The Diagnostic Value Of N-Terminal Pro-Brain Natriuretic Peptide Levels In Cardioembolic Stroke

There are 1.6 million patients died from cerebrovascular disease every year, and cerebrovascular disease has become a major disease which hazard people' physical and mental health in China. Ischemic cerebrovascular disease accounts for more than 70% of all cerebrovascular disease. Cardioembolic(CE) stroke is the most serious type in ischemic cerebrovascular disease, and CE accounts for about 20% of all ischemic strokes. Although there are a variety of guidelines for diagnosis and treatment of CE stroke in domestic and foreign countries, there is no “gold standard” for the diagnosis of CE stroke. Atrial fibrillation(AF) is a major risk factor for CE. Compared with other types of ischemic stroke, CE stroke caused by non-valvular atrial fibrillation(NVAF) has high recurrence rate and high mortality. It has seriously threatened the patients' physical and mental health. Therefore, it is very important for diagnosis, treatment and secondary prevention of CE stroke caused by AF to identify AF, especially paroxysmal AF. Howere, persistent AF is easy to diagnose and paroxysmal AF is difficult to diagnose. There are about 30% of patients with AF who are difficult to detect by electroencephalo-graph. But, there is no difference in the risk of stroke caused by paroxysmal AF or persistent AF. Undetected paroxysmal AF may be the cause of some case of cryptogenic stroke. So it is possible that these patients are not receiving the most appropriate treatment in secondary prevention. Therefore, to classfy accurately stroke subtype is essential to prescrible the most suitable secondary treatment to prevent recurrence.and reduce recurrence rate and mortality rate of patients with stroke.Nowadays, a number of studies showed that brain natriuretic peptide(BNP), N-terminal pro brain natriuretic peptide precursor(N-terminal pro natriuretic peptide NT pro BNP), C-reactive protein, creatine kinase isoenzyme, D-dimer, fibrin fibrinogen degradation products and tissue factor seemed to be associated with CE stroke. Those serum biomarkers have got attention for predicting CE stroke. The study intends to find the suitable serum marker which can predict CE stroke. Firstly, it is to analyze the optimally cutoff point of the serum marker in predicting NVAFAIS. Using the above cutoff point reclassified the cryptogenic stroke, and improved the diagnostic rate of CE.Part 1 The Diagnostic value of N-terminal Pro-brain natriuretic peptide levels in Patients with NVAFAISObjective: The aim of this study is to investigate the diagnostic value of NT-pro BNP levels in NVAFAIS.Methods: We retrospectively collected patients with acute ischemic stroke within 7 days of onset, who admitted in ten cities' department of Neurology in Shaan Xi Province, from January 2012 to June 2015. According to TOAST criteria and the patients with or without AF, they were divided into three groups: NVAFAIS group, large-artery atherosclerotic / small arterial occlusive / stroke of other determined etiology(LAA/SAO/SOE) group and Stroke of Undetermined Etiology(SUE) group. In this study, blood samples were obtained on admission to determine serum NT-pro BNP levels in acute ischemic stroke patients within 3 days or 7 days of onset. Receiver Operating Characteristics(ROC) curve was configured to establish cutoff point of serum NT-pro BNP levels that optimally predicted NVAFAIS.Results: A total 1169 acute ischemic stroke patients were included(age 67(58-75) years, 726 male, 492 female). Amongst the enrolled patients, 261(22.3%) had NVAF upon admission(NVAFAIS group). ROC analysis revealed that the best cut off point of serum NT-pro BNP within 1 day of onset to predict NVAFAIS was 431 pg/ml(area under the curve 0.871, sensitivity 93%, specificity 69.8%, P < 0.0001) and of serum NT-pro BNP within 3 days of onset to predict NVAFAIS was 504.3 pg/ml(area under the curve 0.905, sensitivity 80.5%, specificity 88.5%, P < 0.0001) and of serum NT-pro BNP within 7 days of onset to predict NVAFAIS was 434.5 pg/ml(area under the curve0.899, sensitivity 90.4%, specificity 77.7%, P < 0.0001). On multivariate logistic regression analysis demonstrated that age, history of coronary heart disease, the serum NT-pro BNP ? 431 pg/ml(odds ratio, 25.7; 95% confidence interval, 10.069 to 65.62, P = 0.0001) within 1 day of onset and the serum NT-pro BNP ? 504.3pg/ml(odds ratio, 22.661; 95% confidence interval, 13.819 to 37.161, P = 0.0001) within 3 days of onset and the serum NT-pro BNP ? 434.5 pg/ml(odds ratio, 23.319; 95% confidence interval, 14.35 to 37.894, P = 0.0001) within 7 days of onset were major risk factors to predict NVAFAIS.Conclusion: Compared with the LAA/SAO/SOE group, the serum NT-pro BNP levels are significantly higher in NVAFAIS group. The serum NT-pro BNP levels could be a useful indicator to classfy the ischemic stroke subtype.Part 2 High serum NT-pro BNP levels identify cardioembolic origin in cryptogenic strokeObjective: The aim of this study is to investigate whether serum NT-pro BNP levels was useful to reclassify cryptogenic stroke.Methods: We retrospectively collected patients with cryptogenic stroke within 7 days of onset, who admitted in ten cities' department of Neurology in Shaan Xi Province, from January 2012 to June 2015. Patients were followed every 3 month for 1 year. The endpoint was the development of AF. On multivariate logistic regression analysis observed the predictive value of the cut-off point of serum NT-pro BNP within 3 days of onset or within 7 days onset in cryptogenic stroke associated with AF.Results: A total 218 cryptogenic stroke patients were included. Seven patients(3.2%) developed AF during the follow-up period. Serum NT-pro BNP levels were higher in patients who developed AF. In a further analysis of cryptogenic stroke, 51 patients(29.5%) were serum NT-pro BNP ? 504.3 pg/ml within 3 days of onset, and 63 patients(28.9%) were serum NT-pro BNP ? 434.5 pg/ml within 7 days of onset. We found a higher percentage of patients with serum NT-pro BNP ? 504.3 pg/ml within 3 days of onset in those who developed AF(6 [11.8%] vs. 1 [0.8%], P = 0.001), and with serum NT-pro BNP ? 434.5 pg/ml within 7 days of onset in those who developed AF(6 [9.5%] vs. 1 [0.6%], P = 0.001).Conclusion: Serum NT-pro BNP ? 434.5pg/ml within 7 days of onset in patients with cryptogenic stroke was reclassified as CE stroke likely. It is essential to prescribe the most suitable secondary treatment to prevent recurrences.