高血压指南亮点H型高血压PPT演示课件

中国高血压防治指南2010中国亮点 H型高血压在中国,内容提要,H型高血压新指南、新策略、新开始H型高血压是中国脑卒中高发的最主要危险因素中西方高血压患者靶器官损害及危险因素差异中国H型高血压及脑卒中高发的遗传学基础H型高血压治疗方案的循证之路H型高血压临床研究进展,新指南相关原文征引,前言：“我国有研究提示，有较高比例的高血压人群中伴有高同型半胱氨酸血症” 新因素：“影响高血压患者心血管预后的重要因素：血同型半胱氨酸升高（10umol/L）。” 综合防治： “高血压患者的风险不仅取决于血压水平，还取决于患者的并发症、合并症以及其他危险因素”,中华人民共和国卫生部疾病预防控制局中国高血压防治指南修订委员会,新指南，新策略，新办法，新开始！,“H型”高血压H-type Hypertension,伴有血浆同型半胱氨酸升高(hcy10mol/L)的原发性高血压称为“H型”高血压,胡大一，徐希平中华内科杂志 2008, 47 (12)：976-7,H型高血压在中国的特殊意义,Am J Hypertens 2000;13(suppl 1):S3-S10,80%以上的高血压人群多种危险因素并存,内容提要,H型高血压新指南、新策略、新开始H型高血压是中国脑卒中高发的最主要危险因素中西方高血压患者靶器官损害及危险因素差异中国H型高血压及脑卒中高发的遗传学基础H型高血压治疗方案的循证之路H型高血压临床研究进展,NOTES: Estimates are age-adjusted. Starting with 1999 data,causes of death were coded according to ICD10.,SOURCE: CDC/NCHS, National Vital Statistics System.,Chartbook,Health, United States, 2008,中美心脑血管疾病死亡率趋势比较,Stroke,1950,1960,1970,1980,1990,2000,2005,Year,10,000,100,10,Deathsper100,000population(logscale),Heart disease,1985,1990,1995,2000,2005,Year,150,100,0,Mortality(1/100000),50,USA,Lisheng Liu, Cardiovascular diseases in China, Biochem. Cell Biol. 85: 157163 (2007) Zhao et al, Stroke, 2008 (国际“卒中”杂志上发表的中国-MONICA-北京调查结果 ),Stroke,CHD,138,54,211.1,46.6,China,以每年8.7%的速度增加，2008年全国居民死因调查显示脑血管病已成为我国居民首位死因！,在不同人群高血压患者中心血管靶器官损害的差异,Blood Pressure 2001; 10: 190-2,Blood Pressure 2001；10:190-2,亚洲人群，尤其是中国人群的脑卒中和心梗比例远大于西方人群,SOURCE: CDC/NCHS, National Vital Statistics SystemReport on Cardiovascular Diseases in China (2008-2009)N Engl J Med 2006;2010；北京大学学报(医学版) 2007(39),心血管高危因素的中美差异,Hcy病理作用,氧化应激反应，导致内皮细胞和内质网损伤破坏机体凝血和纤溶之间的平衡，使机体处于血栓前状态 引起血管平滑肌细胞的增殖和胶原的合成,Stroke. 2004;35:345-347.,全程参与动脉粥样硬化的发生与发展,多项大型流行病学研究荟萃分析血浆Hcy增加5mol/L，脑卒中风险增加59%,BMJ,2002,325:1202-1206,JANA.2004；7；11-24,血同型半胱氨酸水平与心脑血管事件呈正相关,2006美国卒中指南定义HCY超过10mol/L为高同型半胱氨酸血症（HHCY）,Circulation 2006;113;e409-e449,H型高血压心脑血管疾病极高危危险因素,Relative Risk (Vascular Disease),JAMA. 1997;277:1775-1781,H型高血压增加血管性事件风险28倍,H型高血压,H型高血压心脑血管疾病极高危危险因素,H型高血压,美国,中国,J Neurol Sci 298,153-157北京大学学报（医学版） 2007;39:614-618,H-型高血压发生率 H-type Hypertension,伴同型半胱氨酸升高的高血压定义为H型高血压，需要防治新对策,伴有血浆同型半胱氨酸水平升高（10mol/l）的高血压六大城市研究（北京、上海、南京、沈阳、哈尔滨、西安）显示中国高血压人群75%是H型,Hu and Xu: J Chinese Intern Med 2008,Li J et al. J Peking University (Health Sciences) 2007;(39)614-618,91%,60%,75%,全球40年一级证据RCT研究：Meta分析确认叶酸降Hcy预防脑卒中有效,Lancet 2007;369:1876-82,一级预防应用降低脑卒中风险25%；能使Hcy下降超过20%则脑卒中风险下降23%；用于未接受食品叶酸强化人群脑卒中风险下降25%；根据林县研究，叶酸降低我国脑卒中死亡率37%,2010年10月21日首次被美国最新脑卒中防治二级指南所引用,内容提要,H型高血压新指南、新策略、新开始H型高血压是中国脑卒中高发的最主要危险因素中西方高血压患者靶器官损害及危险因素差异中国H型高血压及脑卒中高发的遗传学基础H型高血压治疗方案的循证之路H型高血压临床研究进展,Hcy的代谢,同型半胱氨酸是一种含硫基氨基酸，是蛋氨酸代谢产物,677位点,高血压患者TT基因型Hcy水平约比CC/CT基因型高一倍,Huo et al. 2011 (paper under review),中国叶酸缺乏率高达60%，而美国仅为0.6%,J Med Genet 2003;40:619-25Acta Universitatis Medicinalis Anhui 2006;41:639-42,MTHFR 基因 C677T 变异率的地区及种族差异,Lancet 2005; 365: 22432Cerebrovasc Dis 2008;26:4862,荟萃分析表明MTHFR C677T TT基因型与脑卒中发生显著正相关,(OR=1.26; 95%CI: 1.14-1.40),(OR=1.50; 95%CI: 1.23-1.84),欧美,中国,MTHFR基因型、血浆Hcy水平与脑卒中风险的剂量反应图,BMJ 2006;333;1114-1117,中间水平： Hcy每增加3mol/l-卒中风险增加33% （95%CI： -25% - 119%）高水平： Hcy每增加3mol/l-卒中风险增加36% （95%CI： 16% - 64%),内容提要,H型高血压新指南、新策略、新开始H型高血压是中国脑卒中高发的最主要危险因素中西方高血压患者靶器官损害及危险因素差异中国H型高血压及脑卒中高发的遗传学基础H型高血压治疗方案的循证之路H型高血压临床研究进展,高血压患者往往同时存在多个心血管危险组分。