利用生物标志物患者急性心血管疾病演示课件

1、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) Luscher, 19972.5

2、 (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 Angina” Without ST Se

3、gment 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; 1.38-2.40,1.64;

4、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,Correspondence Between Commercial Assays and Western Blotting,Assay Positive WBDSA Negative WBDSA Total,Beckman 10% CV + 17 20 37 - 11 106 117 Roche 10% CV

5、+ 16 8 24 - 12 118 130 Beckman 99th% + 20 38 58- 8 88 96 Roche 99th% + 21 44 65 - 7 82 89,MyeloperoxidasePredictions of Events When cTNT “Negative”,CP1131968-3,NEJM 349:1600, 2003,Odds ratio,Odds ratio,Revascularization Myeloperoxidase quartile 2 Myeloperoxidase quartile 3 Myeloperoxidase quartile 4

6、 Major adverse cardiac events Myeloperoxidase quartile 2 Myeloperoxidase quartile 3 Myeloperoxidase quartile 4,30 Days,6 Months,Prognostic Effects of MPO at 72 Hours,CP1132618-7,Death,MI(%),Circulation 108:1443, 2003,Before PCI,Adjusted hazard ratio2.04 (0.65-6.42),Adjusted hazard ratio3.07 (1.21-4.

7、26),MPO high,MPO low,After PCI,Hours,cTnI Negative ACS?,Circulation 107:533, 2003,CP1104508-19,Sensitivity of cTnI, CK-MB, and Myoglobin with Sensitive Contemporary Assays,AHJ 148:577, 2004,TnI (0.1 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

8、 hrSpecificity,TnI (0.4 g/L)TnI (0.1 g/L)TnI (0.07 g/L),cTnT and Angiographic Measures,CP1179389-5,TnT (0.01),Prog Cardiovasc Dis 47(3), 2004,P0.001,Stenosis (%),TnT (0.01),P=0.02,Thrombus (%),P=0.03,TFG 0/1 (%),P0.001,TMPG 0/1 (%),JACC 36(3):970-1062, 2000,Medical and Interventional Response to GP

9、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=0.016,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=0.0

10、01,5.8%,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,CP956024-13,LMW Heparin vs VF Heparin in TIMI 11B,J Am Coll Cardiol 36:1812, 2000,CP1008642-5,TACTICS (TIMI 18),CP1036852-9,ConservativeInva

11、siveNo.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/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,

12、Relation Between Creatinine Clearance,Troponin T, and Outcomes,CURERates and Relative Risks of First Primary Outcome,CP1019654-1,NEJM 345:494, 2001,CP1189452-4,4 peptides related with each other regarding biochemistry and physiological function Atrial natriureticpeptide (ANP) Brain (or B type)natriu

13、retic peptide(BNP) C-type natriuretic peptide(CNP) Urodilatin, a slightly extended form of ANP,Natriuretic Peptide Family,Common 17-amino acidring structure Ring structure highlyconserved 11/17 amino acidsare homologous Ring structure essentialfor physiological activity,CP1189452-5,Natriuretic Pepti

14、de FamilyBiochemistry,Cardiomyocyte,Blood,proBNP (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,CP1189452-20,

15、97.5%percentile(pg/mL),3030-3940-4950-5960,Age groups,Age-Specific Reference Rangefor NT-proBNP,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,CP1189452-21,38 4,BNPconcent

16、ration (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,BNP Levels in Heart Failure,MedianBNP level (pg/mL),CP1189452-26,BNP Levels in Normal S

17、ubjects and Inpatientswith Heart Failure,Normal,I,II,III,IV,Class,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,70727476788082,74.0,81.2,81.5,n=1,538,BNP Stud

18、y Primary End Point,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,AJC 95, April 15, 2005,Optimal cut-point SensSpecPPVNPVAccuracy(%) (%)(%)(%)(%) (%) Rule-in cut

19、points 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,McCullough PA et al for the BNP Multinational Study Investigators: J Am Coll Cardiol 41:278A

20、, 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,CP1189452-31,CP1189452-32,pg/mL Coronary pulmonale200-500 Primary pulmonary300-500 hypertension Acute

21、 pulmonary150-500 embolism,BNP ElevationsRight-Sided Coronary Heart Failure,CP1189452-33,Acute or chronic systolic or diastolic HF LV hypertrophy Inflammatory cardiac diseases Systemic arterial hypertension with LVH Pulmonary hypertension Acute or chronic renal failure Ascitic liver cirrhosis Endocr

22、ine disorders (eg, hyper-aldosteronism, Cushings syndrome),When Can Non-CHF Patients Present with BNP Elevations?,CP1189452-34,Well HF patients Acute mitral regurgitation Pulmonary edema 1 hour old Other cases “up-stream” fromleft ventricle Mitral stenosis Atrial myoxma,When Will CHF PresentWithout BNP Elevations?,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,CP1173030-6,Relationship of NT-proBNP and cTnT,*P0.01 vs NT-proBNP 250 ng/L Circulation 110:3206, 2004,*,*,Death/MI at 6 months,Test for int