1. OST 524 Diet Therapy and Coronary Heart Disease (CHD) I.Risk Factors for Developing CHD II.Diet-Responsive Risk Factors for CHD A.American Heart Association “Step” Diets B.Role for Dietary Supplements? III.Diet Therapy in the Secondary Prevention of IHD IV.Diet Therapy in the Primary Prevention of IHD V.Are AHA Step I and II Guidelines Enough? http://www.msu.edu/course/hnf/470

2. Source: http://www.bmj.com Figure 1: Annual trends in incidence and case fatality rate of CHD by country. United States Russia, E. Europe, China

3. Source: http://www.bmj.com

4. Risk Factors for CHD: The Framingham Heart Study Major Risk Factors“Important” Risk Factors Cigarette SmokingObesity* Hypertension*Physical Inactivity High Total Serum Cholesterol*Family Hx of Premature CHD Low HDL Cholesterol*Hypertriglyceridemia* Diabetes Mellitus*Increased Lipoprotein [a] Increased serum homocysteine* Abnormal levels of various coagulation factors Inflammatory Mediators *Dietary factors contribute strongly to the control of or in the etiology of these risk factors.

5. C-Recative Protein and CVD Risk

8. Role of Diet in the Modification of Blood Cholesterol Levels Assumptions: Blood cholesterol [ ] is an important and modifiable risk factor for coronary heart disease. Sustained reduction of total cholesterol [ ] of 1% is associated with a 2-3% reduction in the incidence of coronary heart disease.

9. Total Cholesterol Levels (mg/dl) in the U.S. (National Health and Nutrition Examination Surveys) Age Group1976-80 1988-1994 Adults 213 203 Adolescents (ages 12-17) 167 160

10. Role of Diet in the Modification of Blood Cholesterol Levels-3 Tang et al. (1998) BMJ 316: 1213-1220 Systematic review of dietary intervention trials to lower blood total cholesterol in free-living subjects. Efficacy of Dietary Intervention Trials to Lower Total Cholesterol Diet Types% Reduction in Total Cholesterol AHA Step 2 Lower Total Fat 6.0 Raise PUFA:SFA Ratio AHA Step 1 3.0

12. New Features of ATP III Focus on Multiple Risk Factors Diabetes: CHD risk equivalent Framingham projections of 10-year CHD risk –Identify certain patients with multiple risk factors for more intensive treatment Multiple metabolic risk factors (metabolic syndrome) –Intensified therapeutic lifestyle changes

13. New Features of ATP III (continued) Modification of Lipid and Lipoprotein Classification LDL cholesterol <100 mg/dL—optimal HDL cholesterol <40 mg/dL –Categorical risk factor –Raised from <35 mg/dL Lower triglyceride classification cut points –More attention to moderate elevations

14. New Features of ATP III (continued) New Recommendation for Screening/Detection Complete lipoprotein profile preferred –Fasting total cholesterol, LDL, HDL, triglycerides Secondary option –Non-fasting total cholesterol and HDL –Proceed to lipoprotein profile if TC  200 mg/dL or HDL <40 mg/dL

15. New Features of ATP III (continued) Therapeutic diet lowers saturated fat and cholesterol intakes to levels of previous Step II Adds dietary options to enhance LDL lowering –Plant stanols/sterols (2 g/d) –Viscous (soluble) fiber (10–25 g/d) Increased emphasis on weight management and physical activity More Intensive Lifestyle Intervention (Therapeutic Lifestyle Changes = TLC)

16. New Features of ATP III (continued) New strategies for Promoting Adherence In both: Therapeutic Lifestyle Changes (TLC) Drug therapies

17. New Features of ATP III (continued) For patients with triglycerides  200 mg/dL –LDL cholesterol: primary target of therapy –Non-HDL cholesterol: secondary target of therapy Non HDL-C = total cholesterol – HDL cholesterol

18. ATP III Guidelines Therapeutic Lifestyle Changes (TLC)

19. Therapeutic Lifestyle Changes in LDL-Lowering Therapy Major Features TLC Diet –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

