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1、北京大学人民医院刘文玲 Still waters run deep.流静水深流静水深,人静心深人静心深 Where there is life,there is hope。有生命必有希望。有生命必有希望Copyright restrictions may apply.Elliott,P.et al.Eur Heart J 2008 29:270-276;doi:10.1093/eurheartj/ehm342Summary of proposed classification systemCopyright 2006 American Heart AssociationMaron,B.J.et
2、 al.Circulation 2006;113:1807-1816Primary cardiomyopathies in which the clinically relevant disease processes solely or predominantly involve the myocardium 近近十十年年来来，丙丙型型肝肝炎炎病病毒毒（HCVHCV）感感染染与与心心肌肌炎炎、心心肌肌病病、动动脉脉粥粥样样硬硬化化等等心心血血管管疾疾病病相相关关研研究究陆陆续续开开展展，对对HCVHCV是是否否是是CVDCVD的的相相关危险因素进行了深入研究。关危险因素进行了深入研究。然然而
3、而，不不同同国国家家（地地区区）、不不同同人人群群的的研究结果研究结果不尽一致不尽一致。1995 1995 Japan Matsumori DCMJapan Matsumori DCM1997 1997 Japan Okabe MyocarditisJapan Okabe Myocarditis1999 Japan Takeda1999 Japan Takeda MyocarditisMyocarditis2002 2002 Japan Frustaci Japan Frustaci MyocarditisMyocarditis 1996 1996 Japan Matsumori HCMJap
4、an Matsumori HCMTime Country Author DiseaseTime Country Author Disease阳性结论阳性结论1998 1998 Greece Greece Dalekos DCMDalekos DCM1998 Germany Grumbach Myocarditis,DCM1998 Germany Grumbach Myocarditis,DCMTime Country Author DiseaseTime Country Author Disease阴性结论阴性结论1999 1999 Italy Prati DCMItaly Prati DCM
5、 20 pg/ml 20 pg/mlIncreased BNP(%)31*25*55.4%*Cardiac Troponin T 10 pg/ml,Troponin I 100 pg/mlPlasma BNP in Patients with HCV HepatitisDetection of Negative Strands of HCV RNA in the Heart of a Patients with DCM by in situ Hybridization 200HCV HepatitisDCMImmunohistochemical Staining against HCV Pro
6、teinImmunohistochemical Staining of HCV Core Protein in the Heart from Patients with ARVC/DChronic InflammationDCMARVC/DHCMHypertrophyHCV InfectionMyocyte LossFibrosisAcute HepatitisChronic HepatitisLiver CirrhosisMyocardialFibrosisDCMAcute MyocarditisChronicInflammationHepaticFailureHCCHCM85%20%6%4
7、%HCV HepatitisHCV CardiomyopathiesViral Infection of the HeartDiffuseCHF/DCMSystolic HFRegionalAneurysmSubendocardialRCMDiastolic HFARVC/DLV AneurysmRandomHypertrophy/HCMVirusReceptorMyocyteFibroblastCompleterecoveryDiffusehypokinesisRegionalabnormalitySubendocardiallesionsIncreasedwall thicknessUnc
8、lassifiedabnormalityViral MyocarditisCHF/DCMSystolic HFHCMRCMARVC/DDiastolic HFHepatitis C Virus LV AneurysmARVCHCMDCMMyocarditisMatsumori A Circ Res 2005;96:144-147我国我国HCV患者心脏损害的研究患者心脏损害的研究 我国一般人群抗我国一般人群抗-HCV-HCV阳性率为阳性率为3.2%3.2%，丙型肝炎抗体阳性患者约丙型肝炎抗体阳性患者约40004000万；万；与心血管疾病一样，与心血管疾病一样，HCVHCV感染也是严感染也是严重危
9、害人民健康的卫生问题。重危害人民健康的卫生问题。研研 究究 对对 象象n病例组：连续选取病例组：连续选取2006年年3月月2007年年7月于月于北京佑安医院及解放军北京佑安医院及解放军302医院两家三级甲等医院两家三级甲等传染病专科医院诊治的传染病专科医院诊治的HCV感染患者感染患者n对照组：随机选取与入选病例年龄、性别、体对照组：随机选取与入选病例年龄、性别、体重匹配的正常健康人作为对照。重匹配的正常健康人作为对照。研 究 对 象HCV感染者入选标准感染者入选标准 血清抗血清抗HCV抗体阳性；抗体阳性；血清血清HCV RNA 阳性；阳性；HCV感染者排除标准感染者排除标准 其他肝病、包括艾滋
10、病毒、立克次体或螺旋 体在内的其他感染性疾病、妊娠、产后妇女、现有或既往酗酒或吸毒、肿瘤、心血管系统 外其他各系统慢性疾病、不同意参与者。对照选择对照选择 研 究 对 象 与入选病例年龄、性别匹配的与入选病例年龄、性别匹配的 正常健康人作为对照。正常健康人作为对照。研 究 路 线阶段阶段阶段阶段阶段阶段阶段阶段 II II阶段阶段阶段阶段 III III 研究对象收集研究对象收集 设计调查表格设计调查表格 收集临床资料收集临床资料 超声心动图、心电图检查超声心动图、心电图检查 留取非抗凝血留取非抗凝血10ml 2006.1 2007.8血清生化标志物检测血清生化标志物检测 cTnIcTnI N
11、T-proBNP NT-proBNP hs-CRP hs-CRP MMP-9 MMP-9 FLC FLC 2007.3 2007.9 数据总结分析数据总结分析 临床评估临床评估 血清生化标志物评估血清生化标志物评估 超声心动图评估超声心动图评估 2007.10 本文将本文将“心电图异常和心电图异常和/或具有心血或具有心血管病史管病史”定义为定义为“心血管异常心血管异常”，有心，有心血管异常患者共血管异常患者共2727例。例。心脏血清生化标志物评估心脏血清生化标志物评估病例组与健康对照组间比较*P P0.050.05，中位数，中位数，n=131n=131 无心血管异常病例与相应健康对照间比较*P
12、 P0.050.05，中位数，中位数,n=104,n=104*心血管异常患者与相应健康对照间比较*P P0.050.05，中位数，中位数,n=27,n=27*病例组与对照组血清病例组与对照组血清NT-proBNP水平比较（中位数，水平比较（中位数，*P0.05）超声心动图没有显示出心脏结构的超声心动图没有显示出心脏结构的异常，但心血管异常风险较高患者的左异常，但心血管异常风险较高患者的左室收缩功能降低室收缩功能降低。nHCVHCV感染导致血清感染导致血清NT-proBNPNT-proBNP、FLCFLC、FLCFLC水平及水平及FLC/FLC/升高。升高。n上述指标是心肌损伤的标志上述指标是心
