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

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.

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;291:1071-1080.

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 (Men ages 35-74) 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 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 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 low fat v fish v fiber low fat v fruit/veg+fish+fiber control v ultra-low fat control v Mediterranean

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

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 CP1095424-1

Lifestyle Heart Trial 1-Year Results 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 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 CP1059685-22

Lyon Heart Study - Lipids

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

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

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

strategy to reduce cardiovascular disease by more than 75% 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) 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 20% 15% 65% Diet 2 20% 25% 55% Diet 3 40% 15% 45% Diet 4 40% 25% 35% 750 kcal per day caloric deficit Sacks FM et al. NEJM 2009;360:859-873

Bon Appetit!

Comments? Questions?