20. Benefit Beyond LDL Lowering: The Metabolic Syndrome as a Secondary Target of Therapy General Features of the Metabolic Syndrome Abdominal obesity Atherogenic dyslipidemia –Elevated triglycerides –Small LDL particles –Low HDL cholesterol Raised blood pressure Insulin resistance (  glucose intolerance) Prothrombotic state Proinflammatory state

21. Therapeutic Lifestyle Changes Nutrient Composition of TLC Diet NutrientRecommended Intake Saturated fatLess than 7% of total calories Polyunsaturated fatUp to 10% of total calories Monounsaturated fat Up to 20% of total calories Total fat25–35% of total calories Carbohydrate50–60% of total calories Fiber20–30 grams per day ProteinApproximately 15% of total calories CholesterolLess than 200 mg/day Total calories (energy)Balance energy intake and expenditure to maintain desirable body weight/ prevent weight gain

22. Reinforce reduction in saturated fat and cholesterol Consider adding plant stanols/sterols Increase fiber intake Consider referral to a dietitian Initiate Tx for Metabolic Syndrome Intensify weight management & physical activity Consider referral to a dietitian 6 wks Q 4-6 mo Emphasize reduction in saturated fat & cholesterol Encourage moderate physical activity Consider referral to a dietitian Visit I Begin Lifestyle Therapies Visit 2 Evaluate LDL response If LDL goal not achieved, intensify LDL-Lowering Tx Visit 3 Evaluate LDL response If LDL goal not achieved, consider adding drug Tx A Model of Steps in Therapeutic Lifestyle Changes (TLC) Monitor Adherence to TLC Visit N

23. Steps in Therapeutic Lifestyle Changes (TLC) First Visit Begin Therapeutic Lifestyle Changes Emphasize reduction in saturated fats and cholesterol Initiate moderate physical activity Consider referral to a dietitian (medical nutrition therapy) Return visit in about 6 weeks

24. Steps in Therapeutic Lifestyle Changes (TLC) (continued) Second Visit Evaluate LDL response Intensify LDL-lowering therapy (if goal not achieved) –Reinforce reduction in saturated fat and cholesterol –Consider plant stanols/sterols –Increase viscous (soluble) fiber –Consider referral for medical nutrition therapy Return visit in about 6 weeks

25. Steps in Therapeutic Lifestyle Changes (TLC) (continued) Third Visit Evaluate LDL response Continue lifestyle therapy (if LDL goal is achieved) Consider LDL-lowering drug (if LDL goal not achieved) Initiate management of metabolic syndrome (if necessary) –Intensify weight management and physical activity Consider referral to a dietitian

26. Physicians Health Study Hennekens et al. (1996) N Engl J Med 334:1145. 22,071 male physicians randomized to alternate-day22,071 male physicians randomized to alternate-day ß-carotene (50 mg), aspirin (325 mg), both active treatments, or both placebos. Aspirin component terminated early (1988) due toAspirin component terminated early (1988) due to statistically extreme 44% reduction in risk of first myocardial infarction. After 12 years of treatment with ßC, there was noAfter 12 years of treatment with ßC, there was no effect on any CA endpoint, MI, stroke, or CHD deaths.

27. Vitamin E Supplementation and CHD Evidence from prospective trials (Physicians HealthEvidence from prospective trials (Physicians Health Study, Nurses Health Study) showed ~40% reduction in CHD incidence with > 2 yrs intake of >100 I.U. AT. The Iowa Women’s Health Study showed that vitamin EThe Iowa Women’s Health Study showed that vitamin E content in FOOD, not supplements, was inversely associated with risk of death from CHD (lowest vs. highest quintile of consumption: RR= 0.38;p=0.004)

28. Cambridge Heart Antioxidant Study Cambridge Heart Antioxidant Study (Stephens et al. (1996) Lancet 347: 781-86) (Stephens et al. (1996) Lancet 347: 781-86) *Double-blinded study of the prevention of CVD death and non-fatal MI in patients with angiographically proven coronary atherosclerosis receiving alpha tocopherol or a placebo. *2002 patients 546 (800 I.U.) *2002 patients 546 (800 I.U.) 489 (400 I.U.) 489 (400 I.U.) 967 (placebo) 967 (placebo) *Median follow-up: 510 days (range 3-981) *Median follow-up: 510 days (range 3-981)

