Transcript Chest Pain: New Methods Applied to an Old Problem

Alternative Therapies in
Coronary Artery Disease:
Vitamins, Supplements, Diets and
Associated Topics
Carl R. Szot, MD
December 2, 2002
Vitamin E
• Fat soluble compounds with alpha-tocopherol being the most
common
• Natural sources include vegetables, nuts and nut oils
• Deficiency is rare and associated with posterior column
degeneration and loss of large caliber peripheral nerves
• Excess is only an issue in people on coumadin or in premature
infants
Vitamin E
Proposed Mechanisms of Action
• Decreases oxidation of
LDL
• Improves endothelial
function
• Inhibits smooth muscle
cell growth
• In fat fed rabbits
reduces atherosclerosis
• Inhibits platelet
adhesion
Clinical Cardiology 1993: 16: 116-118
Vitamin E
Human Studies
• Iowa Women’s Health
• Prospective study of 34,000 postmenopausal
women
• High dietary Vitamin E intake was associated
with lower CAD risk
NEJM 1996: 334 (18): 1156-62
Vitamin E
Human Observational Studies
• Health Professionals follow up to the
Physicians Health Study
• 39,910 men ages 40-70
• Subjects with the highest Vitamin E intake
had a 36% lower risk of CAD events after 4
years
NEJM 1993: 328 (20): 1450-1466
Vitamin E
Human Studies
• Nurse’s Health Study
• 87,245 women ages 34-59 with no prior CAD
• Those taking > 100 iu of Vitamin E for > 2
years Had 40% lower risk of developing CAD
after 8 years.
NEJM 1993; 328 (20): 1444-49
Vitamin E
Randomized Trials
• Cambridge Heart Antioxidant Study (CHAOS)
• 2002 patients with prior CAD prospectively
randomized to Vitamin E (400-800 iu/day)
• 77% reduction in nonfatal MI
• No change in overall mortality
Lancet 1996; 347 (9004): 781-86
Vitamin E
Randomized Trials
• Alpha-tocopheral Beta Carotene Prevention Trial
(ABC)
• 50mg/day of Vitamin E had no effect on the risk of MI or
death
• 50mg/day of Vitamin E plus 20mg/day of beta-carotene
resulted in greater rate of coronary death
• Trial was mainly for lung cancer prevention
NEJM 1994; 330 (15): 1029-35
Vitamin C
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Less potent antioxidant than E
Inhibits platelet aggregation
Deficiency = Scurvy
Excess may lead to B12 deficiency or oxalate
stones
• Less evidence than exists for Vitamin E
Vitamin C
Human Studies
• NHANES I
• 11,349 subjects taking Vitamin C supplements
• Subjects taking Vitamin C had a lower relative
risk of CV death (.58)
Epidemiology 1992; 3(3): 194-202
Vitamin C
Human Studies
• The Nurse’s Health and the Health
Professionals Follow up Study
• Slightly lower relative risk (.8) in subjects in
highest quintile of Vitamin C consumption
Vitamin C and E
Heart Protection Study
• 2x2 Trial
• simvistatin 40 mg vs. placebo
• vitamin E 600 mg, vitamin C 250 mg, beta carotene 20
mg vs. placebo
• Over 10,000 patients randomized to vitamin
arm
Lancet 2002; 360: 23-33
Vitamin C and E
Heart Protection Study
• No difference in vascular and nonvascular
mortality
• No difference in cancer rate
• No difference in major vascular events
Lancet 2002; 360: 23-33
Fish Oil
Omega -3 Fatty Acids
• Epidemiologic data suggests improved outcomes in patients
eating fish
• DART ( Diet and Reinfarction Trial) showed 29% reduction in
all cause mortality after 2 years of increased fish/fish oil
intake
• GISSI Prevenzione showed a 45% decrease in SCD and 20%
decrease in all cause mortality after 3 1/2 years of
supplementation
Lancet 1989; 2 (8666) : 757-61
Lancet 1999; 354 (9177) : 447-55
Olive Oil
• Oleic acid ( monounsaturated )
• In a trial comparing an AHA Step I diet, an average American
control diet and an olive oil enriched diet showed similar
reductions of LDL compared to control, but unchanged HDL
with olive oil ( decreased 4 % with Step II.) Triglycerides fell
13% with olive oil but increased 11% with the Step II diet.
