当今我国动脉血管硬化的危险因素-英文课件

1、Atherosclerotic Risk Factors in Modernizing China当今我国动脉血管硬化的危险因素Prof Woo Kam Sang and Fung Kwok PuiDepartment of BiochemistryThe Chinese University of Hong Kong香港中文大学生物化学系胡锦生教授，冯国培教授Chinese Atherosclerosis Study in the Aged and YoungCATHAY StudyPan Yu, Hong Kong, Macau, Sydney, San Francisco, Shanxi

2、, Three Gorges2617 asymptomatic subjectsAge: 18-70 yrsVascular EpidemiologyAdpated from Pepine CJ Am J Cardiol 1998;82(10A):23S-27S.OLeary NEJM 1999NoNormal intima-media thickness (IMT) of CCAAtherosclerotic plaques of common carotid arterysCV=1%Comparison of CCA IMT by 2 InvestigatorsInvestigatorIM

3、T (mm)Mean SDMean absolute difference (mm)Coefficient Variation %P.C.0.77 0.110.003 0.0111.0A.L.0.77 0.12P.C.10.69 0.140.034 0.0949.2P.C.20.75 0.21P.C.10.74 0.160.032 0.0959.3P.C.20.71 0.13AutoCCAManualRCCAManualLCCAEffects of HDL Cholesterol on Carotid IMTWCNCSubclinical Atherosclerosis in the Chin

4、ese (Carotid Intima-Media Thickening)(* Age & gender matched; mean age: 42 yr, 44% male)Chinese Community *IMTPan Yu (n=116)0.50+0.10mmHK/Sydney (n=116)0.56+0.12mmMacau (n=116)0.55+0.07mmSan Francisco (n=116)0.69+0.11mmPan YuHong KongSydneySan FranciscoDairy ProductMeat ProteinGreen TeaVegetablesDie

5、tary Patterns in Rural and Westernized Chinese 050100150200250(p0.001)(p0.02)(p0.001)(p0.001)Mean Daily Intake ml or g/1000 Kcal*p-value: Pan Yu vs others(0.490.09)*(0.560.13)*(0.590.15)*(0.680.15)*Effects of Smoking (Pack Years) on Carotid IMTWCNCHeavy Tobacco Smoke Pollution is Associated with Hig

6、her Atherosclerosis RiskYip TWC, Chook P, Feng XH, Chiu ML, Poon WH, Evora ML, Koon KV, Chan YK, Leong HC, Chu CL, Woo KS On multiple regression, carotid IMT was associated with age and passive smoking, independent of blood pressures, blood cholesterol and glucose (R2=0.5; F value 3.6; p0.05).Brachi

7、al FMD and Carotid IMT (Casino Employees vs CATHAY Controls)(n=59)(n=100)(n=59)(n=100)CAHTAY Cohort:HomocysteineCathay Study Result*We hypothesise hyperhomocysteinaemia contributes to atherogenesis process beyond the lipid effect - two unique (low blood lipid) and novel clinical models of hyperhomoc

8、ysteinaemia :Hong Kong Voluntary vegan-vegetarianNorthern rural ChineseObligatory vegetarian6.311.796.341.446.881.907.371.71* P0.05* P0.01* P0.001 (n=41)Change in FMD during the B12 Supplementation in Vegetarians Baseline Placebo B12 B12 3 mth DB 6mth open label(16.8%)0.690.090.680.090.670.090.650.0

9、9* P0.05, * P0.01, *P0.001 (n=41)Change in IMT during the B12 Supplementation in Vegetarians Baseline Placebo B12 B12 3 mth DB 6mth open label*(5.7%)Yu CountyHong KongN=121Yu CountyN=186Age 49.110.639.110.1*Gender (male)67 (59.8%)94 (50.5%)Smoking (yes)22 (19.6%)66 (35.5%)*SBP (mmHg)117.015.3120.312

