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1、BNP/NT-proBNP监测在心力衰竭诊治中的应用,中国医学科学院 中国协和医科大学 心血管病研究所 阜外心血管病医院心力衰竭诊治中心张 健,BNP/NT-proBNP在心衰中的作用,诊断预后判定有效监测人群筛选治疗,ZJ,利钠肽（Natriuretic Peptides,NPs）,ANP：心钠素(Atrial NP)(Kangawak,1984)BNP：脑钠素(Brain NP)，又称B型利钠肽(Sudoh T,1988)CNP：C型利钠肽(C-type NP)(Sudoh T,1990)CNP-53 CNP-22,ZJ,NP:起源和应激反应,Adapted from Burnett JC
2、,J Hypertens 2000;17(Suppl 1):S37-S43,ANP=心房促尿钠排泄缩氨酸BNP=B-型促尿钠排泄缩氨酸CNP=C-型促尿钠排泄缩氨酸,ZJ,BNP/NT-proBNP的分泌和释放,ZJ,ZJ,BNP的形成和分解,pre-proBNP1-134,proBNP1-108,proBNP1-108,Signal peptide(26 amino acids),Wilkins MR.Redondo J.Brown LA.Lancet 1997;349:1307-1310,Ventricular overload,Urodilatin,NPR-A,IncreasedNa/H
3、20 Excretion,ANP+BNP,NPR-A/NPR-B,DecreasedBlood Pressure,NeutralEndopeptidase Cytokines,Clearance,NPR-C,DecreasedVascular Growth,CNP,+,-,+,ZJ,Biology of the Natriuretic Peptides,The natriuretic peptide system has complex genetic regulationSynthesis of an intracellular precursor,proBNP1-108,precedes
4、release of BNP1-32 and NT-proBNP1-76BNP1-32 rapidly undergoes processing and degradation into several circulating forms,including BNP3-32 and BNP7-32proBNP1-108 and NT-proBNP1-76 have absent biologic activity,while BNP3-32 and BNP7-32 have less biologic activity than BNP1-32,表1 心衰患者测定BNP的主要意义,ZJ,表1
5、心衰患者测定BNP的主要意义,ZJ,Lainchbury et al,J Am Coll Cardiol,2003;42:728,NT-proBNP is Strongly Correlated to BNP in Acute Dyspnea,Lainchbury et al,J Am Coll Cardiol,2003;42:728,NT-proBNP Has Equal Diagnostic Accuracy to BNP in Acute Dyspnea,Specificity,Sensitivity,Sensitivity,Specificity,AUC 0.89,Roche NT-B
6、NPOptimal Value:340 pmol/L,Biosite BNPOptimal Value:60 pmol/L,AUC 0.89,Optimal“rule out”cut point=253 ng/LOptimal“rule in”cut point=973 ng/L,Bayes-Genis et al,Eur J Heart Fail,2004;6:301,1-Specificity,Sensitivity,Mueller et al,Heart,2005;91:606,Among 251 Dyspneic Patients,NT-proBNP(Black)and BNP(Blu
7、e)had Equivalent Diagnostic Accuracy,Expected NT-proBNP values in Apparently Healthy Individuals(n=2264)*,60,50,40,30,20,70,80,Age,*From Elecsys NT-proBNP package insert,125 pg/mL,95th percentile(95%of the individuals have NT-proBNP values below this value),Median,NT-proBNP pg/mL,Age-stratified“Rule
8、 In”Cut Point,To Diagnose Acute HF:The“Triple Cut Point,Januzzi et al,Eur H Jour 2006;27:330,Final Diagnoses,#of subjects,Januzzi et al,Am J Cardiol 2005;95:948,Acute HF(N=209),No prior HF(N=355),Prior HF(N=35),Not acute HF(N=390),Januzzi et al,Am J Cardiol 2005;95:948,NT-proBNP(pg/mL),P0.001,Result
9、s:NT-proBNP Levels,NYHA,Class II(n=17),Class III(n=80),Class IV(n=112),1591,3438,5564,NT-proBNP Levels and HF Symptom Severity,0,1000,2000,3000,4000,5000,6000,NT-proBNP(pg/ml),P=.001,Januzzi et al,Am J Cardiol 2005;95:948,1591,3438,5564,Natriuretic Peptides and LVEF,Januzzi et al,Eur Heart Journal,2
10、006;27:330,1.8,2.4,3.0,3.6,Log-NT-proBNP,4.2,4.8,15,30,45,60,70,90,r=0.289P.001,Left Ventricular Ejection Fraction(%),NT-proBNP in Aortic Stenosis,Weber et al,Am J Cardiol,2004;94(6):740,P.001,NT-proBNP(pg/mL),Prognostic Evaluation of Patients with Acute Acutely Destabilized Heart Failure,Januzzi et
