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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: 

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

Is the use of vitamins justified: 

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

Epidemiologic Evidence: 

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

Lipid Oxidation Hypothesis: 

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

Antioxidants: 

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

Vitamin E: 

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

Vitamin E laboratory and animal studies: 

Vitamin E laboratory 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

Vitamin E human studies: 

Vitamin E human 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

Vitamin E human studies: 

Vitamin E human 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

Vitamin E human studies: 

Vitamin E human 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

Vitamin E randomized trials: 

Vitamin E randomized 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

Vitamin E randomized trials: 

Vitamin E randomized 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

Vitamin C: 

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

Vitamin C human studies: 

Vitamin C human 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

Vitamin C human studies: 

Vitamin C human 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

Vitamin C human studies: 

Vitamin C human 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

Beta-carotene: 

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

Beta-carotene human studies: 

Beta-carotene human 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

Beta-carotene human studies: 

Beta-carotene human 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

Beta-carotene human studies: 

Beta-carotene human 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

Beta-carotene human studies: 

Beta-carotene human 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

Beta-carotene human studies: 

Beta-carotene human studies The CARET Study subjects 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

Flavonoids human studies: 

Flavonoids human studies The Zutphen Elderly Study the consumption of flavonoid was inversely related to the occurrence of coronary heart disease Lancet 1993;342:1007-1011

Antioxidants at a glance: 

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)

Summary: 

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

Summary: 

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”

References: 

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

References: 

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