The Value Of Blood Brain Natriuretic Peptide For Predicting Prognosis In Patients With Acute Coronary Syndromes

Background and objective:Acute coronary syndromes (ACS) encompass a continuum of cardiac ischemic events, ranging from unstable angina pectoris with no biochemical evidence of myocardial necrosis to ST-elevation acute myocardial infarction (AMI). The common denominator of ACS is a pathophysiologic process characterized by rupture of an atherosclerotic plaque, altered coronary vasomotor tone, platelet aggregation, and thrombosis. It covers 30 to 40 percent of coronary artery disease (CAD). Current studies demonstrate that the incidence of ACS is increasing year by year. The 21^st North America Pacing and Electrophysiology Conference reported that CAD accounts for 80 percent of sudden cardiac death (SCD). ACS even has a higher incidence of SCD than arrhythmia, contributing to 20 percent of SCD for CAD. Evidence Based Medicine verified that risk stratification of patients with ACS is fundamental in determining prognosis and choosing appropriate care (such as anti-coagulation, anti-platelet, anti-thrombotic, and revascularization therapies) . This improves the cost-effectiveness of patients care since who are most likely to benefit fromtheir use. Traditionally, risk assessment is based on the clinical history, examination findings, electrocardiographic (ECG) changes, and markers of myocardial damage, particularly cardiac troponin. The prognostic indicators should be available at the time of initial patient evaluation, in order to maximize the potential benefit of early risk-assessment. Currently, despite careful integration of key prognostic variables, risk prediction based on clinical, electrocardiographic, and biochemical markers (cardiac troponin) is relatively inaccurate. Therefore, there is still room for new prognostic indicators.B-type / brain natriuretic peptide (BNP), firstly isolated from porcine brain and subsequently from the humans heart, is a member of natriuretic peptides family secreted from human heart. Natriuretic peptides ( NPs ) consist of atrial natriuretic peptide ( ANP), BNP and C-type natriuretic peptide ( CNP ). ANP mainly secrets from atria. BNP excretes mainly from ventricles. CNP is secreted by vascular endothelium and has local vasodilatory effect. BNP is a 32-amino-acid polypeptide secreted by the cardiac ventricles in response to increased stretch or wall tension . It is broadly involved in the regulation of blood pressure, blood volume and sodium balance. Early studies have shown that BNP could be used to diagnose cardiac dysfunction, to evaluate the prognosis in patients with cardiac dysfunction and to guide therapies in patients with congestive heart failure ( CHF ). Current studies suggest that BNP is becoming more and more important for evaluating the prognosis in patients with ACS. However, the prognostic value of circulating BNP in Chinese patients with ACS has not been fully established. This study was designed to investigate the changes of BNP in Chinese patients with ACS and to assess the value of measurement of circulating BNP for predicting prognosis in Chinese patients with ACS. MethodsA total of 106 ACS patients admitted to the coronary care unit (CCU) and / or ordinary wards at the First Affiliated Hospital of Zhengzhou University, whose blood BNP levels were measured with Triage BNP test within 1-3days of admission, were enrolled in the study between September 2003 and June 2004. The end events were defined as cardiac death, non-fetal myocardial infarction, and re-hospitalision. After 1 month follow-up, theywere divided into 2 groups: the survival and the non-survival. The difference of circulating BNP between 2 groups were compared. Step-wise Logistic regression and the receiver-operating-characteristic (ROC) curve were employed to evaluate the prognostic value of BNP for predicting prognosis in patients with ACS. 20 patients with stable angina pectoris (SAP) were also chosen from outpatients and inpatients at this period as control group for investigating the changes of blood BNP levels in patients with ACS. Results1. The median of circulating BNP in ACS group and SAP group were 172 pg/ml and 18 pg/ml, respectively. Wilcoxon signed rank test for two independent samples showed that the difference