Clinical significance of plasma levels of brain natriuretic peptide and cardiac troponin T in patients with sepsis.

Sepsis is a systemic inflammatory response of the body to an antigen and can become a life-threatening condition by triggering a cascade of changes leading to multiple organ failure such as heart failure. The aim of the present study was to examine the changes of the plasma levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) in patients with sepsis and to analyze their prognostic significance. A total of 38 hospitalized patients with sepsis were included in the present study. The patients were divided into the survival and death groups, based on their prognosis. The plasma levels of NT-proBNP and cTnT for the two groups were measured for all the patients on the 1st, 3rd and 7th day of admission. The plasma levels of NT-proBNP and cTnT between the two groups were compared and their association with prognosis were analyzed. The plasma levels of NT-proBNP and cTnT in the death group were significantly higher than those in the survival group (P<0.05). Additionally, a positive assocciation of the plasma levels of NT-proBNP and cTnT was identified (P<0.05). In conclusion, the plasma levels of NT-proBNP and cTnT may be used as routine clinical biomarkers to assess the prognosis of patients with sepsis.

Introduction

Sepsis is a systemic inflammatory response of the body to an antigen (1) caused by infection. Severe sepsis can lead to 27 organ dysfunction and/or tissue perfusion, and even shock (2). It can become a life-threatening condition by triggering a cascade of changes leading to multiple organ failure. Sepsis has a relatively high incidence in intensive care unit (ICU) in Poland (3). The majority of deaths associated with sepsis are incurred by organ failures, especially heart failures (4,5). However, there is a lack of effective biomarkers that facilitate prognosis. N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) are myocardial injury markers. These markers are used as a screening tool for the diagnosis of cardiovascular complications (6). Different levels of NT-proBNP and cTnT in the plasma of patients with sepsis may play different roles on the prognosis of the disease (7–9).

In the present study, 38 cases of hospitalized patients having sepsis were investigated to examine the plasma levels of NT-proBNP and cTnT and to investigate their prognostic significance. The results showed that the plasma levels of NT-proBNP and cTnT may be used as routine clinical biomarkers to assess the prognosis of patients with sepsis.

Materials and methods

Patients

A total of 38 cases were identified from the ICU of the Xiangyang Hospital Affiliated to Hubei University of Medicine (Hubei, China). Patient diagnosis was confirmed as per the criteria issued in 2001, by the American College of Chest Physicians or Society of Critical Care Medicine (10). Any patients with acute coronary syndrome, congestive heart failure and increasing levels of NT-proBNP and cTnT incurred by cardiopulmonary resuscitation, cardiothoracic surgery, hepatic and renal dysfunction within one month, were excluded. Of the 38 cases, 21 cases were male and 17 cases were female, with an age of 52–71 years. Following admission, the patients were administered early fluid resuscitation and bundle treatment in accordance with the guidelines (2). The levels of NT-proBNP and cTnT as well as organ functions were monitored. Based on their prognosis, the patients were divided into the survival and death groups. The survival group comprised 22 cases, 13 cases were male and 9 cases were female, with an average age of 57.96±13.66 years. The infection sites identified were as follows: 13 cases, lung; 5 cases, abdomen; 1 case, urinary tract and 3 cases, other sites. The death group included 16 cases with 8 cases being male and 8 cases being female, with an average age of 60.94±10.03 years. The infection sites for this group were: 11 cases, lung; 3 cases, abdomen; 1 case, urinary tract and 1 case, other site. Differences regarding age, gender, and infection site between the two groups were not statistically significant (P>0.05).

Blood sampling

Venous blood (3 ml) was collected from patients under quiescent condition every morning on the 1st, 3rd and 7th day of admission. The blood samples were placed into test tubes with EDTA to prevent anticoagulation and were immediately sent for analysis to determine NT-proBNP and cTnT levels.

Analysis for NT-proBNP and cTnT

The NT-proBNP detector was provided by Roche Diagnostics GmbH (Mannheim, Germany), combined with electrochemiluminescence for detection of plasma levels. Detection was carried out strictly by a specially-assigned pathologist. The normal reference value was taken as <900 pg/ml. Electrochemiluminescence was applied to measure the level of serum cTnT. A detector was produced using the kit provided by Roche Diagnostics GmbH. The normal reference value was considered as 0.1 ng/ml.

Statistical analysis

SPSS 20.0 statistical software (IBM SPSS, Armonk, NY, USA) was used for statistical analysis. Measurement data were presented by mean ± standard deviation, and the t-test was applied to make comparisons between groups. The linear correlation analysis was performed to determine any correlations between NT-proBNP and cTnT. P<0.05 was considered to indicate a statistically significant difference.

Results

As shown in Table I, the level of NT-proBNP in the death group was significantly higher than that in the survival group and the difference was statistically significant (P<0.05). Similarly the levels of cTnT were significantly higher than those in the survival group (P<0.05) (Table II).