10、.1*DBP (mmHg)75.49.380.29.0*TC (mmol/l)5.51.0 4.00.8 *Hong KongN=121Yu CountyN=186LDL (mmol/l)3.60.9 2.20.7*Folate (nmol/l)34.51.411.91.5*B12 (pmol/l)291.51.5140.71.6*tHcy (mol/l)8.51.220.01.9*IMT (mm)0.550.140.600.10*EDD (%)9.402.807.151.82* p0.001, Log-transferred dataThe clinical characteristics

11、of study subjects Odds Ratio (95% CI)P-valueAge (yr)1.09 (1.07-1.12)0.001Sex (male)2.14 (1.35-3.38)0.001Hypertension2.90 (1.44-5.84)0.003Hyperglycemia1.96 (1.08-3.58)0.027Low folate level2.06 (1.24-3.40)0.005Risk Factors for Carotid AtherosclerosisFMD increased significantly at 6 months after the 3

12、active treatment but not after placebo.B12 and FA Supplementation in Yu CountyMean FMD (%)Placebo(n=53)B12(n=52)Folate(n=51)B12+Folate(n=51)BaselineDB 6mthsOL 12mthsP0.0001P0.0001P0.0001P0.0001P0.0001P0.0001P0.0001P=0.001P0.0001P0.0001Three Gorges Reservoir DamThe Impact of Lifestyle Changes on Athe

13、rogenesis in Mainland China: A Tale of Three Gorges in Yangtze River YJ Hu, P Chook, AN Wei, MJ Wu, XL Wang, L Li, PG Dong, Celermajer DS, KS Woo Chongqing University of Medical Sciences, Chongqing The Chinese University of Hong Kong, Hong Kong Chongqing Center for Disease Control and Prevention, Ch

14、onqing Wu Shan Center for Disease Control and Prevention, Chongqing University of Sydney, Sydney BMI: body mass index, WHR: waist-hip ratio, TC: total plasma cholesterol, TG: triglyceride, MMS: prevalence of multiple metabolic syndrome Da Chang Wu Shan p-value (n=87) (n=95)Age(year) 48.8 10.0 49.8 9

15、SBP(mmHg) 122.3 18.1 121.8 18.9 0.86DBP(mmHg) 79.4 11.7 77.4 10.8 0.24 BMI 22.9 4.9 23.7 3.3 0.1 WHR 0.84 0.06 0.89 0.07 0.0001 TC(mmol/L) 4.2 0.9 5.1 1.0 0.0001 TG(mmol/L) 1.0 0.7 2.2 3.0 0.001HDL(mmol/L) 1.22 0.31 1.25 0.24 0.5 MMS(%) 4.6 20 0.001 IMT(mm) 0.64 0.11 0.71 0.16 0.001 Clinical Feature

16、s of 2 Cohorts0.001Mean IMT (mm)Wu Shan Carotid IMT was correlated with MMS (R2=0.68) independent of blood pressures and HDL-cholesterol. Dai CheongCarotid IMT of 2 CohortsP0.001 Conclusion: Sedentary lifestyle changes in Yangtze river Three-Gorges territories are associated with accelerated atherog

17、enic process, with great implications in atherosclerosis prevention in China, now in fast modernization process. Effects of Diet and Exercise on Obesity-Related Vascular Dysfunction in ChildrenP0.001P0.001Effects of Diet and Exercise on Obesity-Related Vascular Dysfunction in ChildrenP0.001Detrainin

18、g after 6 weeksContinued trainingP0.001Carotid IMT in Dietary / Exercise Intervention-1 year ResultDietary only(mm)Detraining(mm)Continuing Training(mm)(Baseline)0.470.050.470.050.480.04(1 Year)0.450.040.460.030.460.03 0.015 (95% CI 0.006-0.025) P=0.020.018(95% CI 0.008-0.028)P0.001GenesExternalEnvi

