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1、CP887679- 0Use of Biomarkers in Patients with Acute Cardiovascular DiseaseAllan S. Jaffe, MD.*Consultant - Cardiology & Laboratory MedicineProfessor of MedicineMayo Clinic and Medical SchoolRochester, Minnesota *Dr. Jaffe is a consultant and receives research support from Roche, Dade Behring and Bec
2、kmann Coulter. He has been or presently is a consultant to Ortho Diagnostics, Sensera, Diadexus, Abbott, Hawaii Biotech and Tartagen.CP1051812-1Clinical Outcomes by Braunwald ClassClinical Outcomes by Braunwald ClassDaysDaysDaysDaysDaysDaysPrimary Unstable AnginaPrimary Unstable AnginaPrimary Unstab
3、le AnginaClass BClass BClass BPostinfarction AnginaPostinfarction AnginaPostinfarction AnginaClass CClass CClass CAccelerated AnginaAccelerated AnginaAccelerated AnginaClass IClass IClass ISubacute Angina at RestSubacute Angina at RestSubacute Angina at RestClass IIClass IIClass IIAcute Angina at Re
4、stAcute Angina at RestAcute Angina at RestClass IIIClass IIIClass IIIP PPP PPSurvivalSurvivalSurvivalInfarct freeInfarct freeInfarct freeInfarct free withoutInfarct free withoutInfarct free withoutinterventioninterventionintervention0.970.970.970.910.910.910.530.530.530.960.960.960.880.880.880.720.7
5、20.720.940.940.940.860.860.860.350.350.350.970.970.970.890.890.890.550.550.550.890.890.890.800.800.800.370.370.37JACC 25:1286, 1995JACC 25:1286, 1995JACC 25:1286, 1995CP887679- 2ECG Risk Factors in Patients with ACSDeath or MIDeath or MI(%)(%)DaysDaysJACC 36(3):970-1062, 2000JACC 36(3):970-1062, 200
6、0ST elevation and depressionST elevation and depressionST depression onlyST depression onlyST elevation onlyST elevation onlyT-wave inversion onlyT-wave inversion onlyNo ST or T-wave changeNo ST or T-wave changen=237n=237n=287n=287n=93n=93n=216n=216n=78n=78CP956024-12CP887679- 3Relationship of ECG C
7、hanges and FPA*FPAFPA(nM)(nM)* *JACC 18:898-903, 1991JACC 18:898-903, 1991100nl 1.5nl 1.5CP887679- 4Long-Term Prognostic Value of ElevatedcTnI in Unstable Angina% % freefreefromfromdeathdeathand/orand/orAMIAMITime from admission (days)Time from admission (days)Normal cTnINormal cTnILog rank 6.63, P=
8、0.01Log rank 6.63, P=0.01Elevated cTnIElevated cTnICirculation. 1997;95:2053-2059 CP887679- 5Antman, 1998Antman, 19981.1 (0.4-3.5)1.1 (0.4-3.5)Benamer, 1998Benamer, 199813.7 (3.9-48.3)13.7 (3.9-48.3)Brisisc, 1998Brisisc, 19988.0 (0.9-65.1)8.0 (0.9-65.1)Cin, 1996Cin, 199617.9 (5.2-61.2)17.9 (5.2-61.2
9、)Galvani, 1997Galvani, 19976.6 (1.3-32.3)6.6 (1.3-32.3)Hamm, 1992Hamm, 199211.7 (3.2-42.6)11.7 (3.2-42.6)Luscher, 1997Luscher, 19972.5 (1.3-4.8)2.5 (1.3-4.8)Ohman, 1996Ohman, 19964.7 (1.7-12.7)4.7 (1.7-12.7)Olatidoye, 1998Olatidoye, 1998156.1 (17.4-1,402)156.1 (17.4-1,402)Ottani, 1997Ottani, 19976.6
10、 (2.0-22.1)6.6 (2.0-22.1)Rebuzzi, 1998Rebuzzi, 199825.3 (5.2-123.2)25.3 (5.2-123.2)Solymoss, 1997Solymoss, 19972.4 (0.7-8.1)2.4 (0.7-8.1)Stubbs, 1996Stubbs, 19961.5 (0.5-4.2)1.5 (0.5-4.2)Wu, 1995Wu, 199531.5 (6.7-144.9)31.5 (6.7-144.9)Antman, 1996Antman, 19963.8 (1.8-8.03)3.8 (1.8-8.03)Individual St
