1. Best Diet for CHD Prevention
Dr. Thomas G. Allison
Mayo Clinic Rochester

2. Fatty Streaks in Aorta of 19-Year Old Male

3. Advanced Lesion with Large Lipid Core

4. Plaque Rupture with Torn Cap

6. Major Statin Trials % with CAD event LDL-C (mg/dL) 25 Secondary 20
PROVE IT 25 4S
Secondary
HPS 20
Mixed 15
PROSPER
% with CAD event
Primary
LIPID
CARE 10
WOSCOPS
TNT
In primary prevention trials, reduction of LDL-C levels with statins was associated with a reduction in the risk of CAD events, both in patients with elevated (WOSCOPS) and average (AFCAPS/TexCAPS) LDL-C serum concentrations.
Similarly, in secondary prevention trials, reduction of LDL-C levels with statins was associated with a reduction in the risk of CAD events, both in patients with elevated (4S) and average (CARE, LIPID) LDL-C serum concentrations. 5
ASCOT-LLA
JUPITER
AFCAPS 50 70 90
110
130
150
170
190
210
LDL-C (mg/dL)
Illingworth DR. Management of hypercholesterolemia. Med Clin North Am. 2000;84:23-42.

8. Intravascular Ultrasound Images at Baseline and Follow-up
REVERSAL Trial
Intravascular Ultrasound Images at Baseline and Follow-up
Nissen, S. E. et al. JAMA 2004;291:

9. Limitations to Pharmacologic Lipid Management
Cost of treatment
Not an issue if generic drug will control LDL-C
Treatment cost ~ $1000 per year if non-generic agent needed
Not all patients tolerant of statins
Myalgia most common complaint (5-15%)
Alternative drugs (intestinal agents, niacin, fibrates) have limited effect on LDL-C, limited outcome data
Benefits of add-on drug therapy not established

10. International Comparisons
2002 AHA Heart and Stroke Statistical Update
(Men ages 35-74)
International rates not due to differences in statin therapy rates!

11. Diets and CAD: What’s the Evidence?
Dietary therapy can be an alternative to pharmacologic management of lipids in primary prevention
Important adjunctive therapy in secondary prevention
What is the best diet for CHD prevention?

12. East Finland

13. Mortality from Coronary Heart Disease Men 35-64 Years (1969-1994)
800
Cardiac death rates have dropped by 75%!
700
600
Now 80%
500
Per 100,000
North Karelia
400
300
All Finland
200
100
Puska P: Cardiovasc Risk factors 6:203-10, 1996 CP

14. Trends in Women’s Lifestyles 1980-82 versus 1992-94
31% decline in CHD incidence across all ages
41% decrease in smoking (27%  16%)
Diet changes
31% decrease in trans fatty acid intake
69% increase in P/S ratio
90% increase in cereal fiber
180% increase in -3 fatty acids
12% increase in folate
Nurses’ Health Study -- Hu et al: NEJM 2000;343:

15. Trends in Women’s Lifestyles 1980-82 versus 1992-94
38% increase in overweight (BMI>25)
average BMI 24.5  26.1 kg/m2
22% increase in glycemic load

16. Regional Diets with Low CHD Rates
Seventh Day Adventist
Japanese
Rural Chinese
Eskimo
Mediterranean

17. Crete

18. Adherence to Mediterranean Diet and Survival in a Greek Population
Prospective, population-based investigation of CHD mortality versus diet
22,043 healthy adults in Greece
44-month follow-up
Diet assessed by 10-point scale (0-9)
vegetables, legumes, fruits and nuts, cereals, fish, alcohol, monounsaturated/saturated fat ratio (+)
meat, poultry, dairy products (-)
Trichopoulou A et al, NEJM 2003:348:

19. Results Two single nutrients predicted CHD death
Fruits and nuts: +200 g/day = 18% reduction
Monounsaturated/saturated fat ratio: = 14% reduction
2-point increase in Mediterranean diet score
25% reduction in total mortality
33% reduction in CHD mortality
24% reduction in cancer mortality
Adjusted for age, sex, WHR, energy expenditure, smoking, BMI, potato and egg consumption, and total caloric intake

20. Epidemiologic Studies
Inherently flawed
Problems with ascertainment of both independent (diets) and dependent (mortality, heart attacks, etc.) variables
Not all non-dietary variables can be measured (and none controlled)
Assumes constancy of exposure to dietary factors

21. Diet-Heart Studies with Outcomes
Location N Year f/u
England (Rose) y
Middlesex y
Oslo y
London y
Sydney y
DART y
Moradabad y
LHT (invite) y
Leon y
Intervention
control v corn oil v olive oil
control v low fat
control v low fat + PUF
control v soya-bean oil
low fat v fish v fiber
low fat v fruit/veg+fish+fiber
control v ultra-low fat
control v Mediterranean

23. Lifestyle Heart Trial
Randomized invitational design (recruitment in ~1987)
28 experimental patients, 20 usual care
Intervention:
vegetarian, low fat diet (10% fat, 5 mg cholesterol/day)
smoking cessation, moderate exercise, stress management
Ornish et al: Lancet1990;336:

24. No calorie restriction
Original Dean Ornish Plan
No calorie restriction
Moderate exercise
Stress reduction
Smoking cessation
Fats (<10%)
Nonfat dairy products – yogurt, cheese, egg whites
Nonfat products – cereal, soups, tofu, crackers, egg beaters
Whole grain – corn, rice, oats, wheat, etc
Beans and legumes
Ban
All oils
All meats
Olives
Avocados
Nuts – seeds
High or low fat products
Sugar – syrup – honey
Alcohol
Fruits
Vegetables CP