19、ronmentInternalEnvironmentEndothelialIntima-MediaDysfunction ThickeningAtheroscleroticDiseaseDietary Habits: Green Tea Vegetables Carotene Folate Animal Protein Fish, Fat or Dairy ProductLife-style: Exercise SmokingAlcoholPsychological StressBlood glucose/InsulinLipid DisordersLDL-Chol Oxidizability

20、AntioxidantsFolateHomocysteineFibrinogen/ThromboticFactorsHypertensionObesityVCAMSUB-CLINICALCLINICAL ATHEROSCLEROSIS *Gene-Environment InteractionsHypothesis 1: High prevalence of atherosclerosis in westernized than native ChineseHypothesis 2: Genetic homogenity in main steam Chinese ethnicHypothes

21、is 3: Gene-environmental interaction atherogenesis in modernizing communities#*Adpated from Pepine CJ Am J Cardiol 1998;82(10A):23S-27S.Chinese BreakfastBreakfast Western StyleLeft upper: Steamed Grass Carp with Tofu in Bean PasteLeft lower: Dace Fish Balls with Chinese LettuceRight: Braised Fish wi

22、th Sweet Bean Sheets and Winter MelonLeft: Fish CutletRight: Pan-fried Fish SteakLeft upper: Soy Bean Milk Left lower: Scrambled Eggs with ScallionsRight lower: Braised Mixed Soy Products with GlutenLeft: PizzaRight: Macaroni and Cheese with HamRight: Minced Beef with PotatoesLeft: Stir-fried Beef S

23、lices with Chinese BroccoliLeft lower: Sirloin Steak Dinner Right upper: Spahgetti in Meat Ball Sauce with CheeseMiddle: Hamburger and French FriesChanging Dietary Patterns and Subclinical Atherosclerosis in Chinese Americans: The Impact of Prolonged and Early AcculturizationKS Woo1 SW Chan2 P Chook

24、1 RKL Ip1 JLF Woo1 DS Celermajer3The Chinese University of Hong Kong, PR China1The Chinese Hospital, San Francisco, USA2The University of Sydney, NSW, Australia3Changing Dietary Patterns & Subclinical Atherosclerosis in Chinese Americans: The Impact of Prolonged AcculturizationDUR-IM 25 yrs(n=146)Ag

25、e (yrs)47.911.547.911.6IMT (mm)0.670.130.710.18*BMI23.13.324.13.4*CHO (g)137.422.5128.523.1*Protein (g)50.313.856.216.2*DFF (g)8.118.113.118.4*Vegetable (g)135.889.1115.368.7*GTea (ml)75.9190.032.599.4*p0.05; *p0.001Changing Dietary Patterns & Subclinical Atherosclerosis in Chinese Americans: The Im

26、pact of Early AcculturizationAGE-IM 10 yrs(n=120)AGE-IM 10 yrs(n=84)Age (yrs)45.111.545.111.6IMT (mm)0.640.110.670.13*BMI23.43.024.13.6*CHO (g)139.323.3126.920.6*Protein (g)51.514.956.417.4*DFF (g)7.611.914.919.4*Vegetable (g)128.597.3128.170.5GTea (ml)79.9209.230.9101.9*p0.05; *p0.01; *p0.001Athero

27、sclerosis & Endothelial DysfunctionED:A precussor of atherosclerosisED:A marker of early atherosclerosisSmokingCholesterolHypertensionDiabetesObesityEndothelial DysfunctionAtherosclerosisLower LDL cholesterolDietary antioxidant (soy protein, green tea, plant phytoestrogen)Genetic / environmental fac

28、torVessel toneVessel growthEndothelialcellsSmoothmuscle cellstPA PAI-1CAMs PGI2 NO NO ET-1 VEGF MCP-1 CoagulationFibrinolysis MonocytePlatelet interaction adhesionFunction of Endothelium (weight =1.5kg)DILATATIONEndotheliumShear StressEDRF (NO) FlowGTNSmooth MuscleBrachial Artery ScansHigh resolutio

