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Antioxidants and Coronary Artery Disease

Antioxidants and Coronary Artery Disease. Jason M. Lazar, MD George Yiachos, MD Winthrop-University Hospital. 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:

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Antioxidants and Coronary Artery Disease

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  1. Antioxidants and Coronary Artery Disease Jason M. Lazar, MD George Yiachos, MD Winthrop-University Hospital medslides.com

  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 medslides.com

  3. 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 medslides.com

  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 1997;337:408-416 medslides.com

  5. 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 medslides.com

  6. Antioxidants vitamins herbs estrogens flavonoids amino acids beta-carotene lipid-lowering agents monounsaturated fats medslides.com

  7. 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 medslides.com

  8. 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 medslides.com

  9. 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 medslides.com

  10. 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 medslides.com

  11. 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 medslides.com

  12. 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 medslides.com

  13. 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 medslides.com

  14. 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 medslides.com

  15. 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 medslides.com

  16. 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 medslides.com

  17. 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 medslides.com

  18. 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 medslides.com

  19. 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 medslides.com

  20. 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 medslides.com

  21. 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 medslides.com

  22. 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 medslides.com

  23. 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 medslides.com

  24. 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 medslides.com

  25. 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) medslides.com

  26. 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 medslides.com

  27. 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” medslides.com

  28. 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 medslides.com

  29. 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 medslides.com

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