1、Global Disparities in Metabolic Syndrome, Diabetes and Cardiovascular Disease Nathan D. Wong, PhD, FACC, FAHA Professor and Director, Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine Immediate Past President, American Society of Preventive Cardiology,Global
2、Distribution of CVDs as Causes of Death, WHO 2011,Worldwide Mortality from Ischemic Heart Disease and Cerebrovascular Disease 2011,Ischemic Heart Disease,Cerebrovascular Disease,Development of Atherosclerotic Plaques,Normal,Fatty streak,Foam cells,Lipid-rich plaque,Lipid core,Fibrous cap,Thrombus,Ro
3、ss R. Nature. 1993;362:801-809.,Age-Adjusted Coronary Heart Disease Rates by Country,Age-Adjusted Death Rates from Stroke, by Country,CVD will be the top cause for future total DALY lost in China (Per 1000 Population),Morbidity,Mortality,Approaches to Primary and Secondary Prevention of CVD,Primary
4、prevention involves prevention of onset of disease in persons without symptoms. Primordial prevention involves the prevention of risk factors causative o the disease, thereby reducing the likelihood of development of the disease. Secondary prevention refers to the prevention of death or recurrence o
5、f disease in those who are already symptomatic,Risk Factor Concepts in Primary Prevention,Nonmodifiable risk factors include age, sex, race, and family history of CVD, which can identify high-risk populations Behavioral risk factors include sedentary lifestyle, unhealthful diet, heavy alcohol or cig
6、arette consumption. Physiological risk factors include hypertension, obesity, lipid problems, and diabetes, which may be a consequence of behavioral risk factors.,Major Risk Factors,Cigarette smoking (passive smoking?) Elevated total or LDL-cholesterol Hypertension (BP 140/90 mmHg or on antihyperten
7、sive medication) Low HDL cholesterol (40 mg/dL) Family history of premature CHD CHD in male first degree relative 55 years CHD in female first degree relative 65 years Age (men 45 years; women 55 years), HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its presence removes one risk facto
8、r from the total count.,Other Recognized Risk Factors,Obesity: Body Mass Index (BMI) Weight (kg)/height (m2) Weight (lb)/height (in2) x 703 Obesity BMI 30 kg/m2 with overweight defined as 25-40 in. in men, 35 in. in women Physical inactivity: most experts recommend at least 30 minutes moderate activ
9、ity at least 4-5 days/week,Cardiovascular Risk Factors are the Top 6 Leading Causes of Death,Global Distribution of Diabetes, WHO 2011,Risk of Cardiovascular Events in Diabetics Framingham Study,Age-adjustedBiennial Rate Age-adjustedPer 1000 Risk Ratio Cardiovascular Event Men Women Men Women Corona
10、ry Disease 39 21 1.5* 2.2* Stroke 15 6 2.9* 2.6* Peripheral Artery Dis. 18 18 3.4* 6.4* Cardiac Failure 23 21 4.4* 7.8* All CVD Events 76 65 2.2* 3.7*Subjects 35-64 36-year Follow-up *P.001,*P.0001,_,_,Source: NCHS and NHLBI. NH indicates non-Hispanic.,2010 American Heart Association, Inc. All right
11、s reserved.,Roger VL et al. Published online in Circulation Dec. 15, 2010,Global Prevalence of Obesity, WHO 2011,2011 American Heart Association, Inc. All rights reserved.,Roger VL et al. Published online in Circulation Dec. 15, 2011,Data derived from Health, United States, 2010: With Special Featur
12、e on Death and Dying. NCHS, 2011.,2011 American Heart Association, Inc. All rights reserved.,Roger VL et al. Published online in Circulation Dec. 15, 2011,Trends in the prevalence of obesity among US children and adolescents by age and survey year (National Health and Nutrition Examination Survey: 1