29、n external vascular ultrasoundBrachial artery diameter measured following hyperemia and GTN sprayTests endothelium-dependent and independent dilatation10 mins rest4.5 mins cuff inflation15 minsrest3 minsScan B2Scan B3Scan B4Scan B1GTNCuff releaseFlow - Dependent Dilatation(Schachinger Circulation 20

30、00;101:1899-1906)Folic Acid and Vitamin B-12 Supplementation Improve Atherogenic Process in Rural Chinese: A Novel and Affordable Strategy of Atherosclerosis Prevention in ChinaSK Kwong1, P Chook2, TWC Yip3, YJ Hu4, XS Huang5, GG Wang6, MJ Wu4, YM Liu7, WK Lam2, DS Celermajer8, KS Woo2Alice Ho Miu L

31、ing Nethersole Hospital1, The Chinese University of Hong Kong2, Yan Chai Hospital3, Chongqing University of Medical Science4, Guangdong Provincial Cardiovascular Institute5, Fu Wai Hospital6, Sun Yat San University Second Affiliated Hospital7, The University of Sydney8Possible Contributory FactorsRe

32、duced physical activities (job and lifestyle)Dietary changesSociopsychological stressMetabolic syndromeThese will be further analysed, and effect of early health-education intervention assessedChanges in laser-Doppler cutaneous blood flow over timeMean and individual circulating levels of sCD40L(Pos

33、t Tonsillectomy) Atherogenesis in Kawasaki Disease / SLESLE* / Kawasaki disease(left upper)Steamed Grass Carp with Tofu in Bean Paste(left lower)Dace Fish Balls with Chinese Lettuce(right)Braised Fish with Sweet Bean Sheets and Winter Melon(left)Fish Cutlet(right)Pan-fried Fish Steak(left upper)Soya

34、 Bean Milk(left lower)Scrambled Eggs with Scallions(right lower)Braised Mixed Soy Products with Gluten(left)Pizza(right)Macaroni and Cheese with HamBlack TeaChinese TeaGenesExternalEnvironmentInternalEnvironmentEndothelialIntima-MediaDysfunction ThickeningAtheroscleroticDiseaseDietary Habits: Green

35、Tea Vegetables Carotene Folate Animal Protein Fish, Fat or Dairy ProductLife-style: Exercise SmokingAlcoholPsychological StressBlood glucose/InsulinLipid DisordersLDL-Chol OxidizabilityAntioxidantsFolateHomocysteineFibrinogen/ThromboticFactorsHypertensionObesityVCAMSUB-CLINICALCLINICAL ATHEROSCLEROS

36、IS *Gene-Environment InteractionsHypothesis 1: High prevalence of atherosclerosis in westernized than native ChineseHypothesis 2: Genetic homogenity in main steam Chinese ethnicHypothesis 3: Gene-environmental interaction atherogenesis in modernizing communities#*Adpated from Pepine CJ Am J Cardiol

37、1998;82(10A):23S-27S.Centre for Atherosclerosis StudiesThe founding members of the Centre are:Hong KongDept of Medicine & TherapeuticsThmoas YK Chan, Professor Kam Sang Woo, Professor (Director of the Gregory Cheng, Associate Professor Centre)John E Sanderson, Professor (Julian AJH Critchley, Profes

38、sor) Ping Chook, Research FellowDept of BiochemistryKwok Pui Fung, ProfessorDept of Chemical PathologyChris WK Lam, Professor & ChairmanSchool of Public HealthJean LF Woo, Professor & DirectorDept of Diagnostic Radiology & Organ-ImagingCon Metreweli, Professor Dept of PaediatricsRita YT Sung, Associ

39、ate ProfessorCentre for Clinical Trials & Epidemiological ResearchJoseph TF Lau, DirectorDr Shirley XuMainland ChinaThe Chinese Academy of Medical Sciences, BeijingLi Sheung Liu, ProfessorThe Chinese Academy of Medical Sciences, Beijing Guo Gan Wang, ProfessorThe Guangdong Provinicial Cardiovascular

