| As the rising of people living standard, changing of lifestyle and theincreasing of working pressure, the coronary heart disease has become one ofthe most important diseases which threaten the elderly people’s lives andhealth in China, and the episode age tends to be younger. Unstable anginapectoris (UAP) is a high morbidity of coronary heart disease, it dued tocoronary artery atheromatous plaque unstable fractures and the surface ofthrombosis that bring about incomplete lesion of vascular obstruction andwhat lead to a group of myocardial ischemia syndrome. UAP can developmyocardial infarction at any time because of its unstable condition. AndClinical symptoms and electrocardiogram (ECG) are not very typical,Therefore, it’s urgent need an important way to reduce coronary heart diseasemortality that we diagnose UAP early and accurately, and take effectivetreatment measures. Brain natriuretic peptide (BNP)， is an importantneurohormone whose production and secretion can be adjusted mainly byventricular volume and tension of ventricular wall, which makes it be asensitive indicator of cardiac function[1]. N-terminal pro-brain natriureticpeptide (NT-proBNP) is a polypeptide comes from the same source andreleases at the same time and equal quantity as BNP. NT-proBNP is consideredto be more suitable for clinical test due to its biological characteristics, such aslarge molecular weight, long half-life, strong stability in vitro and so on[2]. Alot of researches[3-5]done in recent years discovered that plasma NT-proBNPin acute coronary syndrome (ACS) is evidently higher than normal level andrelated to the order of severity of myocardial ischemic and lesion of coronaryartery. Myocardial ischemia is another important factor to cause the secretionincreases of NT-proBNP myocardial ischemia is also a cause of NT-proBNPsecretion. We aim at observing the change of NT-proBNP at UAP patients to explore the diagnosis and prognosis value of plasma NT-proBNP for UAPpatients with normal cardiac function.Objective：By detecting plasma NT-proBNP in different time after chest pain toexplor the diagnosis and the recent prognosis value of plasma NT-proBNPfor UAP patients with normal cardiac function.Method:1Preliminary testIn order to determine the blood sampling time that we selected threetypical angina patients to detect NT-proBNP. After soliciting opinions fromthe patients，plasma NT-proBNP was detected every2hours after symptomonset until24h in one case. And plasma NT-proBNP was detected every2hours at12h after symptoms happened in another two cases. We found that thepeak time of NT-proBNP level after symptoms happened was at18h. So wechose this timing as the first blood sampling time.2The subjects of study72patients with "chest pain or precordium discomfort" hospitalized incardiovascular department of the Chaoyang Center Hospital from June toDecember in2012were enrolled in this study, and symptom happened in18hours. A history, physical examination, ECG and cardiac markers wereobtained in all patients initially when they were admitted in hospital. However,there were no ST-T changes in ECG and myocardial markers did not rise. Allpatients underwent coronary angiography (CAG) and divided into two groups(positive for a narrow≥50%): UAP group included52patients and CAG(-)that contorl group20patients.3The measurement of plasma NT-proBNPRespectively collected all patients’ elbow vein blood of4ml at18h and96h after symptom broke out, and injected the blood into anticoagulation tubeswith ethlenediamine tetraacetic (EDTA). Plasma was separated aftercentrifuging (3000r/min) for10minutes and stored at4℃.Plasma NT-proBNP was measured with double antibody sandwich ELCA(electrochemical luminescence immunoassay) by Elecsys2010fully automaticbiochemistry analyzer and "NT-proBNP diagnostic kit" from Roche Company.The two levels of NT-proBNP were recorded, and D-value ratio=(level18h-level96h)/level96h.4Coronary angiography (CAG)All patients accepted with routine CAG to make a definite diagnosis,radiography result was judged by two professional doctor with intercurrentcertification, positive for a narrow≥50%.5Follow-up resultUAP patients were observed at the end of30days after admission.Main adverse cardiovascular event(MACE) were recorded by the way ofmedical records and telephone.