Prognostic Value Of Brain Natriuretic Peptide In Patients With Acute Myocardial Infarction Undergoing Primary Coronary Angioplasty

Background and objective: Acute myocardial infarction (AMI) is a common clinical cardiovascular disease with higher mortality . In the past decade, substantial progress has been made in the understanding of the pathophysiology of AMI. In most cases, disruption of the endothelial surface of an atherosclerotic plaque leads to platelet activation and thrombin formation, culminating incomplete occlusion of the epicardial coronary vessel by a thrombus. Patient'benefit is directly related to the time between coronary occlusion and reperfusion of therapy. Primary percutaneous coronary intervention, (primary PCI) is an effective reperfusion strategy, with early restoration of adequate coronary flow occurring in >90% of AMI patients. Primary PCI in acute AMI has been shown to result in lower rates of death congestive heart failure recurrent myocardial infarction stroke severe residual stenotic lesion, but higher rate of patency of the infarct-related artery and better left ventricular function compared with thrombolysis. However, despite successful revascularization, a substantial number of patients still fail to obtain complete and sustained myocardial reperfusion. Previous studies with myocardial contrast echocardiography have revealed zones of impaired tissue flow, termed the 'no-reflow' phenomenon, in one-quarter to one-third of reperfused AMI patients, and this is accompanied by ST segment elevation on the 12-lead ECG . No-reflow phenomenon, defined as inadequate myocardial perfusion of the adequately dilated target vessel without evidence of angiographic mechanical obstruction, results in prolonged myocardial ischemia after reperfusion of a target coronary artery. Multiple factors (eg, microvascular spasm, endothelial cell damage, tissue edema, platelet aggregation, and neutrophil, clot, and atheromatous plaque plugging of the microvessels) contribute to the development of AMI no-reflow phenomenon. Several studies have examined the implication of persistent ST segment elevation as a marker of impaired microvascular reperfusion for prognosis after AMI. Claeys et al reported that impaired microvascular reperfusion, as evidenced by persistent ST segment elevation after successful revascularization, was observed in more than one-third of AMI patients, and was associated with more extensive infarction, a worse clinical outcome and worse recovery of left ventricular function. So the prognosis of patients with AMI varies greatly, the clinicians urgently need a simple ,rapid and accurate means to stratify AMI and to identifies high-risk patients in early period of AMI. Furthermore patients with AMI can be stratified earlier and given aggressive intervention to improve prognosis. Brain natriuretic peptide (BNP), first purified in 1988 by Japan's Sudoh from porcine brain, is a 32-amino acid peptide. Although BNP was initially purified from brain—hence its name—it is present at the highest concentration in the heart, especially in ventricular myocytes. Release of BNP results from cardiac wall stretch, ventricular dilation, or increased pressures from circulatory volume overload The synthesis of BNP in myocytes increases markedly leading to increasing of plasma level. BNP have powerful diuretic, natriuretic, and vascular smooth muscle relaxing actions. Importantly, they also work as antagonists to the sympathetic nervous system and the rennin-angiotensin-aldosterone system (RAAS), which lead to a higher BNP level in plasma. The effects of BNP result in lowering blood volume and pressure. Multiple trials recently have demonstrated that BNP elevation is a powerful marker for the diagnosis and prognosis of heart failure(HF), elevated plasma concentration of BNP was associated with increased mortality risk, independently of left ventricular function. The BNP Consensus Panel of 2004 has provided expert panel approaches for the use of BNP for the diagnosis and treatment of HF Lately , BNP has been shown to provide valuable prognostic information in patients with ACS in some reports. Few studies were done to look at whether early plasma concentration of BNP, which was measured at the beginning of AMI presentation to the hospital, was associated with adverse prognosis. In our study, we analyzed plasma BNP levels in acute phase of AMI, and study the value of BNP in forecasting long-term prognosis in patients with ST-segment elevation acute myocardial infarction (STEMI) who underwent emergency direct PCI.Methods : From July 2005 to March 2006 in Department of Cardiologyof Renji Hospital in Shanghai, consecutive 92 patients with first acute ST-segment elevation myocardial infarction (STEMI)(75 males, 17 females ; age from 43 to 83y, mean age 64.5±10.5 y), successfully reperfused by primary PCI within 12 hours from the onset of AMI were enrolled in this study. STEMI patients were included if (1) continuous chest pain for at least 30 min (2) ST-segment elevation≥1 mm (0.1 mV) in two or more contiguous leads on the 12-lead ECG . (3) peak elevation of plasma creatine kinase to at least twice normal level. Patients were excluded if they had primary pulmonary hypertension, congestive heart failure, valvular heart disease, chronic renal failure. BNP concentration levels in plasma were measured by fluorescence immunoassay. The Triage BNP assay system (Biosite, Inc, San Diego) was used and measurable BNP levels ranged from 5 to 5000 pg/mL. Venous blood samples were obtained in EDTA tubes at 24 h after the onset of symptoms. Tubes were centrifuged immediately for 20 minutes and the plasma was frozen at -70℃until analyses. According to BNP concentration, patients were divided into three groups : group A ( <100pg/mL, n=15); group B (100-400 pg/mL, n=56); group C (>400 pg/mL , n=21). The patients were followed up one year. According to one year death., patients were divided into two groups : the death group and survival group. A successful PCI was considered as a reduction of stenosis to <50% residual narrowing after the procedure. Data were analyzed by Spss 14.0 software , Continuous variables were expressed as mean±SD and compared by use of Student's test or ANOVA (Analysis of Variance), The x~2 test was used to compare categorical variables , or a Fisher's exact test was used when appropriate. Multivariate logistic models were used to identify the independent predictors of BNP; Logistic regression and thereceiver-operating-characteristic (ROC) curve were employed to evaluate the prognostic value of BNP for the prognosis in patients with AMI. All statistical tests were 2-tailed. P< 0.05 was considered significant.Results : 1. Patients in group C were significantly older than that in group B and C (70.29±8.06 y VS 63.96±9.76y VS 58.13±12.18y, P< 0.01, respectively ). Compared with group A , patients in group B and C had significantly higher proportion of multi-vessel lesion (71.4%, 57.1% VS 20.0% P <0.01, respectively ),and significantly higher proportion of left anterior descending artery (LAD) lesion in infarct-related coronary artery(66.7% 48.2% VS 20.0%, P <0.05, respectively). Compared with group A and B, patients in group C had significantly higher one-year-mortality (33.3% VS 3.6%,6.7%. P <0.01, respectively). 2. Patients in death group were significantly older than that in survival group (76.1±6.2 y VS 63.0±9.9 y, P <0.001); BNP concentration in death group were significantly higher than that in death group (603±306 pg. VS 244±162 pg, P <0.001); Compared with survival group, death group had significantly higher proportion of multi-vessel lesion (90% VS 50% , P < 0.05) , and three- vessel lesion (50% VS 9.8, P < 0.05. 3. Multiple logistic regression analysis suggested that BNP alone predicted one-year mortality of STEMI with primary PCI independently of all the other risk factors (OR 1.006, 95% CI 1.002 to 1.010, P = 0.006). Area under the curve of the receiver-operating-characteristic(ROC) of BNP to predict long-term death in patients with AMI was 0.921, 95% confidence interval 0.848-0.993, P<0.0001. A circulating BNP cut-off value of 360 pg/mL had a sensitivity of 90 percent, a specificity of 80.5 percent for predicting death at one year. Conclusion : Early-phase BNP plasma concentrations in patients with ST elevated acute myocardial infarction after successful PCI may be a strong predictor for one-year mortality.