Table I.

Comparison of the level of NT-proBNP between the survival and death groups on the 1st, 3rd and 7th day of admission.

	NT-proBNP (pg/ml)
Group	Day 1	Day 3	Day 7
Survival group	1839.14±1060.27	2786.21±1206.23	2074.08±970.43
Death group	3965.74±1462.65	6268.56±1825.49	5384.46±1049.62
P-value	<0.05	<0.05	<0.05

NT-proBNP, N-terminal of the prohormone brain natriuretic peptide.

Table II.

Comparison of the level of cTnT between survival and death groups on the 1st, 3rd and 7th day of admission.

	cTnT (pg/ml)
Group	Day 1	Day 3	Day 7
Survival group	0.53±0.21	0.68±0.17	0.62±0.23
Death group	1.03±1.04	1.57±0.86	1.38±0.53
P-value	<0.05	<0.05	<0.05

cTnT, cardiac troponin T.

The correlation analysis between NT-proBNP and cTnT showed that the blood levels of NT-proBNP and cTnT in patients with sepsis showed a significantly positive correlation (r=0.756, P<0.05). Thus, NT-proBNP and cTnT levels are increased in the plasma collectively in a directly proportional manner.

Discussion

Sepsis is a type of systemic inflammatory response syndrome resulting from infection. Myocardial damages incurred by sepsis, also known as pyemic cardiomyopathy or pyemic myocardial dysfunction, likely increases the mortality risk of sepsis (7,8). At least one half of mortalities associated with sepsis were caused by the impairment of the cardiovascular system (10). During sepsis, regional blood flows abnormally, leading to microcirculation disturbance and resulting in the ischemia of various organs, including the heart as well as mitochondrial structural change on myocardial cells. This condition eventually results in cell metabolic dysfunction and eventually death (11,12). In clinic, NT-proBNP and cTnT are usually used as markers to reflect myocardial injury.

Sepsis usually concurs with cardiac insufficiency (13–15). Under sepsis condition, a large amount of fluids or media produces a toxic effect on the heart. When the entire body becomes affected by a strong inflammatory reaction, the homeostasis of cardiovascular system changes, leading to cardiac insufficiency. Early ventricular systolic dysfunction has been proven in patients with sepsis (16). NT-proBNP mainly primarily stems from ventricle. Patients with cardiac failures showed higher levels of NT-proBNP in plasma, suggesting an important indication for heart failure diagnosis, treatment and prognosis. Current investigations have confirmed that the level of NT-proBNP on patients with sepsis is likely to increase (17–19). However, myocardial function impairment was not the only factor likely to result in the increase of NT-proBNP. Charpentier and other authors (20–22,28) have determined that the increase of certain NT-proBNP was associated with the increased secretion or reduced inactivation of NT-proBNP under an inflammatory response. Therefore, the basic pathophysiological changes of sepsis may be a reason for the increase of the NT-proBNP level (23–25). The results of our study have shown that the plasma level of NT-proBNP in patients with sepsis was significantly increased and that of the death group was significantly higher in comparison to the survival group. The result was consistent with the abovementioned study results.

Cardiac troponin is an important protein that could adjust the contraction of striated muscle (17,26,27). When the myocardium cell membrane of heart is intact, cTnT is unable to get into the blood circulation. Thus, the plasma in healthy individuals usually has no or a low level of cTnT. The mechanism for the increasing level of cTnT in patients with sepsis remains to be determined. It was estimated that myocardial damage in patients with plasma may be associated with the direct damage on myocardial cells incurred by the release of a large amount of cytokines and reactive oxygen species and the toxic effect of bacterial endotoxin on myocardial cells subsequent to bacterial infection (28). Sepsis is always accompanied with microcirculation disturbance, which results in the ischemia of myocardial cells and reperfusion damage. When myocardial cells are impaired, the cytomembrane suffers damage and therefore cTnT is released into the blood, and becomes evident as higher levels in plasma. The increasing level of troponin may reflect a worse myocardial function, and is potentially associated with the patient prognosis (29). The results of our study have shown that the change of level of myocardial injury markers was significantly different between the survival and death groups. The level of cTnT in the death group was significantly higher than that in the survival group, indicating that the myocardial troponin level in patients with sepsis was positively associated with the severity of disease. There are currently no reports confirming that the level of troponin may be used as an independent predictor for prognosis of patients with sepsis. Therefore, this aspect remains to be investigated.

The result of the correlation analysis showed that the plasma levels of NT-proBNP and cTnT in the death group were significantly higher than those in the survival group, and the plasma levels of NT-proBNP and cTnT were positively correlated, indicating that the increasing levels of NT-proBNP and cTnT exert a predictive effect on the prognosis of patients with sepsis.

In conclusion, monitoring of the levels of NT-proBNP and cTnT is crucial and can demonstrate the status of cardiac health with a potential to circumvent the severity of disease.