11、udies of Patients with“Unstable Angina”Individual Studies of Patients with“Unstable Angina” Without Without ST Segment ElevationST Segment ElevationPeto OR & 95% CI (fixed)Peto OR & 95% CI (fixed)Pooled OR P0.0001Pooled OR P0.00010.20.11 51050FavorsFavorslower risklower riskFavorsFavorshigher riskhi
12、gher risk4.8 (3.6-6.5)4.8 (3.6-6.5)CP887679- 6Antman, 1996Antman, 19963.82 (1.03-14.18)3.82 (1.03-14.18)Benamer, 1998Benamer, 199813.68 (3.87-48.33)13.68 (3.87-48.33)Brisisc, 1998Brisisc, 19987.96 (0.97-65.25)7.96 (0.97-65.25)Cin, 1996Cin, 199617.91 (5.24-61.25)17.91 (5.24-61.25)Galvani, 1997Galvani
13、, 19976.55 (1.32-32.38)6.55 (1.32-32.38)Hamm, 1992Hamm, 199211.71 (3.22-42.57)11.71 (3.22-42.57)Luscher, 1997Luscher, 19975.93 (1.61-21.79)5.93 (1.61-21.79)Olatidoye, 1998Olatidoye, 1998156.17 (17.39-1,402.09)156.17 (17.39-1,402.09)Rebuzzi, 1998Rebuzzi, 199825.27 (5.18-123.23)25.27 (5.18-123.23)Soly
14、moss, 1997Solymoss, 19974.93 (0.72-33.19)4.93 (0.72-33.19)Wu, 1995Wu, 199531.52 (6.89-144.19)31.52 (6.89-144.19)Individual Studies of Individual Studies of Patients with “Unstable Angina” and Normal Patients with “Unstable Angina” and Normal CKMB ValuesCKMB ValuesPeto OR & 95% CI (fixed)Peto OR & 95
15、% CI (fixed)Pooled ORPooled ORP0.0001P0.00010.20.11 51050FavorsFavorslower risklower riskFavorsFavorshigher riskhigher risk11.83 (7.56-18.51)11.83 (7.56-18.51)CP887679- 7cTnI in Patients with Unstable AnginaMortality at 42 daysMortality at 42 days(% of patients)(% of patients)CP886232- 7NEJM 335:134
16、2-1349, 1996NEJM 335:1342-1349, 1996Cardiac Troponin I (ng/mL)Cardiac Troponin I (ng/mL)83117414813450671.01.83.53.96.27.8Risk ratio-95% CI CP887679- 8Synergism of ECG and Elevated Troponins (PARAGON)CP1099500-8JACC 41:376, 2003JACC 41:376, 2003JACC 41:376, 20036-6-6-momomodeath/death/death/MI rateM
17、I rateMI raten=262ST-depressionST-depressionST-depressionP=0.20P=0.20P=0.20n=125n=259n=174n=57n=82P=0.13P=0.13P=0.13P=0.15P=0.15P=0.15TroponinTroponinTroponinTroponin+Troponin+Troponin+CP887679- 9FRISC-II GUSTO IV (Death and MI)CP1142356-17James et al: Am J Med 115:181, 2003James et al: Am J Med 115
18、:181, 2003James et al: Am J Med 115:181, 20031414141212121010108 886 664 442 220 000.01 0.01 0.01 g/Lg/Lg/LFRISC-IIFRISC-IIFRISC-IIDeath and MI at 30 days (%)Death and MI at 30 days (%)Death and MI at 30 days (%)0.03 0.03 0.03 g/Lg/Lg/LP=0.04P=0.04P=0.04Below cutoffBelow cutoffBelow cutoffAbove cuto
19、ffAbove cutoffAbove cutoff0.1 0.1 0.1 g/Lg/Lg/LP=0.01P=0.01P=0.01P=0.15P=0.15P=0.15CutoffCutoffCutoff0.01 0.01 0.01 g/Lg/Lg/LGUSTO-IVGUSTO-IVGUSTO-IV0.03 0.03 0.03 g/Lg/Lg/LP0.001P0.001P0.0010.1 0.1 0.1 g/Lg/Lg/LP0.001P0.001P0.001P0.001P0.001P0.001CutoffCutoffCutoff1111118080801717177474743030306161
