3/98 medslides.com 1 Antioxidants and Coronary Artery Disease Jason M. Lazar, MD George Yiachos, MD Winthrop-University Hospital
Dec 25, 2015
3/98 medslides.com 1
Antioxidants and
Coronary Artery Disease
Jason M. Lazar, MD
George Yiachos, MD
Winthrop-University Hospital
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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
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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 1997;337:408-416
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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 1989;320:915-924
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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 1993;16:I16-18
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Vitamin Ehuman studies
• Nurse’s 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 1993;328(20):1444-1449
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Vitamin Ehuman studies
• Health Professional’s Follow-up to the Physician’s Health Study– 39,910 men, ages 40-70– subjects with the highest vitamin E intake (>
60 IU / day) had a 36% lower risk of coronary disease after 4 years
NEJM 1993;328(20):1450-1466
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Vitamin Ehuman studies
• Iowa Women’s 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 1996;334(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 1996;347(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 1994;330(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 1992;3(3):194-202
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Vitamin Chuman studies
• The Nurse’s Health and the Health Professional’s 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 1993;328(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 (p=0.046)– the analysis was limited by its borderline p-
value and post hoc nature
Circ 1990;82s:202
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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 1996;334(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 1996;334(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 1993;342:1007-1011
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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 lowercotton-seed, safflower, sunflower), heart disease risk bynuts, sunflower seed, wheat germ 30%-40%
Vitamin C 60 mg Citrus fruits, strawberries, tomatoes, no evidence that RDI incantaloupe, broccoli, asparagus, supplement form canpeppers, spinach, potatoes prevent CHD or cancer
ß-carotene NA Dark green, yellow, and orange may protect againstvegetables: spinach, collard green CHD and macularbroccoli, carrots, peppers, sweet degenerationpotatoes; 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 riskselenium-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 1997;337:408-416
• Beyond cholesterol:modifications of low-density lipoprotein that increase its atherogenicity.Steinberg D, ParthasarathyS, et al. NEJM 1989;320:915-924
• Vitamin E: more than an antioxidant.Steiner M. Clin Cardiol 1993;16 (4 Suppl 1):I16-18
• Vitamin E consumption and the risk of coronary disease in women.Stampfer MJ, Hennekens CH, et al. NEJM 1993;328(20):1444-1449
• Vitamin E consumption and the risk of coronary disease in men.Rimm EB, Stampfer MJ, et al. NEJM 1993;328(20):1450-1466
• Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. Kushi LH, et al. NEJM 1996;334:1156-1162
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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 1996;347(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 1994;330(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 1996;334(18):11150-1155