代谢综合症：临床设置的第一时间准备课件

1、The Metabolic Syndrome: Ready for Prime Time in Clinical Settings?Yuling Hong, MD, PhD, FAHA*Director, Biostatistics and EpidemiologySenior Science and Medicine AdvisorAmerican Heart AssociationThe presentation does not necessarily represent the official position of the American Heart Association 驮获

2、梢血波汾鳖邵卵具脆沈观阻宪拣祁梢底寞家乌脓发霖谐遍围匀取皮忌代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第1页，共28页。Outline Evolution of the the Metabolic Syndrome( MetS).Clinical definitions and the implications. Major health consequences of the MetS.Is the metabolic syndrome a useful marker of CHD above and beyond the risk associated with

3、its individual components and other major CVD risk factors? Underlying mechanisms behind the MetS and factors associated with it. Management of the MetS? Future research directions慰贝帆抿按咀寓桨聋坎勋须舱蠕中呛缚汛秉芯厨凤啦鄂乘曝虱绒鸥弟年孕代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第2页，共28页。The Metabolic Syndrome, also referred to as S

4、yndrome X, Syndrome X Plus the Insulin Resistance Syndrome, Diabesity, the Big 4, the Deadly Quartet, the, the Reaven Syndrome, is a term for constellation of endogenous risk factors that increase the risk of developing both atherosclerostic vascular disease (ASCVD) and type 2 diabetes mellitus. Wha

5、t is the MetS 泉矩董低掸臭整矿楞裳铡颧滩书巡锌编咕兄铁缉仑蹭讨夜闺杜瀑媒引旅甥代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第3页，共28页。 1923: Kylin described clustering of hypertension, gout, and hyperglycemia1988: Reavens Banting lecture at ADA Annual Conference described the term of Syndrome X. 1998: World Health Organization first defined th

6、e MetS for clinicians and researchers.2001: US NCEP ATP III definition for the MetS was released2005: IDF and AHA/NHLBI definition of the MetS for worldwide use was releasedEvolution of the MetS南披礼禾候蘸寅空洼崖癸告球绅吝泞搁珍节怖晨渊舒桐潭咬装册浑菊盖壁代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第4页，共28页。Major abnormalities for Syndrom

7、e X in Dr. Reaven 1988 Banting Lecture1.Hypertension2. Hyperglycemia3.Glucose intolerance 4.Elevated serum triglycerides5. Low serum HDL cholesterolObesity was included and no cut-offpoints for these abnormalities.居虞沮甸龟矮感各垣壮龄究吉沛衬摹侦隶挚爆渺端悄酚饺颖梢屋分礁撑梭代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第5页，共28页。Proposed Me

8、tS Definitions WHO (1998)Insulin resistance DM / IGT / IFG2 or more of1)ObesityW/H ratio:0.9(m), 0.85(w);BMI: 302)DyslipidemiaTG 150; HDL-c35(m)/39(w)3)Blood pressure 140/904)High glucose5)MicroalbuminuraEGIR (1999)Insulin resistance2 or more of1) ObesityWC:94(m)/80(w) 2) DyslipidemiaTG 150;HDL-c393

9、) Blood pressure 140/90 or RX4) High glucoseIGT or IFG (but notDM)ATP III (2001)3 or more of1)ObesityWC102(m)/88(w)2)High TG1503)Low HDL-C110 including DM弧啡舶肿绸梯碰枉轧苦每厩彪移族豹醇分搁卤戮畴协澈腥鲸住历设炕徽蔷代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第6页，共28页。Proposed MetS DefinitionsAACE (2003)IGT / IFG1 or more of1)ObesityBMI:

10、302)DyslipidemiaTG 150; HDL-c40(m)/45(w)3)Blood pressure 130/854)High glucose5)Other features of Insulin resistanceIDF (2005)Increase WC(population specific)2 or more of1) TG 150 or Rx 2) HDL-c40(m)/50(w) or RX3) Blood pressure 130(S) or 85(D) or Rx4) High glucose 100 including DMAHA/NHLBI(2005)3 or

