Antioxidants and Coronary Artery Disease

1
Antioxidants and Coronary Artery Disease

• Jason M. Lazar, MD
• George Yiachos, MD
• Winthrop-University Hospital

2
Coronary ArteryDisease

• In 1997, the direct and indirect cost for CAD was
  90.9 billion in the U.S.
• only 50 of CAD can be attributed to conventional
  risk factors
• smoking hypertension
• diabetes hyperlipidemia
• family history

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Is the use of vitamins justified

• Although observational studies support a
  cardio-protective effects of antioxidants,
  clinical trials are disappointing
• In the mean time, Americans spend an estimate
  700 million on vitamin supplements

4
Epidemiologic Evidence

• In Europe, those living in the south consume
  greater amounts of fruits and vegetables
  containing the antioxidants beta-carotene,
  vitamin E and vitamin C, have lower rates of CAD
  than those living in the north

NEJM 1997337408-416
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Lipid Oxidation Hypothesis

• Lipid uptake across the cell wall is greatly
  enhanced by oxidized LDL-C.
• Antioxidants may therefore be beneficial in
  reducing the risk of coronary artery disease

NEJM 1989320915-924
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Antioxidants

• vitamins herbs
• estrogens flavonoids
• amino acids beta-carotene
• lipid-lowering agents
• monounsaturated fats

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Vitamin E

• A family of fat-soluble compounds, the
  tocopherols. Alpha-tocopherol is the most common
  and most active.
• Best sources of vitamin E
• vegetable, seeds, nut oils
• recommended daily allowance is 15 IU

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Vitamin Elaboratory and animal studies

• Vitamin E ? the oxidation of LDL-C
• inhibit smooth-muscle cell growth
• inhibit platelet adhesion
• improves endothelial function
• reduced the number and severity of
  atherosclerotic lesions in rabbits fed high-fat
  diets

Clin Cardiol 199316I16-18
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Vitamin Ehuman studies

• Nurses Health Study
• 87,245 women, ages 34-59, with no prior heart
  disease
• those taking ? 100 IU/d of vitamin E for ? 2
  years, had 40 lower risk of developing CAD after
  8 years

NEJM 1993328(20)1444-1449
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Vitamin Ehuman studies

• Health Professionals Follow-up to the
  Physicians Health Study
• 39,910 men, ages 40-70
• subjects with the highest vitamin E intake (gt 60
  IU / day) had a 36 lower risk of coronary
  disease after 4 years

NEJM 1993328(20)1450-1466
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Vitamin Ehuman studies

• Iowa Womens Health
• a prospective cohort study of 34,000
  postmenopausal women
• subjects with the highest vitamin E intake from
  diet (but no vitamin supplements) had a lower
  risk for CAD

NEJM 1996334(18)1156-1162
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Vitamin Erandomized trials

• CHAOS Study(Cambridge Heart Antioxidant Study)
• a prospective randomized trial of 2,002 patients
  with prior coronary disease
• treated with vitamin E (400-800 IU / day) for 3
  years
• 77 reduction in nonfatal MI
• no change in total mortality

Lancet 1996347(9004)781-786
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Vitamin Erandomized trials

• ABC Prevention Trial(Alpha-tocopherol
  Beta-carotene Cancer Prevention Trial)
• a lung cancer prevention trial
• 50 mg/d of vitamin E had no effect on the rate of
  MI or death
• 50 mg/d vit E 20 mg/d beta-carotene resulted in
  greater coronary death

NEJM 1994330(15)1029-1035
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Vitamin C

• a water-soluble vitamin
• found in many fruits and vegetables
• a less potent antioxidant than vit E
• associated with lower LDL-C, higher HDL-C, and
  lower BP
• inhibits platelet aggregation
• recommended daily allowance 60 mg

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Vitamin Chuman studies

• The benefit of vitamin C in CAD is inconsistent
  and inconclusive
• only 3 of 8 observational studies found an
  inverse relationship between vitamin C intake and
  CAD

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Vitamin Chuman studies

• First National Health and Nutritional Examination
  Survey
• 11,349 subjects received vitamin C supplements
• subjects taking vitamin C had a lower relative
  risk of cardiovascular death of .58

Epidemiology 19923(3)194-202
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Vitamin Chuman studies

• The Nurses Health and the Health Professionals
  Follow-Up Study
• subjects in the highest quintile of vitamin C
  intake had relative risk of cardiovascular
  disease of .8

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Beta-carotene

• A plant-derived nutrient
• contained in yellow and orange vegetables and
  fruits, and leafy green vegetables
• provides up to half of dietary vit A
• recommended daily allowance is 5,000 IU