40、 InstituteJian Zhang Feng, ProfessorYu County Cardiovascular InstituteGuo D.S.Tsinghua University Medical SchoolMing Zhe Chen, ProfessorOverseasUniversity of Sydney (Royal Prince Alfred Hospital)David S Celermajer, ProfessorClay Street Medical Centre, San FranciscoShu Wing Chan, CardiologistUniversi

41、ty of California, (Veterans Affairs Medical Centre)Edmund Keung, CardiologistAcknowledgementResearch CollaboratorsCUHKKS WooP ChookM QiaoJE SandersonJean LF WooCWK LamN ThomasSLY XuAlice CheungLindy ChanC MetreweliYK ChanTWC YipSK KwongU S ASW ChanE KeungMainlandChinaZJ MaiWK LaiJZ FengZS ZhangLS Li

42、uJX XieXH ZhangDS GuoGG WangXS HuangThe Royal Prince Alfred HospitalDS CelermajerJTC RobinsonS McMahomJA McCrohonMR AdamsB BaileyResultsComparing Non-VEG with VEG(mean age was 458 years)VEGNon-VEGp-ValueSBP (mmHg)128.816.7114.916.70.002DBP (mmHg)80.310.173.79.30.01WHR0.770.040.830.040.0001B-12 (pmol

43、/l)201.8137.4575.44800.001HC (mol/l)11.44.36.81.70.0001LDL-C (mmol/l)2.80.73.40.90.001Fasting glucose4.30.85.80.70.0001Folate68.921.615.44.40.0001DateLocationSubjectsNumbers1/1996Pun YuFarm village16911/1996MacauTown residents20912/1996Hong KongTown residents1706/1997SydneyChinese migrants1412/1998S

44、an FranciscoChinese migrants36711/19995/2000Hong KongVegetarians1257/2000Hong KongObese children814/2001Yu CountyFarmers/Coal miner3666/2005Wu ShanFramers/Town migrants1255/2006Three GorgesFarmers/Town migrants8641996-2006CATHAY Study2617Progress Time TableDifference in the Effect of Cigarette Smoki

45、ng on Endothelial Function in Chinese and White AdultsKam S Woo, Jacqui TC Robinson, Ping Chook, Mark R Adams, Gabriel Yip, ZJ Mai, Chris WK Lam, Keld E Sorensen, John E Deanfield, David S CelermajerYoung Chinese adults have less evidence of arterial endothelial dysfunction than young white adults w

46、ith similar direct or indirect exposure to cigarette smoke.Chinese Adults Are Less Susceptible Than Whites to Age-Related Endothelial DysfunctionKam S Woo, Jane A McCrohon, Ping Chook, Mark R Adams, Jacqui TC Robinson, Robyn J McCredie, Christopher WK Lam, Jian Z Feng, David S CelermajerEndothelium-

47、dependent dilation (EDD) is similar in the arteries of healthy young Chinese and white adults. With older age, however, Chinese subjects are less susceptible to impaired endothelial function.P0.001Westernization of Chinese Adults and Increased Subclinical AtherosclerosisKam S Woo, Ping Chook, Olli T

48、 Raitakari, Brendan McQuillan, Jiang Zheng Feng, David S CelermajerWesternization of Chinese subjects is associated with greater susceptibility to the pro-atherogenic effects of traditional vascular risk factors, such as lipids and smoking, and with evidence of increased IMT as a marker of subclinic

49、al atheroscleosis.The Impact of Heavy Passive Smoking on Arterial Endothelial Function in Modernized ChineseKam S Woo, Ping Chook, Hok C Leong, Xin S Huang, David S CelermajerIn modernized Chinese, as in Caucasians, exposure to heavy environmental tobacco smoke causes arterial endothelial dysfunctio