20、616666665215215211111111114764764762012012013863863862658093287464306441,992 5,1232,563 4,5523,446 3,679CP887679- 100.010.020.030.040.050.060.0ABCDEGHTotal CV, %ACS180CentaurImmuno 1AccessAccess2VidasLiaisonRXL CSOpusImmuliteAlpha DxECiAIA 21IFCC Precision Study(Clinical Chem 2004)CP887679- 11Rapid
21、Troponin I AssayRapid Troponin I AssayRapid Troponin I AssayOutcomes in Relation to Troponin Values: The Issue of Assay SensitivityCP1148152-9Int J Cardiol 93:113, 2004Int J Cardiol 93:113, 2004Int J Cardiol 93:113, 2004%NegNegNegDeathDeathDeathMIMIMIDeath or MIDeath or MIDeath or MI569892130132205T
22、roponin T (0.1 Troponin T (0.1 Troponin T (0.1 g/L)g/L)g/L)Troponin T (0.01 Troponin T (0.01 Troponin T (0.01 g/L)g/L)g/L)PosPosPos%4115113139862513619711636221301CP887679- 12Correspondence Between Commercial Assays and Correspondence Between Commercial Assays and Western BlottingWestern BlottingAss
23、ay Positive WBDSA Negative WBDSA TotalBeckman 10% CV+ 17 20 37- 11 106 117Roche 10% CV+ 16 8 24- 12 118 130Beckman 99th%+ 20 38 58- 8 88 96Roche 99th% + 21 44 65- 7 82 89CP887679- 13MyeloperoxidaseMyeloperoxidasePredictions of Events When cTNT “Negative”Predictions of Events When cTNT “Negative”CP11
24、31968-3NEJM 349:1600, 2003NEJM 349:1600, 2003NEJM 349:1600, 2003Odds ratioOdds ratioOdds ratioOdds ratioOdds ratioOdds ratioRevascularizationRevascularizationRevascularizationMyeloperoxidase quartile 2Myeloperoxidase quartile 2Myeloperoxidase quartile 2Myeloperoxidase quartile 3Myeloperoxidase quart
25、ile 3Myeloperoxidase quartile 3Myeloperoxidase quartile 4Myeloperoxidase quartile 4Myeloperoxidase quartile 4Major adverse cardiac eventsMajor adverse cardiac eventsMajor adverse cardiac eventsMyeloperoxidase quartile 2Myeloperoxidase quartile 2Myeloperoxidase quartile 2Myeloperoxidase quartile 3Mye
26、loperoxidase quartile 3Myeloperoxidase quartile 3Myeloperoxidase quartile 4Myeloperoxidase quartile 4Myeloperoxidase quartile 430 Days30 Days30 Days6 Months6 Months6 MonthsUnadjustedUnadjustedUnadjustedAdjustedAdjustedAdjustedCP887679- 14Prognostic Effects of MPO at 72 HoursPrognostic Effects of MPO
27、 at 72 HoursCP1132618-7Death,Death,Death,MIMIMI(%)(%)(%)Circulation 108:1443, 2003Circulation 108:1443, 2003Before PCIBefore PCIBefore PCIAdjusted hazard ratioAdjusted hazard ratioAdjusted hazard ratio2.04 (0.65-6.42)2.04 (0.65-6.42)2.04 (0.65-6.42)Adjusted hazard ratioAdjusted hazard ratioAdjusted
28、hazard ratio3.07 (1.21-4.26)3.07 (1.21-4.26)3.07 (1.21-4.26)MPO highMPO highMPO highMPO lowMPO lowMPO lowAfter PCIAfter PCIAfter PCIHoursHoursHoursCP887679- 15cTnI Negative ACS?Circulation 107:533, 2003Circulation 107:533, 2003Circulation 107:533, 2003CP1104508-19CP887679- 16Sensitivity of cTnI, CK-
29、MB, and Myoglobin with Sensitive Sensitivity of cTnI, CK-MB, and Myoglobin with Sensitive Contemporary AssaysContemporary AssaysAHJ 148:577, 2004AHJ 148:577, 2004AHJ 148:577, 2004TnI (0.1 g/L)TnI (0.1 g/L)TnI (0.1 g/L)CK-MB (3.5 g/L)CK-MB (3.5 g/L)CK-MB (3.5 g/L)Myo (98/56 g/L)Myo (98/56 g/L)Myo (98
