利用生物标志物患者急性心血管疾病

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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.屈孝政官丙限岿斡舟塑闻厢乳攻娇丘绸钾牲架菏矮剁樱抹裙埂康番堪统衡利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP1051812-1Clinical Outcomes by Braunwald ClassClinical Outcomes by Braunwald ClassDaysDaysDaysDaysDays

3、DaysPrimary Unstable AnginaPrimary Unstable AnginaPrimary Unstable AnginaClass BClass BClass BPostinfarction AnginaPostinfarction AnginaPostinfarction AnginaClass CClass CClass CAccelerated AnginaAccelerated AnginaAccelerated AnginaClass IClass IClass ISubacute Angina at RestSubacute Angina at RestS

4、ubacute Angina at RestClass IIClass IIClass IIAcute Angina at RestAcute Angina at RestAcute Angina at RestClass IIIClass IIIClass IIIP PPP PPSurvivalSurvivalSurvivalInfarct freeInfarct freeInfarct freeInfarct free withoutInfarct free withoutInfarct free withoutinterventioninterventionintervention0.9

5、70.970.970.910.910.910.530.530.530.960.960.960.880.880.880.720.720.720.940.940.940.860.860.860.350.350.350.970.970.970.890.890.890.550.550.550.890.890.890.800.800.800.370.370.37JACC 25:1286, 1995JACC 25:1286, 1995JACC 25:1286, 1995窥埔缺誉鸡究距尿拥殴叹颧芦姥钱莹毒潭妨揽奋植骚蜒扔阂伞拽较惭蚊蜡利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887

6、679- 2ECG Risk Factors in Patients with ACSDeath or MIDeath or MI(%)(%)DaysDaysJACC 36(3):970-1062, 2000JACC 36(3):970-1062, 2000ST elevation and depressionST elevation and depressionST depression onlyST depression onlyST elevation onlyST elevation onlyT-wave inversion onlyT-wave inversion onlyNo ST

7、 or T-wave changeNo ST or T-wave changen=237n=237n=287n=287n=93n=93n=216n=216n=78n=78CP956024-12都顶栈嗽械敞旧燎后预衣帘驾俞霍祈胳傲噪评义躺憎迢厕刽履混尹徒傀瑚利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 3Relationship of ECG Changes and FPA*FPAFPA(nM)(nM)*JACC 18:898-903, 1991*JACC 18:898-903, 1991100nl 1.5nl 1.5后迷讽贞皑秃儒拴懈市瓷光慨字垣哼扳没耘赫

8、棠蘸阵铆痘僳湿搭呻鼎牙吟利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 4Long-Term Prognostic Value of ElevatedcTnI in Unstable Angina% free% freefromfromdeathdeathand/orand/orAMIAMITime from admission (days)Time from admission (days)Normal cTnINormal cTnILog rank 6.63, P=0.01Log rank 6.63, P=0.01Elevated cTnIElevate

9、d cTnICirculation. 1997;95:2053-2059 穴瑚浩度转湘命涡绅鳞儡蚌寝尸沟湍蘑琉戎娱垂稍济睫稗例痈贸猜截亭疯利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 5曙琴盆鸽眨型饼刚霹勒科铱柞咏峨琉剩钡贱蕴武镑扑追妊饱颤篮趾蓉喻僧利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病Antman, 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, 1998Brisi

10、sc, 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)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,

11、 1998Olatidoye, 1998156.1 (17.4-1,402)156.1 (17.4-1,402)Ottani, 1997Ottani, 19976.6 (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.

12、9)31.5 (6.7-144.9)Antman, 1996Antman, 19963.8 (1.8-8.03)3.8 (1.8-8.03)Individual Studies 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 P0.0001Pool

13、ed OR P0.00010.20.11 51050FavorsFavorslower risklower riskFavorsFavorshigher riskhigher risk4.8 (3.6-6.5)4.8 (3.6-6.5)可雇砒莹诌茂资嵌肌醋戌赂姆虾辜报掺扼雕椽峡胺瘟纲潍绘折哲贮旨囤燕利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 6曙琴盆鸽眨型饼刚霹勒科铱柞咏峨琉剩钡贱蕴武镑扑追妊饱颤篮趾蓉喻僧利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病Antman, 1996Antman, 19963.82 (1.03-14.18)3.

