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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
2、from Burnett JC, 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,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,Increase
3、d Na/H20 Excretion,ANP+BNP,NPR-A/NPR-B,Decreased Blood Pressure,Neutral Endopeptidase Cytokines,Clearance,NPR-C,Decreased Vascular Growth,CNP,+,-,+,ZJ,Biology of the Natriuretic Peptides,The natriuretic peptide system has complex genetic regulation Synthesis of an intracellular precursor, proBNP1-10
4、8, precedes release of BNP1-32 and NT-proBNP1-76 BNP1-32 rapidly undergoes processing and degradation into several circulating forms, including BNP3-32 and BNP7-32 proBNP1-108 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
5、定BNP的主要意义,ZJ,表1 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
6、,AUC 0.89,Roche NT-BNP Optimal Value: 340 pmol/L,Biosite BNP Optimal Value: 60 pmol/L,AUC 0.89,Optimal “rule out” cut point=253 ng/L Optimal “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 P
7、atients, NT-proBNP (Black) and BNP (Blue) 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)
8、,Median,NT-proBNP pg/mL,Age-stratified “Rule 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,
9、Am J Cardiol 2005;95:948,NT-proBNP (pg/mL),P0.001,Results: 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,
10、Natriuretic Peptides and LVEF,Januzzi et al, Eur Heart Journal, 2006;27:330,1.8,2.4,3.0,3.6,Log- NT-proBNP,4.2,4.8,15,30,45,60,70,90,r =0.289 P .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 Evalu
11、ation of Patients with Acute Acutely Destabilized Heart Failure,Januzzi et 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 Presentatio
12、n,NT-proBNP 5,180 ng/L,Log rank P value .001,NT-proBNP is a Strong Predictor for Mortality and Morbidity in Patients with HTN,Olsen et al, J Hypertens, 2006; 24:1531,Prior CVD NT-proBNP,Prior CVD NT-proBNP,No prior CVD NT-proBNP,No prior CVD NT-proBNP,Event Rate (%),Outcomes Following Acute HF as a
13、Function of Change in NT-proBNP,Bettencourt et al, Circulation, 2004; 110:2168,1.0 0.8 0.6 0.4 0.2 0.0,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; 26:226
14、9,BNP Levels in patients with dyspnea caused by CHF or chronic obstructive pulmonary disease,J. Cardiac Failure 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 t
15、o BNP values. Values are expressed as mean +/- SEM,Dao, Q., Maisel, A. et al. J. American College of Cardiology, No. 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. Lancet 1994; 343:440-444.,BNP vs. EF by Echocardiography,ZJ,BNP a