30、/56 g/L)CP1176222-20 min30 min60 min90 minSensitivity2 hr3 hr6 hr6 hrSpecificity TnI (0.4 g/L)TnI (0.4 g/L)TnI (0.4 g/L)TnI (0.1 g/L)TnI (0.1 g/L)TnI (0.1 g/L)TnI (0.07 g/L)TnI (0.07 g/L)TnI (0.07 g/L)CP887679- 17cTnT and Angiographic MeasuresCP1179389-5TnT (0.01)TnT (0.01)TnT (0.01)Prog Cardiovasc
31、Dis 47(3), 2004Prog Cardiovasc Dis 47(3), 2004Prog Cardiovasc Dis 47(3), 2004P0.001P0.001P0.01)TnT (0.01)TnT (0.01)P=0.02P=0.02P=0.02Thrombus (%)Thrombus (%)Thrombus (%)P=0.03P=0.03P=0.03TFG 0/1 (%)TFG 0/1 (%)TFG 0/1 (%)P0.001P0.001P0.001TMPG 0/1 (%)TMPG 0/1 (%)TMPG 0/1 (%)CP887679- 18JACC 36(3):970
32、-JACC 36(3):970-1062, 20001062, 2000Medical and Interventional Response to GP IIb/IIIa Agents in Medical and Interventional Response to GP IIb/IIIa Agents in Troponin Positive PatientsTroponin Positive Patients+24h+24h+48h+48h +24h+24h+48h+48h +72h+72hn=1,265n=1,265OR=0.37OR=0.37P=0.032P=0.032CAPTUR
33、ECAPTURE2.8%2.8%1.3%1.3%n=9,461n=9,461OR=0.72OR=0.72P=0.003P=0.003PURSUITPURSUITn=1,570n=1,570OR=0.45OR=0.45P=0.016P=0.016PRISM-PLUSPRISM-PLUSn=12,296n=12,296OR=0.66OR=0.66P=0.001P=0.001AllAlln=1,239n=1,239OR=0.46OR=0.46P=0.009P=0.009n=1,228n=1,228OR=0.71OR=0.71P=0.105P=0.105n=287n=287OR=0.35OR=0.35
34、P=0.062P=0.062n=2,754n=2,754OR=0.59OR=0.59P=0.001P=0.0015.8%5.8%2.8%2.8%10.3%10.3%7.6%7.6%8.0%8.0%2.9%2.9%8.0%8.0%4.9%4.9%4.4%4.4%3.2%3.2%3.8%3.8%1.8%1.8%4.3%4.3%3.9%3.9%Death or MIDeath or MI(%)(%)Start GP IIb/IIIa inhibitor/placeboStart GP IIb/IIIa inhibitor/placeboPercutaneous coronary interventi
35、onPercutaneous coronary interventionCP956024-13CP887679- 19LMW Heparin vs VF Heparin in TIMI 11BLMW Heparin vs VF Heparin in TIMI 11BJ Am Coll Cardiol 36:1812, 2000J Am Coll Cardiol 36:1812, 2000CP1008642-5Clinical events at 14 days (%)Clinical events at 14 days (%)CKMB negative patientsCKMB negativ
36、e patientsEnoxaparinEnoxaparinUFHUFH6 6P=0.006P=0.0066 60 04 46 69 9171710101111404021212828P=0.007P=0.007cTnI NegativecTnI Negativen=179n=179cTnI PositivecTnI Positiven=180n=180CP887679- 20TACTICS (TIMI 18)CP1036852-9ConservativeConservativeConservativeInvasiveInvasiveInvasiveNo.No.No.treatmenttrea
37、tmenttreatmenttreatmenttreatmenttreatmentPrimary endpointPrimary endpointPrimary endpoint0.1 ng/mL0.1 ng/mL0.1 ng/mL734734734 4.3 4.3 4.36.66.66.60.1 - 0.40.1 - 0.40.1 - 0.418118118116.516.516.54.44.44.40.4 - 1.50.4 - 1.50.4 - 1.521321321317.617.617.65.45.45.4 1.51.51.569369369315.615.615.68.88.88.8
38、Death or MIDeath or MIDeath or MI0.1 ng/mL0.1 ng/mL0.1 ng/mL734734734 1.9 1.9 1.93.03.03.00.1 - 0.40.1 - 0.40.1 - 0.418118118112.112.112.14.44.44.40.4 - 1.50.4 - 1.50.4 - 65 yr old65 yr old65 yr old 6,208 6,208 6,20815.315.315.313.313.313.3ST-segment deviationST-segment deviationST-segment deviation
39、 6,275 6,275 6,27514.314.314.311.511.511.5No ST-segment deviationNo ST-segment deviationNo ST-segment deviation 6,287 6,287 6,287 8.6 8.6 8.6 7.0 7.0 7.0Enzymes elevated at entryEnzymes elevated at entryEnzymes elevated at entry 3,176 3,176 3,17613.013.013.010.710.710.7Enzymes not elevated at entryE