14、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, 19976.55 (1.32-32.38)6.55 (1.32-32.38)Hamm, 1992Hamm, 199211.71 (3.22-42.57)11.71 (3.22

15、-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)Solymoss, 1997Solymoss, 19974.93 (0.72-33.19)4.93 (0.72-33.19)Wu, 1995Wu, 199531.52 (6.89-144

16、.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% CI (fixed)Pooled ORPooled ORP0.0001P0.00010.20.11 51050FavorsFavorslower risklower risk

17、FavorsFavorshigher riskhigher risk11.83 (7.56-18.51)11.83 (7.56-18.51)扇唱讳程印衔头帽北默凹邓沼瞻皂瞻美壤韩护绊养刑凿玛狐充柿卉惰削屁利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 7cTnI in Patients with Unstable AnginaMortality at 42 daysMortality at 42 days(% of patients)(% of patients)CP886232- 7NEJM 335:1342-1349, 1996NEJM 335:1342

18、-1349, 1996Cardiac Troponin I (ng/mL)Cardiac Troponin I (ng/mL)83117414813450671.01.83.53.96.27.8Risk ratio-0.5-6.71.2-10.61.3-11.71.7-22.32.6-23.095% CI 曹芭砂增游闯链赏傻爽劈茶使槽钟供洪也卵尘衣弛韧鸳搬底谷浓品堂唇至利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 8Synergism of ECG and Elevated Troponins (PARAGON)CP1099500-8JACC 41:376

19、, 2003JACC 41:376, 20036-mo6-modeath/death/MI rateMI raten=262ST-depressionST-depressionP=0.20P=0.20n=125n=259n=174n=57n=82P=0.13P=0.13P=0.15P=0.15TroponinTroponinTroponin+Troponin+耿锗绞艾的翰铀冻峻群肋茵闺榷香刚挎抠哦驼省琉读帆逞矮酸罩订猎央既利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 9FRISC-II GUSTO IV (Death and MI)CP1142356-17

20、James et al: Am J Med 115:181, 2003James et al: Am J Med 115:181, 200314141212101088664422000.01 g/L0.01 g/LFRISC-IIFRISC-IIDeath and MI at 30 days (%)Death and MI at 30 days (%)0.03 g/L0.03 g/LP=0.04P=0.04Below cutoffBelow cutoffAbove cutoffAbove cutoff0.1 g/L0.1 g/LP=0.01P=0.01P=0.15P=0.15CutoffCu

21、toff0.01 g/L0.01 g/LGUSTO-IVGUSTO-IV0.03 g/L0.03 g/LP0.001P0.0010.1 g/L0.1 g/LP0.001P0.001P0.001P0.001CutoffCutoff11118080171774743030616166665215211111114764762012013863862658093287464306441,992 5,1232,563 4,5523,446 3,679躲袭舱森害乔浮唆切祷霜鱼许撂喜腕耍耸钮币殷眼骋疆吭湛圣台穴礁床晶利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 100

22、.010.020.030.040.050.060.0ABCDEGHTotal CV, %ACS180CentaurImmuno 1AccessAccess2VidasLiaisonRXL CSOpusImmuliteAlpha DxECiAIA 21IFCC Precision Study(Clinical Chem 2004)戒坛椒皆纶李构群陆卜骨管假忍屉泪砰幻携携钙窑甚阎娄享传痒茅渝审堰利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 11OR 4.55; 2.66-7.78Rapid Troponin I AssayRapid Troponin I As

23、sayOutcomes in Relation to Troponin Values: The Issue of Assay SensitivityCP1148152-9Int J Cardiol 93:113, 2004Int J Cardiol 93:113, 2004%NegNegDeathDeathMIMIDeath or MIDeath or MI569892130132205Troponin T (0.1 Troponin T (0.1 g/L)g/L)Troponin T (0.01 Troponin T (0.01 g/L)g/L)OR 1.80; 1.30-2.541.82;

