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” DietsB. 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

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

Source: http://www.bmj.com

Risk Factors for CHD:The Framingham Heart Study

Major Risk Factors “Important” Risk Factors

Cigarette Smoking Obesity*Hypertension* Physical InactivityHigh Total Serum Cholesterol* Family Hx of Premature CHDLow HDL Cholesterol* Hypertriglyceridemia*Diabetes Mellitus* Increased Lipoprotein [a]

Increased serum homocysteine*Abnormal levels of various

coagulation factorsInflammatory Mediators

*Dietary factors contribute strongly to the control of or in the etiology of these risk factors.

C-Recative Protein and CVD Risk

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.

Total Cholesterol Levels (mg/dl) in the U.S.(National Health and Nutrition Examination Surveys)

Age Group 1976-80 1988-1994

Adults 213 203

Adolescents (ages 12-17) 167 160

Role of Diet in the Modification of Blood Cholesterol Levels-3

Tang et al. (1998) BMJ 316: 1213-1220Systematic 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 inTotal Cholesterol

AHA Step 2

Lower Total Fat 6.0

Raise PUFA:SFA Ratio

AHA Step 1 3.0

New Features of ATP IIIFocus 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

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

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

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)

New Features of ATP III (continued)

New strategies for Promoting Adherence

In both:

• Therapeutic Lifestyle Changes (TLC)

• Drug therapies

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

ATP III Guidelines

Therapeutic Lifestyle Changes (TLC)

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

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

Therapeutic Lifestyle ChangesNutrient Composition of TLC Diet

Nutrient Recommended Intake

• Saturated fat Less than 7% of total calories

• 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

• Cholesterol Less than 200 mg/day

• Total calories (energy) Balance energy intake and expenditure to maintain desirable body weight/prevent weight gain

• Reinforce reductionin saturated fat andcholesterol

• Consider addingplant stanols/sterols

• Increase fiber intake

• Consider referral toa dietitian

• Initiate Tx forMetabolicSyndrome

• Intensify weightmanagement &physical activity

• Consider referral to a dietitian

6 wks 6 wks Q 4-6 mo

• Emphasize

reduction insaturated fat &cholesterol

• Encouragemoderate physicalactivity

• Consider referral toa dietitian

Visit IBegin LifestyleTherapies

Visit 2Evaluate LDLresponse

If LDL goal notachieved, intensifyLDL-Lowering Tx

Visit 3Evaluate LDLresponse

If LDL goal notachieved, consideradding drug Tx

A Model of Steps in Therapeutic Lifestyle Changes (TLC)

MonitorAdherenceto TLC

Visit N

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

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

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

Physicians Health StudyHennekens et al. (1996) N Engl J Med 334:1145.

•• 22,071 male physicians randomized to alternate-day22,071 male physicians randomized to alternate-dayß-carotene (50 mg), aspirin (325 mg), both activeß-carotene (50 mg), aspirin (325 mg), both activetreatments, or both placebos.treatments, or both placebos.

•• Aspirin component terminated early (1988) due toAspirin component terminated early (1988) due tostatistically extreme 44% reduction in risk of firststatistically extreme 44% reduction in risk of firstmyocardial infarction.myocardial infarction.

•• After 12 years of treatment with ßC, there was noAfter 12 years of treatment with ßC, there was noeffect on any CA endpoint, MI, stroke, or CHDeffect on any CA endpoint, MI, stroke, or CHDdeaths.deaths.

Vitamin E Supplementation and CHD

•• Evidence from prospective trials (Physicians HealthEvidence from prospective trials (Physicians HealthStudy, Nurses Health Study) showed ~40% reductionStudy, Nurses Health Study) showed ~40% reductionin CHD incidence with > 2 yrs intake of >100 I.U. AT.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 Econtent in FOOD, not supplements, was inverselycontent in FOOD, not supplements, was inverselyassociated with risk of death from CHD (lowest vs.associated with risk of death from CHD (lowest vs.highest quintile of consumption: RR= 0.38;p=0.004)highest quintile of consumption: RR= 0.38;p=0.004)

Cambridge Heart Antioxidant StudyCambridge 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 Double-blinded study of the prevention of CVD death and non-fatal MI in patients with angiographically proven and non-fatal MI in patients with angiographically proven coronary atherosclerosis receiving alpha tocopherol or coronary atherosclerosis receiving alpha tocopherol or a placebo.a placebo.

** 2002 patients2002 patients 546 (800 I.U.) 546 (800 I.U.)

489 (400 I.U.)489 (400 I.U.)

967 (placebo)967 (placebo)

** Median follow-up: Median follow-up: 510 days (range 3-981)510 days (range 3-981)

CHAOS ResultsCHAOS Results

1.1. Alpha tocopherol treatment decreased risk of CVD deathAlpha tocopherol treatment decreased risk of CVD deathand non-fatal MI:and non-fatal MI:

Relative Risk (RR):Relative Risk (RR): 0.53 (95% CI 0.34-0.83; p=0.005)0.53 (95% CI 0.34-0.83; p=0.005)

2.2. Most of this benefit was due to decreased risk of non-fatalMost of this benefit was due to decreased risk of non-fatalMI:MI:

RR:RR: 0.23 (95% CI 0.11-0.47; p=0.005)0.23 (95% CI 0.11-0.47; p=0.005)

3.3. Non-significant INCREASE or excess in cardiovascular Non-significant INCREASE or excess in cardiovascular deaths in the treatment group compared to the placebo group.deaths in the treatment group compared to the placebo group.

Vitamin E: A ReviewFunction: Cell Membrane AntioxidantFunction: Cell Membrane Antioxidant

(prevents lipid peroxidation/free radical generation)(prevents lipid peroxidation/free radical generation)

Alpha-TocopherolAlpha-Tocopherol Gamma-TocopherolGamma-Tocopherol

• • higher vitamin E activityhigher vitamin E activity • principal form of • principal form of • • more potent antioxidantmore potent antioxidant vitamin E in U.S. diet vitamin E in U.S. diet• • primary form of supplemental vitamin Eprimary form of supplemental vitamin E • more rapid uptake and• more rapid uptake and• • low plasma levels are strong predictors oflow plasma levels are strong predictors of cellular turnover cellular turnover risk of certain cancers and CHDrisk of certain cancers and CHD • traps mutagenic• traps mutagenic• • displaces gamma-T in plasma/other tissuesdisplaces gamma-T in plasma/other tissues electrophiles like NOx electrophiles like NOx• • 5-fold higher plasma levels than gamma-T5-fold higher plasma levels than gamma-T

Dietary Effectors of Endothelial Cell Function (“NOT ready for prime time”)

• Arginine: substrate for endothelial nitric oxidesynthase

HeartBar®: 3 grams arginine per barPurports “Heart Healthy” benefits

• Pharmacologic Doses of Vitamins A and C

• Negative Effector: High Fat Diets

Frequent nut consumption and risk ofcoronary heart disease in women: prospective cohort study

Frank B Hu et al. Harvard University School of Public HealthBMJ 1998;317:1341-1345 ( 14 November )

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).

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.

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

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.

Table 1: Number of Events and Risk Ratios

de Lorgeril et al. (1998) Arch. Int. Med. 158: 1181-1187.

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

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

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

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.