1. “CV risk factors and Lifestyle Modification among South Asians – A call to action” Dr. Sonia Anand MD, PhD Associate Professor of Medicine McMaster University

2. Outline Cardiovascular disease among South Asians in Canada Role of Diet Abdominal Obesity Role of Genetics Prevention Strategies

3. Changes in Risk Factors with Migration

4. North America Australia Africa Asia Europe Middle East South and Central America Excess Coronary Heart Disease in South Asian Migrants

5. Mortality for CHD and Cancer Age 35 – 74 (1979-1993) Sheth T et al, CMAJ 1999

6. Data from UK and others ↑ type 2 diabetes ↓ Abdominal obesity ↓ HDL cholesterol ↑ Triglycerides ↑ Lipoprotein (a) ++ other causes ?????

7. South Asian ChineseEuroAboriginal N342317326301 Age49.447.451.353.1 Sample Random Surname Random Surname Random Surname Random Band List LocationHamilton Toronto Edmonton Six Nations Brantford Time1996 to 19981998-00 Study of Health Assessment and Risk in Ethnic groups (SHARE) SHARE 99/10/12 Anand et al SHARE Lancet 2000/1

8. Main Findings in SHARE CVD ATH Thrombosis Insulin Resistance Abdominal Adiposity Dietary Intake Physical inactivity Genetics

9. Insulin Resistance FFAs TG Apo B Glucose Insulin FFAs Expanded Visceral AT 1. Liver Atherogenic dyslipidemia Soft Lipid Risk Core Impaired fibrinolysis IL-6 TNF 2. 3. Adipokines Glucose 4. Skeletal Muscle X IMCL Mitochondria l Dysfunction Adiponectin Leptin Insulin resistance Beta cell dysfunction Coronary Artery

10. Age-Adjusted Prevalence of Metabolic Syndrome by Ethnic Group Age-Adjusted

12. Razak et al Circ 2005 BMI=21 BMI = 30 Relationship of Glucose Factor to Body Mass Index Among South Asians, Chinese, Aboriginal and Europeans

13. You are what you eat! +

14. Dietary Factors in South Asians in Canada Consume excess calories from carbohydrates Low protein intake Higher reported folate intake, low serum folate Higher vegetarianism Higher trans fats

15. SHARE- Nutrition South AsiansChineseEuro N 173167185 Age 46.345.847.7 Calories/Day 191118982072 % Vegetarian 18.82.10.6 Carbohydrates g/day 298.8*240.7269.5 Sugar g/day 11.2*6.98.9 Protein g/day 70.1*100.5*78.0

16. Commonest Sources of Carbohydrate by Ethnic Group RankSouth AsiansChineseEuropean 1Roti, ChapatiRice, Sticky RiceBanana 2Rice, BoiledBananaOrange or Grapefruit juice 3BananaCitrus FruitBread Rolls

17. The effect of Carbohydrate intake on HDL-C.13 mmol/L In HDL for every 100 gld In CHO Tertile CARBOHYDRATE INTAKE * Adjusted for age, sex, ethnicity, physical activity, smoking, WHR, Etoh, total energy, protein, fiber, (excluded diabetes, any CVD) * P for trend <0.001 HDL-C mmol/L * Merchant et al J Nutr 2005

18. Stronger in women…. Note: more servings of sugar containing soft drinks, juices, and snacks associated with HDL P trend = 0.06 (men) P trend =.01 (women)

19. Protein Intake and Abdominal Obesity Substituting a modest amount of protein for carbohydrate may reduce abdominal obesity Physical Activity is inversely associated with abdominal obesity Merchant et al J Nutr 2005 * Independent of age, sex, BMI, height, smoking, physical activity, alcohol, and total ebnergy, and ethnicity

20. Protein Intake vs WHR

21. RankSouth AsiansChineseEuropean 1Roti, ChapatiFish SoupChicken 2Yogurt CurdChickenGround Beef 32% MilkPork2% Milk Commonest Protein Sources

22. SHARE- Fried Foods South Asians ChineseEuro Fried Foods (# serv./week) 4.83.95.0 Total Fat g/day59.170.3*61.8 Saturated Fat g/day19.617.3*21.6 Trans Fats (g)0.340.270.56

23. P/S Ratio Polyunsaturated to Saturated Fat Ratio ↓0.2 = ↑ RR of CHD = 10-20%

24. RankSouth AsiansChineseEuropean 1Roti, ChapatiFish SoupCheese, regular fat 22% MilkStirred Fried Pork or Beef Ground Beef 3Yogurt CurdChicken2% Milk 4NutsPorkFried Egg Commonest Sources of Total Fat

