Diet and Risk of Cardiovascular Disease

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1 Diet and Risk of Cardiovascular Disease Estimating global and regional CVD disease burden March 28, 2011 First Regional Nutrition Conference: Eastern Mediterranean WHO-EMRO and Qatar University Eric L. Ding, PhD Harvard Medical School Harvard School of Public Health

2 Deaths (millions) Projected global deaths (millions): selected specific causes, 2004 to Tuberculosis HIV/AIDS Malaria Diarrhoeal diseases Acute respiratory infections Perinatal causes* Cancers Year Mathers and Loncar 2006 Ischaemic heart disease Cerebrovascular disease Road traffic accidents

3 Demographically and epidemiologically developed regions, GBD 2002 Attributable DALY (% of Regional DALY - Total 214 million) 0% 2% 4% 6% 8% 10% 12% 14% Tobacco High blood pressure Alcohol High cholesterol Overweight and obesity Inadequate fruit and vegetable intake Physical inactivity Illicit drugs Infectious and parasitic Maternal and peri-natal Nutritional deficiency Vascular Cancer Chronic respiratory Neuro-psychiatric Other noncommunicable Intentional injury Unintentional injury Unsafe sex Iron deficiency

4 The Dark Ages (old USDA pyramid)

5 The Classic (OLD) Diet-Heart Hypothesis Saturated fat Cholesterol Polyunsaturated fat Serum Cholesterol Atheromatous Plaque Coronary Artery Narrowing Myocardial Infarction

8 % Change in CHD Types of Fat Intake and CHD Risk Replacing Fat for Carbohydrate: Change in CHD Risk Trans %E 2%E 3%E 4%E 5%E Saturated Monounsaturated Polyunsaturated Hu et al. NEJM 1997

9 Dietary Fats and Blood Cholesterol Replacement of Saturated Fat (10% of total daily calories) with Carbohydrate or Unsaturated Fat LDL-C HDL-C LDL/HDL TG CARB - 8% -10% +2% +14% MONO - 10% -3% - 6% +2% POLY - 12% -4% - 8% -2% Monounsaturated oils: Olive, Canola, Nuts Polyunsaturated oils: Corn, Soy, Sunflower, Safflower From Mensink & Katan. Arterioscl Thromb 1992;8:911

10 8.063

11 Cis Configuration Trans Configuration

12 Effect of Trans and Saturated Fat (10% E) on Blood Lipids (vs Monounsaturated fat) (Mensink & Katan, 1990) Trans fat Saturated fat Total cholesterol +6% +12% LDL cholesterol +14% +18% HDL cholesterol -12% 0% LDL/HDL ratio +29% +18% also, monounsaturated and polyunsaturated fats lower LDL (bad cholesterol) and increase HDL (good cholesterol)

13 Relative Risk of CHD by Trans fat or Polyunsaturated Fat in NHS Relative Risk Ref Q5 Q4 Q3 Q2 Q1 Quintiles of Trans Q5 Q Q3 Poly Q1 & Q2 Hu et al, 1997

14 Nurses Health Study Replacing Saturated or Trans Fat: Change in CHD N=80,052 women, 939 cases. Adjusted for CHD risk factors, dietary monounsaturated, polyunsaturated and trans fatty acids. Sat Carb (5% Energy) Sat Mono (5% energy) Sat Poly (5% Energy) Trans Cis Unsat (2% Energy) Change in CHD Risk (%) Hu, F et al. N Engl J Med 1997

15 Multivariate RR Dietary Fats and Risk of Type 2 Diabetes 1.4 (Salmeron et al, 1999) Saturated Fat Mono Poly Trans 0.6 Q1 Q2 Q3 Q4 Q5 Quintiles of Fat Intake

16 Nuts Albert, Ellsworth, Brown, Hu, Fraser, Fraser, Relative Risk

17 Relative Risk Nut Consumption and Reduced Risk of Type 2 Diabetes P for Trend < Never/Almost never <Once/w k 1-4 Times/w k >=5 Times/w k Intake of Nuts Jiang JAMA 2002

18 N-3 Polyunsaturated Fatty Acids Fish oils, and alpha linolenic acid from vegetables strongly associated with lower fatal CHD incidence. Consistency among clinical trials and epidemiology Sources: soy, canola oils, vegetables fatty fish (e.g. salmon, sardines)