13、971-1974, 1976-1980, 1988-1994, 1999-2002 and 20052008),Data derived from Health, United States, 2010: With Special Feature on Death and Dying. NCHS, 2011.,Causes of Mortality in Patients With Diabetes,Diabetes and CVD,Atherosclerotic complications responsible for 80% of mortality among patients wit
14、h diabetes 75% of cases due to coronary artery disease (CAD) Results in 75% of all hospitalizations for diabetic complications50% of patients with type 2 diabetes have preexisting CAD. (This number may be less now that more younger people are diagnosed with diabetes.) 1/3 of patients presenting with
15、 myocardial infarction have undiagnosed diabetes mellitus,Lewis GF. Can J Cardiol. 1995;11(suppl C):24C-28C Norhammar A, et.al. Lancet 2002;359;2140-2144,AGE=Advanced glycation end products, CRP=C-reactive protein, CHD=Coronary heart disease HDL=High-density lipoprotein, HTN=Hypertension, IL-6=Inter
16、leukin-6, LDL=Low-density lipoprotein, PAI-1=Plasminogen activator inhibitor-1, SAA=Serum amyloid A protein, TF=Tissue factor, TG=Triglycerides, tPA=Tissue plasminogen activator,Subclinical Atherosclerosis,Atherosclerotic Clinical Events,Hyperglycemia, AGE Oxidative stress,Inflammation, IL-6 CRP SAA
17、,Infection, Defense mechanisms Pathogen burden,Biondi-Zoccai GGL et al. JACC 2003;41:1071-1077.,Mechanisms by which Diabetes Mellitus Leads to Coronary Heart Disease,Most Cardiovascular Patients Have Abnormal Glucose Metabolism,35%,31%,34%,37%,18%,45%,37%,27%,36%,GAMI n = 164,EHS n = 1920,CHS n = 22
18、63,GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction study; EHS = Euro Heart Survey; CHS = China Heart Survey,Prediabetes,Normoglycemia,Type 2 Diabetes,Anselmino M, et al. Rev Cardiovasc Med. 2008;9:29-38.,Risk of Cardiovascular Events in Patients with Diabetes: Framingham Study,
19、Age-adjustedBiennial Rate Age-adjustedPer 1000 Risk Ratio Cardiovascular Event Men Women Men Women Coronary Disease 39 21 1.5* 2.2* Stroke 15 6 2.9* 2.6* Peripheral Artery Dis. 18 18 3.4* 6.4* Cardiac Failure 23 21 4.4* 7.8* All CVD Events 76 65 2.2* 3.7*Subjects 35-64 36-year Follow-up *P.001,*P.00
20、01,_,_,Diabetes Across US Ethnic Groups,From 2007-2009 National Survey Data prevalence of diabetes: 8.4% of Asian-Americans 7.1% in non-Hispanic whites 11.8% of Hispanics 12.6% of non-Hispanic blacks.,Source: AHA Heart and Stroke Facts 2013,Prevalence estimates for Diabetes and Borderline Diabetes a
21、cross California racial and ethnic groups (California Health interview Survey 2009),Borderline Diabetes,Diabetes,健康危害糖尿病患病率持续增长,Prevalence（%）,Increasing prevalence of diabetes in urban China,Ministry of Health of the Peoples Republic of China,2008 Diabetes Cases in China Exceeds 2008 and 2016 Projec
22、ted Levels,Sources: Liu et al 2002, Pan et al, US CDC,Changes in Overweight/Obesity Prevalence 1992-2002 in Adults in China (Wang et al., 2007),Increases in Overweight/Obesity Prevalence in China by Urban/Rural and Income Status (Du et al. 2002),Metabolic Syndrome: Clustering of Interconnected Metab
23、olic Risk Factors,Obesity,Insulin Resistance + Hyperglycemia,Hypertension,Atherogenic Dyslipidemia,IDF/IAS/NHLBI/AHA/WHF Joint Scientific Statement on Diagnosis of Metabolic Syndrome (Alberti et al. Circulation 2009) (=3 criteria required for diagnosis),Alberti et al. Circulation 2009,Back,Visceral
24、AT,Subcutaneous AT,Front,Intra-abdominal (Visceral) Fat The dangerous inner fat!,Relative Risk of Diabetes,Waist Circumference (in),Abdominal Adiposity Is AssociatedWith Increased Risk of Diabetes,P value for trend 0.001,Carey VJ, et al. Am J Epidemiol. 1997;145:614-619,Metabolic Syndrome and Diabet
