different bleeding volume

Table 2 indicated the plasma levels of NT-proBNP, copeptin and GCS were decreased along with massive cerebral haemorrhage group, mild cerebral haemorrhage group and small haemorrhage group. There was statistically significant difference in the three groups (small group vs. mild group, q=6.36 P<0.05, small group vs. massive group, q=41.67, P<0.05, mild group vs. massive group, q=38.83, P<0.05).

Groups Number of cases NT-proBNP (pg/ml) Copeptin (ng/ml) GCS
small haemorrhage group 40 165.52 ± 58.36 3.12 ± 0.54 12.90 ± 1.23
mild haemorrhage group 57 417.28 ± 172.54 3.46 ± 0.55 7.95 ± 1.64
massive haemorrhage group 29 2116.30 ± 508.89 4.19 ± 0.58 4.17 ± 0.96
F-value 503.17 31.98 348.08
P-value      
  <0.001 <0.001 <0.001  

Table 2. Comparison of plasma levels of NT-proBNP and copeptin in patients with different bleeding volume and in control group (͞x ± s).

Comparison of plasma levels of NT-proBNP and copeptin in survivors and death patients with acute cerebral haemorrhage

As shown in Table 3, plasma levels of NT-proBNP and copeptin in survival group were significantly lower compared with those in the death group, with statistical significance (P<0.05).

Groups Number of cases NT-proBNP (pg/ml) Copeptin (ng/ml)
Survival group 102 432.38 ± 183.26 3.35 ± 0.56
Death group 24 1986.48 ± 450.73 4.24 ± 0.57
t-value 26.86 6.98
P-value <0.001 <0.001

Table 3. Comparison of plasma levels of NT-proBNP and copeptin in survival and death groups (͞x ± s).

The correlation analysis of plasma NT-proBNP, copeptin, cerebral haemorrhage and GCS score

Pearson correlation analysis showed that plasma NT-proBNP and copeptin in patients with cerebral haemorrhage had significant positive correlation with cerebral bleeding volume and GCS score (P<0.05) (Table 4).

Item Cerebral bleeding volume (ml) GCS score
  r-value P-value r-value P-value
NT-proBNP (pg/ml) 0.54 0.000 0.43 0.001
Copeptin (ng/ml) 0.48 0.001 0.37 0.012

Table 4. Correlation of Plasma NT-proBNP and copeptin with cerebral bleeding volume and GCS score.

Discussion

Cerebrovascular disease, a kind of acute diseases with high incidence, is the second largest cause of human death. Within one year of the incidence, the mortality rate can be as high as 10.1% to 33%, even if the patient survived, about 15% to 38.4% would have a lifelong disability [7,8]. Due to increased acute intracranial pressure, brain herniation and pulmonary infection and other complications, cerebral haemorrhage has the higher mortality and makes patients with sequelaes of limb paralysis and vascular dementia, which has serious impact on the quality of life and brings a heavy burden to patients [9]. The causes of cerebral haemorrhage are more complicated, in addition, the early diagnosis and effective treatment can significantly improve the prognosis of cerebral haemorrhage. Therefore, the diagnosis of cerebral haemorrhage, the severity of the assessment and accurate prognosis is a hot clinical spot.

BNP is a member of the Natriuretic Peptide System stepping with Atrial Natriuretic Peptide (ANP). It can antagonize the vasoconstriction of the Renin-Angiotensin-Aldosterone System (RAAS) and inhibit Plasminogen Activator Inhibitor (PAI) effectively, which plays a role in sodium excretion, micturition, vasodilation and anti-thrombosis [10,11]. Huang Wei et al. [12] found that in 48 patients with hypertensive intracerebral haemorrhage, 18 patients were confirmed with delayed brain oedema by head CT, their BNP concentration was significantly increased, suggesting brain oedema may induce the release of BNP, or BNP may aggravate cerebral oedema. NT-proBNP and BNP are derived from the precursor proBNP, with homology [13], therefore, the metabolic processes of them are more synchronized, with close relationship. However, compared with BNP, NT-proBNP has a longer half-life, higher plasma concentration, and more stable biological properties, making its detection more convenient and more sensitive [14,15].

AVP is a bioactive peptide produced by the hypothalamus, with the function of osmotic pressure regulation, hemodynamic stability maintenance and regulation of the central nervous system. AVP can also effectively reflect the activation level of hypothalamic-pituitary-adrenal axis, as important indicators of critical disease severity and prognosis assessment [16,17]. Copeptin is a combined glycopeptide of AVP, with the same source as AVP, which can indirectly suggest AVP release levels, instead of AVP detection [18]. Studies have shown that copeptin level was significantly increased within 6 h after acute cerebral haemorrhage, and that reached a peak in 24 h, then it would gradually decrease. Within 7 days of the incidence, its average levels were significantly higher than that of normal population [19]. Recently, it is found that plasma copeptin concentration was significantly superior to MBP, GFAP, NSE, S100B, pNF-H, tau and UCH-L1 in the prediction of 6 months death of cerebral haemorrhage and functional prognosis [20].

In this study, the results indicated that plasma levels of NT-proBNP and copeptin in patients with acute cerebral haemorrhage were significantly higher than those of the healthy control group, and they were decreased along with massive cerebral haemorrhage group, mild cerebral haemorrhage group and small haemorrhage group. According to prognosis of diseases, the grouping results of the study showed that plasma levels of NT-proBNP and copeptin in patients of death group were significantly higher than those of the survival group. The correlation analysis showed that plasma levels of NT-proBNP and copeptin had significant positive correlation with bleeding volume and GCS score (P<0.05) in patients with acute cerebral haemorrhage. These results suggested that NT-proBNP and copeptin can participate in the pathophysiology of cerebral haemorrhage, and the higher the plasma levels of the two, the greater the amount of bleeding, the greater the severity of cerebral haemorrhage, which were consistent with others conclusions [15,21].

In summary, early combined detection of plasma levels of NT-proBNP and copeptin in patients with acute cerebral haemorrhage can reflect the severity of cerebral haemorrhage; assess the prognosis of patients, which have a certain clinical referential value. However, this study is a small sample control study, the specific mechanism and reliability remains to be further studied.

References