19 Nurses Health Study Alpha Linolenic Acid and CHD RR Fatal CHD % % Median Intake (% Energy) -33% 1. 4 Nonfatal MI % -8% -6% P- trend = 0.01 P- trend = 0.50 NS %.5-45% N=76,283 women, 232 CHD deaths, 597 nonfatal MI. Adjusted for CHD risk factors, dietary saturated fat and linoleic acid Hu F et al. Am J Clin Nutr 1999;69:8

20 9.129 Multivariate Relative Risk of Sudden Cardiac Death (Albert et al., 2002) P = Quartile of blood N-3 fatty acid (Mean, % of fatty acids)

21 Dietary n-3 Fatty Acids and Sudden Death n-3 Fatty Acid Intake No Seafood: Seafood (N-3): Quartile Mean mg/d Cases n=295 Controls n=398 I II III IV OR (95% CI) Risk Reduction Siscovick DS. JAMA

22 Meta-Analysis of 36 Randomized Controlled Trials of Fish Oil and Blood Pressure 0 Systolic BP Diastolic BP BP Reduction with Fish Oil Intake * *p< * Among adults > age 45 years. Geleijnse JM. J Hypertens 2002

23 Meta-Analysis of Fish Intake and CHD Death in 13 Cohorts Totaling 222,364 Individuals He K. Circulation 2004

24 Relative Risk Fruits and Vegetables and Cardiovascular Disease P-value, test for trend= < Fruit/Vegetable Intake (Serving/Day) (Hung et al., 2004)

25 Relative Risk Fruits and Vegetable Intake and Risk of Total Cancers P-value, test for trend= < Fruit/Vegetable Intake (Serving/Day) (Hung et al., 2004)

26 Milling of Grains Whole Grain All parts milled Refined Grain Endosperm is milled Germ & Bran Source: General Mills

27 Carbohydrate Quality: Glycemic Index (GI)

29 Study Prospective studies of whole grains and CVD Liu, 2000, MI Liu, 1999, Stroke Fraser 1992 Jacobs, 1997 Relative Risk

30 Multivariate relative risk of type 2 diabetes per 1 serving/d increment in whole-grains PLos Medicine 2007

31 GI Values Glucose 100 Lactose 46 Baked Potatoes 93 Orange Juice 46 French Fries 75 Grapes 46 Graham Crackers 74 Pasta 39 White Rice 72 Apple 38 White bread 70 Skim milk 32 Dark bread 69 Whole milk 27 Sucrose 65 Fructose 23 Carrots 49 Peanuts 14

32 Glycemic Load (GL) GL= GI i x CHO i x FPD i GI i = Glycemic index for food i CHO i = grams of carbohydrate per serving of food i FPD i = frequency of servings of food i per day during the past year Each unit of glycemic load represents the equivalent of one gram of carbohydrate from white bread

33 Risk of CHD According to Glycemic Load Nurses Health Study RR of CHD Glycemic Load Quintiles Liu 2000

34 Risk of CHD According to Glycemic Load Nurses Health Study RR of CHD Same study just now stratified by BMI Glycemic Load Quintiles Liu 2000

35 Glycemic Load Intake and Risk of Stroke, stratified by BMI (Oh et al. 2005)

36 Glycemic Load Intake and Risk of Type 2 Diabetes, stratified by BMI (Villegas et al, 2007)

37 Relative Risk of Type 2 Diabetes by Different Levels of Cereal Fiber and Glycemic Load WOMEN Relative Risk High Medium Low 1 (ref) High >5.8 g/day Medium Low <2.5 g/day g/day Cereal Fiber > <143 Glycemic Load (Salmeron et al,1997)

38 Relative Risk Sugar-Sweetened Soft Drinks and Type 2 Diabetes, NHS <1/mo 1-4/mo 2-6/wk >=1/d Sugar-sweetened soft drink consumption multivariate adjusted P<0.001 for trend multivariate + BMI Schulze et al. JAMA 2004

39 Forrest plot of studies evaluating SSB consumption and risk of T2DM, comparing extreme categories of intake (random-effects estimate). Montonen, 2007 Paynter Men, 2006 Paynter Women, 2006 Schulze, 2004 Palmer, 2008 Bazzano, 2008 Odegaard, 2010 Nettleton, 2009 de Koning, 2010 Combined 1.26 (1.12, 1.41) RR Omitting 3 studies that adjusted for BMI and total energy: Random effects: RR 1.28 (1.13, 1.45) Malik et al. Diabetes Care 2010

40 The Vast Majority Of Cardiovascular Disease In Industrialized Countries Is Caused By Nutrition And Lifestyle

41 Primary Prevention of CVD: 5 Attributes to Define Low-Risk 1. Diet in upper 40% of cohort Good fat: Low saturated and trans fat, high polyunsaturated fat, high fish oil Good carbohydrates: Low glycemic load, high fiber (whole grains) High folate (vegetables, fruit) 2. Not currently smoking 3. Moderate alcoholic beverage drinking 1 drink every other day to daily 4. Regular Exercise 1/2 hour daily (e.g. 2 miles/hour walking) 5. Body mass index <25 kg/m 2 (optimal <21 kg/m 2 ) Stampfer MJ, et al. N Engl J Med. 2000;343:16-22.