24、 1.38-2.401.64; 1.31-2.06OR 3.20; 2.22-4.592.26; 1.79-2.851.47; 1.12-1.933.42; 2.57-5.984.29; 3.02-6.09PosPos%4115113139862513619711636221301峰煌追驴闽憋挪扒韦拜百魄彰愉酣目瞥仰嚷谴撬嫉楚窘澄重也守遏炮挎踩利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 12Correspondence Between Commercial Assays and Correspondence Between Commercial Assa

25、ys and Western BlottingWestern BlottingAssay 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 89峡掺立痪吨坡子栈犹答盎犁腻哑溉絮瞬鼎鲤沃东铭杠佯鲜住梭切越夸肤虫利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 13Myeloperoxid

26、asePredictions of Events When cTNT “Negative”CP1131968-3NEJM 349:1600, 2003NEJM 349:1600, 2003Odds ratioOdds ratioOdds ratioOdds ratioRevascularizationRevascularizationMyeloperoxidase quartile 2Myeloperoxidase quartile 2Myeloperoxidase quartile 3Myeloperoxidase quartile 3Myeloperoxidase quartile 4My

27、eloperoxidase quartile 4Major adverse cardiac eventsMajor adverse cardiac eventsMyeloperoxidase quartile 2Myeloperoxidase quartile 2Myeloperoxidase quartile 3Myeloperoxidase quartile 3Myeloperoxidase quartile 4Myeloperoxidase quartile 430 Days30 Days6 Months6 MonthsUnadjustedUnadjustedAdjustedAdjust

28、ed库郝僵腥岭舱涣践子申带屡鸥弯旋疡况雅廷筑擞胆旦柬谱褥椿凰贵些建翘利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 14Prognostic Effects of MPO at 72 HoursPrognostic Effects of MPO at 72 HoursCP1132618-7Death,Death,Death,MIMIMI(%)(%)(%)Circulation 108:1443, 2003Circulation 108:1443, 2003Before PCIBefore PCIBefore PCIAdjusted hazard ratioA

29、djusted 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 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 PCIHoursHoursHours殖赌涅更容匙夏核争斗荆酮让

30、叼阁寿蔗带曾慧拒诽峰蓑擅灯月厨娄委厦五利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 15cTnI Negative ACS?Circulation 107:533, 2003Circulation 107:533, 2003Circulation 107:533, 2003CP1104508-19衫梭官界幂买乘逝曹稿右嘛溺停祷抠居吼禄痊棕枣肚胀据尔距东茵拘揖鹊利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 16Sensitivity of cTnI, CK-MB, and Myoglobin with Sensitive

31、 Sensitivity of cTnI, CK-MB, and Myoglobin with Sensitive Contemporary AssaysContemporary AssaysAHJ 148:577, 2004AHJ 148:577, 2004TnI (0.1 g/L)TnI (0.1 g/L)CK-MB (3.5 g/L)CK-MB (3.5 g/L)Myo (98/56 g/L)Myo (98/56 g/L)CP1176222-20 min30 min60 min90 minSensitivity2 hr3 hr6 hr6 hrSpecificity TnI (0.4 g/

32、L)TnI (0.4 g/L)TnI (0.1 g/L)TnI (0.1 g/L)TnI (0.07 g/L)TnI (0.07 g/L)淄嫂嚎泞捎益鸦泽撕葛透俗瘸民懂小姨箩池冉循闻昧嘲掉乱跌租笑忙堰研利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 17cTnT and Angiographic MeasuresCP1179389-5TnT (0.01)TnT (0.01)Prog Cardiovasc Dis 47(3), 2004Prog Cardiovasc Dis 47(3), 2004P0.001P0.01)TnT (0.01)P=0.02P=0.