40、nzymes not elevated at entryEnzymes not elevated at entry 9,386 9,386 9,38610.910.910.9 8.8 8.8 8.8DiabetesDiabetesDiabetes 2,840 2,840 2,84016.716.716.714.214.214.2No diabetesNo diabetesNo diabetes 9,722 9,722 9,722 9.9 9.9 9.9 7.9 7.9 7.9Low riskLow riskLow risk 4,187 4,187 4,187 6.7 6.7 6.7 5.1 5
41、.1 5.1Intermediate riskIntermediate riskIntermediate risk 4,185 4,185 4,185 9.4 9.4 9.4 6.5 6.5 6.5High riskHigh riskHigh risk 4,184 4,184 4,18418.018.018.016.316.316.3History of revascularizationHistory of revascularizationHistory of revascularization 2,246 2,246 2,24614.414.414.4 8.4 8.4 8.4No his
42、tory of revascularizationNo history of revascularizationNo history of revascularization10,31610,31610,31610.710.710.7 9.5 9.5 9.5Revascularization after randomization Revascularization after randomization Revascularization after randomization 4,577 4,577 4,57713.913.913.911.511.511.5No revasculariza
43、tion after randomization No revascularization after randomization No revascularization after randomization 7,985 7,985 7,98510.010.010.0 8.1 8.1 8.1Relative risk (95% CI)Relative risk (95% CI)Relative risk (95% CI)ClopidogrelClopidogrelClopidogrelbetterbetterbetterPlaceboPlaceboPlacebobetterbetterbe
44、tterNEJM 345:494, 2001NEJM 345:494, 2001CP887679- 23CP1189452-44 4 4 peptides related with each other regarding peptides related with each other regarding peptides related with each other regarding biochemistry and physiological functionbiochemistry and physiological functionbiochemistry and physiol
45、ogical function Atrial natriureticAtrial natriureticAtrial natriureticpeptide (ANP)peptide (ANP)peptide (ANP) Brain (or B type)Brain (or B type)Brain (or B type)natriuretic peptidenatriuretic peptidenatriuretic peptide(BNP)(BNP)(BNP) C-type natriuretic peptideC-type natriuretic peptideC-type natriur
46、etic peptide(CNP)(CNP)(CNP) Urodilatin, a slightly extended form of ANPUrodilatin, a slightly extended form of ANPUrodilatin, a slightly extended form of ANPH H2 2N NCOOHCOOHCOOHCFCDRISGLCCNatriuretic Peptide Family CP887679- 24 Common 17-amino acidCommon 17-amino acidCommon 17-amino acidring struct
47、urering structurering structure Ring structure highlyRing structure highlyRing structure highlyconservedconservedconserved 11/17 amino acids11/17 amino acids11/17 amino acidsare homologousare homologousare homologous Ring structure essentialRing structure essentialRing structure essentialfor physiol
48、ogical activityfor physiological activityfor physiological activityH H2 2N NCOOHCOOHCOOHCFCDRISGLCCCP1189452-5Natriuretic Peptide FamilyBiochemistryCP887679- 25CardiomyocyteBloodBloodproBNPproBNPproBNP (108 aa) (108 aa) (108 aa)BNP-32 (proBNP 77-108) BNP-32 (proBNP 77-108) BNP-32 (proBNP 77-108) BNP