42 RISK OF CHD IN LOW-RISK GROUPS IN THE NURSES HEALTH STUDY, THREE LOW-RISK FACTORS 1. Diet score in upper 2 quintiles 2. Nonsmoking 3. Moderate to vigorous exercise 30 min/day Percentage of Women in Group No. of CHD Events Relative Risk (95%CI) Population Attributable Risk (95% CI) ( ) (42-64)

43 RISK OF CHD IN LOW-RISK GROUPS IN THE NURSES HEALTH STUDY, FOUR LOW-RISK FACTORS 1. Diet score in upper 2 quintiles 2. Nonsmoking 3. Moderate to vigorous exercise 30 min/day 4. Body-mass index < 25 Percentage of Women in Group No. of CHD Events Relative Risk (95%CI) Population Attributable Risk (95% CI) ( ) (46-76)

44 RISK OF CHD IN LOW-RISK GROUPS IN THE NURSES HEALTH STUDY, Percentage of Women in Group 3.1 FOUR LOW-RISK FACTORS 1. Diet score in upper 2 quintiles 2. Nonsmoking 3. Moderate to vigorous exercise 30 min/day 4. Body-mass index < Alcohol 5 g/day No. of CHD Events 5 Relative Risk (95%CI) 0.17 ( ) Population Attributable Risk (95% CI) 82 (58-93)

45 Risk of Type 2 Diabetes in Low Risk Groups In the Nurses Health Study, Percentage of Women in Group 3.4 FIVE LOW-RISK FACTORS 1. Diet score in upper 2 quintiles 2. BMI<25 3. Moderate to vigorous exercise 30 min/day 4. Nonsmoking 5. Alcohol 5 g/day No. of diabetes Events 10 Relative Risk (95%CI) 0.09 ( ) Population Attributable Risk (95% CI) 91% (83-95) Hu et al. NEJM 2001

46 How do we estimate country/regional disease burden more formally?

47 Burden of disease from leading risk factors 2002 WHO report Underweight Unsafe sex High blood pressure Tobacco Alcohol Unsafe water, sanitation, and hygiene High cholesterol Indoor smoke from solid fuels Iron deficiency Overweight and obesity Zinc deficiency Low fruit and vegetable intake Vitamin A deficiency Physical inactivity Lead exposure Illicit drugs Occupational risk factors for injury Contaminated health care injections Lack of contraception Childhood sexual abuse High-mortality developing Lower-mortality developing Developed 0% 1% 2% 3% 4% 5% 6% 7% 8% 9% 10% DALYs (% of global DALYs - Total 1.46 billion)

48 Population Attributable Fraction (PAF) Proportional reduction in population disease or mortality that would occur if exposure to a risk factor were reduced to an alternative exposure scenario (, ceteris paribus)

49 Graphical notation used 20,000 deaths 15,000 deaths 5,000 deaths No risk factor exposure All deaths from a disease (e.g. lung cancer) Deaths avoided if there had not been exposure to a risk factor (e.g. smoking) Risk-factor-attributable deaths = population attributable fraction total deaths

50 Attributable fraction versus attributable deaths Country B Country A Country C 10,000 deaths 20,000 deaths 20,000 deaths 2,500 (25%) 5,000 (25%) 2,000 (10%) Risk-factor-attributable deaths = population attributable fraction total deaths

51 Exposure change and PAF in the same population Country A Exposure reduced to zero Country A Current exposure Country A Exposure reduced by ~60% 15,000 20,000 17,000 5,000 (25%) 2,000 (11%)

52 Total attributable deaths from all diseases Disease 1 20,000 deaths 25% (5,000) Total Attr deaths = 5, ,000 = 7,000 Attr deaths disease 1 = PAF1 total deaths disease 1 = 5,000 Disease 2 10,000 deaths 20% (2,000) Attr deaths disease 2 = PAF2 total deaths disease 2 = 2,000

