Introduction
Pro-BNP was synthesized as a pro-hormone by cardiac myocytes then cleaved by enzyme to N-teminal proBNP (NT-proBNP) and BNP (brain naturetic peptide). Conventional cardiac markers, such as troponin-T (Tn -T), and creatine kinase (CK)-MB isozyme, detect the development of minor myocardial necrosis [1]. A direct release of BNP from ischemic cardiomyocytes and ischemia induced by increase in ventricular wall stress was postulated. Natriuretic peptides have cyto-protective effect in myocardium related to cGMP accumulation and opening of ATP-sensitive K+ channels which is potentially exploitable therapeutically [2].
The objective of this study is to investigate the differences in the secretion of NT-proBNP and conventional cardiac markers in patients with STE-ACS vs. NSTE-ACS as a trial to solve the dilemma of the early detection of myocardial ischemia in NSTE-ACS.
Methods
Sixty two patients with acute coronary syndrome (ACS) were divided into 2 groups according to ECG: group1 with elevated ST segment (STE-ACS) and group 2 with non elevated ST segment (NSTE-ACS). Twenty healthy subjects with matched age and sex were enrolled as control group. In the sera of all subjects, levels of NT –proBNP, CK-MB and Tn- T were measured by different commercial kits. Serum CK-MB levels measured kinetically by UV method whereas Tn-T determined by chemiluminescent immunoassay using available kit. NT-proBNP measured by ELISA. SPSS version 16 was used for data analysis. Mann-Whitney U test, ANOVA test and ROC curve were used for comparing the data.
Results
CK-MB and Tn-T were both significantly higher in STE-ACS patients compared with NSTE-ACS patients. Conversely, NT-proBNP was significantly higher in NSTE-ACS patients than STE-ACS especially within 4 hours from onset of chest pain (Figures 1, 2 and 3). This suggested a larger ischemic insult despite the smaller extent of myocardial necrosis compared with STE-ACS patients. Comparison between NT-proBNP, Tn-Tand CK-MB levels by ROC curve (Figure 4) revealed a marked difference of area under the curves with higher sensitivity and specificity of NT-proBNP in NSTE-ACS patients.
Figure 1:
NT-proBNP in patients with ACS.
Figure 2:
Tn-T in patients with ACS.
Figure 3:
CK-MB in patients with ACS.
Figure 4:
ROC curve in NSTE-ACS: The area under the curve was 0.58 (NT-pro BNP); 0.31 (Tn-T); 0.17 (CK-MB)
Discussion
The increment of NT-proBNP in NSTE-ACS patients was inversely proportional to the duration of chest pain. It was more significant increased when the duration of chest pain was ≤ 4 hours, compared to when the duration was between 6 and 8 hours. It increased during the hyper acute phase in NSTE-ACS patients, and wasn’t raised by the process of myocardial necrosis but the ischemic insult per se. The ischemic area or area at risk showed different spectrum in these 2 groups. STEMI caused by acute total coronary occlusion, whereas NSTEMI associated with vulnerable plaque and sub-occlusive thrombosis [3]. NTpro-BNP may be a powerful indicator of long-term mortality in patients with ACS and Provide prognostic information above and beyond conventional risk markers [4]. We conclude that NT-proBNP may be a sensitive and specific marker in the early diagnosis of NSTE-ACS than other traditional cardiac markers. NT-proBNP might be superior to clinical judgment in the diagnostic evaluation of NSTE-ACS patients.
References
- 1.Haastrup B, et al. Biochemical markers of ischemia for the early identification of acute myocardial infarction without St segment elevation. Cardiology. 2000;94:254–261. doi: 10.1159/000047326. [DOI] [PubMed] [Google Scholar]
- 2.Rautureau Y, et al. Acute actions of natriuretic peptides in coronary vasculature and Ischaemic myocardium. Curr Pharm Des. 2004;10(20):2477–82. doi: 10.2174/1381612043383854. [DOI] [PubMed] [Google Scholar]
- 3.Lorgis L, et al. Prognostic value of N-terminal pro-brain natriuretic peptide in elderly people with acute myocardial infarction: prospective observational study. BMJ. 2009;6:1605–1609. doi: 10.1136/bmj.b1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Omland T, et al. Prognostic value of N-terminal pro-atrial and pro-brain natriuretic peptide in patients with acute coronary syndromes. Am J Cardiol. 2002;89:463–5. doi: 10.1016/s0002-9149(01)02271-8. [DOI] [PubMed] [Google Scholar]