49、-32BNP-32BNP-32Physiologically active formPhysiologically active formPhysiologically active formNT-proBNP 1-76NT-proBNP 1-76NT-proBNP 1-76SecretionSecretionSecretionLV stretchLV stretchLV stretchWall tensionWall tensionWall tensionPre-proBNP (134 aa)Pre-proBNP (134 aa)Pre-proBNP (134 aa)Signal pepti
50、de (26 aa)Signal peptide (26 aa)Signal peptide (26 aa)proBNPproBNPproBNPSerin proteaseSerin proteaseSerin protease(Corin?)(Corin?)(Corin?)Mair: Scand J Clin Lab Invest, 1999Mair: Scand J Clin Lab Invest, 1999Mair: Scand J Clin Lab Invest, 1999CP1189452-10CP887679- 26CP1189452-2097.5%97.5%97.5%percen
51、tilepercentilepercentile(pg/mL)(pg/mL)(pg/mL)30303030-3930-3930-3940-4940-4940-4950-5950-5950-59 606060Age groupsAge groupsAge groupsMalesMalesMalesFemalesFemalesFemalesAge-Specific Reference Rangefor NT-proBNPCP887679- 27AHJ 149(4), April 2005AHJ 149(4), April 2005AHJ 149(4), April 2005pg/mLpg/mLpg
52、/mLNT-proBNPNT-proBNPNT-proBNPpg/mLpg/mLpg/mLBNPBNPBNPWeight categories (BMI)Weight categories (BMI)Weight categories (BMI)Weight categories (BMI)Weight categories (BMI)Weight categories (BMI) 252525 25-29.925-29.925-29.9 303030 252525 25-29.925-29.925-29.9 303030 P0.001P0.001P0.001 P0.001P0.001P0.0
53、01 Values of BNP and NTproBNP by WeightCP1189452-21CP887679- 2838 438 438 4BNPBNPBNPconcentrationconcentrationconcentration(pg/mL)(pg/mL)(pg/mL)DiagnosisDiagnosisDiagnosisn=139n=139n=1391,076 1381,076 1381,076 138No CHFNo CHFNo CHFCP1189452-25n=97n=97n=97CHFCHFCHFLV dysfunctionLV dysfunctionLV dysfu
54、nctionNo acute CHFNo acute CHFNo acute CHFn=14n=14n=14141 31141 31141 31BNP Levels of Patients Diagnosed Without CHF, with BNP Levels of Patients Diagnosed Without CHF, with Baseline Left Ventricular Dysfunction, and with CHFBaseline Left Ventricular Dysfunction, and with CHFCP887679- 29BNP Levels i
55、n Heart FailureMedianMedianMedianBNP BNP BNP levellevellevel(pg/mL)(pg/mL)(pg/mL)CP1189452-26BNP Levels in Normal Subjects and InpatientsBNP Levels in Normal Subjects and InpatientsBNP Levels in Normal Subjects and Inpatientswith Heart Failurewith Heart Failurewith Heart FailureNormalNormalNormalI I
56、 III II IIIIIIIIIIIIVIVIVClassClassClassCP887679- 30CP1189452-27ED Probability of CHF RecordedED Probability of CHF RecordedED Probability of CHF RecordedP0.0001 from clinical judgment to combinedP0.0001 from clinical judgment to combinedP0.0001 from clinical judgment to combinedMcCullough PA et al:
57、 Circulation 106:416, 2002McCullough PA et al: Circulation 106:416, 2002McCullough PA et al: Circulation 106:416, 2002Diagnostic accuracy (%)Diagnostic accuracy (%)Diagnostic accuracy (%)ClinicalClinicalClinicaljudgmentjudgmentjudgmentBNPBNPBNPCombinedCombinedCombined70707072727274747476767678787880
58、808082828274.081.281.5n=1,538n=1,538n=1,538BNP Study Primary End PointCP887679- 31n=1,586; n=1,586; n=1,586; 50% CHF; 56% male;50% CHF; 56% male;50% CHF; 56% male;6417 yo; 41% COPD; 6417 yo; 41% COPD; 6417 yo; 41% COPD; 30% Hx CHF30% Hx CHF30% Hx CHFCP1189452-28 BNPBNPBNP(pg/mL)(pg/mL)(pg/mL)SensSen