53 Multiple attributable risk factors Mortality and morbidity can be attributed to disease outcomes risk factors Occupational exposures 10% Smoking 71% Air pollution 7% Poverty or education 1.2 million lung cancer deaths (of 56 million global deaths)

54 Inputs to estimating risk-factor-attributable deaths Determinants of Population Attributable Fraction (PAF) Exposure level / distribution Proportional increase in disease/mortality per unit exposure (relative risk) Alternative (counterfactual) exposure Determinants of absolute effects Proportional effect (PAF) Total (or background ) disease-specific mortality

55 Population Attributable Risk Fraction: Formula for binary exposure (baseline no-risk) PAF = P(RR-1) P(RR-1)+1

56 Population Attributable Risk Fraction: Formula for multi-category/continuous exposures PIF n P RR P RR i i i i i 1 i 1 n i 1 P i n RR i

57 Relative Risk for continuous exposure distribution (baseline: no risk) RR of IHD Usual SBP (mmhg)

58 Continuous exposure distribution 10% Baseline (counterfactual) Current distribution 7.5% 5% Percent population 2.5% Usual SBP (mmhg) 0 %

59 Continuous exposure distribution + RR % RR of IHD Baseline Current distribution 7.5% 5% Percent population % Usual SBP (mmhg) 0 %

60 Continuous exposure distribution % RR of IHD Baseline RR1 Current distribution 7.5% 5% Percent population % P Usual SBP (mmhg) 0 %

61 Continuous exposure distribution % RR of IHD Baseline Current distribution 7.5% 5% Percent population % Usual SBP (mmhg) 0 %

62 Should the baseline/counterfactual distribution be a constant level or a distribution itself? 10% Baseline Current distribution 7.5% 5% Percent population 2.5% Usual SBP (mmhg) 0 %

63 % of people The prevention paradigm A large number of people at a small risk may give rise to more cases of disease than a small number who are at a high risk." (Rose, Sick individuals and sick populations, 1985) Minimum Current Diastolic blood pressure (mmhg)

64 Attributable DALYs (000s) Distribution of burden attributable to risk factors by exposure levels 7,000 6,000 Hypertension 4000 Hypercholesterolaemia 3000 Obesity 5, , ,000 2, , Systolic blood pressure (mmhg) Cholesterol (mmol/l) Exposure levels Body mass index (kg/m2) Rodgers et al PLoS Medicine 2004

65 Distributional transition and cardiovascular disease risk in Finland and Japan Cholesterol distribution Coronary mortality Blood pressure distribution Stroke mortality

66 Demographically and epidemiologically developed regions, GBD 2002 Attributable DALY (% of Regional DALY - Total 214 million) 0% 2% 4% 6% 8% 10% 12% 14% Tobacco High blood pressure Alcohol High cholesterol Overweight and obesity Inadequate fruit and vegetable intake Physical inactivity Illicit drugs Infectious and parasitic Maternal and peri-natal Nutritional deficiency Vascular Cancer Chronic respiratory Neuro-psychiatric Other noncommunicable Intentional injury Unintentional injury Unsafe sex Iron deficiency

67 Lower-mortality developing regions, GBD 2002 Attributable DALY (% of Regional DALY - Total 408 million) 0% 1% 2% 3% 4% 5% 6% 7% Alcohol High blood pressure Tobacco Underweight Overweight and obesity High cholesterol Inadequate fruit and vegetable intake Indoor smoke from solid fuels Infectious and parasitic Maternal and peri-natal Nutritional deficiency Vascular Cancer Chronic respiratory Neuro-psychiatric Other noncommunicable Intentional injury Unintentional injury Iron deficiency Unsafe water, sanitation, and hygiene

69 Micha et al. Poster AHA NPAM/EPI 2011

70 Poster AHA NPAM/EPI 2011

71 Countries with national diet data: GBD Nutrition Working Group

72 US Attributable Mortality to Risk Factors PAR attributable #deaths if reliable national vital status registry available, such as the U.S. Danaei, Ding, Mozaffarian Ezzati, PLoS Medicine 2008.

73 [GBD 2010 results forthcoming, expected later this year]

74 Disease Burden Avoidable disease burden: Different Futures Exposure reduction at T 0 0% Unavoidable Not caused by the risk factor of interest 100% (lowest risk) Past T 0 Time Future

75 No

76 Thank you Eric L. Ding

Cardiac patient quality of life. How to eat adequately?

Cardiac patient quality of life How to eat adequately? François Paillard CV Prevention Center CHU Rennes JESFC, Paris, 17/01/2013 Mrs. L. 55 yrs, Coronary artery disease, normal weight, mild hypertension