11、 al,Eur Heart J,2006;27:330,Association Between Presentation NT-proBNP Values and Short-term Mortality in Acute Destabilized Heart Failure,0.85,0.90,0.95,1.00,Cumulative Survival,P.00001,0.70,0.75,0.80,Days from Presentation,NT-proBNP 5,180 ng/L,Log rank P value.001,NT-proBNP is a Strong Predictor f
12、or Mortality and Morbidity in Patients with HTN,Olsen et al,J Hypertens,2006;24:1531,Prior CVDNT-proBNP,Prior CVDNT-proBNP,No prior CVDNT-proBNP,No prior CVDNT-proBNP,Event Rate(%),Outcomes Following Acute HF as a Function of Change in NT-proBNP,Bettencourt et al,Circulation,2004;110:2168,1.00.80.60
13、.40.20.0,Cumulative Hospitalization-free Survival,Decrease 30%Change 30%,Time(Days),0,100,200,健康人NT-proBNP的参考值正常人中,妇女和老人有较高的 NT-proBNP,然而,在急性呼吸困难的病人中,则看不到这种现象,Galasko et al,Eur Heart J,2005;26:2269,BNP Levels in patients with dyspnea caused by CHF or chronic obstructive pulmonary disease,J.Cardiac F
14、ailure 7(2):183-9 2001,ZJ,BNP levels in patients with diagnosis of CHF and baseline left ventricular dysfunction.Diagnosis of CHF was based on independent assessment by 2 cardiologists blinded to BNP values.Values are expressed as mean+/-SEM,Dao,Q.,Maisel,A.et al.J.American College of Cardiology,No.
15、2,2001.,ZJ,BNP Concentration(pg/ml),186 22,791 165,2013 266,N=27,N=34,N=36,BNP concentrations for the degree of CHF severity,Mild,Moderate,Severe,J.Cardiac Failure 7(2):183-9 2001,ZJ,BNP levels in patients with CHF NYHA Class,Heart Failure 19:557-71 2001,80 152 332 590 960(pg/mL),ZJ,Davis et al.Lanc
16、et 1994;343:440-444.,BNP vs.EF by Echocardiography,ZJ,BNP and LVEF-Scintigraphy,Source:Clerico et al.J.Endocrinol.Invest 1998;21:170-179.,4,3,2,1,Concentrations Log BNP(ng/l),0 10 20 30 40 50 60 70,%LVEF,1-Specificity(%),Sensitivity(%),82,118,205,-,BNP,ED diagnosis,AUC,0.884,0.9790,-,ROC Curve:BNP a
17、nd ED Diagnosis Diagnosis in All 250 Patients,Dao,Q.et al.J.American College of Cardiology,Vol 37,No.2,2001,ZJ,Cumulative survival rates in CHF patients with LVD,Tsutamoto T.et al.Circulation 1997;96:509-516,Stratification based on Median BNP values at 73 pg/ml,BNP Concentration for the Prediction o
18、f Clinical Events,Maisel A,Ann Emerg Med.February 2002;39:131-138.,ZJ,BNP 和 NT-proBNP 的总结,BNP 是一个应用更广泛的标志物 两种分子的数值不可互换都是心衰中好的诊断标志物都可用于筛查左心室功能障碍都是心衰中较好的预测标志物,ZJ,阜外心血管病医院的一些初步研究,ZJ,左心衰竭组不同NYHA分级的BNP箱线图,注：与对照组比较：*p0.05;*p0.001；与NYHA I级比较：#p0.05;#p0.001；与NYHA级比较：$p0.05;$p0.001；与NYHA 级比较：&p0.001,ZJ,Kapla
19、n-Meier生存曲线分析,以288 pg/ml为BNP的分割点，BNP288 pg/ml组的平均无心源性事件生存时间为18.06个月BNP288 pg/ml组的平均无心源性事件生存时间为9.94个月BNP288 pg/ml组的无心源性事件生存时间显著长于BNP288 pg/ml组（P0.0001），约为其2倍。,ZJ,NT-proBNP与DCM n=(203)的严重程度,中国循环杂志2008年第5期,ZJ,NT-proBNP预测DCHF的住院病死率,中华心血管病杂志2009年6期,ROC分析表明：NT-proBNP 3500fmol/ml为切点预测住院死亡率的敏感性、特异性和准确性均70左右阴性预测值在96以上阳性预测值为17,与实际死亡率相同（n=840）,ZJ,BNP预测AMI患者30天内心原性死亡,ZJ,BNP预测AMI患者6个月内心原性死亡,ZJ,AMI患者1年内心原性死亡与BNP,ZJ,proANP、NT-proBNP、NT-proCNP测定,心衰患者的proANP、NT-proBNP、NT-proCNP均较对照组明显升高,ZJ,proANP、NT-proBNP与NT-proCNP三者间相关性,三者之间均两两相关，其中以logproANP与logNT-proBNP之间的相关性最强,ZJ,Thank you very much!,
