Study On Prognostic Role Of Butyrylcholinesterase In Patients With Acute Myocardial Infarction And It’s Mechanism

ObjectiveButyrylcholinesterase(BCh E, or Bu Ch E), also known as pseudocholinesterase or serum cholinesterase is a non-specific cholinesterase enzyme that hydrolyses different choline esters. It is synthesized mainly in the liver and serum BCh E activity can be used as a biomarker of liver function. Recently, BCh E activity variations have been found in many clinical conditions such as inflammation, injury, and malnutrition beside liver dysfunction, and seems to have a prognostic role in different diseases according to clinical experience. BCh E activity also seems to have a predictive value for cardiovascular diseases, though there is few literature on this field. However, the underlying mechanisms of predictive value of BCh E remain unclear. And there is no study on the predictive value of BCh E on(Acute Myocardial Infarction, AMI).Some results of researches identified that serum BCh E had a diagnosis value for chronic heart failure. And it is well known that AMI patients with heart failure had increased mortality than those without heart failure. This raise a question: whether BCh E activity is associated with cardiac function in AMI, and if so, is this association related with predictive value of BCh E ? However, previous studies lacked data on cardiac function such as cardiac fuction classification and LVEF in assessing the predictive value of BCh E in ACS. So one aim of present study is to find the association between BCh E activity with cardiac fuction assessed by Killip class and LVEF in AMI and try to answer whether the predictive value of BCh E is associated with it’s diagnosis value for chronic heart failure.Inflammation is regarded as an important aspect of cardiovascular diseases.It has been shown that there are over-expression of inflammatory cytokines in the serum of heart failure patients, and that cytokines promote the initiation and development of heart failure by influencing myocardium contractility, inducing hypertrophy and apoptosis, fibross, and contributing to the myocardial remodelling process.Cytokines also often predict adverse cardiovascular events.The other aim of present study is to find the association between BCh E activity with IL-6 and CRP, tow important inflammatory cytokines in AMI and further explore the mechanisms of the predictive role of BCh E in AMI. MethodIn the part one of present study, we retrospectively analyzed consecutive AMI patients admitted to our hospital, a tertiary care center, within 24 hours after syndrome onset between January 2011 and October 2012. The diagnosis was based on symptoms consistent with AMI in conjunction with appropriate, dynamic ECG changes(ST segment elevation mycardial infarction, STEMI) or ST segment / T wave changes(Non-ST segment elevation mycardial infarction, NSTEMI) and elevation in plasma markers of myocardial necrosis(troponin I). Patients excluded from this study were those with a history of liver disease, a history of chronic heart failure and the presence of any predominant severe systemic diseases.Data were collected from the patients’ files and inserted into a predefined form. Conventional cardiovascular risk factors were recorded according to the respective guidelines. Blood samples were collected on the first day morning after admission and processed according to local laboratory’s standard procedure. Serum BCh E activity was measured with an enzyme kinetic assay using butyrylthiocholine iodide as substrate. Killip Class was evaluated on admission according to the classic article. Left ventricular ejection fraction was determined by echocardiography 5-7 days after admission.Survival was estimated from the onset of myocardial infarction to 30 june 2014. All-cause mortality(excluding accidental deaths) was defined as the study end.In the part two of present study, consecutive 75 AMI patients were chosen to continue our research from March to December in 2013. All of them received emergency percutaneous coronary intervention successfully to get coronary revascularization, all patients met diagnostic criteria consistent with part one. All patients underwent emergency coronary stenting. The serum BCh E activity, levels of hs-CRP and IL-6 was examed after admission, and the correlationship between BCh E activity and levels of hs-CRP and IL-6 was analized. Results:Part one:1. we enrolled 350 consecutive AMI patients. Approximately 75% of the patients were male, age 62 ± 13 years old, 82% patients presented with STEMI, 73% patients underwent successful prefusion. The median BCh E activity in serum was 6.8 k U/L for all patients.2. BCh E activity and cardiovascular risk factorsBCh E activity was significantly negatively correlated with age, Killip class and serum creatinine and positively correlated with BMI, glycemia, triglyceride, total cholesterol and LDL cholesterol. We found no association with HDL cholesterol3. BCh E activity and cardiac function variablesBCh E activity was significantly lower in patients with high Killip class( and ⅢⅣ) than in those with low Killip class( or) [ 6.2 ±Ⅰ Ⅱ 1.6 VS 7.0 ± 1.3 or 7.0 ± 1.5( p < 0.01)]. BCh E activity correlated positively with left ventricular ejection fraction(r = 0.24, p < 0.001).4. BCh E activity and all-cause mortalityOf the total 350 patients, 25(7.1%) patients died during follow-up. The mean follow-up period was 29 ± 7 months(range two days to 42 months). BCh E activity were significantly higher in survived patients compared with non-survived patients [7.0 ± 1.4 VS 5.7 ± 1.3(p < 0.001) ]. All variables of the patients, grouped into “low” and “high” BCh E activity according to median value of 6.8 k U/L.The survival rates were 89%, and 97% respectively in the low and high groups of BCh E activity. Kaplan–Meier survival curves according to BCh E activity showed that patients in low group had a significantly lower survival rate than those in high group(log-rank test, p < 0.001).5. Univariate and multivariate predictors of mortalityBy univariate Cox model, BCh E activity, age, Killip class, Prior MI, STEMI, serum creatinine, triglyceride(TG), total cholesterol(TC), heart rate on admission, LVEF and cornary reperfusion were all significantly related with mortality. By multivariate Cox model, BCh E activity was an independent predictor of all-cause mortality after myocardial infarction without adjusting Killip class and LVEF [HR 0.65, 95% CI 0.46- 0.91; p = 0.013]. After adjusting Killip class and LVEF, BCh E activity was not in equation.Part two:Relation between BCh E activity and inflammatory cells / cytokines:Spearman analysis showed that BCh E activity was seemingly negatively correlated with monocyte ratio, but did not reach the statistical significance. BCh E activity was inversely related with serum IL-6 and hs-CRP. IL-6 was positively correlated with hs-CRP. IL-6 and hs-CRP was positively correlated with monocyte ratio. Conclusion:Serum BCh E has predictive value for AMI. The possible mechanisms of BCh E’s predictive value is that BCh E is involve in initiation and development of heart failure during AMI through it’s role in cholinergic anti-inflammatory pathway. Additionally, serum BCh E examination is simple, popular, cost effectively and can be a good predictive marker of AMI.