利用生物标志物患者急性心血管疾病课件

1、利用生物标志物患者急性心血管疾病,Use of Biomarkers in Patients with Acute Cardiovascular Disease,Allan S. Jaffe, MD.* Consultant - Cardiology 95:2053-2059,Antman, 19981.1 (0.4-3.5) Benamer, 199813.7 (3.9-48.3) Brisisc, 19988.0 (0.9-65.1) Cin, 199617.9 (5.2-61.2) Galvani, 19976.6 (1.3-32.3) Hamm, 199211.7 (3.2-42.6)

2、 Luscher, 19972.5 (1.3-4.8) Ohman, 19964.7 (1.7-12.7) Olatidoye, 1998156.1 (17.4-1,402) Ottani, 19976.6 (2.0-22.1) Rebuzzi, 199825.3 (5.2-123.2) Solymoss, 19972.4 (0.7-8.1) Stubbs, 19961.5 (0.5-4.2) Wu, 199531.5 (6.7-144.9) Antman, 19963.8 (1.8-8.03),Individual Studies of Patients with“Unstable Angi

3、na” Without ST Segment Elevation,Peto OR 2.66-7.78,Rapid Troponin I Assay,Outcomes in Relation to Troponin Values: The Issue of Assay Sensitivity,CP1148152-9,Int J Cardiol 93:113, 2004,%,Neg,Death,MI,Death or MI,56,98,92,130,132,205,Troponin T (0.1 g/L),Troponin T (0.01 g/L),OR 1.80; 1.30-2.54,1.82;

4、 1.38-2.40,1.64; 1.31-2.06,OR 3.20; 2.22-4.59,2.26; 1.79-2.85,1.47; 1.12-1.93,3.42; 2.57-5.98,4.29; 3.02-6.09,Pos,%,%,41,15,113,139,86,25,136,197,116,36,221,301,利用生物标志物患者急性心血管疾病,Correspondence Between Commercial Assays and Western Blotting,Assay Positive WBDSA Negative WBDSA Total,Beckman 10% CV + 1

5、7 20 37 - 11 106 117 Roche 10% CV + 16 8 24 - 12 118 130 Beckman 99th% + 20 38 58- 8 88 96 Roche 99th% + 21 44 65 - 7 82 89,利用生物标志物患者急性心血管疾病,MyeloperoxidasePredictions of Events When cTNT “Negative”,CP1131968-3,NEJM 349:1600, 2003,Odds ratio,Odds ratio,Revascularization Myeloperoxidase quartile 2 My

6、eloperoxidase quartile 3 Myeloperoxidase quartile 4 Major adverse cardiac events Myeloperoxidase quartile 2 Myeloperoxidase quartile 3 Myeloperoxidase quartile 4,30 Days,6 Months,利用生物标志物患者急性心血管疾病,Prognostic Effects of MPO at 72 Hours,CP1132618-7,Death,MI(%),Circulation 108:1443, 2003,Before PCI,Adju

7、sted hazard ratio2.04 (0.65-6.42),Adjusted hazard ratio3.07 (1.21-4.26),MPO high,MPO low,After PCI,Hours,利用生物标志物患者急性心血管疾病,cTnI Negative ACS?,Circulation 107:533, 2003,CP1104508-19,利用生物标志物患者急性心血管疾病,Sensitivity of cTnI, CK-MB, and Myoglobin with Sensitive Contemporary Assays,AHJ 148:577, 2004,TnI (0.1

8、 g/L)CK-MB (3.5 g/L)Myo (98/56 g/L),CP1176222-2,0 min,30 min,60 min,90 minSensitivity,2 hr,3 hr,6 hr,6 hrSpecificity,TnI (0.4 g/L)TnI (0.1 g/L)TnI (0.07 g/L),利用生物标志物患者急性心血管疾病,cTnT and Angiographic Measures,CP1179389-5,TnT (0.01),Prog Cardiovasc Dis 47(3), 2004,P0.001,Stenosis (%),TnT (0.01),P=0.02,T

9、hrombus (%),P=0.03,TFG 0/1 (%),P0.001,TMPG 0/1 (%),利用生物标志物患者急性心血管疾病,JACC 36(3):970-1062, 2000,Medical and Interventional Response to GP IIb/IIIa Agents in Troponin Positive Patients,+24h,+48h,+24h,+48h,+72h,n=1,265,OR=0.37,P=0.032,CAPTURE,2.8%,1.3%,n=9,461,OR=0.72,P=0.003,PURSUIT,n=1,570,OR=0.45,P=0

10、.016,PRISM-PLUS,n=12,296,OR=0.66,P=0.001,All,n=1,239,OR=0.46,P=0.009,n=1,228,OR=0.71,P=0.105,n=287,OR=0.35,P=0.062,n=2,754,OR=0.59,P=0.001,5.8%,2.8%,10.3%,7.6%,8.0%,2.9%,8.0%,4.9%,4.4%,3.2%,3.8%,1.8%,4.3%,3.9%,Death or MI(%),Start GP IIb/IIIa inhibitor/placebo,Percutaneous coronary intervention,CP95

11、6024-13,利用生物标志物患者急性心血管疾病,LMW Heparin vs VF Heparin in TIMI 11B,J Am Coll Cardiol 36:1812, 2000,CP1008642-5,利用生物标志物患者急性心血管疾病,TACTICS (TIMI 18),CP1036852-9,ConservativeInvasiveNo.treatmenttreatmentPrimary endpoint0.1 ng/mL734 4.36.60.1 - 0.418116.54.40.4 - 1.521317.65.41.569315.68.8 Death or MI0.1 ng/