(MACE includes recurring angina pectoris,myocardial infarction, hospitalized again, cardiac insufficiency and death)，The same event happened many times only be counted one time, differentevents occurred in succession only be counted the most serious incident.6Statistical analysisAll data was tested for normality. NT-proBNP present positive skewnessdistribution, expressed with M (Quartiles1, Quartiles3). Wilcoxon rank sumtest was used to compare the difference of interior-group, Wilcoxonsigned-rank test was used to compare the difference of inter-group. Othermeasurement data was expressed by means of mean±standard deviation（x±s）, T-test was used. The χ2test was applied to contrast interclass proportion.Receiver operating characteristic (ROC) curve was used for general evaluationof biomarkers. Calculation and illustration were made by software SPSS17.0.Statistical significance was established at P<0.05.Result：1Compare of basis data72patients included52cases of UAP group and20cases of controlgroup. There was no difference between the UAP group and the control groupin clinical characteres of age, gender ratio, heart rate, blood pressure, body mess index(BMI), cardiac troponin T(cTnT), MB isoenzyme of creatinekinase(CK-MB), triglyeride(TG), total cholesterol(TC), high densitylipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol(LDL-C),fasting blood sugar(FBS), creatinine(Cr), blood urea nitrogen(BUN) and leftventricular ejection fraction(LVEF)(P>0.05).2NT-proBNP levels in two groupsThe NT-proBNP level of18h after symptoms happened in UAP group[226.9(123.8，443.5)] was higher than the control group [63.6(32.1，99.8)](P<0.05).The NT-proBNP level of96h after symptoms relieved in UAP group[131.6(70.7，272.9)] was higher than the control group [58.8(30.9，97.8)](P<0.05).The NT-proBNP level of18h after symptoms happened in UAP groupwas higher than the level of96h after symptoms relieved (P<0.05).There was no significant changes between the levels of18h[63.6(32.1，99.8)] and96h[58.8(30.9，97.8)] in the control group (P>0.05).3ROC curve of NT-proBNP for UAP diagnosisAccording to the ROC curve, AUC18h=0.926and AUC96h=0.772,95%CIwere (0.857,0.996) and (0.645-0.898) respectively. We selected theNT-proBNP of18h after symptoms happened to analyse the diagnosis value ofUAP. It would be confirmed as cutoff value when it made a largest sum ofsensitivity and specificity. we ensured the best cutoff value of103.9pg/mlaccording to the curve, the diagnostic sensitivity of UAP was86.5%andspecificity was80%, positive predict value was91.8%, negative predict valuewas61.5%, positive likelihood ratio was4.33, negative likelihood ratio was0.17.The AUCratio=0.725,95%CI(0.602~0.848)，the best cutoff value was0.98,the diagnostic sensitivity of UAP was46.2%and specificity was95%, positivepredict value was96%, negative predict value was40.4%, positive likelihoodratio was9.2, negative likelihood ratio was0.57. Plasma NT-proBNP andD-value ratio can be taken as the diagnostic index for UAP(P<0.05). 5Follow-up result：The52UAP patients,50patients were finished follow-up,2were lossed.We took D-value ratio=0.98as grouping boundary value, patients were dividedinto≥0.98group (n=23)and <0.98group(n=27). A total of28cases of MACE.There were18cases happened in≥0.98group and10cases in <0.98group.The occurrence rate of MACE in D-value ratio≥0.98group was higher than inD-value ratio<0.98group (P<0.05).Conclusions:1. Plasma NT-proBNP in UAP patients significantly higher than thecoronary artery negative patients, NT-proBNP is a sensitive biologicalmarkers of acute myocardial ischemia.2. Early detection of NT-proBNP after angina attacks will make highersensitivity and specificity to the diagnosis, it is better than the diagnostic valueof96h. D-value ratio has high specificity for diagnosis of UAP. PlasmaNT-proBNP can be used as a auxiliary diagnostic biomarker for UAP.3. It will be instructive and meaningful to clinical work that detect theplasma NT-proBNP level. We can sift high-risk patients timely and giveeffective treatment. |
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