13、肌损伤的标志结论结论我国心肌病患者我国心肌病患者HCV感染率研究感染率研究心肌病患者心肌病患者HCV感染回顾性研究感染回顾性研究研究对象研究对象北京大学人民医院北京大学人民医院2003年年-2008年心内年心内科住院的科住院的DCM,HCM患者患者DCM HCM 诊断标准诊断标准nHCM：WHO 1995nDCM Criteria：nEF 20 pg/ml 20 pg/mlIncreased BNP(%)31*25*55.4%*Cardiac Troponin T 10 pg/ml,Troponin I 100 pg/mlPlasma BNP in Patients with HCV Hepa
14、titisDetection of Negative Strands of HCV RNA in the Heart of a Patients with DCM by in situ Hybridization 200HCV HepatitisDCMImmunohistochemical Staining against HCV ProteinImmunohistochemical Staining of HCV Core Protein in the Heart from Patients with ARVC/DChronic InflammationDCMARVC/DHCMHypertr
15、ophyHCV InfectionMyocyte LossFibrosisAcute HepatitisChronic HepatitisLiver CirrhosisMyocardialFibrosisDCMAcute MyocarditisChronicInflammationHepaticFailureHCCHCM85%20%6%4%HCV HepatitisHCV CardiomyopathiesViral Infection of the HeartDiffuseCHF/DCMSystolic HFRegionalAneurysmSubendocardialRCMDiastolic
16、HFARVC/DLV AneurysmRandomHypertrophy/HCMVirusReceptorMyocyteFibroblastCompleterecoveryDiffusehypokinesisRegionalabnormalitySubendocardiallesionsIncreasedwall thicknessUnclassifiedabnormalityViral MyocarditisCHF/DCMSystolic HFHCMRCMARVC/DDiastolic HFHepatitis C Virus LV AneurysmARVCHCMDCMMyocarditisM
17、atsumori A Circ Res 2005;96:144-147 Impairment of myocardium in Patients with Hepatitis C Virus Infection in China nIn China,the prevalence of HCV infection is about 3.2%in the general populationnestimated 40106 individuals infected HCVprevalence of HCV infection in Chinapopulationn87 HCV-infected p
18、atients n87 control healthy individuals serum HCV antibody(+)；serum HCV RNA(+)；diagnosis of HCV infectionMarkersstagestagestage IIstage IIstage IIIstage III cases collection history UCG ECG blood sample 10ml 2006.1 2007.8Serum biomarkers test cTnIcTnI NT-proBNP NT-proBNP hs-CRP hs-CRP MMP-9 MMP-9 FL
19、C FLC 2007.3 2007.9 Data analysis clinical evaluation serum biomarkers evaluation 2007.10 Clinical featuresBiomarkers Total Patients with HCV VS normal controls*P P0.050.05，medianmedian，n=131n=131 patientcontrolPatients with HCV but without cardiac manifestation VS normal controls*P P0.050.05，median
20、,n=104median,n=104*patientcontrolPatients with HCV and cardiac manifestation VS normal controls*P P0.050.05，median,n=27median,n=27*patientcontrolNT-proBNP in Patients with HCV VS normal controls（median，*P0.05）patientcontrol total with cardiac abnormal without cardiac abnormalno difference UCG in Pat
21、ients with HCV and normal controls nHCV infection cause NT-proBNP,FLC,FLCand FLC/increase in ChinesenThese markers indicate the impairment of myocardiumconclusion HCV infection in Patients with Cardiomyopathies in China study-RetrospectivelyPatients with cardiomyopathies hospitalized in Peking Univ.
22、Peoples Hosp.from 2003 to 2008DCM HCM diagnosis criterianHCM diagnosis criteria based on WHO 1995nDCM Criteria：nEjection fraction 117%nExclusion criteria nAbnormal loading conditions(hypertension,valve disease)or coronarynartery disease sufficient to cause global systolic impairment.study-resultscon
23、clusionnHCV infection in HCM increased but have not significent difference between Patients with cardiomypathies and normal control in China General conclusion nHCV infection damage to myocardium nHCV cause cardiomyopathies need more evidence in China谢谢 谢！谢！010-88325940,刘文玲刘文玲E-mail: 中国致心律失常性右室心肌病注册研究中国致心律失常性右室心肌病注册研究(北美北美ARVC/D注册研究中国分中心注册研究中国分中心)