25. Lifestyle Heart Trial 1-Year Results
Not powered (or randomized) for clinical events

26. Lyon Heart Study 423 patients randomized post-MI 1988-92
Mediterranean diet vs “prudent diet” (Step 1) prescribed by patients’ physicians
Planned 5-year follow-up
Study terminated early (4 years) due to favorable interim analysis -- final report on 423 patients
de Lorgeril et al, Circ 1999;99:

27. The Traditional Healthy Mediterranean Diet Pyramid
Meat
Sweets
Eggs
Poultry
Fish
Cheese & yogurt
Olive oil
Fruits
Bread, pasta, rice, couscous, polenta, other whole grains & potatoes
Daily physical activity
Daily beverage recommendations
6 glasses of water
Wine in moderation
Vegetables
Beans, legumes & nuts
Monthly
Weekly
Daily
2000 Oldways Preservation & Exchange Trust CP

28. Lyon Heart Study - Lipids

29. Lyon Heart Study Results consistent with DART and Moradabad trials
p<.0002
p<.0001
p<.0001
Results consistent with DART and Moradabad trials

30. Search for the Perfect CHD Prevention Diet
The Lifestyle Heart Trial achieved marked LDL-C lowering, but adversely affected HDL-C
The Leon Heart Study lowered CHD risk without affecting lipid levels
Can we design a diet that lowers LDL-C without lowering HDL-C while providing the heart protective nutrients?

31. Therapeutic Lifestyle Changes in LDL-Lowering Therapy
Major Features
TLC Diet (Step 2+)
Reduced intake of cholesterol-raising nutrients (same as previous Step II Diet)
Saturated fats <7% of total calories
Dietary cholesterol <200 mg per day
LDL-lowering therapeutic options
Plant stanols/sterols (2 g per day)
Viscous (soluble) fiber (10–25 g per day)
Weight reduction
Increased physical activity
NCEP

32. Other Features of TLC Diet
Nutrient Recommended Intake
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories
Total fat 25–35% of total calories
Carbohydrate 50–60% of total calories
Fiber 20–30 grams per day
Protein Approximately 15% of total calories
Total calories (energy) Balance energy intake and expenditure to maintain desirable body weight/ prevent weight gain

33. Dietary Portfolio 46 healthy, hyperlipidemic adults randomized
Low saturated fat diet
Low saturated fat diet + Lovastatin 20 mg/day
Diet portfolio (based on Step 2+)
Phytosterols 1.0 g/1000 kcal
Soy protein 21.4 g/1000 kcal
Viscous fiber 9.8 g/1000 kcal
Almonds 14 g/1000 kcal
4-week follow-up
Jenkins DJA et al, JAMA 2003:290:

35. Results

36. Summary: Best CHD Prevention Diet
Low in saturated fat and cholesterol
High in monounsaturated fat
Fish 2+ servings per week
Or omega-3 fatty acids supplement
Fresh fruits and vegetables 7+ servings/day
Whole grains in place of refined flour and sugar

37. Best CHD Prevention Diet
Nuts 14+ grams/1000 kcal
Added soy protein, soluble fiber, phytosterols
Low glycemic index, especially if overweight
Calorie control should be automatic
Low caloric density CHO’s
Satiety from monounsaturated fats, proteins
Highly palatable
Variety of foods and seasonings

38. strategy to reduce cardiovascular disease by more than 75%
BMJ  2004;329:  (18 December), doi: /bmj
The limits of medicine
The Polymeal: a more natural, safer, and probably tastier (than the Polypill)
strategy to reduce cardiovascular disease by more than 75%
Oscar H Franco, scientific researcher1, Luc Bonneux, senior researcher2, Chris de Laet, senior researcher1, Anna Peeters, senior researcher3, Ewout W Steyerberg, associate professor1, Johan P Mackenbach, professor1
1 Department of Public Health, Erasmus MC University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands, 2 Belgian Health Care Knowledge Centre (KCE), Wetstraat 155, B-1040, Brussels, Belgium, 3 Department of Epidemiology and Preventive Medicine, Monash University Central and Eastern Clinical School, Melbourne, Australia

39. Ingredients
Percentage reduction (95% CI) in risk of CVD
Source
Wine (150 ml/day)
32 (23 to 41)
Di Castelnuovo et al (MA)6
Fish (114 g four times/week)
14 (8 to 19)
Whelton et al (MA)7
Dark chocolate (100 g/day)
21 (14 to 27)
Taubert et al (RCT)8
Fruit and vegetables (400 g/day)
John et al (RCT)10
Garlic (2.7 g/day)
25 (21 to 27)
Ackermann et al (MA)11
Almonds (68 g/day)
12.5 (10.5 to 13.5)
Jenkins et al (RCT),15 Sabate et al (RCT)16
Combined effect
76 (63 to 84)

40. Other Aspects of Polymeal
Men at age 50 would live an average of 6.6 years longer
Women at age 50, 4.8 years longer
Cost of polymeal estimated at $28.10/week
Addition of other components such as oat bran or olive oil would only enhance effect
No obvious contraindications to combining polymeal with polypill (or any subset of components)

42. Weight Loss Controversy
Americans have substituted refined CHO’s for fats over the past 20 years
Linked to obesity
Low CHO versus low fat for weight loss
Atkins versus Ornish
Much speculation, many popular books
Published data only in past 4-5 years
Does losing weight necessarily mean lowering CHD risk?

43. Effect of Varying Fat, Protein, and CHO Content on Weight Loss
811 overweight adults randomized to 3 weight loss diets for 2 years
Varying content: fat protein CHO
Diet % 15% 65%
Diet % 25% 55%
Diet % 15% 45%
Diet % 25% 35%
750 kcal per day caloric deficit
Sacks FM et al. NEJM 2009;360:

47. Bon Appetit!

49. Comments?
Questions?