AMJ Clinical Nutrition 1999; 70(6): 1009-15
Nuts
• 80% of calories from fat: Monounsaturates and
alpha-linolenic acid ( an omega -3)
• Also rich in Vitamin E, folic acid, K+, Mg,
flavanoids
• 1/4 to 1/3 cup daily can reduce LDL levels by
up to 10 %
Nuts- Data
• Health Professionals Follow Up Study showed increased
intake of alpha-linolenic acid lowered MI risk by 60%
• Nurse’s Health Study showed 35% CAD reduction associated
with nut intake
• Physicians Health Study showed reduction in sudden and
total CAD death, but not in nonfatal MI associated with nut
intake
BMJ 1996; 313 (7049): 84-90. BMJ 1998; 317 (7169): 1341-5
Archives Internal Medicine 2002; 162: 1382-87
Fats
• Good• Bad-
monounsaturated-- olive oil, canola oil, nuts
omega-3 -- fish, nuts
saturated-- red meat, cheese, butter
trans- fatty acids-- processed foods
• Omega-6 oils- (corn, soybean, sunflower) are probably
neutral in effect
Diets
Plan
Fat
Carbohydrate
Ornish
Pritikin
Very Low (10%)
Very High
Low (20-30%)
High
Mediterranean
Zone
Moderate ( 30-35%)
Moderate
Sugar Busters
Protein Power
Atkins
High ( > 45%)
Low
AHA Step I & Step II
Weight Watchers
DASH
Postgraduate Medicine 2002; 112 (2) : 34-44
AHA Diet
• Step I• Total Fat < 30%,
saturated fat <10%,
cholesterol < 300mg
• Step II• Total Fat < 25%,
saturated fat < 7%,
cholesterol < 200mg
A paucity of evidence for improved outcomes exists for the AHA die
and some evidence exists for continued disease progression
BMJ 2001: 322(7289): 757-63
Mediterranean Diet
• Greece, Crete, parts of France and Italy display low
rates of CAD
• Monounsaturates and Omega-3 fatty acids are not
limited
• Fresh fruits and vegetables, fish, nuts, moderate
alcohol
• Low in trans fatty acids
Mediterranean Diet
DATA
• Lyon Diet Heart Study of 605 MI survivors
• 55% reduction in risk of death and 50 %
reduction in recurrent cardiac events over a
4 year period
• Reduction not explained by changes in lipid
factors
Circulation 1999; 99 (6): 779-85
Mediterranean Diet
DATA
• GISSI - Prevenzione
• Multivariate analysis showed fish, fruit,
vegetables and olive oil all conferred benefit
over a 4 year period
Circulation 2002; 105: 1887-903
Mediterranean Diet
Suggestions- Carbs and Proteins
• EAT
• DON’T EAT
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Whole fruits and vegetables
Whole grain cereal
Bran, brown rice
Peas, beans
Lean meat, fish, poultry,
vegetable protein
Refined carbohydrates
White bread, biscuits
Bacon, sausage
Processed fatty meat
High fat dairy
Mediterranean Diet
Suggestions- Fats
• EAT
• Olive oil
• Fish
• Flaxseed, spinach, tree nuts
• DON’T EAT
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Trans-fatty acids
Fast food
Doughnuts
Chips, crackers
Margarine made with partially
hydrogenated oil
Alcohol
• Evidence of cardioprotective effect of alcohol first appeared in
Framingham data
• At levels of consumption of greater than two drinks/day for
men and one drink /day for women all cause mortality
overwhelms cardioprotective effect
• Mechanisms include HDL raising, changes in inflammatory
markers and improvement in insulin resistances.
Lancet 2001; 357 (9258): 763-7