50、n, a key early event in atherosclerosis. This may have serious implications for cardiovascular health in China, currently in a process of rapid modernization.P0.01NSCATHAY Cohort:AgeCathay Study ResultCATHAY Cohort:Total CholesterolCathay Study Result*CATHAY Cohort:Total TriglycerideCathay Study Res

51、ult*CATHAY Cohort:HDL-CholesterolCathay Study Result*CATHAY Cohort:LDL-CholesterolCathay Study Result*CATHAY Cohort:GlucoseCathay Study ResultCATHAY Cohort:FolateCathay Study Result*CATHAY Cohort:Vitamin B12Cathay Study Result*CATHAY Cohort:Flow Mediated Dilatation Cathay Study Result*Vitamin B12 Su

52、pplementation Improves Atherogenic Process in VegetariansLucia WY Tam, Ping Chook, Timothy CY Kwok, Mu Qiao, Peter YK Poon, Jean LF Woo, DS Celermajer, KS WooDepartment of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China Department of Cardiology, The Royal P

53、rince Alfred Hospital, University of Sydney, AustraliaMethods50 vegetariansDouble-Blinded Randomization25 vegetarians25 vegetariansVitamin B12 (500 g/day)(1 capsule)Identical placebo (1 capsule)12 weeks treatment12 weeks treatment10 weeks washoutVitamin B12 (500 g/day)(1 capsule)Identical placebo (1

54、 capsule)DatePress ConferenceVenue30/11/1999Folic acid for heart diseaseUSA (AHA)13/4/2000CATHAY ceremonyHK15/3/2001ObesityHK16/8/2001Job stressHK9/2001Job stressSweden (ESC)11/2001ObesityUSA (AHA)10/2002VegetarianHK27/4/2004ObesityHK6/5/2006FA & B12 supplementationHKBackgroundMicronutrient deficien

55、cy (folic acid and vitamin B12) is prevalent in northern rural China and may be associated with atherosclerosis. (CATHAY Study) Preliminary study suggested folic acid (FA) and B12 supplementation may improve arterial endothelial function (surrogate atherosclerosis marker).ObjectiveTo further test su

56、ch supplementation strategy for atherosclerosis prevention, Methods180 asymptomatic subjects (110 males) in rural Shanxi (Yu County) were randomized to receive oral B12 (500g/day), FA (5mg/day), B12+FA, or image-matched placebos in double-blind 2x2 factorial design for 6 months, followed by open lab

57、el B12+FA for 6 more months. Flow-mediated dilation of brachial artery (FMD) and carotid intima-media thickness (IMT) as surrogate atherosclerosis markers were measured by high resolution B-mode ultrasound at baseline, 6 months and 12 months.MethodsFlow-mediated dilation of brachial artery (FMD) and

58、 carotid intima-media thickness (IMT) as surrogate atherosclerosis markers were measured by high resolution B-mode ultrasound at baseline, 6 months and 12 months.OLeary NEJM 1999Results (Preliminary Analysis of 83 Subjects)Their mean age was 45.28.3 years. Blood B12 and folate were low at baseline,

59、but significantly increased at 6 months after FA, B12 and FA+B12, but not after placebo treatment, FA/B12 was associated with significant decrease in blood homocysteine (HC) and blood pressures (p0.01). Results(Preliminary Analysis of 83 Subjects)Placebo (n=22)B12 (n=20)FA (n=26)B12+FA (n=15)0 mth6m

60、ths0 mth6 mths0 mth6 mths0 mth6 mthsSBP(mmol/l)1301712121*13620129181251511515*1312011513*DBP(mmol/l)8697711*90168118*82107710*88107710*FA(nmo/l)10.04.210.23.010.33.911.37.910.43.929.218.0*13.67.230.520.8*B12(pg/l)1831191556317990284122*18885175110156106273115*HC(mol/l)26.313.324.012.421.911.620.013