Transcript No Slide Title

OST 524
Diet Therapy and Coronary Heart Disease (CHD)
I.
Risk Factors for Developing CHD
II.
Diet-Responsive Risk Factors for CHD
A.
B.
American Heart Association “Step” Diets
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
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
Source: http://www.bmj.com
Risk Factors for CHD:
The Framingham Heart Study
Major Risk Factors
“Important” Risk Factors
Cigarette Smoking
Hypertension*
High Total Serum Cholesterol*
Low HDL Cholesterol*
Diabetes Mellitus*
Obesity*
Physical Inactivity
Family Hx of Premature CHD
Hypertriglyceridemia*
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.
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
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
Tang et al. (1998) BMJ 316: 1213-1220
Systematic review of dietary intervention trials to lower blood total cholesterol in free-living subjects.
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)
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)
More Intensive Lifestyle Intervention
(Therapeutic Lifestyle Changes = TLC)
• 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
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 Changes
Nutrient Composition of TLC Diet
Nutrient
• Saturated fat
calories
• Polyunsaturated fat
• Monounsaturated fat
calories
• Total fat
• Carbohydrate
• Fiber
• Protein
calories
• Cholesterol
Recommended Intake
Less than 7% of total
Up to 10% of total calories
Up to 20% of total
25–35% of total calories
50–60% of total calories
20–30 grams per day
Approximately 15% of total
Less than 200 mg/day
A Model of Steps in
Therapeutic Lifestyle Changes (TLC)
Visit I
Begin Lifestyle
Therapies
Visit 2
Evaluate LDL
6 wks response
• Emphasize
reduction in
saturated fat &
cholesterol
• Encourage
moderate physical
activity
Visit 3
Evaluate LDL
6 wks response
If LDL goal not
achieved,
intensify
LDL-Lowering Tx
• Reinforce reduction
in saturated fat and
cholesterol
• Consider adding
plant stanols/sterols
• Increase fiber intake
• Consider referral to
• Consider referral to
a dietitian
a dietitian
If LDL goal not
achieved,
consider
adding drug Tx
• Initiate Tx for
Metabolic
Syndrome
• Intensify
weight
management
&
physical
activity
• Consider
referral
to a dietitian
Q 4-6 mo
Visit N
Monitor
Adherence
to TLC
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 Study
Hennekens et al. (1996) N Engl J Med 334:1145.
•
22,071 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 to
statistically extreme 44% reduction in risk of first
myocardial infarction.
•
After 12 years of treatment with ßC, there was no
effect on any CA endpoint, MI, stroke, or CHD
deaths.
Vitamin E Supplementation and CHD
•
Evidence 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 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)
Cambridge Heart Antioxidant Study
(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.)
489 (400 I.U.)
967 (placebo)
*
Median follow-up:
510 days (range 3-981)
CHAOS Results
1.
Alpha tocopherol treatment decreased risk of CVD death
and non-fatal MI:
Relative Risk (RR):
2.
Most of this benefit was due to decreased risk of non-fatal
MI:
RR:
3.
0.53 (95% CI 0.34-0.83; p=0.005)
0.23 (95% CI 0.11-0.47; p=0.005)
Non-significant INCREASE or excess in cardiovascular
deaths in the treatment group compared to the placebo group.
Vitamin E: A Review
Function: Cell Membrane Antioxidant
(prevents lipid peroxidation/free radical generation)
Alpha-Tocopherol
Gamma-Tocopherol
•
•
•
•
• principal form of
vitamin E in U.S. diet
• more rapid uptake and
cellular turnover
• traps mutagenic
electrophiles like NOx
higher vitamin E activity
more potent antioxidant
primary form of supplemental vitamin E
low plasma levels are strong predictors of
risk of certain cancers and CHD
• displaces gamma-T in plasma/other tissues
• 5-fold higher plasma levels than gamma-T
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
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 )
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.
imit the amount of simple sugars in the diet.