Secondary Prevention

The most positive results from secondary prevention trials came from the Cambridge Heart Antioxidant Study (CHAOS), a controlled trial on 2002 heart disease patients with angiographically proven coronary atherosclerosis randomly assigned to receive a high dose of vitamin E (400 or 800 IU/day) or placebo (Table 2). Those receiving the supplements were 77% less likely to suffer from nonfatal heart disease over the 1|-year trial period than those who did not receive vitamin E (RR, 0.23; 95% CI, 0.11-0.47), although there was no reduction in CVD deaths. However, other large secondary prevention trials with longer follow-up have been less encouraging. For example, in a further analysis of the ATBC study, the ^-carotene supplementation was associated with an increased risk of coronary heart disease (CHD) deaths among men who had a previous heart attack and were thus at high risk of subsequent coronary events. There were significantly more deaths from fatal CHD in the ^-carotene group (RR, 1.75; 95% CI, 1.16-2.64) and in the combined ^-carotene and vitamin E group compared to the placebo group (RR, 1.58; 95% CI, 1.05-2.40). The Heart Outcomes Prevention Evaluation Study (HOPE) observed no benefit from vitamin E supplementation (400 IU/day) on CVD or all-cause mortality. The Heart Protection Study in the United Kingdom examined the effect of 5 years of

Table 2 Summary of large intervention trials (>1000 subjects) investigating the role of antioxidants and CVD in secondary preventiona

Trial Characteristics of Sex Length of Treatment Effect of antioxidant subjects follow-up (years) supplementation

ATBC

1862 smokers with previous MI, Finland

Male

CHAOS

GISSI

HOPE

1795 heavy smokers with previous angina, Finland 2002 patients with coronary atherosclerosis, United Kingdom 11324 patients with recent MI, Italy

9541 known CVD or diabetes, Canada

20536 with known vascular disease or at high risk, United Kingdom

Male and Female 1|

Male and Female

Male and Female

50 mg «-tocopherol and/or 20 mg ^-carotene

300 or 800IU «-tocopherol

300 mg a-tocopherol and/or 1 g n-3 PUFA 400 IU a-tocopherol and/or ACE inhibitor 20 mg ^-carotene, 600 mg a-tocopherol, and 250 mg vitamin C

No effect on total coronary events (fatal and nonfatal) Increase in deaths from fatal CHD in ^-carotene (+75%) and combined ^-carotene/vitamin E group (+58%) vs placebo No effect on symptoms or progression of angina or on total coronary events Reduction in nonfatal MI (-77%) but no effect on CVD mortality

No benefit from vitamin E

No effect on MI, stroke, or CVD death

No effect on fatal or nonfatal MI or stroke aSecondary prevention is defined as including patients with known or documented vascular disease.

ACE, angiotensin converting enzyme; ATBC, Alpha Tocopherol Beta Carotene Prevention Study; CHAOS, Cambridge Heart Antioxidant Study; GISSI, GISSI Prevenzione Trial; HOPE, Heart Outcomes Prevention Evaluation Study; HPS, Heart Protection Study; CHD, Coronary Heart Disease; CVD, cardiovascular disease; MI, myocardial infarction; PUFA, polyunsatutated fatty acids.

supplementation with a cocktail of antioxidant vitamins (600 mg vitamin E, 250 mg vitamin C, and 20 mg ^-carotene) alone or in combination with the lipid-lowering drug Simvastatin or placebo in more than 20 000 adults with CHD, other occlusive arterial disease, or diabetes mellitus. Although blood levels of antioxidant vitamins were substantially increased, no significant reduction in the 5-year mortality from vascular disease or any other major outcome was noted. In the Italian GISSI-Prevenzione Trial dietary fish oils reduced the risk of fatal or nonfatal CVD in men and women who had recently suffered from a heart attack but vitamin E supplementation (300 mg daily for years) did not provide any benefit. In these three trials, no significant adverse effects of vitamin E were observed.

Systematic reviews and meta-analyses of the clinical trials to date have therefore concluded that despite evidence from observational studies, people with a high occurrence of CVD often have low intakes or plasma levels of antioxidant nutrients. Supplementation with any single antioxidant nutrient or combination of nutrients has not demonstrated any benefit for the treatment or prevention of CVD.

A Disquistion On The Evils Of Using Tobacco

A Disquistion On The Evils Of Using Tobacco

Among the evils which a vitiated appetite has fastened upon mankind, those that arise from the use of Tobacco hold a prominent place, and call loudly for reform. We pity the poor Chinese, who stupifies body and mind with opium, and the wretched Hindoo, who is under a similar slavery to his favorite plant, the Betel but we present the humiliating spectacle of an enlightened and christian nation, wasting annually more than twenty-five millions of dollars, and destroying the health and the lives of thousands, by a practice not at all less degrading than that of the Chinese or Hindoo.

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