59、sSensSpecSpecSpecPPVPPVPPVNPVNPVNPV 50 50 50979797626262717171959595100100100909090767676797979898989150150150858585838383838383858585AUC = 0.91AUC = 0.91AUC = 0.91Breathing Not Proper (BNP)Multicenter TrialCP887679- 32AJC 95, April 15, 2005AJC 95, April 15, 2005AJC 95, April 15, 2005OptimalOptimalO
60、ptimal cut-point cut-point cut-point SensSensSens SpecSpecSpec PPVPPVPPV NPVNPVNPV AccuracyAccuracyAccuracy(%)(%)(%) (%) (%) (%)(%)(%)(%)(%)(%)(%)(%)(%)(%) (%) (%) (%)Rule-in cutpointsRule-in cutpointsRule-in cutpointsAll pt (n=599)All pt (n=599)All pt (n=599)9009009009090908585857676769494948787875
61、0 yr old50 yr old50 yr old450450450939393959595676767999999959595n=144n=144n=144 50 yr old50 yr old50 yr old900900900919191808080777777929292858585n=455n=455n=455Rule-out ptRule-out ptRule-out ptAll pt (n=599)All pt (n=599)All pt (n=599) 300 300 300999999686868626262999999838383CP1189452-30Optimal N
62、T-proBNP Cutpoints for Acute Congestive Heart FailureCP887679- 33McCullough PA et al for the BNP Multinational Study Investigators: McCullough PA et al for the BNP Multinational Study Investigators: McCullough PA et al for the BNP Multinational Study Investigators: J Am Coll Cardiol 41:278A, 2003J A
63、m Coll Cardiol 41:278A, 2003J Am Coll Cardiol 41:278A, 2003Application of BNP Testing in CHF“ “ “Grey Zone” BNPGrey Zone” BNPGrey Zone” BNPBNP (pg/mL)BNP (pg/mL)BNP (pg/mL)“ “Grey Zone” BNPGrey Zone” BNPGrey Zone” BNP100-500 pg/mL100-500 pg/mL100-500 pg/mL26.4% 26.4% 26.4% of all casesof all casesof
64、 all cases16.5%16.5%16.5%CHFCHFCHF7.9%7.9%7.9%No CHFNo CHFNo CHF0 001001001002002002003003003004004004005005005006006006007007007008008008009009009001,0001,0001,0001,1001,1001,1001,2001,2001,2001,3001,3001,300CP1189452-31CP887679- 34CP1189452-32pg/mLpg/mLpg/mLCoronary pulmonaleCoronary pulmonaleCoro
65、nary pulmonale200-500200-500200-500Primary pulmonaryPrimary pulmonaryPrimary pulmonary300-500 300-500 300-500 hypertensionhypertensionhypertensionAcute pulmonaryAcute pulmonaryAcute pulmonary150-500 150-500 150-500 embolismembolismembolismBNP ElevationsRight-Sided Coronary Heart FailureCP887679- 35C
66、P1189452-33 Acute or chronic systolic or diastolic HFAcute or chronic systolic or diastolic HFAcute or chronic systolic or diastolic HF LV hypertrophyLV hypertrophyLV hypertrophy Inflammatory cardiac diseasesInflammatory cardiac diseasesInflammatory cardiac diseases Systemic arterial hypertension wi
67、th LVHSystemic arterial hypertension with LVHSystemic arterial hypertension with LVH Pulmonary hypertensionPulmonary hypertensionPulmonary hypertension Acute or chronic renal failureAcute or chronic renal failureAcute or chronic renal failure Ascitic liver cirrhosisAscitic liver cirrhosisAscitic liv
68、er cirrhosis Endocrine disorders (eg, hyper-Endocrine disorders (eg, hyper-Endocrine disorders (eg, hyper-aldosteronism, Cushings syndrome)aldosteronism, Cushings syndrome)aldosteronism, Cushings syndrome)When Can Non-CHF Patients Present with BNP Elevations?CP887679- 36CP1189452-34 Well HF patients