除了针对某一危险因素组分进行干预外，更应强调综合干预多种危险组分。综合干预有利于全面控制心血管危险因素，有利于及早预防心血管病。,中国关注H型,Unadjusted Adjusted BP response Genotype TT genotype TT genotype Tertiles Mean+SD CC+CT TT OR ( 95%CI) p OR (95%CI) p DBP Lower -1.582.13 121 18 1.0 1.0 Middle 4.491.74 106 41 2.6 (1.4-4.9) 0.003 2.6 (1.3-5.1) 0.005 Upper 12.043.26 111 47 2.8 (1.5-5.2) 0.001 2.5 (1.3-4.7) 0.006,Multiple regression analysis by GEE models for the association between MTHFR C677T and blood pressure response,Jiang et al., Thrombosis Res, 2004,TT基因型的高血压患者对ACEI类药物更敏感， 而TT基因型高血压患者Hcy水平约比CC/CT基因型高一倍,源自药物基因组学发现的组方依据,高HCY经NO-H2S-ACE偶联增加血管应激-高血压,Cell Biochem Biophys. 2010 ; 57: 4958,高Hcy与高血压协同作用的潜在机制,ACEI/叶酸组方进一步降低心脑血管事件19%,JAMA. 2008 May 7;299(17):2027-36.,WAFACS, n=5442，7.3 yrs of follow-up；The combination of ACEI and folic acid further reduced CVD events by 19%.,Arch Intern Med. 2001;161:695-700BMJ.1998; 316; 894-898,叶酸剂量增加（1mg/d），降Hcy无额外获益,治疗H型高血压的最佳配比安全剂量,降hcy减少脑卒中风险的最佳方案,Stroke. 2010;41,依叶：科学组方、个体化治疗,经典ACEI依那普利（10 mg） /新适应症剂量叶酸 （ 0.8mg ）,全球首个用于治疗伴有同型半胱氨酸（Hcy）升高的高血压的原研药物,TT型高血压患者疗效更佳,Huo et al. 2011(paper under review),2010中国高血压防治指南（修订版）,2010中国高血压防治指南,最新的2010高血压指南（修订版）指出：高同型半胱氨酸血症(HHcy）是心脑血管的危险因素高同型半胱氨酸血症(HHcy）的值为10mol/L通过预防多种危险因素、综合干预可以更有效预防心脑血管疾病发生：依叶降压降Hcy，更适合中国人群,依叶：全面阻击H型高血压,拥有JNC7全部强适应症符合JNC7降压药物联合治疗基础用药,服用方法：1/2-1片 qd. 中度/中危以上高血压患者推荐初始即与 利尿剂/CCB联用，早期平稳达标 降hcy疗效：4周显效，3个月后较稳定不良反应： ACEI类共有的干咳，停药即消失,内容提要,H型高血压新指南、新策略、新开始H型高血压是中国脑卒中高发的最主要危险因素中西方高血压患者靶器官损害及危险因素差异中国H型高血压及脑卒中高发的遗传学基础H型高血压治疗方案的循证之路H型高血压临床研究进展,Lancet. 2011 August 13; 378(9791): 584594.,Michael V Holmesa, Paul Newcombef,g, Jaroslav A Hubacekh, Reecha Sofatb, Sally L Rickettsi, Jackie Cooperc, Monique MB Bretelern,o, Leonelo E Bautistap, Pankaj Sharmaq, John C Whittakerf,g, Liam Smeethf, F Gerald R Fowkesr, Ale Algras,v, Veronika Shmelevat, Zoltan Szolnokiu, Mark Roestw, Michael Linnebankx, Jeppe Zachoy, Michael A Nallsz, Andrew B Singletonz, Luigi Ferrucciaa, John Hardye, Bradford B Worrallab, Stephen S Richac, Mar Matarind, Paul E Normanad, Leon Flickerae,ah, Osvaldo P Almeidaaf,ah,ai, Frank M van Bockxmeerag,aj, Hiroshi Shimokataak, Kay-Tee Khawj, Nicholas J Warehamk, Martin Bobaka, Jonathan AC Sterneam, George Davey Smithal, Philippa J Talmudc, Cornelia van Duijnn, Steve E Humphriesc, Jackie F Pricer, Shah Ebrahimf, Debbie A Lawloral, Graeme J Hankeyae, James F Meschiaan, Manjinder S Sandhul,m, Aroon D Hingorania,b, and Juan P Casasa,f,*Research Department of Epidemiology and Public Health, University College London, London, UK bDepartment of Clinical Pharmacology, University College London, London, UK cCentre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK dDepartment of Clinical and Experimental Epilepsy, University College London, London, UK eInstitute of Neurology, University College London, London, UK fFaculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, London, UK gGenetics, R&D, GlaxoSmithKline, Stevenage, UK hInstitute for Clinical and Experimental Medicine and Centre for Cardiovascular Research, Prague, Czech Republic iDepartment of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK jClinical Gerontology Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK kMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK lDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK mGenetic Epidemiology Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK nDepartment of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, Netherlands oGerman Centre for Neurodegenerative diseases (DZNE), Bonn, Germany pDepartment of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin at Madison, Madison, WI, USA qImperial College Cerebrovascular Research Unit (ICCRU), Imperial College London, London, UK rCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK sDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands tRussian Institute of 2011 Elsevier Ltd. All rights reserved. *Correspondence to: Dr Juan P Casas, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 。 Haematology and Transfusion, St Petersburg, Russia uDepartment of Neurology, Pandy County Hospital, Gyula, Hungary vUtrecht Stroke Center, Department of Neurology, and Julius Center, University Medical Center Utrecht, Netherlands wDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Netherlands xDepartment of Neurology, University Hospital Zurich, Zurich, Switzerland yDepartment of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark zLaboratory of Neurogenetics, National Institute on Aging, US National Institute of Health, Bethesda, MD, USA aaNational Institute on Aging, Baltimore, MD, USA abDepartment of Neurology, University of Virginia, Charlottesville, VA, USA acCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA adSchool of Surgery, University of Western Australia, Perth, WA, Australia aeSchool of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia afSchool of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia agSchool of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia ahWestern Australian Centre for Health and Ageing (WACHA), Western Australia Institute for Medical Research, Perth, WA, Australia aiDepartment of Psychiatry, Royal Perth Hospital, Perth, WA, Australia ajCardiovascular Genetics Laboratory, Division of Laboratory Medicine, Royal Perth Hospital, Perth, WA, Australia akNational Center for Geriatrics and Gerontology, Obu City, Japan alMRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK amSchool of Social and Community Medicine, University of Bristol, Bristol, UK anDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA,柳叶刀最新荟萃分析再次证实中国干预Hcy的必要性,1、叶酸水平对MTHFR变异对Hcy水平及卒中风险受到叶酸水平的修饰；（hcy-AAZ，TT/CC，013 mol/L, 085 to 111;亚洲，TT/CC，312 mol/L, 95% CI 223 to 401。卒中-亚洲，168, 95% CI 144 to 197；AAZ，103, 084 to 125）。 2、低叶酸水平地区开展的基因组学研究证实，降hcy对脑卒中的获益达22%（RR 078, 95% CI 068 to 090）,Lancet. 2011 August 13; 378(9791): 584594.,H型高血压临床研究的国际领先性,来自欧洲，美国，澳大利亚，俄罗斯等国著名研究所或大学的46名学者刚刚在柳叶刀杂志上发表了一篇有关叶酸，同型半胱氨酸，脑卒中，MTHFR基因型的大型META分析结果（Lancet. 2011 August 13; 378(9791): 584594.）。CSPPT临床研究被这篇文章在结论中高度评价为划时代工作：“将为补充叶酸降低Hcy是否保护脑卒中提供更加具有决定意义的答案。”,中国脑卒中一级预防研究China Stroke Primary Prevention Trial(CSPPT)Enalapril Maleate and Folic Acid Tablets for Primary Prevention of Stroke in Chinese Hypertensive Patients: A Double-blind Randomized Controlled TrialPI: YONG HUO, XIPING XU,已经开展的RCT,试验流程图,样本量：20702人随访时间：5年（已进展3