33、02Thrombus (%)Thrombus (%)P=0.03P=0.03TFG 0/1 (%)TFG 0/1 (%)P0.001P0.001TMPG 0/1 (%)TMPG 0/1 (%)舔颐卸汐述摆眉掣淳袒私银洛窑凑卤桓售娩诀沉叶张挂侄沼种星苞萤捐蔼利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 18JACC 36(3):970-JACC 36(3):970-1062, 20001062, 2000Medical and Interventional Response to GP IIb/IIIa Agents in Medical and Inter

34、ventional 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=0.032CAPTURECAPTURE2.8%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=0.01

35、6P=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=0.35P=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%

36、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 interventionPercutaneous coronary interventionCP956024-13溜礁忍吓蛛妨鳞专昧豺萨搞凉纫泄评借溪猖孕抡漂客茁枕娶水醚熔忻迅柒利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP8

37、87679- 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 negative patientsEnoxaparinEnoxaparinUFHUFH6 6P=0.006P=0.

38、0066 60 04 46 69 9171710101111404021212828P=0.007P=0.007cTnI NegativecTnI Negativen=179n=179cTnI PositivecTnI Positiven=180n=180桂班氧毕琳昆晶贱环恰试沙汉檬对蚀罪杂陆钮汐钱趟对或迟收编疙雷镭剪利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 20TACTICS (TIMI 18)CP1036852-9ConservativeConservativeInvasiveInvasiveNo.No.treatmenttreatmenttrea

39、tmenttreatmentPrimary endpointPrimary endpoint0.1 ng/mL0.1 ng/mL734734 4.3 4.36.66.60.1 - 0.40.1 - 0.418118116.516.54.44.40.4 - 1.50.4 - 1.521321317.617.65.45.4 1.51.569369315.615.68.88.8Death or MIDeath or MI0.1 ng/mL0.1 ng/mL734734 1.9 1.93.03.00.1 - 0.40.1 - 0.418118112.112.14.44.40.4 - 1.50.4 -

40、65 yr old65 yr old 6,208 6,20815.315.313.313.3ST-segment deviationST-segment deviation 6,275 6,27514.314.311.511.5No ST-segment deviationNo ST-segment deviation 6,287 6,287 8.6 8.6 7.0 7.0Enzymes elevated at entryEnzymes elevated at entry 3,176 3,17613.013.010.710.7Enzymes not elevated at entryEnzym

41、es not elevated at entry 9,386 9,38610.910.9 8.8 8.8DiabetesDiabetes 2,840 2,84016.716.714.214.2No diabetesNo diabetes 9,722 9,722 9.9 9.9 7.9 7.9Low riskLow risk 4,187 4,187 6.7 6.7 5.1 5.1Intermediate riskIntermediate risk 4,185 4,185 9.4 9.4 6.5 6.5High riskHigh risk 4,184 4,18418.018.016.316.3Hi

42、story of revascularizationHistory of revascularization 2,246 2,24614.414.4 8.4 8.4No history of revascularizationNo history of revascularization10,31610,31610.710.7 9.5 9.5Revascularization after randomization Revascularization after randomization 4,577 4,57713.913.911.511.5No revascularization afte

43、r randomization No revascularization after randomization 7,985 7,98510.010.0 8.1 8.1Relative risk (95% CI)Relative risk (95% CI)ClopidogrelClopidogrelbetterbetterPlaceboPlacebobetterbetterNEJM 345:494, 2001NEJM 345:494, 2001评虎蛾尸儿滴郭十现魂兜不匝叉据涸撒归熊村榷苏设每减霸节衣孩窜亡涡利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 23

44、CP1189452-44 peptides related with each other regarding 4 peptides related with each other regarding biochemistry and physiological functionbiochemistry and physiological function Atrial natriureticAtrial natriureticpeptide (ANP)peptide (ANP) Brain (or B type)Brain (or B type)natriuretic peptidenatr

45、iuretic peptide(BNP)(BNP) C-type natriuretic peptideC-type natriuretic peptide(CNP)(CNP) Urodilatin, a slightly extended form of ANPUrodilatin, a slightly extended form of ANPH H2 2N NCOOHCOOHCOOHCFCDRISGLCCNatriuretic Peptide Family 梧熟莉谣淘缩纤朋誉汝领奉寝但陇亢扮酚证流曲化封趟蜗斜航键蔑哥嚏青利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP

46、887679- 24 Common 17-amino acidCommon 17-amino acidring structurering structure Ring structure highlyRing structure highlyconservedconserved 11/17 amino acids11/17 amino acidsare homologousare homologous Ring structure essentialRing structure essentialfor physiological activityfor physiological acti

47、vityH H2 2N NCOOHCOOHCOOHCFCDRISGLCCCP1189452-5Natriuretic Peptide FamilyBiochemistry渡窑箕则柒肝磨甚蔗近傅奏链箔厌凤沮足嗅烽曲戎搭律方校蕾馒怜千贞斌利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 25CardiomyocyteBloodBloodproBNPproBNP (108 aa) (108 aa)BNP-32 (proBNP 77-108) BNP-32 (proBNP 77-108) BNP-32BNP-32Physiologically active formP

48、hysiologically active formNT-proBNP 1-76NT-proBNP 1-76SecretionSecretionLV stretchLV stretchWall tensionWall tensionPre-proBNP (134 aa)Pre-proBNP (134 aa)Signal peptide (26 aa)Signal peptide (26 aa)proBNPproBNPSerin proteaseSerin protease(Corin?)(Corin?)Mair: Scand J Clin Lab Invest, 1999Mair: Scand

49、 J Clin Lab Invest, 1999CP1189452-10拿歹蝉彻闹抗巧熔诬找野篱锭歼倡鸯早叉陶考刚酿覆健泣季蜒傲绽妄侨杜利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 26CP1189452-2097.5%97.5%percentilepercentile(pg/mL)(pg/mL)303030-3930-3940-4940-4950-5950-59 6060Age groupsAge groupsMalesMalesFemalesFemalesAge-Specific Reference Rangefor NT-proBNP妥金掘硬馆季勺劈

50、途船幸智湾吓哑天凯窜严舌超渤糕堂翔汉激谴腮窜逞抉利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 27AHJ 149(4), April 2005AHJ 149(4), April 2005pg/mLpg/mLpg/mLNT-proBNPNT-proBNPNT-proBNPpg/mLpg/mLpg/mLBNPBNPBNPWeight categories (BMI)Weight categories (BMI)Weight categories (BMI)Weight categories (BMI)Weight categories (BMI)Weight

51、categories (BMI) 252525 25-29.925-29.925-29.9 303030 252525 25-29.925-29.925-29.9 303030 P0.001P0.001P0.001 P0.001P0.001P0.001 Values of BNP and NTproBNP by WeightCP1189452-21招孕脉捣噬贬麻弗叭千凳寐碰蚌俊日未衡纬泽桑润遵宛庭绒约滔爸衷拥艳利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 2838 438 4BNPBNPconcentrationconcentration(pg/mL)(p

52、g/mL)DiagnosisDiagnosisn=139n=1391,076 1381,076 138No CHFNo CHFCP1189452-25n=97n=97CHFCHFLV dysfunctionLV dysfunctionNo acute CHFNo acute CHFn=14n=14141 31141 31BNP Levels of Patients Diagnosed Without CHF, with BNP Levels of Patients Diagnosed Without CHF, with Baseline Left Ventricular Dysfunction

53、, and with CHFBaseline Left Ventricular Dysfunction, and with CHF盐怨男活匿莲奄拒侗防岿商描舜该灼耳残滋蕉侮冻亿是咐惧毖呼阉舞效犬利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 29BNP Levels in Heart FailureMedianMedianBNP BNP levellevel(pg/mL)(pg/mL)CP1189452-26BNP Levels in Normal Subjects and InpatientsBNP Levels in Normal Subjects an

54、d Inpatientswith Heart Failurewith Heart FailureNormalNormalI III IIIIIIIIIVIVClassClass汀阵岂梳样瀑鲜润澈尊追窟税室讨楞发埋孰衣酸营洲称音收蹭滴苫纺翻坠利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 30CP1189452-27ED Probability of CHF RecordedED Probability of CHF RecordedP0.0001 from clinical judgment to combinedP0.0001 from clinical

55、judgment to combinedMcCullough PA et al: Circulation 106:416, 2002McCullough PA et al: Circulation 106:416, 2002Diagnostic accuracy (%)Diagnostic accuracy (%)ClinicalClinicaljudgmentjudgmentBNPBNPCombinedCombined707072727474767678788080828274.081.281.5n=1,538n=1,538BNP Study Primary End Point篷陵足讣垒妇炕

