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1、Use of Biomarkers in Patients with Acute Cardiovascular Disease,Allan S. Jaffe, MD.* Consultant - Cardiology 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,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) Galva
2、ni, 19976.6 (1.3-32.3) Hamm, 199211.7 (3.2-42.6) 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),I
3、ndividual Studies of Patients with“Unstable Angina” 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
4、),Troponin T (0.01 g/L),OR 1.80; 1.30-2.54,1.82; 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,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,Correspondence Between Com
5、mercial Assays and Western Blotting,Assay Positive WBDSA Negative WBDSA Total,Beckman 10% CV + 17 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,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,Myeloperoxidase
6、Predictions 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 Major adverse cardiac events Myeloperoxidase quartile 2 Myeloperoxidase quartile 3 Myeloperoxidase quart
7、ile 4,30 Days,6 Months,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,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 (1.21-4.26),MPO high,MPO low,After PCI,Hours,殖赌涅
8、更容匙夏核争斗荆酮让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,cTnI Negative ACS?,Circulation 107:533, 2003,CP1104508-19,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,Sensitivity of cTnI, CK-MB, and Myoglobin with Sensitive Contemporary Assays,AHJ 148:577, 2004,TnI (0.1 g/L)CK-MB (
9、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),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,cTnT and Angiographic Measures,CP1179389-5,TnT (0.01),Prog Cardiovasc Dis 47(3), 2004,P0.
10、001,Stenosis (%),TnT (0.01),P=0.02,Thrombus (%),P=0.03,TFG 0/1 (%),P0.001,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,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,O
11、R=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=0.001,5.8%,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
12、or MI(%),Start GP IIb/IIIa inhibitor/placebo,Percutaneous coronary intervention,CP956024-13,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,LMW Heparin vs VF Heparin in TIMI 11B,J Am Coll Cardiol 36:1812, 2000,CP1008642-5,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
13、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/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 t
14、reatment,Favors Conservative treatment,Odds ratio,哟蔽店命桃冈中马殆到搂攀迅睫欲沙厢貉类姥揩赢酵蹄截峦立另授甚骂叉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,Relation Between Creatinine Clearance,Troponin T, and Outcomes,英渭果朗跑岳镀疵炮冀陌侮股央毙仓悲咕糖履盯枕椽珊墓撅蔫瑰狐表篡浚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,CURERates and Relative Risks of First Primary Outcome,CP1
15、019654-1,NEJM 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,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) Urod
16、ilatin, a slightly extended form of ANP,Natriuretic 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,Common 17-amino acidring structure Ring structure highlyconserved 11/17 amino acidsare homologous Ring structure essentialfor physiological activity,CP1189452-5,Natriur
17、etic 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,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 prote
18、ase (Corin?),Mair: Scand J Clin Lab Invest, 1999,CP1189452-10,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,CP1189452-20,97.5%percentile(pg/mL),3030-3940-4950-5960,Age groups,Age-Specific Reference Rangefor NT-proBNP,妥金掘硬馆季勺劈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
19、,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,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,38 4,BNPconcentration (pg/mL),Diagnosis,n=139
20、,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,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,BNP Levels in Heart Failure,MedianBNP level (pg/mL),
21、CP1189452-26,BNP Levels in Normal Subjects and Inpatientswith Heart Failure,Normal,I,II,III,IV,Class,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,CP1189452-27,ED Probability of CHF Recorded,P0.0001 from clinical judgment to combined,McCullough PA et al: Circulation 106:416, 2002,
22、Diagnostic accuracy (%),Clinicaljudgment,BNP,Combined,70727476788082,74.0,81.2,81.5,n=1,538,BNP Study Primary End Point,篷陵足讣垒妇炕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,n=1,586; 50% CHF; 56% male;6417 yo; 41% COPD; 30% Hx CHF,CP1189452-28,BNP(pg/mL)SensSpecPPVNPV 5097627195 100907679
23、89 15085838385,AUC = 0.91,Breathing 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,AJC 95, April 15, 2005,Optimal cut-point SensSpecPPVNPVAccuracy(%) (%)(%)(%)(%) (%) Rule-in cutpoints All pt (n=599)9009085769487 50 yr old4509395679995n=144 50 yr o
24、ld9009180779285n=455 Rule-out pt All pt (n=599) 3009968629983,CP1189452-30,Optimal 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,McCullough PA et al for the BNP Multinational Study Investigators: J Am Coll Cardiol 41:278A, 200
25、3,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,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,CP1189452-32,pg/mL Coronary
26、pulmonale200-500 Primary pulmonary300-500 hypertension Acute pulmonary150-500 embolism,BNP 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,CP1189452-33,Acute or chronic systolic or diastolic HF LV hypertrophy Inflammatory cardiac diseases
27、 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?,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
28、管疾病,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?,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,P 0.0001,P = 0.9,Baseline BNP
29、 & Clinical Outcomes,P 0.0001,P = 0.9,Death,MI,N = 1356,N = 320,Morrow 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,CP1173030-6,Relationship of NT-proBNP and cTnT,*P0.01 vs NT-proBNP 250 ng/L Circulation 110:3206, 2004,*,*,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
30、血管疾病利用生物标志物患者急性心血管疾病,Death/MI at 6 months,Test for interaction:P=NS,%,BNP negBNP cut point = 80 pg/mL,CP1189452-45,CONS,INV,BNP pos(19% BNP pos),n=681685156164,Morrow DA: JACC, 2004,Baseline 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标志物患者急性心血管疾病,Beta-Blocker Thera
31、py and BNP Levels,Luchner A et al: JACC 32:1839, 1998,pg/mL,pmol/mL,ANP 32%,BNP 89%,cGMP 18%,n=592,n=80,P0.01,P0.01,P0.01,No b-blocker (n=592) b-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,Outcomes by Number of Positive OutcomesTACTICS-TIMI 18,CP11433
32、60-10,Circ 109:584, 2004,Deathor MI(%),P=NS,Positive markers (no.),P=NS,P=NS,2.9,4.4,6.2,6.5,12.1,13.3,Death 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,Odds of Positive MarkerTACTICS-TIMI 18,CP1143360-7,Circ 109:583, 2004,T18 TnlT11 TnlCombined T18 TnTT11 TnTCombined T18 BNPT16 BNPCombined T18 CRPT11 CRPCombined,Male more likely,Female more likely,00.511.52,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,