69、Well HF patientsWell HF patients Acute mitral regurgitationAcute mitral regurgitationAcute mitral regurgitation Pulmonary edema 1 hour oldPulmonary edema 1 hour oldPulmonary edema 1 hour old Other cases “up-stream” fromOther cases “up-stream” fromOther cases “up-stream” fromleft ventricleleft ventri
70、cleleft ventricleMitral stenosisMitral stenosisMitral stenosisAtrial myoxmaAtrial myoxmaAtrial myoxmaWhen Will CHF PresentWithout BNP Elevations?CP887679- 37P 0.0001P = 0.9Baseline BNP & Clinical Outcomes P 0.0001P = 0.9DeathMIN = 1356N = 320Morrow DA JACC 2004 CP887679- 38CP1173030-6Relationship of
71、 NT-proBNP and cTnTRelationship of NT-proBNP and cTnT* *P0.01 vs NT-proBNP 250 ng/LP0.01 vs NT-proBNP 250 ng/LP250 ng/L250 ng/L0.1 g/LNT-proBNPNT-proBNPNT-proBNPTroponin TTroponin TTroponin TDeath, myocardial infarction (%)Death, myocardial infarction (%)Death, myocardial infarction (%)* * * * *CP88
72、7679- 39Death/MI at 6 monthsDeath/MI at 6 monthsDeath/MI at 6 monthsTest for interaction:Test for interaction:Test for interaction:P=NSP=NSP=NS%BNP negBNP negBNP negBNP cut point = 80 pg/mLBNP cut point = 80 pg/mLBNP cut point = 80 pg/mLCP1189452-45CONSCONSCONSINVINVINVBNP posBNP posBNP pos(19% BNP
73、pos)(19% BNP pos)(19% BNP pos)n=681685156164 Morrow DA: JACC, 2004Morrow DA: JACC, 2004Morrow DA: JACC, 2004Baseline BNP: CONS vs INV StrategyCP887679- 40Beta-Blocker Therapy and BNP LevelsLuchner A et al: JACC 32:1839, 1998Luchner A et al: JACC 32:1839, 1998Luchner A et al: JACC 32:1839, 1998pg/pg/
74、pg/mLmLmLpmol/pmol/pmol/mLmLmLANPANPANP 32% 32% 32%BNPBNPBNP 89% 89% 89%cGMPcGMPcGMP 18% 18% 18%n=592n=80P0.01P0.01P0.01P0.01P0.01P0.01P0.01P0.01P0.01No No No b b b bb b-blocker (n=592)-blocker (n=592)-blocker (n=592)b b b b b b-blocker (n=80)-blocker (n=80)-blocker (n=80)CP1189452-59CP887679- 41Out
75、comes by Number of Positive OutcomesTACTICS-TIMI 18CP1143360-10Circ 109:584, 2004Circ 109:584, 2004Circ 109:584, 2004DeathDeathDeathor MIor MIor MI(%)(%)(%)FemaleFemaleFemaleMaleMaleMaleP=NSP=NSP=NSPositive markers (no.)Positive markers (no.)Positive markers (no.)P=NSP=NSP=NSP=NSP=NSP=NS2.92.92.94.4
76、4.44.46.26.26.26.56.56.512.112.112.113.313.313.3Death or MI by Multimarker ApproachDeath or MI by Multimarker ApproachDeath or MI by Multimarker ApproachCP887679- 42Odds of Positive MarkerTACTICS-TIMI 18TACTICS-TIMI 18CP1143360-7Circ 109:583, 2004Circ 109:583, 2004Circ 109:583, 2004T18 TnlT18 TnlT18
77、 TnlT11 TnlT11 TnlT11 TnlCombinedCombinedCombinedT18 TnTT18 TnTT18 TnTT11 TnTT11 TnTT11 TnTCombinedCombinedCombinedT18 BNPT18 BNPT18 BNPT16 BNPT16 BNPT16 BNPCombinedCombinedCombinedT18 CRPT18 CRPT18 CRPT11 CRPT11 CRPT11 CRPCombinedCombinedCombinedMale more likelyMale more likelyMale more likelyFemale more likelyFemale more likelyFemale more likely0 000.50.50.51 111.51.51.52 22