25、es in Relation to CHD, CVD, and Total Mortality: U.S. Men and Women Ages 30-74,* p.05, * p.01, * p.0001 compared to none,*,*,*,*,*,*,*,*,*,*,*,Malik and Wong, et al., Circulation 2004.,(Risk-factor Adjusted Cox Regression) NHANES II Follow-up (n=6255),*,Metabolic Syndrome and CVD Risk: Meta-Analysis
26、: Mottillo et al. JACC 2010,951,083 pts in 83 studies Little variation in risk between definitions Relative risk:2.35 (2.20-2.73) for CVD events2.40 (1.87-3.08) for CVD mortality1.58 (1.39-1.78) for all-cause mortality1.99 (1.61-2.46) for myocardial infarction2.27 (1.80-2.85) for stroke Those with m
27、etabolic syndrome, without diabetes, maintained high CVD risk (RR=1.75, 95% CI=1.19-2.58),Metabolic Syndrome Trends (by NCEP Definition) in Mexico: Mexico City Diabetes Study,Lorenzo C, Haffner SM et al., Diabetes Care 2005,Prevalence of MetS in Middle Eastern Populations,Sliem HA et al. Indian J En
28、docrinol Metab 2012; 16: 67-71,Significant Prevalence of Obesity in Middle East: BMI =30,Oman 30.8% Qatar 40.8% Gaza/West Bank 41.5% Egypt 30.2% of men and 70.9% of women based on IDF European cutpoints (80cm women and 94 cm men), but 31.7% of men and 50.8% of women based on new Egyptian waist circu
29、mference cutpoints (97.5 cm men and 92.3 cm women) Metabolic syndrome present in 26% of obese children in Lebanon,Sliem HA et al. Indian J Endocrinol Metab 2012; 16: 67-71,Lifestyle Issues Contribute to Obesity and MetS in Saudi Arabia,Recent Diabetes and Metabolic Syndrome Prevalence in Africa,Beni
30、n 3% Mauritania 6% Cameroon 6% Congo 7% Zimbabwe 10% Democratic Republic of Congo 14.5% Nigeria 2%; Metabolic syndrome (hypertensive Nigerians) 34% (ATP III), 35% (WHO), 43% (IDF),Prevalence of Metabolic Syndrome in Africa,Prevalence depends greatly on the population setting; increase attributed to
31、the Western lifestyle from reduced physical activity and substitution of the traditional African diet (rich in fruits and vegetables) to energy-laden foods More common in females, with increasing age, and urban setting; some exceptions such as lower prevalence among women in Jos plateau of Nigeria w
32、ho are more active whereas in Sokota region the religious practice of women in Purdah makes them sedentary.,Purdah is the traditional Islamic practice that confines women to the home or compound and so limits their participation in society. Women living in purdah are not allowed to come out of their
33、 homesteads.,Prevalence of Metabolic Syndrome in South Asians (Pandit et al., 2012),Several large surveys of large citys in different parts of India suggest about one-third of the urban population has MetS. Key risk factors are highly prevalent in Asian Indians: 31% abdominal obesity, 46% hypertrigl
34、yceridemia, 66% low HDL, 55% HTN, 27% elevated fasting glucose Study in urban Karachi, Pakistan showed high prevalence of 35% by IDF and 49% by ATP III obesity in urban Pakistan ranges from 46-68%, hypertriglycerdemia 27-54%, and 68-81% low HDL.,Prevalence of MetS in Asian Indians, Malays and Chines
35、e,From Pandit K et al., Indian J Endocrinol Metab 2012,Risk Factors Greater in Asians than in Caucasians (Williams, 1995),Sedentary lifestyle Truncal obesity Hyperinsulinemia and insulin resistance Diabetes mellitus Elevated triglycerides Low HDL-C,Type 2 Diabetes and CHD 7-Year Incidence of Fatal/N
36、onfatal MI (East West Study),No Diabetes,Diabetes,3.5%,18.8%,20.2%,45.0%,P0.001,P0.001,7-Year Incidence Rate of MI,CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitus,Haffner SM et al. N Engl J Med. 1998;339:229-234.,Is DM really a CHD Risk Equivalent? Meta-Analysis of 38,578
