Best Diet for CHD Prevention
Dr. Thomas G. Allison
Mayo Clinic Rochester
Fatty Streaks in Aorta of
19-Year Old Male
Advanced Lesion with Large
Lipid Core
Plaque Rupture with Torn Cap
% with CAD event
Major Statin Trials
PROVE IT
25
4S
Secondary
HPS
20
Mixed
PROSPER
15
CARE
10
Primary
LIPID
WOSCOPS
TNT
ASCOT-LLA
5
JUPITER
AFCAPS
0
50
70
90
110
130
150
LDL-C (mg/dL)
170
190
210
SIMVASTATIN: CAUSE-SPECIFIC MORTALITY
Cause of
death
STATIN
(10269)
PLACEBO
(10267)
CHD
577
701
Other vascular
214
242
791
(7.7%)
943
(9.2%)
Neoplastic
352
337
Respiratory
93
111
Other medical
76
91
Non-medical
16
21
537
(5.2%)
560
(5.5%)
1328
(12.9%)
1503
(14.6%)
ALL VASCULAR
ALL NON-VASCULAR
ALL CAUSES
Risk ratio and 95% CI
STATIN better STATIN worse
17% SE 4.4
reduction
(2P<0.0002)
5% SE 5.9
reduction
0.4
0.6
0.8
1.0
1.2
12% SE 3.5
reduction
(2P<0.001)
1.4
REVERSAL Trial
Intravascular Ultrasound Images at Baseline and Follow-up
Nissen, S. E. et al. JAMA 2004;291:1071-1080.
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
International Comparisons
2002 AHA Heart and Stroke Statistical Update
CHD Death Rates/100,000
(Men ages 35-74)
Russia
638
420
Hungary
USA
202
China - Urban
100
France
87
Japan
57
China - Rural
54
44
Korea
0
100
200
300
400
500
600
700
International rates not due to differences in statin therapy rates!
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?
East Finland
Mortality from Coronary Heart Disease
Men 35-64 Years (1969-1994)
800
700
Cardiac death rates
have dropped by 75%!
600
Per
100,000
Now 80%
500
North
Karelia
400
300
200
All
Finland
100
Puska P: Cardiovasc Risk factors 6:203-10, 1996
CP999299-39
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;343:530-537
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
Regional Diets with Low CHD Rates
•
•
•
•
•
Seventh Day Adventist
Japanese
Rural Chinese
Eskimo
Mediterranean
Crete
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 2003:348:2599-2608
Results
• Two single nutrients predicted CHD death
– Fruits and nuts: +200 g/day = 18% reduction
– Monounsaturated/saturated fat ratio:
+0.5 = 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
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
Diet-Heart Studies with Outcomes
Location
N Year f/u
England (Rose) 80 1965 2y
Middlesex
264 1965 5y
Oslo
412 1966 5y
London
393 1968 5y
Sydney
458 1978 5y
DART
2033 1989 2y
Moradabad
505 1992 1y
LHT (invite)
48 1998 5y
Leon
423 1999 4y
Intervention
control v corn oil v olive oil
control v low fat
control v low fat + PUF
control v soya-bean oil
control v low fat + PUF
low fat v fish v fiber
low fat v fruit/veg+fish+fiber
control v ultra-low fat
control v Mediterranean
n = 423
Leon 1999 (MCE) p < .001
Leon 1994 (MCE) p < .001
n = 605
Moradabad (MCE) p < .01
n = 505
Moradabad (death) p < .01
n = 505
n = 48
LHT (MCE + revascularization) p < .001
n = 48
LHT (MCE)
n = 2033
Risk Change
Cholesterol Change
Dart - fiber (death)
n = 2033
DART - fish (death) p < .05
n = 2033
DART - low fat (death)
n = 458
Sydney (death) p < .05
n = 393
London (MCE)
n = 412
Oslo (MCE) p < .05
Middlesex (MCE)
n = 264
n = 54
Rose -- corn oil (MCE)
Rose - olive oil (MCE)
n = 52
-25%
-20%
-15%
-10%
-5%
0%
5%
10%
15%
20%
25%
30%
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;336:129-133
Original Dean Ornish Plan
No calorie restriction
Fats (<10%)
Moderate exercise
Stress reduction
Smoking cessation
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
Fruits
Vegetables
Ban
All oils
All meats
Olives
Avocados
Nuts – seeds
High or low fat products
Sugar – syrup – honey
Alcohol
CP1095424-1
Lifestyle Heart Trial 1-Year Results
Variable
Experimental Control
p<
LDL mg/dl
95 ± 60
157 ± 45 .0072
HDL mg/dl
37 ± 15
51 ± 15
Progression
18%
53%
Regression
82%
42%
 stenosis
-2.2%
+3.4%
ns
.001
Not powered (or randomized) for clinical events
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;99:779-785
The Traditional
Healthy
Mediterranean Diet
Pyramid
Daily beverage
recommendations
Meat
Monthly
Sweets
Eggs
Weekly
Poultry
Fish
Cheese & yogurt
Olive oil
6 glasses
of water
Wine in
moderation
Fruits
Beans,
legumes
& nuts
Vegetables
Daily
Bread, pasta, rice, couscous, polenta,
other whole grains & potatoes
Daily physical activity
2000 Oldways Preservation & Exchange Trust
CP1059685-22
Lyon Heart Study - Lipids
Control
Experimental
Cholesterol
239 ± 40
239 ± 41
HDL
49 ± 13
50 ± 13
LDL
163 ± 38
161 ± 36
Triglycerides
154 ± 73
171 ± 75
Lyon Heart Study
200
180
160
140
120
100
80
60
40
20
0
p<.0002
Control
Experimental
p<.0001
p<.0001
Primary
Primary +
Secondary
All Endpoints
Results consistent with DART and Moradabad trials
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?
Therapeutic Lifestyle Changes in
LDL-Lowering Therapy
Major Features
NCEP
• 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
Other Features of TLC Diet
Nutrient
• Polyunsaturated fat
• Monounsaturated fat
• Total fat
• Carbohydrate
• Fiber
• Protein
• Total calories (energy)
Recommended Intake
Up to 10% of total calories
Up to 20% of total calories
25–35% of total calories
50–60% of total calories
20–30 grams per day
Approximately 15% of total calories
Balance energy intake and expenditure
to maintain desirable body weight/
prevent weight gain
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 2003:290:502-510
Results
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
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
BMJ 2004;329:1447-1450 (18 December), doi:10.1136/bmj.329.7480.1447
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
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)
21 (14 to 27)
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)
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)
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?
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 1
Diet 2
Diet 3
Diet 4
20%
20%
40%
40%
15%
25%
15%
25%
65%
55%
45%
35%
• 750 kcal per day caloric deficit
Sacks FM et al. NEJM 2009;360:859-873
Bon Appetit!
• Comments?
• Questions?