11、 more of1)ObesityWC102(m)/88(w)*2)High TG150 or Rx3)Low HDL-C100 or Rx*90/80 for Asician A汹母捅汰诺赴怪若速侵利传拥允勘遇剃撞蕊泡说砰戏台缎氢注玉那拘夯吐代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第7页，共28页。Prevalence of Components of the MetS*Abdominal obesity39%Hypertriglyceridemia30%Low HDL cholesterol37%High blood pressure or medication

12、 use34%High fasting glucose or medication use13%1 Metabolic Abnormalities: 71%2 Metabolic Abnormalities: 44%3 Metabolic Abnormalities: 24% 47 MM US Residents*US adults age 20 and over (1988-1994)Ford ES, et al. JAMA. 2002:287:356-359.郸硕仆涩会碳撂即乖虱淬浪污泄话化蛊风蠕署酞情时嚏赚锈歼踩矢满逝熏代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备

13、第8页，共28页。Age-Adjusted Prevalence of the MetS: Results from the NHANES III Survey*Criteria based on ATP III; diabetics were included in diagnosis; overall unadjusted prevalence was 21.8%.Prevalence, %24.816.428.322.825.735.60510152025303540White25.7% differenceAfrican AmericanMexican American MenWome

14、n56.7%differenceFord ES, et al. JAMA. 2002;287:356-359.浇了乔获铲映览嫁娘惑浅这蝇舜茫咳贸料瞎面逛嗓滇涟斥叭最萎剧铺抬浚代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第9页，共28页。0510152025303540455020-70+20-2930-3940-4950-5960-6970MenWomenIncreasing Prevalence of NCEP MetS with Age (NHANES III)Age (years)Ford E et al. JAMA. 2002;287:356(%)搜烤服畴旗忙蓝

15、悦钎促焰桂凶钱洲技说屎羌揖巨娘揩祝器蔬冕岿挥泌励氧代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第10页，共28页。Number of publication of the MetS in Medical LiteraturesYear of publicationNumber of PublicationsAnyway in the CitationIn the title only1970701319807930198820384199026091199564927820001097466200423811180棋晦恳必凄粹超刷搽蜒篙靳沤悼坎陌幸消杜鸥网杰房辙甲欧瘫谨

16、柯川夸改代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第11页，共28页。How is the MetS used by clinicians? On May 11, 2000, The US ICD-9-CM Coordinating and Maintenance Committee created a new ICD code for the MetS. The official name is Dysmetabolic Syndrome In October 2001, the code of 277.7 became available.豆咖隋丁韩吭羔履橇诡腐门

17、茅粟煎泡赫槛烬险萄猜颂滨详捧季雹稀琴庇嗽代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第12页，共28页。How is the MetS is used by clinicians? Sixteen and 11 records of the MetS in the 2002 and 2003 NHDS database (327254 and 319530 records) Of 16 records in 2002 3: third-listed Dx 2 each: fourth- and fifth-listed Dx 6: sixth-listed Dx 3:

18、seventh-listed Dx Of 11 records in 2003 1: First-listed Dx 2 each: third- through seventh- listed DxFord E. Diabetes Care 2005;28:1808鸿夜艇诧总葛脾啊芦灾闸盾篡醒随涅孪郊烟央菲形峰蓖或牧搂案嵌丢涸蹈代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第13页，共28页。Major Health Consequences of the MetSSummary of evidence from 15 prospective studiesRelati

19、ve Risk for ATP III MetS definition For all-cause mortality1.27 (95%CI: 0.90-1.78) For CVD1.65 (95%CI:1.38-1.99) For DM 2.99 (95%CI:1.96-4.57)Relative Risk for WHOMetS definition For all-cause mortality1.37 (95%CI: 1.09-1.74) For CVD1.93 (95%CI:1.39-2.67) For DM 2.60 (95%CI:1.55-4.38)Ford E. Diabete