29. CHAOS Results 1.Alpha tocopherol treatment decreased risk of CVD death and non-fatal MI: Relative Risk (RR):0.53 (95% CI 0.34-0.83; p=0.005) 2.Most of this benefit was due to decreased risk of non-fatal MI: RR:0.23 (95% CI 0.11-0.47; p=0.005) 3.Non-significant INCREASE or excess in cardiovascular deaths in the treatment group compared to the placebo group.

30. Vitamin E: A Review Function: Cell Membrane Antioxidant (prevents lipid peroxidation/free radical generation) Alpha-TocopherolGamma-Tocopherol higher vitamin E activity principal form of higher vitamin E activity principal form of more potent antioxidant vitamin E in U.S. diet more potent antioxidant vitamin E in U.S. diet primary form of supplemental vitamin E more rapid uptake and primary form of supplemental vitamin E more rapid uptake and low plasma levels are strong predictors of cellular turnover low plasma levels are strong predictors of cellular turnover risk of certain cancers and CHD traps mutagenic risk of certain cancers and CHD traps mutagenic displaces gamma-T in plasma/other tissues electrophiles like NOx displaces gamma-T in plasma/other tissues electrophiles like NOx 5-fold higher plasma levels than gamma-T 5-fold higher plasma levels than gamma-T

31. Dietary Effectors of Endothelial Cell Function (“NOT ready for prime time”) Arginine:substrate for endothelial nitric oxide synthase HeartBar®:3 grams arginine per bar Purports “Heart Healthy” benefits Pharmacologic Doses of Vitamins A and C Negative Effector: High Fat Diets

32. Frequent nut consumption and risk ofcoronary heart disease in women: prospective cohort study Frank B Hu et al. Harvard University School of Public Health BMJ 1998;317:1341-1345 ( 14 November )

33. After adjusting for age, smoking, and other known risk factors for CHD: Women consuming > five ounces of nuts a week (frequent consumption) vs. women who never ate nuts or who ate < one ounce a month (rare consumption) had a significantly lower risk of total coronary heart disease (RR = 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009).

34. The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) & non-fatal MI (0.68, 0.47 to1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking, use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits.

35. Key messages Nuts are high in fat, but most of the fatty acids are unsaturated This study suggests that frequent consumption of nuts, including peanuts, may reduce the risk of coronary heart disease This protective effect may be partly mediated through serum lipids because unsaturated fats have benefical effects on serum lipids. Other potentially protective constituents include vegetable protein, magnesium, vitamin E, fibre, and potassium Nuts can be included as part of a healthy diet

36. Lyon Diet Heart Study (de Lorgeril et al., Arch Int Med 158: 1181-1187) Randomized secondary prevention trial; 605 patients with coronary artery disease randomized to either a Meditarranean-type diet or control (A.H.A. Step 1-like) diet; After ~ 4 years of follow-up, Cox proportional hazards model was used to estimate risk ratios for cancer, total or cardiac death, combined total death, nonfatal cancer, and nonfatal MI.

37. Table 1: Number of Events and Risk Ratios de Lorgeril et al. (1998) Arch. Int. Med. 158: 1181-1187.

38. Table 2: Characteristics of patients who developed cancer in the two groups

39. Figure 1: Cumulative survival without nonfatal cancer among patients in the experimental and control groups.

40. Figure 2: Cumulative survival without nonfatal cancer and recurrent acute MI among patients in the experimental and control groups.

42. Eat a variety of foods. Choose most foods from plant sources. Eat at least 5 servings of fruits and vegetables every day. Eat at least 6 servings of whole grain foods each day. Minimize the consumption of high-fat foods, especially those from animals. Choose low-fat, low-cholesterol foods. Limit the amount of simple sugars in the diet.