was statistically significant U=136, i><0.0005 ). The difference of left ventricular ejection fraction ( 50.12%±12.81% vs. 56.31%±9.60%, f=².090, P= 0.031), Leads number of ST segment deviation (2.75 + 3.43 vs. 0.53 ± 1.13, t=2.550, P =0.015 ) and the degree of ST segment deviation (0.076+0.103 mV vs. 0.023+0.071mV, f=2.33, P=0.042 ) between 2 groups were statistically significant.2. Spearman rank correlation analysis showed that age, gender, blood pressure, smoking, drinking, history of Diabetes Mellitus, history of essential hypertension, serum C-reactive protein (CRP) were not related to blood BNP concentration. The BNP level were positively correlated with heart rate ( r =0.229, P=0.035 ), Leads number of ST segment deviation ( r =0.281, P=0.009 ), the degree of ST segment deviation ( r =0.284, P—0.008) , left ventricular end-diastolic dimension ( r =0.429, F<0.0005 ) , history of heart failure ( r =0.372, P<0.0005 ), history of myocardial infarction ( r =0.220, P=0.043 ) and negatively correlated with left ventricular ejection fraction (r =—0.625, P <0.0005 ).3. After 1 month follow-up, 13 patients died, 2 patient experienced non-fatal myocardial infarction in ACS group. There were no end events in the SAP group at the end of 1 month follow-up. 12 patients' BNP levels were above 172pg/ml (median) and 10 patients' BNP levels were above 596 pg/ml (75% percentile). (1) The median of BNP in the survival and the non-survival were 116 pg/ml and 1132pg/ml, respectively. The difference was statistically significant ( U=148, P <0.0005 ); (2) univariate analysis indicated that the degree of ST segment deviation ( r =0.289, P=0.007 ), leads number ofST segment deviation ( r =0.415, /><0.0005 ), BNP levels (r =0.469, /><0.0005 ) and Killip class ( r =0.316, P =0.001 ) were risk factors of short-term prognosis; (3) step-wise logistic regression demonstrated that ST segment deviations 0.1 mV and BNP s596 pg/ml were independent predictors of short-term death in patients ACS ( OR=3.467, 95% confidence interval 1.366-32.836 , P=0.002; OR=21.168, 95% confidence interval 4.419-107.990 , F<0.0005 ; (covariate were age, sex ,history of heart failure, history of myocardial infarction, diabetes mellitus, LVEF, circulating BNPs 596 pg/ml and ST segment deviation s O.lmV); (4) area under the curve of the receiver-operating-characteristic ( ROC ) of BNP to predict short-term death in patients with ACS was 0.878, 95% confidence interval 0.781-0.974, P<0.0005. A circulating BNP cut-off value of 596 pg/ml had a sensitivity of 76.9 percent, a specificity of 86.2 percent for predicting death at 1 month.4. Kaplan-Meier survival curve showed that the survival curve of patients with BNP above 596 pg/ml was significantly lower than that of patients with BNP below 596 pg/ml. Log-rank test indicated that the difference was statistically significant (P<0.0005). Cox proportional hazards regression models demonstrated that BNP & 596 pg/ml and myocardial infarction were risk factors which related to ACS prognosis ( RR=2.507, 95% confidence interval 1.081-3.914, />=0.028; RR =2.208, 95% confidence interval 1.069-3.874, P =0.030). Conclusions:1. The blood BNP levels in patients with ACS are significantly higher than that with stable angina pectoris. Myocardial ischemia and / or left ventricular systolic dysfunction are the main cause of stimulating BNP secretion in patients with ACS.2. Measuring blood BNP within 1-3 days of admission could provide important clinical value for predicting clinical severity and prognosis. The risk of death in patients with circulating BNP level above 596 pg/ml is 21 times higher than those with circulating BNP level under 596 pg/ml. Therefore, for patients with very high circulating BNP levels (above 596 pg/ml), no matter whether the symptoms are serious or mild, clinical doctors should attach great importance to these patients and treat them aggressively( anti-coagulation, anti- platelet, anti-thrombotic, and revascularization therapies as early as possible ) in order to improve the short-term to long-term prognosis.3. BNP can be used for risk stratification in patients with ACS, especially when there is only ischemia without infarction and when blood is sampled very early after the onset of ischemia, that would be missed by markers of myocyte necrosis.