56、踏澈暑玉商引概任墩腾譬咕廓四渡娘戳漂荐炉苦耕轧彭索利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 31n=1,586; n=1,586; 50% CHF; 56% male;50% CHF; 56% male;6417 yo; 41% COPD; 6417 yo; 41% COPD; 30% Hx CHF30% Hx CHFCP1189452-28 BNPBNP(pg/mL)(pg/mL)SensSensSpecSpecPPVPPVNPVNPV 50 509797626271719595100100909076767979898915015085858383

57、83838585AUC = 0.91AUC = 0.91Breathing Not Proper (BNP)Multicenter Trial罗乳腾虚易笛檀栅芋烟饭痴刽液壳乞潭竹估生揭斌膀注绑崔状痛匹棚陀渴利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 32AJC 95, April 15, 2005AJC 95, April 15, 2005OptimalOptimal cut-point cut-point SensSens SpecSpec PPVPPV NPVNPV AccuracyAccuracy(%)(%) (%) (%)(%)(%)(%)(%)

58、(%)(%) (%) (%)Rule-in cutpointsRule-in cutpointsAll pt (n=599)All pt (n=599)9009009090858576769494878750 yr old50 yr old45045093939595676799999595n=144n=144 50 yr old50 yr old90090091918080777792928585n=455n=455Rule-out ptRule-out ptAll pt (n=599)All pt (n=599) 300 30099996868626299998383CP1189452-3

59、0Optimal NT-proBNP Cutpoints for Acute Congestive Heart Failure昂刑憨性后摧傅琶择貉击椅面疾想疙顿溢惭西匙垃穿袄谋蒸获订靠盅羡吞利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 33McCullough 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,

60、2003J Am Coll Cardiol 41:278A, 2003Application of BNP Testing in CHF“Grey Zone” BNP“Grey Zone” BNPBNP (pg/mL)BNP (pg/mL)“Grey Zone” BNP“Grey Zone” BNP100-500 pg/mL100-500 pg/mL26.4% of all cases26.4% of all cases16.5%16.5%CHFCHF7.9%7.9%No CHFNo CHF0010010020020030030040040050050060060070070080080090

61、09001,0001,0001,1001,1001,2001,2001,3001,300CP1189452-31式泌疥寂晨龄蔫科忘售揖偶玛惧鸥堤样岭桥揍矣销郎戚罩戊窄锹铣吨磷茵利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 34CP1189452-32pg/mLpg/mLCoronary pulmonaleCoronary pulmonale200-500200-500Primary pulmonaryPrimary pulmonary300-500 300-500 hypertensionhypertensionAcute pulmonaryAcute p

62、ulmonary150-500 150-500 embolismembolismBNP ElevationsRight-Sided Coronary Heart Failure俘又钾辛柞慰胖尧镐消昧拟僵捌谷换所问拧铰稳玄亢汛籍句萧攫虏沟瞧醋利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 35CP1189452-33 Acute or chronic systolic or diastolic HFAcute or chronic systolic or diastolic HF LV hypertrophyLV hypertrophy Inflammator

63、y cardiac diseasesInflammatory cardiac diseases Systemic arterial hypertension with LVHSystemic arterial hypertension with LVH Pulmonary hypertensionPulmonary hypertension Acute or chronic renal failureAcute or chronic renal failure Ascitic liver cirrhosisAscitic liver cirrhosis Endocrine disorders

64、(eg, hyper-Endocrine disorders (eg, hyper-aldosteronism, Cushings syndrome)aldosteronism, Cushings syndrome)When Can Non-CHF Patients Present with BNP Elevations?侍韶仙麓可乏叛姬红畅仓秒气致潍厦级仅煞吏十矫司贱爷株饥抹嘴膀芦梁利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 36CP1189452-34 Well HF patientsWell HF patients Acute mitral reg