25. SHARE- Fish South Asian ChineseEuro Fish (# serv./week)1.16.3*1.6 Omega-3 FA0.130.760.04 Omega-6 FA0.370.420.31

26. Ethnic Differences in Folate South Asian ChineseEuro N283275260 Homocysteine * (umol/L) 10.58.79.7 Dietary Folate (ug)385*291352 Serum Folate (nmol/L)18.922.0*21.7 *P<0.001

27. South AsiansChineseEuropean Coffee4.56.120 Tea11.70.365.49 White/Red Wine/Spirits 1.30.523.49 Servings of Fresh Fruit/week 13.811.613.7 Beverages – Servings/week

28. INTERHEART DIETARY ANALYSIS Methods – 6,530 cases and 10,792 controls –19 items food groups questionnaire Dietary Patterns: –Prudent diet: raw and cooked vegetables, legumes and fruits –Oriental diet: tofu, soy sauce and green leafy vegetables –Western diet: dairy, fried foods and meats (high in saturated fats)

29. Adjustment factors Age, sex, region, BMI, WHR, physical activity, alcohol intake, smoking, apoB/apoA1, psycho-social factors, and education Iqbal R et al 2006 INTERHEART: Relative Risk of AMI by Dietary Type ↓ 24% ↑ 29%

30. How active Are We? * SHARE 2005 %

31. Human Genome Program, U.S. Department of Energy, Genomics and Its Impact on Medicine and Society: A 2001 Primer, 2001

32. Clues that suggest South Asians have a Genetic Propensity to CHD Family history of premature MI suggests increased genetic susceptibility Increased propensity to develop type 2 diabetes Lower BMI threshold to develop glucose metabolic abnormalities Risk factors apparent in children

33. Energy Intake Energy Expenditure IR Energy Partitioning Favoring Fat Accretion Adipogenesis Genetic Predisposition Obesity The search for Genes: Thrifty, Gluttonous, or Slothful… Energy Conservation Adapted from Bouchard 2003

34. Population Genetic Studies have yielded few True Positives GenePolymorphismConditionFrequency Factor V Leiden Arg506GlyDVT1.5% APO EE 2/3/4Alzheimers Disease 16-24% PPAR Gamma Pro12 ProType 2 Diabetes85%; RR=1.24

35. Ethnic Group South AsianChineseEuropean Pro12Pro75%93%78% Pro12Ala23%7%20% Ala12Ala1.5%01.4% Ethnic Differences in SNP frequency PPARg Pro12Ala

36. Scanning the Genome Lp(a) Health Status DiabetesLDL Smoking Cholesterol Blood Pressure ObesityExercise Triglycerides Homocysteine Fibrinogen Stress Nutrition Insulin GENES

37. Obesity Predisposition ResistantProne BMI Adapted from Ravussin and Bouchard, 2000 “Obesogenic” environment Restrictive environment Defective Biology

38. Prevention of weight gain If overweight or obese avoid rapid reductions in weight with intensive lifestyle change (regain occurs in 90%) In patients in early 20’s – advise to prevent or minimize weight gain Modest energy intake and regular activity

39. Specific Issues Relevant to Women: Abdominal Obesity “the rolls” are not stylish! Abdominal obesity increases in Post-menopausal women Regular Physical Activity is essential to maintain weight Mothers watch your children- prevent childhood obesity, encourage exercise Mothers watch your cooking – increase raw and lightly cooked vegetables, avoid ghee, increase protein, decrease carbohydrate

40. Benefits of Physical Activity Physical activity has protective effects: –Lowers LDL (bad) cholesterol and triglycerides –Increases HDL (good) cholesterol –Reduces body weight –Lowers blood pressure Lack of physical activity has the reverse effects

41. Walking Walking is a popular and the most commonly reported leisure activity Walking is accepted and easily accessible to everyone 30 minutes of activity corresponds to approximately 3000- 4000 steps/day Goal is 30 minutes/day of walking or 10,000 steps/day

42. Women who increase their physical activity (30 min x 5 days) after age 65 can lower their risk of death by nearly 50% (Women’s Health Study) Moderate physical activity can add 1.5 years of life (free of heart disease) (Netherlands) Substantial Gains from Modest levels of Physical activity

43. Summary South Asians (including women) are among the highest risk group for early CHD in the world Prevention must start in childhood “Turn off the Genetic Effects” by regular exercise, lower carbohydrate modest protein diet, prevention of abdominal obesity, Liberal use of proven medical therapies

44. PPAR  Pro12Ala PPARs –adipogenesis, lipid metabolism, glucose metabolism –nuclear receptors for various ligands fatty acids glitazones (PPAR  ), fibrates (PPAR  Pro12Ala SNP –25% frequency 1 –T2D (relative risk, RR = 0.79) 1 Pro12Pro (wild type) –85% frequency 1 –T2D (relative risk, RR = 1.25) 1 May influence 25% of the risk of T2D 1. Altshuler et al. The common PPAR  Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genetics 2000. 26: 76-80.