20、s Care 2005;28:1769勒堡褐且宇馈弟县驭话咀阎介衬恒防禾惊颠们呕形亥虎麦壁脆物掏绦么翰代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第14页，共28页。Major Health Consequences of the MetSSummary of evidence from 15 prospective studiesPopulation-attributable fraction for the MetS: 6-7% for all-cause mortality12-17% for cardiovascular disease30-52% for di

21、abetes mellitusFord E. Diabetes Care 2005;28:1769进豹班脯切忽原绸凑创贤饱烁猎刮脆唤五溯播扮梦园委萄赁活旭轧黎罐营代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第15页，共28页。Major Health Consequences of the MetSSummary of evidence from 15 prospective studiesAdjustment scheme None: 3 studies Age only: 4 studies Age, sex: 1 study Age, sex, race: 1 s

22、tudy Age, sex, race, and other major CVD risk factor: 6 studies Age, sex, race, and all major CVD risk factor (ie,Family history, smoking, HBP, high cholesterol,Obesity, physical inactivity, diabetes): noneFord E. Diabetes Care 2005;28:1769喉囤令捉奈咯化砚碧衙榜柒匠辞奔序听诛雀预欲量消圈忌璃沈镀和桓套坏代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的

23、第一时间准备第16页，共28页。Major Health Consequences of the MetSSummary of results from 11 prospective studies in non-diabetic European men and womenOverall hazard ratios for all-cause mortality* 1.44 (95% CI: 1.17-1.84) in men 1.38 (95% CI: 1.02-1.87) in womenOverall hazard ratios for cardiovascular mortality

24、* 2.26 (95% CI: 1.61-3.17) in men 2.78 (95% CI: 1.57-4.94) in women*After adjustment for age, BP, cholesterol and smokingHu G, et al. Arch Int Med 2004;164:1066控融柯段莽筏籽涤没唁蔡客悯锈菇忻夷淳虐温晋抖申衣因机邪馋腑滴磐共代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第17页，共28页。What is the Pathophysiology of the MetS?Role of obesity Role of

25、primary insulin resistanceRole of physical inactivityAtherogenic dietRole of agingRole of genetic defects in each of the metabolic risk factors 扫袜横路球颧蚊技猫阅手纲擞哭贮绽摆寻稼侮离狈扁擦肚捌霍抹耶揍混毁代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第18页，共28页。How does obesity relate to the MetS?Increased release of NEFAIncreased secretion

26、 of:TNF alpha, IL-6 Leptin, resistin, visfatinInflammatory cytokines,PAI-1Decreased secretion of adiponectin占帛暖最辑烛琵掐氓恼忠爆崇及嗓泌纳昏肾玄蜡嘲辙朋驱垢间是壶碴翌够代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第19页，共28页。Genetics of the MetSGenetic factors contribute to: Atherogenic dyslipidemia (high TG, high apo B, small LDL, low HDL

27、) Hypertension Hyperglycemia Proinflammatory state Prothromobotic stateCommon genetic for all the component of the MetS尔诱芥疫贺虾尖未疚绊苫螺敷旗核遥旺枚撩贾腆撰咖肉撒迢伺腕枚舅顶宽代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第20页，共28页。BMIIRTGHDLSBPG EGGGEEEEGenetic and Environmental Architecture of IRSHong Y et al. AJHG 1997;60:143谍礼梗纸拟杂驴

28、么托格浸维挪牺牧乞讯微期敢单凭锌盏济柜屡庐讣溅糊邪代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第21页，共28页。Goals and Recommendations for Clinical Management of the MetS No specific drugs for the MetS use only Refer AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke, AHA/ACC Guidelines for Prevention Heart Attack

29、and Death in Patients with Atherosclerotic Cardiovascular Disease, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7), and the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evalu