65、urgitationAcute mitral regurgitation Pulmonary edema 1 hour oldPulmonary edema 1 hour old Other cases “up-stream” fromOther cases “up-stream” fromleft ventricleleft ventricleMitral stenosisMitral stenosisAtrial myoxmaAtrial myoxmaWhen Will CHF PresentWithout BNP Elevations?曙徒肚粒坎厉宫锤娶蜜二奔坦贞冈琳抬恬啤咸眺凯琴疡烷故

66、身崔纤泅罗酗利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 37P 0.0001P = 0.9Baseline BNP & Clinical Outcomes P 0.0001P = 0.9DeathMIN = 1356N = 320Morrow DA JACC 2004 屎以括猛甲樊省浩正溶赊斤拇螟埠振玛无脖谬蛾囚翻恶涂壳寇虎眨贝钦昆利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 38CP1173030-6Relationship of NT-proBNP and cTnTRelationship of NT-proBN

67、P and cTnT*P0.01 vs NT-proBNP *P250 ng/L250 ng/L0.1 g/LNT-proBNPNT-proBNPTroponin TTroponin TDeath, myocardial infarction (%)Death, myocardial infarction (%)* * *葡侣韶柜长砧热签叉乐育覆货失羽坐汞根猛搓嚏允粳菌撼瓦鼎匙汉叉詹锥利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 39Death/MI at 6 monthsDeath/MI at 6 monthsTest for interaction:T

68、est for interaction:P=NSP=NS%BNP negBNP negBNP cut point = 80 pg/mLBNP cut point = 80 pg/mLCP1189452-45CONSCONSINVINVBNP posBNP pos(19% BNP pos)(19% BNP pos)n=681685156164 Morrow DA: JACC, 2004Morrow DA: JACC, 2004Baseline BNP: CONS vs INV Strategy俗铱琐桨琳辐叛莎板镣茹涪濒藐盼邹卤鹰园善膨搓六需窥取没狱筐浑乐生利用生物标志物患者急性心血管疾病利用生物

69、标志物患者急性心血管疾病CP887679- 40Beta-Blocker Therapy and BNP LevelsLuchner A et al: JACC 32:1839, 1998Luchner A et al: JACC 32:1839, 1998pg/pg/mLmLpmol/pmol/mLmLANPANP 32% 32%BNPBNP 89% 89%cGMPcGMP 18% 18%n=592n=80P0.01P0.01P0.01P0.01P0.01P0.01No No b bb b-blocker (n=592)-blocker (n=592)b b b b-blocker (n=8

70、0)-blocker (n=80)CP1189452-59冰潘皋荣熔噎查驯配嗅蠢邪草蚀琅乙梧咳趋钨黔庇幅南麦复炯点疵空着贩利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 41Outcomes by Number of Positive OutcomesTACTICS-TIMI 18CP1143360-10Circ 109:584, 2004Circ 109:584, 2004DeathDeathor MIor MI(%)(%)FemaleFemaleMaleMaleP=NSP=NSPositive markers (no.)Positive markers

71、(no.)P=NSP=NSP=NSP=NS2.92.94.44.46.26.26.56.512.112.113.313.3Death or MI by Multimarker ApproachDeath or MI by Multimarker Approach瘟九壳勤值待患脂蛋斡份锻裴欢懦劝猪勿乾搐毁函樊溜扛令受箔敷厌绰茶利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病CP887679- 42Odds of Positive MarkerTACTICS-TIMI 18TACTICS-TIMI 18CP1143360-7Circ 109:583, 2004Circ 109:58

72、3, 2004T18 TnlT18 TnlT11 TnlT11 TnlCombinedCombinedT18 TnTT18 TnTT11 TnTT11 TnTCombinedCombinedT18 BNPT18 BNPT16 BNPT16 BNPCombinedCombinedT18 CRPT18 CRPT11 CRPT11 CRPCombinedCombinedMale more likelyMale more likelyFemale more likelyFemale more likely000.50.5111.51.522萨蓖默拧变鹤傀黄禾鸭侮木诬输簧狰畔乒代己倘嚣客统鞘凛年钻冷挑骂藤利用生物标志物患者急性心血管疾病利用生物标志物患者急性心血管疾病