12、mL734 1.93.00.1 - 0.418112.14.40.4 - 1.521311.82.71.569310.05.9,Cardiac troponin I,JAMA 286:2405, 2001,Favors invasive treatment,Favors Conservative treatment,Odds ratio,利用生物标志物患者急性心血管疾病,Relation Between Creatinine Clearance,Troponin T, and Outcomes,利用生物标志物患者急性心血管疾病,CURERates and Relative Risks of F

13、irst Primary Outcome,CP1019654-1,NEJM 345:494, 2001,利用生物标志物患者急性心血管疾病,CP1189452-4,4 peptides related with each other regarding biochemistry and physiological function Atrial natriureticpeptide (ANP) Brain (or B type)natriuretic peptide(BNP) C-type natriuretic peptide(CNP) Urodilatin, a slightly exten

14、ded form of ANP,Natriuretic Peptide Family,利用生物标志物患者急性心血管疾病,Common 17-amino acidring structure Ring structure highlyconserved 11/17 amino acidsare homologous Ring structure essentialfor physiological activity,CP1189452-5,Natriuretic Peptide FamilyBiochemistry,利用生物标志物患者急性心血管疾病,Cardiomyocyte,Blood,pro

15、BNP (108 aa) BNP-32 (proBNP 77-108),BNP-32 Physiologically active form,NT-proBNP 1-76,SecretionLV stretch Wall tension,Pre-proBNP (134 aa),Signal peptide (26 aa),proBNP,Serin protease (Corin?),Mair: Scand J Clin Lab Invest, 1999,CP1189452-10,利用生物标志物患者急性心血管疾病,CP1189452-20,97.5%percentile(pg/mL),3030-

16、3940-4950-5960,Age groups,Age-Specific Reference Rangefor NT-proBNP,利用生物标志物患者急性心血管疾病,AHJ 149(4), April 2005,pg/mL,NT-proBNP,pg/mL,BNP,Weight categories (BMI),Weight categories (BMI),25,25-29.9,30,25,25-29.9,30,P0.001,P0.001,Values of BNP and NTproBNP by Weight,CP1189452-21,利用生物标志物患者急性心血管疾病,38 4,BNPc

17、oncentration (pg/mL),Diagnosis,n=139,1,076 138,No CHF,CP1189452-25,n=97,CHF,LV dysfunction No acute CHF,n=14,141 31,BNP Levels of Patients Diagnosed Without CHF, with Baseline Left Ventricular Dysfunction, and with CHF,利用生物标志物患者急性心血管疾病,BNP Levels in Heart Failure,MedianBNP level (pg/mL),CP1189452-26

18、,BNP Levels in Normal Subjects and Inpatientswith Heart Failure,Normal,I,II,III,IV,Class,利用生物标志物患者急性心血管疾病,CP1189452-27,ED Probability of CHF Recorded,P0.0001 from clinical judgment to combined,McCullough PA et al: Circulation 106:416, 2002,Diagnostic accuracy (%),Clinicaljudgment,BNP,Combined,707274

19、76788082,74.0,81.2,81.5,n=1,538,BNP Study Primary End Point,利用生物标志物患者急性心血管疾病,n=1,586; 50% CHF; 56% male;6417 yo; 41% COPD; 30% Hx CHF,CP1189452-28,BNP(pg/mL)SensSpecPPVNPV 5097627195 10090767989AUC = 0.91,Breathing Not Proper (BNP)Multicenter Trial,利用生物标志物患者急性心血管疾病,AJC 95, April 15, 200

20、5,Optimal cut-point SensSpecPPVNPVAccuracy(%) (%)(%)(%)(%) (%) Rule-in cutpoints All pt (n=599)9009085769487 50 yr old4509395679995n=144 50 yr old9009180779285n=455 Rule-out pt All pt (n=599) 3009968629983,CP1189452-30,Optimal NT-proBNP Cutpoints for Acute Congestive Heart Failure,利用生物标志物患者急性心血管疾病,M

21、cCullough PA et al for the BNP Multinational Study Investigators: J Am Coll Cardiol 41:278A, 2003,Application of BNP Testing in CHF,“Grey Zone” BNP,BNP (pg/mL),“Grey Zone” BNP100-500 pg/mL,26.4% of all cases,16.5%CHF,7.9%No CHF,0,100,200,300,400,500,600,700,800,900,1,000,1,100,1,200,1,300,CP1189452-

22、31,利用生物标志物患者急性心血管疾病,CP1189452-32,pg/mL Coronary pulmonale200-500 Primary pulmonary300-500 hypertension Acute pulmonary150-500 embolism,BNP ElevationsRight-Sided Coronary Heart Failure,利用生物标志物患者急性心血管疾病,CP1189452-33,Acute or chronic systolic or diastolic HF LV hypertrophy Inflammatory cardiac diseases

23、 Systemic arterial hypertension with LVH Pulmonary hypertension Acute or chronic renal failure Ascitic liver cirrhosis Endocrine disorders (eg, hyper-aldosteronism, Cushings syndrome),When Can Non-CHF Patients Present with BNP Elevations?,利用生物标志物患者急性心血管疾病,CP1189452-34,Well HF patients Acute mitral r

24、egurgitation Pulmonary edema 1 hour old Other cases “up-stream” fromleft ventricle Mitral stenosis Atrial myoxma,When Will CHF PresentWithout BNP Elevations?,利用生物标志物患者急性心血管疾病,P 0.0001,P = 0.9,Baseline BNP & Clinical Outcomes,P 0.0001,P = 0.9,Death,MI,N = 1356,N = 320,Morrow DA JACC 2004,利用生物标志物患者急性心血管疾病,CP1173030-6,Relationship of NT-proBNP and cTnT,*P0.01 vs NT-proBNP 250 ng/L Circulation 110:3206, 2004,*,*,利用生物标志物患者急性心血管疾病,Death/MI at 6 months,Test for