37、subjects (Bulugahapitiya et al. Diabetic Med 2008),Global Risk Assessment in DM: 10-year Total CVD Risk by Gender (Wong ND et al., Diab Vas Dis Res 2012),Annual CHD Event Rates (in %) by Calcium Score Events by CAC Categories in Subjects with DM, MetS, or Neither Disease (Malik and Wong et al., Diab
38、etes Care 2011),Coronary Heart Disease,Coronary Artery Calcium Score,ACCF/AHA 2010 Guideline: CAC Scoring for CV risk assessment in asymptomatic adults aged 40 and over with diabetes (Class IIa-B),Summary of Care: ABCs for Providers,Control of DM Risk Factors in a Large Multipayer Outpatient Populat
39、ion in Northern California (n=15,826) (Holland et al., J Diab Complic 2013),Individual control of HbA1c, BP, and LDL ranged from 42-78% in Asians Composite control of HbA1c, BP, and LDL ranged from 21-27% in Asians,1. Steering Committee of the Physicians Health Study Research Group. NEJM 1989;321:12
40、9-35 2. ETDRS Investigators. JAMA 1992;268:1292 3. Antiplatelet Trialists Collaboration. BMJ 1994; 308:81,Diabetes Mellitus: Effect of Aspirin,4. Harpaz D et al. Am J Med 1998;105:494 3. Sacco M et al. Diabetes Care 2003;26:3264 4. Belch J et al. BMJ 2008; 337:a1840 5. Ogawa H et al. JAMA 2008; 300:
41、 2134,p=.04,p 0.001,p0.002,p=NS,p=NS,p=NS,NS=Not Significant,p0.05,Variation in Aspirin Use by Ethnicity: MESA Study (Sanchez DR, Am J Cardiol 2011)Regular use of aspirin (=3X per week) examined in 6,452 White, Black, Hispanic, and Chinese patients without CVD. In 2002, prevalence of aspirin use in
42、those at increased (6-=10%), corresponding prevalences were 53%, 43%, 38%, and 28%. Important racial/ethnic disparities exist for unclear reasons.,Recommendations: Antiplatelet Agents (1),Consider aspirin therapy (75162 mg/day) (C) As a primary prevention strategy in those with type 1 or type 2 diab
43、etes at increased cardiovascular risk (10-year risk 10%) Includes most men 50 years of age or women 60 years of age who have at least one additional major risk factor Family history of CVD Hypertension Smoking Dyslipidemia Albuminuria,ADA. VI. Prevention, Management of Complications. Diabetes Care 2
44、013;36(suppl 1):S32-S33.,Recommendations: Antiplatelet Agents (2),Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk, since potential adverse effects from bleeding likely offset potential benefits (C) 10-year CVD risk 5%: men 50 and women 60 years of age wi
45、th no major additional CVD risk factors In patients in these age groups with multiple other risk factors (10-year risk 510%), clinical judgment is required (E),ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33.,Recommendations: Antiplatelet Agents (3),Use aspirin t
46、herapy (75162 mg/day) Secondary prevention strategy in those with diabetes with a history of CVD (A) For patients with CVD and documented aspirin allergy Clopidogrel (75 mg/day) should be used (B) Combination therapy with aspirin (75162 mg/day) and clopidogrel (75 mg/day) Reasonable for up to a year
47、 after an acute coronary syndrome (B),ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33-S34.,CV death, MI, or stroke (%),Standard Therapy,7.2,Intensive Glucose Lowering,9,6,3,0,6.9,P=0.16,All-cause mortality (%),Standard Therapy,4.0,Intensive Glucose Lowering,9,6,3
48、,0,5.0,P=0.04,Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial,10,251 diabetic patients randomized to intensive glucose lowering (HbA1C 6%) or standard glucose lowering (HbA1C 7.0-7.9%) for 3.5 yearsIntensive glucose lowering does not reduce adverse CV events and increases all-cause mortality,ACCORD Study Group. NEJM 2008;358;2545-59,CV=Cardiovascular, HbA1C=Glycated hemoglobin, MI=Myocardial infarction,