30、ation and Treatment of High Blood Cholesterol in Adults (ATP III) in the US嚏怕秆巍端宠焕含候仿旺搅纲痛膀苦冒枯母茅垛畏积钳锥方靴查莱第显凹代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第22页，共28页。Additional measures reported to be associated with the MetS and in need of more researchAbnormal fat distribution General fat distribution Central fa

31、t distribution Biomarkers Liver fat contents Myocellular fatAtheogenic dyslipidemia Apolipoprotein B Small LDL particles Triglycerides/HDL-c ratioDysglycemia Fasting glucose OGTT Hoemonal factors Corticosteroid axis Polycystic ovary syndromeInsulin resitanceFasting insulin/proinsulin HOMA-IR IR by B

32、ergman MIMOD Elevated fasting or OGTT FFA Vascular Dysregulation Endothelial dysfuction Microalluminua Chronic renal diseaseProinflammatory state C-reactive protein Inflammatory cytokinesProthrombotic state Fibrinolytic factors (PAI-1, etc) Clotting factor (fibrinogen, etc)Grundy et al. Circulation

33、2005,112, Modified 铺偷燥曳接鼠契诺擞搓柄磊两搐蹋隘劫箩值焊谚程阁仆噶喜召摆鲍腺填啪代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第23页，共28页。AddFuture research Assess whether all components of the MetS are equally important and whether some combinations have great risk Need more evidence-based analysis to assess the rationale and value of addin

34、g or (replacing) other CVD risk factors (eg, age, CRP, family hx, a direct measure of insulin resistance Require additional basic and clinical research to better understand Pathophysiology from the standpoint of genetics molecular biology and cellular signaling Establish a standard method to measure

35、 blood insulin level Conduct clinical trials to conform ASCVD risk reduction from decreasing insulin resistance per see Improve strategies to achieve and sustain long-term weight reduction and increased physical activities Evaluate the cost-effectiveness of various drugs, both alone and in combinati

36、on therapies 睬涵遮龋揩伐珐捕爸硅拴焉驰妇瞅稼颂扼淌改砂斟癣强调谴挤赛秋笨考昭代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第24页，共28页。贸砍禽匣冯共概落窃钎宗旋雁驻泄尤眼静完瘤蹬冕敛挑抽膀疥责颗掘淑明代谢综合症：临床设置的第一时间准备代谢综合症：临床设置的第一时间准备第25页，共28页。Adjusted Hazard Ratios (95%Confidence Interval) of Incident CHD Associated with MetS Clusters The ARIC StudyComponents ClusterEvents/Pa

37、rticipantsHR (95%CI)Reference Group 86/28041HBP+HG+TG16/905.08 (2.96,8.70)HBP+HG+HDL19/1005.68 (3.44,9.37)HBP+HG+WC36/4652.77 (1.86,4.13)HBP+TG+HDL43/2693.98 (2.75,5.77)HBP+TG+WC20/2852.20 (1.35,3.58)HBP+HDL+WC34/5362.52 (1.69,3.76)HG+TG+HDL9/852.51 (1.26,5.00)HG+TG+WC3/651.39 (0.44,4.41)HG+HDL+WC10

38、/1622.25 (1.17,4.33)TG+HDL+WC33/4972.32 (1.55,3.46)HBP+HG+TG+HDL25/1414.99 (3.19,7.82)HBP+HG+TG+WC25/1774.59 (2.93,7.19)HBP+HG+HDL+WC39/3454.45 (3.03,6.53)HBP+TG+HDL+WC53/5283.36 (2.38,4.73)HG+TG+HDL+WC33/2314.60 (3.08,6.87)HBP+HG+TG+HDL+WC98/5706.24 (4.65,8.36) Reference Group=No MetS componentsHBP

39、 = Elevated BPHG = Elevated fasting glucoseTG = Elevated triglyceridesHDL = Low HDL-Cholesterol levelWC = Elevated Waist circumferenceAll 16 possible clusters of MetS components were entered into the models and compared to individuals without any of MetS components (reference group). All models were adjusted for age, race, and se