代谢综合症：临床设置的第一时间准备

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 1O

2、utline 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 its individual components and other major CVD risk factors? Underlying mec

3、hanisms behind the MetS and factors associated with it. Management of the MetS? Future research directions2The Metabolic Syndrome, also referred to as Syndrome X, Syndrome X Plus the Insulin Resistance Syndrome, Diabesity, the Big 4, the Deadly Quartet, the, the Reaven Syndrome, is a term for conste

4、llation of endogenous risk factors that increase the risk of developing both atherosclerostic vascular disease (ASCVD) and type 2 diabetes mellitus. What is the MetS 3 1923: Kylin described clustering of hypertension, gout, and hyperglycemia1988: Reavens Banting lecture at ADA Annual Conference desc

5、ribed the term of Syndrome X. 1998: World Health Organization first defined the 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 MetS4Major abnormalities for Syn

6、drome 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.5Proposed MetS Definitions WHO (1998)Insulin resistance DM / IGT / IFG2 or more of

7、1)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) Blood pressure 140/90 or RX4) High glucoseIGT or IFG (but notDM)ATP

8、III (2001)3 or more of1)ObesityWC102(m)/88(w)2)High TG1503)Low HDL-C110 including DM6Proposed MetS DefinitionsAACE (2003)IGT / IFG1 or more of1)ObesityBMI: 302)DyslipidemiaTG 150; HDL-c40(m)/45(w)3)Blood pressure 130/854)High glucose5)Other features of Insulin resistanceIDF (2005)Increase WC(populat

9、ion 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 more of1)ObesityWC102(m)/88(w)*2)High TG150 or Rx3)Low HDL-C100 or Rx*90/80 for Asician A7Prevalence of Components of the MetS*Abdominal obesit

10、y39%Hypertriglyceridemia30%Low HDL cholesterol37%High blood pressure or medication 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. 2

11、002:287:356-359.8Age-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

12、 MenWomen56.7%differenceFord ES, et al. JAMA. 2002;287:356-359.90510152025303540455020-70+20-2930-3940-4950-5960-6970MenWomenIncreasing Prevalence of NCEP MetS with Age (NHANES III)Age (years)Ford E et al. JAMA. 2002;287:356(%)10Number of publication of the MetS in Medical LiteraturesYear of publica

13、tionNumber of PublicationsAnyway in the CitationIn the title only197070131980793019882038419902609119956492782000109746620042381118011How 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

14、Dysmetabolic Syndrome In October 2001, the code of 277.7 became available.12How 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-l

15、isted Dx 3: seventh-listed Dx Of 11 records in 2003 1: First-listed Dx 2 each: third- through seventh- listed DxFord E. Diabetes Care 2005;28:180813Major Health Consequences of the MetSSummary of evidence from 15 prospective studiesRelative Risk for ATP III MetS definition For all-cause mortality1.2

16、7 (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. Diabetes Care 2005;28:176914Major Health Consequences of the MetSSumm

17、ary of evidence from 15 prospective studiesPopulation-attributable fraction for the MetS: 6-7% for all-cause mortality12-17% for cardiovascular disease30-52% for diabetes mellitusFord E. Diabetes Care 2005;28:176915Major Health Consequences of the MetSSummary of evidence from 15 prospective studiesA

18、djustment scheme None: 3 studies Age only: 4 studies Age, sex: 1 study Age, sex, race: 1 study 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

19、 E. Diabetes Care 2005;28:176916Major 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 cardiova

20、scular mortality* 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;164:106617What is the Pathophysiology of the MetS?Role of obesity Role of primary insulin resistanceRole of physical inactivityAther

21、ogenic dietRole of agingRole of genetic defects in each of the metabolic risk factors 18How does obesity relate to the MetS?Increased release of NEFAIncreased secretion of:TNF alpha, IL-6 Leptin, resistin, visfatinInflammatory cytokines,PAI-1Decreased secretion of adiponectin19Genetics of the MetSGe

22、netic factors contribute to: Atherogenic dyslipidemia (high TG, high apo B, small LDL, low HDL) Hypertension Hyperglycemia Proinflammatory state Prothromobotic stateCommon genetic for all the component of the MetS20BMIIRTGHDLSBPG EGGGEEEEGenetic and Environmental Architecture of IRSHong Y et al. AJH

23、G 1997;60:14321Goals 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 and Death in Patients with Atherosclerotic Cardiovascu

24、lar 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, Evaluation and Treatment of High Blood Cholesterol in Adult

25、s (ATP III) in the US22Additional measures reported to be associated with the MetS and in need of more researchAbnormal fat distribution General fat distribution Central fat distribution Biomarkers Liver fat contents Myocellular fatAtheogenic dyslipidemia Apolipoprotein B Small LDL particles Triglyc

26、erides/HDL-c ratioDysglycemia Fasting glucose OGTT Hoemonal factors Corticosteroid axis Polycystic ovary syndromeInsulin resitanceFasting insulin/proinsulin HOMA-IR IR by Bergman MIMOD Elevated fasting or OGTT FFA Vascular Dysregulation Endothelial dysfuction Microalluminua Chronic renal diseaseProi

27、nflammatory state C-reactive protein Inflammatory cytokinesProthrombotic state Fibrinolytic factors (PAI-1, etc) Clotting factor (fibrinogen, etc)Grundy et al. Circulation 2005,112, Modified 23AddFuture research Assess whether all components of the MetS are equally important and whether some combina

28、tions have great risk Need more evidence-based analysis to assess the rationale and value of adding 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 stan

29、dpoint of genetics molecular biology and cellular signaling Establish a standard method to measure 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

30、 physical activities Evaluate the cost-effectiveness of various drugs, both alone and in combination therapies 24Adjusted Hazard Ratios (95%Confidence Interval) of Incident CHD Associated with MetS Clusters The ARIC StudyComponents ClusterEvents/ParticipantsHR (95%CI)Reference Group 86/28041HBP+HG+T

31、G16/905.08 (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+WC10/1622.25 (1.17,4.33)TG+HDL+WC33/4972.32 (1.55,3.46)H

32、BP+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 = 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 ag