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Beta-carotenehuman studies

• The antioxidant effects of beta-carotene and
  vitamin A have been well established
• The clinical studies are disappointing
• Only 3 of 6 observational studies found a
  decreased coronary risk associated with
  beta-carotene

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Beta-carotenehuman studies

• The Physician Health Study
• over 22,000 male physicians
• randomized to 50 mg of beta-carotene every other
  day
• after 12 years, there was no difference in
  cardiovascular, cancer, and all-cause mortality

NEJM 1993328(20)1450-1466
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Beta-carotenehuman studies

• The Physician Health Study
• in a subset of 333 subjects with preexisting
  coronary disease
• beta-carotene was associated with a 44 reduction
  of coronary events (p0.046)
• the analysis was limited by its borderline
  p-value and post hoc nature

Circ 199082s202
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Beta-carotenehuman studies

• The CARET Study(Carotene and Retinol Efficacy
  Trial)
• a randomized placebo-controlled trial of 18,000
  male smokers with history of asbestos exposure
• randomized to beta-carotene and vit A
• the trial was terminated 21 months early

N Engl J Med 1996334(18)11150-1155
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Beta-carotenehuman studies

• The CARET Studysubjects treated with 30 mg /d of
  beta-carotene had
• 28 ? in mortality from lung cancer
• 17 ? in all-cause mortality
• 29 ? in cardiovascular mortality

N Engl J Med 1996334(18)11150-1155
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Flavonoidshuman studies

• The Zutphen Elderly Study
• the consumption of flavonoid was inversely
  related to the occurrence of coronary heart
  disease

Lancet 19933421007-1011
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Antioxidants at a glance

• Nutrient RDI Dietary Sources Evidence
• Vitamin E 30 IU Vegetable oils (soy, corn,
  olive, 100-800 IU may lower cotton-seed,
  safflower, sunflower), heart disease risk
  by nuts, sunflower seed, wheat germ 30-40
• Vitamin C 60 mg Citrus fruits, strawberries,
  tomatoes, no evidence that RDI in cantaloupe,
  broccoli, asparagus, supplement form
  can peppers, spinach, potatoes prevent CHD or
  cancer
• ß-carotene NA Dark green, yellow, and orange may
  protect against vegetables spinach, collard
  green CHD and macular broccoli, carrots,
  peppers, sweet degeneration potatoes yellow
  fruits peaches
• Selenium ?70 ug Egg yolks, tuna, seafood,
  chicken, 150-200 ug may lower
• ?55 ug liver, whole grains, plant grown
  in prostate cancer risk selenium-rich soil (
  west of Mississippi)

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Summary

• Current data do not support a large role for the
  use of antioxidant supplements in the prevention
  of CAD
• Nonetheless, many Americans rather consume
  vitamin supplements and neglect modification of
  known coronary risk factors

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Summary

• Until further studies are completed, it is
  reasonable to recommend a diet rich in vegetable
  products, combined with exercise, risk
  modification behaviors, and appropriate
  medications

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References

• Antioxidants and atherosclerotic heart
  disease.Diaz MN, Frei B, Vita JA, et al. NEJM
  1997337408-416
• Beyond cholesterolmodifications of low-density
  lipoprotein that increase its atherogenicity.Stei
  nberg D, ParthasarathyS, et al. NEJM
  1989320915-924
• Vitamin E more than an antioxidant.Steiner M.
  Clin Cardiol 199316 (4 Suppl 1)I16-18
• Vitamin E consumption and the risk of coronary
  disease in women.Stampfer MJ, Hennekens CH, et
  al. NEJM 1993328(20)1444-1449
• Vitamin E consumption and the risk of coronary
  disease in men.Rimm EB, Stampfer MJ, et al.
  NEJM 1993328(20)1450-1466
• Dietary antioxidant vitamins and death from
  coronary heart disease in postmenopausal women.
  Kushi LH, et al. NEJM 19963341156-1162

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References

• Randomized controlled trial of vitamin E in
  patients with coronary disease Cambridge Heart
  Antioxidant Study (CHAOS).Stephens NG, Parson A,
  et al. Lancet 1996347(9004)781-786
• The Alpha-tocopherol Beta-carotene Cancer
  Prevention Sutdy Group the effect of vitamin E
  and beta-carotene on the incidence of lung cancer
  and other cancers in male smokers.NEJM
  1994330(15)1029-1035
• Effects of a combination of beta-carotene and
  vitamin A on lung cancer and cardiovascuar
  disease.Omenn GS, et al. N Engl J Med
  1996334(18)11150-1155